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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TIMP2 Gene

protein-coding GIFtS: 70
GCID: GC17M076850

TIMP metallopeptidase inhibitor 2

(Previous name: tissue inhibitor of metalloproteinase 2 )

Explore 191 diseases affiliated with
TIMP2 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
TIMP Metallopeptidase Inhibitor 2¹ ²
CSC-21K¹ ² ³
Tissue Inhibitor Of Metalloproteinase 2¹ ²
Tissue Inhibitor Of Metalloproteinases 2² ³
TIMP-2² ³
Metalloproteinase Inhibitor 2²

External Ids:	HGNC: 11821¹	Entrez Gene: 7077²	Ensembl: ENSG00000035862⁷	OMIM: 188825⁵	UniProtKB: P16035³

Export aliases for TIMP2 gene to outside databases

Previous GC identifers: GC17M076623 GC17M080115 GC17M077310 GC17M077446 GC17M074363 GC17M072271

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TIMP2:

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)

UniProtKB/Swiss-Prot: TIMP2_HUMAN, P16035

Function: Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to

their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14,

MMP-15, MMP-16 and MMP-19

Gene Wiki entry for TIMP2

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010783.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TIMP2 gene promoter:
Sp1 p53 AP-1 AP-2alpha isoform 3 AP-2alpha isoform 2 AP-2alpha isoform 4 AP-2alpha ATF AP-2alphaA
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TIMP2 promoter sequence

Search SABiosciences Chromatin IP Primers for TIMP2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TIMP2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q25 Ensembl cytogenetic band: 17q25.3 HGNC cytogenetic band: 17q25

TIMP2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TIMP2 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M076850: view genomic region (about GC identifiers)

Start:	76,849,059 bp from pter	End:	76,921,472 bp from pter
Size:	72,414 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TIMP2_HUMAN, P16035 (See protein sequence)

Recommended Name: Metalloproteinase inhibitor 2 precursor

Size: 220 amino acids; 24399 Da

Subunit: Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2

activity

Subcellular location: Secreted

3 PDB 3D structures from and Proteopedia for TIMP2:

1BR9 (3D)

1GXD (3D)

2TMP (3D)

Secondary accessions: Q16121 Q93006 Q9UDF7

Explore the universe of human proteins at neXtProt for TIMP2: NX_P16035

Post-translational modifications:

The activity of TIMP2 is dependent on the presence of disulfide bonds¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P16035

TIMP2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_003246.1

ENSEMBL proteins:

ENSP00000467584 ENSP00000441724 ENSP00000262768 ENSP00000468296 ENSP00000464930

Reactome Protein details: P16035
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant TIMP2 Protein
	R&D Systems Recombinant & Natural Proteins for TIMP2 (TIMP-2)
	Enzo Life Sciences proteins for TIMP2
	OriGene Purified Protein: TIMP2 OriGene Protein Over-expression Lysate: TIMP2 OriGene Custom Protein Services for TIMP2
	GenScript Custom Purified and Recombinant Proteins Services for TIMP2
	Novus Biologicals TIMP2 Proteins Novus Biologicals TIMP2 Lysates
	Sino Biological Recombinant Protein for TIMP2
	ProSpec Recombinant Protein for TIMP2
	Uscn Proteins for TIMP2

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	--
GO:0005604	basement membrane	IEA	--
GO:0005615	extracellular space	IEA	--
GO:0009986	cell surface	IEA	--
GO:0030426	growth cone	IEA	--

TIMP2 for ontologies About GeneDecksing

TIMP2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TIMP2
	R&D Systems Antibodies for TIMP2 (TIMP-2)
	Cell Signaling Technology (CST) Antibodies for TIMP2
	OriGene Antibodies (see all 7): TIMP2 OriGene Custom Antibody Services for TIMP2
	GenScript Custom Superior Antibodies Services for TIMP2
	Novus Biologicals TIMP2 Antibodies
	Abcam antibodies for TIMP2
	Uscn Antibodies for TIMP2
	ThermoFisher Antibody for TIMP2

Assay Products for TIMP2:

	EMD Millipore Kits and Assays for the Analysis of TIMP2
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for TIMP2 (TIMP-2) (see all)
	GenScript Custom Assay Services for TIMP2
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for TIMP2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TIMP2 for domains About GeneDecksing

4 InterPro domains/families:

IPR008993 TIMP-like_OB-fold

IPR015613 TIMP2

IPR001134 Netrin_domain

IPR001820 Prot_inh_TIMP

Graphical View of Domain Structure for InterPro Entry P16035

ProtoNet protein and cluster: P16035

1 Blocks protein family: IPB001820 Tissue inhibitor of metalloproteinase

UniProtKB/Swiss-Prot: TIMP2_HUMAN, P16035

Similarity: Belongs to the protease inhibitor I35 (TIMP) family

Similarity: Contains 1 NTR domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TIMP2_HUMAN, P16035

Function: Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to

their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14,

MMP-15, MMP-16 and MMP-19

Induction: Down-regulated by TGFB1

Genatlas biochemistry entry for TIMP2:

matrix metalloproteinase,tissue inhibitor 2,with two alternatively spliced forms may be associated with SYN4,involved

in the invasive phenotype of acute myelogenous leukemia

miRNA Products:		OriGene 3'-UTR Clone: TIMP2 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TIMP2
		8/71 QIAGEN miScript miRNA Assays for microRNAs that regulate TIMP2 (see all 71):
		hsa-miR-631 hsa-miR-106a hsa-miR-30d hsa-miR-519a hsa-miR-3161 hsa-miR-3142 hsa-miR-30a hsa-miR-93

		SwitchGear 3'UTR luciferase reporter plasmid: TIMP2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TIMP2 (see all 7) OriGene shRNA RFP: TIMP2 OriGene siRNA: TIMP2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TIMP2

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TIMP2

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TIMP2 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TIMP2 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TIMP2 (NM_003255)
		Sino Biological Human cDNA Clone for TIMP2
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TIMP2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TIMP2

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TIMP2
		Search LifeMap BioReagents cell lines for TIMP2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TIMP2

Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005178	integrin binding	IEA	--
GO:0008047	enzyme activator activity	IEA	--
GO:0008191	metalloendopeptidase inhibitor activity	IEA	--
GO:0046872	metal ion binding	IEA	--

TIMP2 for ontologies About GeneDecksing

3 GenomeRNAi human phenotypes for TIMP2:

Increased cell death in HCT116

Increased focal adhesion (FA)

Upregulation of Wnt/beta-caten

Animal Models:
Mouse knock-outs for TIMP2: Timp2^tm1Jjc Timp2^tm1Pds
6 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Timp2):

behavior/neurological	hematopoietic system	homeostasis/metabolism	immune system	nervous system
normal

TIMP2 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/20 super-pathways (see all 20) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Apoptotic Pathways in Synovial Fibroblasts

8/14 pathways (see all 14)
Apoptotic Pathways in Synovial Fibroblasts	1.00	ERK5 Signaling	0.61
p53 Mediated Apoptosis	0.84	eIF2 Pathway	0.60
Mitochondrial Apoptosis	0.73	Rac1 Pathway	0.58
Telomerase Components in Cell Signaling	0.72	Nuclear Receptor Activation by Vitamin-A	0.57

GPCR Pathway

GPCR Pathway	1.00	Estrogen Pathway	0.55
Ras Pathway	0.62	Pancreatic Adenocarcinoma	0.55
Breast Cancer Regulation by Stathmin1	0.58	Paxillin Interactions	0.53
NFAT in Immune Response	0.58

Rho Family GTPases

Rho Family GTPases	1.00	MAPK Signaling	0.51
ERK Signaling	0.61	ILK Signaling	0.45
Molecular Mechanisms of Cancer	0.51

TGF-Beta Pathway

	TGF-Beta Pathway	1.00			JAK-STAT Pathway	0.57
	MAPK Family Pathway	0.60			JNK Pathway	0.50

Nanog in Mammalian ESC Pluripotency

	Nanog in Mammalian ESC Pluripotency	1.00			14-3-3 Induced Intracellular Signaling	0.59
	GSK3 Signaling	0.61			eNOS Signaling	0.48

Pathway sources
See GeneCards unified pathways
Show all pathways

2 EMD Millipore Pathways for TIMP2

	Cell adhesion Cell-matrix glycoconjugates
	Cell adhesion ECM remodeling

5/55 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for TIMP2 (see all 55)

	Nuclear Receptor Activation by Vitamin-A
	Paxillin Interactions
	Telomerase Components in Cell Signaling
	Inhibition of Matrix Metalloproteinases
	Mitochondrial Apoptosis

2 Cell Signaling Technology (CST) Pathways for TIMP2

	Angiogenesis
	Protein Stability

2 GeneGo (Thomson Reuters) Pathways for TIMP2

	Cell adhesion Cell-matrix glycoconjugates
	Cell adhesion ECM remodeling

2 BioSystems Pathways for TIMP2

	Matrix Metalloproteinases
	Angiogenesis

3 Reactome Pathways for TIMP2

	Extracellular matrix organization
	Degradation of the extracellular matrix
	Activation of Matrix Metalloproteinases

TIMP2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TIMP2

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/28 Interacting proteins for TIMP2 (P16035³ ENSP00000262768⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 28)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
MMP2	P08253³, ENSP00000219070⁴	I2D: score=4 STRING: ENSP00000219070
MMP14	P50281³, ENSP00000308208⁴	I2D: score=3 STRING: ENSP00000308208
PSMA7	O14818³, ENSP00000359910⁴	I2D: score=2 STRING: ENSP00000359910
ECHS1	P30084³, ENSP00000357535⁴	I2D: score=1 STRING: ENSP00000357535
HSPA4L	O95757³, ENSP00000296464⁴	I2D: score=1 STRING: ENSP00000296464

About this table

Gene Ontology (GO): 5/19 biological process terms (GO ID links to tree view) (see all 19): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0007417	central nervous system development	IEA	--
GO:0007568	aging	IEA	--
GO:0008285	negative regulation of cell proliferation	IEA	--
GO:0022617	extracellular matrix disassembly	TAS	--
GO:0030198	extracellular matrix organization	TAS	--

TIMP2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TIMP2 for compounds About GeneDecksing

EMD Millipore small molecules for TIMP2:
Small Molecule - inhibitor

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for TIMP2
10/88 Novoseek chemical compound relationships for TIMP2 gene (see all 88) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
matrigel	75.1	17	8740587 (2), 14606648 (2), 18474097 (1), 9462715 (1) (see all 11)
batimastat	73.6	15	17086359 (2), 7563189 (2), 15949468 (1), 10551322 (1) (see all 12)
(4-aminophenyl)mercuric acetate	65.5	2	1646720 (1), 7772054 (1)
vegf	54.6	85	16202678 (4), 16681930 (4), 19787153 (3), 12225633 (2) (see all 51)
norcantharidin	51.1	8	16784656 (3), 16681930 (3)
methyl selenol	43.8	2	16702316 (2)
hydroxamate	38.9	14	8086430 (2), 9733724 (2), 12475252 (1), 11415441 (1) (see all 7)
latanoprost	37.1	6	14638715 (2), 12454040 (1), 18971237 (1), 16936101 (1) (see all 5)
paraffin	30.5	6	20209790 (1), 16776850 (1), 16784656 (1), 16169261 (1) (see all 6)
ribonucleic acid	30.1	1	9661630 (1)

Search CenterWatch for drugs/clinical trials and news about TIMP2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TIMP2 gene:

NM_003255.4

Unigene Cluster for TIMP2:

TIMP metallopeptidase inhibitor 2

Hs.633514 [show with all ESTs]

Unigene Representative Sequence: NM_003255

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000585421 ENST00000536189 ENST00000262768(uc002jwe.3 uc010wty.2 uc002jwf.3)

ENST00000586057 ENST00000592761

miRNA Products:		OriGene 3'-UTR Clone: TIMP2 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TIMP2
		8/71 QIAGEN miScript miRNA Assays for microRNAs that regulate TIMP2 (see all 71):
		hsa-miR-631 hsa-miR-106a hsa-miR-30d hsa-miR-519a hsa-miR-3161 hsa-miR-3142 hsa-miR-30a hsa-miR-93

		SwitchGear 3'UTR luciferase reporter plasmid: TIMP2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TIMP2 (see all 7) OriGene shRNA RFP: TIMP2 OriGene siRNA: TIMP2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TIMP2

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TIMP2 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TIMP2 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TIMP2 (NM_003255)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TIMP2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TIMP2

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TIMP2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat TIMP2
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TIMP2
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TIMP2

Additional cDNA sequence:

AK294290.1 AL110197.1 AL713764.1 BC010410.2 BC039613.1 BC040039.1 BC040445.1 BC052605.1

BC071586.1 BC111089.1 J05593.1 M32304.1 S48568.1 X54533.1

23 DOTS entries:

DT.100884685 DT.320454 DT.101958961 DT.100039281 DT.100039279 DT.91780826 DT.91964592 DT.87011688

DT.95260462 DT.100884682 DT.120897375 DT.91780931 DT.120897359 DT.95242885 DT.100884683 DT.100884688

DT.102844632 DT.91686177 DT.95260440 DT.120897324 DT.120897333 DT.95125209 DT.95260451

24/869 AceView cDNA sequences (see all 869):

BQ004141 AW264017 AW073419 AI497956 BQ010142 CA435310 BU785522 T90117

R97102 AI821338 AW305100 AI270690 BG054929 AA323024 AA679934 BE968429

BM126032 CA444121 BX359449 CA422156 AA595824 BQ183813 N50793 AI087168

GeneLoc Exon Structure

5 Alternative Splicing Database (ASD) splice patterns (SP) for TIMP2 About this scheme

ExUns:	1	^	2	^	3a	·	3b	·	3c	^	4	^	5a	·	5b	^	6a	·	6b	^	7a	·	7b	·	7c	·	7d
SP1:			-		-		-		-										-
SP2:																			-
SP3:
SP4:																			-
SP5:					-		-		-

ECgene alternative splicing isoforms for TIMP2

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TIMP2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TCTCTGATGC

About this image

TIMP2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

7 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Cartilage

Cervical Intervertebral Disc

Intervertebral Disc Nucleus Pulposus Cells

Cartilage

Lumbar Intervertebral Disc

Intervertebral Disc Nucleus Pulposus Cells

Cartilage

Sacral Intervertebral Disc

Intervertebral Disc Nucleus Pulposus Cells

Cartilage

Thoracic Intervertebral Disc

Intervertebral Disc Nucleus Pulposus Cells

Cartilage

Endothelium

Veins

Vascular Smooth Muscle Cells

Smooth Muscle

Heart

Aortic Arch Arteries

Vascular Smooth Muscle Cells

Myocardium, Neural Crest, Smooth Muscle

Heart

Endocardium

Vascular Smooth Muscle Cells

Smooth Muscle

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

Epiblast-like cells (Reconstitution of mo...)

Primordial germ cell-like cells (Reconstitution of mo...)

See TIMP2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TIMP2

SOURCE GeneReport for Unigene cluster: Hs.633514

SABiosciences Expression via Pathway-Focused PCR Arrays including TIMP2 (see all 8):

Fibrosis in human mouse rat

Extracellular Matrix & Adhesion Molecules in human mouse rat

Angiogenic Growth Factors in human mouse rat

Lymphoma in human mouse rat

Prostate Cancer in human mouse rat

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TIMP2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat TIMP2
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TIMP2
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TIMP2

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TIMP2

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for TIMP2 gene from 5/17 species (see all 17) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	TIMP2¹	TIMP metallopeptidase inhibitor 2	77.83(n) 78.44(a)		374178 NM_204298.1 NP_989629.1
lizard (Anolis carolinensis)	Reptilia	TIMP2⁶	--	85(a)	1 ↔ 1	2(101738132-101770090)
African clawed frog (Xenopus laevis)	Amphibia	Xl.26350²	Xenopus laevis transcribed sequence with moderate similarity more	76.11(n)		CF548190.1
zebrafish (Danio rerio)	Actinopterygii	timp2²	tissue inhibitor of metalloproteinase 2	81.31(n)		359835 AY324194.1
fruit fly (Drosophila melanogaster)	Insecta	Timp⁶	Tissue inhibitor of metalloproteases	20(a)	1 → many	3R(6029597-6038726)

ENSEMBL Gene Tree for TIMP2 (if available)
TreeFam Gene Tree for TIMP2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for TIMP2 gene

TIMP4² TIMP3² TIMP1²

4 SIMAP similar genes for TIMP2 using alignment to 3 protein entries: TIMP2_HUMAN (see all proteins):

LOC100653515 TIMP4 TIMP3 TIMP1

TIMP2 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs184437489^1,2		--	76848571(+)	`GCCCCA/GTCTCT`	1	--	ds500¹		0	--	--	--	--
rs146042193^1,2		--	76848582(+)	`GCCACC/TGCATC`	1	--	ds500¹		0	--	--	--	--
rs147823947^1,2		--	76848590(+)	`ATCGCA/GCTTTT`	1	--	ds500¹		0	--	--	--	--
rs142464582^1,2		--	76848698(+)	`CCTCCA/GAGGTT`	1	--	ds500¹		0	--	--	--	--
rs146522361^1,2		--	76848762(+)	`CACCAC/TGCCTA`	1	--	ds500¹		0	--	--	--	--
rs148316195^1,2		--	76848788(+)	`GGGTTA/TTGCGA`	1	--	ds500¹		0	--	--	--	--
rs141426733^1,2		--	76848792(+)	`TTTGCA/GAAGTT`	1	--	ds500¹		0	--	--	--	--
rs7218201^1,2	C	--	76848899(+)	`GCATCC/ACATAT`	1	--	ds500¹		1		NA	2
rs190366275^1,2		--	76848936(+)	`TCTCTA/GGAGGA`	1	--	ds500¹		0	--	--	--	--
rs150390217^1,2		--	76848959(+)	`CCTCCC/TGCCGG`	1	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for TIMP2 (76849059 - 76921472 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for TIMP2
1 Indel: 45604
Human Gene Mutation Database (HGMD): TIMP2

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TIMP2

DNA2.0 Custom Variant and Variant Library Synthesis for TIMP2

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TIMP2 for disorders           About GeneDecksing

OMIM gene information: 188825    OMIM disorders: --

20/191 diseases for TIMP2 (see all 191):    About MalaCards

open-angle glaucoma hereditary neuralgic amyotrophy primary open angle glaucoma lichen planus

spinal stenosis proliferative diabetic retinopathy chronic venous leg ulcers refractive error

corneal neovascularization non-small cell lung carcinoma aortic aneurysm congenital diaphragmatic hernia

oral lichen planus abdominal aortic aneurysm vernal keratoconjunctivitis duchenne muscular dystrophy

conjunctivochalasis retinal detachment cervical squamous cell carcinoma clear cell renal cell carcinoma

3 diseases from the University of Copenhagen DISEASES database for TIMP2:

Carcinoma Vascular disease Arthritis

10/94 Novoseek disease relationships for TIMP2 gene (see all 94) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
metastasis	70.7	160	15946567 (4), 16114547 (4), 10425288 (4), 15546163 (4) (see all 86)
tumors	63.1	367	8674034 (6), 15546163 (6), 16784992 (5), 10366463 (5) (see all 99)
fibrosarcoma	56.8	14	16214327 (2), 18495463 (1), 8112602 (1), 7768948 (1) (see all 9)
cancer	51.4	81	9008095 (3), 9484825 (3), 11796838 (3), 11890687 (3) (see all 49)
liver fibrosis	51.2	24	19517234 (5), 9792032 (3), 11925608 (3), 14695775 (3) (see all 8)
pathological processes	46.3	2	10985804 (1), 11004090 (1)
conjunctivochalasis	45.7	3	10670469 (2)
aortic aneurysm abdominal	43.1	1	10372551 (1)
carcinoma	41.6	67	15781321 (5), 12970394 (5), 15095267 (4), 8302724 (3) (see all 31)
carcinoma squamous cell	41.1	22	12479097 (2), 10657012 (1), 16142392 (1), 18042068 (1) (see all 14)

Genetic Association Database (GAD): TIMP2
Human Genome Epidemiology (HuGE) Navigator: TIMP2 (54 documents)
Tumor Gene Database (TGDB): TIMP2

Export disorders for TIMP2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for TIMP2 gene, integrated from 9 sources (see all 1147):
(articles sorted by number of sources associating them with TIMP2)

Utopia: connect your pdf to the dynamic
world of online information

Isolation and characterization of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) from human rheumatoid synovial fluid. (PubMed id 1730286)^{1, 2, 9} Osthues A.... Tschesche H. (1992)
Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. (PubMed id 2380196)^{1, 2, 9} Stetler-Stevenson W.G.... Liotta L.A. (1990)
The role of genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes in head and neck cancer. (PubMed id 16275157)^{1, 4, 9} O-Charoenrat P. and Khantapura P. (2006)
Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes. (PubMed id 14604886)^{1, 4, 9} Zhou Y....Lin D. (2004)
Tissue inhibitor of metalloproteinases-1, -2, and -3 polymorphisms in a white population with intracranial aneurysms. (PubMed id 14605322)^{1, 4, 9} Krex D....Schackert G. (2003)
Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene. (PubMed id 8810321)^{1, 2, 9} Hammani K.... Declerck Y.A. (1996)
Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2). (PubMed id 8112602)^{1, 2, 9} de Clerck Y.A.... Rousseau G.G. (1994)
Analysis of the MMP-9 (C-1562 T) and TIMP-2 (G-418C) gene promoter polymorphisms in patients with chronic periodontitis. (PubMed id 15691353)^{1, 4} de Souza A.P....Line S.R. (2005)
Association analysis of tissue inhibitor of metalloproteinase2 gene polymorphisms with COPD in Egyptians. (PubMed id 15672858)^{1, 4} Hegab A.E....Sekizawa K. (2005)
Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms. (PubMed id 15944607)^{1, 4} Ogata T....Kuivaniemi H. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 7077	HGNC: 11821	AceView: TIMP2	Ensembl:ENSG00000035862	euGenes: HUgn7077
ECgene: TIMP2	H-InvDB: TIMP2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for TIMP2	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TIMP2	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for TIMP2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TIMP2 gene:
Search GeneIP for patents involving TIMP2

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
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ThermoFisher Antibody for TIMP2

Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TIMP2

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TIMP metallopeptidase inhibitor 2

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TIMP metallopeptidase inhibitor 2

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