ADAMTS12

Protein identityUniProt · HPA

UniProt accession

P58397

Gene

ADAMTS12

Ensembl

ENSG00000151388

Chromosome

5

Canonical length

1594 aa

Protein class

Plasma proteins, Predicted secreted proteins

Subcellular location

Nucleoli,Mitochondria

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS-1) motif. Individual members of this family differ in the number of C-terminal TS-1 motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains eight TS-1 motifs. It may play roles in pulmonary cells during fetal development or in tumor processes through its proteolytic activity or as a molecule potentially involved in regulation of cell adhesion. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1594 residues, UniProt reviewed canonical sequence.

>P58397|ADAMTS12
     1  MPCAQRSWLA NLSVVAQLLN FGALCYGRQP QPGPVRFPDR RQEHFIKGLP EYHVVGPVRV
    61  DASGHFLSYG LHYPITSSRR KRDLDGSEDW VYYRISHEEK DLFFNLTVNQ GFLSNSYIME
   121  KRYGNLSHVK MMASSAPLCH LSGTVLQQGT RVGTAALSAC HGLTGFFQLP HGDFFIEPVK
   181  KHPLVEGGYH PHIVYRRQKV PETKEPTCGL KDSVNISQKQ ELWREKWERH NLPSRSLSRR
   241  SISKERWVET LVVADTKMIE YHGSENVESY ILTIMNMVTG LFHNPSIGNA IHIVVVRLIL
   301  LEEEEQGLKI VHHAEKTLSS FCKWQKSINP KSDLNPVHHD VAVLLTRKDI CAGFNRPCET
   361  LGLSHLSGMC QPHRSCNINE DSGLPLAFTI AHELGHSFGI QHDGKENDCE PVGRHPYIMS
   421  RQLQYDPTPL TWSKCSEEYI TRFLDRGWGF CLDDIPKKKG LKSKVIAPGV IYDVHHQCQL
   481  QYGPNATFCQ EVENVCQTLW CSVKGFCRSK LDAAADGTQC GEKKWCMAGK CITVGKKPES
   541  IPGGWGRWSP WSHCSRTCGA GVQSAERLCN NPEPKFGGKY CTGERKRYRL CNVHPCRSEA
   601  PTFRQMQCSE FDTVPYKNEL YHWFPIFNPA HPCELYCRPI DGQFSEKMLD AVIDGTPCFE
   661  GGNSRNVCIN GICKMVGCDY EIDSNATEDR CGVCLGDGSS CQTVRKMFKQ KEGSGYVDIG
   721  LIPKGARDIR VMEIEGAGNF LAIRSEDPEK YYLNGGFIIQ WNGNYKLAGT VFQYDRKGDL
   781  EKLMATGPTN ESVWIQLLFQ VTNPGIKYEY TIQKDGLDND VEQQMYFWQY GHWTECSVTC
   841  GTGIRRQTAH CIKKGRGMVK ATFCDPETQP NGRQKKCHEK ACPPRWWAGE WEACSATCGP
   901  HGEKKRTVLC IQTMVSDEQA LPPTDCQHLL KPKTLLSCNR DILCPSDWTV GNWSECSVSC
   961  GGGVRIRSVT CAKNHDEPCD VTRKPNSRAL CGLQQCPSSR RVLKPNKGTI SNGKNPPTLK
  1021  PVPPPTSRPR MLTTPTGPES MSTSTPAISS PSPTTASKEG DLGGKQWQDS STQPELSSRY
  1081  LISTGSTSQP ILTSQSLSIQ PSEENVSSSD TGPTSEGGLV ATTTSGSGLS SSRNPITWPV
  1141  TPFYNTLTKG PEMEIHSGSG EEREQPEDKD ESNPVIWTKI RVPGNDAPVE STEMPLAPPL
  1201  TPDLSRESWW PPFSTVMEGL LPSQRPTTSE TGTPRVEGMV TEKPANTLLP LGGDHQPEPS
  1261  GKTANRNHLK LPNNMNQTKS SEPVLTEEDA TSLITEGFLL NASNYKQLTN GHGSAHWIVG
  1321  NWSECSTTCG LGAYWRRVEC STQMDSDCAA IQRPDPAKRC HLRPCAGWKV GNWSKCSRNC
  1381  SGGFKIREIQ CVDSRDHRNL RPFHCQFLAG IPPPLSMSCN PEPCEAWQVE PWSQCSRSCG
  1441  GGVQERGVFC PGGLCDWTKR PTSTMSCNEH LCCHWATGNW DLCSTSCGGG FQKRTVQCVP
  1501  SEGNKTEDQD QCLCDHKPRP PEFKKCNQQA CKKSADLLCT KDKLSASFCQ TLKAMKKCSV
  1561  PTVRAECCFS CPQTHITHTQ RQRRQRLLQK SKEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADAMTS12 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

8.3 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.69

gnomAD pLI

0

gnomAD missense Z

0.98

DepMap mean gene effect

0.1

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell migration
• cell-matrix adhesion
• cellular response to BMP stimulus
• cellular response to interleukin-1
• cellular response to tumor necrosis factor
• chondrocyte differentiation
• collagen fibril organization
• extracellular matrix organization
• negative regulation of cellular response to vascular endothelial growth factor stimulus
• negative regulation of chondrocyte differentiation
• ossification involved in bone maturation
• proteoglycan catabolic process
• proteolysis
• proteolysis involved in protein catabolic process
• regulation of endothelial tube morphogenesis
• regulation of inflammatory response
• negative regulation of cellular response to hepatocyte growth factor stimulus
• negative regulation of hepatocyte growth factor receptor signaling pathway

Molecular functions

• metal ion binding
• metalloendopeptidase activity

Cellular components

• extracellular matrix

Protein domainsUniProt · Pfam · InterPro

• Thrombospondin type-1 (TSP1) repeat
• Peptidase M12B, ADAM/reprolysin
• Peptidase M12B, propeptide
• ADAMTS/ADAMTS-like, Spacer 1
• PLAC
• ADAMTS/ADAMTS-like
• Metallopeptidase, catalytic domain superfamily
• Thrombospondin type-1 repeat superfamily
• ADAMTS, cysteine-rich domain 2
• ADAMTS/ADAMTS-like, cysteine-rich domain 3
• ADAMTS and ADAMTS-like
• Thrombospondin type 1 domain
• Reprolysin (M12B) family zinc metalloprotease
• Reprolysin family propeptide
• ADAM-TS Spacer 1
• ADAMTS cysteine-rich domain 2
• Thrombospondin type 1 domain
• ADAMTS cysteine-rich domain

KeywordsUniProt

• Cleavage on pair of basic residues
• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Hydrolase
• Metal-binding
• Metalloprotease
• Protease
• Repeat
• Secreted
• Signal
• Zinc
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of ADAMTS12 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• COMP