ADAMTS3

Protein identityUniProt · HPA

UniProt accession

O15072

Gene

ADAMTS3

Ensembl

ENSG00000156140

Chromosome

4

Canonical length

1205 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted secreted proteins

Subcellular location

Intermediate filaments

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) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease, a member of the procollagen aminopropeptidase subfamily of proteins, may play a role in the processing of type II fibrillar collagen in articular cartilage. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

1205 residues, UniProt reviewed canonical sequence.

>O15072|ADAMTS3
     1  MVLLSLWLIA AALVEVRTSA DGQAGNEEMV QIDLPIKRYR EYELVTPVST NLEGRYLSHT
    61  LSASHKKRSA RDVSSNPEQL FFNITAFGKD FHLRLKPNTQ LVAPGAVVEW HETSLVPGNI
   121  TDPINNHQPG SATYRIRRTE PLQTNCAYVG DIVDIPGTSV AISNCDGLAG MIKSDNEEYF
   181  IEPLERGKQM EEEKGRIHVV YKRSAVEQAP IDMSKDFHYR ESDLEGLDDL GTVYGNIHQQ
   241  LNETMRRRRH AGENDYNIEV LLGVDDSVVR FHGKEHVQNY LLTLMNIVNE IYHDESLGVH
   301  INVVLVRMIM LGYAKSISLI ERGNPSRSLE NVCRWASQQQ RSDLNHSEHH DHAIFLTRQD
   361  FGPAGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG QGNRCGDETA
   421  MGSVMAPLVQ AAFHRYHWSR CSGQELKRYI HSYDCLLDDP FDHDWPKLPE LPGINYSMDE
   481  QCRFDFGVGY KMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTECA AGKWCYKGHC
   541  MWKNANQQKQ DGNWGSWTKF GSCSRTCGTG VRFRTRQCNN PMPINGGQDC PGVNFEYQLC
   601  NTEECQKHFE DFRAQQCQQR NSHFEYQNTK HHWLPYEHPD PKKRCHLYCQ SKETGDVAYM
   661  KQLVHDGTHC SYKDPYSICV RGECVKVGCD KEIGSNKVED KCGVCGGDNS HCRTVKGTFT
   721  RTPRKLGYLK MFDIPPGARH VLIQEDEASP HILAIKNQAT GHYILNGKGE EAKSRTFIDL
   781  GVEWDYNIED DIESLHTDGP LHDPVIVLII PQENDTRSSL TYKYIIHEDS VPTINSNNVI
   841  QEELDTFEWA LKSWSQCSKP CGGGFQYTKY GCRRKSDNKM VHRSFCEANK KPKPIRRMCN
   901  IQECTHPLWV AEEWEHCTKT CGSSGYQLRT VRCLQPLLDG TNRSVHSKYC MGDRPESRRP
   961  CNRVPCPAQW KTGPWSECSV TCGEGTEVRQ VLCRAGDHCD GEKPESVRAC QLPPCNDEPC
  1021  LGDKSIFCQM EVLARYCSIP GYNKLCCESC SKRSSTLPPP YLLEAAETHD DVISNPSDLP
  1081  RSLVMPTSLV PYHSETPAKK MSLSSISSVG GPNAYAAFRP NSKPDGANLR QRSAQQAGSK
  1141  TVRLVTVPSS PPTKRVHLSS ASQMAAASFF AASDSIGASS QARTSKKDGK IIDNRRPTRS
  1201  STLER

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADAMTS3 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)

0.37

Highest tissue expression

7.8 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ADAMTS3.

Disease | AllUniProt

Conditions ADAMTS3 is implicated in, by any mechanism.

• Hennekam lymphangiectasia-lymphedema syndrome 3 (HKLLS3) MIM:618154

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 231 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hennekam lymphangiectasia-lymphedema syndrome 3
• Inborn genetic diseases

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)

0.6

gnomAD pLI

0

gnomAD missense Z

0.55

DepMap mean gene effect

-0.11

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• collagen biosynthetic process
• collagen catabolic process
• collagen fibril organization
• extracellular matrix organization
• in utero embryonic development
• positive regulation of vascular endothelial growth factor signaling pathway
• protein processing
• proteolysis
• supramolecular fiber organization
• vascular endothelial growth factor production

Molecular functions

• endopeptidase activity
• heparin binding
• metalloendopeptidase activity
• zinc ion binding

Cellular components

• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space

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
• Heparin-binding
• Hydrolase
• Metal-binding
• Metalloprotease
• Protease
• Repeat
• Secreted
• Signal
• Zinc
• Zymogen