ATS12_MOUSE
ID ATS12_MOUSE Reviewed; 1600 AA.
AC Q811B3; E9QKD6; Q8BK92; Q8BKY1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 12;
DE Short=ADAM-TS 12;
DE Short=ADAM-TS12;
DE Short=ADAMTS-12;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=Adamts12;
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] (ISOFORM 1).
RA Cal S., Lopez-Otin C.;
RT "Mouse ADAMTS-12.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-1009 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryonic head, and Oviduct;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
CC -!- FUNCTION: Metalloprotease that plays a role in the degradation of COMP
CC (By similarity). Cleaves also alpha-2 macroglobulin and aggregan. Has
CC anti-tumorigenic properties (By similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by alpha-2 macroglobulin. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with COMP. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q811B3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q811B3-2; Sequence=VSP_013149, VSP_013150;
CC -!- DOMAIN: The C-terminal four TSP1-like repeats are necessary and
CC sufficient for binding COMP. {ECO:0000250}.
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: Subjected to an intracellular maturation process yielding a 120
CC kDa N-terminal fragment containing the metalloproteinase, disintegrin,
CC one TSP type-1 and the Cys-rich domains and a 83 kDa C-terminal
CC fragment containing the spacer 2 and four TSP type-1 domains.
CC {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}.
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DR EMBL; AJ537452; CAD60967.1; -; mRNA.
DR EMBL; AK048612; BAC33391.1; -; mRNA.
DR EMBL; AK054015; BAC35621.1; -; mRNA.
DR EMBL; AC102219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC156609; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC159963; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS27384.1; -. [Q811B3-1]
DR RefSeq; NP_780710.2; NM_175501.3. [Q811B3-1]
DR AlphaFoldDB; Q811B3; -.
DR SMR; Q811B3; -.
DR BioGRID; 232071; 3.
DR STRING; 10090.ENSMUSP00000057796; -.
DR MEROPS; M12.237; -.
DR GlyGen; Q811B3; 1 site.
DR iPTMnet; Q811B3; -.
DR PhosphoSitePlus; Q811B3; -.
DR MaxQB; Q811B3; -.
DR PaxDb; Q811B3; -.
DR PRIDE; Q811B3; -.
DR ProteomicsDB; 277220; -. [Q811B3-1]
DR ProteomicsDB; 277221; -. [Q811B3-2]
DR Antibodypedia; 22743; 143 antibodies from 22 providers.
DR DNASU; 239337; -.
DR Ensembl; ENSMUST00000061318; ENSMUSP00000057796; ENSMUSG00000047497. [Q811B3-1]
DR GeneID; 239337; -.
DR KEGG; mmu:239337; -.
DR UCSC; uc007vha.1; mouse. [Q811B3-2]
DR UCSC; uc007vhb.1; mouse. [Q811B3-1]
DR CTD; 81792; -.
DR MGI; MGI:2146046; Adamts12.
DR VEuPathDB; HostDB:ENSMUSG00000047497; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000155855; -.
DR HOGENOM; CLU_000660_2_1_1; -.
DR InParanoid; Q811B3; -.
DR OMA; MFNQSEG; -.
DR PhylomeDB; Q811B3; -.
DR TreeFam; TF313537; -.
DR Reactome; R-MMU-5173214; O-glycosylation of TSR domain-containing proteins.
DR BioGRID-ORCS; 239337; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Adamts12; mouse.
DR PRO; PR:Q811B3; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q811B3; protein.
DR Bgee; ENSMUSG00000047497; Expressed in dermis and 143 other tissues.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISO:MGI.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; ISO:MGI.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IGI:MGI.
DR GO; GO:0030199; P:collagen fibril organization; IGI:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:2001113; P:negative regulation of cellular response to hepatocyte growth factor stimulus; ISO:MGI.
DR GO; GO:1902548; P:negative regulation of cellular response to vascular endothelial growth factor stimulus; ISO:MGI.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISO:MGI.
DR GO; GO:1902203; P:negative regulation of hepatocyte growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0001503; P:ossification; IGI:MGI.
DR GO; GO:0043931; P:ossification involved in bone maturation; IGI:MGI.
DR GO; GO:0030167; P:proteoglycan catabolic process; ISO:MGI.
DR GO; GO:0006029; P:proteoglycan metabolic process; IGI:MGI.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISO:MGI.
DR GO; GO:1901509; P:regulation of endothelial tube morphogenesis; ISO:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; ISO:MGI.
DR Gene3D; 2.20.100.10; -; 8.
DR Gene3D; 3.40.390.10; -; 1.
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; IPR010909; PLAC.
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; SM00209; TSP1; 8.
DR SUPFAM; SSF82895; SSF82895; 8.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50900; PLAC; 1.
DR PROSITE; PS50092; TSP1; 6.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cleavage on pair of basic residues; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Zinc; Zymogen.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..244
FT /evidence="ECO:0000250"
FT /id="PRO_0000029188"
FT CHAIN 245..1600
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 12"
FT /id="PRO_0000029189"
FT DOMAIN 250..460
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 469..548
FT /note="Disintegrin"
FT DOMAIN 546..601
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 827..887
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 891..947
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 948..1001
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1318..1371
FT /note="TSP type-1 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1373..1428
FT /note="TSP type-1 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1429..1477
FT /note="TSP type-1 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1478..1538
FT /note="TSP type-1 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1541..1581
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 705..831
FT /note="Spacer 1"
FT REGION 1001..1321
FT /note="Spacer 2"
FT REGION 1006..1140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1158..1179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 210..217
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT COMPBIAS 1042..1140
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 397
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 212
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 396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 400
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 326..380
FT /evidence="ECO:0000250"
FT DISULFID 355..362
FT /evidence="ECO:0000250"
FT DISULFID 374..455
FT /evidence="ECO:0000250"
FT DISULFID 413..439
FT /evidence="ECO:0000250"
FT DISULFID 482..505
FT /evidence="ECO:0000250"
FT DISULFID 493..511
FT /evidence="ECO:0000250"
FT DISULFID 500..530
FT /evidence="ECO:0000250"
FT DISULFID 524..535
FT /evidence="ECO:0000250"
FT DISULFID 558..595
FT /evidence="ECO:0000250"
FT DISULFID 562..600
FT /evidence="ECO:0000250"
FT DISULFID 573..585
FT /evidence="ECO:0000250"
FT VAR_SEQ 167..171
FT /note="GFFHL -> VLITL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013149"
FT VAR_SEQ 172..1600
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013150"
FT CONFLICT 1010
FT /note="N -> H (in Ref. 1; CAD60967)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1600 AA; 177769 MW; F125753A42D4AD04 CRC64;
MPCARGSWLA KLSIVAQLIN FGAFCHGRQT QPWPVRFPDP RQEHFIKSLP EYHIVSPVQV
DAGGHVLSYG LHHPVTSSRK KRAAGGSGDQ LYYRISHEEK DLFFNLTVNW EFLSNGYVVE
KRYGNLSHVK MVASSGQPCH LRGTVLQQGT TVGIGTAALS ACQGLTGFFH LPHGDFFIEP
VKKHPLTEEG SYPHVVYRRQ SIRAPETKEP ICGLKDSLDN SVKQELQREK WERKTLRSRS
LSRRSISKER WVETLVVADT KTVEYHGSEN VESYILTIMN MVTGLFHSPS IGNLVHIVVV
RLILLEEEEQ GLKIVHHAEK TLSSFCKWQK SINPKSDLNP VHHDVAVLIT RKDICAGVNR
PCETLGLSQL SGMCQPHRSC NINEDSGLPL AFTIAHELGH SFGIQHDGKE NDCEPVGRHP
YIMSQQIQYD PTPLTWSKCS KEYITRFLDR GRGFCLDDIP SKKGLKSNVI APGVIYDVHH
QCQLQYGPNA TFCQEVENVC QTLWCSVKGF CRSKLDAAAD GTRCGEKKWC MAGKCITVGK
KPESIPGGWG RWSPWSHCSR TCGAGAQSAE RLCNNPEPKF GGKYCTGERK RYRLCNVHPC
RSDTPTFRQM QCSEFDTVPY KNQFYRWFPV FNAAHPCELY CRPIDEQFSE RMLEAVIDGT
PCFEGGNSRN VCINGICKRV GCDYEIDSNA TEDRCGVCLG DGSACQTVKK LFRQKEGSGY
VDIGLIPKGA RDIRVMEIKA AGNFLAIRSE DPEKYYLNGG FIIQWNGNYK LAGTVFQYDR
KGDLEKLIAP GPTNESVWLQ LLFQVTNPGI KYEYTVRKDG LDNDVEKLLY FWQFGRWTEC
SVTCGTGIRR QAAHCVKKGH GIVKTTFCNP ETQPSVRQKK CHEKDCPPRW WAGEWEACST
TCGPYGEKKR TVLCIQTMGS DEQALPATDC QHLLKPKALV SCNRDILCPS DWTVGNWSEC
SVSCGGGVRI RSVTCAKNLN EPCDKTRKPN SRALCGLQQC PFSRRVLKPN KDIAPSGKNQ
STAEHDPFKP IPAPTSRPTP LSTPTVPESM STSTPTINSL GSTIASQEDA NGMGWQNNST
QAEEGSHFPT SSGSTSQVPV TSWSLSIQPD DENVSSSAIG PTSEGDFWAT TTSDSGLSSS
DAMTWQVTPF YSTMTTDPEV EIHSGSGEDS DQPLNKDKSN SVIWNKIGVP EHDAPMETDA
ELPLGPPPTS YMGEEPSWPP FSTKMEGSLP AWSFKNETPR DDGMIAEKSR KIPLPLAGDH
HPATSEKLEN HDKLALPNTT NPTQGFGPVL TEEDASNLIA EGFLLNASDY KHLMKDHSPA
YWIVGNWSKC STTCGLGAYW RSVECSSGVD ADCTTIQRPD PAKKCHLRPC AGWRVGNWSK
CSRNCSGGFK IREVQCMDSL DHHRSLRPFH CQFLAGAPPP LSMSCNLEPC GEWQVEPWSQ
CSRSCGGGVQ ERGVSCPGGL CDWTKRPATT VPCNRHLCCH WATGNWELCN TSCGGGSQKR
TIHCIPSENS TTEDQDQCLC DHQVKPPEFQ TCNQQACRKS ADLTCLKDRL SISFCQTLKS
MRKCSVPSVR AQCCLSCPQA PSIHTQRQRK QQLLQNHDML
