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Protein

Adenylate kinase 2, mitochondrial

Gene

AK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis.UniRule annotation1 Publication

Catalytic activityi

ATP + AMP = 2 ADP.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei46AMPUniRule annotation1
Binding sitei51AMPUniRule annotation1
Binding sitei107AMPUniRule annotation1
Binding sitei138ATP1 Publication1
Binding sitei142ATPUniRule annotation1
Binding sitei175AMPUniRule annotation1 Publication1
Binding sitei186AMPUniRule annotation1
Binding sitei214ATP; via carbonyl oxygenUniRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi25 – 30ATPUniRule annotation1 Publication6
Nucleotide bindingi72 – 74AMPUniRule annotation3
Nucleotide bindingi100 – 103AMPUniRule annotation4
Nucleotide bindingi151 – 152ATPUniRule annotation1 Publication2

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00102-MONOMER.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate kinase 2, mitochondrialUniRule annotation (EC:2.7.4.3UniRule annotation)
Short name:
AK 2UniRule annotation
Alternative name(s):
ATP-AMP transphosphorylase 2UniRule annotation
ATP:AMP phosphotransferaseUniRule annotation
Adenylate monophosphate kinaseUniRule annotation
Cleaved into the following chain:
Adenylate kinase 2, mitochondrial, N-terminally processedUniRule annotation
Gene namesi
Name:AK2UniRule annotation
Synonyms:ADK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:362. AK2.

Subcellular locationi

  • Mitochondrion intermembrane space UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Reticular dysgenesis (RDYS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMost severe form of inborn severe combined immunodeficiencies (SCID) and is characterized by absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immune functions, leading to fatal septicemia within days after birth. In bone marrow of individuals with reticular dysgenesis, myeloid differentiation is blocked at the promyelocytic stage, whereas erythro- and megakaryocytic maturation is generally normal. In addition, affected newborns have bilateral sensorineural deafness. Defects may be due to its absence in leukocytes and inner ear, in which its absence can not be compensated by AK1.
See also OMIM:267500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054630103R → W in RDYS. 1 PublicationCorresponds to variant rs267606648dbSNPEnsembl.1
Natural variantiVAR_054631165D → G in RDYS. 1 PublicationCorresponds to variant rs267606643dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi204.
MalaCardsiAK2.
MIMi267500. phenotype.
OpenTargetsiENSG00000004455.
Orphaneti33355. Reticular dysgenesis.
PharmGKBiPA24656.

Chemistry databases

ChEMBLiCHEMBL4938.
DrugBankiDB00718. Adefovir Dipivoxil.
DB00300. Tenofovir.

Polymorphism and mutation databases

BioMutaiAK2.
DMDMi1708596.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004232121 – 239Adenylate kinase 2, mitochondrialAdd BLAST239
Initiator methionineiRemoved; alternateUniRule annotationCombined sources1 Publication
ChainiPRO_00001589172 – 239Adenylate kinase 2, mitochondrial, N-terminally processedAdd BLAST238

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei4PhosphoserineCombined sources1
Disulfide bondi42 ↔ 92UniRule annotation1 Publication
Modified residuei58PhosphoserineCombined sources1
Modified residuei62N6-succinyllysineBy similarity1
Modified residuei93N6-succinyllysineBy similarity1
Modified residuei133PhosphoserineCombined sources1
Modified residuei181N6-acetyllysineBy similarity1
Modified residuei195PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP54819.
MaxQBiP54819.
PaxDbiP54819.
PeptideAtlasiP54819.
PRIDEiP54819.

2D gel databases

OGPiP54819.
REPRODUCTION-2DPAGEIPI00218988.
UCD-2DPAGEP54819.

PTM databases

iPTMnetiP54819.
PhosphoSitePlusiP54819.
SwissPalmiP54819.

Expressioni

Tissue specificityi

Present in most tissues. Present at high level in heart, liver and kidney, and at low level in brain, skeletal muscle and skin. Present in thrombocytes but not in erythrocytes, which lack mitochondria. Present in all nucleated cell populations from blood, while AK1 is mostly absent. In spleen and lymph nodes, mononuclear cells lack AK1, whereas AK2 is readily detectable. These results indicate that leukocytes may be susceptible to defects caused by the lack of AK2, as they do not express AK1 in sufficient amounts to compensate for the AK2 functional deficits (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000004455.
CleanExiHS_AK2.
ExpressionAtlasiP54819. baseline and differential.
GenevisibleiP54819. HS.

Organism-specific databases

HPAiHPA018479.

Interactioni

Subunit structurei

Monomer.UniRule annotation

Protein-protein interaction databases

BioGridi106707. 38 interactors.
IntActiP54819. 12 interactors.
STRINGi9606.ENSP00000346921.

Chemistry databases

BindingDBiP54819.

Structurei

Secondary structure

1239
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 21Combined sources6
Helixi28 – 39Combined sources12
Beta strandi42 – 45Combined sources4
Helixi46 – 56Combined sources11
Helixi59 – 69Combined sources11
Helixi76 – 87Combined sources12
Helixi90 – 92Combined sources3
Beta strandi95 – 100Combined sources6
Helixi105 – 117Combined sources13
Beta strandi124 – 129Combined sources6
Helixi132 – 140Combined sources9
Turni146 – 148Combined sources3
Beta strandi151 – 153Combined sources3
Turni154 – 156Combined sources3
Beta strandi166 – 168Combined sources3
Helixi180 – 203Combined sources24
Beta strandi207 – 211Combined sources5
Helixi216 – 230Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C9YX-ray2.10A1-239[»]
ProteinModelPortaliP54819.
SMRiP54819.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54819.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni45 – 74NMPbindUniRule annotation1 PublicationAdd BLAST30
Regioni141 – 178LIDUniRule annotation1 PublicationAdd BLAST38

Domaini

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.UniRule annotation1 Publication

Sequence similaritiesi

Belongs to the adenylate kinase family. AK2 subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG3078. Eukaryota.
COG0563. LUCA.
GeneTreeiENSGT00830000128340.
HOVERGENiHBG000458.
InParanoidiP54819.
KOiK00939.
OMAiCPKGIRA.
OrthoDBiEOG091G06BH.
PhylomeDBiP54819.
TreeFamiTF300896.

Family and domain databases

CDDicd01428. ADK. 1 hit.
Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_00235. Adenylate_kinase_Adk. 1 hit.
MF_03168. Adenylate_kinase_AK2. 1 hit.
InterProiIPR006259. Adenyl_kin_sub.
IPR000850. Adenylat/UMP-CMP_kin.
IPR033690. Adenylat_kinase_CS.
IPR007862. Adenylate_kinase_lid-dom.
IPR028587. AK2.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR23359. PTHR23359. 1 hit.
PfamiPF05191. ADK_lid. 1 hit.
[Graphical view]
PRINTSiPR00094. ADENYLTKNASE.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01351. adk. 1 hit.
PROSITEiPS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

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

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P54819-1) [UniParc]FASTAAdd to basket
Also known as: AK2A, AK2isoA

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
MAPSVPAAEP EYPKGIRAVL LGPPGAGKGT QAPRLAENFC VCHLATGDML
60 70 80 90 100
RAMVASGSEL GKKLKATMDA GKLVSDEMVV ELIEKNLETP LCKNGFLLDG
110 120 130 140 150
FPRTVRQAEM LDDLMEKRKE KLDSVIEFSI PDSLLIRRIT GRLIHPKSGR
160 170 180 190 200
SYHEEFNPPK EPMKDDITGE PLIRRSDDNE KALKIRLQAY HTQTTPLIEY
210 220 230
YRKRGIHSAI DASQTPDVVF ASILAAFSKA TCKDLVMFI
Length:239
Mass (Da):26,478
Last modified:January 23, 2007 - v2
Checksum:i86FA94F9EE33629F
GO
Isoform 2 (identifier: P54819-2) [UniParc]FASTAAdd to basket
Also known as: AK2B, AK2isoB

The sequence of this isoform differs from the canonical sequence as follows:
     232-239: CKDLVMFI → S

Show »
Length:232
Mass (Da):25,615
Checksum:i64AEE1A97D81D401
GO
Isoform 3 (identifier: P54819-3) [UniParc]FASTAAdd to basket
Also known as: AK2C

The sequence of this isoform differs from the canonical sequence as follows:
     178-239: DNEKALKIRL...ATCKDLVMFI → IGQAKRSFLRLAKISFDVLIKKALA

Show »
Length:202
Mass (Da):22,265
Checksum:iAE7593A8ADBD00CF
GO
Isoform 4 (identifier: P54819-4) [UniParc]FASTAAdd to basket
Also known as: AK2D

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: Missing.
     177-178: DD → GL
     179-239: Missing.

Show »
Length:130
Mass (Da):14,709
Checksum:iC6FEB90B2BFF7845
GO
Isoform 5 (identifier: P54819-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     135-142: Missing.
     232-239: CKDLVMFI → S

Note: No experimental confirmation available.
Show »
Length:224
Mass (Da):24,648
Checksum:i1A769D71DDBB0B8A
GO
Isoform 6 (identifier: P54819-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: Missing.

Note: No experimental confirmation available.
Show »
Length:191
Mass (Da):21,636
Checksum:iA6535F6453550852
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054630103R → W in RDYS. 1 PublicationCorresponds to variant rs267606648dbSNPEnsembl.1
Natural variantiVAR_054631165D → G in RDYS. 1 PublicationCorresponds to variant rs267606643dbSNPEnsembl.1
Natural variantiVAR_050032209A → T.Corresponds to variant rs12116440dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0027921 – 48Missing in isoform 4 and isoform 6. 2 PublicationsAdd BLAST48
Alternative sequenceiVSP_036503135 – 142Missing in isoform 5. 1 Publication8
Alternative sequenceiVSP_002793177 – 178DD → GL in isoform 4. 1 Publication2
Alternative sequenceiVSP_002791178 – 239DNEKA…LVMFI → IGQAKRSFLRLAKISFDVLI KKALA in isoform 3. 1 PublicationAdd BLAST62
Alternative sequenceiVSP_002794179 – 239Missing in isoform 4. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_002790232 – 239CKDLVMFI → S in isoform 2 and isoform 5. 5 Publications8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39945 mRNA. Translation: AAC52061.1.
U84371 mRNA. Translation: AAB41790.1.
U54645 mRNA. Translation: AAC13881.1.
AB005621 mRNA. Translation: BAC16747.1.
AB005622 mRNA. Translation: BAC16748.1.
AY080899 mRNA. Translation: AAL87027.1.
AY080900 mRNA. Translation: AAL87028.1.
AK291676 mRNA. Translation: BAF84365.1.
AK295105 mRNA. Translation: BAG58139.1.
AK296863 mRNA. Translation: BAG59426.1.
AB451267 mRNA. Translation: BAG70081.1.
AB451394 mRNA. Translation: BAG70208.1.
AL020995 Genomic DNA. Translation: CAI19351.1.
AL020995 Genomic DNA. Translation: CAI19352.1.
CH471059 Genomic DNA. Translation: EAX07484.1.
CH471059 Genomic DNA. Translation: EAX07486.1.
BC009405 mRNA. Translation: AAH09405.1.
BC070127 mRNA. Translation: AAH70127.1.
BC090040 mRNA. Translation: AAH90040.1.
CCDSiCCDS373.1. [P54819-2]
CCDS374.1. [P54819-1]
PIRiG02248.
JC5893.
RefSeqiNP_001186128.1. NM_001199199.1. [P54819-5]
NP_001306068.1. NM_001319139.1.
NP_001306069.1. NM_001319140.1. [P54819-6]
NP_001616.1. NM_001625.3. [P54819-1]
NP_037543.1. NM_013411.4. [P54819-2]
UniGeneiHs.470907.

Genome annotation databases

EnsembliENST00000354858; ENSP00000346921; ENSG00000004455. [P54819-1]
ENST00000373449; ENSP00000362548; ENSG00000004455. [P54819-2]
GeneIDi204.
KEGGihsa:204.
UCSCiuc001bwo.3. human. [P54819-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39945 mRNA. Translation: AAC52061.1.
U84371 mRNA. Translation: AAB41790.1.
U54645 mRNA. Translation: AAC13881.1.
AB005621 mRNA. Translation: BAC16747.1.
AB005622 mRNA. Translation: BAC16748.1.
AY080899 mRNA. Translation: AAL87027.1.
AY080900 mRNA. Translation: AAL87028.1.
AK291676 mRNA. Translation: BAF84365.1.
AK295105 mRNA. Translation: BAG58139.1.
AK296863 mRNA. Translation: BAG59426.1.
AB451267 mRNA. Translation: BAG70081.1.
AB451394 mRNA. Translation: BAG70208.1.
AL020995 Genomic DNA. Translation: CAI19351.1.
AL020995 Genomic DNA. Translation: CAI19352.1.
CH471059 Genomic DNA. Translation: EAX07484.1.
CH471059 Genomic DNA. Translation: EAX07486.1.
BC009405 mRNA. Translation: AAH09405.1.
BC070127 mRNA. Translation: AAH70127.1.
BC090040 mRNA. Translation: AAH90040.1.
CCDSiCCDS373.1. [P54819-2]
CCDS374.1. [P54819-1]
PIRiG02248.
JC5893.
RefSeqiNP_001186128.1. NM_001199199.1. [P54819-5]
NP_001306068.1. NM_001319139.1.
NP_001306069.1. NM_001319140.1. [P54819-6]
NP_001616.1. NM_001625.3. [P54819-1]
NP_037543.1. NM_013411.4. [P54819-2]
UniGeneiHs.470907.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C9YX-ray2.10A1-239[»]
ProteinModelPortaliP54819.
SMRiP54819.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106707. 38 interactors.
IntActiP54819. 12 interactors.
STRINGi9606.ENSP00000346921.

Chemistry databases

BindingDBiP54819.
ChEMBLiCHEMBL4938.
DrugBankiDB00718. Adefovir Dipivoxil.
DB00300. Tenofovir.

PTM databases

iPTMnetiP54819.
PhosphoSitePlusiP54819.
SwissPalmiP54819.

Polymorphism and mutation databases

BioMutaiAK2.
DMDMi1708596.

2D gel databases

OGPiP54819.
REPRODUCTION-2DPAGEIPI00218988.
UCD-2DPAGEP54819.

Proteomic databases

EPDiP54819.
MaxQBiP54819.
PaxDbiP54819.
PeptideAtlasiP54819.
PRIDEiP54819.

Protocols and materials databases

DNASUi204.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000354858; ENSP00000346921; ENSG00000004455. [P54819-1]
ENST00000373449; ENSP00000362548; ENSG00000004455. [P54819-2]
GeneIDi204.
KEGGihsa:204.
UCSCiuc001bwo.3. human. [P54819-1]

Organism-specific databases

CTDi204.
DisGeNETi204.
GeneCardsiAK2.
HGNCiHGNC:362. AK2.
HPAiHPA018479.
MalaCardsiAK2.
MIMi103020. gene.
267500. phenotype.
neXtProtiNX_P54819.
OpenTargetsiENSG00000004455.
Orphaneti33355. Reticular dysgenesis.
PharmGKBiPA24656.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3078. Eukaryota.
COG0563. LUCA.
GeneTreeiENSGT00830000128340.
HOVERGENiHBG000458.
InParanoidiP54819.
KOiK00939.
OMAiCPKGIRA.
OrthoDBiEOG091G06BH.
PhylomeDBiP54819.
TreeFamiTF300896.

Enzyme and pathway databases

BioCyciZFISH:HS00102-MONOMER.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.

Miscellaneous databases

EvolutionaryTraceiP54819.
GeneWikiiAK2.
GenomeRNAii204.
PROiP54819.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000004455.
CleanExiHS_AK2.
ExpressionAtlasiP54819. baseline and differential.
GenevisibleiP54819. HS.

Family and domain databases

CDDicd01428. ADK. 1 hit.
Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_00235. Adenylate_kinase_Adk. 1 hit.
MF_03168. Adenylate_kinase_AK2. 1 hit.
InterProiIPR006259. Adenyl_kin_sub.
IPR000850. Adenylat/UMP-CMP_kin.
IPR033690. Adenylat_kinase_CS.
IPR007862. Adenylate_kinase_lid-dom.
IPR028587. AK2.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR23359. PTHR23359. 1 hit.
PfamiPF05191. ADK_lid. 1 hit.
[Graphical view]
PRINTSiPR00094. ADENYLTKNASE.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01351. adk. 1 hit.
PROSITEiPS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKAD2_HUMAN
AccessioniPrimary (citable) accession number: P54819
Secondary accession number(s): A8K6L1
, B4DHH7, B4DL64, Q16856, Q5EB54, Q5TIF7, Q8TCY2, Q8TCY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 175 of the entry and version 2 of the sequence. [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 1
    Human chromosome 1: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.