ADA15_RAT
ID ADA15_RAT Reviewed; 864 AA.
AC Q9QYV0; Q6P779;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 15;
DE Short=ADAM 15;
DE EC=3.4.24.-;
DE AltName: Full=CRII-7;
DE AltName: Full=Metalloprotease RGD disintegrin protein;
DE AltName: Full=Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 15;
DE Short=MDC-15;
DE AltName: Full=Metargidin;
DE Flags: Precursor;
GN Name=Adam15; Synonyms=Mdc15;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Sciatic nerve;
RX PubMed=11102971;
RX DOI=10.1002/1098-1136(200012)32:3<313::aid-glia100>3.0.co;2-g;
RA Bosse F., Petzold G., Greiner-Petter R., Pippirs U., Gillen C.,
RA Mueller H.-W.;
RT "Cellular localization of the disintegrin CRII-7/rMDC15 mRNA in rat PNS and
RT CNS and regulated expression in postnatal development and after nerve
RT injury.";
RL Glia 32:313-327(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
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).
CC -!- FUNCTION: Active metalloproteinase with gelatinolytic and
CC collagenolytic activity. Plays a role in the wound healing process.
CC Mediates both heterotypic intraepithelial cell/T-cell interactions and
CC homotypic T-cell aggregation. Inhibits beta-1 integrin-mediated cell
CC adhesion and migration of airway smooth muscle cells. Suppresses cell
CC motility on or towards fibronectin possibly by driving alpha-v/beta-1
CC integrin (ITAGV-ITGB1) cell surface expression via ERK1/2 inactivation.
CC Cleaves E-cadherin in response to growth factor deprivation. Plays a
CC role in glomerular cell migration. Plays a role in pathological
CC neovascularization. May play a role in cartilage remodeling. May be
CC proteolytically processed, during sperm epididymal maturation and the
CC acrosome reaction. May play a role in sperm-egg binding through its
CC disintegrin domain (By similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000305};
CC -!- SUBUNIT: Interacts with ITAGV-ITGB3 (vitronectin receptor). Interacts
CC with SH3GL2 and SNX9; this interaction occurs preferentially with
CC ADAM15 precursor, rather than the processed form, suggesting it occurs
CC in a secretory pathway compartment prior to the medial Golgi (By
CC similarity). Interacts with ITAG9-ITGB1. Interacts specifically with
CC Src family protein-tyrosine kinases (PTKs). Interacts with SH3PXD2A.
CC Interacts with ITAGV-ITGB1. Interacts with GRB2, HCK, ITSN1, ITSN2,
CC LYN, MAPK1, MAPK3, NCF1, NCK1, nephrocystin, PTK6, SNX33, LCK and SRC
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Single-pass
CC type I membrane protein {ECO:0000250}. Cell junction, adherens junction
CC {ECO:0000250}. Cell projection, cilium, flagellum {ECO:0000250}.
CC Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250}.
CC Note=The majority of the protein is localized in a perinuclear
CC compartment which may correspond to the trans-Golgi network or the late
CC endosome. The pro-protein is the major detectable form on the cell
CC surface, whereas the majority of the protein in the cell is processed
CC (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QYV0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QYV0-2; Sequence=VSP_039534;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain, spinal cord,
CC sciatic nerve and lung. Expressed at lower levels in all other tissues.
CC In the peripheral nervous system, expressed predominantly by Schwann
CC cells. In the central nervous system, preferentially expressed by
CC neuronal cells.
CC -!- INDUCTION: In response to sciatic nerve injury.
CC -!- DOMAIN: The cytoplasmic domain is required for SH3GL2- and SNX9-
CC binding. {ECO:0000250}.
CC -!- DOMAIN: Disintegrin domain binds to integrin alphaV-beta3.
CC {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 -!- PTM: Phosphorylation increases association with PTKs. {ECO:0000250}.
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DR EMBL; AJ251198; CAB61762.1; -; mRNA.
DR EMBL; BC061796; AAH61796.1; -; mRNA.
DR RefSeq; NP_064704.1; NM_020308.1. [Q9QYV0-2]
DR RefSeq; XP_006232804.1; XM_006232742.3. [Q9QYV0-1]
DR AlphaFoldDB; Q9QYV0; -.
DR SMR; Q9QYV0; -.
DR BioGRID; 248604; 1.
DR STRING; 10116.ENSRNOP00000039351; -.
DR ChEMBL; CHEMBL4802019; -.
DR MEROPS; M12.215; -.
DR GlyGen; Q9QYV0; 6 sites.
DR PaxDb; Q9QYV0; -.
DR Ensembl; ENSRNOT00000027970; ENSRNOP00000027970; ENSRNOG00000020590. [Q9QYV0-2]
DR Ensembl; ENSRNOT00000050868; ENSRNOP00000039351; ENSRNOG00000020590. [Q9QYV0-1]
DR GeneID; 57025; -.
DR KEGG; rno:57025; -.
DR UCSC; RGD:620402; rat. [Q9QYV0-1]
DR CTD; 8751; -.
DR RGD; 620402; Adam15.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000159822; -.
DR HOGENOM; CLU_012714_7_2_1; -.
DR InParanoid; Q9QYV0; -.
DR OMA; VCAAGHC; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q9QYV0; -.
DR TreeFam; TF314733; -.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-8941237; Invadopodia formation.
DR PRO; PR:Q9QYV0; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000020590; Expressed in esophagus and 19 other tissues.
DR Genevisible; Q9QYV0; RN.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; TAS:RGD.
DR GO; GO:0008237; F:metallopeptidase activity; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; TAS:RGD.
DR GO; GO:1904628; P:cellular response to phorbol 13-acetate 12-myristate; ISO:RGD.
DR GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0002418; P:immune response to tumor cell; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; ISO:RGD.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; ISO:RGD.
DR GO; GO:1900121; P:negative regulation of receptor binding; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:1990910; P:response to hypobaric hypoxia; IEP:RGD.
DR GO; GO:0042246; P:tissue regeneration; IEP:RGD.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR033605; ADAM15.
DR InterPro; IPR006586; ADAM_Cys-rich.
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 PANTHER; PTHR11905:SF130; PTHR11905:SF130; 1.
DR Pfam; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Angiogenesis; Cell adhesion; Cell junction;
KW Cell projection; Cilium; Cleavage on pair of basic residues;
KW Collagen degradation; Cytoplasmic vesicle; Disulfide bond; EGF-like domain;
KW Flagellum; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Phosphoprotein; Protease; Reference proteome; SH3-binding;
KW Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..208
FT /evidence="ECO:0000250"
FT /id="PRO_0000029086"
FT CHAIN 209..864
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 15"
FT /id="PRO_0000029087"
FT TOPO_DOM 209..698
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 699..719
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 720..864
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 215..416
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 423..510
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 659..687
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 17..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 738..864
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 178..185
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT MOTIF 816..822
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 851..857
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 27..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 796..834
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 849..864
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 351
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 180
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 /evidence="ECO:0000255"
FT BINDING 354
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 360
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT MOD_RES 717
FT /note="Phosphotyrosine; by HCK and LCK"
FT /evidence="ECO:0000250|UniProtKB:Q13444"
FT MOD_RES 737
FT /note="Phosphotyrosine; by HCK and LCK"
FT /evidence="ECO:0000250|UniProtKB:Q13444"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 391
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 394
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 608
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 613
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 659..669
FT /evidence="ECO:0000250"
FT DISULFID 663..675
FT /evidence="ECO:0000250"
FT DISULFID 677..686
FT /evidence="ECO:0000250"
FT VAR_SEQ 762..809
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11102971"
FT /id="VSP_039534"
FT CONFLICT 202
FT /note="H -> R (in Ref. 2; AAH61796)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 864 AA; 93308 MW; 5D46466922A89196 CRC64;
MRLALLWALG LLGAGSPRPS PPLPNIGGTE EEQQASPERT QSRSLENQVV QDSPPINLTE
VLQTGLPETL RIGLELDGEN HILELQQNRD LVPGRPTLVW YQPDGTRMVS EGHSLENCCY
RGRVQGRPSS WVSLCACSGI RGLVVLSPER SYTLELGPGD LQRPLIVSRI QDLLLPGHTC
APSWHAFVPT EAAPDLLLEQ HHLRRLKRDV VTETKIVELV IVADNSEVRK YPDFQQLLNR
TLEVALLLDT FFQPLNVRVA LVGLEAWTQR DLIEMSSNPA VLLDNFLRWR RTDLLPRLPH
DSAQLVTVTS FSGPMVGMAI QNSICSPDFS GGVNMDHSTS ILGVASSIAH ELGHSLGLDH
DSPGNSCPCP GPAPAKSCIM EASTDFLPGL NFSNCSRWAL EKALLDGMGS CLFEWPPSRA
PMSSLCGNMF VDPGEQCDCG FPDECTDPCC DYFTCQLRPG AQCASDGPCC QNCKLQPAGW
QCRLPTDDCD LPEFCLGDSS QCPPDIRLGD GEPCASGEAV CMHGRCASYT RQCQSLWGPG
AQPAAPLCLQ TANTRGNAFG SCGRSPSGSY MPCNLRDAIC GQLQCQWGRN QPLLGSVQDQ
LSEVLEANGT QLNCSWVDLD LGNDVAQPLL ALPGTACGPG LVCIGHRCQP VDLLGAQECR
SKCHGHGVCD SSRHCHCDEG WAPPDCMTQL RATSSLTTGL LLSLLLLLVL VLLGASYWYR
ARLHQRLCQL KGSSCQYRAA QSGPPERPGP PQRAQQMPGT KQANVSFPVP PSRPLPPNPV
PKKLQAELAD RSNPPTRPLP ADPVVWRPKP QGPTKPPPPR KPLPANPQGR PPLGDLPGPG
DGSLQLVVPS RPAPPPPAAS SLYL
