ID   ATS4_MOUSE              Reviewed;         833 AA.
AC   Q8BNJ2; Q8K384;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2005, sequence version 2.
DT   27-MAR-2024, entry version 155.
DE   RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 4;
DE            Short=ADAM-TS 4;
DE            Short=ADAM-TS4;
DE            Short=ADAMTS-4;
DE            EC=3.4.24.82;
DE   AltName: Full=Aggrecanase-1;
DE   Flags: Precursor;
GN   Name=Adamts4;
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;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   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).
CC   -!- FUNCTION: Cleaves aggrecan, a cartilage proteoglycan, and may be
CC       involved in its turnover. May play an important role in the destruction
CC       of aggrecan in arthritic diseases. Cleaves aggrecan at the '392-Glu-|-
CC       Ala-393' site (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Glutamyl endopeptidase. Bonds cleaved include 370-Thr-Glu-Gly-
CC         Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian
CC         aggrecan.; EC=3.4.24.82;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:O75173};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O75173};
CC   -!- SUBUNIT: Interacts with SRPX2. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
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. {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   -!- SEQUENCE CAUTION:
CC       Sequence=BAC38944.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AK083534; BAC38944.1; ALT_INIT; mRNA.
DR   EMBL; BC027773; AAH27773.1; -; mRNA.
DR   CCDS; CCDS15485.2; -.
DR   RefSeq; NP_766433.2; NM_172845.3.
DR   AlphaFoldDB; Q8BNJ2; -.
DR   SMR; Q8BNJ2; -.
DR   STRING; 10090.ENSMUSP00000151387; -.
DR   MEROPS; M12.221; -.
DR   GlyCosmos; Q8BNJ2; 2 sites, No reported glycans.
DR   GlyGen; Q8BNJ2; 2 sites.
DR   PhosphoSitePlus; Q8BNJ2; -.
DR   MaxQB; Q8BNJ2; -.
DR   PaxDb; 10090-ENSMUSP00000006570; -.
DR   ProteomicsDB; 277228; -.
DR   Antibodypedia; 20503; 625 antibodies from 36 providers.
DR   DNASU; 240913; -.
DR   Ensembl; ENSMUST00000111315.9; ENSMUSP00000106947.4; ENSMUSG00000006403.14.
DR   GeneID; 240913; -.
DR   KEGG; mmu:240913; -.
DR   AGR; MGI:1339949; -.
DR   CTD; 9507; -.
DR   MGI; MGI:1339949; Adamts4.
DR   VEuPathDB; HostDB:ENSMUSG00000006403; -.
DR   eggNOG; KOG3538; Eukaryota.
DR   GeneTree; ENSGT00940000160966; -.
DR   InParanoid; Q8BNJ2; -.
DR   OMA; MHHDGTG; -.
DR   OrthoDB; 2910701at2759; -.
DR   BRENDA; 3.4.24.82; 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; 240913; 1 hit in 78 CRISPR screens.
DR   ChiTaRS; Adamts4; mouse.
DR   PRO; PR:Q8BNJ2; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q8BNJ2; Protein.
DR   Bgee; ENSMUSG00000006403; Expressed in lumbar subsegment of spinal cord and 174 other cell types or tissues.
DR   ExpressionAtlas; Q8BNJ2; baseline and differential.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IDA:MGI.
DR   GO; GO:0008237; F:metallopeptidase activity; IDA:MGI.
DR   GO; GO:0008233; F:peptidase activity; ISO:MGI.
DR   GO; GO:0002020; F:protease binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR   GO; GO:0042742; P:defense response to bacterium; IGI:MGI.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; IDA:MGI.
DR   CDD; cd04273; ZnMc_ADAMTS_like; 1.
DR   Gene3D; 2.60.120.830; -; 1.
DR   Gene3D; 3.40.1620.60; -; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 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; IPR001590; Peptidase_M12B.
DR   InterPro; IPR000884; TSP1_rpt.
DR   InterPro; IPR036383; TSP1_rpt_sf.
DR   PANTHER; PTHR13723:SF38; A DISINTEGRIN AND METALLOPROTEINASE WITH THROMBOSPONDIN MOTIFS 4; 1.
DR   PANTHER; PTHR13723; ADAMTS A DISINTEGRIN AND METALLOPROTEASE WITH THROMBOSPONDIN MOTIFS PROTEASE; 1.
DR   Pfam; PF17771; ADAMTS_CR_2; 1.
DR   Pfam; PF19236; ADAMTS_CR_3; 1.
DR   Pfam; PF05986; ADAMTS_spacer1; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   Pfam; PF00090; TSP_1; 1.
DR   PRINTS; PR01857; ADAMTSFAMILY.
DR   SMART; SM00608; ACR; 1.
DR   SMART; SM00209; TSP1; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF82895; TSP-1 type 1 repeat; 1.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS50092; TSP1; 1.
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; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..49
FT                   /evidence="ECO:0000255"
FT   PROPEP          50..208
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000029166"
FT   CHAIN           209..833
FT                   /note="A disintegrin and metalloproteinase with
FT                   thrombospondin motifs 4"
FT                   /id="PRO_0000029167"
FT   DOMAIN          214..424
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          433..515
FT                   /note="Disintegrin"
FT   DOMAIN          516..571
FT                   /note="TSP type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   REGION          180..204
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          682..833
FT                   /note="Spacer"
FT   MOTIF           188..195
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        184..204
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        358
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         190
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         357
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   BINDING         361
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   BINDING         367
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   CARBOHYD        63
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        289..341
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        318..323
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        335..419
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        373..403
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        445..468
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        456..478
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        463..497
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        491..502
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        528..565
FT                   /evidence="ECO:0000250"
FT   DISULFID        532..570
FT                   /evidence="ECO:0000250"
FT   DISULFID        543..555
FT                   /evidence="ECO:0000250"
FT   CONFLICT        18
FT                   /note="Q -> R (in Ref. 2; AAH27773)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   833 AA;  90070 MW;  6512B9ED2617F3A4 CRC64;
     MSQMGLHPRR GLTGHWLQRF QPCLPLHTVQ WRRLLLLAFL LSLAWPASPL PREEEIVFPE
     KLNGSSILPG SGVPARLLYR LPAFGEMLLL ELEQDPGVQV EGLTVQYLGQ APEMLGGAEP
     GTYLTGTING DPESVASLHW DGGALLGVLQ YRGAELHLQP LEGGALNSAG GPGAHILRRK
     SPASSQGPMC TVKAPSGSPS PISRRTKRFA SLSRFVETLV VADDKMAAFH GTGLKRYLLT
     VMAAAAKAFK HPSIRNPVNL VVTRLVILGS GQEGPQVGPS AAQTLRSFCT WQRGLNTPND
     SDPDHFDTAI LFTRQDLCGV STCDTLGMAD VGTVCDPARS CAIVEDDGLQ SAFTAAHELG
     HVFNMLHDNS KPCTNLNGQG GSSRHVMAPV MAHVDPEEPW SPCSARFITD FLDNGYGHCL
     LDKPEAPLHL PATFPGKDYD ADRQCQLTFG PDSSHCPQLP PPCAALWCSG HLNGHAMCQT
     KHSPWADGTP CGSSQACMGG RCLHVDQLKD FNVPQAGGWG PWGPWGDCSR TCGGGVQFSS
     RDCTRPVPRN GGKYCEGRRT RFRSCNTENC PHGSALTFRE EQCAAYNHRT DLFKSFPGPM
     DWVPRYTGVA PRDQCKLTCQ ARALGYYYVL EPRVADGTPC SPDTSSVCVQ GRCIHAGCDR
     IIGSKKKFDK CMVCGGDGSR CSKQSGSFKK FRYGYSDVVT IPAGATHILV RQQGGSGLKS
     IYLALKLSDG SYALNGEYTL MPSPTDVVLP GAVSLRYSGA TAASETLSGH GPLAQPLTLQ
     VLVAGNPQNA RLRYSFFVPR PVPSTPRPPP QDWLQRRAEI LKILRKRPWA GRK
//