ID   ATS12_HUMAN             Reviewed;        1594 AA.
AC   P58397; A2RRN9; A5D6V6; Q6UWL3;
DT   16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT   22-SEP-2009, sequence version 2.
DT   27-MAR-2024, entry version 204.
DE   RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 12;
DE            Short=ADAM-TS 12;
DE            Short=ADAM-TS12;
DE            Short=ADAMTS-12;
DE            EC=3.4.24.-;
DE   Flags: Precursor;
GN   Name=ADAMTS12; ORFNames=UNQ1918/PRO4389;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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   [4]
RP   RETRACTED PAPER.
RC   TISSUE=Fetal lung;
RX   PubMed=11279086; DOI=10.1074/jbc.m100534200;
RA   Cal S., Argueelles J.M., Fernandez P.L., Lopez-Otin C.;
RT   "Identification, characterization, and intracellular processing of ADAM-
RT   TS12, a novel human disintegrin with a complex structural organization
RT   involving multiple thrombospondin-1 repeats.";
RL   J. Biol. Chem. 276:17932-17940(2001).
RN   [5]
RP   RETRACTION NOTICE OF PUBMED:11279086.
RX   PubMed=30808000; DOI=10.1074/jbc.w118.007323;
RA   Cal S., Argueelles J.M., Fernandez P.L., Lopez-Otin C.;
RL   J. Biol. Chem. 294:1429-1429(2019).
RN   [6]
RP   FUNCTION, INTERACTION WITH COMP, PH DEPENDENCE, TISSUE SPECIFICITY, AND
RP   INDUCTION.
RX   PubMed=16611630; DOI=10.1074/jbc.m513433200;
RA   Liu C.-J., Kong W., Xu K., Luan Y., Ilalov K., Sehgal B., Yu S.,
RA   Howell R.D., Di Cesare P.E.;
RT   "ADAMTS-12 associates with and degrades cartilage oligomeric matrix
RT   protein.";
RL   J. Biol. Chem. 281:15800-15808(2006).
RN   [7]
RP   FUNCTION.
RX   PubMed=17895370; DOI=10.1242/jcs.005751;
RA   Llamazares M., Obaya A.J., Moncada-Pazos A., Heljasvaara R., Espada J.,
RA   Lopez-Otin C., Cal S.;
RT   "The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties
RT   through modulation of the Ras-dependent ERK signalling pathway.";
RL   J. Cell Sci. 120:3544-3552(2007).
RN   [8]
RP   FUNCTION, ACTIVITY REGULATION, AND INDUCTION.
RX   PubMed=18485748; DOI=10.1016/j.joca.2008.03.017;
RA   Luan Y., Kong L., Howell D.R., Ilalov K., Fajardo M., Bai X.-H.,
RA   Di Cesare P.E., Goldring M.B., Abramson S.B., Liu C.-J.;
RT   "Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric
RT   matrix protein by alpha-2-macroglobulin.";
RL   Osteoarthritis Cartilage 16:1413-1420(2008).
CC   -!- FUNCTION: Metalloprotease that may play a role in the degradation of
CC       COMP. Cleaves also alpha-2 macroglobulin and aggregan. Has anti-
CC       tumorigenic properties. {ECO:0000269|PubMed:16611630,
CC       ECO:0000269|PubMed:17895370, ECO:0000269|PubMed:18485748}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Inhibited by alpha-2 macroglobulin.
CC       {ECO:0000269|PubMed:18485748}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is between 7.5 and 9.5 with COMP for substrate.
CC         {ECO:0000269|PubMed:16611630};
CC   -!- SUBUNIT: Interacts with COMP. {ECO:0000269|PubMed:16611630}.
CC   -!- INTERACTION:
CC       P58397; B4DJ51: CALM1; NbExp=3; IntAct=EBI-9028051, EBI-10171450;
CC       P58397; P49747: COMP; NbExp=3; IntAct=EBI-9028051, EBI-2531022;
CC       P58397; P50222: MEOX2; NbExp=3; IntAct=EBI-9028051, EBI-748397;
CC       P58397; P60660: MYL6; NbExp=4; IntAct=EBI-9028051, EBI-300817;
CC       P58397; Q9R0G6: Comp; Xeno; NbExp=3; IntAct=EBI-9028051, EBI-9028018;
CC       P58397-3; P38432: COIL; NbExp=3; IntAct=EBI-12048761, EBI-945751;
CC       P58397-3; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-12048761, EBI-8638439;
CC       P58397-3; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-12048761, EBI-11952721;
CC       P58397-3; Q14142: TRIM14; NbExp=3; IntAct=EBI-12048761, EBI-2820256;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P58397-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P58397-2; Sequence=VSP_013141, VSP_013142;
CC       Name=3;
CC         IsoId=P58397-3; Sequence=VSP_038151;
CC   -!- TISSUE SPECIFICITY: Expressed in skeletal muscle and fat.
CC       {ECO:0000269|PubMed:16611630}.
CC   -!- INDUCTION: By IFN-alpha and by IL1B/interleukin-1 beta. Up-regulated in
CC       articular cartilage and synovium from arthritis patients. Up-regulared
CC       in chondrocytes. {ECO:0000269|PubMed:16611630,
CC       ECO:0000269|PubMed:18485748}.
CC   -!- DOMAIN: The spacer domain and the TSP type-1 domains are important for
CC       a tight interaction with the extracellular matrix. {ECO:0000250}.
CC   -!- DOMAIN: The C-terminal four TSP1-like repeats are necessary and
CC       sufficient for binding COMP.
CC   -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC       binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC       dissociation of the cysteine from the zinc ion upon the activation-
CC       peptide release activates the enzyme.
CC   -!- PTM: The precursor is cleaved by a furin endopeptidase.
CC   -!- PTM: Subjected to an intracellular maturation process yielding a 120
CC       kDa N-terminal fragment containing the metalloproteinase, disintegrin,
CC       one TSP type-1 and the Cys-rich domains and a 83 kDa C-terminal
CC       fragment containing the spacer 2 and four TSP type-1 domains.
CC   -!- PTM: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a
CC       threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-
CC       G of the TSP type-1 repeat domains where C1 and C2 are the first and
CC       second cysteine residue of the repeat, respectively. Fucosylated
CC       repeats can then be further glycosylated by the addition of a beta-1,3-
CC       glucose residue by the glucosyltransferase, B3GALTL. Fucosylation
CC       mediates the efficient secretion of ADAMTS family members. Can also be
CC       C-glycosylated with one or two mannose molecules on tryptophan residues
CC       within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated.
CC       These other glycosylations can also facilitate secretion (By
CC       similarity). {ECO:0000250}.
CC   -!- CAUTION: Was reported to be expressed in adult skeletal muscle and fat,
CC       in fetal lung, and in gastric carcinomas and cancer cells of diverse
CC       origin (PubMed:11279086). However, this paper has been retracted
CC       because data in one figure has been falsified (PubMed:30808000).
CC       {ECO:0000269|PubMed:11279086, ECO:0000269|PubMed:30808000}.
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DR   EMBL; AJ250725; CAC20419.1; -; mRNA.
DR   EMBL; AY358745; AAQ89105.1; -; mRNA.
DR   EMBL; AC008880; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC034232; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC109491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC139777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC058841; AAH58841.1; -; mRNA.
DR   EMBL; BC131733; AAI31734.1; -; mRNA.
DR   EMBL; BC139900; AAI39901.1; -; mRNA.
DR   CCDS; CCDS34140.1; -. [P58397-1]
DR   CCDS; CCDS87293.1; -. [P58397-3]
DR   RefSeq; NP_001311440.1; NM_001324511.1.
DR   RefSeq; NP_001311441.1; NM_001324512.1. [P58397-3]
DR   RefSeq; NP_112217.2; NM_030955.3. [P58397-1]
DR   AlphaFoldDB; P58397; -.
DR   SMR; P58397; -.
DR   BioGRID; 123584; 50.
DR   IntAct; P58397; 18.
DR   STRING; 9606.ENSP00000422554; -.
DR   MEROPS; M12.237; -.
DR   GlyConnect; 996; 5 N-Linked glycans (3 sites).
DR   GlyCosmos; P58397; 15 sites, 6 glycans.
DR   GlyGen; P58397; 15 sites, 5 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; P58397; -.
DR   PhosphoSitePlus; P58397; -.
DR   BioMuta; ADAMTS12; -.
DR   DMDM; 259016182; -.
DR   CPTAC; CPTAC-2207; -.
DR   MassIVE; P58397; -.
DR   PaxDb; 9606-ENSP00000422554; -.
DR   PeptideAtlas; P58397; -.
DR   ProteomicsDB; 57068; -. [P58397-1]
DR   ProteomicsDB; 57069; -. [P58397-2]
DR   ProteomicsDB; 57070; -. [P58397-3]
DR   Pumba; P58397; -.
DR   Antibodypedia; 22743; 158 antibodies from 23 providers.
DR   DNASU; 81792; -.
DR   Ensembl; ENST00000352040.7; ENSP00000344847.3; ENSG00000151388.11. [P58397-3]
DR   Ensembl; ENST00000504830.6; ENSP00000422554.1; ENSG00000151388.11. [P58397-1]
DR   GeneID; 81792; -.
DR   KEGG; hsa:81792; -.
DR   MANE-Select; ENST00000504830.6; ENSP00000422554.1; NM_030955.4; NP_112217.2.
DR   UCSC; uc003jia.3; human. [P58397-1]
DR   AGR; HGNC:14605; -.
DR   CTD; 81792; -.
DR   DisGeNET; 81792; -.
DR   GeneCards; ADAMTS12; -.
DR   HGNC; HGNC:14605; ADAMTS12.
DR   HPA; ENSG00000151388; Low tissue specificity.
DR   MIM; 606184; gene.
DR   neXtProt; NX_P58397; -.
DR   OpenTargets; ENSG00000151388; -.
DR   PharmGKB; PA24538; -.
DR   VEuPathDB; HostDB:ENSG00000151388; -.
DR   eggNOG; KOG3538; Eukaryota.
DR   GeneTree; ENSGT00940000155855; -.
DR   HOGENOM; CLU_000660_2_1_1; -.
DR   InParanoid; P58397; -.
DR   OMA; HCNNPEP; -.
DR   OrthoDB; 2910701at2759; -.
DR   PhylomeDB; P58397; -.
DR   TreeFam; TF313537; -.
DR   PathwayCommons; P58397; -.
DR   Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR   Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR   SignaLink; P58397; -.
DR   BioGRID-ORCS; 81792; 14 hits in 1144 CRISPR screens.
DR   ChiTaRS; ADAMTS12; human.
DR   GeneWiki; ADAMTS12; -.
DR   GenomeRNAi; 81792; -.
DR   Pharos; P58397; Tbio.
DR   PRO; PR:P58397; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P58397; Protein.
DR   Bgee; ENSG00000151388; Expressed in adrenal tissue and 121 other cell types or tissues.
DR   ExpressionAtlas; P58397; baseline and differential.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IDA:BHF-UCL.
DR   GO; GO:0016477; P:cell migration; IMP:BHF-UCL.
DR   GO; GO:0007160; P:cell-matrix adhesion; IMP:BHF-UCL.
DR   GO; GO:0071773; P:cellular response to BMP stimulus; IDA:BHF-UCL.
DR   GO; GO:0071347; P:cellular response to interleukin-1; IMP:BHF-UCL.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL.
DR   GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:2001113; P:negative regulation of cellular response to hepatocyte growth factor stimulus; IDA:BHF-UCL.
DR   GO; GO:1902548; P:negative regulation of cellular response to vascular endothelial growth factor stimulus; IDA:BHF-UCL.
DR   GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IDA:BHF-UCL.
DR   GO; GO:1902203; P:negative regulation of hepatocyte growth factor receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0043931; P:ossification involved in bone maturation; IEA:Ensembl.
DR   GO; GO:0030167; P:proteoglycan catabolic process; IDA:BHF-UCL.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL.
DR   GO; GO:1901509; P:regulation of endothelial tube morphogenesis; IDA:BHF-UCL.
DR   GO; GO:0050727; P:regulation of inflammatory response; IDA:BHF-UCL.
DR   CDD; cd04273; ZnMc_ADAMTS_like; 1.
DR   Gene3D; 2.60.120.830; -; 1.
DR   Gene3D; 3.40.1620.60; -; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 8.
DR   InterPro; IPR013273; ADAMTS/ADAMTS-like.
DR   InterPro; IPR041645; ADAMTS_CR_2.
DR   InterPro; IPR045371; ADAMTS_CR_3.
DR   InterPro; IPR010294; ADAMTS_spacer1.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001590; Peptidase_M12B.
DR   InterPro; IPR002870; Peptidase_M12B_N.
DR   InterPro; IPR010909; PLAC.
DR   InterPro; IPR000884; TSP1_rpt.
DR   InterPro; IPR036383; TSP1_rpt_sf.
DR   PANTHER; PTHR13723:SF189; A DISINTEGRIN AND METALLOPROTEINASE WITH THROMBOSPONDIN MOTIFS 12; 1.
DR   PANTHER; PTHR13723; ADAMTS A DISINTEGRIN AND METALLOPROTEASE WITH THROMBOSPONDIN MOTIFS PROTEASE; 1.
DR   Pfam; PF17771; ADAMTS_CR_2; 1.
DR   Pfam; PF19236; ADAMTS_CR_3; 1.
DR   Pfam; PF05986; ADAMTS_spacer1; 1.
DR   Pfam; PF01562; Pep_M12B_propep; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   Pfam; PF19030; TSP1_ADAMTS; 7.
DR   Pfam; PF00090; TSP_1; 1.
DR   PRINTS; PR01857; ADAMTSFAMILY.
DR   SMART; SM00209; TSP1; 8.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF82895; TSP-1 type 1 repeat; 8.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS50900; PLAC; 1.
DR   PROSITE; PS50092; TSP1; 6.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; P58397; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cleavage on pair of basic residues; Disulfide bond;
KW   Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding;
KW   Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW   Zinc; Zymogen.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..240
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000029186"
FT   CHAIN           241..1594
FT                   /note="A disintegrin and metalloproteinase with
FT                   thrombospondin motifs 12"
FT                   /id="PRO_0000029187"
FT   DOMAIN          246..456
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          465..544
FT                   /note="Disintegrin"
FT   DOMAIN          542..597
FT                   /note="TSP type-1 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          823..883
FT                   /note="TSP type-1 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          887..943
FT                   /note="TSP type-1 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          944..997
FT                   /note="TSP type-1 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          1313..1366
FT                   /note="TSP type-1 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          1368..1422
FT                   /note="TSP type-1 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          1423..1471
FT                   /note="TSP type-1 7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          1472..1532
FT                   /note="TSP type-1 8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          1535..1575
FT                   /note="PLAC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT   REGION          701..827
FT                   /note="Spacer 1"
FT   REGION          997..1316
FT                   /note="Spacer 2"
FT   REGION          1002..1076
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1095..1174
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1249..1283
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           208..213
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        1002..1016
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1017..1031
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1032..1076
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1095..1144
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1155..1174
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1260..1283
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        393
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         208
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /note="in inhibited form"
FT                   /evidence="ECO:0000250"
FT   BINDING         392
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         396
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         402
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        105
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        125
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        215
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        485
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        685
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        790
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        952
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1105
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1276
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1301
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1321
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1372
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1379
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1504
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        322..376
FT                   /evidence="ECO:0000250"
FT   DISULFID        351..358
FT                   /evidence="ECO:0000250"
FT   DISULFID        370..451
FT                   /evidence="ECO:0000250"
FT   DISULFID        409..435
FT                   /evidence="ECO:0000250"
FT   DISULFID        478..501
FT                   /evidence="ECO:0000250"
FT   DISULFID        489..507
FT                   /evidence="ECO:0000250"
FT   DISULFID        496..526
FT                   /evidence="ECO:0000250"
FT   DISULFID        520..531
FT                   /evidence="ECO:0000250"
FT   DISULFID        554..591
FT                   /evidence="ECO:0000250"
FT   DISULFID        558..596
FT                   /evidence="ECO:0000250"
FT   DISULFID        569..581
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         212..229
FT                   /note="DSVNISQKQELWREKWER -> GIVTHMSSWVEESVLFFW (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:12975309,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013141"
FT   VAR_SEQ         230..1594
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12975309,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013142"
FT   VAR_SEQ         630..714
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_038151"
FT   VARIANT         110
FT                   /note="Q -> E (in dbSNP:rs16891862)"
FT                   /id="VAR_057074"
FT   VARIANT         1000
FT                   /note="R -> Q (in dbSNP:rs13362345)"
FT                   /id="VAR_057075"
FT   VARIANT         1177
FT                   /note="W -> R (in dbSNP:rs3813474)"
FT                   /id="VAR_059761"
FT   VARIANT         1495
FT                   /note="T -> I (in dbSNP:rs25754)"
FT                   /id="VAR_058972"
FT   VARIANT         1591
FT                   /note="S -> P (in dbSNP:rs16891281)"
FT                   /id="VAR_059762"
FT   CONFLICT        1578
FT                   /note="H -> R (in Ref. 3; AAI31734)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1594 AA;  177676 MW;  C88563125F0F90D8 CRC64;
     MPCAQRSWLA NLSVVAQLLN FGALCYGRQP QPGPVRFPDR RQEHFIKGLP EYHVVGPVRV
     DASGHFLSYG LHYPITSSRR KRDLDGSEDW VYYRISHEEK DLFFNLTVNQ GFLSNSYIME
     KRYGNLSHVK MMASSAPLCH LSGTVLQQGT RVGTAALSAC HGLTGFFQLP HGDFFIEPVK
     KHPLVEGGYH PHIVYRRQKV PETKEPTCGL KDSVNISQKQ ELWREKWERH NLPSRSLSRR
     SISKERWVET LVVADTKMIE YHGSENVESY ILTIMNMVTG LFHNPSIGNA IHIVVVRLIL
     LEEEEQGLKI VHHAEKTLSS FCKWQKSINP KSDLNPVHHD VAVLLTRKDI CAGFNRPCET
     LGLSHLSGMC QPHRSCNINE DSGLPLAFTI AHELGHSFGI QHDGKENDCE PVGRHPYIMS
     RQLQYDPTPL TWSKCSEEYI TRFLDRGWGF CLDDIPKKKG LKSKVIAPGV IYDVHHQCQL
     QYGPNATFCQ EVENVCQTLW CSVKGFCRSK LDAAADGTQC GEKKWCMAGK CITVGKKPES
     IPGGWGRWSP WSHCSRTCGA GVQSAERLCN NPEPKFGGKY CTGERKRYRL CNVHPCRSEA
     PTFRQMQCSE FDTVPYKNEL YHWFPIFNPA HPCELYCRPI DGQFSEKMLD AVIDGTPCFE
     GGNSRNVCIN GICKMVGCDY EIDSNATEDR CGVCLGDGSS CQTVRKMFKQ KEGSGYVDIG
     LIPKGARDIR VMEIEGAGNF LAIRSEDPEK YYLNGGFIIQ WNGNYKLAGT VFQYDRKGDL
     EKLMATGPTN ESVWIQLLFQ VTNPGIKYEY TIQKDGLDND VEQQMYFWQY GHWTECSVTC
     GTGIRRQTAH CIKKGRGMVK ATFCDPETQP NGRQKKCHEK ACPPRWWAGE WEACSATCGP
     HGEKKRTVLC IQTMVSDEQA LPPTDCQHLL KPKTLLSCNR DILCPSDWTV GNWSECSVSC
     GGGVRIRSVT CAKNHDEPCD VTRKPNSRAL CGLQQCPSSR RVLKPNKGTI SNGKNPPTLK
     PVPPPTSRPR MLTTPTGPES MSTSTPAISS PSPTTASKEG DLGGKQWQDS STQPELSSRY
     LISTGSTSQP ILTSQSLSIQ PSEENVSSSD TGPTSEGGLV ATTTSGSGLS SSRNPITWPV
     TPFYNTLTKG PEMEIHSGSG EEREQPEDKD ESNPVIWTKI RVPGNDAPVE STEMPLAPPL
     TPDLSRESWW PPFSTVMEGL LPSQRPTTSE TGTPRVEGMV TEKPANTLLP LGGDHQPEPS
     GKTANRNHLK LPNNMNQTKS SEPVLTEEDA TSLITEGFLL NASNYKQLTN GHGSAHWIVG
     NWSECSTTCG LGAYWRRVEC STQMDSDCAA IQRPDPAKRC HLRPCAGWKV GNWSKCSRNC
     SGGFKIREIQ CVDSRDHRNL RPFHCQFLAG IPPPLSMSCN PEPCEAWQVE PWSQCSRSCG
     GGVQERGVFC PGGLCDWTKR PTSTMSCNEH LCCHWATGNW DLCSTSCGGG FQKRTVQCVP
     SEGNKTEDQD QCLCDHKPRP PEFKKCNQQA CKKSADLLCT KDKLSASFCQ TLKAMKKCSV
     PTVRAECCFS CPQTHITHTQ RQRRQRLLQK SKEL
//