NME4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | NME4 , NDPK-D, NM23H4, nm23-H4, NME/NM23 nucleoside diphosphate kinase 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 601818 MGI: 1931148 HomoloGene: 3673 GeneCards: NME4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Non-metastatic cells 4, protein expressed in, also known as NME4, is a protein which in humans is encoded by the NME4 gene. [5] [6]
The nucleoside diphosphate (NDP) kinases (EC 2.7.4.6) are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates. The enzymes are products of the nm23 gene family, which includes NME4. The first nm23 gene, nm23-H1 (NME1), was isolated based on its reduced expression in a highly metastatic murine melanoma cell line and was proposed to be a metastasis suppressing gene. The human equivalent was obtained by cDNA library screening using the murine gene as a probe and found to be homologous to the Drosophila awd gene. A second human gene, nm23-H2 (NME2), encoding a protein 88% identical to nm23-H1, was subsequently isolated. Both genes were localized on 17q21.3 and their gene products were formerly identified as the A and B subunits of NDP kinases. In mammals, functional NDP kinases are heterohexamers of the A and B monomers, which can combine at variable ratios to form different types of hybrids. [6] These enzymes are highly expressed in tumors as compared with normal tissues. In some cell lines and in certain solid tumors, decreased expression of NME1 is associated with increased metastatic potential; moreover, when transfected into very aggressive cell lines, such as human breast carcinoma, NME1 decreased the metastatic potential. A third human gene, DR-nm23 (NME3), was identified and found to share high sequence similarity with the NME1 and NME2 genes. It is highly expressed in blast crisis transition of chronic myeloid leukemia. When overexpressed by transfection, NME3 suppressed granulocyte differentiation and induced apoptosis of myeloid precursor cells. [5]
Adenylate kinase is a phosphotransferase enzyme that catalyzes the interconversion of the various adenosine phosphates. By constantly monitoring phosphate nucleotide levels inside the cell, ADK plays an important role in cellular energy homeostasis.
Nucleoside-diphosphate kinases are enzymes that catalyze the exchange of terminal phosphate between different nucleoside diphosphates (NDP) and triphosphates (NTP) in a reversible manner to produce nucleotide triphosphates. Many NDP serve as acceptor while NTP are donors of phosphate group. The general reaction via ping-pong mechanism is as follows: XDP + YTP ←→ XTP + YDP. NDPK activities maintain an equilibrium between the concentrations of different nucleoside triphosphates such as, for example, when guanosine triphosphate (GTP) produced in the citric acid (Krebs) cycle is converted to adenosine triphosphate (ATP). Other activities include cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor, endocytosis, and gene expression.
Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase is an enzyme that in humans is encoded by the NP gene. It catalyzes the chemical reaction
Deoxycytidine kinase (dCK) is an enzyme which is encoded by the DCK gene in humans. dCK predominantly phosphorylates deoxycytidine (dC) and converts dC into deoxycytidine monophosphate. dCK catalyzes one of the initial steps in the nucleoside salvage pathway and has the potential to phosphorylate other preformed nucleosides, specifically deoxyadenosine (dA) and deoxyguanosine (dG), and convert them into their monophosphate forms. There has been recent biomedical research interest in investigating dCK's potential as a therapeutic target for different types of cancer.
RAR-related orphan receptor beta (ROR-beta), also known as NR1F2 is a nuclear receptor that in humans is encoded by the RORB gene.
RAR-related orphan receptor alpha (RORα), also known as NR1F1 is a nuclear receptor that in humans is encoded by the RORA gene. RORα participates in the transcriptional regulation of some genes involved in circadian rhythm. In mice, RORα is essential for development of cerebellum through direct regulation of genes expressed in Purkinje cells. It also plays an essential role in the development of type 2 innate lymphoid cells (ILC2) and mutant animals are ILC2 deficient. In addition, although present in normal numbers, the ILC3 and Th17 cells from RORα deficient mice are defective for cytokine production.
Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene. It is thought to be a metastasis suppressor.
Telomeric repeat-binding factor 1 is a protein that in humans is encoded by the TERF1 gene.
Nucleoside diphosphate kinase B is an enzyme that in humans is encoded by the NME2 gene.
Deoxyguanosine kinase, mitochondrial is an enzyme that in humans is encoded by the DGUOK gene.
Uridine-cytidine kinase 2 (UCK2) is an enzyme that in humans is encoded by the UCK2 gene.
UMP-CMP kinase is an enzyme that in humans is encoded by the CMPK1 gene.
Fas-activated serine/threonine kinase is an enzyme that in humans is encoded by the FASTK gene.
Death-associated protein kinase 2 is an enzyme that in humans is encoded by the DAPK2 gene.
Nucleoside diphosphate kinase 3 is an enzyme that in humans is encoded by the NME3 gene.
Thioredoxin domain-containing protein 3 (TXNDC3), also known as spermatid-specific thioredoxin-2 (Sptrx-2), is a protein that in humans is encoded by the NME8 gene on chromosome 7.
EVI5L is a protein that in humans is encoded by the EVI5L gene. EVI5L is a member of the Ras superfamily of monomeric guanine nucleotide-binding (G) proteins, and functions as a GTPase-activating protein (GAP) with a broad specificity. Measurement of in vitro Rab-GAP activity has shown that EVI5L has significant Rab2A- and Rab10-GAP activity.
5',3'-nucleotidase, mitochondrial, also known as 5'(3')-deoxyribonucleotidase, mitochondrial (mdN) or deoxy-5'-nucleotidase 2 (dNT-2), is an enzyme that in humans is encoded by the NT5M gene. This gene encodes a 5' nucleotidase that localizes to the mitochondrial matrix. This enzyme dephosphorylates the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The gene is located within the Smith–Magenis syndrome region on chromosome 17.
Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial is an enzyme that in humans is encoded by the SUCLG2 gene on chromosome 3.
Adenylate kinase 1 is a protein that in humans is encoded by the AK1 gene.