TIMP2

Protein identityUniProt · HPA

UniProt accession

P16035

Gene

TIMP2

Ensembl

ENSG00000035862

Chromosome

17

Canonical length

220 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

220 residues, UniProt reviewed canonical sequence.

>P16035|TIMP2
     1  MGAAARTLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV SEKEVDSGND
    61  IYGNPIKRIQ YEIKQIKMFK GPEKDIEFIY TAPSSAVCGV SLDVGGKKEY LIAGKAEGDG
   121  KMHITLCDFI VPWDTLSTTQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE
   181  KNINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TIMP2 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)

0.33

Highest tissue expression

934 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)

0.5

gnomAD pLI

0.79

gnomAD missense Z

1.61

DepMap mean gene effect

-0.03

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

• negative regulation of membrane protein ectodomain proteolysis
• negative regulation of metallopeptidase activity
• response to cytokine
• response to hormone

Molecular functions

• metalloendopeptidase inhibitor activity
• molecular function inhibitor activity
• peptidase inhibitor activity
• protease binding
• zinc ion binding

Cellular components

• extracellular matrix
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• specific granule lumen
• tertiary 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
• Metal-binding
• Metalloenzyme inhibitor
• Metalloprotease inhibitor
• Protease inhibitor
• Secreted
• Signal
• Zinc

InteractionsUniProt · HPA

Protein binding partners of TIMP2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MMP13
• MMP14
• MMP2