P55263 (ADK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenosine kinase
Short name=AK
EC=2.7.1.20

Alternative name(s):
Adenosine 5'-phosphotransferase

Gene names

Name:

ADK

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	362 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	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 activity	ATP + adenosine = ADP + AMP.
Cofactor	Binds 3 magnesium ions per subunit.
Pathway	Purine metabolism; AMP biosynthesis via salvage pathway; AMP from adenosine: step 1/1.
Subunit structure	Monomer.
Tissue specificity	Widely expressed. Highest level in placenta, liver, muscle and kidney.
Involvement in disease	Defects in ADK are the cause of hypermethioninemia due to adenosine kinase deficiency (HMAKD) [MIM:614300]. A 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. Ref.11
Sequence similarities	Belongs to the carbohydrate kinase pfkB family.
Sequence caution	The sequence AAB01689.1 differs from that shown. Reason: Frameshift at position 17.

Ontologies

Keywords
Biological process	Purine salvage
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	purine base metabolic process Traceable author statement. Source: Reactome purine ribonucleoside salvage Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenosine kinase activity Inferred from experiment. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphotransferase activity, alcohol group as acceptor Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P55263-1)

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.

Isoform Short (identifier: P55263-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 362

361

Adenosine kinase

PRO_0000080053

Sites

Active site

317

1

Metal binding

49

1

Magnesium 1

Metal binding

147

1

Magnesium 2

Metal binding

148

1

Magnesium 2

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.7

Modified residue

77

1

Phosphotyrosine Ref.10

Natural variations

Alternative sequence

1 – 21

21

MAAAE…APQAL → MTSV in isoform Short.

VSP_004668

Natural variant

30

1

G → E in HMAKD; the mutant shows some residual activity. Ref.11

VAR_066640

Natural variant

235

1

D → A in HMAKD; the mutant shows some residual activity. Ref.11

VAR_066641

Natural variant

318

1

A → E in HMAKD; complete loss of activity. Ref.11

VAR_066642

Experimental info

Sequence conflict

98

1

H → A AA sequence Ref.1

Sequence conflict

133

1

N → D in AAB01689. Ref.2

Sequence conflict

171

1

K → R in AAB01689. Ref.2

Sequence conflict

190

1

T → H in AAA97893. Ref.1

Sequence conflict

219

1

I → F in AAH03568. Ref.6

Sequence conflict

273

1

S → V AA sequence Ref.1

Sequence conflict

289

1

I → N AA sequence Ref.1

Sequence conflict

307

1

K → R in AAB01689. Ref.2

Secondary structure

1

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362

Helix Strand Turn

Details...

Beta strand

26 – 29

4

Beta strand

33 – 39

7

Helix

42 – 47

6

Beta strand

52 – 57

6

Helix

60 – 62

3

Helix

63 – 72

10

Beta strand

76 – 80

5

Helix

82 – 94

13

Beta strand

101 – 110

10

Helix

111 – 122

12

Beta strand

126 – 135

10

Beta strand

139 – 145

7

Beta strand

148 – 154

7

Helix

156 – 160

5

Helix

163 – 165

3

Turn

166 – 168

3

Helix

170 – 178

9

Beta strand

180 – 185

6

Helix

186 – 190

5

Helix

193 – 205

13

Beta strand

209 – 213

5

Helix

217 – 222

6

Helix

224 – 230

7

Helix

231 – 233

3

Beta strand

235 – 240

6

Helix

241 – 250

10

Helix

258 – 266

9

Beta strand

278 – 283

6

Beta strand

286 – 291

6

Beta strand

296 – 299

4

Helix

312 – 327

16

Turn

328 – 330

3

Helix

333 – 347

15

Beta strand

350 – 353

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 48AA4925865BFE70	FASTA	362	40,545
	10 20 30 40 50 60 MAAAEEEPKP KKLKVEAPQA LRENILFGMG NPLLDISAVV DKDFLDKYSL KPNDQILAED 70 80 90 100 110 120 KHKELFDELV KKFKVEYHAG GSTQNSIKVA QWMIQQPHKA ATFFGCIGID KFGEILKRKA 130 140 150 160 170 180 AEAHVDAHYY EQNEQPTGTC AACITGDNRS LIANLAAANC YKKEKHLDLE KNWMLVEKAR 190 200 210 220 230 240 VCYIAGFFLT VSPESVLKVA HHASENNRIF TLNLSAPFIS QFYKESLMKV MPYVDILFGN 250 260 270 280 290 300 ETEAATFARE QGFETKDIKE IAKKTQALPK MNSKRQRIVI FTQGRDDTIM ATESEVTAFA 310 320 330 340 350 360 VLDQDQKEII DTNGAGDAFV GGFLSQLVSD KPLTECIRAG HYAASIIIRR TGCTFPEKPD FH
	Isoform Short [UniParc]. Checksum: 7DC20F364E63D944	FASTA	345	38,703
	10 20 30 40 50 60 MTSVRENILF GMGNPLLDIS AVVDKDFLDK YSLKPNDQIL AEDKHKELFD ELVKKFKVEY 70 80 90 100 110 120 HAGGSTQNSI KVAQWMIQQP HKAATFFGCI GIDKFGEILK RKAAEAHVDA HYYEQNEQPT 130 140 150 160 170 180 GTCAACITGD NRSLIANLAA ANCYKKEKHL DLEKNWMLVE KARVCYIAGF FLTVSPESVL 190 200 210 220 230 240 KVAHHASENN RIFTLNLSAP FISQFYKESL MKVMPYVDIL FGNETEAATF AREQGFETKD 250 260 270 280 290 300 IKEIAKKTQA LPKMNSKRQR IVIFTQGRDD TIMATESEVT AFAVLDQDQK EIIDTNGAGD 310 320 330 340 AFVGGFLSQL VSDKPLTECI RAGHYAASII IRRTGCTFPE KPDFH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human adenosine kinase cDNA: sequence similarity to microbial ribokinases and fructokinases." Spychala J., Datta N.S., Takabayashi K., Datta M., Fox I.H., Gribbin T., Mitchell B.S. Proc. Natl. Acad. Sci. U.S.A. 93:1232-1237(1996) [PubMed: 8577746] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 94-133; 175-200 AND 272-289. Tissue: Liver.
[2]	"Cloning and characterization of cDNA for adenosine kinase from mammalian (Chinese hamster, mouse, human and rat) species. High frequency mutants of Chinese hamster ovary cells involve structural alterations in the gene." Singh B., Hao W., Wu Z.-C., Eigl B., Gupta R.S. Eur. J. Biochem. 241:564-571(1996) [PubMed: 8917457] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[3]	"Cloning and expression of the adenosine kinase gene from rat and human tissues." McNally T., Helfrich R.J., Cowart M., Dorwin S.A., Meuth J.L., Idler K.B., Klute K.A., Simmer R.L., Kowaluk E.A., Halbert D.N. Biochem. Biophys. Res. Commun. 231:645-650(1997) [PubMed: 9070863] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM SHORT). Tissue: Skin.
[7]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"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].
[9]	"Structure of human adenosine kinase at 1.5-A resolution." Mathews I.I., Erion M.D., Ealick S.E. Biochemistry 37:15607-15620(1998) [PubMed: 9843365] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF SHORT ISOFORM.
[10]	"Identification of the phosphotyrosine proteome from thrombin activated platelets." Maguire P.B., Wynne K.J., Harney D.F., O'Donoghue N.M., Stephens G., Fitzgerald D.J. Proteomics 2:642-648(2002) [PubMed: 12112843] [Abstract] Cited for: PHOSPHORYLATION AT TYR-77.
[11]	"Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function." Bjursell M.K., Blom H.J., Cayuela J.A., Engvall M.L., Lesko N., Balasubramaniam S., Brandberg G., Halldin M., Falkenberg M., Jakobs C., Smith D., Struys E., von Dobeln U., Gustafsson C.M., Lundeberg J., Wedell A. Am. J. Hum. Genet. 89:507-515(2011) [PubMed: 21963049] [Abstract] Cited for: VARIANTS HMAKD GLU-30; ALA-235 AND GLU-318, CHARACTERIZATION OF VARIANTS HMAKD GLU-30; ALA-235 AND GLU-318.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U50196 mRNA. Translation: AAA97893.1.
U33936 mRNA. Translation: AAB01689.1. Frameshift.
U90338 mRNA. Translation: AAB50234.1.
U90339 mRNA. Translation: AAB50235.1.
AL357037 , AC012046, AC022026, AC022540, AC091699, AL731576 Genomic DNA. Translation: CAH73202.1.
AL731576 , AC012046, AC022026, AC022540, AC091699, AL357037 Genomic DNA. Translation: CAI39671.1.
CH471083 Genomic DNA. Translation: EAW54556.1.
BC003568 mRNA. Translation: AAH03568.1.

IPI

IPI00234368.
IPI00290279.

PIR

JC5363.
JC5364.

RefSeq

NP_001114.2. NM_001123.3.
NP_001189378.1. NM_001202449.1.
NP_006712.2. NM_006721.3.

UniGene

Hs.656586.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BX4	X-ray	1.50	A	22-362	[»]
2I6A	X-ray	2.20	A/B/C/D	22-362	[»]
2I6B	X-ray	2.30	A/B	22-362	[»]

ProteinModelPortal

P55263.

SMR

P55263. Positions 20-362.

ModBase

Search...

Protein-protein interaction databases

IntAct

P55263. 3 interactions.

STRING

P55263.

PTM databases

PhosphoSite

P55263.

Polymorphism databases

DMDM

6840802.

2D gel databases

REPRODUCTION-2DPAGE

IPI00234368.

Proteomic databases

PRIDE

P55263.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000286621; ENSP00000286621; ENSG00000156110.

GeneID

132.

KEGG

hsa:132.

UCSC

uc001jwi.1. human.

Organism-specific databases

CTD

132.

GeneCards

GC10P075910.

H-InvDB

HIX0021617.

HGNC

HGNC:257. ADK.

HPA

HPA038409.

MIM

102750. gene.
614300. phenotype.

neXtProt

NX_P55263.

PharmGKB

PA24579.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09330.

HOGENOM

HBG314716.

HOVERGEN

HBG002367.

InParanoid

P55263.

OMA

AQWMIQQ.

OrthoDB

EOG4S4PGM.

PhylomeDB

P55263.

Enzyme and pathway databases

BioCyc

MetaCyc:HS08097-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P55263.

Bgee

P55263.

CleanEx

HS_ADK.

Genevestigator

P55263.

GermOnline

ENSG00000156110. Homo sapiens.

Family and domain databases

InterPro

IPR001805. Adenokinase.
IPR011611. Carb/pur_kinase.
IPR002173. Carboh/pur_kinase_PfkB_CS.
[Graphical view]

KO

K00856.

PANTHER

PTHR10584:SF24. Adenokinase. 1 hit.

Pfam

PF00294. PfkB. 1 hit.
[Graphical view]

PRINTS

PR00989. ADENOKINASE.

PROSITE

PS00583. PFKB_KINASES_1. False negative.
PS00584. PFKB_KINASES_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00640. Adenosine.
DB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.
DB00061. Pegademase bovine.
DB00811. Ribavirin.

NextBio

527.

SOURCE

Search...

Entry information

Entry name

ADK_HUMAN

Accession

Primary (citable) accession number: P55263
Secondary accession number(s): O00741 , O00742, Q16710, Q5JQ11, Q9BTN2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 30, 2000
Last modified:	January 25, 2012
This is version 130 of the entry and version 2 of the sequence. [Complete 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.