ATS5_MOUSE
ID ATS5_MOUSE Reviewed; 930 AA.
AC Q9R001; B2RRX9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 5;
DE Short=ADAM-TS 5;
DE Short=ADAM-TS5;
DE Short=ADAMTS-5;
DE EC=3.4.24.-;
DE AltName: Full=ADMP-2;
DE AltName: Full=Aggrecanase-2;
DE AltName: Full=Implantin;
DE Flags: Precursor;
GN Name=Adamts5;
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 [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=10464288; DOI=10.1074/jbc.274.36.25555;
RA Hurskainen T.L., Hirohata S., Seldin M.F., Apte S.S.;
RT "ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc
RT metalloproteases.";
RL J. Biol. Chem. 274:25555-25563(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15800625; DOI=10.1038/nature03417;
RA Stanton H., Rogerson F.M., East C.J., Golub S.B., Lawlor K.E., Meeker C.T.,
RA Little C.B., Last K., Farmer P.J., Campbell I.K., Fourie A.M., Fosang A.J.;
RT "ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in
RT vitro.";
RL Nature 434:648-652(2005).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27855162; DOI=10.1371/journal.pbio.1002580;
RA McMahon M., Ye S., Izzard L., Dlugolenski D., Tripp R.A., Bean A.G.,
RA McCulloch D.R., Stambas J.;
RT "ADAMTS5 is a critical regulator of virus-specific T cell immunity.";
RL PLoS Biol. 14:E1002580-E1002580(2016).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28702327; DOI=10.1016/j.molmet.2017.05.004;
RA Bauters D., Cobbaut M., Geys L., Van Lint J., Hemmeryckx B., Lijnen H.R.;
RT "Loss of ADAMTS5 enhances brown adipose tissue mass and promotes browning
RT of white adipose tissue via CREB signaling.";
RL Mol. Metab. 6:715-724(2017).
CC -!- FUNCTION: Metalloproteinase that plays an important role in connective
CC tissue organization, development, inflammation and cell migration.
CC Extracellular matrix (ECM) degrading enzyme that shows proteolytic
CC activity toward the hyalectan group of chondroitin sulfate
CC proteoglycans (CSPGs) including ACAN, VCAN, BCAN and NCAN. Cleavage
CC within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a
CC role in embryonic development, including limb and cardiac
CC morphogenesis, and skeletal muscle development through its VCAN
CC remodeling properties. Cleaves VCAN in the pericellular matrix
CC surrounding myoblasts, facilitating myoblast contact and fusion which
CC is required for skeletal muscle development and regeneration
CC (PubMed:23233679). Participates in the development of brown adipose
CC tissue and browning of white adipose tissue (PubMed:28702327). Plays an
CC important role for T-lymphocyte migration from draining lymph nodes
CC following viral infection (PubMed:27855162).
CC {ECO:0000269|PubMed:15800625, ECO:0000269|PubMed:23233679,
CC ECO:0000269|PubMed:27855162, ECO:0000269|PubMed:28702327}.
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:0000250|UniProtKB:Q9UNA0}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle.
CC {ECO:0000269|PubMed:23233679}.
CC -!- DEVELOPMENTAL STAGE: Expressed specifically in the peri-implantation
CC period in embryo and trophoblast and at low or undetectable level
CC thereafter (PubMed:10464288). In embryonic skeletal muscle, levels
CC significantly increase between 13.5 dpc and 15.5 dpc with maximal
CC expression observed at 15.5 dpc (PubMed:23233679). Decreased levels in
CC postnatal skeletal muscle (PubMed:23233679). In myoblasts, up-regulated
CC soon after induction of myoblast differentiation (PubMed:23233679).
CC {ECO:0000269|PubMed:10464288, 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.
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 furin and PCSK7 outside of the cell.
CC {ECO:0000250|UniProtKB:Q9UNA0}.
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 -!- DISRUPTION PHENOTYPE: Mice are viable and fertile (PubMed:15800625).
CC Significantly increased mass of brown adipose tissue (PubMed:28702327).
CC Delayed virus clearance and compromised T cell migration during viral
CC infection (PubMed:27855162). No effect on VCAN cleavage in embryonic
CC skeletal muscle, potentially as a result of participation by other
CC proteinases, but absence of VCAN cleavage and greater number of
CC centrally located nuclei in postnatal skeletal muscle
CC (PubMed:23233679). {ECO:0000269|PubMed:15800625,
CC ECO:0000269|PubMed:23233679, ECO:0000269|PubMed:27855162,
CC ECO:0000269|PubMed:28702327}.
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DR EMBL; AF140673; AAD56356.1; -; mRNA.
DR EMBL; BC138619; AAI38620.1; -; mRNA.
DR EMBL; BC138620; AAI38621.1; -; mRNA.
DR CCDS; CCDS28288.1; -.
DR RefSeq; NP_035912.2; NM_011782.2.
DR AlphaFoldDB; Q9R001; -.
DR SMR; Q9R001; -.
DR BioGRID; 204717; 2.
DR STRING; 10090.ENSMUSP00000023611; -.
DR MEROPS; M12.225; -.
DR GlyGen; Q9R001; 7 sites.
DR PhosphoSitePlus; Q9R001; -.
DR MaxQB; Q9R001; -.
DR PaxDb; Q9R001; -.
DR PeptideAtlas; Q9R001; -.
DR PRIDE; Q9R001; -.
DR ProteomicsDB; 273586; -.
DR Antibodypedia; 986; 434 antibodies from 34 providers.
DR DNASU; 23794; -.
DR Ensembl; ENSMUST00000023611; ENSMUSP00000023611; ENSMUSG00000022894.
DR GeneID; 23794; -.
DR KEGG; mmu:23794; -.
DR UCSC; uc007ztw.1; mouse.
DR CTD; 11096; -.
DR MGI; MGI:1346321; Adamts5.
DR VEuPathDB; HostDB:ENSMUSG00000022894; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000159090; -.
DR HOGENOM; CLU_000660_3_0_1; -.
DR InParanoid; Q9R001; -.
DR OMA; TPCPPNG; -.
DR OrthoDB; 125522at2759; -.
DR PhylomeDB; Q9R001; -.
DR TreeFam; TF331949; -.
DR BRENDA; 3.4.24.B12; 3474.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR Reactome; R-MMU-5173214; O-glycosylation of TSR domain-containing proteins.
DR BioGRID-ORCS; 23794; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Adamts5; mouse.
DR PRO; PR:Q9R001; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9R001; protein.
DR Bgee; ENSMUSG00000022894; Expressed in decidua and 234 other tissues.
DR Genevisible; Q9R001; MM.
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; IMP:UniProtKB.
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:0008237; F:metallopeptidase activity; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0042742; P:defense response to bacterium; IGI:MGI.
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:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0044691; P:tooth eruption; IEA:Ensembl.
DR Gene3D; 2.20.100.10; -; 2.
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; IPR013276; Pept_M12B_ADAM-TS5.
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; PR01860; ADAMTS5.
DR PRINTS; PR01857; ADAMTSFAMILY.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00209; TSP1; 2.
DR SUPFAM; SSF82895; SSF82895; 2.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50092; TSP1; 2.
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..21
FT /evidence="ECO:0000255"
FT PROPEP 22..261
FT /evidence="ECO:0000255"
FT /id="PRO_0000029172"
FT CHAIN 262..930
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 5"
FT /id="PRO_0000029173"
FT DOMAIN 267..476
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 485..566
FT /note="Disintegrin"
FT DOMAIN 567..622
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 875..929
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 31..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 207..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..874
FT /note="Spacer"
FT MOTIF 207..214
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 411
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 209
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 410
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT BINDING 414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT BINDING 420
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 570
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT CARBOHYD 573
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT CARBOHYD 582
FT /note="O-linked (Fuc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT CARBOHYD 728
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 802
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 807
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 342..394
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 371..376
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 388..471
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 426..455
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 497..519
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 508..529
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 514..548
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 542..553
FT /evidence="ECO:0000250|UniProtKB:Q9UNA0"
FT DISULFID 579..616
FT /evidence="ECO:0000250"
FT DISULFID 583..621
FT /evidence="ECO:0000250"
FT DISULFID 594..606
FT /evidence="ECO:0000250"
FT CONFLICT 7
FT /note="P -> S (in Ref. 1; AAD56356)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="Q -> H (in Ref. 1; AAD56356)"
FT /evidence="ECO:0000305"
FT CONFLICT 772
FT /note="T -> P (in Ref. 1; AAD56356)"
FT /evidence="ECO:0000305"
FT CONFLICT 844
FT /note="D -> G (in Ref. 1; AAD56356)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 930 AA; 101844 MW; 0CF1B264C782FF49 CRC64;
MRLEWAPLLL LLLLLSASCL SLAADSPAAA PAQDKTRQPQ AAAAAAEPDQ PQGEETRERG
HLQPLAGQRR SGGLVQNIDQ LYSGGGKVGY LVYAGGRRFL LDLERDDTVG AAGSIVTAGG
GLSASSGHRG HCFYRGTVDG SPRSLAVFDL CGGLDGFFAV KHARYTLKPL LRGSWAEYER
IYGDGSSRIL HVYNREGFSF EALPPRASCE TPASPSGPQE SPSVHSRSRR RSALAPQLLD
HSAFSPSGNA GPQTWWRRRR RSISRARQVE LLLVADSSMA RMYGRGLQHY LLTLASIANR
LYSHASIENH IRLAVVKVVV LTDKDTSLEV SKNAATTLKN FCKWQHQHNQ LGDDHEEHYD
AAILFTREDL CGHHSCDTLG MADVGTICSP ERSCAVIEDD GLHAAFTVAH EIGHLLGLSH
DDSKFCEENF GTTEDKRLMS SILTSIDASK PWSKCTSATI TEFLDDGHGN CLLDLPRKQI
LGPEELPGQT YDATQQCNLT FGPEYSVCPG MDVCARLWCA VVRQGQMVCL TKKLPAVEGT
PCGKGRVCLQ GKCVDKTKKK YYSTSSHGNW GSWGPWGQCS RSCGGGVQFA YRHCNNPAPR
NSGRYCTGKR AIYRSCSVTP CPPNGKSFRH EQCEAKNGYQ SDAKGVKTFV EWVPKYAGVL
PADVCKLTCR AKGTGYYVVF SPKVTDGTEC RPYSNSVCVR GRCVRTGCDG IIGSKLQYDK
CGVCGGDNSS CTKIIGTFNK KSKGYTDVVR IPEGATHIKV RQFKAKDQTR FTAYLALKKK
TGEYLINGKY MISTSETIID INGTVMNYSG WSHRDDFLHG MGYSATKEIL IVQILATDPT
KALDVRYSFF VPKKTTQKVN SVISHGSNKV GPHSTQLQWV TGPWLACSRT CDTGWHTRTV
QCQDGNRKLA KGCLLSQRPS AFKQCLLKKC
