CBPB2_HUMAN
ID CBPB2_HUMAN Reviewed; 423 AA.
AC Q96IY4; A8K464; Q15114; Q5T9K1; Q5T9K2; Q9P2Y6;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Carboxypeptidase B2;
DE EC=3.4.17.20 {ECO:0000269|PubMed:10574983};
DE AltName: Full=Carboxypeptidase U;
DE Short=CPU;
DE AltName: Full=Plasma carboxypeptidase B;
DE Short=pCPB;
DE AltName: Full=Thrombin-activable fibrinolysis inhibitor;
DE Short=TAFI;
DE Flags: Precursor;
GN Name=CPB2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE,
RP INTERACTION WITH PLASMINOGEN, AND VARIANTS THR-169 AND THR-347.
RC TISSUE=Liver;
RX PubMed=1939207; DOI=10.1016/s0021-9258(18)54713-x;
RA Eaton D.L., Malloy B.E., Tsai S.P., Henzel W., Drayna D.;
RT "Isolation, molecular cloning, and partial characterization of a novel
RT carboxypeptidase B from human plasma.";
RL J. Biol. Chem. 266:21833-21838(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Matsumoto A.;
RT "Isolation, molecular cloning, and partial characterization of a novel
RT carboxypeptidase B from human plasma.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-347.
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 vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS THR-169
RP AND THR-347.
RC TISSUE=Liver;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-347.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-347.
RC TISSUE=Skeletal muscle;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10574983; DOI=10.1074/jbc.274.49.35046;
RA Mao S.S., Cooper C.M., Wood T., Shafer J.A., Gardell S.J.;
RT "Characterization of plasmin-mediated activation of plasma
RT procarboxypeptidase B. Modulation by glycosaminoglycans.";
RL J. Biol. Chem. 274:35046-35052(1999).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44; ASN-73 AND ASN-108.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [10]
RP GLYCOSYLATION AT ASN-44; ASN-73; ASN-85; ASN-108 AND ASN-241, AND DISULFIDE
RP BONDS.
RX PubMed=16445295; DOI=10.1021/bi051956v;
RA Valnickova Z., Christensen T., Skottrup P., Thogersen I.B., Hojrup P.,
RA Enghild J.J.;
RT "Post-translational modifications of human thrombin-activatable
RT fibrinolysis inhibitor (TAFI): evidence for a large shift in the
RT isoelectric point and reduced solubility upon activation.";
RL Biochemistry 45:1525-1535(2006).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-108.
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 multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP GLYCOSYLATION AT ASN-108, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 24-423 ALONE AND IN COMPLEX WITH
RP ZINC IONS AND INHIBITOR, GLYCOSYLATION AT ASN-44; ASN-73; ASN-85 AND
RP ASN-108, ZINC-BINDING SITES, COFACTOR, ACTIVITY REGULATION, AND DISULFIDE
RP BONDS.
RX PubMed=18559974; DOI=10.1182/blood-2008-03-146001;
RA Marx P.F., Brondijk T.H., Plug T., Romijn R.A., Hemrika W., Meijers J.C.,
RA Huizinga E.G.;
RT "Crystal structures of TAFI elucidate the inactivation mechanism of
RT activated TAFI: a novel mechanism for enzyme autoregulation.";
RL Blood 112:2803-2809(2008).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 115-423 IN COMPLEX WITH ZINC AND
RP INHIBITOR, DISULFIDE BONDS, AND COFACTOR.
RX PubMed=20088943; DOI=10.1111/j.1538-7836.2010.03740.x;
RA Sanglas L., Arolas J.L., Valnickova Z., Aviles F.X., Enghild J.J.,
RA Gomis-Ruth F.X.;
RT "Insights into the molecular inactivation mechanism of human activated
RT thrombin-activatable fibrinolysis inhibitor.";
RL J. Thromb. Haemost. 8:1056-1065(2010).
CC -!- FUNCTION: Cleaves C-terminal arginine or lysine residues from
CC biologically active peptides such as kinins or anaphylatoxins in the
CC circulation thereby regulating their activities. Down-regulates
CC fibrinolysis by removing C-terminal lysine residues from fibrin that
CC has already been partially degraded by plasmin.
CC {ECO:0000269|PubMed:10574983}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of C-terminal Arg and Lys from a polypeptide.;
CC EC=3.4.17.20; Evidence={ECO:0000269|PubMed:10574983};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18559974, ECO:0000269|PubMed:20088943};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18559974,
CC ECO:0000269|PubMed:20088943};
CC -!- ACTIVITY REGULATION: TAFI/CPB2 is unique among carboxypeptidases in
CC that it spontaneously inactivates with a short half-life, a property
CC that is crucial for its role in controlling blood clot lysis. The
CC zymogen is stabilized by interactions with the activation peptide.
CC Release of the activation peptide increases a dynamic flap mobility and
CC in time this leads to conformational changes that disrupt the catalytic
CC site and expose a cryptic thrombin-cleavage site present at Arg-324.
CC {ECO:0000269|PubMed:18559974}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96IY4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96IY4-2; Sequence=VSP_013446, VSP_013447;
CC -!- TISSUE SPECIFICITY: Plasma; synthesized in the liver.
CC -!- PTM: N-glycosylated. N-glycan at Asn-108: Hex5HexNAc4.
CC {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16445295,
CC ECO:0000269|PubMed:18559974, ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:22171320}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cpb2/";
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DR EMBL; M75106; AAA60042.1; -; mRNA.
DR EMBL; AB011969; BAA90475.1; -; mRNA.
DR EMBL; BT006936; AAP35582.1; -; mRNA.
DR EMBL; AK290829; BAF83518.1; -; mRNA.
DR EMBL; AY714780; AAT97987.1; -; Genomic_DNA.
DR EMBL; AL137141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157758; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007057; AAH07057.1; -; mRNA.
DR CCDS; CCDS9401.1; -. [Q96IY4-1]
DR PIR; A41204; A41204.
DR RefSeq; NP_001265470.1; NM_001278541.1.
DR RefSeq; NP_001863.3; NM_001872.4. [Q96IY4-1]
DR PDB; 3D66; X-ray; 3.10 A; A/B/C=24-423.
DR PDB; 3D67; X-ray; 3.40 A; A/B/C=24-423.
DR PDB; 3D68; X-ray; 2.80 A; A/B/C=24-423.
DR PDB; 3LMS; X-ray; 2.50 A; A=115-423.
DR PDB; 4P10; X-ray; 2.00 A; A=23-423.
DR PDB; 5HVF; X-ray; 2.85 A; A=23-423.
DR PDB; 5HVG; X-ray; 3.05 A; A/C=23-423.
DR PDB; 5HVH; X-ray; 3.00 A; A=23-423.
DR PDB; 7NEE; X-ray; 2.55 A; A=24-423.
DR PDB; 7NEU; X-ray; 2.80 A; A=24-423.
DR PDBsum; 3D66; -.
DR PDBsum; 3D67; -.
DR PDBsum; 3D68; -.
DR PDBsum; 3LMS; -.
DR PDBsum; 4P10; -.
DR PDBsum; 5HVF; -.
DR PDBsum; 5HVG; -.
DR PDBsum; 5HVH; -.
DR PDBsum; 7NEE; -.
DR PDBsum; 7NEU; -.
DR AlphaFoldDB; Q96IY4; -.
DR SMR; Q96IY4; -.
DR BioGRID; 107753; 7.
DR IntAct; Q96IY4; 1.
DR STRING; 9606.ENSP00000181383; -.
DR BindingDB; Q96IY4; -.
DR ChEMBL; CHEMBL3419; -.
DR DrugBank; DB05712; AZD-9684.
DR DrugBank; DB11311; Prothrombin.
DR GuidetoPHARMACOLOGY; 1594; -.
DR MEROPS; M14.009; -.
DR GlyConnect; 699; 16 N-Linked glycans (3 sites).
DR GlyGen; Q96IY4; 5 sites, 19 N-linked glycans (3 sites).
DR iPTMnet; Q96IY4; -.
DR PhosphoSitePlus; Q96IY4; -.
DR BioMuta; CPB2; -.
DR DMDM; 317373332; -.
DR CPTAC; CPTAC-657; -.
DR CPTAC; non-CPTAC-2639; -.
DR jPOST; Q96IY4; -.
DR MassIVE; Q96IY4; -.
DR PaxDb; Q96IY4; -.
DR PeptideAtlas; Q96IY4; -.
DR PRIDE; Q96IY4; -.
DR ProteomicsDB; 76868; -. [Q96IY4-1]
DR ProteomicsDB; 76869; -. [Q96IY4-2]
DR ABCD; Q96IY4; 2 sequenced antibodies.
DR Antibodypedia; 1324; 624 antibodies from 35 providers.
DR DNASU; 1361; -.
DR Ensembl; ENST00000181383.10; ENSP00000181383.4; ENSG00000080618.17. [Q96IY4-1]
DR GeneID; 1361; -.
DR KEGG; hsa:1361; -.
DR MANE-Select; ENST00000181383.10; ENSP00000181383.4; NM_001872.5; NP_001863.3.
DR UCSC; uc001vaw.4; human. [Q96IY4-1]
DR CTD; 1361; -.
DR DisGeNET; 1361; -.
DR GeneCards; CPB2; -.
DR HGNC; HGNC:2300; CPB2.
DR HPA; ENSG00000080618; Tissue enriched (liver).
DR MIM; 603101; gene.
DR neXtProt; NX_Q96IY4; -.
DR OpenTargets; ENSG00000080618; -.
DR PharmGKB; PA26822; -.
DR VEuPathDB; HostDB:ENSG00000080618; -.
DR eggNOG; KOG2650; Eukaryota.
DR GeneTree; ENSGT00940000159160; -.
DR HOGENOM; CLU_019326_0_0_1; -.
DR InParanoid; Q96IY4; -.
DR OMA; WPYGYDC; -.
DR OrthoDB; 524270at2759; -.
DR PhylomeDB; Q96IY4; -.
DR TreeFam; TF317197; -.
DR BRENDA; 3.4.17.20; 2681.
DR PathwayCommons; Q96IY4; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; Q96IY4; -.
DR BioGRID-ORCS; 1361; 9 hits in 1065 CRISPR screens.
DR ChiTaRS; CPB2; human.
DR EvolutionaryTrace; Q96IY4; -.
DR GeneWiki; Carboxypeptidase_B2; -.
DR GenomeRNAi; 1361; -.
DR Pharos; Q96IY4; Tchem.
DR PRO; PR:Q96IY4; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q96IY4; protein.
DR Bgee; ENSG00000080618; Expressed in right lobe of liver and 88 other tissues.
DR ExpressionAtlas; Q96IY4; baseline and differential.
DR Genevisible; Q96IY4; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0042730; P:fibrinolysis; IBA:GO_Central.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0051918; P:negative regulation of fibrinolysis; IEA:Ensembl.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:0010757; P:negative regulation of plasminogen activation; IEA:Ensembl.
DR GO; GO:0003331; P:positive regulation of extracellular matrix constituent secretion; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR CDD; cd06246; M14_CPB2; 1.
DR Gene3D; 3.30.70.340; -; 1.
DR InterPro; IPR033849; CPB2.
DR InterPro; IPR036990; M14A-like_propep.
DR InterPro; IPR003146; M14A_act_pep.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF00246; Peptidase_M14; 1.
DR Pfam; PF02244; Propep_M14; 1.
DR PRINTS; PR00765; CRBOXYPTASEA.
DR SMART; SM00631; Zn_pept; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood coagulation; Carboxypeptidase;
KW Direct protein sequencing; Disulfide bond; Fibrinolysis; Glycoprotein;
KW Hemostasis; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..114
FT /note="Activation peptide"
FT /id="PRO_0000004377"
FT CHAIN 115..423
FT /note="Carboxypeptidase B2"
FT /id="PRO_0000004378"
FT ACT_SITE 385
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00732"
FT BINDING 181..184
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18559974,
FT ECO:0000269|PubMed:20088943"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18559974,
FT ECO:0000269|PubMed:20088943"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 256..257
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18559974,
FT ECO:0000269|PubMed:20088943"
FT BINDING 311..312
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 363
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT SITE 324..325
FT /note="Cleavage; by thrombin"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:16445295, ECO:0000269|PubMed:18559974"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:16445295, ECO:0000269|PubMed:18559974"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16445295,
FT ECO:0000269|PubMed:18559974"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:16445295, ECO:0000269|PubMed:18559974,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22171320"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:16445295"
FT DISULFID 178..191
FT /evidence="ECO:0000269|PubMed:18559974,
FT ECO:0000269|PubMed:20088943"
FT DISULFID 250..274
FT /evidence="ECO:0000269|PubMed:18559974,
FT ECO:0000269|PubMed:20088943"
FT DISULFID 265..279
FT /evidence="ECO:0000269|PubMed:18559974,
FT ECO:0000269|PubMed:20088943"
FT VAR_SEQ 198..234
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_013446"
FT VAR_SEQ 384..423
FT /note="IELRDTGTYGFLLPERYIKPTCREAFAAVSKIAWHVIRNV -> SNPPVEKL
FT LPLSLK (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_013447"
FT VARIANT 169
FT /note="A -> T (in dbSNP:rs3742264)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:1939207"
FT /id="VAR_032565"
FT VARIANT 347
FT /note="I -> T (in dbSNP:rs1926447)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1939207,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5"
FT /id="VAR_022258"
FT CONFLICT 25
FT /note="S -> T (in Ref. 2; BAA90475)"
FT /evidence="ECO:0000305"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 36..48
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 51..58
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 77..87
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 98..107
FT /evidence="ECO:0007829|PDB:4P10"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 117..121
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:4P10"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 144..151
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:7NEE"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 186..201
FT /evidence="ECO:0007829|PDB:4P10"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 206..214
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:4P10"
FT TURN 262..265
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 287..298
FT /evidence="ECO:0007829|PDB:4P10"
FT TURN 299..302
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 303..319
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 321..325
FT /evidence="ECO:0007829|PDB:3LMS"
FT HELIX 330..347
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:7NEE"
FT STRAND 354..358
FT /evidence="ECO:0007829|PDB:4P10"
FT TURN 359..362
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 369..374
FT /evidence="ECO:0007829|PDB:4P10"
FT TURN 375..377
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 380..387
FT /evidence="ECO:0007829|PDB:4P10"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:3D68"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:4P10"
FT HELIX 401..422
FT /evidence="ECO:0007829|PDB:4P10"
SQ SEQUENCE 423 AA; 48424 MW; B4D20E03ECDD55EF CRC64;
MKLCSLAVLV PIVLFCEQHV FAFQSGQVLA ALPRTSRQVQ VLQNLTTTYE IVLWQPVTAD
LIVKKKQVHF FVNASDVDNV KAHLNVSGIP CSVLLADVED LIQQQISNDT VSPRASASYY
EQYHSLNEIY SWIEFITERH PDMLTKIHIG SSFEKYPLYV LKVSGKEQAA KNAIWIDCGI
HAREWISPAF CLWFIGHITQ FYGIIGQYTN LLRLVDFYVM PVVNVDGYDY SWKKNRMWRK
NRSFYANNHC IGTDLNRNFA SKHWCEEGAS SSSCSETYCG LYPESEPEVK AVASFLRRNI
NQIKAYISMH SYSQHIVFPY SYTRSKSKDH EELSLVASEA VRAIEKISKN TRYTHGHGSE
TLYLAPGGGD DWIYDLGIKY SFTIELRDTG TYGFLLPERY IKPTCREAFA AVSKIAWHVI
RNV
