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Protein

Acylglycerol kinase, mitochondrial

Gene

AGK

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

Functioni

Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively (PubMed:15939762). Does not phosphorylate sphingosine (PubMed:15939762). Independently of its lipid kinase activity, acts as a component of the TIM22 complex (PubMed:28712724, PubMed:28712726). The TIM22 complex mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane by forming a twin-pore translocase that uses the membrane potential as the external driving force (PubMed:28712724, PubMed:28712726). In the TIM22 complex, required for the import of a subset of metabolite carriers into mitochtondria, such as ANT1/SLC25A4 and SLC25A24, while it is not required for the import of TIMM23 (PubMed:28712724). Overexpression increases the formation and secretion of LPA, resulting in transactivation of EGFR and activation of the downstream MAPK signaling pathway, leading to increased cell growth (PubMed:15939762).3 Publications

Catalytic activityi

ATP + acylglycerol = ADP + acyl-sn-glycerol 3-phosphate.1 Publication
ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate.1 Publication

Cofactori

Mg2+1 Publication

Pathwayi: glycerolipid metabolism

This protein is involved in the pathway glycerolipid metabolism, which is part of Lipid metabolism.1 Publication
View all proteins of this organism that are known to be involved in the pathway glycerolipid metabolism and in Lipid metabolism.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.94. 2681.
ReactomeiR-HSA-1483206. Glycerophospholipid biosynthesis.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
SABIO-RKiQ53H12.
UniPathwayiUPA00230.

Chemistry databases

SwissLipidsiSLP:000000638.

Names & Taxonomyi

Protein namesi
Recommended name:
Acylglycerol kinase, mitochondrial1 Publication (EC:2.7.1.1071 Publication, EC:2.7.1.941 Publication)
Short name:
hAGK1 Publication
Alternative name(s):
Multiple substrate lipid kinase1 Publication
Short name:
HsMuLK1 Publication
Short name:
MuLK1 Publication
Short name:
Multi-substrate lipid kinase1 Publication
Gene namesi
Name:AGK1 PublicationImported
Synonyms:MULK1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000006530.15.
HGNCiHGNC:21869. AGK.

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

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Mitochondrial DNA depletion syndrome 10 (MTDPS10)5 Publications
The disease is caused by mutations affecting the gene represented in this entry. The TIM22 complex and import of proteins into mitochondrion are affected in patients suffering of MTDPS10 (PubMed:28712726).1 Publication
Disease descriptionAn autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy.
See also OMIM:212350
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079050137 – 422Missing in MTDPS10. 1 PublicationAdd BLAST286
Natural variantiVAR_079051291 – 422Missing in MTDPS10. 1 PublicationAdd BLAST132
Natural variantiVAR_079052327 – 422Missing in MTDPS10. 1 PublicationAdd BLAST96
Cataract 38 (CTRCT38)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn opacification of the crystalline lens of the eye becoming evident at birth. It frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function.
See also OMIM:614691

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi126G → E: Abolishes lipid kinase activity. Does not affect ability to associate with the TIM22 complex and mediate import of transmembrane proteins into the mitochondrial inner membrane. 3 Publications1

Keywords - Diseasei

Cardiomyopathy, Cataract, Disease mutation, Primary mitochondrial disease

Organism-specific databases

DisGeNETi55750.
MalaCardsiAGK.
MIMi212350. phenotype.
614691. phenotype.
OpenTargetsiENSG00000006530.
Orphaneti1369. Congenital cataract - hypertrophic cardiomyopathy - mitochondrial myopathy.
91492. Non-syndromic congenital cataract.
PharmGKBiPA162375851.

Chemistry databases

ChEMBLiCHEMBL2417354.

Polymorphism and mutation databases

BioMutaiAGK.
DMDMi116248550.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002523801 – 422Acylglycerol kinase, mitochondrialAdd BLAST422

Proteomic databases

EPDiQ53H12.
MaxQBiQ53H12.
PaxDbiQ53H12.
PeptideAtlasiQ53H12.
PRIDEiQ53H12.

PTM databases

iPTMnetiQ53H12.
PhosphoSitePlusiQ53H12.
SwissPalmiQ53H12.

Expressioni

Tissue specificityi

Highly expressed in muscle, heart, kidney and brain.1 Publication

Inductioni

Overexpressed in prostate cancer, suggesting that it may play a role in initiation and progression of prostate cancer, processes in which lysophosphatidic acid (LPA) plays key roles.1 Publication

Gene expression databases

BgeeiENSG00000006530.
CleanExiHS_AGK.
ExpressionAtlasiQ53H12. baseline and differential.
GenevisibleiQ53H12. HS.

Organism-specific databases

HPAiHPA020959.
HPA053471.

Interactioni

Subunit structurei

Component of the TIM22 complex, which core is composed of TIMM22, associated with TIMM10 (TIMM10A and/or TIMM10B), TIMM9, AGK and TIMM29 (PubMed:28712724, PubMed:28712726).2 Publications

Protein-protein interaction databases

BioGridi120868. 29 interactors.
IntActiQ53H12. 21 interactors.
MINTiMINT-1378485.
STRINGi9606.ENSP00000347581.

Structurei

3D structure databases

ProteinModelPortaliQ53H12.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini58 – 199DAGKcPROSITE-ProRule annotationAdd BLAST142

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 31HydrophobicCuratedAdd BLAST17

Sequence similaritiesi

Belongs to the AGK family.Curated

Phylogenomic databases

eggNOGiKOG4435. Eukaryota.
COG1597. LUCA.
GeneTreeiENSGT00690000101761.
HOGENOMiHOG000252977.
HOVERGENiHBG080751.
InParanoidiQ53H12.
KOiK09881.
OMAiTKAAHFF.
OrthoDBiEOG091G06YD.
PhylomeDBiQ53H12.
TreeFamiTF320485.

Family and domain databases

Gene3Di3.40.50.10330. 1 hit.
InterProiView protein in InterPro
IPR017438. ATP-NAD_kinase_N.
IPR001206. Diacylglycerol_kinase_cat_dom.
IPR016064. NAD/diacylglycerol_kinase_sf.
PfamiView protein in Pfam
PF00781. DAGK_cat. 1 hit.
SMARTiView protein in SMART
SM00046. DAGKc. 1 hit.
SUPFAMiSSF111331. SSF111331. 2 hits.
PROSITEiView protein in PROSITE
PS50146. DAGK. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q53H12-1) [UniParc]FASTAAdd to basket

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
MTVFFKTLRN HWKKTTAGLC LLTWGGHWLY GKHCDNLLRR AACQEAQVFG
60 70 80 90 100
NQLIPPNAQV KKATVFLNPA ACKGKARTLF EKNAAPILHL SGMDVTIVKT
110 120 130 140 150
DYEGQAKKLL ELMENTDVII VAGGDGTLQE VVTGVLRRTD EATFSKIPIG
160 170 180 190 200
FIPLGETSSL SHTLFAESGN KVQHITDATL AIVKGETVPL DVLQIKGEKE
210 220 230 240 250
QPVFAMTGLR WGSFRDAGVK VSKYWYLGPL KIKAAHFFST LKEWPQTHQA
260 270 280 290 300
SISYTGPTER PPNEPEETPV QRPSLYRRIL RRLASYWAQP QDALSQEVSP
310 320 330 340 350
EVWKDVQLST IELSITTRNN QLDPTSKEDF LNICIEPDTI SKGDFITIGS
360 370 380 390 400
RKVRNPKLHV EGTECLQASQ CTLLIPEGAG GSFSIDSEEY EAMPVEVKLL
410 420
PRKLQFFCDP RKREQMLTSP TQ
Length:422
Mass (Da):47,137
Last modified:October 17, 2006 - v2
Checksum:iF9D85658616B8970
GO
Isoform 2 (identifier: Q53H12-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-65: VFGNQLIPPNAQVKKATV → HYQDESRWEPTLSRTPGS
     66-422: Missing.

Note: No experimental confirmation available.
Show »
Length:65
Mass (Da):7,634
Checksum:i8F3133CE9A0B6D70
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti94D → V in BAD96489 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0278483V → M. Corresponds to variant dbSNP:rs10262855Ensembl.1
Natural variantiVAR_079050137 – 422Missing in MTDPS10. 1 PublicationAdd BLAST286
Natural variantiVAR_079051291 – 422Missing in MTDPS10. 1 PublicationAdd BLAST132
Natural variantiVAR_079052327 – 422Missing in MTDPS10. 1 PublicationAdd BLAST96

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02092548 – 65VFGNQ…KKATV → HYQDESRWEPTLSRTPGS in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_02092666 – 422Missing in isoform 2. 1 PublicationAdd BLAST357

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ278150 mRNA. Translation: CAB93536.1.
AK001704 mRNA. Translation: BAA91848.1.
AK222769 mRNA. Translation: BAD96489.1.
AC004918 Genomic DNA. No translation available.
AC073878 Genomic DNA. No translation available.
AC099547 Genomic DNA. Translation: AAS07537.1.
BC009775 mRNA. Translation: AAH09775.1.
BC022777 mRNA. Translation: AAH22777.1.
CCDSiCCDS5865.1. [Q53H12-1]
RefSeqiNP_060708.1. NM_018238.3. [Q53H12-1]
XP_011514699.1. XM_011516397.2. [Q53H12-1]
UniGeneiHs.743318.

Genome annotation databases

EnsembliENST00000355413; ENSP00000347581; ENSG00000006530. [Q53H12-1]
ENST00000492693; ENSP00000418789; ENSG00000006530. [Q53H12-2]
ENST00000575872; ENSP00000458417; ENSG00000262327.
GeneIDi55750.
KEGGihsa:55750.
UCSCiuc003vwi.3. human. [Q53H12-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAGK_HUMAN
AccessioniPrimary (citable) accession number: Q53H12
Secondary accession number(s): Q75KN1, Q96GC3, Q9NP48
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 17, 2006
Last modified: November 22, 2017
This is version 121 of the entry and version 2 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

Caution

According to a report, the N-terminal hydrophobic region forms a transmembrane region that crosses the mitochondrion inner membrane (PubMed:28712726). According to another report, the N-terminal hydrophobic region associates with the membrane without crossing it (PubMed:28712724).2 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families