ATS10_HUMAN
ID ATS10_HUMAN Reviewed; 1103 AA.
AC Q9H324; M0QZE4;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 10;
DE Short=ADAM-TS 10;
DE Short=ADAM-TS10;
DE Short=ADAMTS-10;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=ADAMTS10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 27-1103 (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT SER-134.
RX PubMed=15355968; DOI=10.1074/jbc.m409036200;
RA Somerville R.P.T., Jungers K.A., Apte S.S.;
RT "Discovery and characterization of a novel, widely expressed
RT metalloprotease, ADAMTS10, and its proteolytic activation.";
RL J. Biol. Chem. 279:51208-51217(2004).
RN [3]
RP INVOLVEMENT IN WMS1.
RX PubMed=15368195; DOI=10.1086/425231;
RA Dagoneau N., Benoist-Lasselin C., Huber C., Faivre L., Megarbane A.,
RA Alswaid A., Dollfus H., Alembik Y., Munnich A., Legeai-Mallet L.,
RA Cormier-Daire V.;
RT "ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome.";
RL Am. J. Hum. Genet. 75:801-806(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FBN1.
RX PubMed=21402694; DOI=10.1074/jbc.m111.231571;
RA Kutz W.E., Wang L.W., Bader H.L., Majors A.K., Iwata K., Traboulsi E.I.,
RA Sakai L.Y., Keene D.R., Apte S.S.;
RT "ADAMTS10 protein interacts with fibrillin-1 and promotes its deposition in
RT extracellular matrix of cultured fibroblasts.";
RL J. Biol. Chem. 286:17156-17167(2011).
RN [5]
RP VARIANT WMS1 THR-25, AND CHARACTERIZATION OF VARIANT WMS1 THR-25.
RX PubMed=18567016; DOI=10.1002/humu.20797;
RA Kutz W.E., Wang L.W., Dagoneau N., Odrcic K.J., Cormier-Daire V.,
RA Traboulsi E.I., Apte S.S.;
RT "Functional analysis of an ADAMTS10 signal peptide mutation in Weill-
RT Marchesani syndrome demonstrates a long-range effect on secretion of the
RT full-length enzyme.";
RL Hum. Mutat. 29:1425-1434(2008).
CC -!- FUNCTION: Metalloprotease that participate in microfibrils assembly.
CC Microfibrils are extracellular matrix components occurring
CC independently or along with elastin in the formation of elastic
CC tissues. {ECO:0000269|PubMed:21402694}.
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 FBN1; this interaction promotes microfibrils
CC assembly. {ECO:0000269|PubMed:21402694}.
CC -!- INTERACTION:
CC Q9H324; P28301: Lox; Xeno; NbExp=3; IntAct=EBI-7096115, EBI-642911;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:21402694}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H324-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H324-2; Sequence=VSP_054707;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult tissues.
CC {ECO:0000269|PubMed:15355968}.
CC -!- DOMAIN: The spacer domain and the TSP type-1 domains are important for
CC a tight interaction with the extracellular matrix. {ECO:0000250}.
CC -!- PTM: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a
CC threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-
CC G of the TSP type-1 repeat domains where C1 and C2 are the first and
CC second cysteine residue of the repeat, respectively. Fucosylated
CC repeats can then be further glycosylated by the addition of a beta-1,3-
CC glucose residue by the glucosyltransferase, B3GALTL. Fucosylation
CC mediates the efficient secretion of ADAMTS family members. Can also be
CC C-glycosylated with one or two mannose molecules on tryptophan residues
CC within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated.
CC These other glycosylations can also facilitate secretion (By
CC similarity). {ECO:0000250}.
CC -!- DISEASE: Weill-Marchesani syndrome 1 (WMS1) [MIM:277600]: A rare
CC connective tissue disorder characterized by short stature,
CC brachydactyly, joint stiffness, and eye abnormalities including
CC microspherophakia, ectopia lentis, severe myopia and glaucoma.
CC {ECO:0000269|PubMed:15368195, ECO:0000269|PubMed:18567016}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; AC092315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC130469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF163762; AAG35563.1; -; mRNA.
DR CCDS; CCDS12206.1; -. [Q9H324-1]
DR CCDS; CCDS62529.1; -. [Q9H324-2]
DR RefSeq; NP_001269281.1; NM_001282352.1. [Q9H324-2]
DR RefSeq; NP_112219.3; NM_030957.3.
DR AlphaFoldDB; Q9H324; -.
DR SMR; Q9H324; -.
DR BioGRID; 123586; 11.
DR IntAct; Q9H324; 12.
DR MINT; Q9H324; -.
DR STRING; 9606.ENSP00000270328; -.
DR MEROPS; M12.235; -.
DR GlyGen; Q9H324; 6 sites.
DR iPTMnet; Q9H324; -.
DR PhosphoSitePlus; Q9H324; -.
DR BioMuta; ADAMTS10; -.
DR DMDM; 148887344; -.
DR MassIVE; Q9H324; -.
DR PaxDb; Q9H324; -.
DR PeptideAtlas; Q9H324; -.
DR PRIDE; Q9H324; -.
DR Antibodypedia; 51079; 163 antibodies from 29 providers.
DR DNASU; 81794; -.
DR Ensembl; ENST00000595838.5; ENSP00000470501.1; ENSG00000142303.14. [Q9H324-2]
DR GeneID; 81794; -.
DR KEGG; hsa:81794; -.
DR UCSC; uc002mki.3; human. [Q9H324-1]
DR CTD; 81794; -.
DR DisGeNET; 81794; -.
DR GeneCards; ADAMTS10; -.
DR GeneReviews; ADAMTS10; -.
DR HGNC; HGNC:13201; ADAMTS10.
DR HPA; ENSG00000142303; Low tissue specificity.
DR MalaCards; ADAMTS10; -.
DR MIM; 277600; phenotype.
DR MIM; 608990; gene.
DR neXtProt; NX_Q9H324; -.
DR OpenTargets; ENSG00000142303; -.
DR Orphanet; 3449; Weill-Marchesani syndrome.
DR PharmGKB; PA24537; -.
DR VEuPathDB; HostDB:ENSG00000142303; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000158404; -.
DR HOGENOM; CLU_554988_0_0_1; -.
DR InParanoid; Q9H324; -.
DR PhylomeDB; Q9H324; -.
DR TreeFam; TF313537; -.
DR PathwayCommons; Q9H324; -.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; Q9H324; -.
DR BioGRID-ORCS; 81794; 16 hits in 1068 CRISPR screens.
DR ChiTaRS; ADAMTS10; human.
DR GeneWiki; ADAMTS10; -.
DR GenomeRNAi; 81794; -.
DR Pharos; Q9H324; Tbio.
DR PRO; PR:Q9H324; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H324; protein.
DR Bgee; ENSG00000142303; Expressed in descending thoracic aorta and 178 other tissues.
DR ExpressionAtlas; Q9H324; baseline and differential.
DR Genevisible; Q9H324; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0001527; C:microfibril; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.20.100.10; -; 5.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR013273; ADAMTS/ADAMTS-like.
DR InterPro; IPR041645; ADAMTS_CR_2.
DR InterPro; IPR045371; ADAMTS_CR_3.
DR InterPro; IPR010294; ADAMTS_spacer1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR010909; PLAC.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF17771; ADAM_CR_2; 1.
DR Pfam; PF19236; ADAM_CR_3; 1.
DR Pfam; PF05986; ADAM_spacer1; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF08686; PLAC; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR Pfam; PF00090; TSP_1; 1.
DR PRINTS; PR01857; ADAMTSFAMILY.
DR SMART; SM00209; TSP1; 5.
DR SUPFAM; SSF82895; SSF82895; 5.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50900; PLAC; 1.
DR PROSITE; PS50092; TSP1; 5.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues; Disease variant;
KW Disulfide bond; Dwarfism; Extracellular matrix; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..233
FT /evidence="ECO:0000250"
FT /id="PRO_0000029184"
FT CHAIN 234..1103
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 10"
FT /id="PRO_0000029185"
FT DOMAIN 239..457
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 460..546
FT /note="Disintegrin"
FT DOMAIN 547..602
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 825..883
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 884..945
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 947..1001
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1003..1058
FT /note="TSP type-1 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1065..1103
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 213..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 706..828
FT /note="Spacer"
FT ACT_SITE 393
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 740
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 795
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 892
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 315..376
FT /evidence="ECO:0000250"
FT DISULFID 351..358
FT /evidence="ECO:0000250"
FT DISULFID 370..452
FT /evidence="ECO:0000250"
FT DISULFID 409..436
FT /evidence="ECO:0000250"
FT DISULFID 479..501
FT /evidence="ECO:0000250"
FT DISULFID 490..508
FT /evidence="ECO:0000250"
FT DISULFID 496..531
FT /evidence="ECO:0000250"
FT DISULFID 521..536
FT /evidence="ECO:0000250"
FT DISULFID 559..596
FT /evidence="ECO:0000250"
FT DISULFID 563..601
FT /evidence="ECO:0000250"
FT DISULFID 574..586
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..637
FT /note="MAPACQILRWALALGLGLMFEVTHAFRSQDEFLSSLESYEIAFPTRVDHNGA
FT LLAFSPPPPRRQRRGTGATAESRLFYKVASPSTHFLLNLTRSSRLLAGHVSVEYWTREG
FT LAWQRAARPHCLYAGHLQGQASTSHVAISTCGGLHGLIVADEEEYLIEPLHGGPKGSRS
FT PEESGPHVVYKRSSLRHPHLDTACGVRDEKPWKGRPWWLRTLKPPPARPLGNETERGQP
FT GLKRSVSRERYVETLVVADKMMVAYHGRRDVEQYVLAIMNIVAKLFQDSSLGSTVNILV
FT TRLILLTEDQPTLEITHHAGKSLDSFCKWQKSIVNHSGHGNAIPENGVANHDTAVLITR
FT YDICIYKNKPCGTLGLAPVGGMCERERSCSVNEDIGLATAFTIAHEIGHTFGMNHDGVG
FT NSCGARGQDPAKLMAAHITMKTNPFVWSSCSRDYITSFLDSGLGLCLNNRPPRQDFVYP
FT TVAPGQAYDADEQCRFQHGVKSRQCKYGEVCSELWCLSKSNRCITNSIPAAEGTLCQTH
FT TIDKGWCYKRVCVPFGSRPEGVDGAWGPWTPWGDCSRTCGGGVSSSSRHCDSPRPTIGG
FT KYCLGERRRHRSCNTDDCPPGSQDFREVQCSEFDSIPFRGKFYKWKTYRGGGVK -> M
FT GPTSVLRAGLTPSCLPPPSGATNGSVSPLGRAQRVWTEPGGRGLHGATAAGPVAAACPL
FT LAVTATAPGQPSGASTVWVREGGTAPATRMTVPLAPRTSEKCSVLNLTASLSVGNSTSG
FT KRTGE (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054707"
FT VARIANT 25
FT /note="A -> T (in WMS1; shows consistent and significantly
FT diminished protein secretion)"
FT /evidence="ECO:0000269|PubMed:18567016"
FT /id="VAR_054439"
FT VARIANT 119
FT /note="R -> Q (in dbSNP:rs3814291)"
FT /id="VAR_054440"
FT VARIANT 134
FT /note="T -> S (in dbSNP:rs7255721)"
FT /evidence="ECO:0000269|PubMed:15355968"
FT /id="VAR_054441"
FT CONFLICT 385..386
FT /note="AT -> PQ (in Ref. 2; AAG35563)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="S -> N (in Ref. 2; AAG35563)"
FT /evidence="ECO:0000305"
FT CONFLICT 643
FT /note="C -> S (in Ref. 2; AAG35563)"
FT /evidence="ECO:0000305"
FT CONFLICT 1101
FT /note="H -> Q (in Ref. 2; AAG35563)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1103 AA; 120874 MW; D7558271C303A87C CRC64;
MAPACQILRW ALALGLGLMF EVTHAFRSQD EFLSSLESYE IAFPTRVDHN GALLAFSPPP
PRRQRRGTGA TAESRLFYKV ASPSTHFLLN LTRSSRLLAG HVSVEYWTRE GLAWQRAARP
HCLYAGHLQG QASTSHVAIS TCGGLHGLIV ADEEEYLIEP LHGGPKGSRS PEESGPHVVY
KRSSLRHPHL DTACGVRDEK PWKGRPWWLR TLKPPPARPL GNETERGQPG LKRSVSRERY
VETLVVADKM MVAYHGRRDV EQYVLAIMNI VAKLFQDSSL GSTVNILVTR LILLTEDQPT
LEITHHAGKS LDSFCKWQKS IVNHSGHGNA IPENGVANHD TAVLITRYDI CIYKNKPCGT
LGLAPVGGMC ERERSCSVNE DIGLATAFTI AHEIGHTFGM NHDGVGNSCG ARGQDPAKLM
AAHITMKTNP FVWSSCSRDY ITSFLDSGLG LCLNNRPPRQ DFVYPTVAPG QAYDADEQCR
FQHGVKSRQC KYGEVCSELW CLSKSNRCIT NSIPAAEGTL CQTHTIDKGW CYKRVCVPFG
SRPEGVDGAW GPWTPWGDCS RTCGGGVSSS SRHCDSPRPT IGGKYCLGER RRHRSCNTDD
CPPGSQDFRE VQCSEFDSIP FRGKFYKWKT YRGGGVKACS LTCLAEGFNF YTERAAAVVD
GTPCRPDTVD ICVSGECKHV GCDRVLGSDL REDKCRVCGG DGSACETIEG VFSPASPGAG
YEDVVWIPKG SVHIFIQDLN LSLSHLALKG DQESLLLEGL PGTPQPHRLP LAGTTFQLRQ
GPDQVQSLEA LGPINASLIV MVLARTELPA LRYRFNAPIA RDSLPPYSWH YAPWTKCSAQ
CAGGSQVQAV ECRNQLDSSA VAPHYCSAHS KLPKRQRACN TEPCPPDWVV GNWSLCSRSC
DAGVRSRSVV CQRRVSAAEE KALDDSACPQ PRPPVLEACH GPTCPPEWAA LDWSECTPSC
GPGLRHRVVL CKSADHRATL PPAHCSPAAK PPATMRCNLR RCPPARWVAG EWGECSAQCG
VGQRQRSVRC TSHTGQASHE CTEALRPPTT QQCEAKCDSP TPGDGPEECK DVNKVAYCPL
VLKFQFCSRA YFRQMCCKTC HGH
