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Protein

Adenylate kinase 4, mitochondrial

Gene

AK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 monophosphate kinase activity Source: Reactome
  • nucleoside triphosphate adenylate kinase activity Source: BHF-UCL

GO - Biological processi

  • 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

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.4.3 2681
ReactomeiR-HSA-499943 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

EuPathDBiHostDB:ENSG00000162433.14
HGNCiHGNC:363 AK4
MIMi103030 gene
neXtProtiNX_P27144

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi54375
TopDownProteomicsiP27144

2D gel databases

UCD-2DPAGEiP27144

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, 18 interactors
IntActiP27144, 8 interactors
MINTiP27144
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

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
OMAiGRVYNMG
OrthoDBiEOG091G06BH
PhylomeDBiP27144
TreeFamiTF312916

Family and domain databases

CDDicd01428 ADK, 1 hit
HAMAPiMF_00235 Adenylate_kinase_Adk, 1 hit
MF_03169 Adenylate_kinase_AK3, 1 hit
MF_03170 Adenylate_kinase_AK4, 1 hit
InterProiView protein in InterPro
IPR006259 Adenyl_kin_sub
IPR000850 Adenylat/UMP-CMP_kin
IPR033690 Adenylat_kinase_CS
IPR007862 Adenylate_kinase_lid-dom
IPR036193 ADK_active_lid_dom_sf
IPR028586 AK3/Ak4_mitochondrial
IPR028585 AK4_mitochondrial
IPR027417 P-loop_NTPase
PANTHERiPTHR23359 PTHR23359, 1 hit
PfamiView protein in Pfam
PF05191 ADK_lid, 1 hit
PRINTSiPR00094 ADENYLTKNASE
SUPFAMiSSF52540 SSF52540, 2 hits
SSF57774 SSF57774, 1 hit
TIGRFAMsiTIGR01351 adk, 1 hit
PROSITEiView protein in PROSITE
PS00113 ADENYLATE_KINASE, 1 hit

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
AC099680 Genomic DNA No translation available.
AL356212 Genomic DNA No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiKAD4_HUMAN
AccessioniPrimary (citable) accession number: P27144
Secondary accession number(s): B2R927
, D3DQ62, Q6IBH4, Q6NXQ5, Q8IUU9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: July 18, 2018
This is version 182 of the entry and version 1 of the sequence. See 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

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