ADA12_HUMAN
ID ADA12_HUMAN Reviewed; 909 AA.
AC O43184; O60470; Q5JRP0; Q5JRP1; Q6P9E3; Q6UWB0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 12;
DE Short=ADAM 12;
DE EC=3.4.24.-;
DE AltName: Full=Meltrin-alpha;
DE Flags: Precursor;
GN Name=ADAM12; Synonyms=MLTN; ORFNames=UNQ346/PRO545;
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] (ISOFORMS 1 AND 2), AND VARIANT ARG-48.
RC TISSUE=Placenta;
RX PubMed=9417060; DOI=10.1074/jbc.273.1.157;
RA Gilpin B.J., Loechel F., Mattei M.-G., Engvall E., Albrechtsen R.,
RA Wewer U.M.;
RT "A novel, secreted form of human ADAM 12 (meltrin alpha) provokes
RT myogenesis in vivo.";
RL J. Biol. Chem. 273:157-166(1998).
RN [2]
RP SEQUENCE REVISION TO 36.
RA Gilpin B.J., Loechel F., Mattei M.-G., Engvall E., Albrechtsen R.,
RA Wewer U.M.;
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ARG-48.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-48.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT ARG-48.
RC TISSUE=Placenta;
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 [7]
RP CHARACTERIZATION.
RX PubMed=9642263; DOI=10.1074/jbc.273.27.16993;
RA Loechel F., Gilpin B.J., Engvall E., Albrechtsen R., Wewer U.M.;
RT "Human ADAM 12 (meltrin alpha) is an active metalloprotease.";
RL J. Biol. Chem. 273:16993-16997(1998).
RN [8]
RP INTERACTION WITH SYNDECANS.
RX PubMed=10831617; DOI=10.1083/jcb.149.5.1143;
RA Iba K., Albrechtsen R., Gilpin B.J., Froehlich C., Loechel F.,
RA Zolkiewska A., Ishiguro K., Kojima T., Liu W., Langford J.K.,
RA Sanderson R.D., Brakebusch C., Faessler R., Wewer U.M.;
RT "The cysteine-rich domain of human ADAM 12 supports cell adhesion through
RT syndecans and triggers signaling events that lead to beta1 integrin-
RT dependent cell spreading.";
RL J. Cell Biol. 149:1143-1156(2000).
RN [9]
RP INTERACTION WITH SH3PXD2A.
RX PubMed=12615925; DOI=10.1074/jbc.m300267200;
RA Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M.,
RA Courtneidge S.A.;
RT "The adaptor protein fish associates with members of the ADAMs family and
RT localizes to podosomes of Src-transformed cells.";
RL J. Biol. Chem. 278:16844-16851(2003).
RN [10]
RP INTERACTION WITH FST3.
RX PubMed=15574124; DOI=10.1042/bc20040506;
RA Bartholin L., Destaing O., Forissier S., Martel S., Maguer-Satta V.,
RA Jurdic P., Rimokh R.;
RT "FLRG, a new ADAM12-associated protein, modulates osteoclast
RT differentiation.";
RL Biol. Cell 97:577-588(2005).
RN [11]
RP INTERACTION WITH RACK1.
RX PubMed=18621736; DOI=10.1074/jbc.m709829200;
RA Bourd-Boittin K., Le Pabic H., Bonnier D., L'Helgoualc'h A., Theret N.;
RT "RACK1, a new ADAM12 interacting protein. Contribution to liver
RT fibrogenesis.";
RL J. Biol. Chem. 283:26000-26009(2008).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-301; GLU-479 AND PHE-792.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [13]
RP VARIANTS GLU-712 AND SER-893.
RX PubMed=21618342; DOI=10.1002/humu.21477;
RA Wei X., Moncada-Pazos A., Cal S., Soria-Valles C., Gartner J., Rudloff U.,
RA Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y.;
RT "Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and
RT ADAM7 are often mutated in melanoma.";
RL Hum. Mutat. 32:E2148-E2175(2011).
CC -!- FUNCTION: Involved in skeletal muscle regeneration, specifically at the
CC onset of cell fusion. Also involved in macrophage-derived giant cells
CC (MGC) and osteoclast formation from mononuclear precursors (By
CC similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- SUBUNIT: Interacts with alpha-actinin-2 and with syndecans (By
CC similarity). Interacts with SH3PXD2A. Interacts with FST3. Interacts
CC with RACK1; the interaction is required for PKC-dependent translocation
CC of ADAM12 to the cell membrane. {ECO:0000250,
CC ECO:0000269|PubMed:10831617, ECO:0000269|PubMed:12615925,
CC ECO:0000269|PubMed:15574124, ECO:0000269|PubMed:18621736}.
CC -!- INTERACTION:
CC O43184; Q8N157: AHI1; NbExp=2; IntAct=EBI-2625825, EBI-1049056;
CC O43184; P08631: HCK; NbExp=2; IntAct=EBI-2625825, EBI-346340;
CC O43184; P07948: LYN; NbExp=2; IntAct=EBI-2625825, EBI-79452;
CC O43184; P12931: SRC; NbExp=2; IntAct=EBI-2625825, EBI-621482;
CC O43184-2; O95633: FSTL3; NbExp=4; IntAct=EBI-2625865, EBI-2625790;
CC O43184-4; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-12006944, EBI-10173507;
CC O43184-4; A8MQ03: CYSRT1; NbExp=6; IntAct=EBI-12006944, EBI-3867333;
CC O43184-4; Q9NQ30: ESM1; NbExp=3; IntAct=EBI-12006944, EBI-12260294;
CC O43184-4; Q5TD97: FHL5; NbExp=3; IntAct=EBI-12006944, EBI-750641;
CC O43184-4; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-12006944, EBI-11978177;
CC O43184-4; P49639: HOXA1; NbExp=3; IntAct=EBI-12006944, EBI-740785;
CC O43184-4; P78385: KRT83; NbExp=3; IntAct=EBI-12006944, EBI-10221390;
CC O43184-4; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-12006944, EBI-11959885;
CC O43184-4; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-12006944, EBI-11749135;
CC O43184-4; P60410: KRTAP10-8; NbExp=5; IntAct=EBI-12006944, EBI-10171774;
CC O43184-4; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-12006944, EBI-10176379;
CC O43184-4; Q9BYR8: KRTAP3-1; NbExp=5; IntAct=EBI-12006944, EBI-9996449;
CC O43184-4; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-12006944, EBI-751260;
CC O43184-4; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-12006944, EBI-739863;
CC O43184-4; Q6L8G9: KRTAP5-6; NbExp=3; IntAct=EBI-12006944, EBI-10250562;
CC O43184-4; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-12006944, EBI-3958099;
CC O43184-4; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-12006944, EBI-11962084;
CC O43184-4; Q9BYQ4: KRTAP9-2; NbExp=5; IntAct=EBI-12006944, EBI-1044640;
CC O43184-4; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-12006944, EBI-11958364;
CC O43184-4; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-12006944, EBI-11955689;
CC O43184-4; O60336: MAPKBP1; NbExp=3; IntAct=EBI-12006944, EBI-947402;
CC O43184-4; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-12006944, EBI-22310682;
CC O43184-4; P32242: OTX1; NbExp=3; IntAct=EBI-12006944, EBI-740446;
CC O43184-4; Q6P9E2: RECK; NbExp=3; IntAct=EBI-12006944, EBI-10253121;
CC O43184-4; Q16348: SLC15A2; NbExp=3; IntAct=EBI-12006944, EBI-12806032;
CC O43184-4; O43609: SPRY1; NbExp=4; IntAct=EBI-12006944, EBI-3866665;
CC O43184-4; Q9C004: SPRY4; NbExp=3; IntAct=EBI-12006944, EBI-354861;
CC O43184-4; Q7Z6R9: TFAP2D; NbExp=3; IntAct=EBI-12006944, EBI-11952651;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=12L;
CC IsoId=O43184-1; Sequence=Displayed;
CC Name=2; Synonyms=12S;
CC IsoId=O43184-2; Sequence=VSP_005476, VSP_005477;
CC Name=3;
CC IsoId=O43184-3; Sequence=VSP_031001, VSP_005476, VSP_005477;
CC Name=4;
CC IsoId=O43184-4; Sequence=VSP_031001, VSP_031002, VSP_031003;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in placenta and skeletal,
CC cardiac, and smooth muscle. Isoform 2 seems to be expressed only in
CC placenta or in embryo and fetus. Both forms were expressed in some
CC tumor cells lines. Not detected in brain, lung, liver, kidney or
CC pancreas.
CC -!- DOMAIN: The cysteine-rich domain supports cell adhesion through
CC syndecans and triggers signaling events that lead to beta-1 integrin-
CC dependent cell spreading. In carcinomas cells the binding of this
CC domain to syndecans does not allow the integrin-mediated cell
CC spreading.
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. {ECO:0000250}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ADAM12ID44084ch10q26.html";
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DR EMBL; AF023476; AAC08702.2; -; mRNA.
DR EMBL; AF023477; AAC08703.2; -; mRNA.
DR EMBL; AY358878; AAQ89237.1; -; mRNA.
DR EMBL; AC022015; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC063963; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL589787; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49206.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49209.1; -; Genomic_DNA.
DR EMBL; BC060804; AAH60804.1; -; mRNA.
DR CCDS; CCDS7653.1; -. [O43184-1]
DR CCDS; CCDS7654.1; -. [O43184-2]
DR RefSeq; NP_001275903.1; NM_001288974.1. [O43184-4]
DR RefSeq; NP_001275904.1; NM_001288975.1. [O43184-3]
DR RefSeq; NP_003465.3; NM_003474.5. [O43184-1]
DR RefSeq; NP_067673.2; NM_021641.4. [O43184-2]
DR AlphaFoldDB; O43184; -.
DR SMR; O43184; -.
DR BioGRID; 113731; 39.
DR CORUM; O43184; -.
DR IntAct; O43184; 46.
DR MINT; O43184; -.
DR STRING; 9606.ENSP00000357668; -.
DR BindingDB; O43184; -.
DR ChEMBL; CHEMBL5030; -.
DR GuidetoPHARMACOLOGY; 1660; -.
DR MEROPS; M12.212; -.
DR TCDB; 8.A.77.1.5; the sheddase (sheddase) family.
DR CarbonylDB; O43184; -.
DR GlyGen; O43184; 5 sites.
DR iPTMnet; O43184; -.
DR PhosphoSitePlus; O43184; -.
DR BioMuta; ADAM12; -.
DR jPOST; O43184; -.
DR MassIVE; O43184; -.
DR MaxQB; O43184; -.
DR PaxDb; O43184; -.
DR PeptideAtlas; O43184; -.
DR PRIDE; O43184; -.
DR ProteomicsDB; 48799; -. [O43184-1]
DR ProteomicsDB; 48800; -. [O43184-2]
DR ProteomicsDB; 48801; -. [O43184-3]
DR ProteomicsDB; 48802; -. [O43184-4]
DR Antibodypedia; 19223; 477 antibodies from 40 providers.
DR DNASU; 8038; -.
DR Ensembl; ENST00000368676.8; ENSP00000357665.4; ENSG00000148848.15. [O43184-2]
DR Ensembl; ENST00000368679.8; ENSP00000357668.4; ENSG00000148848.15. [O43184-1]
DR GeneID; 8038; -.
DR KEGG; hsa:8038; -.
DR UCSC; uc001ljk.4; human. [O43184-1]
DR CTD; 8038; -.
DR DisGeNET; 8038; -.
DR GeneCards; ADAM12; -.
DR HGNC; HGNC:190; ADAM12.
DR HPA; ENSG00000148848; Tissue enriched (placenta).
DR MIM; 602714; gene.
DR neXtProt; NX_O43184; -.
DR OpenTargets; ENSG00000148848; -.
DR PharmGKB; PA24507; -.
DR VEuPathDB; HostDB:ENSG00000148848; -.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000155495; -.
DR HOGENOM; CLU_012714_7_0_1; -.
DR InParanoid; O43184; -.
DR OMA; SYMLEPC; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; O43184; -.
DR TreeFam; TF314733; -.
DR BRENDA; 3.4.24.B10; 2681.
DR PathwayCommons; O43184; -.
DR Reactome; R-HSA-177929; Signaling by EGFR.
DR Reactome; R-HSA-8941237; Invadopodia formation.
DR SignaLink; O43184; -.
DR SIGNOR; O43184; -.
DR BioGRID-ORCS; 8038; 11 hits in 1074 CRISPR screens.
DR ChiTaRS; ADAM12; human.
DR GeneWiki; ADAM12; -.
DR GenomeRNAi; 8038; -.
DR Pharos; O43184; Tchem.
DR PRO; PR:O43184; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O43184; protein.
DR Bgee; ENSG00000148848; Expressed in placenta and 143 other tissues.
DR ExpressionAtlas; O43184; baseline and differential.
DR Genevisible; O43184; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0017124; F:SH3 domain binding; IPI:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007520; P:myoblast fusion; TAS:ProtInc.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
DR InterPro; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00427; DISINTEGRIN_1; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane;
KW Cleavage on pair of basic residues; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Phosphoprotein; Protease; Reference proteome; Secreted; SH3-binding;
KW Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT PROPEP 29..207
FT /evidence="ECO:0000250"
FT /id="PRO_0000029078"
FT CHAIN 208..909
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 12"
FT /id="PRO_0000029079"
FT TOPO_DOM 208..708
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 709..729
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 730..909
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 214..416
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 424..510
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 656..688
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 822..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 177..184
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT MOTIF 828..834
FT /note="SH3-binding; class II"
FT /evidence="ECO:0000250"
FT MOTIF 834..841
FT /note="SH3-binding; class I"
FT /evidence="ECO:0000250"
FT MOTIF 885..891
FT /note="SH3-binding; class I"
FT /evidence="ECO:0000250"
FT ACT_SITE 351
FT BINDING 179
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 350
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 354
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 360
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT MOD_RES 907
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 452
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 325..411
FT /evidence="ECO:0000250"
FT DISULFID 367..395
FT /evidence="ECO:0000250"
FT DISULFID 369..378
FT /evidence="ECO:0000250"
FT DISULFID 482..502
FT /evidence="ECO:0000250"
FT DISULFID 660..670
FT /evidence="ECO:0000250"
FT DISULFID 664..676
FT /evidence="ECO:0000250"
FT DISULFID 678..687
FT /evidence="ECO:0000250"
FT VAR_SEQ 114..116
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_031001"
FT VAR_SEQ 705..740
FT /note="DNQGLTIGILVTILCLLAAGFVVYLKRKTLIRLLFT -> GKEARQEAAESN
FT RERGQGQEPVGSQEHASTASLTLI (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031002"
FT VAR_SEQ 705..738
FT /note="DNQGLTIGILVTILCLLAAGFVVYLKRKTLIRLL -> EARQEAAESNRERG
FT QGQEPVGSQEHASTASLTLI (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:9417060"
FT /id="VSP_005476"
FT VAR_SEQ 739..909
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:9417060"
FT /id="VSP_005477"
FT VAR_SEQ 741..909
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031003"
FT VARIANT 48
FT /note="G -> R (in dbSNP:rs3740199)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9417060,
FT ECO:0000269|Ref.5"
FT /id="VAR_038542"
FT VARIANT 301
FT /note="D -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036143"
FT VARIANT 479
FT /note="G -> E (in a breast cancer sample; somatic mutation;
FT dbSNP:rs1459457663)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036144"
FT VARIANT 712
FT /note="G -> E (in a cutaneous metastatic melanoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066310"
FT VARIANT 792
FT /note="L -> F (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036145"
FT VARIANT 893
FT /note="P -> S (in a cutaneous metastatic melanoma sample;
FT somatic mutation; dbSNP:rs151030407)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066311"
SQ SEQUENCE 909 AA; 99542 MW; E28131C64C4304AB CRC64;
MAARPLPVSP ARALLLALAG ALLAPCEARG VSLWNQGRAD EVVSASVGSG DLWIPVKSFD
SKNHPEVLNI RLQRESKELI INLERNEGLI ASSFTETHYL QDGTDVSLAR NYTVILGHCY
YHGHVRGYSD SAVSLSTCSG LRGLIVFENE SYVLEPMKSA TNRYKLFPAK KLKSVRGSCG
SHHNTPNLAA KNVFPPPSQT WARRHKRETL KATKYVELVI VADNREFQRQ GKDLEKVKQR
LIEIANHVDK FYRPLNIRIV LVGVEVWNDM DKCSVSQDPF TSLHEFLDWR KMKLLPRKSH
DNAQLVSGVY FQGTTIGMAP IMSMCTADQS GGIVMDHSDN PLGAAVTLAH ELGHNFGMNH
DTLDRGCSCQ MAVEKGGCIM NASTGYPFPM VFSSCSRKDL ETSLEKGMGV CLFNLPEVRE
SFGGQKCGNR FVEEGEECDC GEPEECMNRC CNATTCTLKP DAVCAHGLCC EDCQLKPAGT
ACRDSSNSCD LPEFCTGASP HCPANVYLHD GHSCQDVDGY CYNGICQTHE QQCVTLWGPG
AKPAPGICFE RVNSAGDPYG NCGKVSKSSF AKCEMRDAKC GKIQCQGGAS RPVIGTNAVS
IETNIPLQQG GRILCRGTHV YLGDDMPDPG LVLAGTKCAD GKICLNRQCQ NISVFGVHEC
AMQCHGRGVC NNRKNCHCEA HWAPPFCDKF GFGGSTDSGP IRQADNQGLT IGILVTILCL
LAAGFVVYLK RKTLIRLLFT NKKTTIEKLR CVRPSRPPRG FQPCQAHLGH LGKGLMRKPP
DSYPPKDNPR RLLQCQNVDI SRPLNGLNVP QPQSTQRVLP PLHRAPRAPS VPARPLPAKP
ALRQAQGTCK PNPPQKPLPA DPLARTTRLT HALARTPGQW ETGLRLAPLR PAPQYPHQVP
RSTHTAYIK
