ATS15_HUMAN
ID ATS15_HUMAN Reviewed; 950 AA.
AC Q8TE58; Q32MI6;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 15;
DE Short=ADAM-TS 15;
DE Short=ADAM-TS15;
DE Short=ADAMTS-15;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=ADAMTS15;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11867212; DOI=10.1016/s0378-1119(01)00861-7;
RA Cal S., Obaya A.J., Llamazares M., Garabaya C., Quesada V., Lopez-Otin C.;
RT "Cloning, expression analysis, and structural characterization of seven
RT novel human ADAMTSs, a family of metalloproteinases with disintegrin and
RT thrombospondin-1 domains.";
RL Gene 283:49-62(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN [3]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-770 AND GLY-878.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Metalloprotease which has proteolytic activity against the
CC proteoglycan VCAN, cleaving it at the 'Glu-1428-|-1429-Ala' site.
CC Cleaves VCAN in the pericellular matrix surrounding myoblasts,
CC facilitating myoblast contact and fusion which is required for skeletal
CC muscle development and regeneration. {ECO:0000250|UniProtKB:P59384}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9UHI8};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9UHI8};
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:P59384}. Cell surface
CC {ECO:0000250|UniProtKB:P59384}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal liver and kidney, but not in any
CC of the adult tissues examined. {ECO:0000269|PubMed:11867212}.
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 -!- 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.
CC {ECO:0000250|UniProtKB:P59384}.
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 be C-
CC glycosylated with one or two mannose molecules on tryptophan residues
CC within the consensus sequence W-X-X-W of the TPRs. Also N-glycosylated.
CC These other glycosylations can also facilitate secretion.
CC {ECO:0000250|UniProtKB:Q76LX8}.
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DR EMBL; AJ315733; CAC86014.1; -; mRNA.
DR EMBL; BC109114; AAI09115.1; -; mRNA.
DR CCDS; CCDS8488.1; -.
DR RefSeq; NP_620686.1; NM_139055.3.
DR AlphaFoldDB; Q8TE58; -.
DR SMR; Q8TE58; -.
DR BioGRID; 128081; 8.
DR STRING; 9606.ENSP00000299164; -.
DR MEROPS; M12.025; -.
DR GlyGen; Q8TE58; 4 sites.
DR iPTMnet; Q8TE58; -.
DR PhosphoSitePlus; Q8TE58; -.
DR BioMuta; ADAMTS15; -.
DR DMDM; 48474504; -.
DR jPOST; Q8TE58; -.
DR MassIVE; Q8TE58; -.
DR MaxQB; Q8TE58; -.
DR PaxDb; Q8TE58; -.
DR PeptideAtlas; Q8TE58; -.
DR PRIDE; Q8TE58; -.
DR ProteomicsDB; 74400; -.
DR Antibodypedia; 33110; 143 antibodies from 20 providers.
DR DNASU; 170689; -.
DR Ensembl; ENST00000299164.4; ENSP00000299164.2; ENSG00000166106.4.
DR GeneID; 170689; -.
DR KEGG; hsa:170689; -.
DR MANE-Select; ENST00000299164.4; ENSP00000299164.2; NM_139055.4; NP_620686.1.
DR UCSC; uc010scd.3; human.
DR CTD; 170689; -.
DR DisGeNET; 170689; -.
DR GeneCards; ADAMTS15; -.
DR HGNC; HGNC:16305; ADAMTS15.
DR HPA; ENSG00000166106; Tissue enhanced (adipose).
DR MIM; 607509; gene.
DR neXtProt; NX_Q8TE58; -.
DR OpenTargets; ENSG00000166106; -.
DR PharmGKB; PA24541; -.
DR VEuPathDB; HostDB:ENSG00000166106; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000155801; -.
DR HOGENOM; CLU_000660_3_0_1; -.
DR InParanoid; Q8TE58; -.
DR OMA; HNLNKYR; -.
DR OrthoDB; 125522at2759; -.
DR PhylomeDB; Q8TE58; -.
DR TreeFam; TF331949; -.
DR BRENDA; 3.4.24.B12; 2681.
DR PathwayCommons; Q8TE58; -.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR BioGRID-ORCS; 170689; 7 hits in 1069 CRISPR screens.
DR ChiTaRS; ADAMTS15; human.
DR GenomeRNAi; 170689; -.
DR Pharos; Q8TE58; Tbio.
DR PRO; PR:Q8TE58; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8TE58; protein.
DR Bgee; ENSG00000166106; Expressed in decidua and 120 other tissues.
DR Genevisible; Q8TE58; HS.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0050840; F:extracellular matrix binding; IEA:Ensembl.
DR GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0022617; P:extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0007520; P:myoblast fusion; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.20.100.10; -; 3.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
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; IPR013277; Pept_M12B_ADAM-TS8.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
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; PF01421; Reprolysin; 1.
DR Pfam; PF00090; TSP_1; 1.
DR PRINTS; PR01861; ADAMTS8.
DR PRINTS; PR01857; ADAMTSFAMILY.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00209; TSP1; 3.
DR SUPFAM; SSF82895; SSF82895; 3.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50092; TSP1; 3.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..212
FT /evidence="ECO:0000250|UniProtKB:P59384"
FT /id="PRO_0000029192"
FT CHAIN 213..950
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 15"
FT /id="PRO_0000029193"
FT DOMAIN 218..427
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 428..515
FT /note="Disintegrin"
FT DOMAIN 516..571
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 839..895
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 896..949
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 151..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..838
FT /note="Spacer"
FT REGION 798..822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 172..179
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT COMPBIAS 799..815
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 362
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 174
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 361
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 591
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 679
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 293..345
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 322..327
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 339..422
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 377..406
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 448..470
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 459..480
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 465..499
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 493..504
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 528..565
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 532..570
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 543..555
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT VARIANT 623
FT /note="N -> S (in dbSNP:rs11222114)"
FT /id="VAR_051594"
FT VARIANT 770
FT /note="Q -> R (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs776537988)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036150"
FT VARIANT 878
FT /note="C -> G (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036151"
SQ SEQUENCE 950 AA; 103287 MW; 5DFBE18285CCCC3B CRC64;
MLLLGILTLA FAGRTAGGSE PEREVVVPIR LDPDINGRRY YWRGPEDSGD QGLIFQITAF
QEDFYLHLTP DAQFLAPAFS TEHLGVPLQG LTGGSSDLRR CFYSGDVNAE PDSFAAVSLC
GGLRGAFGYR GAEYVISPLP NASAPAAQRN SQGAHLLQRR GVPGGPSGDP TSRCGVASGW
NPAILRALDP YKPRRAGFGE SRSRRRSGRA KRFVSIPRYV ETLVVADESM VKFHGADLEH
YLLTLLATAA RLYRHPSILN PINIVVVKVL LLRDRDSGPK VTGNAALTLR NFCAWQKKLN
KVSDKHPEYW DTAILFTRQD LCGATTCDTL GMADVGTMCD PKRSCSVIED DGLPSAFTTA
HELGHVFNMP HDNVKVCEEV FGKLRANHMM SPTLIQIDRA NPWSACSAAI ITDFLDSGHG
DCLLDQPSKP ISLPEDLPGA SYTLSQQCEL AFGVGSKPCP YMQYCTKLWC TGKAKGQMVC
QTRHFPWADG TSCGEGKLCL KGACVERHNL NKHRVDGSWA KWDPYGPCSR TCGGGVQLAR
RQCTNPTPAN GGKYCEGVRV KYRSCNLEPC PSSASGKSFR EEQCEAFNGY NHSTNRLTLA
VAWVPKYSGV SPRDKCKLIC RANGTGYFYV LAPKVVDGTL CSPDSTSVCV QGKCIKAGCD
GNLGSKKRFD KCGVCGGDNK SCKKVTGLFT KPMHGYNFVV AIPAGASSID IRQRGYKGLI
GDDNYLALKN SQGKYLLNGH FVVSAVERDL VVKGSLLRYS GTGTAVESLQ ASRPILEPLT
VEVLSVGKMT PPRVRYSFYL PKEPREDKSS HPKDPRGPSV LHNSVLSLSN QVEQPDDRPP
ARWVAGSWGP CSASCGSGLQ KRAVDCRGSA GQRTVPACDA AHRPVETQAC GEPCPTWELS
AWSPCSKSCG RGFQRRSLKC VGHGGRLLAR DQCNLHRKPQ ELDFCVLRPC
