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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 12

Gene

Adamts12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Inhibited by alpha-2 macroglobulin.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi212Zinc; in inhibited formBy similarity1
Metal bindingi396Zinc; catalyticBy similarity1
Active sitei397PROSITE-ProRule annotation1
Metal bindingi400Zinc; catalyticBy similarity1
Metal bindingi406Zinc; catalyticBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:2146046. Adamts12.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
PropeptideiPRO_000002918826 – 244By similarityAdd BLAST219
ChainiPRO_0000029189245 – 1600A disintegrin and metalloproteinase with thrombospondin motifs 12Add BLAST1356

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi105N-linked (GlcNAc...)Sequence analysis1
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

PaxDbiQ811B3.
PRIDEiQ811B3.

PTM databases

iPTMnetiQ811B3.
PhosphoSitePlusiQ811B3.

Expressioni

Gene expression databases

BgeeiENSMUSG00000047497.

Interactioni

Subunit structurei

Interacts with COMP.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000057796.

Structurei

3D structure databases

ProteinModelPortaliQ811B3.
SMRiQ811B3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini250 – 460Peptidase M12BPROSITE-ProRule annotationAdd BLAST211
Domaini469 – 548DisintegrinAdd BLAST80
Domaini546 – 601TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini827 – 887TSP type-1 2PROSITE-ProRule annotationAdd BLAST61
Domaini891 – 947TSP type-1 3PROSITE-ProRule annotationAdd BLAST57
Domaini948 – 1001TSP type-1 4PROSITE-ProRule annotationAdd BLAST54
Domaini1318 – 1371TSP type-1 5PROSITE-ProRule annotationAdd BLAST54
Domaini1373 – 1428TSP type-1 6PROSITE-ProRule annotationAdd BLAST56
Domaini1429 – 1477TSP type-1 7PROSITE-ProRule annotationAdd BLAST49
Domaini1478 – 1538TSP type-1 8PROSITE-ProRule annotationAdd BLAST61
Domaini1541 – 1581PLACPROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni705 – 831Spacer 1Add BLAST127
Regioni1001 – 1321Spacer 2Add BLAST321

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi210 – 217Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi306 – 309Poly-Glu4
Compositional biasi601 – 704Cys-richAdd BLAST104

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

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000015092.
HOVERGENiHBG050620.
InParanoidiQ811B3.
KOiK08626.
OMAiSGMCQPS.
OrthoDBiEOG091G14M8.
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. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 8 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. AlignAdd to basket

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

        10         20         30         40         50
MPCARGSWLA KLSIVAQLIN FGAFCHGRQT QPWPVRFPDP RQEHFIKSLP
60 70 80 90 100
EYHIVSPVQV DAGGHVLSYG LHHPVTSSRK KRAAGGSGDQ LYYRISHEEK
110 120 130 140 150
DLFFNLTVNW EFLSNGYVVE KRYGNLSHVK MVASSGQPCH LRGTVLQQGT
160 170 180 190 200
TVGIGTAALS ACQGLTGFFH LPHGDFFIEP VKKHPLTEEG SYPHVVYRRQ
210 220 230 240 250
SIRAPETKEP ICGLKDSLDN SVKQELQREK WERKTLRSRS LSRRSISKER
260 270 280 290 300
WVETLVVADT KTVEYHGSEN VESYILTIMN MVTGLFHSPS IGNLVHIVVV
310 320 330 340 350
RLILLEEEEQ GLKIVHHAEK TLSSFCKWQK SINPKSDLNP VHHDVAVLIT
360 370 380 390 400
RKDICAGVNR PCETLGLSQL SGMCQPHRSC NINEDSGLPL AFTIAHELGH
410 420 430 440 450
SFGIQHDGKE NDCEPVGRHP YIMSQQIQYD PTPLTWSKCS KEYITRFLDR
460 470 480 490 500
GRGFCLDDIP SKKGLKSNVI APGVIYDVHH QCQLQYGPNA TFCQEVENVC
510 520 530 540 550
QTLWCSVKGF CRSKLDAAAD GTRCGEKKWC MAGKCITVGK KPESIPGGWG
560 570 580 590 600
RWSPWSHCSR TCGAGAQSAE RLCNNPEPKF GGKYCTGERK RYRLCNVHPC
610 620 630 640 650
RSDTPTFRQM QCSEFDTVPY KNQFYRWFPV FNAAHPCELY CRPIDEQFSE
660 670 680 690 700
RMLEAVIDGT PCFEGGNSRN VCINGICKRV GCDYEIDSNA TEDRCGVCLG
710 720 730 740 750
DGSACQTVKK LFRQKEGSGY VDIGLIPKGA RDIRVMEIKA AGNFLAIRSE
760 770 780 790 800
DPEKYYLNGG FIIQWNGNYK LAGTVFQYDR KGDLEKLIAP GPTNESVWLQ
810 820 830 840 850
LLFQVTNPGI KYEYTVRKDG LDNDVEKLLY FWQFGRWTEC SVTCGTGIRR
860 870 880 890 900
QAAHCVKKGH GIVKTTFCNP ETQPSVRQKK CHEKDCPPRW WAGEWEACST
910 920 930 940 950
TCGPYGEKKR TVLCIQTMGS DEQALPATDC QHLLKPKALV SCNRDILCPS
960 970 980 990 1000
DWTVGNWSEC SVSCGGGVRI RSVTCAKNLN EPCDKTRKPN SRALCGLQQC
1010 1020 1030 1040 1050
PFSRRVLKPN KDIAPSGKNQ STAEHDPFKP IPAPTSRPTP LSTPTVPESM
1060 1070 1080 1090 1100
STSTPTINSL GSTIASQEDA NGMGWQNNST QAEEGSHFPT SSGSTSQVPV
1110 1120 1130 1140 1150
TSWSLSIQPD DENVSSSAIG PTSEGDFWAT TTSDSGLSSS DAMTWQVTPF
1160 1170 1180 1190 1200
YSTMTTDPEV EIHSGSGEDS DQPLNKDKSN SVIWNKIGVP EHDAPMETDA
1210 1220 1230 1240 1250
ELPLGPPPTS YMGEEPSWPP FSTKMEGSLP AWSFKNETPR DDGMIAEKSR
1260 1270 1280 1290 1300
KIPLPLAGDH HPATSEKLEN HDKLALPNTT NPTQGFGPVL TEEDASNLIA
1310 1320 1330 1340 1350
EGFLLNASDY KHLMKDHSPA YWIVGNWSKC STTCGLGAYW RSVECSSGVD
1360 1370 1380 1390 1400
ADCTTIQRPD PAKKCHLRPC AGWRVGNWSK CSRNCSGGFK IREVQCMDSL
1410 1420 1430 1440 1450
DHHRSLRPFH CQFLAGAPPP LSMSCNLEPC GEWQVEPWSQ CSRSCGGGVQ
1460 1470 1480 1490 1500
ERGVSCPGGL CDWTKRPATT VPCNRHLCCH WATGNWELCN TSCGGGSQKR
1510 1520 1530 1540 1550
TIHCIPSENS TTEDQDQCLC DHQVKPPEFQ TCNQQACRKS ADLTCLKDRL
1560 1570 1580 1590 1600
SISFCQTLKS MRKCSVPSVR AQCCLSCPQA PSIHTQRQRK QQLLQNHDML
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)DescriptionActionsGraphical viewLength
Sequence conflicti1010N → H in CAD60967 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013149167 – 171GFFHL → VLITL in isoform 2. 1 Publication5
Alternative sequenceiVSP_013150172 – 1600Missing in isoform 2. 1 PublicationAdd BLAST1429

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_175501.3. [Q811B3-1]
UniGeneiMm.224825.
Mm.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:
EMBLi
GenBanki
DDBJi
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_175501.3. [Q811B3-1]
UniGeneiMm.224825.
Mm.482727.

3D structure databases

ProteinModelPortaliQ811B3.
SMRiQ811B3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000057796.

Protein family/group databases

MEROPSiM12.237.

PTM databases

iPTMnetiQ811B3.
PhosphoSitePlusiQ811B3.

Proteomic databases

PaxDbiQ811B3.
PRIDEiQ811B3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi81792.
MGIiMGI:2146046. Adamts12.

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000015092.
HOVERGENiHBG050620.
InParanoidiQ811B3.
KOiK08626.
OMAiSGMCQPS.
OrthoDBiEOG091G14M8.
TreeFamiTF313537.

Miscellaneous databases

PROiQ811B3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000047497.

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. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 8 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]
ProtoNetiSearch...

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: November 30, 2016
This is version 108 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.