Endometriosis Knowledgebase

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Gene id

7077

Gene Summary Protein Summary Gene ontology KEGG pathways Diseases PubMed references

Gene Summary

Gene Symbol

TIMP2 Gene UCSC Ensembl

Aliases

CSC-21K, DDC8

Gene name

TIMP metallopeptidase inhibitor 2

Alternate names

metalloproteinase inhibitor 2, testicular secretory protein Li 57, tissue inhibitor of metalloproteinases 2,

Gene location

17q25.3 (78925389: 78852976) Exons: 5 NC_000017.11

Gene summary(Entrez)

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]

OMIM

188825

Protein Summary

Protein general information

P16035

Name: Metalloproteinase inhibitor 2 (CSC 21K) (Tissue inhibitor of metalloproteinases 2) (TIMP 2)

Length: 220 Mass: 24,399

Sequence

MGAAARTLRLALGLLLLATLLRPADACSCSPVHPQQAFCNADVVIRAKAVSEKEVDSGNDIYGNPIKRIQYEIKQ
IKMFKGPEKDIEFIYTAPSSAVCGVSLDVGGKKEYLIAGKAEGDGKMHITLCDFIVPWDTLSTTQKKSLNHRYQM
GCECKITRCPMIPCYISSPDECLWMDWVTEKNINGHQAKFFACIKRSDGSCAWYRGAAPPKQEFLDIEDP

Structural information

Protein Domains	NTR. (27-152)
Interpro:	IPR001134 IPR001820 IPR008993 IPR015613 IPR027465 IPR030490
Prosite:	PS50189 PS00288
Pfam:	PF00965
PDB:	1BR9 1GXD 2TMP 4ILW
PDBsum:	1BR9 1GXD 2TMP 4ILW
STRING:	ENSP00000262768;

Other Databases

GeneCards: TIMP2; Malacards: TIMP2

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0002020	protease binding	IBA	molecular_function
GO:0005178	integrin binding	IEA	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005578	proteinaceous extracellul ar matrix	IBA	cellular_component
GO:0005615	extracellular space	IBA	cellular_component
GO:0007417	central nervous system de velopment	IEA	biological_process
GO:0007568	aging	IEA	biological_process
GO:0008191	metalloendopeptidase inhi bitor activity	IEA	molecular_function
GO:0008285	negative regulation of ce ll proliferation	IEA	biological_process
GO:0009725	response to hormone	IBA	biological_process
GO:0009986	cell surface	IEA	cellular_component
GO:0010951	negative regulation of en dopeptidase activity	IEA	biological_process
GO:0022617	extracellular matrix disa ssembly	TAS	biological_process
GO:0030426	growth cone	IEA	cellular_component
GO:0032487	regulation of Rap protein signal transduction	IEA	biological_process
GO:0034097	response to cytokine	IBA	biological_process
GO:0042493	response to drug	IEA	biological_process
GO:0043025	neuronal cell body	IEA	cellular_component
GO:0043410	positive regulation of MA PK cascade	IEA	biological_process
GO:0045666	positive regulation of ne uron differentiation	IEA	biological_process
GO:0045762	positive regulation of ad enylate cyclase activity	IEA	biological_process
GO:0045930	negative regulation of mi totic cell cycle	IEA	biological_process
GO:0046580	negative regulation of Ra s protein signal transduc tion	IEA	biological_process
GO:0046872	metal ion binding	IEA	molecular_function
GO:0051045	negative regulation of me mbrane protein ectodomain proteolysis	IBA	biological_process
GO:0070062	extracellular exosome	IDA	cellular_component
GO:0002020	protease binding	IBA	molecular_function
GO:0004857	enzyme inhibitor activity	IEA	molecular_function
GO:0005178	integrin binding	IEA	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005576	extracellular region	IEA	cellular_component
GO:0005576	extracellular region	IEA	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005578	proteinaceous extracellul ar matrix	IBA	cellular_component
GO:0005615	extracellular space	IEA	cellular_component
GO:0005615	extracellular space	IBA	cellular_component
GO:0007417	central nervous system de velopment	IEA	biological_process
GO:0007568	aging	IEA	biological_process
GO:0008191	metalloendopeptidase inhi bitor activity	IEA	molecular_function
GO:0008191	metalloendopeptidase inhi bitor activity	IEA	molecular_function
GO:0008191	metalloendopeptidase inhi bitor activity	IEA	molecular_function
GO:0008191	metalloendopeptidase inhi bitor activity	TAS	molecular_function
GO:0008285	negative regulation of ce ll proliferation	IEA	biological_process
GO:0009725	response to hormone	IBA	biological_process
GO:0009986	cell surface	IEA	cellular_component
GO:0010466	negative regulation of pe ptidase activity	IEA	biological_process
GO:0010951	negative regulation of en dopeptidase activity	IEA	biological_process
GO:0010951	negative regulation of en dopeptidase activity	IEA	biological_process
GO:0022617	extracellular matrix disa ssembly	TAS	biological_process
GO:0030414	peptidase inhibitor activ ity	IEA	molecular_function
GO:0030426	growth cone	IEA	cellular_component
GO:0032487	regulation of Rap protein signal transduction	IEA	biological_process
GO:0034097	response to cytokine	IEA	biological_process
GO:0034097	response to cytokine	IBA	biological_process
GO:0042493	response to drug	IEA	biological_process
GO:0043005	neuron projection	IEA	cellular_component
GO:0043025	neuronal cell body	IEA	cellular_component
GO:0043410	positive regulation of MA PK cascade	IEA	biological_process
GO:0045666	positive regulation of ne uron differentiation	IEA	biological_process
GO:0045762	positive regulation of ad enylate cyclase activity	IEA	biological_process
GO:0045861	negative regulation of pr oteolysis	IEA	biological_process
GO:0045930	negative regulation of mi totic cell cycle	IEA	biological_process
GO:0046580	negative regulation of Ra s protein signal transduc tion	IEA	biological_process
GO:0046872	metal ion binding	IEA	molecular_function
GO:0051045	negative regulation of me mbrane protein ectodomain proteolysis	IBA	biological_process
GO:0070062	extracellular exosome	IDA	cellular_component
GO:0002020	protease binding	IBA	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005576	extracellular region	TAS	cellular_component
GO:0005578	proteinaceous extracellul ar matrix	IBA	cellular_component
GO:0005615	extracellular space	IBA	cellular_component
GO:0008191	metalloendopeptidase inhi bitor activity	TAS	molecular_function
GO:0009725	response to hormone	IBA	biological_process
GO:0022617	extracellular matrix disa ssembly	TAS	biological_process
GO:0034097	response to cytokine	IBA	biological_process
GO:0051045	negative regulation of me mbrane protein ectodomain proteolysis	IBA	biological_process
GO:0070062	extracellular exosome	IDA	cellular_component

Diseases

Associated diseases	References
Aortic aneurysm	PMID: 15944607
Azoospermia	PMID: 12406369
Bowel endometriosis	PMID: 15452706
Bowel endometriosis	PMID: 15452706
Cancer	PMID: 17954022
Carotid artery diseases	PMID: 14605322
Chronic obstructive pulmonary disease (COPD)	PMID: 15193960
Crohn's disease	PMID: 17589947
Dupuytren contracture	PMID: 21732829
Endometriosis	PMID: 10027627
Implantation defects	INFBASE23011643
Endometriosis	INFBASE23011643
Adenomyosis	INFBASE16468658
Peritoneal, ovarian and bowel endometriotic tissues	INFBASE15452706
Ovarian endometriosis	PMID: 15452706
Ovarian endometriosis	PMID: 15452706
Periodontitis	PMID: 15691353
Peritoneal endometriosis	PMID: 15452706
Peritoneal endometriotic tissues	PMID: 15452706
Polycystic ovary syndrome (PCOS)	PMID: 21437624

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Associated_genes	Abstract
21111772	Endometrio sis				PGE2 COX-2 MMP1 MMP2 MMP3 MMP7 MMP9 TIMP1 TIMP2 TIMP3 TIMP4	Show abstract
10849774	Endometrio sis				MMP-1 -2 -3 and -9 TIMP-1 and -2 TACE TNF-alpha	Show abstract
18584412	Endometrio sis			37 (15 mild end ometriosis, 22 severe endometr iosis)	MMP-2 MMP-9 TIMP-1 and TIMP-2	Show abstract
22985025	Endometrio sis	MMP-2 (9082A>G, 9152A>G, 105330C>T, 14931T>C, 15918T>C, 18796G>A, 19033G>A, 19218A>G, 25190A>G, and 28542C>T) and TMIP-2 gene (42138327C>T, 42141169G>A, 42144611A>G, 42152781C>T, 42155855G>A, 42175617C>T, 42181597G>A, 42183387T>C, 42196041G>C, and 4219643		384 (201 patien ts, 183 control s)	MMP-2 TIMP-2	Show abstract
18177649	Endometrio sis	MMP-2 (-1306C-->T, -735C-->T), TIMP-2 (-418G-->C)	Chinese		MMP-2 TIMP-2	Show abstract
12372458	Endometrio sis	MMP-2, MT1-MMP, TIMP-2		53 (23 with end ometriosis and 30 without endo metriosis)	MMP-2 MT1-MMP TIMP-2	Show abstract
10027627	Endometrio sis				TIMP-2 progestin	Show abstract
16468658	Endometrio sis				MMP-2 MMP-3 TIMP-2	Show abstract
23011643	Endometrio sis			265 (194 patien ts affected by endometriosis, 71 patients wit h normal endome trium)	MMP-2 MT1-MMP TIMP-2	Show abstract
15452706	Endometrio sis (perit oneal, ova rian, bowe l)			87 (9 women wit h endometriosis , 18 women with out endometrios is, 20 with per itoneal endomet riosis, 20 ovar ian endometrios is, 20 colorect al endometriosi s)	MMP-2 MMP-3 MMP-11 TIMP-1 and TIMP-2	Show abstract