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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TIMP3 Gene

protein-coding GIFtS: 65
GCID: GC22P033196

TIMP metallopeptidase inhibitor 3

(Previous names: tissue inhibitor of metalloproteinase 3 (Sorsby fundus...)
(Previous symbol: SFD)

Explore 140 diseases affiliated with
TIMP3 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 3¹ ²		HSMRK222²
SFD¹ ² ⁵		K222²
Protein MIG-5² ³		K222TA2²
Tissue Inhibitor Of Metalloproteinases 3² ³		Metalloproteinase Inhibitor 3²
TIMP-3² ³		MIG-5 Protein²
Tissue Inhibitor Of Metalloproteinase 3 (Sorsby Fundus Dystrophy, Pseudoinflammatory)¹

External Ids:	HGNC: 11822¹	Entrez Gene: 7078²	Ensembl: ENSG00000100234⁷	OMIM: 188826⁵	UniProtKB: P35625³

Export aliases for TIMP3 gene to outside databases

Previous GC identifers: GC22P029893 GC22P031521 GC22P016154

(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 TIMP3:

This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix

metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix (ECM). Expression of

this gene is induced in response to mitogenic stimulation and this netrin domain-containing protein is localized to

the ECM. Mutations in this gene have been associated with the autosomal dominant disorder Sorsby's fundus dystrophy.

(provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: TIMP3_HUMAN, P35625

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

their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli. Known to act

on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15

Gene Wiki entry for TIMP3

(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_000022.10 NC_018933.1 NT_011520.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TIMP3 gene promoter:
Sp1 AP-1 ATF-2 COUP MyoD c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): TIMP3 promoter sequence

Search SABiosciences Chromatin IP Primers for TIMP3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TIMP3

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

Entrez Gene cytogenetic band: 22q12.3 Ensembl cytogenetic band: 22q12.3 HGNC cytogenetic band: 22q12.3

TIMP3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TIMP3 gene location

GeneLoc information about chromosome 22 GeneLoc Exon Structure

GeneLoc location for GC22P033196: view genomic region (about GC identifiers)

Start:	33,196,802 bp from pter	End:	33,259,030 bp from pter
Size:	62,229 bases	Orientation:	plus 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: TIMP3_HUMAN, P35625 (See protein sequence)

Recommended Name: Metalloproteinase inhibitor 3 precursor

Size: 211 amino acids; 24145 Da

Subunit: Interacts with EFEMP1

Subcellular location: Secreted, extracellular space, extracellular matrix

1 PDB 3D structure from and Proteopedia for TIMP3:

3CKI (3D)

Secondary accessions: B2RBY9 Q5THV4 Q9UC74 Q9UGS2

Explore the universe of human proteins at neXtProt for TIMP3: NX_P35625

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P35625

TIMP3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000353.1

ENSEMBL proteins:

ENSP00000266085 ENSP00000371481

Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for TIMP3 (TIMP-3)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate: TIMP3 OriGene Custom Protein Services for TIMP3
	GenScript Custom Purified and Recombinant Proteins Services for TIMP3
	Novus Biologicals TIMP3 Proteins Novus Biologicals TIMP3 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for TIMP3

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

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	--	--
GO:0005604	basement membrane	IEA	--
GO:0005737	cytoplasm	--	--
GO:0031012	colocalizes with extracellular matrix	IDA	--

TIMP3 for ontologies About GeneDecksing

TIMP3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TIMP3
	R&D Systems Antibodies for TIMP3 (TIMP-3)
	Cell Signaling Technology (CST) Antibodies for TIMP3
	Browse OriGene Antibodies OriGene Custom Antibody Services for TIMP3
	GenScript Custom Superior Antibodies Services for TIMP3
	Novus Biologicals TIMP3 Antibodies
	Search for Antibodies for TIMP3 at Abcam
	Uscn Antibodies for TIMP3
	ThermoFisher Antibody for TIMP3

Assay Products for TIMP3:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for TIMP3 (TIMP-3) (see all)
	GenScript Custom Assay Services for TIMP3
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for TIMP3

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

TIMP3 for domains About GeneDecksing

4 InterPro domains/families:

IPR008993 TIMP-like_OB-fold

IPR001134 Netrin_domain

IPR015612 Tissue_inhib_metalloprotease_3

IPR001820 Prot_inh_TIMP

Graphical View of Domain Structure for InterPro Entry P35625

ProtoNet protein and cluster: P35625

1 Blocks protein family: IPB001820 Tissue inhibitor of metalloproteinase

UniProtKB/Swiss-Prot: TIMP3_HUMAN, P35625

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: TIMP3_HUMAN, P35625

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

their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli. Known to act

on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15

Genatlas biochemistry entry for TIMP3:

matrix metalloproteinase,tissue inhibitor 3,expressed in retinal pigment epithelium,placenta,localized in extracellular

matrix (glycosylated or not form),embedded in intron V of SYN3,inactivated by methylation in

uterus,breast,renal,colon,brain carcinomas

miRNA Products:		miRTarBase miRNAs that target TIMP3: hsa-mir-181b (MIRT000637), hsa-mir-1 (MIRT002807), hsa-mir-21 (MIRT000954)

		OriGene 3'-UTR Clone: TIMP3 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TIMP3
		8/95 QIAGEN miScript miRNA Assays for microRNAs that regulate TIMP3 (see all 95):
		hsa-miR-323-3p hsa-miR-3607-3p hsa-miR-607 hsa-miR-520e hsa-miR-1321 hsa-miR-30d hsa-miR-890 hsa-miR-30a

		SwitchGear 3'UTR luciferase reporter plasmid: TIMP3 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 TIMP3 (see all 7) OriGene shRNA RFP: TIMP3 OriGene siRNA: TIMP3
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TIMP3

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TIMP3

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 TIMP3 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TIMP3 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TIMP3 (NM_000362)
		Sino Biological Human cDNA Clone for TIMP3
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TIMP3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TIMP3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TIMP3
		Search LifeMap BioReagents cell lines for TIMP3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TIMP3

Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	18638486
GO:0008191	metalloendopeptidase inhibitor activity	TAS	18638486
GO:0046872	metal ion binding	IEA	--

TIMP3 for ontologies           About GeneDecksing

Animal Models:
     Mouse knock-outs for TIMP3: Timp3^tm1Rkho Timp3^tm1Hest Timp3^tm1Osya
     15/16 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Timp3) (see all 16):

behavior/neurological	cardiovascular system	cellular	endocrine/exocrine gland	growth/size
hematopoietic system	homeostasis/metabolism	immune system	integument	liver/biliary system
mortality/aging	muscle	pigmentation	renal/urinary system	respiratory system

TIMP3 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

1 EMD Millipore Pathway for TIMP3

Cell adhesion ECM remodeling

5/55 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for TIMP3 (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 TIMP3

	Angiogenesis
	Protein Stability

1 GeneGo (Thomson Reuters) Pathway for TIMP3

Cell adhesion ECM remodeling

4 BioSystems Pathways for TIMP3

	Angiogenesis
	Oncostatin M Signaling Pathway
	Matrix Metalloproteinases
	Endochondral Ossification

1 PharmGKB Pathway for TIMP3

VEGF Signaling Pathway

TIMP3 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TIMP3

STRING Interaction Network Preview (showing 5 interactants - click image to see 10)

5/10 Interacting proteins for TIMP3 (P35625^{1, 3} ENSP00000266085⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 10)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
AGTR2	P50052¹^,³, ENSP00000360973⁴	EBI-1748085,EBI-1748067 I2D: score=1 STRING: ENSP00000360973
MMP2	P08253³, ENSP00000219070⁴	I2D: score=2 STRING: ENSP00000219070
MMP9	P14780³, ENSP00000361405⁴	I2D: score=2 STRING: ENSP00000361405
MMP13	P45452³, ENSP00000260302⁴	I2D: score=1 STRING: ENSP00000260302
MMP14	P50281³, ENSP00000308208⁴	I2D: score=1 STRING: ENSP00000308208

About this table

Gene Ontology (GO): 5/14 biological process terms (GO ID links to tree view) (see all 14): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0007417	central nervous system development	--	--
GO:0007568	aging	--	--
GO:0007601	visual perception	IEA	--
GO:0009612	response to mechanical stimulus	--	--
GO:0009725	response to hormone stimulus	--	--

TIMP3 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

TIMP3 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for TIMP3
10/42 Novoseek chemical compound relationships for TIMP3 gene (see all 42) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
adamalysin	67.4	1	15095265 (1)
batimastat	63.7	3	11774278 (1), 16230401 (1), 17216595 (1)
5-aza-2'deoxycytidine	48.5	2	10797283 (1), 15297175 (1)
o6-methylguanine	47.2	5	12845678 (1), 16502411 (1), 14654977 (1), 15197802 (1) (see all 5)
tgf beta1	42.4	8	15599946 (3), 11869079 (3), 15883123 (1), 19625257 (1)
matrigel	39.1	1	9622064 (1)
vegf	28.2	19	20060952 (2), 12652295 (2), 12828172 (1), 18097337 (1) (see all 10)
cysteine	22.4	11	15203191 (1), 9643018 (1), 9760202 (1), 11821400 (1) (see all 10)
progesterone	22.2	11	9160717 (2), 7588231 (1), 11344207 (1), 19389837 (1) (see all 7)
tetrahydrofolate	22	3	16981189 (1)

Search CenterWatch for drugs/clinical trials and news about TIMP3

(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 TIMP3 gene:

NM_000362.4

Unigene Cluster for TIMP3:

TIMP metallopeptidase inhibitor 3

Hs.644633 [show with all ESTs]

Unigene Representative Sequence: NM_000362

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

ENST00000266085(uc003anb.3) ENST00000382049

miRNA Products:		OriGene 3'-UTR Clone: TIMP3 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TIMP3
		8/95 QIAGEN miScript miRNA Assays for microRNAs that regulate TIMP3 (see all 95):
		hsa-miR-323-3p hsa-miR-3607-3p hsa-miR-607 hsa-miR-520e hsa-miR-1321 hsa-miR-30d hsa-miR-890 hsa-miR-30a

		SwitchGear 3'UTR luciferase reporter plasmid: TIMP3 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 TIMP3 (see all 7) OriGene shRNA RFP: TIMP3 OriGene siRNA: TIMP3
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TIMP3

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TIMP3 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TIMP3 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TIMP3 (NM_000362)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TIMP3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TIMP3

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TIMP3 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat TIMP3
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TIMP3
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TIMP3

Additional cDNA sequence:

AF035289.1 AK098517.1 AK298126.1 AK311702.1 AK314871.1 BC014277.2 BT006848.1 CR456593.1

D45917.1 L15078.1 S78453.1 U02571.1 U14394.1 U67195.1 X76227.1 X77690.1

X80791.1

24/55 DOTS entries (see all 55):

DT.100045220 DT.95100610 DT.95100669 DT.91646034 DT.100829527 DT.95237947 DT.95316138 DT.100830114

DT.100893513 DT.100893530 DT.100893475 DT.101977541 DT.120661402 DT.95100608 DT.100893483 DT.100893520

DT.100893534 DT.100893485 DT.100893490 DT.100893503 DT.100893508 DT.91707000 DT.100765761 DT.100771946

24/1504 AceView cDNA sequences (see all 1504):

AI813792 BQ019591 BF724200 BX952401 BU624586 BX952362 AI090127 BP377224

BF343706 AA936208 CR593372 BM846618 CD518117 BX509183 BQ933298 BP345730

BU686884 CA394143 BX955198 AA191396 CR616306 BU684289 BQ924223 AA369052

GeneLoc Exon Structure

(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

TIMP3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TTATTTATGA

About this image

TIMP3 expression in embryonic tissues and stem cells

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

10/13 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 13)

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Gut Tube

Midgut

Midgut Endoderm Cells

Endoderm

Kidney

Spinal Ventral Columns

Ventral Spinal Cord Progenitor Cells

Motor Neurons

Brain

Brain

Gut Tube

Interventricular Septum

Heart

Left Ventricle

Heart

Right Ventricle

Heart

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 7 LifeMap Cells

Name

Category

PureStem™ mesenchymal progenitor SM30 (Embryonic Progenitor Cell)

Adipose, Bone, Cartilage

PureStem™ mesenchymal progenitor 7SMOO32 (Embryonic Progenitor Cell)

Adipose, Bone, Cartilage

PureStem™ mesenchymal progenitor 4D20.8 (Embryonic Progenitor Cell)

Lateral Plate Mesoderm, Neural Crest

PureStem™ progenitor E44 (Embryonic Progenitor Cell)

PureStem™ progenitor RASMO12 (Embryonic Progenitor Cell)

PureStem™ progenitor Z1 (Embryonic Progenitor Cell)

Definitive endoderm-like cells (A scalable, suspensi...)

See TIMP3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TIMP3

SOURCE GeneReport for Unigene cluster: Hs.644633

SABiosciences Expression via Pathway-Focused PCR Arrays including TIMP3 (see all 9):

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 TIMP3 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat TIMP3
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TIMP3
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TIMP3

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TIMP3

(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 TIMP3 gene from 3/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	TIMP3¹	TIMP metallopeptidase inhibitor 3	77.73(n) 81.04(a)		396483 NM_205487.1 NP_990818.1
lizard (Anolis carolinensis)	Reptilia	TIMP3⁶	--	87(a)	1 ↔ 1	5(20118001-20124811)
fruit fly (Drosophila melanogaster)	Insecta	Timp⁶	Tissue inhibitor of metalloproteases	19(a)	1 → many	3R(6029597-6038726)

ENSEMBL Gene Tree for TIMP3 (if available)
TreeFam Gene Tree for TIMP3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for TIMP3 gene

TIMP4² TIMP1² TIMP2²

3 SIMAP similar genes for TIMP3 using alignment to 1 protein entry: TIMP3_HUMAN:

TIMP2 TIMP4 TIMP1

TIMP3 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)
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SNP ID	Valid	Clinical significance	Chr 22 pos	Sequence	#	AA Chg	Type	More	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs73885105^1,2	C,	--	16153639(+)	`CTGCTC/TAGGAC`	3	--	int¹		1	WA	2
rs7290885^1,2	C,F,H,	--	16153808(+)	`CAGTGC/TTAGAA`	3	--	int¹		10	NS EA NA WA	1382
rs58394026^1,2	C,	--	16154211(+)	`TTAGAT/CGGAAC`	3	--	int¹		3	WA CSA	122
rs5749511^1,2	C,	--	16154282(+)	`GGTGAC/TGAGTT`	3	--	int¹		3	CSA WA NA	240
rs11703366^1,2	C,H	--	16154388(+)	`TATTGT/GGAGAG`	3	--	int¹		4	NS EA	384
rs73158308^1,2	C,F,	--	16154410(+)	`TGAGAT/AACAGA`	3	--	int¹		1	NA	120
rs2234920^1,2	F,	--	16154988(+)	`AACAGT/ACTTCT`	3	--	int¹		1	WA	118
rs12169569^1,2	F,	--	16156481(+)	`CCTGCG/ACCTAT`	3	--	int¹		1	WA	118
rs79738219^1,2		--	16156513(+)	`GACCCA/CACCCA`	3	--	int¹		2	CSA WA	119
rs76674051^1,2		--	16157373(+)	`ACCCTT/AGTAAG`	3	--	int¹		1	WA	118

HapMap Linkage Disequilibrium report for TIMP3 (33196802 - 33259030 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for TIMP3: --
Human Gene Mutation Database (HGMD): TIMP3

Locus Specific Mutation Databases (LSDB): TIMP3

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TIMP3

DNA2.0 Custom Variant and Variant Library Synthesis for TIMP3

(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.)
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TIMP3 for disorders           About GeneDecksing

OMIM gene information: 188826
OMIM disorders: 136900
UniProtKB/Swiss-Prot: TIMP3_HUMAN, P35625

Defects in TIMP3 are the cause of Sorsby fundus dystrophy (SFD) [MIM:136900]. SFD is a rare autosomal dominant

macular disorder with an age of onset in the fourth decade. It is characterized by loss of central vision from

subretinal neovascularization and atrophy of the ocular tissues. Generally, macular disciform degeneration develops in

the patients eye within 6 months to 6 years

20/140 diseases for TIMP3 (see all 140): About MalaCards

sorsby fundus dystrophy fundus dystrophy cone-rod dystrophy central nervous system lymphoma

pseudoinflammatory fundus dystrophy partial central choroid dystrophy proliferative diabetic retinopathy age related macular degeneration

refractive error graft versus host disease night blindness diabetic retinopathy

abdominal aortic aneurysm pilocytic astrocytoma choroidal dystrophy maculopathy

clear cell renal cell carcinoma familial adenomatous polyposis soft tissue sarcoma type 2 diabetes mellitus

3 diseases from the University of Copenhagen DISEASES database for TIMP3:

Fundus dystrophy Age related macular degeneration Carcinoma

10/96 Novoseek disease relationships for TIMP3 gene (see all 96) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
drusen	63.9	7	11878827 (2), 11450763 (1), 10476804 (1), 12391305 (1) (see all 5)
choroidal dystrophy central areolar	58.4	1	9152224 (1)
tumors	57.7	192	9164653 (5), 19799609 (4), 17032447 (4), 15714128 (4) (see all 99)
macular dystrophy, vitelliform	57.2	2	17491602 (1), 9152224 (1)
night blindness	53.4	1	7550309 (1)
cancer	50.3	56	17032447 (4), 10188875 (4), 18516293 (4), 15467768 (3) (see all 31)
maculopathy	49.3	2	20385819 (1), 9643018 (1)
choroidal neovascularization	45.2	7	19478078 (1), 12652295 (1), 8759363 (1), 9006347 (1) (see all 5)
metastasis	44.8	31	15467768 (3), 17657847 (3), 12828172 (2), 12629131 (2) (see all 21)
blindness	36.4	5	7920634 (1), 10854443 (1), 12372614 (1), 9112976 (1) (see all 5)

Genetic Association Database (GAD): TIMP3
Human Genome Epidemiology (HuGE) Navigator: TIMP3 (27 documents)

Export disorders for TIMP3 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)
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PubMed articles for TIMP3 gene, integrated from 9 sources (see all 643):
(articles sorted by number of sources associating them with TIMP3)

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Cloning of the cDNA encoding human tissue inhibitor of metalloproteinases-3 (TIMP-3) and mapping of the TIMP3 gene to chromosome 22. (PubMed id 8188246)^{1, 2, 3, 9} Apte S.S.... Olsen B.R. (1994)
Structural determinants of the ADAM inhibition by TIMP-3: crystal structure of the TACE-N-TIMP-3 complex. (PubMed id 18638486)^{1, 2, 9} Wisniewska M....Bode W. (2008)
Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations. (PubMed id 15123717)^{1, 2, 9} Klenotic P.A....Anand-Apte B. (2004)
TIMP-3 is expressed in the human retinal pigment epithelium. (PubMed id 8806658)^{1, 2, 9} Ruiz A.C.... Bok D. (1996)
Structure and expression in breast tumors of human TIMP-3, a new member of the metalloproteinase inhibitor family. (PubMed id 8174111)^{1, 2, 9} Uria J.A.... Lopez-Otin C. (1994)
Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms. (PubMed id 15944607)^{1, 4, 9} Ogata T....Kuivaniemi H. (2005)
A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. (PubMed id 12652295)^{1, 3, 9} Qi J.H....Anand-Apte B. (2003)
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)
Night blindness in Sorsby's fundus dystrophy reversed by vitamin A. (PubMed id 7550309)^{1, 2, 9} Jacobson S.G.... Stone E.M. (1995)
Cloning of cDNAs encoding human TIMP-3, a novel member of the tissue inhibitor of metalloproteinase family. (PubMed id 8163205)^{1, 2, 9} Silbiger S.M.... Koski R.A. (1994)

(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: 7078	HGNC: 11822	AceView: TIMP3	Ensembl:ENSG00000100234	euGenes: HUgn7078
ECgene: TIMP3	H-InvDB: TIMP3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for TIMP3	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TIMP3	Genetics and Cytogenetics in Oncology and Haematology
Mutations of the TIMP3 gene	http://www.retina-international.org/files/sci-news/timpmut.htm
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TIMP3

Intellectual Property for TIMP3 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 TIMP3 gene:
Search GeneIP for patents involving TIMP3

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

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TIMP metallopeptidase inhibitor 3

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Choroidal dystrophy central areolar
Renal Cancer
Blindness
Microsatellite Instability
Thyroid Nodule
LUNG CARCINOMA
Retinitis Pigmentosa
Atherosclerosis
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Metaplasia
Neovascularization
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primary tumor
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HEPATOCELLULAR CARCINOMA
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metastatic melanoma
Hepatitis Chronic Active
Carcinoma Renal Cell
HEART FAILURE
Proliferative diabetic retinopathy
Adenoma
Scar
benign prostatic hyperplasia
uveal melanoma
Bleeding
Prostatic Intraepithelial Neoplasia
Cholangiocarcinoma
OVARIAN CARCINOMA
MACULOPATHY
Carcinoma Squamous Cell
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MACULAR DYSTROPHY, VITELLIFORM
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THYROID CARCINOMA
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TIMP3 Gene

TIMP metallopeptidase inhibitor 3

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