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Details on Person UniProt:P22392 NME2

Class:Id	ReferenceGeneProduct:60025
_chainChangeLog	initiator methionine:1 added on Sat February 7 2015;chain:2-152 added on Sat February 7 2015;initiator methionine:1 removed on Fri May 8 2015;chain:2-152 removed on Fri May 8 2015;chain:1-152 added on Fri May 8 2015
_displayName	UniProt:P22392 NME2
_timestamp	2026-02-20 21:32:24
chain	chain:1-152
checksum	1A5C3F84D7AD272C
comment	FUNCTION Catalyzes the transfer of a gamma-phosphoryl group from a nucleoside triphosphate, mainly ATP, to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, therefore contributing to the nucleoside triphosphate homeostasis (PubMed:11121025, PubMed:16313181, PubMed:1851158, PubMed:25679041). Also functions as a histidine protein kinase by transferring the phosphoryl group from the phosphohistidine intermediate to a histidine residue in target proteins (PubMed:17157250, PubMed:20946858). Phosphorylates the GNB1 subunit of heterotrimeric G proteins at 'His-266', generating a high-energy phosphate group that promotes GTP formation and enables receptor-independent activation of heterotrimeric G proteins (By similarity). Also phosphorylates KCNN4 at 'His-358', leading to activation of its intermediate conductance calcium-activated potassium channel activity, Ca(2+) influx, and subsequent activation of B and T cells (PubMed:17157250). Additionally involved in transcriptional regulation through direct DNA binding and chromatin remodeling (PubMed:11121025, PubMed:11694515, PubMed:19033359, PubMed:19435876, PubMed:25679041, PubMed:8392752). In this context, functions as a single-stranded DNA binding protein that binds and stabilizes the G-quadruplex (G4) structures within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter, facilitating recruitment of additional single-strand DNA binding proteins and activation of MYC transcription (PubMed:19033359, PubMed:19435876, PubMed:25679041, PubMed:8392752). G4 DNA-binding activity is independent of its nucleoside diphosphate kinase function and recognizes both folded and unfolded G4 structures (PubMed:25679041). With NME1, may regulate acetyl-CoA (AcCoA) usage between histone acetylation and fatty acid synthesis by targeting AcCoA release at ATP-rich, HAT-associated chromatin regions (By similarity). Also negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197).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 IDP + ATP = ITP + ADPCATALYTIC ACTIVITY GDP + ATP = GTP + ADPCATALYTIC ACTIVITY ADP + ATP = ADP + ATPCATALYTIC ACTIVITY UDP + ATP = UTP + ADPCATALYTIC ACTIVITY CDP + ATP = CTP + ADPCATALYTIC ACTIVITY dTDP + ATP = dTTP + ADPCATALYTIC ACTIVITY ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.COFACTOR Homohexamer (PubMed:1851158, PubMed:19435876, PubMed:7658474, PubMed:8747457). Heterohexamer of two different chains: A/NME1 and B/NME2 (A5B or A4B2 or A3B3 or A2B4 or AB5) (PubMed:1851158). Interacts with CAPN8 (By similarity). Interacts with AKAP13 (PubMed:15249197). Interacts with ITGB1BP1 (via C-terminal domain region); this interaction leads to their recruitment to ITGB1-rich cell adhesion sites in cell spreading on FN1 (PubMed:11919189). Interacts with BCL2L10 (PubMed:17532299).INTERACTION Colocalizes with ITGB1 and ITGB1BP1 at the edge or peripheral ruffles and lamellipodia during the early stages of cell spreading on fibronectin or collagen but not on vitronectin or laminin substrates.SUBCELLULAR LOCATION Ubiquitously expressed.TISSUE SPECIFICITY Ubiquitously expressed.PTM Autophosphorylated.MISCELLANEOUS Involved in the activation pathway of bemnifosbuvir (AT-527) and its epimer, AT-752 (PubMed:39190717). AT-527 and AT-752 are two guanosine analogs tested in clinical trials against several RNA viruses, which are activated into their common 5'-triphosphate AT-9010 in human cells (PubMed:39190717). Mediates the last activation step by catalyzing transformation of AT-8500 into AT-9010 (PubMed:39190717).MISCELLANEOUS Based on a naturally occurring readthrough transcript which produces an NME1-NME2 fusion protein.SIMILARITY Belongs to the NDK family.CAUTION Originnally, in addition to its DNA binding activity, some reports shown that exhibited an intrinsic nuclease activity (PubMed:11121025, PubMed:11694515). Bound DNA within the nuclease hypersensitive element (NHE) III(1) region and cleaved the phosphodiester bond by transiently forming a covalent protein-DNA intermediate through a nucleophilic attack (PubMed:11121025). However, this nuclease activity has not been confirmed (PubMed:19435876).
description	recommendedName: fullName evidence="24"Nucleoside diphosphate kinase B shortName evidence="25"NDP kinase B shortName evidence="25"NDPK B ecNumber evidence="4 8 12 16"2.7.4.6 alternativeName: fullName evidence="27"C-myc purine-binding transcription factor PUF alternativeName: Histidine protein kinase NDKB ecNumber evidence="10 15"2.7.13.3 alternativeName: fullName evidence="22"Nucleoside diphoshate kinase 2 shortName evidence="22"NDK2 alternativeName: fullName evidence="26"nm23-H2
geneName	NME2 NDK2 NM23B
identifier	P22392
isSequenceChanged	FALSE
keyword	3D-structure Activator Alternative splicing Cell projection Cytoplasm Direct protein sequencing DNA-binding Kinase Magnesium Metal-binding Nucleotide metabolism Nucleus Proteomics identification Reference proteome Transcription Transcription regulation Transferase
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
name	NME2
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8957612] ENSEMBL:ENSG00000243678 NME2 [Homo sapiens]
secondaryIdentifier	NDKB_HUMAN A8MWA3 Q1WM23 Q6LCT6
sequenceLength	152
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:424402] UniProt:P22392-1 NME2 [Homo sapiens] [ReferenceIsoform:8974786] UniProt:P22392-2 NME2 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:60024] NME2 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:6803277] NME2 [secretory granule lumen] [Homo sapiens] [EntityWithAccessionedSequence:6803324] NME2 [ficolin-1-rich granule lumen] [Homo sapiens] [EntityWithAccessionedSequence:6803357] NME2 [extracellular exosome] [Homo sapiens] [EntityWithAccessionedSequence:6806464] NME2 [extracellular region] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P22392 NME2 (60025)