UniProtKB - Q6P4H8 (ACKMT_HUMAN)
Protein
ATP synthase subunit C lysine N-methyltransferase
Gene
ATPSCKMT
Organism
Homo sapiens (Human)
Status
Functioni
Mitochondrial protein-lysine N-methyltransferase that trimethylates ATP synthase subunit C, ATP5MC1 and ATP5MC2. Trimethylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration (PubMed:29444090, PubMed:30530489). Promotes chronic pain (PubMed:29444090). Involved in persistent inflammatory and neuropathic pain: methyltransferase activity in the mitochondria of sensory neurons promotes chronic pain via a pathway that depends on the production of reactive oxygen species (ROS) and on the engagement of spinal cord microglia (PubMed:29444090).2 Publications
Catalytic activityi
- L-lysyl-[protein] + 3 S-adenosyl-L-methionine = 3 H+ + N6,N6,N6-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-homocysteine2 PublicationsThis reaction proceeds in the forward2 Publications direction.
GO - Molecular functioni
- protein-lysine N-methyltransferase activity Source: UniProtKB
GO - Biological processi
- peptidyl-lysine methylation Source: UniProtKB
- peptidyl-lysine trimethylation Source: UniProtKB
- positive regulation of proton-transporting ATP synthase activity, rotational mechanism Source: UniProtKB
- positive regulation of sensory perception of pain Source: UniProtKB
- regulation of mitochondrial ATP synthesis coupled proton transport Source: UniProtKB
Keywordsi
Molecular function | Methyltransferase, Transferase |
Ligand | S-adenosyl-L-methionine |
Enzyme and pathway databases
PathwayCommonsi | Q6P4H8 |
Names & Taxonomyi
Protein namesi | Recommended name: ATP synthase subunit C lysine N-methyltransferase1 PublicationCurated (EC:2.1.1.-2 Publications)Alternative name(s): Protein N-lysine methyltransferase FAM173BCurated Short name: hFAM173B1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:27029, ATPSCKMT |
MIMi | 618568, gene |
neXtProti | NX_Q6P4H8 |
VEuPathDBi | HostDB:ENSG00000150756.13 |
Subcellular locationi
Mitochondrion
- Mitochondrion membrane 1 Publication1 Publication; Single-pass membrane protein Sequence analysis
Note: Localizes to mitochondrial cristae.1 Publication
Mitochondrion
- mitochondrial crista Source: UniProtKB
- mitochondrion Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 38 – 58 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Membrane, MitochondrionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 94 | D → A: Abolished protein-lysine N-methyltransferase activity and ability to promote chronic pain. 1 Publication | 1 | |
Mutagenesisi | 117 | E → A: Abolished protein-lysine N-methyltransferase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 134145 |
OpenTargetsi | ENSG00000150756 |
PharmGKBi | PA162387281 |
Miscellaneous databases
Pharosi | Q6P4H8, Tdark |
Genetic variation databases
BioMutai | FAM173B |
DMDMi | 190360174 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000321536 | 1 – 233 | ATP synthase subunit C lysine N-methyltransferaseAdd BLAST | 233 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
MassIVEi | Q6P4H8 |
MaxQBi | Q6P4H8 |
PaxDbi | Q6P4H8 |
PeptideAtlasi | Q6P4H8 |
PRIDEi | Q6P4H8 |
ProteomicsDBi | 19326 66979 [Q6P4H8-1] |
PTM databases
iPTMneti | Q6P4H8 |
PhosphoSitePlusi | Q6P4H8 |
Expressioni
Tissue specificityi
Ubiquitously expressed.1 Publication
Gene expression databases
Bgeei | ENSG00000150756, Expressed in corpus callosum and 202 other tissues |
ExpressionAtlasi | Q6P4H8, baseline and differential |
Genevisiblei | Q6P4H8, HS |
Organism-specific databases
HPAi | ENSG00000150756, Low tissue specificity |
Interactioni
Binary interactionsi
Q6P4H8
With | #Exp. | IntAct |
---|---|---|
MEOX2 [Q6FHY5] | 3 | EBI-12382465,EBI-16439278 |
Protein-protein interaction databases
BioGRIDi | 126386, 3 interactors |
IntActi | Q6P4H8, 1 interactor |
STRINGi | 9606.ENSP00000422338 |
Miscellaneous databases
RNActi | Q6P4H8, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 56 – 90 | Required for mitochondrial location1 PublicationAdd BLAST | 35 |
Domaini
Contains an atypical, non-cleavable mitochondrial targeting sequence responsible for its localization to mitochondria.1 Publication
Sequence similaritiesi
Belongs to the ANT/ATPSC lysine N-methyltransferase family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4058, Eukaryota |
GeneTreei | ENSGT00390000014771 |
HOGENOMi | CLU_068443_4_0_1 |
InParanoidi | Q6P4H8 |
OMAi | GVNTVWF |
OrthoDBi | 1605787at2759 |
PhylomeDBi | Q6P4H8 |
TreeFami | TF314984 |
Family and domain databases
InterProi | View protein in InterPro IPR026170, FAM173A/B IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR13610, PTHR13610, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q6P4H8-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEGGGGIPLE TLKEESQSRH VLPASFEVNS LQKSNWGFLL TGLVGGTLVA
60 70 80 90 100
VYAVATPFVT PALRKVCLPF VPATTKQIEN VVKMLRCRRG SLVDIGSGDG
110 120 130 140 150
RIVIAAAKKG FTAVGYELNP WLVWYSRYRA WREGVHGSAK FYISDLWKVT
160 170 180 190 200
FSQYSNVVIF GVPQMMLQLE KKLERELEDD ARVIACRFPF PHWTPDHVTG
210 220 230
EGIDTVWAYD ASTFRGREKR PCTSMHFQLP IQA
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD6RIE0 | D6RIE0_HUMAN | ATP synthase subunit C lysine N-met... | ATPSCKMT | 149 | Annotation score: | ||
D6RBE3 | D6RBE3_HUMAN | ATP synthase subunit C lysine N-met... | ATPSCKMT | 109 | Annotation score: | ||
J3KN90 | J3KN90_HUMAN | ATP synthase subunit C lysine N-met... | ATPSCKMT LOC134145, hCG_36858 | 69 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_039345 | 75 | T → M2 PublicationsCorresponds to variant dbSNP:rs2438652Ensembl. | 1 | |
Natural variantiVAR_039346 | 105 | A → V. Corresponds to variant dbSNP:rs16884350Ensembl. | 1 | |
Natural variantiVAR_039347 | 114 | V → A. Corresponds to variant dbSNP:rs17360625Ensembl. | 1 | |
Natural variantiVAR_039348 | 229 | L → M. Corresponds to variant dbSNP:rs15757Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044724 | 149 – 165 | Missing in isoform 2. 1 PublicationAdd BLAST | 17 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK300042 mRNA Translation: BAG61853.1 AK302012 mRNA Translation: BAG63414.1 AC012640 Genomic DNA No translation available. AC034229 Genomic DNA No translation available. CH471102 Genomic DNA Translation: EAX08074.1 BC063406 mRNA Translation: AAH63406.1 |
CCDSi | CCDS43301.1 [Q6P4H8-1] CCDS58942.1 [Q6P4H8-2] |
RefSeqi | NP_001245317.1, NM_001258388.1 [Q6P4H8-2] NP_954584.2, NM_199133.3 [Q6P4H8-1] |
Genome annotation databases
Ensembli | ENST00000510047; ENSP00000420876; ENSG00000150756 [Q6P4H8-2] ENST00000511437; ENSP00000422338; ENSG00000150756 [Q6P4H8-1] |
GeneIDi | 134145 |
KEGGi | hsa:134145 |
UCSCi | uc003jeo.4, human [Q6P4H8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK300042 mRNA Translation: BAG61853.1 AK302012 mRNA Translation: BAG63414.1 AC012640 Genomic DNA No translation available. AC034229 Genomic DNA No translation available. CH471102 Genomic DNA Translation: EAX08074.1 BC063406 mRNA Translation: AAH63406.1 |
CCDSi | CCDS43301.1 [Q6P4H8-1] CCDS58942.1 [Q6P4H8-2] |
RefSeqi | NP_001245317.1, NM_001258388.1 [Q6P4H8-2] NP_954584.2, NM_199133.3 [Q6P4H8-1] |
3D structure databases
SMRi | Q6P4H8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 126386, 3 interactors |
IntActi | Q6P4H8, 1 interactor |
STRINGi | 9606.ENSP00000422338 |
PTM databases
iPTMneti | Q6P4H8 |
PhosphoSitePlusi | Q6P4H8 |
Genetic variation databases
BioMutai | FAM173B |
DMDMi | 190360174 |
Proteomic databases
MassIVEi | Q6P4H8 |
MaxQBi | Q6P4H8 |
PaxDbi | Q6P4H8 |
PeptideAtlasi | Q6P4H8 |
PRIDEi | Q6P4H8 |
ProteomicsDBi | 19326 66979 [Q6P4H8-1] |
Protocols and materials databases
Antibodypediai | 22448, 68 antibodies |
DNASUi | 134145 |
Genome annotation databases
Ensembli | ENST00000510047; ENSP00000420876; ENSG00000150756 [Q6P4H8-2] ENST00000511437; ENSP00000422338; ENSG00000150756 [Q6P4H8-1] |
GeneIDi | 134145 |
KEGGi | hsa:134145 |
UCSCi | uc003jeo.4, human [Q6P4H8-1] |
Organism-specific databases
CTDi | 134145 |
DisGeNETi | 134145 |
GeneCardsi | ATPSCKMT |
HGNCi | HGNC:27029, ATPSCKMT |
HPAi | ENSG00000150756, Low tissue specificity |
MIMi | 618568, gene |
neXtProti | NX_Q6P4H8 |
OpenTargetsi | ENSG00000150756 |
PharmGKBi | PA162387281 |
VEuPathDBi | HostDB:ENSG00000150756.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4058, Eukaryota |
GeneTreei | ENSGT00390000014771 |
HOGENOMi | CLU_068443_4_0_1 |
InParanoidi | Q6P4H8 |
OMAi | GVNTVWF |
OrthoDBi | 1605787at2759 |
PhylomeDBi | Q6P4H8 |
TreeFami | TF314984 |
Enzyme and pathway databases
PathwayCommonsi | Q6P4H8 |
Miscellaneous databases
BioGRID-ORCSi | 134145, 7 hits in 1000 CRISPR screens |
ChiTaRSi | FAM173B, human |
GenomeRNAii | 134145 |
Pharosi | Q6P4H8, Tdark |
PROi | PR:Q6P4H8 |
RNActi | Q6P4H8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000150756, Expressed in corpus callosum and 202 other tissues |
ExpressionAtlasi | Q6P4H8, baseline and differential |
Genevisiblei | Q6P4H8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR026170, FAM173A/B IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR13610, PTHR13610, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ACKMT_HUMAN | |
Accessioni | Q6P4H8Primary (citable) accession number: Q6P4H8 Secondary accession number(s): B4DT41, B4DXK2, E9PBZ4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 26, 2008 |
Last sequence update: | February 26, 2008 | |
Last modified: | April 7, 2021 | |
This is version 131 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families