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
Myokinase

Gene names

Name:

AK1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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. Small ubiquitous enzyme involved in energy metabolism and nucleotide synthesis that is essential for maintenance and cell growth.
Catalytic activity	ATP + AMP = 2 ADP.
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
Polymorphism	This enzyme represents the most common of at least five alleles.
Involvement in disease	Defects in AK1 are the cause of hemolytic anemia due to adenylate kinase deficiency [MIM:612631].
Sequence similarities	Belongs to the adenylate kinase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	ATP metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylate kinase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MLL3	Q8NEZ4	1	EBI-1044943,EBI-1042997

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

15 – 23

9

ATP

Nucleotide binding

94 – 101

8

AMP By similarity

Sites

Binding site

39

1

AMP

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.1

Natural variations

Natural variant

40

1

G → R in hemolytic anemia. Ref.10

VAR_055337

Natural variant

64

1

G → R in hemolytic anemia. Ref.10

VAR_055338

Natural variant

123

1

E → Q. [dbSNP:rs8192462]

VAR_034046

Natural variant

128

1

R → W in hemolytic anemia. [dbSNP:rs28930974] Ref.2

VAR_004021

Natural variant

140

1

Missing in hemolytic anemia.

VAR_055339

Natural variant

164

1

Y → C in hemolytic anemia. Ref.9

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 – 6

6

Beta strand

10 – 15

6

Helix

21 – 32

12

Beta strand

35 – 38

4

Helix

39 – 47

9

Turn

48 – 50

3

Helix

52 – 61

10

Turn

62 – 64

3

Helix

69 – 83

15

Helix

84 – 86

3

Beta strand

90 – 94

5

Helix

99 – 108

10

Beta strand

113 – 119

7

Helix

122 – 135

14

Helix

143 – 156

14

Helix

158 – 165

8

Turn

166 – 168

3

Beta strand

170 – 174

5

Helix

179 – 191

13

Sequences

	Sequence		Length	Mass (Da)
	P00568-1 [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: 183954] [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: 2542324] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HEMOLYTIC ANEMIA 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: 15489334] [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]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB 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 SUBSTRATE ANALOG.
[9]	"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: 9432020] [Abstract] Cited for: VARIANT HEMOLYTIC ANEMIA CYS-164.
[10]	"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: 12649162] [Abstract] Cited for: VARIANTS HEMOLYTIC ANEMIA 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.

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. 2 interactions.

STRING

P00568.

2-D gel databases

OGP

P00568.

REPRODUCTION-2DPAGE

IPI00018342.

UCD-2DPAGE

P00568.

Proteomic databases

PRIDE

P00568.

Genome annotation databases

Ensembl

ENST00000373156; ENSP00000362249; ENSG00000106992; Homo sapiens. [Genome view]
ENST00000373176; ENSP00000362271; ENSG00000106992; Homo sapiens. [Genome view]

GeneID

203.

KEGG

hsa:203.

UCSC

uc004bsm.2. human.

Organism-specific databases

CTD

203.

GeneCards

GC09M130628.

H-InvDB

HIX0008412.

HGNC

HGNC:361. AK1.

HPA

CAB009893.
HPA006456.

MIM

103000. gene.
612631. phenotype.

Orphanet

86817. Hemolytic anemia due to adenylate kinase deficiency.

PharmGKB

PA134990616.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06455.

HOVERGEN

HBG108060.

OrthoDB

EOG96MF3T.

PhylomeDB

P00568.

Enzyme and pathway databases

BRENDA

2.7.4.3. 247.

Reactome

REACT_1698. Metabolism of nucleotides.

Gene expression databases

ArrayExpress

P00568.

Bgee

P00568.

CleanEx

HS_AK1.

Genevestigator

P00568.

GermOnline

ENSG00000106992. Homo sapiens.

Family and domain databases

InterPro

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

PANTHER

PTHR23359. Adenylate_kin. 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 Resources

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:	August 10, 2010
This is version 120 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.