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Protein

Adenosine kinase

Gene

ADK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.

Catalytic activityi

ATP + adenosine = ADP + AMP.

Cofactori

Mg2+Note: Binds 3 Mg2+ ions per subunit.

Pathwayi: AMP biosynthesis via salvage pathway

This protein is involved in step 1 of the subpathway that synthesizes AMP from adenosine.
Proteins known to be involved in this subpathway in this organism are:
  1. Adenosine kinase (ADK)
This subpathway is part of the pathway AMP biosynthesis via salvage pathway, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from adenosine, the pathway AMP biosynthesis via salvage pathway and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi49Magnesium 11
Metal bindingi147Magnesium 21
Metal bindingi148Magnesium 21
Active sitei3171

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
Biological processPurine salvage
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08097-MONOMER
BRENDAi2.7.1.20 2681
ReactomeiR-HSA-74217 Purine salvage
SABIO-RKiP55263
UniPathwayiUPA00588; UER00659

Names & Taxonomyi

Protein namesi
Recommended name:
Adenosine kinase (EC:2.7.1.20)
Short name:
AK
Alternative name(s):
Adenosine 5'-phosphotransferase
Gene namesi
Name:ADK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000156110.13
HGNCiHGNC:257 ADK
MIMi102750 gene
neXtProtiNX_P55263

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Hypermethioninemia due to adenosine kinase deficiency (HMAKD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.
See also OMIM:614300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06664030G → E in HMAKD; the mutant shows some residual activity. 1 PublicationCorresponds to variant dbSNP:rs397514454EnsemblClinVar.1
Natural variantiVAR_066641235D → A in HMAKD; the mutant shows some residual activity. 1 PublicationCorresponds to variant dbSNP:rs397514453EnsemblClinVar.1
Natural variantiVAR_066642318A → E in HMAKD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs397514452Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi11 – 12KK → AA or AD: Abolishes nuclear localization. 1 Publication2

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi132
MalaCardsiADK
MIMi614300 phenotype
OpenTargetsiENSG00000156110
Orphaneti289290 Hypermethioninemia encephalopathy due to adenosine kinase deficiency
PharmGKBiPA24579

Chemistry databases

ChEMBLiCHEMBL3589
DrugBankiDB07280 5-[4-(DIMETHYLAMINO)PHENYL]-6-[(6-MORPHOLIN-4-YLPYRIDIN-3-YL)ETHYNYL]PYRIMIDIN-4-AMINE
DB01048 Abacavir
DB00640 Adenosine
DB00131 Adenosine monophosphate
DB00171 Adenosine triphosphate
DB00811 Ribavirin
GuidetoPHARMACOLOGYi1231

Polymorphism and mutation databases

BioMutaiADK
DMDMi6840802

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000800532 – 362Adenosine kinaseAdd BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei77Phosphotyrosine1 Publication1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP55263
MaxQBiP55263
PaxDbiP55263
PeptideAtlasiP55263
PRIDEiP55263
ProteomicsDBi56823
56824 [P55263-2]
56825 [P55263-3]

2D gel databases

REPRODUCTION-2DPAGEiIPI00234368

PTM databases

iPTMnetiP55263
PhosphoSitePlusiP55263
SwissPalmiP55263

Expressioni

Tissue specificityi

Widely expressed. Highest level in placenta, liver, muscle and kidney.

Gene expression databases

BgeeiENSG00000156110
CleanExiHS_ADK
ExpressionAtlasiP55263 baseline and differential
GenevisibleiP55263 HS

Organism-specific databases

HPAiCAB032876
HPA038391
HPA038409

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi106644, 17 interactors
IntActiP55263, 3 interactors
STRINGi9606.ENSP00000286621

Chemistry databases

BindingDBiP55263

Structurei

Secondary structure

1362
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 29Combined sources4
Beta strandi33 – 39Combined sources7
Helixi42 – 47Combined sources6
Beta strandi52 – 57Combined sources6
Helixi60 – 62Combined sources3
Helixi63 – 72Combined sources10
Beta strandi76 – 80Combined sources5
Helixi82 – 94Combined sources13
Beta strandi96 – 99Combined sources4
Beta strandi101 – 110Combined sources10
Helixi111 – 122Combined sources12
Beta strandi126 – 135Combined sources10
Beta strandi139 – 145Combined sources7
Beta strandi148 – 154Combined sources7
Helixi156 – 160Combined sources5
Helixi163 – 165Combined sources3
Turni166 – 168Combined sources3
Helixi170 – 178Combined sources9
Beta strandi180 – 185Combined sources6
Helixi186 – 190Combined sources5
Helixi193 – 205Combined sources13
Beta strandi209 – 213Combined sources5
Helixi217 – 222Combined sources6
Helixi224 – 230Combined sources7
Helixi231 – 233Combined sources3
Beta strandi235 – 240Combined sources6
Helixi241 – 250Combined sources10
Helixi258 – 266Combined sources9
Beta strandi278 – 283Combined sources6
Beta strandi286 – 291Combined sources6
Beta strandi296 – 299Combined sources4
Helixi312 – 327Combined sources16
Turni328 – 330Combined sources3
Helixi333 – 347Combined sources15
Beta strandi350 – 353Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BX4X-ray1.50A22-362[»]
2I6AX-ray2.20A/B/C/D22-362[»]
2I6BX-ray2.30A/B22-362[»]
4O1LX-ray2.50A/B17-362[»]
ProteinModelPortaliP55263
SMRiP55263
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55263

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi8 – 16Nuclear localization signal1 Publication9

Sequence similaritiesi

Belongs to the carbohydrate kinase PfkB family.Curated

Phylogenomic databases

eggNOGiKOG2854 Eukaryota
COG0524 LUCA
GeneTreeiENSGT00390000014320
HOGENOMiHOG000172419
HOVERGENiHBG002367
InParanoidiP55263
KOiK00856
OMAiAPFIAQF
OrthoDBiEOG091G0JQC
PhylomeDBiP55263
TreeFamiTF300745

Family and domain databases

Gene3Di3.40.1190.20, 3 hits
InterProiView protein in InterPro
IPR001805 Adenokinase
IPR002173 Carboh/pur_kinase_PfkB_CS
IPR011611 PfkB_dom
IPR029056 Ribokinase-like
PfamiView protein in Pfam
PF00294 PfkB, 1 hit
PRINTSiPR00989 ADENOKINASE
SUPFAMiSSF53613 SSF53613, 1 hit
PROSITEiView protein in PROSITE
PS00584 PFKB_KINASES_2, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P55263-1) [UniParc]FASTAAdd to basket
Also known as: Long

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.

« Hide

        10         20         30         40         50
MAAAEEEPKP KKLKVEAPQA LRENILFGMG NPLLDISAVV DKDFLDKYSL
60 70 80 90 100
KPNDQILAED KHKELFDELV KKFKVEYHAG GSTQNSIKVA QWMIQQPHKA
110 120 130 140 150
ATFFGCIGID KFGEILKRKA AEAHVDAHYY EQNEQPTGTC AACITGDNRS
160 170 180 190 200
LIANLAAANC YKKEKHLDLE KNWMLVEKAR VCYIAGFFLT VSPESVLKVA
210 220 230 240 250
HHASENNRIF TLNLSAPFIS QFYKESLMKV MPYVDILFGN ETEAATFARE
260 270 280 290 300
QGFETKDIKE IAKKTQALPK MNSKRQRIVI FTQGRDDTIM ATESEVTAFA
310 320 330 340 350
VLDQDQKEII DTNGAGDAFV GGFLSQLVSD KPLTECIRAG HYAASIIIRR
360
TGCTFPEKPD FH
Length:362
Mass (Da):40,545
Last modified:May 30, 2000 - v2
Checksum:i48AA4925865BFE70
GO
Isoform 2 (identifier: P55263-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MAAAEEEPKPKKLKVEAPQAL → MTSV

Show »
Length:345
Mass (Da):38,703
Checksum:i7DC20F364E63D944
GO
Isoform 3 (identifier: P55263-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     186-242: Missing.

Show »
Length:305
Mass (Da):34,084
Checksum:iDC7E0245659B0F06
GO
Isoform 4 (identifier: P55263-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: MAAAEEEPKP...ILAEDKHKEL → MTSVRENILFGMGNPLLDISAVVDKDFLDK

Note: No experimental confirmation available.
Show »
Length:327
Mass (Da):36,580
Checksum:iE5A9FDBDB77E7357
GO

Sequence cautioni

The sequence AAB01689 differs from that shown. Reason: Frameshift at position 17.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti98H → A AA sequence (PubMed:8577746).Curated1
Sequence conflicti133N → D in AAB01689 (PubMed:8917457).Curated1
Sequence conflicti171K → R in AAB01689 (PubMed:8917457).Curated1
Sequence conflicti190T → H in AAA97893 (PubMed:8577746).Curated1
Sequence conflicti219I → F in AAH03568 (PubMed:15489334).Curated1
Sequence conflicti273S → V AA sequence (PubMed:8577746).Curated1
Sequence conflicti289I → N AA sequence (PubMed:8577746).Curated1
Sequence conflicti307K → R in AAB01689 (PubMed:8917457).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06664030G → E in HMAKD; the mutant shows some residual activity. 1 PublicationCorresponds to variant dbSNP:rs397514454EnsemblClinVar.1
Natural variantiVAR_066641235D → A in HMAKD; the mutant shows some residual activity. 1 PublicationCorresponds to variant dbSNP:rs397514453EnsemblClinVar.1
Natural variantiVAR_066642318A → E in HMAKD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs397514452Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0046681 – 65MAAAE…KHKEL → MTSVRENILFGMGNPLLDIS AVVDKDFLDK in isoform 4. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_0467131 – 21MAAAE…APQAL → MTSV in isoform 2. 4 PublicationsAdd BLAST21
Alternative sequenceiVSP_043526186 – 242Missing in isoform 3. 1 PublicationAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50196 mRNA Translation: AAA97893.1
U33936 mRNA Translation: AAB01689.1 Frameshift.
U90338 mRNA Translation: AAB50234.1
U90339 mRNA Translation: AAB50235.1
AK290633 mRNA Translation: BAF83322.1
AK301590 mRNA Translation: BAH13519.1
AK302706 mRNA Translation: BAH13786.1
AC012046 Genomic DNA No translation available.
AC022026 Genomic DNA No translation available.
AC022540 Genomic DNA No translation available.
AC091699 Genomic DNA No translation available.
AL357037 Genomic DNA No translation available.
AL731576 Genomic DNA No translation available.
CH471083 Genomic DNA Translation: EAW54555.1
CH471083 Genomic DNA Translation: EAW54556.1
BC003568 mRNA Translation: AAH03568.1
CCDSiCCDS55716.1 [P55263-3]
CCDS55717.1 [P55263-4]
CCDS7343.1 [P55263-1]
CCDS7344.1 [P55263-2]
PIRiJC5363
JC5364
RefSeqiNP_001114.2, NM_001123.3 [P55263-2]
NP_001189378.1, NM_001202449.1 [P55263-4]
NP_001189379.1, NM_001202450.1 [P55263-3]
NP_006712.2, NM_006721.3 [P55263-1]
UniGeneiHs.656586

Genome annotation databases

EnsembliENST00000286621; ENSP00000286621; ENSG00000156110 [P55263-1]
ENST00000372734; ENSP00000361819; ENSG00000156110 [P55263-2]
ENST00000539909; ENSP00000443965; ENSG00000156110 [P55263-3]
ENST00000541550; ENSP00000438321; ENSG00000156110 [P55263-4]
GeneIDi132
KEGGihsa:132
UCSCiuc001jwi.4 human [P55263-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiADK_HUMAN
AccessioniPrimary (citable) accession number: P55263
Secondary accession number(s): B7Z783
, B7Z800, O00741, O00742, Q16710, Q5JQ10, Q5JQ11, Q9BTN2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 30, 2000
Last modified: June 20, 2018
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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