ADA10_PIG
ID ADA10_PIG Reviewed; 748 AA.
AC O77633; B3VKE8; K7GKL8;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2018, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 10;
DE Short=ADAM 10;
DE EC=3.4.24.81 {ECO:0000250|UniProtKB:O14672};
DE AltName: Full=Kuzbanian protein homolog;
DE AltName: Full=Mammalian disintegrin-metalloprotease;
DE AltName: CD_antigen=CD156c;
DE Flags: Precursor;
GN Name=ADAM10;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11230111; DOI=10.1161/01.res.88.4.430;
RA Boulday G., Coupel S., Coulon F., Soulillou J.P., Charreau B.;
RT "Antigraft antibody-mediated expression of metalloproteinases on
RT endothelial cells. Differential expression of TIMP-1 and ADAM-10 depends on
RT antibody specificity and isotype.";
RL Circ. Res. 88:430-437(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Duroc;
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 392-446.
RX PubMed=10429942; DOI=10.1016/s0945-053x(99)00024-4;
RA Flannery C.R., Little C.B., Caterson B., Hughes C.E.;
RT "Effects of culture conditions and exposure to catabolic stimulators (IL-1
RT and retinoic acid) on the expression of matrix metalloproteinases (MMPs)
RT and disintegrin metalloproteinases (ADAMs) by articular cartilage
RT chondrocytes.";
RL Matrix Biol. 18:225-237(1999).
CC -!- FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha to its
CC mature soluble form. Responsible for the proteolytical release of
CC soluble JAM3 from endothelial cells surface. Responsible for the
CC proteolytic release of several other cell-surface proteins, including
CC heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and
CC for constitutive and regulated alpha-secretase cleavage of amyloid
CC precursor protein (APP). Contributes to the normal cleavage of the
CC cellular prion protein. Involved in the cleavage of the adhesion
CC molecule L1 at the cell surface and in released membrane vesicles,
CC suggesting a vesicle-based protease activity. Controls also the
CC proteolytic processing of Notch and mediates lateral inhibition during
CC neurogenesis. Responsible for the FasL ectodomain shedding and for the
CC generation of the remnant ADAM10-processed FasL (FasL APL)
CC transmembrane form. Also cleaves the ectodomain of the integral
CC membrane proteins CORIN and ITM2B. Mediates the proteolytic cleavage of
CC LAG3, leading to release the secreted form of LAG3. Mediates the
CC proteolytic cleavage of IL6R and IL11RA, leading to the release of
CC secreted forms of IL6R and IL11RA (By similarity). Enhances the
CC cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By
CC similarity). Cleaves TREM2, resulting in shedding of the TREM2
CC ectodomain (By similarity). Involved in the development and maturation
CC of glomerular and coronary vasculature (By similarity). During
CC development of the cochlear organ of Corti, promotes pillar cell
CC separation by forming a ternary complex with CADH1 and EPHA4 and
CC cleaving CADH1 at adherens junctions (By similarity). May regulate the
CC EFNA5-EPHA3 signaling (By similarity). {ECO:0000250|UniProtKB:O14672,
CC ECO:0000250|UniProtKB:O35598}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endopeptidase of broad specificity.; EC=3.4.24.81;
CC Evidence={ECO:0000250|UniProtKB:O14672};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O14672};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O14672};
CC -!- ACTIVITY REGULATION: Catalytically inactive when the propeptide is
CC intact and associated with the mature enzyme (By similarity). The
CC disintegrin and cysteine-rich regions modulate access of substrates to
CC exerts an inhibitory effect on the cleavage of ADAM10 substrates (By
CC similarity). {ECO:0000250|UniProtKB:O14672,
CC ECO:0000250|UniProtKB:Q10741}.
CC -!- SUBUNIT: Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5
CC extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3
CC complex internalization and function (By similarity). Interacts with
CC the clathrin adapter AP2 complex subunits AP2A1, AP2A2, AP2B1, and
CC AP2M1; this interaction facilitates ADAM10 endocytosis from the plasma
CC membrane during long-term potentiation in hippocampal neurons (By
CC similarity). Interacts (via extracellular domain) with TSPAN33 (via
CC extracellular domain) and (via cytoplasmic domain) with AFDN;
CC interaction with TSPAN33 allows the docking of ADAM10 to zonula
CC adherens through a PDZ11-dependent interaction between TSPAN33 and
CC PLEKHA7 while interaction with AFDN locks ADAM10 at zonula adherens (By
CC similarity). Forms a ternary complex composed of ADAM10, EPHA4 and
CC CADH1; within the complex, ADAM10 cleaves CADH1 which disrupts adherens
CC junctions (By similarity). Interacts with EPHA2 (By similarity).
CC Interacts with NGF in a divalent cation-dependent manner (By
CC similarity). Interacts with TSPAN14; the interaction promotes ADAM10
CC maturation and cell surface expression (By similarity). Interacts with
CC TSPAN5, TSPAN10, TSPAN15, TSPAN17 and TSPAN33; these interactions
CC regulate the ADAM10 substrate cleaving (By similarity). Interacts with
CC DLG1; this interaction recruits ADAM10 to the cell membrane during
CC long-term depression in hippocampal neurons (By similarity). Interacts
CC (via extracellular domain) with BACE1 (via extracellular domain) (By
CC similarity). Interacts with FAM171A1 (By similarity).
CC {ECO:0000250|UniProtKB:O14672, ECO:0000250|UniProtKB:O35598}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O14672};
CC Single-pass type I membrane protein {ECO:0000305}. Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:O14672}; Single-pass type I membrane
CC protein {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000250|UniProtKB:O14672}. Cell projection, axon
CC {ECO:0000250|UniProtKB:O35598}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:O35598}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:O14672}. Cytoplasm
CC {ECO:0000250|UniProtKB:O14672}. Note=Is localized in the plasma
CC membrane but is also expressed in the Golgi apparatus and in clathrin-
CC coated vesicles derived likely from the Golgi (By similarity). During
CC long term depression, it is recruited to the cell membrane by DLG1 (By
CC similarity). The immature form is mainly located near cytoplasmic
CC fibrillar structures, while the mature form is predominantly located at
CC zonula adherens and the cell membrane (By similarity). The localization
CC and clustering of mature ADAM10 to zonula adherens is regulated by
CC AFDN, TSPAN33, PLEKHA7 and PDZD11 (By similarity).
CC {ECO:0000250|UniProtKB:O14672, ECO:0000250|UniProtKB:O35598}.
CC -!- TISSUE SPECIFICITY: Expressed in chondrocytes.
CC -!- INDUCTION: Up-regulared in chondrocytes culture by interleukin-1 and
CC reduced by retinoic acid.
CC -!- DOMAIN: The propeptide keeps the metalloprotease in a latent form via a
CC cysteine switch mechanism. This mechanism may be mediated by a highly
CC conserved cysteine (Cys-173) in the propeptide, which interacts and
CC neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the
CC metalloprotease domain. The dissociation of the cysteine from the zinc
CC ion upon the activation-peptide release activates the enzyme.
CC {ECO:0000250|UniProtKB:P03956}.
CC -!- PTM: The precursor is cleaved by furin and PCSK7.
CC {ECO:0000250|UniProtKB:Q10741}.
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DR EMBL; EU753851; ACE80208.1; -; mRNA.
DR EMBL; AEMK02000004; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF069645; AAC23529.1; -; mRNA.
DR RefSeq; NP_001124003.1; NM_001130531.1.
DR AlphaFoldDB; O77633; -.
DR SMR; O77633; -.
DR STRING; 9823.ENSSSCP00000004952; -.
DR MEROPS; M12.210; -.
DR PaxDb; O77633; -.
DR PeptideAtlas; O77633; -.
DR Ensembl; ENSSSCT00000088907; ENSSSCP00000067539; ENSSSCG00000004595.
DR Ensembl; ENSSSCT00070020096; ENSSSCP00070016711; ENSSSCG00070010280.
DR GeneID; 397345; -.
DR KEGG; ssc:397345; -.
DR CTD; 102; -.
DR VGNC; VGNC:85061; ADAM10.
DR eggNOG; KOG3658; Eukaryota.
DR GeneTree; ENSGT00940000160579; -.
DR HOGENOM; CLU_004602_0_1_1; -.
DR InParanoid; O77633; -.
DR OMA; GICERYK; -.
DR OrthoDB; 162519at2759; -.
DR ChiTaRS; ADAM10; pig.
DR Proteomes; UP000008227; Chromosome 1.
DR Proteomes; UP000314985; Chromosome 1.
DR Bgee; ENSSSCG00000004595; Expressed in lung and 42 other tissues.
DR ExpressionAtlas; O77633; baseline and differential.
DR Genevisible; O77633; SS.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005798; C:Golgi-associated vesicle; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046930; C:pore complex; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0097060; C:synaptic membrane; IBA:GO_Central.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IEA:Ensembl.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:Ensembl.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0090102; P:cochlea development; IEA:Ensembl.
DR GO; GO:0051089; P:constitutive protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0038004; P:epidermal growth factor receptor ligand maturation; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0042117; P:monocyte activation; IEA:Ensembl.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0046931; P:pore complex assembly; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IEA:Ensembl.
DR GO; GO:0099173; P:postsynapse organization; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:1901342; P:regulation of vasculature development; IEA:Ensembl.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:1901998; P:toxin transport; IEA:Ensembl.
DR CDD; cd04270; ZnMc_TACE_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR034025; ADAM10_ADAM17.
DR InterPro; IPR027053; ADAM_10.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR PANTHER; PTHR45702:SF4; PTHR45702:SF4; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 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; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Cell junction; Cell membrane; Cell projection;
KW Cleavage on pair of basic residues; Cytoplasm; Cytoplasmic vesicle;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Notch signaling pathway; Phosphoprotein;
KW Protease; Reference proteome; SH3-binding; Signal; Transmembrane;
KW Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..213
FT /evidence="ECO:0000250|UniProtKB:Q10741"
FT /id="PRO_0000444476"
FT CHAIN 214..748
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 10"
FT /evidence="ECO:0000255"
FT /id="PRO_0000078205"
FT TRANSMEM 673..693
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 220..456
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 457..551
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT REGION 704..748
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 734..748
FT /note="Interaction with AP2A1, AP2A2 and AP2M1"
FT /evidence="ECO:0000250|UniProtKB:O35598"
FT MOTIF 171..178
FT /note="Cysteine switch"
FT /evidence="ECO:0000305"
FT MOTIF 708..715
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 722..728
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 706..720
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 384
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 393
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT SITE 213..214
FT /note="Cleavage; by furin and PCSK7"
FT /evidence="ECO:0000250|UniProtKB:Q10741"
FT MOD_RES 719
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 222..313
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 344..451
FT /evidence="ECO:0000250|UniProtKB:O14672,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 399..435
FT /evidence="ECO:0000250|UniProtKB:O14672,
FT ECO:0000255|PROSITE-ProRule:PRU00276"
FT DISULFID 460..495
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 471..484
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 473..479
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 483..515
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 503..511
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 510..536
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 524..543
FT /evidence="ECO:0000250|UniProtKB:O14672,
FT ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 530..562
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 555..567
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 572..598
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 580..607
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 582..597
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 594..639
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 632..645
FT /evidence="ECO:0000250|UniProtKB:O14672"
SQ SEQUENCE 748 AA; 84383 MW; 00A646E9445E04FC CRC64;
MVLLRVLILL LSWAAGLGGQ YGNPLNKYIR HYEGLSYDVD SLHQKHQRAK RAVSHEDQFL
RLNFHAHGRH FNLRMKRDTS LFSDEFRVET SNKVLDYDTS HIYTGHIYGE EGSFSHGSVI
DGRFEGFIQT HGGTFYIEPA ERYIKDRTLP FHSVIYHEDD INYPHKYGPQ GGCADHSVFE
RMRKYQMTGV EEVTQTPQEK HANNGPELLR KKRTTSAEKN TCQLYIQTDH LFFKYYGTRE
AVIAQISSHV KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF
LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY SDGKKKSLNT
GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT PGESKNLGQK ENGNYIMYAR
ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN CFVESGQPIC GNGMVEQGEQ CDCGYSDQCK
DECCYDANQP EGKKCRLKPE KECSPSQGPC CTAQCKFKSK TEKCRDDSDC AKEGICNGIT
ALCPASDPKP NFTDCNRHTQ VCINGQCAGS ICEKYGLEEC TCASSDGKDD KELCHVCCMK
KMEPLTCAST GSEKWKKHFL GRTITLQPGS PCNDFRGYCD VFMRCRLVDA DGPLARLKKA
IFSPELYENI AEWIVAYWWA VLLMGIALIM LMAGFIKICS VHTPSSNPKL PPPKPLPGTL
KRRRPPQTIQ PPQRQRPRES YQMGHMRR
