TIMP1 TIMP metallopeptidase inhibitor 1 [Homo sapiens (human)] - Gene

Summary

Go to the top of the page Help

Official Symbol: TIMP1provided by HGNC
Official Full Name: TIMP metallopeptidase inhibitor 1provided by HGNC
Primary source: HGNC:11820
Locus tag: RP1-230G1.3
See related: Ensembl:ENSG00000102265; HPRD:02371; MIM:305370; Vega:OTTHUMG00000021447
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EPA; EPO; HCI; CLGI; TIMP
Summary: 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]

Genomic context

Go to the top of the page Help

Location :: Xp11.3-p11.23

Sequence :: Chromosome: X; NC_000023.10 (47441690..47446190)

See TIMP1 in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Abnormal expression of MMP-2 and TIMP-1 might play roles in the development of renal fibrosis in chronic antibody-mediated renal graft rejection.
Title: Expression of MMP-2 and TIMP-1 in renal tissue of patients with chronic active antibody-mediated renal graft rejection.
Abnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic active antibody-mediated renal graft rejection.
Title: [Expression of MMP-2 and TIMP-1 in renal tissues of patients with chronic active antibody-mediated renal graft rejection].
Expressions of TIMP-1 and nm-23, tumor size and lymph node involvement were independent prognostic factors in HER-2-positive breast cancer.
Title: [Significance of TIMP-1 and nm-23 expressions in HER-2-positive breast cancer].
Gambogic acid reduces the invasive potential of osteosarcoma cells via attenuation of MMP-9 and upregulation of TIMP-1.
Title: Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.
Serum levels of TIMP-1 were associated with the grade of liver inflammation in chronic hepatitis B patients.
Title: Serum levels of tissue inhibitor of metalloproteinase-1 are correlated with liver fibrosis in patients with chronic hepatitis B.
Higher level of circulating TIMP-1 is independently associated with worse left ventricular function and with acute heart failure.
Title: The association between levels of tissue inhibitor of metalloproteinase-1 with acute heart failure and left ventricular dysfunction in patients with ST elevation myocardial infarction treated by primary percutaneous coronary intervention.
Identification of novel molecules associated with a LIF-mediated increase in trophoblastic cell invasion may facilitate our understanding of implantation biology.
Title: Leukemia inhibitory factor increases the invasiveness of trophoblastic cells through integrated increase in the expression of adhesion molecules and pappalysin 1 with a concomitant decrease in the expression of tissue inhibitor of matrix metalloproteinases.
MMP-2, MMP-9 and TIMP-2, TIMP-1 may play an important role in the development, progression, invasion and metastasis of non-melanoma skin cancer.
Title: [Expression and significance of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase in non-melanoma skin cancer].
In a previously unrecognized overgrowth syndrome the increased proliferation of fibroblasts and defective collagen I deposition is due to increased MMP3 activitiy and reduced TIMP1 levels.
Title: Overgrowth with increased proliferation of fibroblast and matrix metalloproteinase activity related to reduced TIMP1: a newly recognized syndrome?
tumors with high TIMP-1 and NOS2 behave more aggressively by mechanisms that favor Akt pathway activation
Title: Nitric oxide synthase and breast cancer: role of TIMP-1 in NO-mediated Akt activation.

Submit: New GeneRIF Correction See all (358)

Phenotypes

Go to the top of the page Help

Review eQTL and phenotype association data in this region using PheGenI

HIV-1 protein interactions

Go to the top of the page Help

Protein	Gene	Interaction	Pubs
Tat, p14	tat	HIV-1 Tat induced monocyte invasion is inhibited by anti-beta integrin Ab or tissue inhibitor of metalloproteinase (TIMP), indicating an interaction with beta integrins and TIMP	PubMed
	tat	HIV-1 Tat downregulates both basal and bFGF-induced secretion of TIMP-1 and TIMP-2, an effect involved in the Tat and bFGF induced increase in MMP-2 secretion	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Source	Pubs	Description
P01033	P08962	CD63	HPRD	PubMed
P01033	Q13011	ECH1	HPRD	PubMed
P01033	P24534	EEF1B2	HPRD	PubMed
P01033	P03956	MMP1	HPRD	PubMed
P01033	P08253	MMP2	HPRD	PubMed
P01033	P08254	MMP3	HPRD	PubMed
P01033	Q99972	MYOC	HPRD	PubMed
P01033	O94762	RECQL5	HPRD	PubMed
BioGRID:112932	BioGRID:108220	ECH1	BioGRID	PubMed	Two-hybrid
BioGRID:112932	BioGRID:108253	EEF1B2	BioGRID	PubMed	Two-hybrid
BioGRID:112932	BioGRID:110456	MMP1	BioGRID	PubMed	Reconstituted Complex
BioGRID:112932	BioGRID:110458	MMP3	BioGRID	PubMed	Co-crystal Structure
BioGRID:112932	BioGRID:110736	MYOC	BioGRID	PubMed	Two-hybrid
BioGRID:112932	BioGRID:114797	RECQL5	BioGRID	PubMed	Two-hybrid
BioGRID:112932	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112932	BioGRID:113498	ZBTB16	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid

Pathways from BioSystems

Go to the top of the page Help

Activation of Matrix Metalloproteinases, organism-specific biosystem (from REACTOME)
Activation of Matrix Metalloproteinases, organism-specific biosystemThe matrix metalloproteinases (MMPs), previously known as matrixins, are classically known to be involved in the turnover of extracellular matrix (ECM) components. However, recent high throughput pro...
Degradation of the extracellular matrix, organism-specific biosystem (from REACTOME)
Degradation of the extracellular matrix, organism-specific biosystemMatrix metalloproteinases (MMPs), previously referred to as matrixins because of their role in degradation of the extracellular matrix (ECM), are zinc and calcium dependent proteases belonging to the...
Extracellular matrix organization, organism-specific biosystem (from REACTOME)
Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin, fibronectin and laminin embedded in a viscoelastic gel of ani...
HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
IL6-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
IL6-mediated signaling events, organism-specific biosystem
IL6-mediated signaling events
Matrix Metalloproteinases, organism-specific biosystem (from WikiPathways)
Matrix Metalloproteinases, organism-specific biosystemMatrix metalloproteinases (MMPs) are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzi...
Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
Platelet degranulation, organism-specific biosystem (from REACTOME)
Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...

General gene information

Go to the top of the page Help

Markers

STS-AA001911 (e-PCR)
- UniSTS:74040

GDB:178392 (e-PCR)
- UniSTS:155002

GDB:192509 (e-PCR)
- UniSTS:98973

GDB:182149 (e-PCR)
- UniSTS:155357

GDB:182150 (e-PCR)
- UniSTS:155358

Homology

Homologs of the TIMP1 gene: The TIMP1 gene is conserved in Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
metal ion binding	IEA Inferred from Electronic Annotation more info
metalloendopeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
aging	IEA Inferred from Electronic Annotation more info
blood coagulation	TAS Traceable Author Statement more info
erythrocyte maturation	IEA Inferred from Electronic Annotation more info
extracellular matrix disassembly	TAS Traceable Author Statement more info
extracellular matrix organization	TAS Traceable Author Statement more info
negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
negative regulation of membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
negative regulation of trophoblast cell migration	IMP Inferred from Mutant Phenotype more info
platelet activation	TAS Traceable Author Statement more info
platelet degranulation	TAS Traceable Author Statement more info
positive regulation of cell proliferation	TAS Traceable Author Statement more info	PubMed
response to cytokine stimulus	IEA Inferred from Electronic Annotation more info
response to peptide hormone stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
basement membrane	IEA Inferred from Electronic Annotation more info
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular region	TAS Traceable Author Statement more info
platelet alpha granule lumen	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: metalloproteinase inhibitor 1

Names: metalloproteinase inhibitor 1; TIMP-1; collagenase inhibitor; erythroid potentiating activity; erythroid-potentiating activity; fibroblast collagenase inhibitor; tissue inhibitor of metalloproteinases 1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012533.1 RefSeqGene

Range

5001..9501

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003254.2 → NP_003245.1 metalloproteinase inhibitor 1 precursor

Status: REVIEWED

Source sequence(s)

BC000866, BC007097, BQ181804, BU857950

Consensus CDS

CCDS14281.1

UniProtKB/Swiss-Prot

P01033

UniProtKB/TrEMBL

Q6FGX5

Related

ENSP00000218388, OTTHUMP00000023214, ENST00000218388, OTTHUMT00000056423

Conserved Domains (1) summary

cd03585
Location:24 – 205
Blast Score: 637

NTR_TIMP; NTR domain, TIMP subfamily; TIMPs, or tissue inibitors of metalloproteases, are essential regulators of extracellular matrix turnover and remodeling. They form complexes with matrix metalloproteases (MMPs) and inactivate them irreversibly by ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p10 Primary Assembly

Range

47441690..47446190

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

45154211..45158632

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018934.1 Alternate CHM1_1.0

Range

47361258..47365758

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01052381.1	None
genomic	ABBA01052382.1	None
genomic	AMYH01022264.1 (7904..12404)	None
genomic	AY932824.1	AAX47478.1
genomic	CH471164.1	EAW59315.1
		EAW59316.1
genomic	D11139.1	BAA01913.1
genomic	FB571112.1	CAR95107.1
genomic	FB668243.1	CAS92765.1
genomic	HI574166.1	CBX47572.1
genomic	L47361.1	AAA75558.1
genomic	Z84466.2 (17184..21684)	None
mRNA	AK074854.1	BAG52016.1
mRNA	AK296116.1	BAG58865.1
mRNA	AK310206.1	None
mRNA	AK311937.1	BAG34878.1
mRNA	BC000866.1	AAH00866.1
mRNA	BC007097.1	None
mRNA	BQ181804.1	None
mRNA	BU857950.1	None
mRNA	CR407638.1	CAG28566.1
mRNA	CR541982.1	CAG46779.1
mRNA	M12670.1	AAA52436.1
mRNA	M59906.1	AAA63234.1
mRNA	S68252.1	AAD14009.1
mRNA	X02598.1	CAA26443.1
mRNA	X03124.1	CAA26902.1
mRNA	A10416.1	CAA00898.1
other-genetic	DQ891122.2	ABM82048.1
other-genetic	DQ894301.2	ABM85227.1