P00568 (KAD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenylate kinase isoenzyme 1
Short name=AK 1
EC=2.7.4.3

Alternative name(s):
ATP-AMP transphosphorylase 1
ATP:AMP phosphotransferase
Adenylate monophosphate kinase
Myokinase

Gene names

Name:

AK1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	194 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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.
Catalytic activity	ATP + AMP = 2 ADP.
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
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.
Polymorphism	This enzyme represents the most common of at least five alleles.
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.
Sequence similarities	Belongs to the adenylate kinase family. AK1 subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary hemolytic anemia
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ATP metabolic process Inferred from electronic annotation. Source: InterPro cell cycle arrest Inferred from electronic annotation. Source: Compara nucleobase-containing small molecule interconversion Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome outer dense fiber Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: Compara sperm flagellum Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylate kinase activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 194

194

Adenylate kinase isoenzyme 1

PRO_0000158910

Regions

Nucleotide binding

18 – 23

6

ATP

Nucleotide binding

65 – 67

3

AMP

Nucleotide binding

94 – 97

4

AMP

Region

38 – 67

30

NMPbind

Region

131 – 141

11

LID

Sites

Binding site

39

1

AMP

Binding site

44

1

AMP

Binding site

101

1

AMP

Binding site

132

1

ATP

Binding site

138

1

AMP

Binding site

149

1

AMP

Binding site

177

1

ATP; via carbonyl oxygen

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.1

Natural variations

Natural variant

40

1

G → R in HAAKD.

VAR_055337

Natural variant

64

1

G → R in HAAKD.

VAR_055338

Natural variant

123

1

E → Q.
Corresponds to variant rs8192462 [ dbSNP | Ensembl ].

VAR_034046

Natural variant

128

1

R → W in HAAKD.
Corresponds to variant rs28930974 [ dbSNP | Ensembl ].

VAR_004021

Natural variant

140

1

Missing in HAAKD.

VAR_055339

Natural variant

164

1

Y → C in HAAKD.

VAR_055340

Experimental info

Sequence conflict

9

1

K → N in AAH01116. Ref.5

Sequence conflict

127

1

Q → R AA sequence Ref.1

Sequence conflict

181

1

S → E AA sequence Ref.1

Secondary structure

1

.

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194

Helix Strand Turn

Details...

Helix

1 – 5

5

Beta strand

10 – 15

6

Helix

21 – 32

12

Beta strand

35 – 38

4

Helix

39 – 48

10

Helix

52 – 62

11

Helix

69 – 83

15

Turn

84 – 86

3

Beta strand

90 – 94

5

Helix

99 – 108

10

Beta strand

113 – 119

7

Helix

122 – 133

12

Beta strand

135 – 137

3

Helix

139 – 141

3

Helix

143 – 156

14

Helix

158 – 167

10

Beta strand

170 – 174

5

Helix

179 – 193

15

Sequences

	Sequence		Length	Mass (Da)
	P00568 [UniParc]. Last modified April 16, 2002. Version 3. Checksum: 95EC5AAA92D1F00F	FASTA	194	21,635
	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

References

	« Hide 'large scale' referencesShow '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, 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]	"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.
[9]	"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.
[10]	"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.
[11]	"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.

IPI

IPI00018342.

PIR

KIHUA. A33508.

RefSeq

NP_000467.1. NM_000476.2.

UniGene

Hs.175473.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z83	X-ray	1.90	A/B/C	1-193	[»]
2C95	X-ray	1.71	A/B	1-193	[»]

ProteinModelPortal

P00568.

ModBase

Search...

Protein-protein interaction databases

IntAct

P00568. 1 interaction.

STRING

9606.ENSP00000362249.

PTM databases

PhosphoSite

P00568.

Polymorphism databases

DMDM

20178288.

2D gel databases

OGP

P00568.

REPRODUCTION-2DPAGE

IPI00018342.

UCD-2DPAGE

P00568.

Proteomic databases

PaxDb

P00568.

PRIDE

P00568.

Protocols and materials databases

DNASU

203.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373156; ENSP00000362249; ENSG00000106992.
ENST00000373176; ENSP00000362271; ENSG00000106992.

GeneID

203.

KEGG

hsa:203.

UCSC

uc004bsm.4. human.

Organism-specific databases

CTD

203.

GeneCards

GC09M130628.

HGNC

HGNC:361. AK1.

HPA

CAB009893.
HPA006456.

MIM

103000. gene.
612631. phenotype.

neXtProt

NX_P00568.

Orphanet

86817. Hemolytic anemia due to adenylate kinase deficiency.

PharmGKB

PA24655.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0563.

HOGENOM

HOG000238771.

HOVERGEN

HBG108060.

KO

K00939.

OrthoDB

EOG402WT6.

PhylomeDB

P00568.

Enzyme and pathway databases

BRENDA

2.7.4.3. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P00568.

Gene expression databases

ArrayExpress

P00568.

Bgee

P00568.

CleanEx

HS_AK1.

Genevestigator

P00568.

GermOnline

ENSG00000106992. Homo sapiens.

Family and domain databases

HAMAP

MF_00235. Adenylate_kinase_Adk.
MF_03171. Adenylate_kinase_AK1.

InterPro

IPR000850. Adenylate_kin.
IPR006267. Adenylate_kin1.
[Graphical view]

PANTHER

PTHR23359. PTHR23359. 1 hit.

Pfam

PF00406. ADK. 1 hit.
[Graphical view]

PRINTS

PR00094. ADENYLTKNASE.

TIGRFAMs

TIGR01360. aden_kin_iso1. 1 hit.

PROSITE

PS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL4925.

EvolutionaryTrace

P00568.

GenomeRNAi

203.

NextBio

808.

SOURCE

Search...

Entry information

Entry name

KAD1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 147 of the entry and version 3 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.