ATS4_MOUSE
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 03-AUG-2022, entry version 146.
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.ENSMUSP00000006570; -.
DR MEROPS; M12.221; -.
DR GlyGen; Q8BNJ2; 2 sites.
DR PhosphoSitePlus; Q8BNJ2; -.
DR MaxQB; Q8BNJ2; -.
DR PaxDb; Q8BNJ2; -.
DR PRIDE; Q8BNJ2; -.
DR ProteomicsDB; 277228; -.
DR Antibodypedia; 20503; 567 antibodies from 36 providers.
DR DNASU; 240913; -.
DR Ensembl; ENSMUST00000111315; ENSMUSP00000106947; ENSMUSG00000006403.
DR GeneID; 240913; -.
DR KEGG; mmu:240913; -.
DR CTD; 9507; -.
DR MGI; MGI:1339949; Adamts4.
DR VEuPathDB; HostDB:ENSMUSG00000006403; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000160966; -.
DR InParanoid; Q8BNJ2; -.
DR OMA; CGPSQAC; -.
DR OrthoDB; 125522at2759; -.
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 73 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 173 other 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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: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 Gene3D; 2.20.100.10; -; 1.
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; 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; PR01857; ADAMTSFAMILY.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF82895; SSF82895; 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
