Human Gene TIMP2 (ENST00000262768.11) from GENCODE V44
  Description: Homo sapiens TIMP metallopeptidase inhibitor 2 (TIMP2), mRNA. (from RefSeq NM_003255)
RefSeq Summary (NM_003255): 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].
Gencode Transcript: ENST00000262768.11
Gencode Gene: ENSG00000035862.13
Transcript (Including UTRs)
   Position: hg38 chr17:78,852,977-78,925,387 Size: 72,411 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg38 chr17:78,855,667-78,925,088 Size: 69,422 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:78,852,977-78,925,387)mRNA (may differ from genome)Protein (220 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid 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
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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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           more ... click here to view the complete list

-  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

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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-  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
Genome BrowserGenome BrowserGenome BrowserNo orthologGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl WormBase 
Protein SequenceProtein SequenceProtein Sequence Protein Sequence 
AlignmentAlignmentAlignment 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
  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.
MA620398 - JP 2018138019-A/192324: Polycomb-Associated Non-Coding RNAs.
AK294290 - Homo sapiens cDNA FLJ57920 complete cds, highly similar to Metalloproteinase inhibitor 2 precursor.
J05593 - Human metalloproteinase-2 inhibitor (TIMP-2) mRNA, complete cds.
S48568 - Homo sapiens tissue inhibitor of metalloproteinase 2 mRNA, complete cds.
BC052605 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone MGC:59751 IMAGE:6267022), complete cds.
M32304 - Human metalloproteinase inhibitor mRNA, complete cds.
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.
X54533 - H.sapiens mRNA for tissue inhibitor of metalloproteinases, Type-2.
AL110197 - Homo sapiens mRNA; cDNA DKFZp586J021 (from clone DKFZp586J021).
BC040445 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone IMAGE:6061436).
LF328486 - JP 2014500723-A/135989: Polycomb-Associated Non-Coding RNAs.
MA564063 - JP 2018138019-A/135989: Polycomb-Associated Non-Coding RNAs.
LF328487 - JP 2014500723-A/135990: Polycomb-Associated Non-Coding RNAs.
MA564064 - JP 2018138019-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.
MA564065 - JP 2018138019-A/135991: Polycomb-Associated Non-Coding RNAs.
LF328489 - JP 2014500723-A/135992: Polycomb-Associated Non-Coding RNAs.
MA564066 - JP 2018138019-A/135992: Polycomb-Associated Non-Coding RNAs.
LF328490 - JP 2014500723-A/135993: Polycomb-Associated Non-Coding RNAs.
MA564067 - JP 2018138019-A/135993: Polycomb-Associated Non-Coding RNAs.
LF328491 - JP 2014500723-A/135994: Polycomb-Associated Non-Coding RNAs.
MA564068 - JP 2018138019-A/135994: Polycomb-Associated Non-Coding RNAs.
LF328492 - JP 2014500723-A/135995: Polycomb-Associated Non-Coding RNAs.
MA564069 - JP 2018138019-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.
MA564070 - JP 2018138019-A/135996: Polycomb-Associated Non-Coding RNAs.
LF328494 - JP 2014500723-A/135997: Polycomb-Associated Non-Coding RNAs.
MA564071 - JP 2018138019-A/135997: Polycomb-Associated Non-Coding RNAs.
LF328495 - JP 2014500723-A/135998: Polycomb-Associated Non-Coding RNAs.
MA564072 - JP 2018138019-A/135998: Polycomb-Associated Non-Coding RNAs.
JD025835 - Sequence 6859 from Patent EP1572962.
LF328496 - JP 2014500723-A/135999: Polycomb-Associated Non-Coding RNAs.
MA564073 - JP 2018138019-A/135999: Polycomb-Associated Non-Coding RNAs.
LF328497 - JP 2014500723-A/136000: Polycomb-Associated Non-Coding RNAs.
MA564074 - JP 2018138019-A/136000: Polycomb-Associated Non-Coding RNAs.
LF328498 - JP 2014500723-A/136001: Polycomb-Associated Non-Coding RNAs.
MA564075 - JP 2018138019-A/136001: Polycomb-Associated Non-Coding RNAs.
LF328499 - JP 2014500723-A/136002: Polycomb-Associated Non-Coding RNAs.
MA564076 - JP 2018138019-A/136002: Polycomb-Associated Non-Coding RNAs.
LF328500 - JP 2014500723-A/136003: Polycomb-Associated Non-Coding RNAs.
MA564077 - JP 2018138019-A/136003: Polycomb-Associated Non-Coding RNAs.
BC040039 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone IMAGE:6065728).
BC039613 - Homo sapiens TIMP metallopeptidase inhibitor 2, mRNA (cDNA clone IMAGE:6055429).
AL713764 - Homo sapiens mRNA; cDNA DKFZp761A0617 (from clone DKFZp761A0617).
JD060832 - Sequence 41856 from Patent EP1572962.
LF328501 - JP 2014500723-A/136004: Polycomb-Associated Non-Coding RNAs.
MA564078 - JP 2018138019-A/136004: Polycomb-Associated Non-Coding RNAs.
LF328502 - JP 2014500723-A/136005: Polycomb-Associated Non-Coding RNAs.
MA564079 - JP 2018138019-A/136005: Polycomb-Associated Non-Coding RNAs.
LF328503 - JP 2014500723-A/136006: Polycomb-Associated Non-Coding RNAs.
MA564080 - JP 2018138019-A/136006: Polycomb-Associated Non-Coding RNAs.
LF328504 - JP 2014500723-A/136007: Polycomb-Associated Non-Coding RNAs.
MA564081 - JP 2018138019-A/136007: Polycomb-Associated Non-Coding RNAs.
LF328505 - JP 2014500723-A/136008: Polycomb-Associated Non-Coding RNAs.
MA564082 - JP 2018138019-A/136008: Polycomb-Associated Non-Coding RNAs.
LF212473 - JP 2014500723-A/19976: Polycomb-Associated Non-Coding RNAs.
MA448050 - JP 2018138019-A/19976: Polycomb-Associated Non-Coding RNAs.
LF328512 - JP 2014500723-A/136015: Polycomb-Associated Non-Coding RNAs.
MA564089 - JP 2018138019-A/136015: Polycomb-Associated Non-Coding RNAs.
JD481760 - Sequence 462784 from Patent EP1572962.
JD476015 - Sequence 457039 from Patent EP1572962.

-  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, uc002jwf.1, uc002jwf.2, uc002jwf.3, uc002jwf.4
UCSC ID: ENST00000262768.11
RefSeq Accession: NM_003255
Protein: P16035 (aka TIMP2_HUMAN)
CCDS: CCDS11758.1

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