ADA12_MOUSE
ID ADA12_MOUSE Reviewed; 903 AA.
AC Q61824; F8VQN4;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 188.
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=Mltna;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryonic fibroblast;
RX PubMed=7566181; DOI=10.1038/377652a0;
RA Yagami-Hiromasa T., Sato T., Kurisaki T., Kamijo K., Nabeshima Y.,
RA Fujisawa-Sehara A.;
RT "A metalloprotease-disintegrin participating in myoblast fusion.";
RL Nature 377:652-656(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=9622634; DOI=10.1016/s0925-4773(98)00043-4;
RA Kurisaki T., Masuda A., Osumi N., Nabeshima Y., Fujisawa-Sehara A.;
RT "Spatially- and temporally-restricted expression of meltrin alpha (ADAM12)
RT and beta (ADAM19) in mouse embryo.";
RL Mech. Dev. 73:211-215(1998).
RN [4]
RP INTERACTION WITH ALPHA-ACTININ-2.
RX PubMed=10788519; DOI=10.1074/jbc.275.18.13933;
RA Galliano M.-F., Huet C., Frygelius J., Polgren A., Wewer U.M., Engvall E.;
RT "Binding of ADAM12, a marker of skeletal muscle regeneration, to the
RT muscle-specific actin-binding protein, alpha-actinin-2, is required for
RT myoblast fusion.";
RL J. Biol. Chem. 275:13933-13939(2000).
RN [5]
RP PHOSPHORYLATION AT TYR-901.
RX PubMed=11127814; DOI=10.1038/sj.onc.1203986;
RA Suzuki A., Kadota N., Hara T., Nakagami Y., Izumi T., Takenawa T., Sabe H.,
RA Endo T.;
RT "Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and
RT Grb2 and is phosphorylated by v-Src.";
RL Oncogene 19:5842-5850(2000).
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.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Interacts with alpha-actinin-2 and with syndecans. Interacts
CC with SH3PXD2A. Interacts with FST3. Interacts with RACK1; the
CC interaction is required for PKC-dependent translocation of ADAM12 to
CC the cell membrane (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q61824; P35609: ACTN2; Xeno; NbExp=3; IntAct=EBI-77785, EBI-77797;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed during early developing mesenchymal cells
CC that give rise to skeletal muscle, bones and visceral organs. Not
CC expressed in adult normal muscle but expressed in regenerating muscle.
CC {ECO:0000269|PubMed:9622634}.
CC -!- INDUCTION: At the onset of myoblast fusion.
CC -!- DOMAIN: The first 30 amino acids of the cytoplasmic domain contain a
CC major binding site to alpha-actinin-2. This interaction is necessary to
CC promote muscle cell fusion.
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 carcinoma cells the binding of this domain
CC to syndecans does not allow the integrin-mediated cell spreading (By
CC similarity). {ECO:0000250}.
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 -!- MISCELLANEOUS: Marker of skeletal muscle regeneration.
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DR EMBL; D50411; BAA08912.1; -; mRNA.
DR EMBL; AC125372; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC126676; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC140055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS21938.1; -.
DR PIR; S60257; S60257.
DR RefSeq; NP_031426.2; NM_007400.2.
DR AlphaFoldDB; Q61824; -.
DR SMR; Q61824; -.
DR BioGRID; 197962; 14.
DR IntAct; Q61824; 1.
DR MINT; Q61824; -.
DR STRING; 10090.ENSMUSP00000065213; -.
DR MEROPS; M12.212; -.
DR GlyGen; Q61824; 7 sites.
DR iPTMnet; Q61824; -.
DR PhosphoSitePlus; Q61824; -.
DR PaxDb; Q61824; -.
DR PRIDE; Q61824; -.
DR ProteomicsDB; 285602; -.
DR Antibodypedia; 19223; 477 antibodies from 40 providers.
DR DNASU; 11489; -.
DR Ensembl; ENSMUST00000067680; ENSMUSP00000065213; ENSMUSG00000054555.
DR GeneID; 11489; -.
DR KEGG; mmu:11489; -.
DR UCSC; uc009kdo.2; mouse.
DR CTD; 8038; -.
DR MGI; MGI:105378; Adam12.
DR VEuPathDB; HostDB:ENSMUSG00000054555; -.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000155495; -.
DR HOGENOM; CLU_012714_7_0_1; -.
DR InParanoid; Q61824; -.
DR OMA; SYMLEPC; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q61824; -.
DR TreeFam; TF314733; -.
DR BRENDA; 3.4.24.B10; 3474.
DR Reactome; R-MMU-8941237; Invadopodia formation.
DR BioGRID-ORCS; 11489; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Adam12; mouse.
DR PRO; PR:Q61824; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q61824; protein.
DR Bgee; ENSMUSG00000054555; Expressed in hindlimb mesenchyme and 206 other tissues.
DR ExpressionAtlas; Q61824; baseline and differential.
DR Genevisible; Q61824; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
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 Cell adhesion; Cleavage on pair of basic residues; Disulfide bond;
KW EGF-like domain; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Phosphoprotein; Protease; Reference proteome; SH3-binding;
KW Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT PROPEP 32..205
FT /evidence="ECO:0000250"
FT /id="PRO_0000029080"
FT CHAIN 206..903
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 12"
FT /id="PRO_0000029081"
FT TOPO_DOM 206..706
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 707..727
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 728..903
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 212..414
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 422..508
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 654..686
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 753..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 819..903
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 175..182
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT MOTIF 824..830
FT /note="SH3-binding; class II"
FT MOTIF 830..837
FT /note="SH3-binding; class I"
FT MOTIF 846..852
FT /note="SH3-binding; class II"
FT MOTIF 852..858
FT /note="SH3-binding; class I"
FT MOTIF 881..887
FT /note="SH3-binding; class I"
FT ACT_SITE 349
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 177
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 348
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 352
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT MOD_RES 901
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000305|PubMed:11127814"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 450
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 649
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 323..409
FT /evidence="ECO:0000250"
FT DISULFID 365..393
FT /evidence="ECO:0000250"
FT DISULFID 367..376
FT /evidence="ECO:0000250"
FT DISULFID 480..500
FT /evidence="ECO:0000250"
FT DISULFID 658..668
FT /evidence="ECO:0000250"
FT DISULFID 662..674
FT /evidence="ECO:0000250"
FT DISULFID 676..685
FT /evidence="ECO:0000250"
FT CONFLICT 40
FT /note="T -> A (in Ref. 1; BAA08912)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="G -> D (in Ref. 1; BAA08912)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="S -> R (in Ref. 1; BAA08912)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 903 AA; 98504 MW; B6A1D0816E4A73FC CRC64;
MAERPARRAP PARALLLALA GALLAPRAAR GMSLWDQRGT YEVARASLLS KDPGIPGQSI
PAKDHPDVLT VQLQLESRDL ILSLERNEGL IANGFTETHY LQDGTDVSLT RNHTDHCYYH
GHVQGDAASV VSLSTCSGLR GLIMFENKTY SLEPMKNTTD SYKLVPAESM TNIQGLCGSQ
HNKSNLTMED VSPGTSQMRA RRHKRETLKM TKYVELVIVA DNREFQRQGK DLEKVKQRLI
EIANHVDKFY RPLNIRIVLV GVEVWNDIDK CSISQDPFTS LHEFLDWRKI KLLPRKSHDN
AQLISGVYFQ GTTIGMAPIM SMCTAEQSGG VVMDHSDSPL GAAVTLAHEL GHNFGMNHDT
LERGCSCRMA AEKGGCIMNP STGFPFPMVF SSCSRKDLEA SLEKGMGMCL FNLPEVKQAF
GGRKCGNGYV EEGEECDCGE PEECTNRCCN ATTCTLKPDA VCAHGQCCED CQLKPPGTAC
RGSSNSCDLP EFCTGTAPHC PANVYLHDGH PCQGVDGYCY NGICQTHEQQ CVTLWGPGAK
PAPGICFERV NSAGDPYGNC GKDSKSAFAK CELRDAKCGK IQCQGGASRP VIGTNAVSIE
TNIPQQEGGR ILCRGTHVYL GDDMPDPGLV LAGTKCAEGK ICLNRRCQNI SVFGVHKCAM
QCHGRGVCNN RKNCHCEAHW APPFCDKFGF GGSTDSGPIR QADNQGLTVG ILVSILCLLA
AGFVVYLKRK TLMRLLFTHK KTTMEKLRCV HPSRTPSGPH LGQAHHTPGK GLLMNRAPHF
NTPKDRHSLK CQNMDISRPL DARAVPQLQS PQRVLLPLHQ TPRAPSGPAR PLPASPAVRQ
AQGIRKPSPP QKPLPADPLS RTSRLTSALV RTPGQQEPGH RPAPIRPAPK HQVPRPSHNA
YIK
