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MT000646

UniProt Annotations

Entry Information

Gene Name	ADAM metallopeptidase domain 12
Protein Entry
UniProt ID	U5NE98
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=4; Name=1; Synonyms=12L; IsoId=O43184-1; Sequence=Displayed; Name=2; Synonyms=12S; IsoId=O43184-2; Sequence=VSP_005476, VSP_005477; Name=3; IsoId=O43184-3; Sequence=VSP_031001, VSP_005476, VSP_005477; Note=No experimental confirmation available.; Name=4; IsoId=O43184-4; Sequence=VSP_031001, VSP_031002, VSP_031003; Note=No experimental confirmation available.;
Cofactor	Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
Domain	The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Domain	The cysteine-rich domain supports cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. In carcinomas cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading.
Function	Involved in skeletal muscle regeneration, specifically at the onset of cell fusion. Also involved in macrophage-derived giant cells (MGC) and osteoclast formation from mononuclear precursors (By similarity). {ECO:0000250}.
Interaction	O95633:FSTL3; NbExp=4; IntAct=EBI-2625865, EBI-2625790;
Ptm	The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
Similarity	Contains 1 disintegrin domain. {ECO:0000255\|PROSITE- ProRule:PRU00068}.
Similarity	Contains 1 EGF-like domain. {ECO:0000255\|PROSITE- ProRule:PRU00076}.
Similarity	Contains 1 peptidase M12B domain. {ECO:0000255\|PROSITE-ProRule:PRU00276}.
Subcellular Location	Isoform 1: Cell membrane; Single-pass type I membrane protein.
Subcellular Location	Isoform 2: Secreted.
Subcellular Location	Isoform 3: Secreted {ECO:0000305}.
Subcellular Location	Isoform 4: Secreted {ECO:0000305}.
Subunit	Interacts with alpha-actinin-2 and with syndecans (By similarity). Interacts with SH3PXD2A. Interacts with FST3. Interacts with GNB2L1/RACK1; the interaction is required for PKC- dependent translocation of ADAM12 to the cell membrane. {ECO:0000250, ECO:0000269\|PubMed:10831617, ECO:0000269\|PubMed:12615925, ECO:0000269\|PubMed:15574124, ECO:0000269\|PubMed:18621736}.
Tissue Specificity	Isoform 1 is expressed in placenta and skeletal, cardiac, and smooth muscle. Isoform 2 seems to be expressed only in placenta or in embryo and fetus. Both forms were expressed in some tumor cells lines. Not detected in brain, lung, liver, kidney or pancreas.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ADAM12ID44084ch10q26.html";