NME4 NME/NM23 nucleoside diphosphate kinase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NME4provided by HGNC
Official Full Name: NME/NM23 nucleoside diphosphate kinase 4provided by HGNC
Primary source: HGNC:HGNC:7852
See related: Ensembl:ENSG00000103202 MIM:601818; AllianceGenome:HGNC:7852
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NDPK-D; NM23H4; nm23-H4
Summary: 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 (Milon et al., 1997 [PubMed 9099850]).[supplied by OMIM, May 2008]
Expression: Ubiquitous expression in prostate (RPKM 37.4), fat (RPKM 31.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p13.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (396729..400754)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (392618..396999)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (446729..450754)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential Expression of NME4 in Trophoblast Stem-Like Cells and Peripheral Blood Mononuclear Cells of Normal Pregnancy and Preeclampsia.
Title: Differential Expression of NME4 in Trophoblast Stem-Like Cells and Peripheral Blood Mononuclear Cells of Normal Pregnancy and Preeclampsia.
Widely targeted metabolomic analyses unveil the metabolic variations after stable knock-down of NME4 in esophageal squamous cell carcinoma cells.
Title: Widely targeted metabolomic analyses unveil the metabolic variations after stable knock-down of NME4 in esophageal squamous cell carcinoma cells.
NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma.
Title: NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma.
After knockdown of NME4 with short hairpin RNA, the cell cycle was arrest at the G1 phase, and proliferation and colony formation were inhibited in the NCIH1299 and A549 cell lines.
Title: NME4 may enhance non‑small cell lung cancer progression by overcoming cell cycle arrest and promoting cellular proliferation.
Nucleoside diphosphate kinase D (NME4/NDPK-D) shows intermembrane phospholipid transfer activity in vitro and in cellular systems, which relies on NME4/NDPK-D interaction with cardiolipin [Review].
Title: NME4/nucleoside diphosphate kinase D in cardiolipin signaling and mitophagy.
NDPK-D has an important role in the early stages of mitophagy as induced by carbonyl cyanide m-chlorophenylhydrazone as well as by PINK1-Parkin-independent stimuli such as rotenone and 6-hydroxydopamine.
Title: NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy.
Mitochondrial NM23-H4/NDPK-D: a bifunctional nanoswitch for bioenergetics and lipid signaling
Title: Mitochondrial NM23-H4/NDPK-D: a bifunctional nanoswitch for bioenergetics and lipid signaling.
miR-196 performed it's their function by inhibiting NME4 expression and further activating p-JNK, suppressing TIMP1, and augmenting MMP1/9.
Title: OncomiR-196 promotes an invasive phenotype in oral cancer through the NME4-JNK-TIMP1-MMP signaling pathway.
NDPK-B and NDPK-D were shown to bind efficiently to liposomes mimicking plasma membrane and mitochondrial inner membrane
Title: Structural comparison of highly similar nucleoside-diphosphate kinases: Molecular explanation of distinct membrane-binding behavior.
findings show NDPKs (NM23-H1/H2/H4) interact with and provide GTP to dynamins, allowing these motor proteins to work with high thermodynamic efficiency for membrane remodeling
Title: Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G54084 (e-PCR)
- UniSTS:109321

REN95820 (e-PCR)
- UniSTS:420618

REN95821 (e-PCR)
- UniSTS:420619

REN95823 (e-PCR)
- UniSTS:420621

REN95824 (e-PCR)
- UniSTS:420622

REN95825 (e-PCR)
- UniSTS:420623

REN95826 (e-PCR)
- UniSTS:420624

REN95827 (e-PCR)
- UniSTS:420625

REN95828 (e-PCR)
- UniSTS:420626

REN95829 (e-PCR)
- UniSTS:420627

REN95830 (e-PCR)
- UniSTS:420628

REN95831 (e-PCR)
- UniSTS:420629

REN95832 (e-PCR)
- UniSTS:420630

ECD04648 (e-PCR)
- UniSTS:285719

REN95833 (e-PCR)
- UniSTS:420631

ECD04649 (e-PCR)
- UniSTS:285720

REN95834 (e-PCR)
- UniSTS:420632

REN95835 (e-PCR)
- UniSTS:420633

REN95836 (e-PCR)
- UniSTS:420634

REN95837 (e-PCR)
- UniSTS:420635

REN95838 (e-PCR)
- UniSTS:420636

REN95839 (e-PCR)
- UniSTS:420637

REN95840 (e-PCR)
- UniSTS:420638

REN95841 (e-PCR)
- UniSTS:420639

REN95842 (e-PCR)
- UniSTS:420640

ECD07753 (e-PCR)
- UniSTS:288803

RH70775 (e-PCR)
- UniSTS:61044

ECD04510 (e-PCR)
- UniSTS:285582

G06857 (e-PCR)
- UniSTS:47810

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables cardiolipin binding	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleoside diphosphate kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in CTP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in GTP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in UTP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in lipid transport	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleoside metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	TAS Traceable Author Statement more info
located_in mitochondrial intermembrane space	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: nucleoside diphosphate kinase, mitochondrial

Names: NDK; NDP kinase D; NDP kinase, mitochondrial; NDPKD; non-metastatic cells 4, protein expressed in; nucleoside diphosphate kinase D

NP_001273362.1

EC 2.7.4.6

NP_001273364.1

EC 2.7.4.6

NP_001273365.1

EC 2.7.4.6

NP_001273367.1

EC 2.7.4.6

NP_001273368.1

EC 2.7.4.6

NP_001273369.1

EC 2.7.4.6

NP_005000.1

EC 2.7.4.6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001286433.2 → NP_001273362.1 nucleoside diphosphate kinase, mitochondrial isoform b

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

BC004880, BC017067, HY182358

Consensus CDS

CCDS73797.1

UniProtKB/TrEMBL

A0A087WVT9

Related

ENSP00000479681.1, ENST00000621774.4

Conserved Domains (2) summary

cd04413
Location:38 → 133

NDPk_I; Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside ...

pfam00334
Location:38 → 138

NDK; Nucleoside diphosphate kinase
NM_001286435.2 → NP_001273364.1 nucleoside diphosphate kinase, mitochondrial isoform c

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate splice junction at the 5' end of the last exon compared to isoform 1. The resulting isoform (c) has a shorter and distinct C-terminus compared to isoform a.

Source sequence(s)

BC004880, BC017067, BE266496

UniProtKB/TrEMBL

H0Y6J0

Related

ENSP00000405925.1, ENST00000433358.5

Conserved Domains (2) summary

cd04413
Location:38 → 145

NDPk_I; Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside ...

pfam00334
Location:38 → 159

NDK; Nucleoside diphosphate kinase
NM_001286436.2 → NP_001273365.1 nucleoside diphosphate kinase, mitochondrial isoform d

See identical proteins and their annotated locations for NP_001273365.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) contains an alternate exon in the 5' UTR and initiates translation at an alternate downstream start codon compared to variant 1. The resulting isoform (d) is shorter at the N-terminus compared to isoform a. Variants 4, 5, 6, and 7 all encode the same isoform (d).

Source sequence(s)

BC004880, BQ650649, CB143020, Z97634

Consensus CDS

CCDS66886.1

UniProtKB/Swiss-Prot

O00746

Related

ENSP00000380834.1, ENST00000397722.5

Conserved Domains (1) summary

cd04413
Location:1 → 97

NDPk_I; Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside ...
NM_001286438.2 → NP_001273367.1 nucleoside diphosphate kinase, mitochondrial isoform d

See identical proteins and their annotated locations for NP_001273367.1

Status: VALIDATED

Description

Transcript Variant: This variant (5) contains an alternate exon and initiates translation at an alternate downstream start codon compared to variant 1. The resulting isoform (d) is shorter at the N-terminus compared to isoform a. Variants 4, 5, 6, and 7 all encode the same isoform (d).

Source sequence(s)

BC004880, BC017067, BP328820

Consensus CDS

CCDS66886.1

UniProtKB/Swiss-Prot

O00746

Conserved Domains (1) summary

cd04413
Location:1 → 97

NDPk_I; Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside ...
NM_001286439.2 → NP_001273368.1 nucleoside diphosphate kinase, mitochondrial isoform d

See identical proteins and their annotated locations for NP_001273368.1

Status: VALIDATED

Description

Transcript Variant: This variant (6) contains an alternate exon in the 5' UTR and initiates translation at an alternate downstream start codon compared to variant 1. The resulting isoform (d) is shorter at the N-terminus compared to isoform a. Variants 4, 5, 6, and 7 all encode the same isoform (d).

Source sequence(s)

BC004880, BC017067, CF126980

Consensus CDS

CCDS66886.1

UniProtKB/Swiss-Prot

O00746

Related

ENSP00000479996.1, ENST00000620944.4

Conserved Domains (1) summary

cd04413
Location:1 → 97

NDPk_I; Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside ...
NM_001286440.2 → NP_001273369.1 nucleoside diphosphate kinase, mitochondrial isoform d

See identical proteins and their annotated locations for NP_001273369.1

Status: VALIDATED

Description

Transcript Variant: This variant (7) contains an alternate exon and initiates translation at an alternate downstream start codon compared to variant 1. The resulting isoform (d) is shorter at the N-terminus compared to isoform a. Variants 4, 5, 6, and 7 all encode the same isoform (d).

Source sequence(s)

BC004880, BG472605, BQ932845

Consensus CDS

CCDS66886.1

UniProtKB/Swiss-Prot

O00746

Related

ENSP00000389048.1, ENST00000450036.1

Conserved Domains (1) summary

cd04413
Location:1 → 97

NDPk_I; Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside ...
NM_005009.3 → NP_005000.1 nucleoside diphosphate kinase, mitochondrial isoform a precursor

See identical proteins and their annotated locations for NP_005000.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

BC004880, BC017067

Consensus CDS

CCDS10408.1

UniProtKB/Swiss-Prot

A2IDD0, O00746, Q5U0M9

UniProtKB/TrEMBL

Q4TT34

Related

ENSP00000219479.2, ENST00000219479.7

Conserved Domains (2) summary

smart00562
Location:38 → 172

NDK; Enzymes that catalyze nonsubstrate specific conversions of nucleoside diphosphates to nucleoside triphosphates

cd04413
Location:38 → 167

NDPk_I; Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside ...