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P00568 (KAD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adenylate kinase isoenzyme 1

Short name=AK 1
EC=2.7.4.3
EC=2.7.4.6
Alternative name(s):
ATP-AMP transphosphorylase 1
ATP:AMP phosphotransferase
Adenylate monophosphate kinase
Myokinase
Gene names
Name:AK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length194 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Ref.8

Catalytic activity

ATP + AMP = 2 ADP. Ref.8

ATP + nucleoside diphosphate = ADP + nucleoside triphosphate. Ref.8

Subunit structure

Monomer.

Subcellular location

Cytoplasm HAMAP-Rule MF_03171.

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. HAMAP-Rule MF_03171

Polymorphism

This enzyme represents the most common of at least five alleles. HAMAP-Rule MF_03171

Involvement in disease

Hemolytic anemia due to adenylate kinase deficiency (HAAKD) [MIM:612631]: A disease characterized by hemolytic anemia and undetectable erythrocyte adenylate kinase activity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.11 Ref.12

Sequence similarities

Belongs to the adenylate kinase family. AK1 subfamily.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Hereditary hemolytic anemia
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processATP metabolic process

Inferred from electronic annotation. Source: InterPro

cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

nucleobase-containing small molecule interconversion

Traceable author statement. Source: Reactome

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

nucleoside diphosphate phosphorylation

Inferred from direct assay Ref.8. Source: UniProtKB

nucleoside triphosphate biosynthetic process

Inferred from direct assay Ref.8. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

outer dense fiber

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: Ensembl

sperm flagellum

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

adenylate kinase activity

Traceable author statement Ref.2. Source: ProtInc

nucleoside diphosphate kinase activity

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 194194Adenylate kinase isoenzyme 1 HAMAP-Rule MF_03171
PRO_0000158910

Regions

Nucleotide binding18 – 236ATP HAMAP-Rule MF_03171
Nucleotide binding65 – 673AMP HAMAP-Rule MF_03171
Nucleotide binding94 – 974AMP HAMAP-Rule MF_03171
Region38 – 6730NMPbind HAMAP-Rule MF_03171
Region131 – 14111LID HAMAP-Rule MF_03171

Sites

Binding site391AMP
Binding site441AMP
Binding site1011AMP
Binding site1321ATP
Binding site1381AMP
Binding site1491AMP
Binding site1771ATP; via carbonyl oxygen

Amino acid modifications

Modified residue11N-acetylmethionine HAMAP-Rule MF_03171

Natural variations

Natural variant401G → R in HAAKD. Ref.12
VAR_055337
Natural variant641G → R in HAAKD. Ref.12
VAR_055338
Natural variant1231E → Q.
Corresponds to variant rs8192462 [ dbSNP | Ensembl ].
VAR_034046
Natural variant1281R → W in HAAKD. Ref.2
Corresponds to variant rs28930974 [ dbSNP | Ensembl ].
VAR_004021
Natural variant1401Missing in HAAKD. Ref.12
VAR_055339
Natural variant1641Y → C in HAAKD. Ref.11
VAR_055340

Experimental info

Sequence conflict91K → N in AAH01116. Ref.5
Sequence conflict1271Q → R AA sequence Ref.1
Sequence conflict1811S → E AA sequence Ref.1

Secondary structure

.................................. 194
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00568 [UniParc].

Last modified April 16, 2002. Version 3.
Checksum: 95EC5AAA92D1F00F

FASTA19421,635
        10         20         30         40         50         60 
MEEKLKKTKI IFVVGGPGSG KGTQCEKIVQ KYGYTHLSTG DLLRSEVSSG SARGKKLSEI 

        70         80         90        100        110        120 
MEKGQLVPLE TVLDMLRDAM VAKVNTSKGF LIDGYPREVQ QGEEFERRIG QPTLLLYVDA 

       130        140        150        160        170        180 
GPETMTQRLL KRGETSGRVD DNEETIKKRL ETYYKATEPV IAFYEKRGIV RKVNAEGSVD 

       190 
SVFSQVCTHL DALK 

« Hide

References

« Hide 'large scale' references
[1]"Primary and tertiary structure of the principal human adenylate kinase."
von Zabern I., Wittmann-Liebold B., Untucht-Grau R., Schirmer R.H., Pai E.F.
Eur. J. Biochem. 68:281-290(1976) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE.
Tissue: Skeletal muscle.
[2]"Human adenylate kinase deficiency associated with hemolytic anemia. A single base substitution affecting solubility and catalytic activity of the cytosolic adenylate kinase."
Matsuura S., Igarashi M., Tanizawa Y., Yamada M., Kishi F., Kajii T., Fujii H., Miwa S., Sakurai M., Nakazawa A.
J. Biol. Chem. 264:10148-10155(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HAAKD TRP-128.
[3]Noma T.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Retina.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon.
[6]Lubec G., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 10-21; 32-44; 64-77; 89-97; 108-128; 156-166 AND 172-194, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Fetal brain cortex.
[7]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"The human adenylate kinase 9 is a nucleoside mono- and diphosphate kinase."
Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.
Int. J. Biochem. Cell Biol. 45:925-931(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[9]"Crystal structure of human AK1A in complex with AP5A."
Structural genomics consortium (SGC)
Submitted (MAR-2007) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH BI-SUBSTRATE ANALOG AP5A.
[10]"Structure of adenylate kinase 1 in complex with P1, P4-di(adenosine)tetraphosphate."
Structural genomics consortium (SGC)
Submitted (DEC-2005) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) IN COMPLEX WITH BI-SUBSTRATE ANALOG AP4A.
[11]"Severe erythrocyte adenylate kinase deficiency due to homozygous A-->G substitution at codon 164 of human AK1 gene associated with chronic haemolytic anaemia."
Qualtieri A., Pedace V., Bisconte M.G., Bria M., Gulino B., Andreoli V., Brancati C.
Br. J. Haematol. 99:770-776(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HAAKD CYS-164.
[12]"Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G>A, 190G>A, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia."
Corrons J.-L., Garcia E., Tusell J.J., Varughese K.I., West C., Beutler E.
Blood 102:353-356(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HAAKD ARG-40; ARG-64 AND ASP-140 DEL.
+Additional computationally mapped references.

Web resources

Wikipedia

Adenylate kinase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04809 Genomic DNA. Translation: AAA51686.1.
AB021871 mRNA. Translation: BAA78534.1.
BT019580 mRNA. Translation: AAV38387.1.
BC001116 mRNA. Translation: AAH01116.1.
PIRKIHUA. A33508.
RefSeqNP_000467.1. NM_000476.2.
UniGeneHs.175473.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z83X-ray1.90A/B/C1-193[»]
2C95X-ray1.71A/B1-193[»]
ProteinModelPortalP00568.
SMRP00568. Positions 1-193.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106706. 9 interactions.
IntActP00568. 1 interaction.
STRING9606.ENSP00000362249.

PTM databases

PhosphoSiteP00568.

Polymorphism databases

DMDM20178288.

2D gel databases

OGPP00568.
REPRODUCTION-2DPAGEIPI00018342.
UCD-2DPAGEP00568.

Proteomic databases

PaxDbP00568.
PRIDEP00568.

Protocols and materials databases

DNASU203.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373156; ENSP00000362249; ENSG00000106992.
ENST00000373176; ENSP00000362271; ENSG00000106992.
GeneID203.
KEGGhsa:203.
UCSCuc004bsm.4. human.

Organism-specific databases

CTD203.
GeneCardsGC09M130628.
HGNCHGNC:361. AK1.
HPACAB009893.
HPA006456.
MIM103000. gene.
612631. phenotype.
neXtProtNX_P00568.
Orphanet86817. Hemolytic anemia due to adenylate kinase deficiency.
PharmGKBPA24655.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0563.
HOGENOMHOG000238771.
HOVERGENHBG108060.
KOK00939.
OrthoDBEOG7060S3.
PhylomeDBP00568.
TreeFamTF354283.

Enzyme and pathway databases

BRENDA2.7.4.3. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP00568.

Gene expression databases

ArrayExpressP00568.
BgeeP00568.
CleanExHS_AK1.
GenevestigatorP00568.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
HAMAPMF_00235. Adenylate_kinase_Adk.
MF_03171. Adenylate_kinase_AK1.
InterProIPR000850. Adenylat/UMP-CMP_kin.
IPR028582. AK1.
IPR006267. AK1/5.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR23359. PTHR23359. 1 hit.
PRINTSPR00094. ADENYLTKNASE.
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR01360. aden_kin_iso1. 1 hit.
PROSITEPS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00568.
GenomeRNAi203.
NextBio808.
PROP00568.
SOURCESearch...

Entry information

Entry nameKAD1_HUMAN
AccessionPrimary (citable) accession number: P00568
Secondary accession number(s): Q9BVK9, Q9UQC7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 16, 2002
Last modified: April 16, 2014
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM