P54819 · KAD2_HUMAN
- ProteinAdenylate kinase 2, mitochondrial
- GeneAK2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids239 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis.
Catalytic activity
- AMP + ATP = 2 ADP
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 25-30 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GAGKGT | ||||||
Binding site | 46 | AMP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 51 | AMP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 72-74 | AMP (UniProtKB | ChEBI) | ||||
Sequence: KLV | ||||||
Binding site | 100-103 | AMP (UniProtKB | ChEBI) | ||||
Sequence: GFPR | ||||||
Binding site | 107 | AMP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 138 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 142 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 151-152 | ATP (UniProtKB | ChEBI) | ||||
Sequence: SY | ||||||
Binding site | 175 | AMP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 186 | AMP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 214 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Q |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | extracellular exosome | |
Cellular Component | mitochondrial intermembrane space | |
Cellular Component | mitochondrion | |
Cellular Component | sperm mitochondrial sheath | |
Molecular Function | adenylate kinase activity | |
Molecular Function | ATP binding | |
Biological Process | ADP biosynthetic process | |
Biological Process | AMP metabolic process | |
Biological Process | ATP metabolic process | |
Biological Process | nucleobase-containing small molecule interconversion |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAdenylate kinase 2, mitochondrial
- EC number
- Short namesAK 2
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP54819
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Reticular dysgenesis (RDYS)
- Note
- DescriptionA fatal form of severe combined immunodeficiency, characterized by absence of granulocytes, almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immunity, leading to fatal septicemia within days after birth. In bone marrow of individuals with reticular dysgenesis, myeloid differentiation is blocked at the promyelocytic stage, whereas erythro- and megakaryocytic maturation is generally normal. Inheritance is autosomal recessive.
- See alsoMIM:267500
Natural variants in RDYS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_054630 | 103 | R>W | in RDYS; dbSNP:rs267606648 | |
VAR_054631 | 165 | D>G | in RDYS; dbSNP:rs267606643 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_054630 | 103 | in RDYS; dbSNP:rs267606648 | |||
Sequence: R → W | ||||||
Natural variant | VAR_054631 | 165 | in RDYS; dbSNP:rs267606643 | |||
Sequence: D → G | ||||||
Natural variant | VAR_050032 | 209 | in dbSNP:rs12116440 | |||
Sequence: A → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 322 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data), disulfide bond.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed; alternate | ||||
Sequence: M | |||||||
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000423212 | 1-239 | UniProt | Adenylate kinase 2, mitochondrial | |||
Sequence: MAPSVPAAEPEYPKGIRAVLLGPPGAGKGTQAPRLAENFCVCHLATGDMLRAMVASGSELGKKLKATMDAGKLVSDEMVVELIEKNLETPLCKNGFLLDGFPRTVRQAEMLDDLMEKRKEKLDSVIEFSIPDSLLIRRITGRLIHPKSGRSYHEEFNPPKEPMKDDITGEPLIRRSDDNEKALKIRLQAYHTQTTPLIEYYRKRGIHSAIDASQTPDVVFASILAAFSKATCKDLVMFI | |||||||
Chain | PRO_0000158917 | 2-239 | UniProt | Adenylate kinase 2, mitochondrial, N-terminally processed | |||
Sequence: APSVPAAEPEYPKGIRAVLLGPPGAGKGTQAPRLAENFCVCHLATGDMLRAMVASGSELGKKLKATMDAGKLVSDEMVVELIEKNLETPLCKNGFLLDGFPRTVRQAEMLDDLMEKRKEKLDSVIEFSIPDSLLIRRITGRLIHPKSGRSYHEEFNPPKEPMKDDITGEPLIRRSDDNEKALKIRLQAYHTQTTPLIEYYRKRGIHSAIDASQTPDVVFASILAAFSKATCKDLVMFI | |||||||
Modified residue | 4 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 4 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 30 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Disulfide bond | 42↔92 | UniProt | |||||
Sequence: CHLATGDMLRAMVASGSELGKKLKATMDAGKLVSDEMVVELIEKNLETPLC | |||||||
Modified residue | 58 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 62 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue | 93 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue | 133 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 148 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 151 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 176 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 181 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 195 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 195 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Present in most tissues. Present at high level in heart, liver and kidney, and at low level in brain, skeletal muscle and skin. Present in thrombocytes but not in erythrocytes, which lack mitochondria. Present in all nucleated cell populations from blood, while AK1 is mostly absent. In spleen and lymph nodes, mononuclear cells lack AK1, whereas AK2 is readily detectable. These results indicate that leukocytes may be susceptible to defects caused by the lack of AK2, as they do not express AK1 in sufficient amounts to compensate for the AK2 functional deficits (at protein level).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Monomer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P54819 | ATXN1 P54253 | 3 | EBI-1056291, EBI-930964 | |
BINARY | P54819 | PECAM1 P16284 | 3 | EBI-1056291, EBI-716404 | |
BINARY | P54819 | PMP22 A0A6Q8PF08 | 3 | EBI-1056291, EBI-50433196 | |
BINARY | P54819 | PRKACA P17612 | 3 | EBI-1056291, EBI-476586 | |
BINARY | P54819 | PSEN2 P49810 | 3 | EBI-1056291, EBI-2010251 | |
BINARY | P54819 | SERPINH1 P50454 | 3 | EBI-1056291, EBI-350723 | |
BINARY | P54819 | TGFBR2 P37173 | 3 | EBI-1056291, EBI-296151 | |
BINARY | P54819 | VIM P08670 | 3 | EBI-1056291, EBI-353844 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 45-74 | NMP | ||||
Sequence: ATGDMLRAMVASGSELGKKLKATMDAGKLV | ||||||
Region | 141-178 | LID | ||||
Sequence: GRLIHPKSGRSYHEEFNPPKEPMKDDITGEPLIRRSDD | ||||||
Region | 150-169 | Disordered | ||||
Sequence: RSYHEEFNPPKEPMKDDITG |
Domain
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis.
Sequence similarities
Belongs to the adenylate kinase family. AK2 subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
P54819-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsAK2A, AK2isoA
- Length239
- Mass (Da)26,478
- Last updated2007-01-23 v2
- Checksum86FA94F9EE33629F
P54819-2
- Name2
- SynonymsAK2B, AK2isoB
- Differences from canonical
- 232-239: CKDLVMFI → S
P54819-3
- Name3
- SynonymsAK2C
- Differences from canonical
- 178-239: DNEKALKIRLQAYHTQTTPLIEYYRKRGIHSAIDASQTPDVVFASILAAFSKATCKDLVMFI → IGQAKRSFLRLAKISFDVLIKKALA
P54819-4
- Name4
- SynonymsAK2D
P54819-5
- Name5
P54819-6
- Name6
- Differences from canonical
- 1-48: Missing
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F8VZG5 | F8VZG5_HUMAN | AK2 | 162 | ||
F8VY04 | F8VY04_HUMAN | AK2 | 190 | ||
F8W1A4 | F8W1A4_HUMAN | AK2 | 232 | ||
F8VPP1 | F8VPP1_HUMAN | AK2 | 42 | ||
G3V213 | G3V213_HUMAN | AK2 | 133 | ||
A0A5F9ZHP2 | A0A5F9ZHP2_HUMAN | AK2 | 162 | ||
A0A5K1VW67 | A0A5K1VW67_HUMAN | AK2 | 197 | ||
A0A8Q3SHW4 | A0A8Q3SHW4_HUMAN | AK2 | 43 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_002792 | 1-48 | in isoform 4 and isoform 6 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_036503 | 135-142 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_002793 | 177-178 | in isoform 4 | |||
Sequence: DD → GL | ||||||
Alternative sequence | VSP_002791 | 178-239 | in isoform 3 | |||
Sequence: DNEKALKIRLQAYHTQTTPLIEYYRKRGIHSAIDASQTPDVVFASILAAFSKATCKDLVMFI → IGQAKRSFLRLAKISFDVLIKKALA | ||||||
Alternative sequence | VSP_002794 | 179-239 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_002790 | 232-239 | in isoform 2 and isoform 5 | |||
Sequence: CKDLVMFI → S |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U39945 EMBL· GenBank· DDBJ | AAC52061.1 EMBL· GenBank· DDBJ | mRNA | ||
U84371 EMBL· GenBank· DDBJ | AAB41790.1 EMBL· GenBank· DDBJ | mRNA | ||
U54645 EMBL· GenBank· DDBJ | AAC13881.1 EMBL· GenBank· DDBJ | mRNA | ||
AB005621 EMBL· GenBank· DDBJ | BAC16747.1 EMBL· GenBank· DDBJ | mRNA | ||
AB005622 EMBL· GenBank· DDBJ | BAC16748.1 EMBL· GenBank· DDBJ | mRNA | ||
AY080899 EMBL· GenBank· DDBJ | AAL87027.1 EMBL· GenBank· DDBJ | mRNA | ||
AY080900 EMBL· GenBank· DDBJ | AAL87028.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291676 EMBL· GenBank· DDBJ | BAF84365.1 EMBL· GenBank· DDBJ | mRNA | ||
AK295105 EMBL· GenBank· DDBJ | BAG58139.1 EMBL· GenBank· DDBJ | mRNA | ||
AK296863 EMBL· GenBank· DDBJ | BAG59426.1 EMBL· GenBank· DDBJ | mRNA | ||
AB451267 EMBL· GenBank· DDBJ | BAG70081.1 EMBL· GenBank· DDBJ | mRNA | ||
AB451394 EMBL· GenBank· DDBJ | BAG70208.1 EMBL· GenBank· DDBJ | mRNA | ||
AL020995 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471059 EMBL· GenBank· DDBJ | EAX07484.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471059 EMBL· GenBank· DDBJ | EAX07486.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC009405 EMBL· GenBank· DDBJ | AAH09405.1 EMBL· GenBank· DDBJ | mRNA | ||
BC070127 EMBL· GenBank· DDBJ | AAH70127.1 EMBL· GenBank· DDBJ | mRNA | ||
BC090040 EMBL· GenBank· DDBJ | AAH90040.1 EMBL· GenBank· DDBJ | mRNA |