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Details on Person UniProt:O00746-1 NME4

Class:IdReferenceIsoform:8972029
_chainChangeLogtransit peptide:1-33 added on Fri February 17 2017;chain:34-187 added on Fri February 17 2017
_displayNameUniProt:O00746-1 NME4
_timestamp2026-02-20 22:24:20
chaintransit peptide:1-28
chain:29-187
checksumA56FEF18A7D712D4
commentFUNCTION Mitochondria-specific nucleoside diphosphate kinase that catalyzes the transfer of a gamma-phosphoryl group from ATP to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, participating in nucleoside triphosphate homeostasis (PubMed:10799505, PubMed:16313181, PubMed:18635542, PubMed:23150663). In vitro, purine nucleoside triphosphates are much more effective as donors and acceptors than pyrimidine nucleoside triphosphates, and ribonucleosides derivatives are superior to their deoxyribonucleosides counterparts (By similarity). Associates with cardiolipin-containing mitochondrial inner membrane and locally produces ADP in the mitochondrial intermembrane space, which is directly taken up via the ADP/ATP translocase (ANT) into the matrix to stimulate respiratory ATP regeneration (PubMed:18635542, PubMed:24970086). Also directly provides GTP for mitochondrial GTPases, such as the dynamin-related GTPase OPA1 (PubMed:24970086). Additionally, catalyzes the anionic phospholipid transfer, namely cardiolipin, from the mitochondrial inner membrane (IM) to the outer membrane (OM) through the formation of contact sites between IM and OM, in a nucleoside diphosphate kinase-independent manner (PubMed:17028143, PubMed:23150663). The switch between the nucleoside diphosphate kinase and the phospholipid transfer activity may depend on the availability and accessibility of cardiolipin and other anionic phospholipids in the IM outer leaflet and OM inner leaflet (PubMed:23150663).CATALYTIC ACTIVITY a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADPCATALYTIC ACTIVITY a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'-triphosphate + ADPCATALYTIC ACTIVITY dTDP + ATP = dTTP + ADPCATALYTIC ACTIVITY a cardiolipin(in) = a cardiolipin(out)CATALYTIC ACTIVITY GDP + ATP = GTP + ADPCATALYTIC ACTIVITY CDP + ATP = CTP + ADPCATALYTIC ACTIVITY UDP + ATP = UTP + ADPCATALYTIC ACTIVITY dCDP + ATP = dCTP + ADPCATALYTIC ACTIVITY dGDP + ATP = dGTP + ADPCOFACTOR Binding to anionic phospholipids, predominantly to cardiolipin inhibits its phosphotransfer activity.SUBUNIT Homohexamer (PubMed:10799505). Interacts with OPA1 (PubMed:23150663). Interacts with CAPN8 (By similarity).INTERACTION Predominantly localized in the mitochondrion intermembrane space (PubMed:18635542). Colocalizes with OPA1 in mitochondria (Probable) (PubMed:24970086). Phospholipid binding mediates mitochondrial inner membrane binding (Probable) (PubMed:18635542). Fully membrane-bound, when attached simultaneously to inner membrane (IM) and outer membrane (OM) through the formation of contact sites between IM and OM (Probable) (PubMed:17028143). The additional binding to OM may depend on the availability or accessibility of cardiolipin and/or other anionic phospholipids in the IM outer leaflet and the OM inner leaflet (Probable).ALTERNATIVE PRODUCTS Widely distributed. Found at very high levels in prostate, heart, liver, small intestine, and skeletal muscle tissues, and in low amounts in the brain and in blood leukocytes.SIMILARITY Belongs to the NDK family.
created[InstanceEdit:8964659] Weiser, JD
descriptionrecommendedName: fullName evidence="16"Nucleoside diphosphate kinase D, mitochondrial shortName evidence="11"NDPK-D ecNumber evidence="4 5 7 8"2.7.4.6 alternativeName: fullName evidence="15"Nucleoside diphosphate kinase 4 shortName evidence="10"NDK4 alternativeName: fullName evidence="12"nm23-H4
geneNameNME4
NM23D
identifierO00746
isoformParent
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
ATP-binding
Direct protein sequencing
Kinase
Lipid-binding
Magnesium
Membrane
Metal-binding
Mitochondrion
Mitochondrion outer membrane
Nucleotide metabolism
Nucleotide-binding
Proteomics identification
Reference proteome
Transferase
Transit peptide
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9862192] Weiser, Joel, 2024-02-26
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameNME4
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:9004831] ENSEMBL:ENSG00000103202 NME4 [Homo sapiens]
secondaryIdentifierNDKD_HUMAN
A2IDD0
Q5U0M9
sequenceLength187
species[Species:48887] Homo sapiens
variantIdentifierO00746-1
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