TYMP (gene)

Last updated
TYMP
Protein ECGF1 PDB 1uou.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TYMP , thymidine phosphorylase, ECGF, ECGF1, MEDPS1, MNGIE, MTDPS1, PDECGF, TP, hPD-ECGF
External IDs OMIM: 131222 MGI: 1920212 HomoloGene: 1474 GeneCards: TYMP
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001953
NM_001113755
NM_001113756
NM_001257988
NM_001257989

Contents

NM_138302

RefSeq (protein)

NP_001107227
NP_001107228
NP_001244917
NP_001244918
NP_001944

NP_612175

Location (UCSC) Chr 22: 50.53 – 50.53 Mb n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

TYMP is a gene that encodes for the enzyme thymidine phosphorylase. [4] [5] The TYMP gene is also known as ECGF1 (endothelial cell growth factor 1, platelet-derived) and MNGIE due to its role in MNGIE syndrome. [6]

Structure

The TYMP gene is located on chromosome 22 in humans and contains 10 exons spanning more than 4.3 kb.

Function

TYMP encodes for the enzyme thymidine phosphorylase. TYMP and thymidine phosphorylase are associated with angiogenesis, growth of endothelial cells, and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Thymidine phosphorylase is angiogenic growth factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. Thymidine phosphorylase has a highly restricted target cell specificity acting only on endothelial cells, hence its alternative name of ECGF1. Because it limits glial cell proliferation, thymidine phosphorylase is also known as gliostatin. Thymidine phosphorylase activity in leukocytes from mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients was less than 5 percent of controls, indicating that loss-of-function mutations in TYMP cause MNGIE. [7]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

[[File:
FluoropyrimidineActivity WP1601.png go to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to PubChem Compoundgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
[[<div style="display:block; width:58px; height:0px; overflow:hidden; position:relative; left:174.0px; top:75px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:53px; height:0px; overflow:hidden; position:relative; left:308.0px; top:87px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:53px; height:0px; overflow:hidden; position:relative; left:308.0px; top:67px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:51px; height:0px; overflow:hidden; position:relative; left:72.0px; top:120px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:59px; height:0px; overflow:hidden; position:relative; left:54.0px; top:178px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:80px; height:0px; overflow:hidden; position:relative; left:519.0px; top:112px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:436.5px; top:97px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:436.5px; top:117px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:34px; height:0px; overflow:hidden; position:relative; left:403.0px; top:155px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:46px; height:0px; overflow:hidden; position:relative; left:344.0px; top:130px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:46px; height:0px; overflow:hidden; position:relative; left:344.0px; top:150px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:46px; height:0px; overflow:hidden; position:relative; left:344.0px; top:170px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:39px; height:0px; overflow:hidden; position:relative; left:245.0px; top:352px; background:transparent; border-top:3px green solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:350.0px; top:238px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:440.0px; top:302px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:544.0px; top:301px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:321.0px; top:400px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:46px; height:0px; overflow:hidden; position:relative; left:311.0px; top:310px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:46px; height:0px; overflow:hidden; position:relative; left:311.0px; top:330px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:321.0px; top:420px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:188.0px; top:293px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:188.0px; top:313px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:53.0px; top:326px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:46px; height:0px; overflow:hidden; position:relative; left:75.0px; top:259px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:197.0px; top:448px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:197.0px; top:468px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:208.5px; top:809px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:326.5px; top:566px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:326.5px; top:526px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:326.5px; top:546px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:56px; height:0px; overflow:hidden; position:relative; left:491.0px; top:545px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:163px; height:0px; overflow:hidden; position:relative; left:79.0px; top:866px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:77px; height:0px; overflow:hidden; position:relative; left:164.0px; top:912px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:288.0px; top:854px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:308.0px; top:892px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:80px; height:0px; overflow:hidden; position:relative; left:437.0px; top:816px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:80px; height:0px; overflow:hidden; position:relative; left:389.0px; top:863px; background:transparent; border-top:3px green solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:487.5px; top:842px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:386.5px; top:890px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:430.5px; top:890px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:386.5px; top:910px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:430.5px; top:910px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:180.5px; top:966px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:224.5px; top:966px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:180.5px; top:946px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:44px; height:0px; overflow:hidden; position:relative; left:224.5px; top:946px; background:transparent; border-top:3px blue solid"></div>]]
[[<div style="display:block; width:39px; height:12px; overflow:hidden; position:relative; left:344.0px; top:153px; background:transparent; border:4px black solid"></div>]]
FluoropyrimidineActivity WP1601.png go to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to PubChem Compoundgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
|alt=Fluorouracil (5-FU) Activity edit]]
Fluorouracil (5-FU) Activity edit
  1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

Related Research Articles

Angiogenesis

Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.

Endothelium Cells that line the Inner surface of blood vessels

Endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels, and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue.

Platelet-derived growth factor Signaling glycoprotein regulating cell proliferation

Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood vessel tissue, mitogenesis, i.e. proliferation, of mesenchymal cells such as fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells and mesenchymal stem cells as well as chemotaxis, the directed migration, of mesenchymal cells. Platelet-derived growth factor is a dimeric glycoprotein that can be composed of two A subunits (PDGF-AA), two B subunits (PDGF-BB), or one of each (PDGF-AB).

Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis and angiogenesis.

An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.

Endostatin

Endostatin is a naturally occurring, 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin.

Angiopoietin Protein family

Angiopoietin is part of a family of vascular growth factors that play a role in embryonic and postnatal angiogenesis. Angiopoietin signaling most directly corresponds with angiogenesis, the process by which new arteries and veins form from preexisting blood vessels. Angiogenesis proceeds through sprouting, endothelial cell migration, proliferation, and vessel destabilization and stabilization. They are responsible for assembling and disassembling the endothelial lining of blood vessels. Angiopoietin cytokines are involved with controlling microvascular permeability, vasodilation, and vasoconstriction by signaling smooth muscle cells surrounding vessels. There are now four identified angiopoietins: ANGPT1, ANGPT2, ANGPTL3, ANGPT4.

Neuropilin

Neuropilin is a protein receptor active in neurons.

CTGF

CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins. CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers.

Mitochondrial neurogastrointestinal encephalopathy syndrome Medical condition

Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is a rare autosomal recessive mitochondrial disease. It has been previously referred to as polyneuropathy, ophthalmoplegia, leukoencephalopathy, and POLIP syndrome. The disease presents in childhood, but often goes unnoticed for decades. Unlike typical mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, MNGIE is caused by mutations in the TYMP gene, which encodes the enzyme thymidine phosphorylase. Mutations in this gene result in impaired mitochondrial function, leading to intestinal symptoms as well as neuro-ophthalmologic abnormalities. A secondary form of MNGIE, called MNGIE without leukoencephalopathy, can be caused by mutations in the POLG gene.

CXCL7

Chemokine ligand 7 (CXCL7) is a human gene.

CYR61

Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene.

PDGFA

Platelet-derived growth factor subunit A is a protein that in humans is encoded by the PDGFA gene.

Vascular endothelial growth factor C

Vascular endothelial growth factor C (VEGF-C) is a protein that is a member of the platelet-derived growth factor / vascular endothelial growth factor (PDGF/VEGF) family. It is encoded in humans by the VEGFC gene, which is located on chromosome 4q34.

Thymidine phosphorylase

Thymidine phosphorylase is an enzyme that is encoded by the TYMP gene and catalyzes the reaction:

C-fos-induced growth factor

C-fos-induced growth factor (FIGF) is a vascular endothelial growth factor that in humans is encoded by the FIGF gene.

Hepatoma-derived growth factor

Hepatoma-derived growth factor (HDGF) also known as high mobility group protein 1-like 2 (HMG-1L2) is a protein that in humans is encoded by the HDGF gene.

PDGFC

Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid protein that in humans is encoded by the PDGFC gene. Platelet-derived growth factors are important in connective tissue growth, survival and function, and consist of disulphide-linked dimers involving two polypeptide chains, PDGF-A and PDGF-B. PDGF-C is a member of the PDGF/VEGF family of growth factors with a unique two-domain structure and expression pattern. PDGF-C was not previously identified with PDGF-A and PDGF-B, possibly because it may be that it is synthesized and secreted as a latent growth factor, requiring proteolytic removal of the N-terminal CUB domain for receptor binding and activation.

PDGFD

Platelet-derived growth factor D is a protein that in humans is encoded by the PDGFD gene.

Angiogenesis is the process of forming new blood vessels from existing blood vessels. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteases (MMPs), a disintegrin and metalloprotease domain (ADAM), a disintegrin and metalloprotease domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000025708 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. Usuki K, Saras J, Waltenberger J, Miyazono K, Pierce G, Thomason A, Heldin CH (Jun 1992). "Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity". Biochem Biophys Res Commun. 184 (3): 1311–6. doi:10.1016/S0006-291X(05)80025-7. PMID   1590793.
  5. Spinazzola A, Marti R, Nishino I, Andreu AL, Naini A, Tadesse S, Pela I, Zammarchi E, Donati MA, Oliver JA, Hirano M (Feb 2002). "Altered thymidine metabolism due to defects of thymidine phosphorylase". J Biol Chem. 277 (6): 4128–33. doi: 10.1074/jbc.M111028200 . PMID   11733540.
  6. "Gene symbol report | HUGO Gene Nomenclature Committee".
  7. "Entrez Gene: ECGF1 endothelial cell growth factor 1 (platelet-derived)".

Further reading