ATS15_MOUSE
ID ATS15_MOUSE Reviewed; 950 AA.
AC P59384; Q504Z2; Q91Z56;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 149.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Kidney;
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 [2]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=23233679; DOI=10.1074/jbc.m112.429647;
RA Stupka N., Kintakas C., White J.D., Fraser F.W., Hanciu M.,
RA Aramaki-Hattori N., Martin S., Coles C., Collier F., Ward A.C., Apte S.S.,
RA McCulloch D.R.;
RT "Versican processing by a disintegrin-like and metalloproteinase domain
RT with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast
RT fusion.";
RL J. Biol. Chem. 288:1907-1917(2013).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PROTEOLYTIC CLEAVAGE,
RP GLYCOSYLATION AT ASN-141, AND MUTAGENESIS OF ASN-141 AND ARG-212.
RX PubMed=24220035; DOI=10.1074/jbc.m112.418624;
RA Dancevic C.M., Fraser F.W., Smith A.D., Stupka N., Ward A.C.,
RA McCulloch D.R.;
RT "Biosynthesis and expression of a disintegrin-like and metalloproteinase
RT domain with thrombospondin-1 repeats-15: a novel versican-cleaving
RT proteoglycanase.";
RL J. Biol. Chem. 288:37267-37276(2013).
CC -!- FUNCTION: Metalloprotease which has proteolytic activity against the
CC proteoglycan VCAN, cleaving it at the 'Glu-1401-|-1402-Ala' site
CC (PubMed:24220035). Cleaves VCAN in the pericellular matrix surrounding
CC myoblasts, facilitating myoblast contact and fusion which is required
CC for skeletal muscle development and regeneration (PubMed:23233679).
CC {ECO:0000269|PubMed:23233679, ECO:0000269|PubMed:24220035}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9UNA0};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9UNA0};
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:24220035}. Cell surface
CC {ECO:0000269|PubMed:24220035}.
CC -!- TISSUE SPECIFICITY: At 10.5 dpc, strongly and specifically expressed in
CC the developing heart tubes (PubMed:24220035). By 13.5 dpc, widely
CC expressed including in the perichondrium in the developing autopod,
CC brain, ear, whisker follicles, vertebral column and epidermis
CC (PubMed:24220035). Also localizes to the myocardium of the developing
CC right atrium, the bulbous cordis and the airway epithelia of the main
CC bronchiole in the lung bud at 11.5 dpc, the vertebral column and dorsal
CC root ganglia at 14.5 dpc, and the developing hind limb at 15.5 dpc
CC (PubMed:24220035). In the adult colon, highly expressed in the
CC muscularis externa (inner circular smooth muscle and outer longitudinal
CC smooth muscle), muscularis mucosa, submucosal glands, crypt, villi
CC epithelial cells, goblet cells and lamina propria (PubMed:24220035).
CC {ECO:0000269|PubMed:24220035}.
CC -!- DEVELOPMENTAL STAGE: In embryonic skeletal muscle, significantly
CC increased levels between 13.5 dpc and 15.5 dpc with maximal expression
CC observed at 15.5 dpc (PubMed:23233679). Decreased levels in postnatal
CC skeletal muscle (PubMed:23233679). In myoblasts, up-regulated soon
CC after induction of myoblast differentiation (PubMed:23233679).
CC {ECO:0000269|PubMed:23233679}.
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:0000269|PubMed:24220035}.
CC -!- PTM: Glycosylated (PubMed:24220035). Can be O-fucosylated by POFUT2 on
CC a serine or a threonine residue found within the consensus sequence C1-
CC X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are
CC the first and second cysteine residue of the repeat, respectively (By
CC similarity). Fucosylated repeats can then be further glycosylated by
CC the addition of a beta-1,3-glucose residue by the glucosyltransferase,
CC B3GALTL (By similarity). Fucosylation mediates the efficient secretion
CC of ADAMTS family members (By similarity). Can be C-glycosylated with
CC one or two mannose molecules on tryptophan residues within the
CC consensus sequence W-X-X-W of the TPRs (By similarity). Also N-
CC glycosylated (PubMed:24220035). These other glycosylations can also
CC facilitate secretion (By similarity). {ECO:0000250|UniProtKB:Q76LX8,
CC ECO:0000269|PubMed:24220035}.
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DR EMBL; BC009667; AAH09667.1; -; mRNA.
DR EMBL; BC043308; AAH43308.1; -; mRNA.
DR EMBL; BC094677; AAH94677.1; -; mRNA.
DR CCDS; CCDS22945.1; -.
DR RefSeq; NP_001019310.1; NM_001024139.1.
DR RefSeq; NP_001316349.1; NM_001329420.1.
DR AlphaFoldDB; P59384; -.
DR SMR; P59384; -.
DR BioGRID; 231622; 2.
DR STRING; 10090.ENSMUSP00000067022; -.
DR MEROPS; M12.025; -.
DR GlyGen; P59384; 4 sites.
DR iPTMnet; P59384; -.
DR PhosphoSitePlus; P59384; -.
DR MaxQB; P59384; -.
DR PaxDb; P59384; -.
DR PRIDE; P59384; -.
DR ProteomicsDB; 277200; -.
DR Antibodypedia; 33110; 143 antibodies from 20 providers.
DR DNASU; 235130; -.
DR Ensembl; ENSMUST00000065112; ENSMUSP00000067022; ENSMUSG00000033453.
DR GeneID; 235130; -.
DR KEGG; mmu:235130; -.
DR UCSC; uc009oqz.1; mouse.
DR CTD; 170689; -.
DR MGI; MGI:2449569; Adamts15.
DR VEuPathDB; HostDB:ENSMUSG00000033453; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000155801; -.
DR HOGENOM; CLU_000660_3_0_1; -.
DR InParanoid; P59384; -.
DR OMA; HNLNKYR; -.
DR OrthoDB; 125522at2759; -.
DR PhylomeDB; P59384; -.
DR TreeFam; TF331949; -.
DR BRENDA; 3.4.24.B12; 3474.
DR Reactome; R-MMU-5173214; O-glycosylation of TSR domain-containing proteins.
DR BioGRID-ORCS; 235130; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Adamts15; mouse.
DR PRO; PR:P59384; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P59384; protein.
DR Bgee; ENSMUSG00000033453; Expressed in aortic valve and 149 other tissues.
DR ExpressionAtlas; P59384; baseline and differential.
DR Genevisible; P59384; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0004175; F:endopeptidase activity; IDA:MGI.
DR GO; GO:0050840; F:extracellular matrix binding; IDA:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
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; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0007520; P:myoblast fusion; IMP: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 1: Evidence at protein 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..18
FT /evidence="ECO:0000255"
FT PROPEP 19..212
FT /evidence="ECO:0000269|PubMed:24220035"
FT /id="PRO_0000270787"
FT CHAIN 213..950
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 15"
FT /id="PRO_0000078212"
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 144..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..838
FT /note="Spacer"
FT /evidence="ECO:0000250"
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|UniProtKB:Q9UNA0"
FT BINDING 365
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT SITE 212..213
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000269|PubMed:24220035"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24220035"
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 MUTAGEN 141
FT /note="N->Q: Reduced glycosylation."
FT /evidence="ECO:0000269|PubMed:24220035"
FT MUTAGEN 212
FT /note="R->A: Reduced propeptide cleavage."
FT /evidence="ECO:0000269|PubMed:24220035"
FT CONFLICT 389..396
FT /note="MMSPTLIQ -> AIPAGASS (in Ref. 1; AAH43308)"
FT /evidence="ECO:0000305"
FT CONFLICT 611..614
FT /note="SPRD -> PRVR (in Ref. 1; AAH09667)"
FT /evidence="ECO:0000305"
FT CONFLICT 819
FT /note="P -> L (in Ref. 1; AAH09667)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 950 AA; 103938 MW; 891926F281E92010 CRC64;
MLLLGISILA LAWRPAGSSE PEWEVVVPIR RDPDINGRHY YRRGTEDSGD QGLIFQITAF
QQDFYLHLTP DAQFLAPAFA TEYLGVPLQR LTGSSLDLRR CFYSGYVNAE PDSFAAVSLC
GGLRGAFGYR GAEYVISPLP NTSAPEAQRH SQGAHLLQRR GAPVGPSGDP TSRCGVASGW
NPAILRALDP YKPRRTGAGE SHNRRRSGRA KRFVSIPRYV ETLVVADESM VKFHGADLEH
YLLTLLATAA RLYRHPSILN PINIVVVKVL LLGDRDTGPK VTGNAALTLR NFCAWQKKLN
KVSDKHPEYW DTAILFTRQD LCGATTCDTL GMADVGTMCD PKRSCSVIED DGLPSAFTTA
HELGHVFNMP HDNVKVCEEV FGKLRANHMM SPTLIQIDRA NPWSACSAAI ITDFLDSGHG
DCLLDQPSKP ITLPEDLPGT SYSLSQQCEL AFGVGSKPCP YMQYCTKLWC TGKAKGQMVC
QTRHFPWADG TSCGEGKFCL KGACVERHNP NKYRVDGSWA KWEPYGSCSR TCGGGVQLAR
RQCSNPTPAN GGKYCEGVRV KYRSCNLEPC PSSASGKSFR EEQCEAFNGY NHSTNRLTLA
VAWVPKYSGV SPRDKCKLIC RANGTGYFYV LAPKVVDGTL CTPDSTSVCV QGKCIKAGCD
GNLGSKKKFD KCGVCGGDNK SCKRVTGLFT KPMHGYNFVV AIPAGASSID IRQRGYKGLI
GDDNYLALKN SQGKYLLNGH FVVSAVERDL VVKGSVLRYS GTGTAVESLQ ASRPILEPLT
VEVLSVGKMT PPRVRYSFYL PKEPREDKST RPKDPRGSPV LRNSVLSLSN QVEQPDNRPP
ARWVAGSWGP CSVSCGSGLQ KRAVDCRDSP GQQGASACDV DHRPLEKRAC GEPCPTWELG
NWSPCSKSCG RGFKRRPLKC VGHGGRLLAR DQCDLRRKPQ ELDFCVLRPC
