Q13232 · NDK3_HUMAN
- ProteinNucleoside diphosphate kinase 3
- GeneNME3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids169 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the phosphorylation of ribonucleosides and deoxyribonucleoside diphosphates, other than ATP, into the corresponding triphosphates with ATP as the major phosphate donor (PubMed:11277919, PubMed:30587587).
The ATP gamma phosphate is transferred to the nucleoside diphosphate beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Through the catalyzed exchange of gamma-phosphate between di- and triphosphonucleosides participates in regulation of intracellular nucleotide homeostasis (PubMed:11277919, PubMed:30587587).
Inhibits granulocyte differentiation (PubMed:7638209).
May be required for ciliary function during renal development (By similarity).
The ATP gamma phosphate is transferred to the nucleoside diphosphate beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Through the catalyzed exchange of gamma-phosphate between di- and triphosphonucleosides participates in regulation of intracellular nucleotide homeostasis (PubMed:11277919, PubMed:30587587).
Inhibits granulocyte differentiation (PubMed:7638209).
May be required for ciliary function during renal development (By similarity).
Independently of its kinase activity, facilitates mitochondrial tethering prior to membrane fusion through its direct membrane-binding and hexamerization (PubMed:30587587, PubMed:37584589).
Implicated in repair of both single- and double-stranded breaks in DNA through its association with the ribonucleotide reductase complex (RNR complex) via its interaction with the histone acetyltransferase KAT5, this interaction enables recruitment of NME3 at DNA damage sites where it plays a role in the repair of DNA, independently of its kinase activity (PubMed:37584589).
Implicated in repair of both single- and double-stranded breaks in DNA through its association with the ribonucleotide reductase complex (RNR complex) via its interaction with the histone acetyltransferase KAT5, this interaction enables recruitment of NME3 at DNA damage sites where it plays a role in the repair of DNA, independently of its kinase activity (PubMed:37584589).
Catalytic activity
- a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADPThis reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
25 μM | ATP | |||||
220 μM | TDP |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 29 | ADP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 105 | ADP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 111 | ADP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 122 | ADP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 129 | ADP (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 132 | ADP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 135 | Pros-phosphohistidine intermediate | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | ciliary basal body | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | mitochondrial outer membrane | |
Molecular Function | ATP binding | |
Molecular Function | metal ion binding | |
Molecular Function | nucleoside diphosphate kinase activity | |
Biological Process | apoptotic process | |
Biological Process | CTP biosynthetic process | |
Biological Process | DNA repair | |
Biological Process | GTP biosynthetic process | |
Biological Process | mitochondrial fusion | |
Biological Process | nucleoside triphosphate biosynthetic process | |
Biological Process | UTP biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNucleoside diphosphate kinase 3
- EC number
- Short namesNDK 3; NDP kinase 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ13232
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion outer membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 9 | Lacks phosphatidic acid binding activity; when associated with A-13. Decreases NME3 enrichement at the mitochondrial contact interface; when associated with A-13. | ||||
Sequence: F → A | ||||||
Mutagenesis | 13 | Lacks phosphatidic acid binding activity; when associated with A-9. Decreases NME3 enrichement at the mitochondrial contact interface; when associated with A-9. | ||||
Sequence: F → A | ||||||
Mutagenesis | 40 | Impairs hexamerization; when associated with D-46. Decreases mitochondrial tethering activity; when associated with D-46. | ||||
Sequence: E → D | ||||||
Mutagenesis | 46 | Impairs hexamerization; when associated with D-40. Decreases mitochondrial tethering activity; when associated with D-40. | ||||
Sequence: E → D | ||||||
Mutagenesis | 135 | Lacks of nucleoside diphosphate kinase activity. Does not affect mitochondrial fusion activity. | ||||
Sequence: H → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 276 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000137123 | 1-169 | UniProt | Nucleoside diphosphate kinase 3 | |||
Sequence: MICLVLTIFANLFPAACTGAHERTFLAVKPDGVQRRLVGEIVRRFERKGFKLVALKLVQASEELLREHYAELRERPFYGRLVKYMASGPVVAMVWQGLDVVRTSRALIGATNPADAPPGTIRGDFCIEVGKNLIHGSDSVESARREIALWFRADELLCWEDSAGHWLYE | |||||||
Modified residue (large scale data) | 142 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Developmental stage
Preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homohexamer (PubMed:30587587).
Interacts (via its N-terminal region) with KAT5; this interaction enables recruitment of NME3 at DNA damage sites where it plays a role in the repair of DNA (PubMed:26945015).
Found in association with several ciliary nephronophthisis proteins, including NEK8, CEP164, ANKS6 (PubMed:30111592).
Interacts (via its N-terminal region) with KAT5; this interaction enables recruitment of NME3 at DNA damage sites where it plays a role in the repair of DNA (PubMed:26945015).
Found in association with several ciliary nephronophthisis proteins, including NEK8, CEP164, ANKS6 (PubMed:30111592).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q13232 | DESI1 Q6ICB0 | 6 | EBI-713684, EBI-2806959 | |
BINARY | Q13232 | NME1 P15531 | 7 | EBI-713684, EBI-741141 | |
BINARY | Q13232 | NME2 P22392 | 4 | EBI-713684, EBI-713693 | |
BINARY | Q13232 | SGTA O43765 | 12 | EBI-713684, EBI-347996 | |
BINARY | Q13232 | SGTB Q96EQ0 | 5 | EBI-713684, EBI-744081 | |
BINARY | Q13232 | UBQLN1 Q9UMX0 | 6 | EBI-713684, EBI-741480 | |
BINARY | Q13232 | UBQLN1 Q9UMX0-2 | 3 | EBI-713684, EBI-10173939 | |
BINARY | Q13232 | UBQLN2 Q9UHD9 | 3 | EBI-713684, EBI-947187 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Domain
The N-terminal hydrophobic region (1-17) is critical for mitochondrial outer membrane targeting and phosphatidic acid binding.
Sequence similarities
Belongs to the NDK family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length169
- Mass (Da)19,015
- Last updated2002-05-27 v2
- ChecksumCCA41A122A37202D
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 60 | in Ref. 1; AAA85097 | ||||
Sequence: A → S | ||||||
Sequence conflict | 131 | in Ref. 1; AAA85097 | ||||
Sequence: Missing |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U29656 EMBL· GenBank· DDBJ | AAA85097.1 EMBL· GenBank· DDBJ | mRNA | ||
AE006639 EMBL· GenBank· DDBJ | AAK61291.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC000250 EMBL· GenBank· DDBJ | AAH00250.1 EMBL· GenBank· DDBJ | mRNA |