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Protein

Adenylate kinase 4, mitochondrial

Gene

AK4

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

Functioni

Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor. Also displays broad nucleoside diphosphate kinase activity.UniRule annotation3 Publications

Catalytic activityi

NTP + AMP = NDP + ADP.UniRule annotation
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.UniRule annotation

Kineticsi

  1. KM=5.3 µM for AMP with ATP as phosphate donor1 Publication
  2. KM=1.4 µM for AMP with GTP as phosphate donor1 Publication
  3. KM=507 µM for dAMP with ATP as phosphate donor1 Publication
  1. Vmax=90 pmol/min/µg enzyme with AMP as substrate and ATP as phosphate donor1 Publication
  2. Vmax=80 pmol/min/µg enzyme with AMP as substrate and GTP as phosphate donor1 Publication
  3. Vmax=88 pmol/min/µg enzyme with dAMP as substrate and ATP as phosphate donor1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei36AMPUniRule annotation1 Publication1
Binding sitei41AMPUniRule annotation1
Binding sitei96AMPUniRule annotation1
Binding sitei126NTPUniRule annotation1 Publication1
Binding sitei170AMPUniRule annotation1 Publication1
Binding sitei199NTP; via carbonyl oxygenUniRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 20NTPUniRule annotation1 Publication6
Nucleotide bindingi62 – 64AMPUniRule annotation1 Publication3
Nucleotide bindingi89 – 92AMPUniRule annotation1 Publication4
Nucleotide bindingi135 – 136NTPUniRule annotation2

GO - Molecular functioni

  • adenylate kinase activity Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • GTP binding Source: UniProtKB-KW
  • nucleoside diphosphate kinase activity Source: UniProtKB
  • nucleoside phosphate kinase activity Source: Reactome
  • nucleoside triphosphate adenylate kinase activity Source: BHF-UCL

GO - Biological processi

  • ADP biosynthetic process Source: UniProtKB-HAMAP
  • AMP metabolic process Source: BHF-UCL
  • ATP metabolic process Source: BHF-UCL
  • brain development Source: Ensembl
  • GTP metabolic process Source: BHF-UCL
  • liver development Source: Ensembl
  • nucleobase-containing small molecule interconversion Source: Reactome
  • nucleoside diphosphate phosphorylation Source: UniProtKB
  • nucleoside triphosphate biosynthetic process Source: UniProtKB
  • response to drug Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS10823-MONOMER.
BRENDAi2.7.4.3. 2681.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate kinase 4, mitochondrialUniRule annotation (EC:2.7.4.10UniRule annotation, EC:2.7.4.6UniRule annotation)
Short name:
AK 4UniRule annotation
Alternative name(s):
Adenylate kinase 3-likeUniRule annotation
GTP:AMP phosphotransferase AK4UniRule annotation
Gene namesi
Name:AK4UniRule annotation
Synonyms:AK3, AK3L1UniRule annotation
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:363. AK4.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrial matrix Source: BHF-UCL
  • mitochondrion Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi4K → G: Abolishes mitochondrial import; when associated with G-7. 1 Publication1
Mutagenesisi7R → G: Abolishes mitochondrial import; when associated with G-4. 1 Publication1

Organism-specific databases

DisGeNETi205.
OpenTargetsiENSG00000162433.
PharmGKBiPA165750325.

Chemistry databases

ChEMBLiCHEMBL4926.
DrugBankiDB00718. Adefovir Dipivoxil.
DB00300. Tenofovir.

Polymorphism and mutation databases

BioMutaiAK4.
DMDMi125157.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001589261 – 223Adenylate kinase 4, mitochondrialAdd BLAST223

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei60N6-succinyllysineBy similarity1
Modified residuei175N6-acetyllysineBy similarity1
Modified residuei179N6-acetyllysine; alternateBy similarity1
Modified residuei179N6-succinyllysine; alternateBy similarity1
Modified residuei186N6-acetyllysine; alternateBy similarity1
Modified residuei186N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP27144.
MaxQBiP27144.
PaxDbiP27144.
PeptideAtlasiP27144.
PRIDEiP27144.
TopDownProteomicsiP27144.

2D gel databases

UCD-2DPAGEP27144.

PTM databases

iPTMnetiP27144.
PhosphoSitePlusiP27144.

Expressioni

Tissue specificityi

Highly expressed in kidney, moderately expressed in heart and liver and weakly expressed in brain.1 Publication

Gene expression databases

BgeeiENSG00000162433.
CleanExiHS_AK3.
HS_AK3L1.
ExpressionAtlasiP27144. baseline and differential.
GenevisibleiP27144. HS.

Organism-specific databases

HPAiHPA042753.
HPA049461.

Interactioni

Subunit structurei

Monomer.UniRule annotation1 Publication

Protein-protein interaction databases

BioGridi106708. 12 interactors.
IntActiP27144. 4 interactors.
STRINGi9606.ENSP00000322175.

Chemistry databases

BindingDBiP27144.

Structurei

Secondary structure

1223
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 11Combined sources5
Helixi18 – 29Combined sources12
Beta strandi32 – 34Combined sources3
Helixi36 – 45Combined sources10
Helixi49 – 59Combined sources11
Helixi66 – 78Combined sources13
Turni79 – 82Combined sources4
Beta strandi85 – 89Combined sources5
Helixi94 – 101Combined sources8
Beta strandi108 – 113Combined sources6
Helixi116 – 124Combined sources9
Beta strandi126 – 129Combined sources4
Turni130 – 133Combined sources4
Beta strandi134 – 137Combined sources4
Turni138 – 140Combined sources3
Turni150 – 152Combined sources3
Helixi160 – 162Combined sources3
Helixi164 – 187Combined sources24
Beta strandi191 – 195Combined sources5
Helixi199 – 211Combined sources13
Helixi217 – 219Combined sources3
Helixi220 – 222Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AR7X-ray2.15A/B1-223[»]
2BBWX-ray2.05A/B1-223[»]
3NDPX-ray2.30A/B1-223[»]
ProteinModelPortaliP27144.
SMRiP27144.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27144.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni35 – 64NMPbindUniRule annotation1 PublicationAdd BLAST30
Regioni125 – 162LIDUniRule 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 GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis.UniRule annotation1 Publication

Sequence similaritiesi

Belongs to the adenylate kinase family. AK3 subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG3078. Eukaryota.
COG0563. LUCA.
GeneTreeiENSGT00550000074679.
HOGENOMiHOG000238772.
HOVERGENiHBG000458.
InParanoidiP27144.
KOiK00939.
OMAiCLLDGYP.
OrthoDBiEOG091G06BH.
PhylomeDBiP27144.
TreeFamiTF312916.

Family and domain databases

CDDicd01428. ADK. 1 hit.
Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_00235. Adenylate_kinase_Adk. 1 hit.
MF_03169. Adenylate_kinase_AK3. 1 hit.
MF_03170. Adenylate_kinase_AK4. 1 hit.
InterProiIPR006259. Adenyl_kin_sub.
IPR000850. Adenylat/UMP-CMP_kin.
IPR033690. Adenylat_kinase_CS.
IPR007862. Adenylate_kinase_lid-dom.
IPR028586. AK3/Ak4_mitochondrial.
IPR028585. AK4_mitochondrial.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR23359. PTHR23359. 1 hit.
PfamiPF05191. ADK_lid. 1 hit.
[Graphical view]
PRINTSiPR00094. ADENYLTKNASE.
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF57774. SSF57774. 1 hit.
TIGRFAMsiTIGR01351. adk. 1 hit.
PROSITEiPS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P27144-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASKLLRAVI LGPPGSGKGT VCQRIAQNFG LQHLSSGHFL RENIKASTEV
60 70 80 90 100
GEMAKQYIEK SLLVPDHVIT RLMMSELENR RGQHWLLDGF PRTLGQAEAL
110 120 130 140 150
DKICEVDLVI SLNIPFETLK DRLSRRWIHP PSGRVYNLDF NPPHVHGIDD
160 170 180 190 200
VTGEPLVQQE DDKPEAVAAR LRQYKDVAKP VIELYKSRGV LHQFSGTETN
210 220
KIWPYVYTLF SNKITPIQSK EAY
Length:223
Mass (Da):25,268
Last modified:August 1, 1992 - v1
Checksum:i653341A8EB3BC723
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22C → S in AAH40224 (PubMed:15489334).Curated1
Sequence conflicti22C → S in AAI46654 (PubMed:15489334).Curated1
Sequence conflicti23Q → R in AAH66944 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60673 mRNA. Translation: CAA43088.1.
CR456830 mRNA. Translation: CAG33111.1.
AK313611 mRNA. Translation: BAG36374.1.
AL356212, AC099680 Genomic DNA. Translation: CAI22412.1.
CH471059 Genomic DNA. Translation: EAX06538.1.
CH471059 Genomic DNA. Translation: EAX06540.1.
CH471059 Genomic DNA. Translation: EAX06544.1.
BC016180 mRNA. Translation: AAH16180.1.
BC040224 mRNA. Translation: AAH40224.1.
BC066944 mRNA. Translation: AAH66944.1.
BC136886 mRNA. Translation: AAI36887.1.
BC136887 mRNA. Translation: AAI36888.1.
BC148270 mRNA. Translation: AAI48271.1.
BC146653 mRNA. Translation: AAI46654.1.
CCDSiCCDS629.1.
PIRiA42820. KIHUA3.
RefSeqiNP_001005353.1. NM_001005353.2.
NP_037542.1. NM_013410.3.
NP_982289.1. NM_203464.2.
UniGeneiHs.10862.

Genome annotation databases

EnsembliENST00000327299; ENSP00000322175; ENSG00000162433.
ENST00000395334; ENSP00000378743; ENSG00000162433.
ENST00000545314; ENSP00000445912; ENSG00000162433.
GeneIDi205.
KEGGihsa:205.
UCSCiuc001dby.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60673 mRNA. Translation: CAA43088.1.
CR456830 mRNA. Translation: CAG33111.1.
AK313611 mRNA. Translation: BAG36374.1.
AL356212, AC099680 Genomic DNA. Translation: CAI22412.1.
CH471059 Genomic DNA. Translation: EAX06538.1.
CH471059 Genomic DNA. Translation: EAX06540.1.
CH471059 Genomic DNA. Translation: EAX06544.1.
BC016180 mRNA. Translation: AAH16180.1.
BC040224 mRNA. Translation: AAH40224.1.
BC066944 mRNA. Translation: AAH66944.1.
BC136886 mRNA. Translation: AAI36887.1.
BC136887 mRNA. Translation: AAI36888.1.
BC148270 mRNA. Translation: AAI48271.1.
BC146653 mRNA. Translation: AAI46654.1.
CCDSiCCDS629.1.
PIRiA42820. KIHUA3.
RefSeqiNP_001005353.1. NM_001005353.2.
NP_037542.1. NM_013410.3.
NP_982289.1. NM_203464.2.
UniGeneiHs.10862.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AR7X-ray2.15A/B1-223[»]
2BBWX-ray2.05A/B1-223[»]
3NDPX-ray2.30A/B1-223[»]
ProteinModelPortaliP27144.
SMRiP27144.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106708. 12 interactors.
IntActiP27144. 4 interactors.
STRINGi9606.ENSP00000322175.

Chemistry databases

BindingDBiP27144.
ChEMBLiCHEMBL4926.
DrugBankiDB00718. Adefovir Dipivoxil.
DB00300. Tenofovir.

PTM databases

iPTMnetiP27144.
PhosphoSitePlusiP27144.

Polymorphism and mutation databases

BioMutaiAK4.
DMDMi125157.

2D gel databases

UCD-2DPAGEP27144.

Proteomic databases

EPDiP27144.
MaxQBiP27144.
PaxDbiP27144.
PeptideAtlasiP27144.
PRIDEiP27144.
TopDownProteomicsiP27144.

Protocols and materials databases

DNASUi205.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000327299; ENSP00000322175; ENSG00000162433.
ENST00000395334; ENSP00000378743; ENSG00000162433.
ENST00000545314; ENSP00000445912; ENSG00000162433.
GeneIDi205.
KEGGihsa:205.
UCSCiuc001dby.3. human.

Organism-specific databases

CTDi205.
DisGeNETi205.
GeneCardsiAK4.
HGNCiHGNC:363. AK4.
HPAiHPA042753.
HPA049461.
MIMi103030. gene.
neXtProtiNX_P27144.
OpenTargetsiENSG00000162433.
PharmGKBiPA165750325.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3078. Eukaryota.
COG0563. LUCA.
GeneTreeiENSGT00550000074679.
HOGENOMiHOG000238772.
HOVERGENiHBG000458.
InParanoidiP27144.
KOiK00939.
OMAiCLLDGYP.
OrthoDBiEOG091G06BH.
PhylomeDBiP27144.
TreeFamiTF312916.

Enzyme and pathway databases

BioCyciZFISH:HS10823-MONOMER.
BRENDAi2.7.4.3. 2681.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.

Miscellaneous databases

EvolutionaryTraceiP27144.
GeneWikiiAK3L1.
GenomeRNAii205.
PROiP27144.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162433.
CleanExiHS_AK3.
HS_AK3L1.
ExpressionAtlasiP27144. baseline and differential.
GenevisibleiP27144. HS.

Family and domain databases

CDDicd01428. ADK. 1 hit.
Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_00235. Adenylate_kinase_Adk. 1 hit.
MF_03169. Adenylate_kinase_AK3. 1 hit.
MF_03170. Adenylate_kinase_AK4. 1 hit.
InterProiIPR006259. Adenyl_kin_sub.
IPR000850. Adenylat/UMP-CMP_kin.
IPR033690. Adenylat_kinase_CS.
IPR007862. Adenylate_kinase_lid-dom.
IPR028586. AK3/Ak4_mitochondrial.
IPR028585. AK4_mitochondrial.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR23359. PTHR23359. 1 hit.
PfamiPF05191. ADK_lid. 1 hit.
[Graphical view]
PRINTSiPR00094. ADENYLTKNASE.
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF57774. SSF57774. 1 hit.
TIGRFAMsiTIGR01351. adk. 1 hit.
PROSITEiPS00113. ADENYLATE_KINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKAD4_HUMAN
AccessioniPrimary (citable) accession number: P27144
Secondary accession number(s): B2R927
, D3DQ62, Q6IBH4, Q6NXQ5, Q8IUU9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 30, 2016
This is version 170 of the entry and version 1 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, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.