Human Gene TIMP2 (ENST00000262768.11_7) from GENCODE V47lift37
  Description: TIMP metallopeptidase inhibitor 2 (from RefSeq NM_003255.5)
Gencode Transcript: ENST00000262768.11_7
Gencode Gene: ENSG00000035862.13_13
Transcript (Including UTRs)
   Position: hg19 chr17:76,849,059-76,921,469 Size: 72,411 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg19 chr17:76,851,749-76,921,170 Size: 69,422 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:76,849,059-76,921,469)mRNA (may differ from genome)Protein (220 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TIMP2_HUMAN
DESCRIPTION: RecName: Full=Metalloproteinase inhibitor 2; AltName: Full=CSC-21K; AltName: Full=Tissue inhibitor of metalloproteinases 2; Short=TIMP-2; Flags: Precursor;
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.
SUBUNIT: Interacts (via the C-terminal) with MMP2 (via the C- terminal PEX domain); the interaction inhibits the MMP2 activity.
SUBCELLULAR LOCATION: Secreted.
INDUCTION: Down-regulated by TGFB1.
PTM: The activity of TIMP2 is dependent on the presence of disulfide bonds.
SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
SIMILARITY: Contains 1 NTR domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TIMP2ID42572ch17q25.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TIMP2
Diseases sorted by gene-association score: conjunctivochalasis (16), abdominal aortic aneurysm (12), lipodermatosclerosis (12), gallbladder cancer (10), inguinal hernia (10), tonsil squamous cell carcinoma (10), moyamoya disease (9), gingival hypertrophy (9), fibrosarcoma (8), pulmonary emphysema (8), dupuytren contracture (8), spinal stenosis (8), microcystic meningioma (7), preterm premature rupture of the membranes (7), adenomyosis (7), sorsby fundus dystrophy (6), oral lichen planus (6), vulvar intraepithelial neoplasia (6), viral meningitis (6), adamantinoma of long bones (6), nasal cavity squamous cell carcinoma (5), nodular malignant melanoma (5), appendix adenocarcinoma (4), tonsil cancer (4), periodontal disease (3), fundus dystrophy (3), breast cancer (3), lung cancer (3), endometrial cancer (3), refractive error (3), ovarian cancer, somatic (2), colorectal cancer (2), obesity (2), bladder cancer, somatic (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 449.65 RPKM in Artery - Aorta
Total median expression: 6005.77 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -140.00299-0.468 Picture PostScript Text
3' UTR -875.802690-0.326 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001134 - Netrin_domain
IPR001820 - Prot_inh_TIMP
IPR008993 - TIMP-like_OB-fold
IPR015613 - TIMP2

Pfam Domains:
PF00965 - Tissue inhibitor of metalloproteinase

SCOP Domains:
50242 - TIMP-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1BR9 - X-ray MuPIT 1GXD - X-ray 2TMP - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P16035
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologGenome BrowserNo ortholog
Gene DetailsGene Details  Gene Details 
Gene SorterGene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
    Protein Sequence 
    Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002020 protease binding
GO:0004857 enzyme inhibitor activity
GO:0005178 integrin binding
GO:0005515 protein binding
GO:0008191 metalloendopeptidase inhibitor activity
GO:0008270 zinc ion binding
GO:0030414 peptidase inhibitor activity
GO:0046872 metal ion binding

Biological Process:
GO:0007417 central nervous system development
GO:0007568 aging
GO:0008285 negative regulation of cell proliferation
GO:0009725 response to hormone
GO:0010466 negative regulation of peptidase activity
GO:0010951 negative regulation of endopeptidase activity
GO:0022617 extracellular matrix disassembly
GO:0032487 regulation of Rap protein signal transduction
GO:0034097 response to cytokine
GO:0042493 response to drug
GO:0043312 neutrophil degranulation
GO:0043410 positive regulation of MAPK cascade
GO:0045666 positive regulation of neuron differentiation
GO:0045762 positive regulation of adenylate cyclase activity
GO:0045861 negative regulation of proteolysis
GO:0045930 negative regulation of mitotic cell cycle
GO:0046580 negative regulation of Ras protein signal transduction
GO:0051045 negative regulation of membrane protein ectodomain proteolysis
GO:1905049 negative regulation of metallopeptidase activity

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0009986 cell surface
GO:0030426 growth cone
GO:0031012 extracellular matrix
GO:0035580 specific granule lumen
GO:0043005 neuron projection
GO:0043025 neuronal cell body
GO:1904724 tertiary granule lumen
GO:1904813 ficolin-1-rich granule lumen


-  Descriptions from all associated GenBank mRNAs
  AL110197 - Homo sapiens mRNA; cDNA DKFZp586J021 (from clone DKFZp586J021).
BC040445 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone IMAGE:6061436).
BC071586 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone MGC:87301 IMAGE:30337524), complete cds.
HM005597 - Homo sapiens clone HTL-S-57 testicular secretory protein Li 57 mRNA, complete cds.
HW418420 - JP 2013543722-A/2: MODULATION of TIMP1 and TIMP2 EXPRESSION.
JB810681 - Sequence 2 from Patent EP2621502.
LF384821 - JP 2014500723-A/192324: Polycomb-Associated Non-Coding RNAs.
LF791225 - JP 2016185150-A/2: MODULATION of TIMP1 and TIMP2 EXPRESSION.
LF328486 - JP 2014500723-A/135989: Polycomb-Associated Non-Coding RNAs.
LF328487 - JP 2014500723-A/135990: Polycomb-Associated Non-Coding RNAs.
BC010410 - Homo sapiens cDNA clone IMAGE:3628920, partial cds.
LF328488 - JP 2014500723-A/135991: Polycomb-Associated Non-Coding RNAs.
LF328489 - JP 2014500723-A/135992: Polycomb-Associated Non-Coding RNAs.
LF328490 - JP 2014500723-A/135993: Polycomb-Associated Non-Coding RNAs.
LF328491 - JP 2014500723-A/135994: Polycomb-Associated Non-Coding RNAs.
LF328492 - JP 2014500723-A/135995: Polycomb-Associated Non-Coding RNAs.
JD022244 - Sequence 3268 from Patent EP1572962.
JD036109 - Sequence 17133 from Patent EP1572962.
LF328493 - JP 2014500723-A/135996: Polycomb-Associated Non-Coding RNAs.
LF328494 - JP 2014500723-A/135997: Polycomb-Associated Non-Coding RNAs.
LF328495 - JP 2014500723-A/135998: Polycomb-Associated Non-Coding RNAs.
JD025835 - Sequence 6859 from Patent EP1572962.
LF328496 - JP 2014500723-A/135999: Polycomb-Associated Non-Coding RNAs.
LF328497 - JP 2014500723-A/136000: Polycomb-Associated Non-Coding RNAs.
LF328498 - JP 2014500723-A/136001: Polycomb-Associated Non-Coding RNAs.
AK294290 - Homo sapiens cDNA FLJ57920 complete cds, highly similar to Metalloproteinase inhibitor 2 precursor.
LF328499 - JP 2014500723-A/136002: Polycomb-Associated Non-Coding RNAs.
LF328500 - JP 2014500723-A/136003: Polycomb-Associated Non-Coding RNAs.
BC040039 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone IMAGE:6065728).
J05593 - Human metalloproteinase-2 inhibitor (TIMP-2) mRNA, complete cds.
S48568 - Homo sapiens tissue inhibitor of metalloproteinase 2 mRNA, complete cds.
BC039613 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone IMAGE:6055429).
AL713764 - Homo sapiens mRNA; cDNA DKFZp761A0617 (from clone DKFZp761A0617).
BC052605 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone MGC:59751 IMAGE:6267022), complete cds.
M32304 - Human metalloproteinase inhibitor mRNA, complete cds.
JD060832 - Sequence 41856 from Patent EP1572962.
KJ892278 - Synthetic construct Homo sapiens clone ccsbBroadEn_01672 TIMP2 gene, encodes complete protein.
KR711311 - Synthetic construct Homo sapiens clone CCSBHm_00022595 TIMP2 (TIMP2) mRNA, encodes complete protein.
HQ448393 - Synthetic construct Homo sapiens clone IMAGE:100071820; CCSB013689_02 TIMP metallopeptidase inhibitor 2 (TIMP2) gene, encodes complete protein.
LF328501 - JP 2014500723-A/136004: Polycomb-Associated Non-Coding RNAs.
X54533 - H.sapiens mRNA for tissue inhibitor of metalloproteinases, Type-2.
LF328502 - JP 2014500723-A/136005: Polycomb-Associated Non-Coding RNAs.
LF328503 - JP 2014500723-A/136006: Polycomb-Associated Non-Coding RNAs.
LF328504 - JP 2014500723-A/136007: Polycomb-Associated Non-Coding RNAs.
LF328505 - JP 2014500723-A/136008: Polycomb-Associated Non-Coding RNAs.
LF212473 - JP 2014500723-A/19976: Polycomb-Associated Non-Coding RNAs.
LF328512 - JP 2014500723-A/136015: Polycomb-Associated Non-Coding RNAs.
JD481760 - Sequence 462784 from Patent EP1572962.
JD476015 - Sequence 457039 from Patent EP1572962.
MA620398 - JP 2018138019-A/192324: Polycomb-Associated Non-Coding RNAs.
MA564063 - JP 2018138019-A/135989: Polycomb-Associated Non-Coding RNAs.
MA564064 - JP 2018138019-A/135990: Polycomb-Associated Non-Coding RNAs.
MA564065 - JP 2018138019-A/135991: Polycomb-Associated Non-Coding RNAs.
MA564066 - JP 2018138019-A/135992: Polycomb-Associated Non-Coding RNAs.
MA564067 - JP 2018138019-A/135993: Polycomb-Associated Non-Coding RNAs.
MA564068 - JP 2018138019-A/135994: Polycomb-Associated Non-Coding RNAs.
MA564069 - JP 2018138019-A/135995: Polycomb-Associated Non-Coding RNAs.
MA564070 - JP 2018138019-A/135996: Polycomb-Associated Non-Coding RNAs.
MA564071 - JP 2018138019-A/135997: Polycomb-Associated Non-Coding RNAs.
MA564072 - JP 2018138019-A/135998: Polycomb-Associated Non-Coding RNAs.
MA564073 - JP 2018138019-A/135999: Polycomb-Associated Non-Coding RNAs.
MA564074 - JP 2018138019-A/136000: Polycomb-Associated Non-Coding RNAs.
MA564075 - JP 2018138019-A/136001: Polycomb-Associated Non-Coding RNAs.
MA564076 - JP 2018138019-A/136002: Polycomb-Associated Non-Coding RNAs.
MA564077 - JP 2018138019-A/136003: Polycomb-Associated Non-Coding RNAs.
MA564078 - JP 2018138019-A/136004: Polycomb-Associated Non-Coding RNAs.
MA564079 - JP 2018138019-A/136005: Polycomb-Associated Non-Coding RNAs.
MA564080 - JP 2018138019-A/136006: Polycomb-Associated Non-Coding RNAs.
MA564081 - JP 2018138019-A/136007: Polycomb-Associated Non-Coding RNAs.
MA564082 - JP 2018138019-A/136008: Polycomb-Associated Non-Coding RNAs.
MA564089 - JP 2018138019-A/136015: Polycomb-Associated Non-Coding RNAs.
MA448050 - JP 2018138019-A/19976: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_reckPathway - Inhibition of Matrix Metalloproteinases

Reactome (by CSHL, EBI, and GO)

Protein P16035 (Reactome details) participates in the following event(s):

R-HSA-1592349 MMP14 (MT1-MMP) binds TIMP2
R-HSA-1604350 MMP14:TIMP2 binds proMMP2
R-HSA-6798749 Exocytosis of specific granule lumen proteins
R-HSA-6798745 Exocytosis of tertiary granule lumen proteins
R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins
R-HSA-1604368 Autocatalytic activation of bound proMMP2
R-HSA-1604360 Initial activation of proMMP2 by MMP14
R-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-6798695 Neutrophil degranulation
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-168249 Innate Immune System
R-HSA-1474244 Extracellular matrix organization
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000262768.1, ENST00000262768.10, ENST00000262768.2, ENST00000262768.3, ENST00000262768.4, ENST00000262768.5, ENST00000262768.6, ENST00000262768.7, ENST00000262768.8, ENST00000262768.9, NM_003255, P16035, Q16121, Q93006, Q9UDF7, TIMP2_HUMAN, uc317hdh.1, uc317hdh.2
UCSC ID: ENST00000262768.11_7
RefSeq Accession: NM_003255.5
Protein: P16035 (aka TIMP2_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.