ADA10_XENLA
ID ADA10_XENLA Reviewed; 749 AA.
AC Q8JIY1; O42568;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 111.
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 Short=xKuz;
DE Flags: Precursor;
GN Name=adam10; Synonyms=kuz;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12460986; DOI=10.1083/jcb.200206023;
RA Smith K.M., Gaultier A., Cousin H., Alfandari D., White J.M.,
RA DeSimone D.W.;
RT "The cysteine-rich domain regulates ADAM protease function in vivo.";
RL J. Cell Biol. 159:893-902(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 476-637, AND FUNCTION.
RX PubMed=9244301; DOI=10.1016/s0092-8674(00)80335-9;
RA Pan D., Rubin G.M.;
RT "Kuzbanian controls proteolytic processing of Notch and mediates lateral
RT inhibition during Drosophila and vertebrate neurogenesis.";
RL Cell 90:271-280(1997).
CC -!- FUNCTION: Controls the proteolytic processing of Notch and mediates
CC lateral inhibition during neurogenesis. {ECO:0000250,
CC ECO:0000269|PubMed:9244301}.
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 -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- DEVELOPMENTAL STAGE: Expressed maternally throughout the embryo and
CC then becomes restricted to a pan-neural expression pattern.
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 -!- 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-172) 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; AF508151; AAM34686.1; -; mRNA.
DR EMBL; AF011380; AAC60248.1; -; mRNA.
DR RefSeq; NP_001083912.1; NM_001090443.1.
DR AlphaFoldDB; Q8JIY1; -.
DR SMR; Q8JIY1; -.
DR MEROPS; M12.210; -.
DR GeneID; 399187; -.
DR KEGG; xla:399187; -.
DR CTD; 399187; -.
DR Xenbase; XB-GENE-945394; adam10.S.
DR OrthoDB; 162519at2759; -.
DR Proteomes; UP000186698; Chromosome 3S.
DR Bgee; 399187; Expressed in egg cell and 19 other tissues.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005798; C:Golgi-associated vesicle; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
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 Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Notch signaling pathway; Phosphoprotein; Protease; Reference proteome;
KW SH3-binding; Signal; Transmembrane; 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_0000029072"
FT CHAIN 214..749
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 10"
FT /id="PRO_0000029073"
FT TOPO_DOM 19..673
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 674..694
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 695..749
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 220..457
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 458..552
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT REGION 705..749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 170..177
FT /note="Cysteine switch"
FT /evidence="ECO:0000305"
FT MOTIF 709..716
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 723..729
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 707..721
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 724..739
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 385
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 172
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 384
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT SITE 213..214
FT /note="Cleavage; by furin and PCSK7"
FT /evidence="ECO:0000250|UniProtKB:Q10741"
FT MOD_RES 720
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 552
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 222..314
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 345..452
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 400..436
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 461..496
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 472..485
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 474..480
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 484..516
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 504..512
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 511..537
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 525..544
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 531..563
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 556..568
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 573..599
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 581..608
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 583..598
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 595..640
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT DISULFID 633..646
FT /evidence="ECO:0000250|UniProtKB:O14672"
FT CONFLICT 515
FT /note="D -> G (in Ref. 2; AAC60248)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="S -> G (in Ref. 2; AAC60248)"
FT /evidence="ECO:0000305"
FT CONFLICT 604
FT /note="K -> I (in Ref. 2; AAC60248)"
FT /evidence="ECO:0000305"
FT CONFLICT 615
FT /note="A -> V (in Ref. 2; AAC60248)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 749 AA; 84068 MW; FC7A2FEEE7016A6A CRC64;
MGLLRLVFLL SWAASAGGLY GNPLNKYIRH YEGLSYNVDS LHQKHQRAKR AVSQEDQFVH
LDFQAHGRQF NLRMKKDTSL FSPDFKLEVG GETVNYDTSH IYTGQLFGEQ GTLSHGSVVD
GKSKGLLKPL KAHSYVEPSE RFFKDQAVPF HSVMYHEDDI KYPHKYGSEG GCADSSVFKR
MKEYQMSVQE EPEKHDHKED HEDSGPVILR KKRAAQAEKN TCQLFIQTDH LFYKRYGETR
EAVIAQISSH VKAIDTIYQS TDFSGIRNIS FMVKRIRINV TSDEKDPTNP FRFPNIGVEK
FLELNSEQNH DDYCLAYVFT DRDFDDGVLG LAWVGAPSGS SGGICERNKL YSDGKKKSLN
TGIITVQNYG SHVPPKVSHI TFAHEVGHNF GSPHDSGNEC TPGEAKNLGF KENGNFIMYA
RTTSGDKLNN NKFSICSVRN ISQVLDKKEN SCFVESGQPI CGNGLVEPGE QCDCGYSDQC
KDECCYDANQ PENLKCTLKP GKQCSPSQGP CCTTDCTFKR ASENCREESD CAKMGTCNGN
SAQCPPSEPR ENLTECNRAT QVCIKGQCSG SICERYDLEE CTCGSTDEKD DKELCHVCCM
EKMKPHTCAS TGSEAWKAYF KGKTITLQPG SPCNEFKGYC DVFMRCRLVD ADGPLARLKK
AIFNPELYEN IAEWIVAHWW AVLLMGIALI MLMAGFIKIC SVHTPSSNPK LPPPKPLPGT
LKRRRPPQTT QQPSRQRPRE NYQMGHMRH
