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Q811B3

- ATS12_MOUSE

UniProt

Q811B3 - ATS12_MOUSE

Protein

A disintegrin and metalloproteinase with thrombospondin motifs 12

Gene

Adamts12

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Metalloprotease that plays a role in the degradation of COMP By similarity. Cleaves also alpha-2 macroglobulin and aggregan. Has anti-tumorigenic properties By similarity.By similarity

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Enzyme regulationi

    Inhibited by alpha-2 macroglobulin.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi212 – 2121Zinc; in inhibited formBy similarity
    Metal bindingi396 – 3961Zinc; catalyticBy similarity
    Active sitei397 – 3971PROSITE-ProRule annotation
    Metal bindingi400 – 4001Zinc; catalyticBy similarity
    Metal bindingi406 – 4061Zinc; catalyticBy similarity

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: InterPro
    2. zinc ion binding Source: InterPro

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiM12.237.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 12 (EC:3.4.24.-)
    Short name:
    ADAM-TS 12
    Short name:
    ADAM-TS12
    Short name:
    ADAMTS-12
    Gene namesi
    Name:Adamts12
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:2146046. Adamts12.

    Subcellular locationi

    GO - Cellular componenti

    1. proteinaceous extracellular matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525Sequence AnalysisAdd
    BLAST
    Propeptidei26 – 244219By similarityPRO_0000029188Add
    BLAST
    Chaini245 – 16001356A disintegrin and metalloproteinase with thrombospondin motifs 12PRO_0000029189Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi105 – 1051N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi326 ↔ 380By similarity
    Disulfide bondi355 ↔ 362By similarity
    Disulfide bondi374 ↔ 455By similarity
    Disulfide bondi413 ↔ 439By similarity
    Disulfide bondi482 ↔ 505By similarity
    Disulfide bondi493 ↔ 511By similarity
    Disulfide bondi500 ↔ 530By similarity
    Disulfide bondi524 ↔ 535By similarity
    Disulfide bondi558 ↔ 595By similarity
    Disulfide bondi562 ↔ 600By similarity
    Disulfide bondi573 ↔ 585By similarity

    Post-translational modificationi

    The precursor is cleaved by a furin endopeptidase.By similarity
    Subjected to an intracellular maturation process yielding a 120 kDa N-terminal fragment containing the metalloproteinase, disintegrin, one TSP type-1 and the Cys-rich domains and a 83 kDa C-terminal fragment containing the spacer 2 and four TSP type-1 domains.By similarity
    Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion By similarity.By similarity

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PRIDEiQ811B3.

    PTM databases

    PhosphoSiteiQ811B3.

    Expressioni

    Gene expression databases

    BgeeiQ811B3.
    GenevestigatoriQ811B3.

    Interactioni

    Subunit structurei

    Interacts with COMP.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ811B3.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini250 – 460211Peptidase M12BPROSITE-ProRule annotationAdd
    BLAST
    Domaini469 – 54880DisintegrinAdd
    BLAST
    Domaini546 – 60156TSP type-1 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini827 – 88761TSP type-1 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini891 – 94757TSP type-1 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini948 – 100154TSP type-1 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini1318 – 137154TSP type-1 5PROSITE-ProRule annotationAdd
    BLAST
    Domaini1373 – 142856TSP type-1 6PROSITE-ProRule annotationAdd
    BLAST
    Domaini1429 – 147749TSP type-1 7PROSITE-ProRule annotationAdd
    BLAST
    Domaini1478 – 153861TSP type-1 8PROSITE-ProRule annotationAdd
    BLAST
    Domaini1541 – 158141PLACPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni705 – 831127Spacer 1Add
    BLAST
    Regioni1001 – 1321321Spacer 2Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi210 – 2178Cysteine switchBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi306 – 3094Poly-Glu
    Compositional biasi601 – 704104Cys-richAdd
    BLAST

    Domaini

    The C-terminal four TSP1-like repeats are necessary and sufficient for binding COMP.By similarity
    The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.By similarity
    The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

    Sequence similaritiesi

    Contains 1 disintegrin domain.Curated
    Contains 1 peptidase M12B domain.PROSITE-ProRule annotation
    Contains 1 PLAC domain.PROSITE-ProRule annotation
    Contains 8 TSP type-1 domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG237764.
    GeneTreeiENSGT00750000117354.
    HOGENOMiHOG000015092.
    HOVERGENiHBG050620.
    InParanoidiQ811B3.
    KOiK08626.
    OMAiPFIMSRQ.
    OrthoDBiEOG7V765X.
    TreeFamiTF313537.

    Family and domain databases

    Gene3Di3.40.390.10. 1 hit.
    InterProiIPR010294. ADAM_spacer1.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR013273. Peptidase_M12B_ADAM-TS.
    IPR002870. Peptidase_M12B_N.
    IPR010909. PLAC.
    IPR000884. Thrombospondin_1_rpt.
    [Graphical view]
    PfamiPF05986. ADAM_spacer1. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    PF01421. Reprolysin. 1 hit.
    PF00090. TSP_1. 7 hits.
    [Graphical view]
    PRINTSiPR01857. ADAMTSFAMILY.
    SMARTiSM00209. TSP1. 8 hits.
    [Graphical view]
    SUPFAMiSSF82895. SSF82895. 8 hits.
    PROSITEiPS50215. ADAM_MEPRO. 1 hit.
    PS50900. PLAC. 1 hit.
    PS50092. TSP1. 6 hits.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q811B3-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPCARGSWLA KLSIVAQLIN FGAFCHGRQT QPWPVRFPDP RQEHFIKSLP     50
    EYHIVSPVQV DAGGHVLSYG LHHPVTSSRK KRAAGGSGDQ LYYRISHEEK 100
    DLFFNLTVNW EFLSNGYVVE KRYGNLSHVK MVASSGQPCH LRGTVLQQGT 150
    TVGIGTAALS ACQGLTGFFH LPHGDFFIEP VKKHPLTEEG SYPHVVYRRQ 200
    SIRAPETKEP ICGLKDSLDN SVKQELQREK WERKTLRSRS LSRRSISKER 250
    WVETLVVADT KTVEYHGSEN VESYILTIMN MVTGLFHSPS IGNLVHIVVV 300
    RLILLEEEEQ GLKIVHHAEK TLSSFCKWQK SINPKSDLNP VHHDVAVLIT 350
    RKDICAGVNR PCETLGLSQL SGMCQPHRSC NINEDSGLPL AFTIAHELGH 400
    SFGIQHDGKE NDCEPVGRHP YIMSQQIQYD PTPLTWSKCS KEYITRFLDR 450
    GRGFCLDDIP SKKGLKSNVI APGVIYDVHH QCQLQYGPNA TFCQEVENVC 500
    QTLWCSVKGF CRSKLDAAAD GTRCGEKKWC MAGKCITVGK KPESIPGGWG 550
    RWSPWSHCSR TCGAGAQSAE RLCNNPEPKF GGKYCTGERK RYRLCNVHPC 600
    RSDTPTFRQM QCSEFDTVPY KNQFYRWFPV FNAAHPCELY CRPIDEQFSE 650
    RMLEAVIDGT PCFEGGNSRN VCINGICKRV GCDYEIDSNA TEDRCGVCLG 700
    DGSACQTVKK LFRQKEGSGY VDIGLIPKGA RDIRVMEIKA AGNFLAIRSE 750
    DPEKYYLNGG FIIQWNGNYK LAGTVFQYDR KGDLEKLIAP GPTNESVWLQ 800
    LLFQVTNPGI KYEYTVRKDG LDNDVEKLLY FWQFGRWTEC SVTCGTGIRR 850
    QAAHCVKKGH GIVKTTFCNP ETQPSVRQKK CHEKDCPPRW WAGEWEACST 900
    TCGPYGEKKR TVLCIQTMGS DEQALPATDC QHLLKPKALV SCNRDILCPS 950
    DWTVGNWSEC SVSCGGGVRI RSVTCAKNLN EPCDKTRKPN SRALCGLQQC 1000
    PFSRRVLKPN KDIAPSGKNQ STAEHDPFKP IPAPTSRPTP LSTPTVPESM 1050
    STSTPTINSL GSTIASQEDA NGMGWQNNST QAEEGSHFPT SSGSTSQVPV 1100
    TSWSLSIQPD DENVSSSAIG PTSEGDFWAT TTSDSGLSSS DAMTWQVTPF 1150
    YSTMTTDPEV EIHSGSGEDS DQPLNKDKSN SVIWNKIGVP EHDAPMETDA 1200
    ELPLGPPPTS YMGEEPSWPP FSTKMEGSLP AWSFKNETPR DDGMIAEKSR 1250
    KIPLPLAGDH HPATSEKLEN HDKLALPNTT NPTQGFGPVL TEEDASNLIA 1300
    EGFLLNASDY KHLMKDHSPA YWIVGNWSKC STTCGLGAYW RSVECSSGVD 1350
    ADCTTIQRPD PAKKCHLRPC AGWRVGNWSK CSRNCSGGFK IREVQCMDSL 1400
    DHHRSLRPFH CQFLAGAPPP LSMSCNLEPC GEWQVEPWSQ CSRSCGGGVQ 1450
    ERGVSCPGGL CDWTKRPATT VPCNRHLCCH WATGNWELCN TSCGGGSQKR 1500
    TIHCIPSENS TTEDQDQCLC DHQVKPPEFQ TCNQQACRKS ADLTCLKDRL 1550
    SISFCQTLKS MRKCSVPSVR AQCCLSCPQA PSIHTQRQRK QQLLQNHDML 1600
    Length:1,600
    Mass (Da):177,769
    Last modified:July 27, 2011 - v2
    Checksum:iF125753A42D4AD04
    GO
    Isoform 2 (identifier: Q811B3-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         167-171: GFFHL → VLITL
         172-1600: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:171
    Mass (Da):18,843
    Checksum:i6846F3A8C242B832
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1010 – 10101N → H in CAD60967. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei167 – 1715GFFHL → VLITL in isoform 2. 1 PublicationVSP_013149
    Alternative sequencei172 – 16001429Missing in isoform 2. 1 PublicationVSP_013150Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ537452 mRNA. Translation: CAD60967.1.
    AK048612 mRNA. Translation: BAC33391.1.
    AK054015 mRNA. Translation: BAC35621.1.
    AC102219 Genomic DNA. No translation available.
    AC156609 Genomic DNA. No translation available.
    AC159963 Genomic DNA. No translation available.
    CCDSiCCDS27384.1. [Q811B3-1]
    RefSeqiNP_780710.2. NM_175501.2. [Q811B3-1]
    UniGeneiMm.482727.

    Genome annotation databases

    EnsembliENSMUST00000061318; ENSMUSP00000057796; ENSMUSG00000047497. [Q811B3-1]
    GeneIDi239337.
    KEGGimmu:239337.
    UCSCiuc007vha.1. mouse. [Q811B3-2]
    uc007vhb.1. mouse. [Q811B3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ537452 mRNA. Translation: CAD60967.1 .
    AK048612 mRNA. Translation: BAC33391.1 .
    AK054015 mRNA. Translation: BAC35621.1 .
    AC102219 Genomic DNA. No translation available.
    AC156609 Genomic DNA. No translation available.
    AC159963 Genomic DNA. No translation available.
    CCDSi CCDS27384.1. [Q811B3-1 ]
    RefSeqi NP_780710.2. NM_175501.2. [Q811B3-1 ]
    UniGenei Mm.482727.

    3D structure databases

    ProteinModelPortali Q811B3.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi M12.237.

    PTM databases

    PhosphoSitei Q811B3.

    Proteomic databases

    PRIDEi Q811B3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000061318 ; ENSMUSP00000057796 ; ENSMUSG00000047497 . [Q811B3-1 ]
    GeneIDi 239337.
    KEGGi mmu:239337.
    UCSCi uc007vha.1. mouse. [Q811B3-2 ]
    uc007vhb.1. mouse. [Q811B3-1 ]

    Organism-specific databases

    CTDi 81792.
    MGIi MGI:2146046. Adamts12.

    Phylogenomic databases

    eggNOGi NOG237764.
    GeneTreei ENSGT00750000117354.
    HOGENOMi HOG000015092.
    HOVERGENi HBG050620.
    InParanoidi Q811B3.
    KOi K08626.
    OMAi PFIMSRQ.
    OrthoDBi EOG7V765X.
    TreeFami TF313537.

    Miscellaneous databases

    NextBioi 384074.
    PROi Q811B3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q811B3.
    Genevestigatori Q811B3.

    Family and domain databases

    Gene3Di 3.40.390.10. 1 hit.
    InterProi IPR010294. ADAM_spacer1.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR013273. Peptidase_M12B_ADAM-TS.
    IPR002870. Peptidase_M12B_N.
    IPR010909. PLAC.
    IPR000884. Thrombospondin_1_rpt.
    [Graphical view ]
    Pfami PF05986. ADAM_spacer1. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    PF01421. Reprolysin. 1 hit.
    PF00090. TSP_1. 7 hits.
    [Graphical view ]
    PRINTSi PR01857. ADAMTSFAMILY.
    SMARTi SM00209. TSP1. 8 hits.
    [Graphical view ]
    SUPFAMi SSF82895. SSF82895. 8 hits.
    PROSITEi PS50215. ADAM_MEPRO. 1 hit.
    PS50900. PLAC. 1 hit.
    PS50092. TSP1. 6 hits.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mouse ADAMTS-12."
      Cal S., Lopez-Otin C.
      Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1009 (ISOFORM 1).
      Strain: C57BL/6J.
      Tissue: Embryonic head and Oviduct.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.

    Entry informationi

    Entry nameiATS12_MOUSE
    AccessioniPrimary (citable) accession number: Q811B3
    Secondary accession number(s): E9QKD6, Q8BK92, Q8BKY1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 92 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3