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FLASH GENE

Symbol

TIMP1

contributors: mct/npt/pgu - updated : 08-07-2015

HGNC name	TIMP metallopeptidase inhibitor 1
HGNC id	11820

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	gene in gene, escaping inactivation
text	embedded in intron 5 of SYN1
	variable retention of the epigenetic silencing mechanisms associated with X inactivation
STRUCTURE	4.50 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	binding sites for ETS gene family of transcription factor and for AP1

MAPPING

cloned

Y

linked

Y

status

confirmed

Map

see SYN1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003254 6 - 931 NP_003245 - 207 - 2009 19513566

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary     highly Reproductive female system ovary     highly Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly

cells

System Cell Pubmed Species Stage Rna symbol   fibroblast

cell lineage
cell lines	breast carcinoma
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

12 cysteine residues that form six disulfide bridges

conjugated

MetalloP

HOMOLOGY

interspecies

homolog to murine Timp

Homologene

FAMILY

TIMP family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,nucleus
text	binding to the cell surface of MCF-7 breast carcinoma cells and translocating to the nucleus

basic FUNCTION	multifunctional protein, stimulating proliferation of aortic smooth muscle cells and Ras effector pathways
	erythroid potentiating and cell growth-promoting activities
	involved in the regulation of bone modeling and remodeling in normal developing human bone
	inhibits all MMPs, except MMP14
	reducing tumor growth when it's overexpressed
	antiapoptotic activity
	naturally occurring specific inhibitor of matrix metalloproteinases
	inhibits MMP2 activity, protects against cell death and may be of significance in initiating repair processes and curtailing keratoconus
	major serum factors that stimulate the induction of TIMP-1 mRNA in quiescent human gingival fibroblasts
	survival factor of germinal center (GC) B cells functioning as a differentiating and survival factor of GC B cells by modulating CD44 and PTPN6 in the late centrocyte/post-GC stage, regardless of EBV infection
	significantly inhibited both FAS- and activation-induced cell death of lymphocytes
	leads to enlarged adipocytes in the state of overnutrition
	plays an important role in promoting cell growth of breast cancer
	regulates essential stem cell functions, and may also mediate signaling that affects gene expression and inhibits the growth and differentiation of these cells
	important role of TIMP1 in protection and recovery from cutaneous photodamage because of its suppression of ECM degradation and inflammation
	regulates extracellular matrix turnover and also promotes cell growth and has anti-apoptotic activity, which promotes malignant processes in tumor tissue
	KLK1 and TIMP1 are important in inhibiting vascular smooth muscle cell (VSMC) proliferation and improving vascular remodeling, respectively

CELLULAR PROCESS	cell life, antiapoptosis
	protein, degradation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

component with MMP9 (progelatinase B)

INTERACTION

DNA

RNA

small molecule

protein	binding MMPs in a 1:1 stoechiometry
	activating RAS
	emerges as a modulator of neuronal outgrowth and morphology in a paracrine and autrocrine manner through the inhibition, at least in part, of MMP2 and not MMP9
	osteopontin increased TIMP1 secretion by peripheral blood monocytes
	fine balance between CCNL1 and TIMP1, which may contribute to breast cancer development
	HAS2 promotes breast cancer cell invasion by suppression of TIMP1
	colocalizes with CD63 on the surface of mesenchymal stem cells (hMSCs)
	MMP10 interacting with tissue inhibitors of metalloproteinases TIMP1 and TIMP2
	MIR17 targets TIMP1 and TIMP2 to modulate cardiac matrix remodeling

cell & other

REGULATION

activated by

SPHK1 (action of SPHK1 on the promoter is through the AP1-response element)

Other

heparin is able to accelerate the hydrolysis of TIMP1 by neutrophil elastase (PMId: 21731773)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in multiple sclerosis, liver fibrosis and left ventricular diastolic dysfunction with hypertension tumoral     --over   in acute myelogenous leukaemia constitutional     --over   in scarred keratoconic cornea tumoral     --low   in high expression of progesterone receptors in breast carcinoma tumoral   deletion     in colorectal cancer tumoral     --over   CCNL1 and TIMP1 expression was significantly elevated in breast cancer tissues compared with that in peri-breast cancer tissues constitutional     --low   in unrecognized overgrowth syndrome associated with increased cellular proliferation and defective collagen I deposition due to an imbalance between MMP and TIMP in fibroblasts constitutional     --over   plasma TIMP1 was elevated and correlated with TGFB1 in Duchenne muscular dystrophy (DMD) and congenital muscular dystrophy (CMD), but not in Becker muscular dystrophy

Susceptibility

Variant & Polymorphism other	demonstrating polymorphic X-chromosome inactivation

Candidate gene	prognostic marker in colorectal and breast cancer
Marker	relationship between higher plasma levels of TIMP1 and an adverse prognosis in patients with liver metastases, and plasma TIMP1 levels could help the detection of patients with worse outcome
	biomarker for thyroid cancer exhibiting differences in the correlation coefficients between benign and malignant samples that indicate its discriminatory power
Therapy target

ANIMAL & CELL MODELS