TIMP3

Protein identityUniProt · HPA

UniProt accession

P35625

Gene

TIMP3

Ensembl

ENSG00000100234

Chromosome

22

Canonical length

211 aa

Protein class

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

Subcellular location

Golgi apparatus,Vesicles

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix (ECM). Expression of this gene is induced in response to mitogenic stimulation and this netrin domain-containing protein is localized to the ECM. Mutations in this gene have been associated with the autosomal dominant disorder Sorsby's fundus dystrophy. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

211 residues, UniProt reviewed canonical sequence.

>P35625|TIMP3
     1  MTPWLGLIVL LGSWSLGDWG AEACTCSPSH PQDAFCNSDI VIRAKVVGKK LVKEGPFGTL
    61  VYTIKQMKMY RGFTKMPHVQ YIHTEASESL CGLKLEVNKY QYLLTGRVYD GKMYTGLCNF
   121  VERWDQLTLS QRKGLNYRYH LGCNCKIKSC YYLPCFVTSK NECLWTDMLS NFGYPGYQSK
   181  HYACIRQKGG YCSWYRGWAP PDKSIINATD P

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TIMP3 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

939 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TIMP3.

Disease | AllUniProt

Conditions TIMP3 is implicated in, by any mechanism.

• Sorsby fundus dystrophy (SFD) MIM:136900

Disease | GeneticClinVar

10 pathogenic / likely-pathogenic of 280 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Sorsby fundus dystrophy
• Retinal dystrophy
• Retinal disorder
• Cerebral arteriovenous malformation

Disease | ImmuneIEDB

Conditions an epitope on TIMP3 was assayed in.

• Lyme disease T cell

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)

0.53

gnomAD pLI

0.63

gnomAD missense Z

1.83

DepMap mean gene effect

0

DepMap dependency class

none

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

• negative regulation of extracellular matrix disassembly
• negative regulation of membrane protein ectodomain proteolysis
• response to cytokine
• response to hormone
• visual perception

Molecular functions

• metal ion binding
• metalloendopeptidase inhibitor activity

Cellular components

• basement membrane
• extracellular matrix
• extracellular region
• extracellular space
• nucleus
• platelet dense granule lumen

Protein domainsUniProt · Pfam · InterPro

• Netrin domain
• Protease inhibitor I35 (TIMP)
• Tissue inhibitor of metalloproteinases-like, OB-fold
• Proteinase inhibitor I35b (TIMP), C-terminal
• Tissue inhibitor of metalloproteinase, conserved site
• Tissue inhibitor of metalloproteinase

KeywordsUniProt

• Disulfide bond
• Extracellular matrix
• Metal-binding
• Metalloenzyme inhibitor
• Metalloprotease inhibitor
• Protease inhibitor
• Secreted
• Sensory transduction
• Signal
• Vision
• Zinc

InteractionsUniProt · HPA

Protein binding partners of TIMP3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EFEMP1
• KDR
• MMP13
• ADAM17
• AGTR2