ADAMTS4

Protein identityUniProt · HPA

UniProt accession

O75173

Gene

ADAMTS4

Ensembl

ENSG00000158859

Chromosome

1

Canonical length

837 aa

Protein class

Cancer-related genes, Enzymes, Predicted intracellular proteins, Predicted secreted proteins, Transporters

Subcellular location

Nuclear speckles

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 this 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 enzyme encoded by this gene lacks a C-terminal TS motif. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease is responsible for the degradation of aggrecan, a major proteoglycan of cartilage, and brevican, a brain-specific extracellular matrix protein. The expression of this gene is upregulated in arthritic disease and this may contribute to disease progression through the degradation of aggrecan. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

837 residues, UniProt reviewed canonical sequence.

>O75173|ADAMTS4
     1  MSQTGSHPGR GLAGRWLWGA QPCLLLPIVP LSWLVWLLLL LLASLLPSAR LASPLPREEE
    61  IVFPEKLNGS VLPGSGAPAR LLCRLQAFGE TLLLELEQDS GVQVEGLTVQ YLGQAPELLG
   121  GAEPGTYLTG TINGDPESVA SLHWDGGALL GVLQYRGAEL HLQPLEGGTP NSAGGPGAHI
   181  LRRKSPASGQ GPMCNVKAPL GSPSPRPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR
   241  YLLTVMAAAA KAFKHPSIRN PVSLVVTRLV ILGSGEEGPQ VGPSAAQTLR SFCAWQRGLN
   301  TPEDSDPDHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED DGLQSAFTAA
   361  HELGHVFNML HDNSKPCISL NGPLSTSRHV MAPVMAHVDP EEPWSPCSAR FITDFLDNGY
   421  GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA
   481  MCQTKHSPWA DGTPCGPAQA CMGGRCLHMD QLQDFNIPQA GGWGPWGPWG DCSRTCGGGV
   541  QFSSRDCTRP VPRNGGKYCE GRRTRFRSCN TEDCPTGSAL TFREEQCAAY NHRTDLFKSF
   601  PGPMDWVPRY TGVAPQDQCK LTCQAQALGY YYVLEPRVVD GTPCSPDSSS VCVQGRCIHA
   661  GCDRIIGSKK KFDKCMVCGG DGSGCSKQSG SFRKFRYGYN NVVTIPAGAT HILVRQQGNP
   721  GHRSIYLALK LPDGSYALNG EYTLMPSPTD VVLPGAVSLR YSGATAASET LSGHGPLAQP
   781  LTLQVLVAGN PQDTRLRYSF FVPRPTPSTP RPTPQDWLHR RAQILEILRR RPWAGRK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADAMTS4 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)

0.34

Highest tissue expression

109 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)

0.71

gnomAD pLI

0

gnomAD missense Z

1.15

DepMap mean gene effect

-0.16

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

• defense response to bacterium
• extracellular matrix disassembly
• extracellular matrix organization
• proteoglycan catabolic process
• proteolysis
• skeletal system development

Molecular functions

• metalloendopeptidase activity
• metallopeptidase activity
• peptidase activity
• protease binding
• zinc ion binding

Cellular components

• extracellular matrix
• extracellular region
• extracellular space
• nuclear speck

Protein domainsUniProt · Pfam · InterPro

• Thrombospondin type-1 (TSP1) repeat
• Peptidase M12B, ADAM/reprolysin
• ADAM, cysteine-rich domain
• ADAMTS/ADAMTS-like, Spacer 1
• 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
• ADAM-TS Spacer 1
• ADAMTS cysteine-rich domain 2
• ADAMTS cysteine-rich domain

KeywordsUniProt

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

InteractionsUniProt · HPA

Protein binding partners of ADAMTS4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SRPX2