ID TPA_HUMAN Reviewed; 562 AA. AC P00750; A8K022; B2R8E8; Q15103; Q503B0; Q6PJA5; Q7Z7N2; Q86YK8; AC Q9BU99; Q9BZW1; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 05-OCT-2010, entry version 160. DE RecName: Full=Tissue-type plasminogen activator; DE Short=t-PA; DE Short=t-plasminogen activator; DE Short=tPA; DE EC=3.4.21.68; DE AltName: INN=Alteplase; DE AltName: INN=Reteplase; DE Contains: DE RecName: Full=Tissue-type plasminogen activator chain A; DE Contains: DE RecName: Full=Tissue-type plasminogen activator chain B; DE Flags: Precursor; GN Name=PLAT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Melanoma; RX MEDLINE=83115262; PubMed=6337343; DOI=10.1038/301214a0; RA Pennica D., Holmes W.E., Kohr W.J., Harkins R.N., Vehar G.A., RA Ward C.A., Bennett W.F., Yelverton E., Seeburg P.H., Heyneker H.L., RA Goeddel D.V., Collen D.; RT "Cloning and expression of human tissue-type plasminogen activator RT cDNA in E. coli."; RL Nature 301:214-221(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=84298137; PubMed=6089198; DOI=10.1073/pnas.81.17.5355; RA Ny T., Elgh F., Lund B.; RT "The structure of the human tissue-type plasminogen activator gene: RT correlation of intron and exon structures to functional and structural RT domains."; RL Proc. Natl. Acad. Sci. U.S.A. 81:5355-5359(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=86196143; PubMed=3009482; RA Friezner Degen S.J., Rajput B., Reich E.; RT "The human tissue plasminogen activator gene."; RL J. Biol. Chem. 261:6972-6985(1986). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=86284200; PubMed=3090401; RA Harris T.J., Patel T., Marston F.A., Little S., Emtage J.S., RA Opdenakker G., Volckaert G., Rombauts W., Billiau A., Somer P.; RT "Cloning of cDNA coding for human tissue-type plasminogen activator RT and its expression in Escherichia coli."; RL Mol. Biol. Med. 3:279-292(1986). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=88054470; PubMed=2824147; RA Reddy V.B., Garramone A.J., Sasak H., Wei C.-M., Watkins P., Galli J., RA Hsiung N.; RT "Expression of human uterine tissue-type plasminogen activator in RT mouse cells using BPV vectors."; RL DNA 6:461-472(1987). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal lung; RX MEDLINE=88262579; PubMed=3133640; DOI=10.1093/nar/16.12.5695; RA Sasaki H., Saito Y., Hayashi M., Otsuka K., Niwa M.; RT "Nucleotide sequence of the tissue-type plasminogen activator cDNA RT from human fetal lung cells."; RL Nucleic Acids Res. 16:5695-5695(1988). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Umbilical vein; RX MEDLINE=90192129; PubMed=2107528; DOI=10.1093/nar/18.4.1086; RA Siebert P.D., Fong K.; RT "Variant tissue-type plasminogen activator (PLAT) cDNA obtained from RT human endothelial cells."; RL Nucleic Acids Res. 18:1086-1086(1990). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RA Dou D.; RT "A brain-type plasminogen activator."; RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Liu Y., Xu L., Zeng Y., He X.; RT "cDNA of tissue plasminogen activator."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-34; SER-136; RP THR-146 AND TRP-164. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, Placenta, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36. RX MEDLINE=85289338; PubMed=3161893; RA Fisher R., Waller E.K., Grossi G., Thompson D., Tizard R., RA Schleuning W.-D.; RT "Isolation and characterization of the human tissue-type plasminogen RT activator structural gene including its 5' flanking region."; RL J. Biol. Chem. 260:11223-11230(1985). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-562. RX MEDLINE=91291340; PubMed=1368681; RA Itagaki Y., Yasuda H., Morinaga T., Mitsuda S., Higashio K.; RT "Purification and characterization of tissue plasminogen activator RT secreted by human embryonic lung diploid fibroblasts, IMR-90 cells."; RL Agric. Biol. Chem. 55:1225-1232(1991). RN [17] RP PROTEIN SEQUENCE OF 33-52 AND 311-330. RC TISSUE=Melanoma; RX MEDLINE=83209620; PubMed=6682760; RX DOI=10.1111/j.1432-1033.1983.tb07418.x; RA Wallen P., Pohl G., Bergsdorf N., Raanby M., Ny T., Joernvall H.; RT "Purification and characterization of a melanoma cell plasminogen RT activator."; RL Eur. J. Biochem. 132:681-686(1983). RN [18] RP PROTEIN SEQUENCE OF 36-562. RC TISSUE=Melanoma; RX MEDLINE=85000468; PubMed=6433976; DOI=10.1021/bi00311a020; RA Pohl G., Kaellstroem M., Bergsdorf N., Wallen P., Joernvall H.; RT "Tissue plasminogen activator: peptide analyses confirm an indirectly RT derived amino acid sequence, identify the active site serine residue, RT establish glycosylation sites, and localize variant differences."; RL Biochemistry 23:3701-3707(1984). RN [19] RP NUCLEOTIDE SEQUENCE [MRNA] OF 251-358. RX MEDLINE=83169656; PubMed=6572897; DOI=10.1073/pnas.80.2.349; RA Edlund T., Ny T., Raanby M., Heden L.-O., Palm G., Holmgren E., RA Josephson S.; RT "Isolation of cDNA sequences coding for a part of human tissue RT plasminogen activator."; RL Proc. Natl. Acad. Sci. U.S.A. 80:349-352(1983). RN [20] RP PARTIAL PROTEIN SEQUENCE, AND SIGNAL SEQUENCE CLEAVAGE SITE. RA Jalah R., Pavlakis G.N., Felber B.J.; RL Submitted (JUL-2007) to UniProtKB. RN [21] RP STRUCTURE OF CARBOHYDRATES. RX MEDLINE=90092112; PubMed=2513186; RX DOI=10.1111/j.1432-1033.1989.tb15206.x; RA Pfeiffer G., Schmidt M., Strube K.-H., Geyer R.; RT "Carbohydrate structure of recombinant human uterine tissue RT plasminogen activator expressed in mouse epithelial cells."; RL Eur. J. Biochem. 186:273-286(1989). RN [22] RP GLYCOSYLATION AT THR-96. RX MEDLINE=91159408; PubMed=1900431; DOI=10.1021/bi00223a004; RA Harris R.J., Leonard C.K., Guzzetta A.W., Spellman M.W.; RT "Tissue plasminogen activator has an O-linked fucose attached to RT threonine-61 in the epidermal growth factor domain."; RL Biochemistry 30:2311-2314(1991). RN [23] RP DISULFIDE BONDS IN KRINGLE 2. RX MEDLINE=91244765; PubMed=1645336; RA Vlahos C.J., Wilhelm O.G., Hassell T., Jaskunas S.R., Bang N.U.; RT "Disulfide pairing of the recombinant kringle-2 domain of tissue RT plasminogen activator produced in Escherichia coli."; RL J. Biol. Chem. 266:10070-10072(1991). RN [24] RP INTERACTION WITH LRP1B. RX MEDLINE=21369943; PubMed=11384978; DOI=10.1074/jbc.M102727200; RA Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G.; RT "The putative tumor suppressor LRP1B, a novel member of the low RT density lipoprotein (LDL) receptor family, exhibits both overlapping RT and distinct properties with the LDL receptor-related protein."; RL J. Biol. Chem. 276:28889-28896(2001). RN [25] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [26] RP STRUCTURE BY NMR OF KRINGLE 2. RX MEDLINE=90122799; PubMed=2558718; DOI=10.1021/bi00450a016; RA Byeon I.-J.L., Kelley R.F., Llinas M.; RT "1H NMR structural characterization of a recombinant kringle 2 domain RT from human tissue-type plasminogen activator."; RL Biochemistry 28:9350-9360(1989). RN [27] RP STRUCTURE BY NMR OF KRINGLE 2. RX MEDLINE=91200042; PubMed=1901789; RX DOI=10.1111/j.1432-1033.1991.tb15894.x; RA Byeon I.-J.L., Kelley R.F., Llinas M.; RT "Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR RT assignments and secondary structure."; RL Eur. J. Biochem. 197:155-165(1991). RN [28] RP STRUCTURE BY NMR OF KRINGLE 2. RX MEDLINE=92106329; PubMed=1762144; DOI=10.1016/0022-2836(91)90592-T; RA Byeon I.-J.L., Llinas M.; RT "Solution structure of the tissue-type plasminogen activator kringle 2 RT domain complexed to 6-aminohexanoic acid an antifibrinolytic drug."; RL J. Mol. Biol. 222:1035-1051(1991). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2. RX MEDLINE=92118803; PubMed=1310033; DOI=10.1021/bi00116a037; RA de Vos A., Ultsch M.H., Kelley R.F., Padmanabhan K., Tulinskly A., RA Westbrook M.L., Kossiakof A.A.; RT "Crystal structure of the kringle 2 domain of tissue plasminogen RT activator at 2.4-A resolution."; RL Biochemistry 31:270-279(1992). RN [30] RP STRUCTURE BY NMR OF 38-85. RX MEDLINE=92292163; PubMed=1602484; DOI=10.1016/0022-2836(92)90403-7; RA Downing A.K., Driscoll P.C., Harvey T.S., Dudgeon T.J., Smith B.O., RA Baron M., Campbell I.D.; RT "Solution structure of the fibrin binding finger domain of tissue-type RT plasminogen activator determined by 1H nuclear magnetic resonance."; RL J. Mol. Biol. 225:821-833(1992). RN [31] RP STRUCTURE BY NMR OF 36-126. RX MEDLINE=96027104; PubMed=7582899; DOI=10.1016/S0969-2126(01)00217-9; RA Smith B.O., Downing A.K., Driscoll P.C., Dudgeon T.J., Campbell I.D.; RT "The solution structure and backbone dynamics of the fibronectin type RT I and epidermal growth factor-like pair of modules of tissue-type RT plasminogen activator."; RL Structure 3:823-833(1995). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN. RX MEDLINE=96200985; PubMed=8613982; DOI=10.1006/jmbi.1996.0238; RA Lamba D., Bauer M., Huber R., Fischer S., Rudolph R., Kohnert U., RA Bode W.; RT "The 2.3 A crystal structure of the catalytic domain of recombinant RT two-chain human tissue-type plasminogen activator."; RL J. Mol. Biol. 258:117-135(1996). RN [33] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN. RX MEDLINE=97449126; PubMed=9305622; DOI=10.1093/emboj/16.16.4797; RA Renatus M., Engh R.A., Stubbs M.T., Huber R., Fischer S., Kohnert U., RA Bode W.; RT "Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray RT crystal structure of single-chain human tPA."; RL EMBO J. 16:4797-4805(1997). CC -!- FUNCTION: Converts the abundant, but inactive, zymogen plasminogen CC to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By CC controlling plasmin-mediated proteolysis, it plays an important CC role in tissue remodeling and degradation, in cell migration and CC many other physiopathological events. Play a direct role in CC facilitating neuronal migration. CC -!- CATALYTIC ACTIVITY: Specific cleavage of Arg-|-Val bond in CC plasminogen to form plasmin. CC -!- SUBUNIT: Heterodimer of chain A and chain B held by a disulfide CC bond. Binds to fibrin with high affinity. This interaction leads CC to an increase in the catalytic efficiency of the enzyme between CC 100-fold and 1000-fold, due to an increase in affinity for CC plasminogen. Similarly, binding to heparin increases the CC activation of plasminogen. Binds to annexin A2, cytokeratin-8, CC fibronectin and laminin. Binds to mannose receptor and the low- CC density lipoprotein receptor-related protein (LRP1); these CC proteins are involved in TPA clearance. Yet unidentified CC interactions on endothelial cells and vascular smooth muscle cells CC (VSMC) lead to a 100-fold stimulation of plasminogen activation. CC In addition, binding to VSMC reduces TPA inhibition by PAI-1 by CC 30-fold. Binds LRP1B; binding is followed by internalization and CC degradation. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Long; CC IsoId=P00750-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P00750-2; Sequence=VSP_005411, VSP_005412; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay; CC Name=3; CC IsoId=P00750-3; Sequence=VSP_015957; CC Note=No experimental confirmation available; CC Name=4; Synonyms=Neonatal; CC IsoId=P00750-4; Sequence=VSP_028029, VSP_028030; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Synthesized in numerous tissues (including CC tumors) and secreted into most extracellular body fluids, such as CC plasma, uterine fluid, saliva, gingival crevicular fluid, tears, CC seminal fluid, and milk. CC -!- DOMAIN: Both FN1 and one of the kringle domains are required for CC binding to fibrin. CC -!- DOMAIN: Both FN1 and EGF-like domains are important for binding to CC LRP1. CC -!- DOMAIN: The FN1 domain mediates binding to annexin A2. CC -!- DOMAIN: The second kringle domain is implicated in binding to CC cytokeratin-8 and to the endothelial cell surface binding site. CC -!- PTM: The single chain, almost fully active enzyme, can be further CC processed into a two-chain fully active form by a cleavage after CC Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa. CC -!- PTM: Differential cell-specific N-linked glycosylation gives rise CC to two glycoforms, type I (glycosylated at Asn-219) and type II CC (not glycosylated at Asn-219). The single chain type I glycoform CC is less readily converted into the two-chain form by plasmin, and CC the two-chain type I glycoform has a lower activity than the two- CC chain type II glycoform in the presence of fibrin. CC -!- PTM: N-glycosylation of Asn-152; the bound oligomannosidic glycan CC is involved in the interaction with the mannose receptor. CC -!- PTM: Characterization of O-linked glycan was studied in Bowes CC melanoma cell line. CC -!- DISEASE: Note=Increased activity of TPA results in increased CC fibrinolysis of fibrin blood clots that is associated with CC excessive bleeding. Defective release of TPA results in CC hypofibrinolysis that can lead to thrombosis or embolism. CC -!- PHARMACEUTICAL: Available under the names Activase (Genentech) and CC Retavase (Centocor and Roche) [Retavase is a fragment of TPA that CC contains kringle 2 and the protease domain; it was also known as CC BM 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute CC Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate CC fibrinolysis. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CC -!- SIMILARITY: Contains 1 EGF-like domain. CC -!- SIMILARITY: Contains 1 fibronectin type-I domain. CC -!- SIMILARITY: Contains 2 kringle domains. CC -!- SIMILARITY: Contains 1 peptidase S1 domain. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tissue plasminogen activator CC entry; CC URL="http://en.wikipedia.org/wiki/Tissue_plasminogen_Activator"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/plat/"; CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and CC polymorphism database; CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PLAT"; CC -!- WEB RESOURCE: Name=Activase; Note=Clinical information on CC Activase; CC URL="http://www.gene.com/gene/products/information/cardiovascular/activase/index.jsp"; CC -!- WEB RESOURCE: Name=Retavase; Note=Clinical information on CC Retavase; CC URL="http://www.retavase.com/pdf/Retavase_PI.pdf"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; L00153; AAB59510.1; -; Genomic_DNA. DR EMBL; L00141; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00142; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00143; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00144; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00145; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00146; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00147; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00148; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00149; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00150; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; L00151; AAB59510.1; JOINED; Genomic_DNA. DR EMBL; K03021; AAA98809.1; -; Genomic_DNA. DR EMBL; M15518; AAA60111.1; -; mRNA. DR EMBL; M18182; AAA36800.1; -; mRNA. DR EMBL; X07393; CAA30302.1; -; mRNA. DR EMBL; X13097; CAA31489.1; -; mRNA. DR EMBL; AF260825; AAK11956.1; -; mRNA. DR EMBL; AY221101; AAO34406.1; -; mRNA. DR EMBL; AK289387; BAF82076.1; -; mRNA. DR EMBL; AK290575; BAF83264.1; -; mRNA. DR EMBL; AK313342; BAG36145.1; -; mRNA. DR EMBL; BT007060; AAP35709.1; -; mRNA. DR EMBL; AY291060; AAP34246.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63235.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63233.1; -; Genomic_DNA. DR EMBL; BC002795; AAH02795.3; -; mRNA. DR EMBL; BC007231; AAH07231.1; -; mRNA. DR EMBL; BC013968; AAH13968.3; -; mRNA. DR EMBL; BC018636; AAH18636.3; -; mRNA. DR EMBL; BC095403; AAH95403.1; -; mRNA. DR EMBL; M11890; AAA61213.1; -; Genomic_DNA. DR EMBL; M11889; AAA61213.1; JOINED; Genomic_DNA. DR EMBL; D01096; BAA00881.1; -; mRNA. DR EMBL; V00570; CAA23833.1; -; mRNA. DR IPI; IPI00019590; -. DR IPI; IPI00479511; -. DR IPI; IPI00910450; -. DR IPI; IPI00953228; -. DR PIR; A94004; UKHUT. DR PIR; I38098; I38098. DR RefSeq; NP_000921.1; -. DR RefSeq; NP_127509.1; -. DR UniGene; Hs.491582; -. DR PDB; 1A5H; X-ray; 2.90 A; A/B=311-562, C/D=298-304. DR PDB; 1BDA; X-ray; 3.35 A; A/B=298-562. DR PDB; 1PK2; NMR; -; A=209-298. DR PDB; 1PML; X-ray; 2.38 A; A/B/C=213-298. DR PDB; 1RTF; X-ray; 2.30 A; B=311-562. DR PDB; 1TPG; NMR; -; A=36-126. DR PDB; 1TPK; X-ray; 2.40 A; A/B/C=211-298. DR PDB; 1TPM; NMR; -; A=36-85. DR PDB; 1TPN; NMR; -; A=36-85. DR PDBsum; 1A5H; -. DR PDBsum; 1BDA; -. DR PDBsum; 1PK2; -. DR PDBsum; 1PML; -. DR PDBsum; 1RTF; -. DR PDBsum; 1TPG; -. DR PDBsum; 1TPK; -. DR PDBsum; 1TPM; -. DR PDBsum; 1TPN; -. DR ProteinModelPortal; P00750; -. DR SMR; P00750; 126-210, 174-299, 212-334. DR STRING; P00750; -. DR MEROPS; S01.232; -. DR GlycoSuiteDB; P00750; -. DR PRIDE; P00750; -. DR Ensembl; ENST00000220809; ENSP00000220809; ENSG00000104368. DR GeneID; 5327; -. DR KEGG; hsa:5327; -. DR UCSC; uc003xos.2; human. DR UCSC; uc003xot.2; human. DR UCSC; uc010lxf.1; human. DR CTD; 5327; -. DR GeneCards; GC08M042050; -. DR H-InvDB; HIX0007476; -. DR HGNC; HGNC:9051; PLAT. DR HPA; CAB009335; -. DR HPA; HPA003412; -. DR MIM; 173370; gene. DR PharmGKB; PA33381; -. DR eggNOG; prNOG16610; -. DR HOVERGEN; HBG008633; -. DR InParanoid; P00750; -. DR OMA; TCGLRQY; -. DR OrthoDB; EOG9TQPVK; -. DR PhylomeDB; P00750; -. DR BRENDA; 3.4.21.68; 247. DR Pathway_Interaction_DB; amb2_neutrophils_pathway; amb2 Integrin signaling. DR Reactome; REACT_16888; Signaling by PDGF. DR Reactome; REACT_604; Hemostasis. DR DrugBank; DB00009; Alteplase. DR DrugBank; DB00513; Aminocaproic Acid. DR DrugBank; DB00029; Anistreplase. DR DrugBank; DB01088; Iloprost. DR DrugBank; DB00015; Reteplase. DR DrugBank; DB00031; Tenecteplase. DR DrugBank; DB00302; Tranexamic Acid. DR DrugBank; DB00013; Urokinase. DR NextBio; 20622; -. DR PMAP-CutDB; P00750; -. DR ArrayExpress; P00750; -. DR Bgee; P00750; -. DR Genevestigator; P00750; -. DR GermOnline; ENSG00000104368; Homo sapiens. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell. DR GO; GO:0005515; F:protein binding; IPI:BHF-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL. DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc. DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:BHF-UCL. DR GO; GO:0006464; P:protein modification process; TAS:ProtInc. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR InterPro; IPR016060; Complement_control_module. DR InterPro; IPR006209; EGF. DR InterPro; IPR006210; EGF-like. DR InterPro; IPR013032; EGF-like_reg_CS. DR InterPro; IPR000742; EGF_3. DR InterPro; IPR000083; Fibrnctn1. DR InterPro; IPR000001; Kringle. DR InterPro; IPR013806; Kringle-like. DR InterPro; IPR018056; Kringle_CS. DR InterPro; IPR018114; Peptidase_S1/S6_AS. DR InterPro; IPR001254; Peptidase_S1_S6. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR009003; Ser/Cys_Pept_Trypsin-like. DR Gene3D; G3DSA:2.10.70.10; Complement_control_module; 1. DR Gene3D; G3DSA:2.40.20.10; Kringle; 2. DR Pfam; PF00008; EGF; 1. DR Pfam; PF00039; fn1; 1. DR Pfam; PF00051; Kringle; 2. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00181; EGF; 1. DR SMART; SM00058; FN1; 1. DR SMART; SM00130; KR; 2. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF57440; Kringle-like; 2. DR SUPFAM; SSF50494; Pept_Ser_Cys; 1. DR PROSITE; PS00022; EGF_1; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS01253; FN1_1; 1. DR PROSITE; PS51091; FN1_2; 1. DR PROSITE; PS00021; KRINGLE_1; 2. DR PROSITE; PS50070; KRINGLE_2; 2. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; KW Cleavage on pair of basic residues; Complete proteome; KW Direct protein sequencing; Disulfide bond; EGF-like domain; KW Glycoprotein; Hydrolase; Kringle; Pharmaceutical; KW Plasminogen activation; Polymorphism; Protease; Repeat; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1 22 FT PROPEP 23 32 FT /FTId=PRO_0000028348. FT PROPEP 33 35 Removed by plasmin. FT /FTId=PRO_0000028349. FT CHAIN 36 562 Tissue-type plasminogen activator. FT /FTId=PRO_0000028350. FT CHAIN 36 310 Tissue-type plasminogen activator chain FT A. FT /FTId=PRO_0000028351. FT CHAIN 311 562 Tissue-type plasminogen activator chain FT B. FT /FTId=PRO_0000028352. FT DOMAIN 39 81 Fibronectin type-I. FT DOMAIN 82 120 EGF-like. FT DOMAIN 127 208 Kringle 1. FT DOMAIN 215 296 Kringle 2. FT DOMAIN 311 561 Peptidase S1. FT REGION 42 52 Important for binding to annexin A2. FT ACT_SITE 357 357 Charge relay system. FT ACT_SITE 406 406 Charge relay system. FT ACT_SITE 513 513 Charge relay system. FT SITE 102 102 Important for binding to LRP1. FT SITE 253 253 Not glycosylated. FT SITE 464 464 Important for single-chain activity. FT SITE 512 512 Important for single-chain activity. FT CARBOHYD 96 96 O-linked (Fuc). FT /FTId=CAR_000029. FT CARBOHYD 152 152 N-linked (GlcNAc...). FT CARBOHYD 219 219 N-linked (GlcNAc...); partial. FT /FTId=CAR_000030. FT CARBOHYD 483 483 N-linked (GlcNAc...). FT /FTId=CAR_000031. FT DISULFID 41 71 FT DISULFID 69 78 FT DISULFID 86 97 FT DISULFID 91 108 FT DISULFID 110 119 FT DISULFID 127 208 By similarity. FT DISULFID 148 190 By similarity. FT DISULFID 179 203 By similarity. FT DISULFID 215 296 FT DISULFID 236 278 FT DISULFID 267 291 FT DISULFID 299 430 Interchain (between A and B chains). FT DISULFID 342 358 By similarity. FT DISULFID 350 419 By similarity. FT DISULFID 444 519 By similarity. FT DISULFID 476 492 By similarity. FT DISULFID 509 537 By similarity. FT VAR_SEQ 1 40 MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVI FT -> MAS (in isoform 4). FT /FTId=VSP_028029. FT VAR_SEQ 39 85 VICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCH FT SVPVKS -> G (in isoform 3). FT /FTId=VSP_015957. FT VAR_SEQ 79 208 Missing (in isoform 4). FT /FTId=VSP_028030. FT VAR_SEQ 269 291 NPDGDAKPWCHVLKNRRLTWEYC -> TGRSVSSPATASMR FT PCPLSIRSG (in isoform 2). FT /FTId=VSP_005411. FT VAR_SEQ 292 562 Missing (in isoform 2). FT /FTId=VSP_005412. FT VARIANT 34 34 A -> D (in dbSNP:rs8178733). FT /FTId=VAR_020181. FT VARIANT 136 136 R -> S (in dbSNP:rs8178747). FT /FTId=VAR_038732. FT VARIANT 146 146 A -> T (in dbSNP:rs8178748). FT /FTId=VAR_038733. FT VARIANT 164 164 R -> W (in dbSNP:rs2020921). FT /FTId=VAR_011783. FT CONFLICT 93 93 N -> T (in Ref. 2; AAB59510). FT CONFLICT 159 160 KP -> NA (in Ref. 7; CAA31489). FT CONFLICT 247 247 K -> N (in Ref. 9; AAO34406). FT CONFLICT 283 283 N -> S (in Ref. 14; AAH95403). FT CONFLICT 333 334 RR -> EE (in Ref. 8; AAK11956). FT CONFLICT 389 389 V -> C (in Ref. 8; AAK11956). FT STRAND 44 46 FT STRAND 55 59 FT STRAND 61 64 FT STRAND 66 70 FT STRAND 72 74 FT STRAND 83 85 FT STRAND 96 104 FT STRAND 106 109 FT STRAND 115 118 FT HELIX 242 244 FT STRAND 248 250 FT HELIX 256 259 FT STRAND 262 264 FT STRAND 277 282 FT STRAND 285 291 FT STRAND 312 316 FT HELIX 319 321 FT STRAND 325 331 FT STRAND 338 346 FT STRAND 348 354 FT HELIX 356 359 FT HELIX 365 367 FT STRAND 368 373 FT STRAND 375 379 FT STRAND 385 394 FT TURN 400 402 FT STRAND 408 412 FT STRAND 415 417 FT STRAND 443 449 FT STRAND 464 470 FT HELIX 473 475 FT TURN 478 483 FT STRAND 490 494 FT STRAND 516 521 FT STRAND 524 533 FT STRAND 535 538 FT STRAND 544 548 FT HELIX 549 552 FT HELIX 553 559 SQ SEQUENCE 562 AA; 62917 MW; B7EC9B1A5E3FDC4D CRC64; MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY QQHQSWLRPV LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA LYFSDFVCQC PEGFAGKCCE IDTRATCYED QGISYRGTWS TAESGAECTN WNSSALAQKP YSGRRPDAIR LGLGNHNYCR NPDRDSKPWC YVFKAGKYSS EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN SMILIGKVYT AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC WILSAAHCFQ ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD DTYDNDIALL QLKSDSSRCA QESSVVRTVC LPPADLQLPD WTECELSGYG KHEALSPFYS ERLKEAHVRL YPSSRCTSQH LLNRTVTDNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK DVPGVYTKVT NYLDWIRDNM RP // ID CBBQ_CHRVI Reviewed; 74 AA. AC P56540; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 1. DT 10-AUG-2010, entry version 31. DE RecName: Full=Protein CbbQ; DE Flags: Fragment; GN Name=cbbQ; OS Chromatium vinosum (Allochromatium vinosum). OC Bacteria; Proteobacteria; Gammaproteobacteria; Chromatiales; OC Chromatiaceae; Allochromatium. OX NCBI_TaxID=1049; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=89213919; PubMed=2708310; RA Viale A.M., Kobayashi H., Akazawa T.; RT "Expressed genes for plant-type ribulose 1,5-bisphosphate RT carboxylase/oxygenase in the photosynthetic bacterium Chromatium RT vinosum, which possesses two complete sets of the genes."; RL J. Bacteriol. 171:2391-2400(1989). RN [2] RP IDENTIFICATION. RX MEDLINE=95189107; PubMed=7883189; DOI=10.1016/0378-1119(94)00808-6; RA Yokoyama K., Hayashi N.R., Arai H., Chung S.Y., Igarashi Y., RA Kodama T.; RT "Genes encoding RubisCO in Pseudomonas hydrogenothermophila are RT followed by a novel cbbQ gene similar to nirQ of the denitrification RT gene cluster from Pseudomonas species."; RL Gene 153:75-79(1995). CC -!- FUNCTION: May affect the post-translational activation and/or CC assembly of the oligomeric structure of RuBisCO. CC -!- SIMILARITY: Belongs to the CbbQ/NirQ/NorQ/GpvN family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M26396; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR ProteinModelPortal; P56540; -. DR SMR; P56540; 10-72. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATPase activity; IEA:InterPro. DR InterPro; IPR011704; ATPase_AAA-5. DR Pfam; PF07728; AAA_5; 1. PE 3: Inferred from homology; KW ATP-binding; Nucleotide-binding. FT CHAIN 1 >74 Protein CbbQ. FT /FTId=PRO_0000219562. FT NP_BIND 41 48 ATP (Potential). FT NON_TER 74 74 SQ SEQUENCE 74 AA; 8377 MW; B7AB23BF4DEA291C CRC64; MSDIDRNQFL IDHEPYYRPV SNEVALYEAA YAARMPVMLK GPTGCGKTRF VEYMAWKLGK PLITVACNED MTAS // ID CBBQ_PSEHY Reviewed; 267 AA. AC Q51858; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 10-AUG-2010, entry version 36. DE RecName: Full=Protein CbbQ; GN Name=cbbQ; OS Pseudomonas hydrogenothermophila. OC Bacteria; Proteobacteria; Betaproteobacteria; Hydrogenophilales; OC Hydrogenophilaceae; Hydrogenophilus. OX NCBI_TaxID=297; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=TH-1; RX MEDLINE=95189107; PubMed=7883189; DOI=10.1016/0378-1119(94)00808-6; RA Yokoyama K., Hayashi N.R., Arai H., Chung S.Y., Igarashi Y., RA Kodama T.; RT "Genes encoding RubisCO in Pseudomonas hydrogenothermophila are RT followed by a novel cbbQ gene similar to nirQ of the denitrification RT gene cluster from Pseudomonas species."; RL Gene 153:75-79(1995). CC -!- FUNCTION: May affect the post-translational activation and/or CC assembly of the oligomeric structure of RuBisCO. CC -!- SIMILARITY: Belongs to the CbbQ/NirQ/NorQ/GpvN family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; D30764; BAA06439.1; -; Genomic_DNA. DR ProteinModelPortal; Q51858; -. DR SMR; Q51858; 21-191. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATPase activity; IEA:InterPro. DR InterPro; IPR011704; ATPase_AAA-5. DR InterPro; IPR013615; CbbQ_C. DR Pfam; PF07728; AAA_5; 1. DR Pfam; PF08406; CbbQ_C; 1. PE 3: Inferred from homology; KW ATP-binding; Nucleotide-binding. FT CHAIN 1 267 Protein CbbQ. FT /FTId=PRO_0000219563. FT NP_BIND 39 46 ATP (Potential). FT NP_BIND 99 106 ATP (Potential). SQ SEQUENCE 267 AA; 29613 MW; EA99FE2DB05B0118 CRC64; MDLRNQYLVR SEPYYHAVGD EIERFEAAYA NRIPMMLKGP TGCGKSRFVE YMAWKLGKPL ITVACNEDMT AADLVGRFLL DKEGTRWQDG PLTTAARIGA ICYLDEVVEA RQDTTVVIHP LTDHRRILPL DKKGEVVEAH PDFQIVISYN PGYQSAMKDL KTSTKQRFAA MDFDYPAPEV ESEIVAHESG VDAATAKKLV EVAIRSRHLK GHGLDEGIST RLLVYAGSLI TKGIAPLIAC EMALICPITD DPDLRYALRA AAQTLFA // ID NIRQ_PSEAE Reviewed; 260 AA. AC Q51481; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 10-AUG-2010, entry version 66. DE RecName: Full=Denitrification regulatory protein nirQ; GN Name=nirQ; OrderedLocusNames=PA0520; OS Pseudomonas aeruginosa. OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales; OC Pseudomonadaceae; Pseudomonas. OX NCBI_TaxID=287; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=PAO1161; RX MEDLINE=94362287; PubMed=7765251; RA Arai H., Igarashi Y., Kodama T.; RT "Structure and ANR-dependent transcription of the nir genes for RT denitrification from Pseudomonas aeruginosa."; RL Biosci. Biotechnol. Biochem. 58:1286-1291(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228; RX MEDLINE=20437337; PubMed=10984043; DOI=10.1038/35023079; RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P., RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M., RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y., RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M., RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., RA Reizer J., Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.; RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an RT opportunistic pathogen."; RL Nature 406:959-964(2000). CC -!- FUNCTION: Activator of nitrite and nitric oxide reductases. CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential). CC -!- INDUCTION: Under denitrifying conditions. CC -!- SIMILARITY: Belongs to the CbbQ/NirQ/NorQ/GpvN family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; D37883; BAA07123.1; -; Genomic_DNA. DR EMBL; AE004091; AAG03909.1; -; Genomic_DNA. DR PIR; JC2288; JC2288. DR RefSeq; NP_249211.1; -. DR ProteinModelPortal; Q51481; -. DR SMR; Q51481; 14-183. DR GeneID; 882214; -. DR GenomeReviews; AE004091_GR; PA0520. DR KEGG; pae:PA0520; -. DR NMPDR; fig|208964.1.peg.521; -. DR PseudoCAP; PA0520; -. DR HOGENOM; HBG295312; -. DR OMA; HEARILV; -. DR ProtClustDB; CLSK865916; -. DR BioCyc; PAER208964:PA0520-MONOMER; -. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATPase activity; IEA:InterPro. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0045449; P:regulation of transcription; IEA:UniProtKB-KW. DR GO; GO:0006350; P:transcription; IEA:UniProtKB-KW. DR InterPro; IPR011704; ATPase_AAA-5. DR InterPro; IPR013615; CbbQ_C. DR Pfam; PF07728; AAA_5; 1. DR Pfam; PF08406; CbbQ_C; 1. PE 2: Evidence at transcript level; KW Activator; ATP-binding; Complete proteome; Cytoplasm; DNA-binding; KW Nucleotide-binding; Transcription; Transcription regulation. FT CHAIN 1 260 Denitrification regulatory protein nirQ. FT /FTId=PRO_0000219569. FT NP_BIND 32 39 ATP (Potential). FT NP_BIND 92 99 ATP (Potential). FT DNA_BIND 234 253 H-T-H motif (Potential). SQ SEQUENCE 260 AA; 28904 MW; 3FD36F19BEBA38B5 CRC64; MRDATPFYEA TGHEIEVFER AWRHGLPVLL KGPTGCGKTR FVQYMARRLE LPLYSVACHD DLGAADLLGR HLIGADGTWW QDGPLTRAVR EGGICYLDEV VEARQDTTVA IHPLADDRRE LYLERTGETL QAPPSFMLVV SYNPGYQNLL KGLKPSTRQR FVALRFDYPA AQQEARILVG ESGCAETLAQ RLVQLGQALR RLEQHDLEEV ASTRLLIFAA RLIGDGMDPR EACRVALAEP LSDDPATVAA LMDIVDLHVA // ID CHDH_HUMAN Reviewed; 594 AA. AC Q8NE62; Q9NY17; DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 05-OCT-2010, entry version 72. DE RecName: Full=Choline dehydrogenase, mitochondrial; DE Short=CDH; DE Short=CHD; DE EC=1.1.99.1; DE Flags: Precursor; GN Name=CHDH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-78. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 113-594. RC TISSUE=Kidney; RA Bugert P., Hanke S., Chudek J., Kovacs G.; RT "Analysis of a putative tumor suppressor gene region of 100 kb at RT chromosome 3p21.1 in conventional renal cell carcinoma."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. CC -!- CATALYTIC ACTIVITY: Choline + acceptor = betaine aldehyde + CC reduced acceptor. CC -!- COFACTOR: FAD (By similarity). CC -!- PATHWAY: Amine and polyamine biosynthesis; betaine biosynthesis CC via choline pathway; betaine aldehyde from choline (cytochrome c CC reductase route): step 1/1. CC -!- SUBCELLULAR LOCATION: Mitochondrion (Potential). CC -!- SIMILARITY: Belongs to the GMC oxidoreductase family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AC012467; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC034502; AAH34502.1; -; mRNA. DR EMBL; AJ272267; CAB75961.1; -; mRNA. DR IPI; IPI00168603; -. DR RefSeq; NP_060867.2; -. DR UniGene; Hs.126688; -. DR ProteinModelPortal; Q8NE62; -. DR STRING; Q8NE62; -. DR PhosphoSite; Q8NE62; -. DR Ensembl; ENST00000315251; ENSP00000319851; ENSG00000016391. DR GeneID; 55349; -. DR KEGG; hsa:55349; -. DR UCSC; uc003dgz.1; human. DR CTD; 55349; -. DR GeneCards; GC03M053826; -. DR HGNC; HGNC:24288; CHDH. DR PharmGKB; PA134873121; -. DR eggNOG; prNOG07180; -. DR HOGENOM; HBG734713; -. DR HOVERGEN; HBG023639; -. DR InParanoid; Q8NE62; -. DR OMA; SRDEYSY; -. DR OrthoDB; EOG9962C6; -. DR PhylomeDB; Q8NE62; -. DR BRENDA; 1.1.99.1; 247. DR DrugBank; DB00122; Choline. DR NextBio; 59691; -. DR ArrayExpress; Q8NE62; -. DR Bgee; Q8NE62; -. DR CleanEx; HS_CHDH; -. DR Genevestigator; Q8NE62; -. DR GermOnline; ENSG00000016391; Homo sapiens. DR GO; GO:0008812; F:choline dehydrogenase activity; IEA:EC. DR GO; GO:0050660; F:FAD or FADH2 binding; IEA:InterPro. DR GO; GO:0006066; P:alcohol metabolic process; IEA:InterPro. DR GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW. DR InterPro; IPR012132; GMC_OxRdtase. DR InterPro; IPR000172; GMC_OxRdtase_N. DR InterPro; IPR007867; GMC_OxRtase_C. DR Pfam; PF05199; GMC_oxred_C; 1. DR Pfam; PF00732; GMC_oxred_N; 1. DR PIRSF; PIRSF000137; Alcohol_oxidase; 1. DR PROSITE; PS00623; GMC_OXRED_1; 1. DR PROSITE; PS00624; GMC_OXRED_2; 1. PE 2: Evidence at transcript level; KW Acetylation; Complete proteome; FAD; Flavoprotein; Mitochondrion; KW Oxidoreductase; Polymorphism; Transit peptide. FT TRANSIT 1 ? Mitochondrion (Potential). FT CHAIN ? 594 Choline dehydrogenase, mitochondrial. FT /FTId=PRO_0000012329. FT NP_BIND 42 71 FAD (By similarity). FT ACT_SITE 511 511 By similarity. FT MOD_RES 496 496 N6-acetyllysine (By similarity). FT VARIANT 40 40 E -> A (in dbSNP:rs9001). FT /FTId=VAR_020421. FT VARIANT 78 78 L -> R (in dbSNP:rs12676). FT /FTId=VAR_055097. FT VARIANT 441 441 N -> S (in dbSNP:rs34974961). FT /FTId=VAR_049357. FT CONFLICT 113 113 R -> A (in Ref. 3; CAB75961). SQ SEQUENCE 594 AA; 65358 MW; E9764CD0F325A501 CRC64; MWCLLRGLGR PGALARGALG QQQSLGARAL ASAGSESRDE YSYVVVGAGS AGCVLAGRLT EDPAERVLLL EAGPKDVLAG SKRLSWKIHM PAALVANLCD DRYNWCYHTE VQRGLDGRVL YWPRGRVWGG SSSLNAMVYV RGHAEDYERW QRQGARGWDY AHCLPYFRKA QGHELGASRY RGADGPLRVS RGKTNHPLHC AFLEATQQAG YPLTEDMNGF QQEGFGWMDM TIHEGKRWSA ACAYLHPALS RTNLKAEAET LVSRVLFEGT RAVGVEYVKN GQSHRAYASK EVILSGGAIN SPQLLMLSGI GNADDLKKLG IPVVCHLPGV GQNLQDHLEI YIQQACTRPI TLHSAQKPLR KVCIGLEWLW KFTGEGATAH LETGGFIRSQ PGVPHPDIQF HFLPSQVIDH GRVPTQQEAY QVHVGPMRGT SVGWLKLRSA NPQDHPVIQP NYLSTETDIE DFRLCVKLTR EIFAQEALAP FRGKELQPGS HIQSDKEIDA FVRAKADSAY HPSCTCKMGQ PSDPTAVVDP QTRVLGVENL RVVDASIMPS MVSGNLNAPT IMIAEKAADI IKGQPALWDK DVPVYKPRTL ATQR // ID IVBKI_DENPO Reviewed; 79 AA. AC P00981; Q91351; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2004, sequence version 2. DT 10-AUG-2010, entry version 84. DE RecName: Full=Dendrotoxin-K; DE Short=DTX-K; DE AltName: Full=Venom basic protease inhibitor K; DE Flags: Precursor; Fragment; OS Dendroaspis polylepis polylepis (Black mamba). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Lepidosauria; Squamata; Scleroglossa; Serpentes; Colubroidea; OC Elapidae; Elapinae; Dendroaspis. OX NCBI_TaxID=8620; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 23-39. RX MEDLINE=93277850; PubMed=8504088; DOI=10.1021/bi00072a026; RA Smith L.A., Lafaye P.J., LaPenotiere H.F., Spain T., Dolly J.O.; RT "Cloning and functional expression of dendrotoxin K from black mamba, RT a K+ channel blocker."; RL Biochemistry 32:5692-5697(1993). RN [2] RP PROTEIN SEQUENCE OF 23-79. RC TISSUE=Venom; RX MEDLINE=77158069; PubMed=857902; DOI=10.1016/0005-2795(77)90279-3; RA Strydom D.J.; RT "Snake venom toxins. The amino acid sequence of toxin Vi2, a homologue RT of pancreatic trypsin inhibitor, from Dendroaspis polylepis polylepis RT (black mamba) venom."; RL Biochim. Biophys. Acta 491:361-369(1977). RN [3] RP STRUCTURE BY NMR OF 23-79. RX MEDLINE=94076347; PubMed=8254670; DOI=10.1006/jmbi.1993.1623; RA Berndt K.D., Guentert P., Wuethrich K.; RT "Nuclear magnetic resonance solution structure of dendrotoxin K from RT the venom of Dendroaspis polylepis polylepis."; RL J. Mol. Biol. 234:735-750(1993). CC -!- FUNCTION: This protein is much less toxic to mice than is whole CC venom. It inhibits trypsin slightly, but chymotrypsin not at all. CC It is a highly selective blocker of voltage-gated potassium CC channels. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. CC -!- TOXIC DOSE: LD(50) is 30 mg/kg by intravenous injection. CC -!- SIMILARITY: Contains 1 BPTI/Kunitz inhibitor domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; S61886; AAB26998.1; -; mRNA. DR PIR; A49291; TIEPVK. DR PDB; 1DTK; NMR; -; A=23-79. DR PDBsum; 1DTK; -. DR ProteinModelPortal; P00981; -. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0019870; F:potassium channel inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW. DR InterPro; IPR002223; Prot_inh_Kunz-m. DR InterPro; IPR020901; Prtase_inh_Kunz-CS. DR Gene3D; G3DSA:4.10.410.10; Prot_inh_Kunz-m; 1. DR Pfam; PF00014; Kunitz_BPTI; 1. DR PRINTS; PR00759; BASICPTASE. DR SMART; SM00131; KU; 1. DR SUPFAM; SSF57362; Prot_inh_Kunz-m; 1. DR PROSITE; PS00280; BPTI_KUNITZ_1; 1. DR PROSITE; PS50279; BPTI_KUNITZ_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disulfide bond; KW Ionic channel inhibitor; Neurotoxin; Potassium channel inhibitor; KW Protease inhibitor; Secreted; Serine protease inhibitor; Signal; KW Toxin. FT SIGNAL <1 ? FT PROPEP ? 22 FT /FTId=PRO_0000016869. FT CHAIN 23 79 Dendrotoxin-K. FT /FTId=PRO_0000016870. FT DOMAIN 27 77 BPTI/Kunitz inhibitor. FT SITE 37 38 Reactive bond. FT DISULFID 27 77 By similarity. FT DISULFID 36 60 By similarity. FT DISULFID 52 73 By similarity. FT NON_TER 1 1 FT HELIX 25 28 FT STRAND 35 37 FT STRAND 40 45 FT TURN 47 49 FT STRAND 50 57 FT STRAND 59 61 FT STRAND 67 69 FT HELIX 70 77 SQ SEQUENCE 79 AA; 8852 MW; DCDFB9AFA07D7D46 CRC64; SGHLLLLLGL LTLWAELTPV SGAAKYCKLP LRIGPCKRKI PSFYYKWKAK QCLPFDYSGC GGNANRFKTI EECRRTCVG // ID GRN_HUMAN Reviewed; 593 AA. AC P28799; P23781; P23782; P23783; P23784; Q53Y88; Q540U8; Q9BWE7; AC Q9UCH0; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 2. DT 02-NOV-2010, entry version 120. DE RecName: Full=Granulins; DE AltName: Full=Proepithelin; DE Short=PEPI; DE Contains: DE RecName: Full=Acrogranin; DE Contains: DE RecName: Full=Paragranulin; DE Contains: DE RecName: Full=Granulin-1; DE AltName: Full=Granulin G; DE Contains: DE RecName: Full=Granulin-2; DE AltName: Full=Granulin F; DE Contains: DE RecName: Full=Granulin-3; DE AltName: Full=Granulin B; DE Contains: DE RecName: Full=Granulin-4; DE AltName: Full=Granulin A; DE Contains: DE RecName: Full=Granulin-5; DE AltName: Full=Granulin C; DE Contains: DE RecName: Full=Granulin-6; DE AltName: Full=Granulin D; DE Contains: DE RecName: Full=Granulin-7; DE AltName: Full=Granulin E; DE Flags: Precursor; GN Name=GRN; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION. RX MEDLINE=93038704; PubMed=1417868; DOI=10.1016/0006-291X(92)92349-3; RA Bhandari V., Bateman A.; RT "Structure and chromosomal location of the human granulin gene."; RL Biochem. Biophys. Res. Commun. 188:57-63(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX MEDLINE=92317004; PubMed=1618805; RA Plowman G.D., Green J.M., Neubauer M.G., Buckley S.D., McDonald V.L., RA Todaro G.J., Shoyab M.; RT "The epithelin precursor encodes two proteins with opposing activities RT on epithelial cell growth."; RL J. Biol. Chem. 267:13073-13078(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Bone marrow; RX MEDLINE=92179253; PubMed=1542665; DOI=10.1073/pnas.89.5.1715; RA Bhandari V., Palfree R.G.E., Bateman A.; RT "Isolation and sequence of the granulin precursor cDNA from human bone RT marrow reveals tandem cysteine-rich granulin domains."; RL Proc. Natl. Acad. Sci. U.S.A. 89:1715-1719(1992). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Lu R., Tian C., Serrero G.; RT "PCDGF sequence from lambda phage human Jurkat T cell cDNA library RT (Clontech)."; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Yu W., Gibbs R.A.; RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cervix, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 206-233; 281-336; 364-396 AND 442-447. RC TISSUE=Leukocyte; RX MEDLINE=91097544; PubMed=2268320; DOI=10.1016/S0006-291X(05)80908-8; RA Bateman A., Belcourt D.R., Bennett H.P., Lazure C., Solomon S.; RT "Granulins, a novel class of peptide from leukocytes."; RL Biochem. Biophys. Res. Commun. 173:1161-1168(1990). RN [10] RP PROTEIN SEQUENCE OF 281-295. RX PubMed=8471426; RA Kardana A., Bagshawe K.D., Coles B., Read D., Taylor M.; RT "Characterisation of UGP and its relationship with beta-core RT fragment."; RL Br. J. Cancer 67:686-692(1993). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265, AND MASS RP SPECTROMETRY. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [12] RP STRUCTURE BY NMR OF 284-311. RX PubMed=10715107; DOI=10.1021/bi992130u; RA Tolkatchev D., Ng A., Vranken W., Ni F.; RT "Design and solution structure of a well-folded stack of two beta- RT hairpins based on the amino-terminal fragment of human granulin A."; RL Biochemistry 39:2878-2886(2000). RN [13] RP INVOLVEMENT IN UP-FTD. RX PubMed=16862116; DOI=10.1038/nature05016; RA Baker M., Mackenzie I.R., Pickering-Brown S.M., Gass J., RA Rademakers R., Lindholm C., Snowden J., Adamson J., Sadovnick A.D., RA Rollinson S., Cannon A., Dwosh E., Neary D., Melquist S., RA Richardson A., Dickson D., Berger Z., Eriksen J., Robinson T., RA Zehr C., Dickey C.A., Crook R., McGowan E., Mann D., Boeve B., RA Feldman H., Hutton M.; RT "Mutations in progranulin cause tau-negative frontotemporal dementia RT linked to chromosome 17."; RL Nature 442:916-919(2006). RN [14] RP VARIANT UP-FTD ASP-9. RX PubMed=16983685; DOI=10.1002/ana.20963; RA Mukherjee O., Pastor P., Cairns N.J., Chakraverty S., Kauwe J.S.K., RA Shears S., Behrens M.I., Budde J., Hinrichs A.L., Norton J., RA Levitch D., Taylor-Reinwald L., Gitcho M., Tu P.-H., RA Tenenholz Grinberg L., Liscic R.M., Armendariz J., Morris J.C., RA Goate A.M.; RT "HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin- RT positive, tau-negative inclusions caused by a missense mutation in the RT signal peptide of progranulin."; RL Ann. Neurol. 60:314-322(2006). RN [15] RP CHARACTERIZATION OF VARIANT UP-FTD ASP-9. RX PubMed=18183624; DOI=10.1002/humu.20681; RA Mukherjee O., Wang J., Gitcho M., Chakraverty S., Taylor-Reinwald L., RA Shears S., Kauwe J.S.K., Norton J., Levitch D., Bigio E.H., RA Hatanpaa K.J., White C.L., Morris J.C., Cairns N.J., Goate A.; RT "Molecular characterization of novel progranulin (GRN) mutations in RT frontotemporal dementia."; RL Hum. Mutat. 29:512-521(2008). CC -!- FUNCTION: Granulins have possible cytokine-like activity. They may CC play a role in inflammation, wound repair, and tissue remodeling. CC -!- FUNCTION: Granulin-4 promotes proliferation of the epithelial cell CC line A431 in culture while granulin-3 acts as an antagonist to CC granulin-4, inhibiting the growth. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P28799-1; Sequence=Displayed; CC Name=2; CC IsoId=P28799-2; Sequence=VSP_001837; CC -!- TISSUE SPECIFICITY: In myelogenous leukemic cell lines of CC promonocytic, promyelocytic, and proerythroid lineage, in CC fibroblasts, and very strongly in epithelial cell lines. Present CC in inflammatory cells and bone marrow. Highest levels in kidney. CC -!- PTM: Granulins are disulfide bridged. CC -!- DISEASE: Defects in GRN are the cause of ubiquitin-positive CC frontotemporal dementia (UP-FTD) [MIM:607485]; also known as tau- CC negative frontotemporal dementia linked to chromosome 17. CC Frontotemporal dementia (FTD) is the second most common cause of CC dementia in people under the age of 65 years. It is an autosomal CC dominant neurodegenerative disease. CC -!- SIMILARITY: Belongs to the granulin family. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/GRNID40757ch17q21.html"; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GRN"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X62320; CAA44196.1; -; mRNA. DR EMBL; AF055008; AAC09359.1; -; mRNA. DR EMBL; M75161; AAA58617.1; ALT_SEQ; mRNA. DR EMBL; AY124489; AAM94026.1; -; mRNA. DR EMBL; BT006844; AAP35490.1; -; mRNA. DR EMBL; CH471178; EAW51599.1; -; Genomic_DNA. DR EMBL; BC000324; AAH00324.1; -; mRNA. DR EMBL; BC010577; AAH10577.1; -; mRNA. DR IPI; IPI00182138; -. DR IPI; IPI00296713; -. DR PIR; JC1284; GYHU. DR RefSeq; NP_002078.1; -. DR UniGene; Hs.514220; -. DR PDB; 1G26; NMR; -; A=284-311. DR PDB; 2JYE; NMR; -; A=281-337. DR PDB; 2JYT; NMR; -; A=364-417. DR PDB; 2JYU; NMR; -; A=364-417. DR PDB; 2JYV; NMR; -; A=123-179. DR PDBsum; 1G26; -. DR PDBsum; 2JYE; -. DR PDBsum; 2JYT; -. DR PDBsum; 2JYU; -. DR PDBsum; 2JYV; -. DR ProteinModelPortal; P28799; -. DR SMR; P28799; 206-236. DR IntAct; P28799; 23. DR MINT; MINT-271687; -. DR STRING; P28799; -. DR PRIDE; P28799; -. DR Ensembl; ENST00000053867; ENSP00000053867; ENSG00000030582. DR GeneID; 2896; -. DR KEGG; hsa:2896; -. DR UCSC; uc002igp.1; human. DR CTD; 2896; -. DR GeneCards; GC17P042433; -. DR H-InvDB; HIX0013882; -. DR HGNC; HGNC:4601; GRN. DR HPA; CAB019394; -. DR HPA; HPA008763; -. DR HPA; HPA028747; -. DR MIM; 138945; gene. DR MIM; 607485; phenotype. DR Orphanet; 98929; Frontotemporal dementia with motor neuron-disease type inclusions. DR PharmGKB; PA24626; -. DR eggNOG; prNOG11069; -. DR HOVERGEN; HBG000845; -. DR InParanoid; P28799; -. DR OMA; CCEDRVH; -. DR OrthoDB; EOG9JQ6HG; -. DR PhylomeDB; P28799; -. DR NextBio; 11459; -. DR PMAP-CutDB; P28799; -. DR ArrayExpress; P28799; -. DR Bgee; P28799; -. DR CleanEx; HS_GRN; -. DR Genevestigator; P28799; -. DR GermOnline; ENSG00000030582; Homo sapiens. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0008083; F:growth factor activity; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR InterPro; IPR006150; Cys_repeat_1. DR InterPro; IPR000118; Granulin. DR Pfam; PF00396; Granulin; 7. DR SMART; SM00277; GRAN; 7. DR SMART; SM00289; WR1; 5. DR PROSITE; PS00799; GRANULINS; 7. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Cytokine; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Polymorphism; KW Repeat; Secreted; Signal. FT SIGNAL 1 17 Potential. FT CHAIN 18 593 Acrogranin. FT /FTId=PRO_0000012693. FT PEPTIDE 18 ?47 Paragranulin. FT /FTId=PRO_0000012694. FT PEPTIDE ?58 ?113 Granulin-1. FT /FTId=PRO_0000012695. FT PEPTIDE ?123 ?179 Granulin-2. FT /FTId=PRO_0000012696. FT PEPTIDE 206 261 Granulin-3. FT /FTId=PRO_0000012697. FT PEPTIDE 281 336 Granulin-4. FT /FTId=PRO_0000012698. FT PEPTIDE 364 ?417 Granulin-5. FT /FTId=PRO_0000012699. FT PEPTIDE 442 ?496 Granulin-6. FT /FTId=PRO_0000012700. FT PEPTIDE ?518 ?573 Granulin-7. FT /FTId=PRO_0000012701. FT CARBOHYD 118 118 N-linked (GlcNAc...) (Potential). FT CARBOHYD 236 236 N-linked (GlcNAc...) (Potential). FT CARBOHYD 265 265 N-linked (GlcNAc...). FT CARBOHYD 368 368 N-linked (GlcNAc...). FT CARBOHYD 530 530 N-linked (GlcNAc...) (Potential). FT DISULFID 284 296 FT DISULFID 290 306 FT VAR_SEQ 377 531 Missing (in isoform 2). FT /FTId=VSP_001837. FT VARIANT 9 9 A -> D (in UP-FTD; no significant FT difference in the total mRNA between FT cases and controls; although the mutant FT protein is expressed it is not secreted FT and appears to be trapped within an FT intracellular compartment). FT /FTId=VAR_044451. FT VARIANT 515 515 G -> A (in dbSNP:rs25647). FT /FTId=VAR_014830. FT CONFLICT 219 219 S -> H (in Ref. 9; AA sequence). FT CONFLICT 290 290 C -> S (in Ref. 10; AA sequence). FT CONFLICT 386 386 W -> H (in Ref. 9; AA sequence). FT CONFLICT 454 454 Q -> G (in Ref. 3; AAA58617). FT STRAND 137 141 FT STRAND 143 145 FT STRAND 147 151 FT STRAND 282 285 FT STRAND 288 290 FT STRAND 294 298 FT STRAND 304 308 FT STRAND 315 319 FT TURN 330 333 FT STRAND 377 380 FT STRAND 382 384 FT STRAND 386 389 FT STRAND 409 411 FT TURN 412 414 FT STRAND 415 417 SQ SEQUENCE 593 AA; 63544 MW; 4E5947F1B4EDE619 CRC64; MWTLVSWVAL TAGLVAGTRC PDGQFCPVAC CLDPGGASYS CCRPLLDKWP TTLSRHLGGP CQVDAHCSAG HSCIFTVSGT SSCCPFPEAV ACGDGHHCCP RGFHCSADGR SCFQRSGNNS VGAIQCPDSQ FECPDFSTCC VMVDGSWGCC PMPQASCCED RVHCCPHGAF CDLVHTRCIT PTGTHPLAKK LPAQRTNRAV ALSSSVMCPD ARSRCPDGST CCELPSGKYG CCPMPNATCC SDHLHCCPQD TVCDLIQSKC LSKENATTDL LTKLPAHTVG DVKCDMEVSC PDGYTCCRLQ SGAWGCCPFT QAVCCEDHIH CCPAGFTCDT QKGTCEQGPH QVPWMEKAPA HLSLPDPQAL KRDVPCDNVS SCPSSDTCCQ LTSGEWGCCP IPEAVCCSDH QHCCPQGYTC VAEGQCQRGS EIVAGLEKMP ARRASLSHPR DIGCDQHTSC PVGQTCCPSL GGSWACCQLP HAVCCEDRQH CCPAGYTCNV KARSCEKEVV SAQPATFLAR SPHVGVKDVE CGEGHFCHDN QTCCRDNRQG WACCPYRQGV CCADRRHCCP AGFRCAARGT KCLRREAPRW DAPLRDPALR QLL // ID CEF_BPT4 Reviewed; 71 AA. AC Q01436; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1993, sequence version 1. DT 15-JUN-2010, entry version 37. DE RecName: Full=Protein cef; GN Name=cef; Synonyms=mb; OS Enterobacteria phage T4 (Bacteriophage T4). OC Viruses; dsDNA viruses, no RNA stage; Caudovirales; Myoviridae; OC T4-like viruses. OX NCBI_TaxID=10665; OH NCBI_TaxID=562; Escherichia coli. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=93015705; PubMed=1400206; RA Sanson B., Uzan M.; RT "Sequence and characterization of the bacteriophage T4 comC alpha gene RT product, a possible transcription antitermination factor."; RL J. Bacteriol. 174:6539-6547(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22514363; PubMed=12626685; DOI=10.1128/MMBR.67.1.86-156.2003; RA Miller E.S., Kutter E., Mosig G., Arisaka F., Kunisawa T., Ruger W.; RT "Bacteriophage T4 genome."; RL Microbiol. Mol. Biol. Rev. 67:86-156(2003). CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M89919; AAA32484.1; -; Genomic_DNA. DR EMBL; AF158101; AAD42588.1; -; Genomic_DNA. DR PIR; B45731; B45731. DR RefSeq; NP_049625.1; -. DR GeneID; 1258628; -. DR GenomeReviews; AF158101_GR; T4p011. DR ProtClustDB; CLSP2343268; -. PE 4: Predicted; KW Virus reference strain. FT CHAIN 1 71 Protein cef. FT /FTId=PRO_0000164920. SQ SEQUENCE 71 AA; 8465 MW; 031505CA6FE414FA CRC64; MKRKIVQNCT NDEFEDVLFD PNLVVVQKEH TSKFTHLTSV YVYEKVGDKQ PIYGVFREIT EDGTTYWKEI Y //