ACKMT_HUMAN
ID ACKMT_HUMAN Reviewed; 233 AA.
AC Q6P4H8; B4DT41; B4DXK2; E9PBZ4;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=ATP synthase subunit C lysine N-methyltransferase {ECO:0000303|PubMed:30530489, ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:29444090, ECO:0000269|PubMed:30530489};
DE AltName: Full=Protein N-lysine methyltransferase FAM173B {ECO:0000305};
DE Short=hFAM173B {ECO:0000303|PubMed:29444090};
GN Name=ATPSCKMT {ECO:0000312|HGNC:HGNC:27029};
GN Synonyms=FAM173B {ECO:0000303|PubMed:29444090};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP MET-75.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-75.
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP ASP-94.
RX PubMed=29444090; DOI=10.1371/journal.pbio.2003452;
RA Willemen H.L.D.M., Kavelaars A., Prado J., Maas M., Versteeg S.,
RA Nellissen L.J.J., Tromp J., Gonzalez Cano R., Zhou W., Jakobsson M.E.,
RA Malecki J., Posthuma G., Habib A.M., Heijnen C.J., Falnes P.O.,
RA Eijkelkamp N.;
RT "Identification of FAM173B as a protein methyltransferase promoting chronic
RT pain.";
RL PLoS Biol. 16:E2003452-E2003452(2018).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS
RP OF GLU-117.
RX PubMed=30530489; DOI=10.1074/jbc.ra118.005473;
RA Malecki J.M., Willemen H.L.D.M., Pinto R., Ho A.Y.Y., Moen A.,
RA Kjoenstad I.F., Burgering B.M.T., Zwartkruis F., Eijkelkamp N.,
RA Falnes P.O.;
RT "Lysine methylation by the mitochondrial methyltransferase FAM173B
RT optimizes the function of mitochondrial ATP synthase.";
RL J. Biol. Chem. 294:1128-1141(2019).
CC -!- FUNCTION: Mitochondrial protein-lysine N-methyltransferase that
CC trimethylates ATP synthase subunit C, ATP5MC1 and ATP5MC2.
CC Trimethylation is required for proper incorporation of the C subunit
CC into the ATP synthase complex and mitochondrial respiration
CC (PubMed:29444090, PubMed:30530489). Promotes chronic pain
CC (PubMed:29444090). Involved in persistent inflammatory and neuropathic
CC pain: methyltransferase activity in the mitochondria of sensory neurons
CC promotes chronic pain via a pathway that depends on the production of
CC reactive oxygen species (ROS) and on the engagement of spinal cord
CC microglia (PubMed:29444090). {ECO:0000269|PubMed:29444090,
CC ECO:0000269|PubMed:30530489}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:54192, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC COMP:13826, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961;
CC Evidence={ECO:0000269|PubMed:29444090, ECO:0000269|PubMed:30530489};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54193;
CC Evidence={ECO:0000269|PubMed:29444090, ECO:0000269|PubMed:30530489};
CC -!- INTERACTION:
CC Q6P4H8; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12382465, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000269|PubMed:30530489, ECO:0000305|PubMed:29444090}; Single-pass
CC membrane protein {ECO:0000255}. Note=Localizes to mitochondrial
CC cristae. {ECO:0000269|PubMed:29444090}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P4H8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P4H8-2; Sequence=VSP_044724;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:29444090}.
CC -!- DOMAIN: Contains an atypical, non-cleavable mitochondrial targeting
CC sequence responsible for its localization to mitochondria.
CC {ECO:0000269|PubMed:30530489}.
CC -!- SIMILARITY: Belongs to the ANT/ATPSC lysine N-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AK300042; BAG61853.1; -; mRNA.
DR EMBL; AK302012; BAG63414.1; -; mRNA.
DR EMBL; AC012640; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034229; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471102; EAX08074.1; -; Genomic_DNA.
DR EMBL; BC063406; AAH63406.1; -; mRNA.
DR CCDS; CCDS43301.1; -. [Q6P4H8-1]
DR CCDS; CCDS58942.1; -. [Q6P4H8-2]
DR RefSeq; NP_001245317.1; NM_001258388.1. [Q6P4H8-2]
DR RefSeq; NP_954584.2; NM_199133.3. [Q6P4H8-1]
DR AlphaFoldDB; Q6P4H8; -.
DR SMR; Q6P4H8; -.
DR BioGRID; 126386; 9.
DR IntAct; Q6P4H8; 1.
DR STRING; 9606.ENSP00000422338; -.
DR iPTMnet; Q6P4H8; -.
DR PhosphoSitePlus; Q6P4H8; -.
DR BioMuta; FAM173B; -.
DR DMDM; 190360174; -.
DR MassIVE; Q6P4H8; -.
DR MaxQB; Q6P4H8; -.
DR PaxDb; Q6P4H8; -.
DR PeptideAtlas; Q6P4H8; -.
DR PRIDE; Q6P4H8; -.
DR ProteomicsDB; 19326; -.
DR ProteomicsDB; 66979; -. [Q6P4H8-1]
DR Antibodypedia; 22448; 69 antibodies from 21 providers.
DR DNASU; 134145; -.
DR Ensembl; ENST00000510047.5; ENSP00000420876.1; ENSG00000150756.14. [Q6P4H8-2]
DR Ensembl; ENST00000511437.6; ENSP00000422338.1; ENSG00000150756.14. [Q6P4H8-1]
DR GeneID; 134145; -.
DR KEGG; hsa:134145; -.
DR MANE-Select; ENST00000511437.6; ENSP00000422338.1; NM_199133.4; NP_954584.2.
DR UCSC; uc003jeo.4; human. [Q6P4H8-1]
DR CTD; 134145; -.
DR DisGeNET; 134145; -.
DR GeneCards; ATPSCKMT; -.
DR HGNC; HGNC:27029; ATPSCKMT.
DR HPA; ENSG00000150756; Low tissue specificity.
DR MIM; 618568; gene.
DR neXtProt; NX_Q6P4H8; -.
DR OpenTargets; ENSG00000150756; -.
DR PharmGKB; PA162387281; -.
DR VEuPathDB; HostDB:ENSG00000150756; -.
DR eggNOG; KOG4058; Eukaryota.
DR GeneTree; ENSGT00390000014771; -.
DR HOGENOM; CLU_068443_4_0_1; -.
DR InParanoid; Q6P4H8; -.
DR OMA; GVNTVWF; -.
DR OrthoDB; 1605787at2759; -.
DR PhylomeDB; Q6P4H8; -.
DR TreeFam; TF314984; -.
DR PathwayCommons; Q6P4H8; -.
DR SignaLink; Q6P4H8; -.
DR BioGRID-ORCS; 134145; 9 hits in 1081 CRISPR screens.
DR ChiTaRS; FAM173B; human.
DR GenomeRNAi; 134145; -.
DR Pharos; Q6P4H8; Tbio.
DR PRO; PR:Q6P4H8; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6P4H8; protein.
DR Bgee; ENSG00000150756; Expressed in ileal mucosa and 167 other tissues.
DR ExpressionAtlas; Q6P4H8; baseline and differential.
DR Genevisible; Q6P4H8; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030061; C:mitochondrial crista; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0018022; P:peptidyl-lysine methylation; IDA:UniProtKB.
DR GO; GO:0018023; P:peptidyl-lysine trimethylation; IMP:UniProtKB.
DR GO; GO:1905273; P:positive regulation of proton-transporting ATP synthase activity, rotational mechanism; IMP:UniProtKB.
DR GO; GO:1904058; P:positive regulation of sensory perception of pain; IMP:UniProtKB.
DR GO; GO:1905706; P:regulation of mitochondrial ATP synthesis coupled proton transport; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR026170; FAM173A/B.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR13610; PTHR13610; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Membrane; Methyltransferase;
KW Mitochondrion; Reference proteome; S-adenosyl-L-methionine; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..233
FT /note="ATP synthase subunit C lysine N-methyltransferase"
FT /id="PRO_0000321536"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 56..90
FT /note="Required for mitochondrial location"
FT /evidence="ECO:0000269|PubMed:30530489"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 149..165
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044724"
FT VARIANT 75
FT /note="T -> M (in dbSNP:rs2438652)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_039345"
FT VARIANT 105
FT /note="A -> V (in dbSNP:rs16884350)"
FT /id="VAR_039346"
FT VARIANT 114
FT /note="V -> A (in dbSNP:rs17360625)"
FT /id="VAR_039347"
FT VARIANT 229
FT /note="L -> M (in dbSNP:rs15757)"
FT /id="VAR_039348"
FT MUTAGEN 94
FT /note="D->A: Abolished protein-lysine N-methyltransferase
FT activity and ability to promote chronic pain."
FT /evidence="ECO:0000269|PubMed:29444090"
FT MUTAGEN 117
FT /note="E->A: Abolished protein-lysine N-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30530489"
SQ SEQUENCE 233 AA; 26110 MW; 7F4D1F9E3AC87854 CRC64;
MEGGGGIPLE TLKEESQSRH VLPASFEVNS LQKSNWGFLL TGLVGGTLVA VYAVATPFVT
PALRKVCLPF VPATTKQIEN VVKMLRCRRG SLVDIGSGDG RIVIAAAKKG FTAVGYELNP
WLVWYSRYRA WREGVHGSAK FYISDLWKVT FSQYSNVVIF GVPQMMLQLE KKLERELEDD
ARVIACRFPF PHWTPDHVTG EGIDTVWAYD ASTFRGREKR PCTSMHFQLP IQA
