P54819 (KAD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 126.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Adenylate kinase 2, mitochondrial Short name=AK 2 EC=2.7.4.3 Alternative name(s): ATP-AMP transphosphorylase 2 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 239 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. This small ubiquitous enzyme involved in energy metabolism and nucleotide synthesis that is essential for maintenance and cell growth. Plays a key role in hematopoiesis. Ref.15 |
| Catalytic activity | ATP + AMP = 2 ADP. |
| Subunit structure | Monomer By similarity. |
| Subcellular location | |
| 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). Ref.14 |
| Involvement in disease | Defects in AK2 are the cause of reticular dysgenesis (RDYS) [MIM:267500]; also known as aleukocytosis. RDYS is the most severe form of inborn severe combined immunodeficiencies (SCID) and is characterized by absence of granulocytes and 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 immune functions, 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.In addition, affected newborns have bilateral sensorineural deafness. Defects may be due to its absence in leukocytes and inner ear, in which its absence can not be compensated by AK1. Ref.14 Ref.15 |
| Sequence similarities | Belongs to the adenylate kinase family. AK2 subfamily. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Mitochondrion |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Kinase Transferase |
| PTM | Acetylation Disulfide bond |
| Technical term | 3D-structure Complete proteome Direct protein sequencing Reference proteome |
| Gene Ontology (GO) | |
| Biological process | nucleobase-containing small molecule interconversion Traceable author statement. Source: Reactome |
| Cellular component | mitochondrial intermembrane space Traceable author statement. Source: Reactome |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylate kinase activityTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P54819-1) Also known as: AK2A; AK2isoA; 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. | ||||||
| Isoform 2 (identifier: P54819-2) Also known as: AK2B; AK2isoB; The sequence of this isoform differs from the canonical sequence as follows: 232-239: CKDLVMFI → S | ||||||
| Isoform 3 (identifier: P54819-3) Also known as: AK2C; The sequence of this isoform differs from the canonical sequence as follows: 178-239: DNEKALKIRL...ATCKDLVMFI → IGQAKRSFLRLAKISFDVLIKKALA | ||||||
| Isoform 4 (identifier: P54819-4) Also known as: AK2D; The sequence of this isoform differs from the canonical sequence as follows: 2-48: Missing. 177-178: DD → GL 179-239: Missing. | ||||||
| Isoform 5 (identifier: P54819-5) The sequence of this isoform differs from the canonical sequence as follows: 135-142: Missing. 232-239: CKDLVMFI → S | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 6 (identifier: P54819-6) The sequence of this isoform differs from the canonical sequence as follows: 2-48: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed Ref.10 | ||||||||||||||||||||||||||||||||||||||||
| Chain | 2 – 239 | 238 | Adenylate kinase 2, mitochondrial | PRO_0000158917 | |||||||||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||||||||
| Nucleotide binding | 22 – 30 | 9 | ATP By similarity | ||||||||||||||||||||||||||||||||||||||||
| Nucleotide binding | 45 – 74 | 30 | AMP By similarity | ||||||||||||||||||||||||||||||||||||||||
Sites | |||||||||||||||||||||||||||||||||||||||||||
| Binding site | 46 | 1 | AMP By similarity | ||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 14 | 1 | N6-acetyllysine Ref.11 | ||||||||||||||||||||||||||||||||||||||||
| Modified residue | 93 | 1 | N6-acetyllysine By similarity | ||||||||||||||||||||||||||||||||||||||||
| Disulfide bond | 42 ↔ 92 | Ref.13 | |||||||||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 2 – 48 | 47 | Missing in isoform 4 and isoform 6. | VSP_002792 | |||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 135 – 142 | 8 | Missing in isoform 5. | VSP_036503 | |||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 177 – 178 | 2 | DD → GL in isoform 4. | VSP_002793 | |||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 178 – 239 | 62 | DNEKA…LVMFI → IGQAKRSFLRLAKISFDVLI KKALA in isoform 3. | VSP_002791 | |||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 179 – 239 | 61 | Missing in isoform 4. | VSP_002794 | |||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 232 – 239 | 8 | CKDLVMFI → S in isoform 2 and isoform 5. | VSP_002790 | |||||||||||||||||||||||||||||||||||||||
| Natural variant | 103 | 1 | R → W in RDYS. Ref.15 | VAR_054630 | |||||||||||||||||||||||||||||||||||||||
| Natural variant | 165 | 1 | D → G in RDYS. Ref.15 | VAR_054631 | |||||||||||||||||||||||||||||||||||||||
| Natural variant | 209 | 1 | A → T. Corresponds to variant rs12116440 [ dbSNP | Ensembl ]. | VAR_050032 | |||||||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 16 – 21 | 6 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 28 – 39 | 12 | |||||||||||||||||||||||||||||||||||||||||
| Beta strand | 42 – 45 | 4 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 46 – 56 | 11 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 59 – 69 | 11 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 76 – 87 | 12 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 90 – 92 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Beta strand | 95 – 100 | 6 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 105 – 117 | 13 | |||||||||||||||||||||||||||||||||||||||||
| Beta strand | 124 – 129 | 6 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 132 – 140 | 9 | |||||||||||||||||||||||||||||||||||||||||
| Turn | 146 – 148 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Beta strand | 151 – 153 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Turn | 154 – 156 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Beta strand | 166 – 168 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 180 – 203 | 24 | |||||||||||||||||||||||||||||||||||||||||
| Beta strand | 207 – 211 | 5 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 216 – 230 | 15 | |||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning and characterization of cDNA for human adenylate kinase 2A." Lee Y., Kim J.W., Lee I.A., Kang H.B., Choe Y.K., Lee H.G., Lim J.S., Kim H.J., Park C., Choe I.S. Biochem. Mol. Biol. Int. 39:833-842(1996) [PubMed: 8843353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver. |
| [2] | "Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues." Lee Y., Kim J.W., Lee S.M., Kim H.J., Lee K.S., Park C., Choe I.S. J. Biochem. 123:47-54(1998) [PubMed: 9504408] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Fetal liver. |
| [3] | "cDNA cloning and tissue-specific expression of the gene encoding human adenylate kinase isozyme 2." Noma T., Song S., Yoon Y.-S., Tanaka S., Nakazawa A. Biochim. Biophys. Acta 1395:34-39(1998) [PubMed: 9434148] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). |
| [4] | "Novel isoforms of human adenylate kinase 2." Guo J. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4). |
| [5] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 5 AND 6). Tissue: Brain, Placenta and Tongue. |
| [6] | "Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. Nomura N.Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). |
| [7] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [9] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Placenta and Uterus. |
| [10] | Bienvenut W.V., Heiserich L., Gottlieb E. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-14; 18-34; 73-85; 94-103; 107-117 AND 120-138, CLEAVAGE OF INITIATOR METHIONINE, MASS SPECTROMETRY. Tissue: Colon carcinoma. |
| [11] | "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-14, MASS SPECTROMETRY. |
| [12] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [13] | "Structure of human adenylate kinase 2." Bunkoczi G., Filippakopoulos P., Debreczeni J.E., Turnbull A., Papagrigoriou E., Savitsky P., Colebrook S., Von Delft F., Arrowsmith C., Edwards A., Sundstrom M., Weigelt J., Knapp S. Submitted (JAN-2006) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), DISULFIDE BONDS. |
| [14] | "Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2." Pannicke U., Hoenig M., Hess I., Friesen C., Holzmann K., Rump E.-M., Barth T.F., Rojewski M.T., Schulz A., Boehm T., Friedrich W., Schwarz K. Nat. Genet. 41:101-105(2009) [PubMed: 19043417] [Abstract] Cited for: INVOLVEMENT IN RDYS, TISSUE SPECIFICITY. |
| [15] | "Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness." Lagresle-Peyrou C., Six E.M., Picard C., Rieux-Laucat F., Michel V., Ditadi A., Chappedelaine C.D., Morillon E., Valensi F., Simon-Stoos K.L., Mullikin J.C., Noroski L.M., Besse C., Wulffraat N.M., Ferster A., Abecasis M.M., Calvo F., Petit C. Cavazzana-Calvo M.Nat. Genet. 41:106-111(2009) [PubMed: 19043416] [Abstract] Cited for: VARIANTS RDYS TRP-103 AND GLY-165, FUNCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | U39945 mRNA. Translation: AAC52061.1. U84371 mRNA. Translation: AAB41790.1. U54645 mRNA. Translation: AAC13881.1. AB005621 mRNA. Translation: BAC16747.1. AB005622 mRNA. Translation: BAC16748.1. AY080899 mRNA. Translation: AAL87027.1. AY080900 mRNA. Translation: AAL87028.1. AK291676 mRNA. Translation: BAF84365.1. AK295105 mRNA. Translation: BAG58139.1. AK296863 mRNA. Translation: BAG59426.1. AB451267 mRNA. Translation: BAG70081.1. AB451394 mRNA. Translation: BAG70208.1. AL020995 Genomic DNA. Translation: CAI19351.1. AL020995 Genomic DNA. Translation: CAI19352.1. CH471059 Genomic DNA. Translation: EAX07484.1. CH471059 Genomic DNA. Translation: EAX07486.1. BC009405 mRNA. Translation: AAH09405.1. BC070127 mRNA. Translation: AAH70127.1. BC090040 mRNA. Translation: AAH90040.1. | ||||||||||||
| IPI | IPI00172460. IPI00215901. IPI00218988. IPI00218989. IPI00921960. IPI00922165. | ||||||||||||
| PIR | G02248. JC5893. | ||||||||||||
| RefSeq | NP_001186128.1. NM_001199199.1. NP_001616.1. NM_001625.3. NP_037543.1. NM_013411.4. | ||||||||||||
| UniGene | Hs.470907. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | P54819. | ||||||||||||
| SMR | P54819. Positions 15-232. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | P54819. 3 interactions. | ||||||||||||
| STRING | P54819. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P54819. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 1708596. | ||||||||||||
2D gel databases | |||||||||||||
| OGP | P54819. | ||||||||||||
| REPRODUCTION-2DPAGE | IPI00218988. | ||||||||||||
| UCD-2DPAGE | P54819. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | P54819. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000354858; ENSP00000346921; ENSG00000004455. | ||||||||||||
| GeneID | 204. | ||||||||||||
| KEGG | hsa:204. | ||||||||||||
| UCSC | uc001bwp.1. human. uc001bwq.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 204. | ||||||||||||
| GeneCards | GC01M033474. | ||||||||||||
| HGNC | HGNC:362. AK2. | ||||||||||||
| HPA | HPA018479. | ||||||||||||
| MIM | 103020. gene. 267500. phenotype. | ||||||||||||
| neXtProt | NX_P54819. | ||||||||||||
| PharmGKB | PA24656. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | prNOG09773. | ||||||||||||
| GeneTree | ENSGT00600000084421. | ||||||||||||
| HOVERGEN | HBG000458. | ||||||||||||
| InParanoid | P54819. | ||||||||||||
| OMA | HEEFHPP. | ||||||||||||
| PhylomeDB | P54819. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| Reactome | REACT_111217. Metabolism. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P54819. | ||||||||||||
| Bgee | P54819. | ||||||||||||
| CleanEx | HS_AK2. | ||||||||||||
| Genevestigator | P54819. | ||||||||||||
| GermOnline | ENSG00000004455. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR006259. Adenyl_kin_sub. IPR000850. Adenylate_kin. IPR007862. Adenylate_kinase_lid-dom. [Graphical view] | ||||||||||||
| KO | K00939. | ||||||||||||
| PANTHER | PTHR23359. Adenylate_kin. 1 hit. | ||||||||||||
| Pfam | PF00406. ADK. 1 hit. PF05191. ADK_lid. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR00094. ADENYLTKNASE. | ||||||||||||
| TIGRFAMs | TIGR01351. Adk. 1 hit. | ||||||||||||
| PROSITE | PS00113. ADENYLATE_KINASE. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| NextBio | 812. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | KAD2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P54819 Secondary accession number(s): A8K6L1 Q8TCY3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with