TIMP1

Protein identityUniProt · HPA

UniProt accession

P01033

Gene

TIMP1

Ensembl

ENSG00000102265

Chromosome

X

Canonical length

207 aa

Protein class

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

Subcellular location

Golgi apparatus,Vesicles

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene belongs to the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. In addition to its inhibitory role against most of the known MMPs, the encoded protein is able to promote cell proliferation in a wide range of cell types, and may also have an anti-apoptotic function. Transcription of this gene is highly inducible in response to many cytokines and hormones. In addition, the expression from some but not all inactive X chromosomes suggests that this gene inactivation is polymorphic in human females. This gene is located within intron 6 of the synapsin I gene and is transcribed in the opposite direction. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

207 residues, UniProt reviewed canonical sequence.

>P01033|TIMP1
     1  MAPFEPLASG ILLLLWLIAP SRACTCVPPH PQTAFCNSDL VIRAKFVGTP EVNQTTLYQR
    61  YEIKMTKMYK GFQALGDAAD IRFVYTPAME SVCGYFHRSH NRSEEFLIAG KLQDGLLHIT
   121  TCSFVAPWNS LSLAQRRGFT KTYTVGCEEC TVFPCLSIPC KLQSGTHCLW TDQLLQGSEK
   181  GFQSRHLACL PREPGLCTWQ SLRSQIA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TIMP1 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

2,943 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TIMP1.

Disease | AutoantibodyPubMed

Conditions in which antibodies against TIMP1 are reported. Each links to that disease's full target list.

• Anemia 8
• Kidney Failure, Chronic 3

ReferencesPubMed · IEDB

Publications for TIMP1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.78

gnomAD pLI

0.5

gnomAD missense Z

1.03

DepMap mean gene effect

-0.02

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

• cartilage development
• cellular response to acetaldehyde
• cellular response to peptide
• cellular response to UV-A
• connective tissue replacement involved in inflammatory response wound healing
• negative regulation of apoptotic process
• negative regulation of catalytic activity
• negative regulation of endopeptidase activity
• negative regulation of membrane protein ectodomain proteolysis
• negative regulation of metallopeptidase activity
• negative regulation of trophoblast cell migration
• positive regulation of cell population proliferation
• regulation of integrin-mediated signaling pathway
• response to cytokine
• response to hormone
• response to peptide hormone

Molecular functions

• cytokine activity
• growth factor activity
• metalloendopeptidase inhibitor activity
• peptidase inhibitor activity
• protease binding
• zinc ion binding

Cellular components

• basement membrane
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• platelet alpha 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
• Glycoprotein
• Growth factor
• Metal-binding
• Metalloenzyme inhibitor
• Metalloprotease inhibitor
• Phosphoprotein
• Protease inhibitor
• Secreted
• Signal
• Zinc

InteractionsUniProt · HPA

Protein binding partners of TIMP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD63
• MMP1
• MMP10
• MMP13
• MMP3
• FBXO6