LOCUS ACKMT_HUMAN 233 aa linear PRI 27-NOV-2024
DEFINITION RecName: Full=ATP synthase subunit C lysine N-methyltransferase;
AltName: Full=Protein N-lysine methyltransferase FAM173B;
Short=hFAM173B.
ACCESSION Q6P4H8
VERSION Q6P4H8.2
DBSOURCE UniProtKB: locus ACKMT_HUMAN, accession Q6P4H8;
class: standard.
extra accessions:B4DT41,B4DXK2,E9PBZ4
created: Feb 26, 2008.
sequence updated: Feb 26, 2008.
annotation updated: Nov 27, 2024.
xrefs: AK300042.1, BAG61853.1, AK302012.1, BAG63414.1, AC012640.12,
AC034229.4, CH471102.2, EAX08074.1, BC063406.1, AAH63406.1,
NP_001245317.1, NP_954584.2
xrefs (non-sequence databases): CCDS:CCDS43301.1, CCDS:CCDS58942.1,
AlphaFoldDB:Q6P4H8, SMR:Q6P4H8, BioGRID:126386, IntAct:Q6P4H8,
STRING:9606.ENSP00000422338, iPTMnet:Q6P4H8,
PhosphoSitePlus:Q6P4H8, BioMuta:FAM173B, DMDM:190360174,
MassIVE:Q6P4H8, PaxDb:9606-ENSP00000422338, PeptideAtlas:Q6P4H8,
ProteomicsDB:19326, ProteomicsDB:66979, Pumba:Q6P4H8,
Antibodypedia:22448, DNASU:134145, Ensembl:ENST00000510047.5,
Ensembl:ENSP00000420876.1, Ensembl:ENSG00000150756.14,
Ensembl:ENST00000511437.6, Ensembl:ENSP00000422338.1,
GeneID:134145, KEGG:hsa:134145, MANE-Select:ENST00000511437.6,
UCSC:uc003jeo.4, AGR:HGNC:27029, CTD:134145, DisGeNET:134145,
GeneCards:ATPSCKMT, HGNC:27029, HPA:ENSG00000150756, MIM 618568,
neXtProt:NX_Q6P4H8, OpenTargets:ENSG00000150756,
PharmGKB:PA162387281, VEuPathDB:HostDB:ENSG00000150756,
eggNOG:KOG4058, GeneTree:ENSGT00390000014771,
HOGENOM:CLU_068443_4_0_1, InParanoid:Q6P4H8, OMA:FRKFCLP,
OrthoDB:2963877at2759, PhylomeDB:Q6P4H8, TreeFam:TF314984,
PathwayCommons:Q6P4H8, SignaLink:Q6P4H8, BioGRID-ORCS:134145,
ChiTaRS:FAM173B, GenomeRNAi:134145, Pharos:Q6P4H8, PRO:PR:Q6P4H8,
Proteomes:UP000005640, RNAct:Q6P4H8, Bgee:ENSG00000150756,
ExpressionAtlas:Q6P4H8, GO:0030061, GO:0005739, GO:0042054,
GO:0016279, GO:0018022, GO:0018023, GO:1905273, GO:1904058,
GO:1905706, FunFam:3.40.50.150:FF:000141, Gene3D:3.40.50.150,
InterPro:IPR026170, InterPro:IPR029063, PANTHER:PTHR13610:SF8,
PANTHER:PTHR13610, SUPFAM:SSF53335
KEYWORDS Acetylation; Alternative splicing; Membrane; Methyltransferase;
Mitochondrion; Proteomics identification; Reference proteome;
S-adenosyl-L-methionine; Transferase; Transmembrane; Transmembrane
helix.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 233)
AUTHORS Ota,T., Suzuki,Y., Nishikawa,T., Otsuki,T., Sugiyama,T., Irie,R.,
Wakamatsu,A., Hayashi,K., Sato,H., Nagai,K., Kimura,K., Makita,H.,
Sekine,M., Obayashi,M., Nishi,T., Shibahara,T., Tanaka,T.,
Ishii,S., Yamamoto,J., Saito,K., Kawai,Y., Isono,Y., Nakamura,Y.,
Nagahari,K., Murakami,K., Yasuda,T., Iwayanagi,T., Wagatsuma,M.,
Shiratori,A., Sudo,H., Hosoiri,T., Kaku,Y., Kodaira,H., Kondo,H.,
Sugawara,M., Takahashi,M., Kanda,K., Yokoi,T., Furuya,T.,
Kikkawa,E., Omura,Y., Abe,K., Kamihara,K., Katsuta,N., Sato,K.,
Tanikawa,M., Yamazaki,M., Ninomiya,K., Ishibashi,T., Yamashita,H.,
Murakawa,K., Fujimori,K., Tanai,H., Kimata,M., Watanabe,M.,
Hiraoka,S., Chiba,Y., Ishida,S., Ono,Y., Takiguchi,S., Watanabe,S.,
Yosida,M., Hotuta,T., Kusano,J., Kanehori,K., Takahashi-Fujii,A.,
Hara,H., Tanase,T.O., Nomura,Y., Togiya,S., Komai,F., Hara,R.,
Takeuchi,K., Arita,M., Imose,N., Musashino,K., Yuuki,H., Oshima,A.,
Sasaki,N., Aotsuka,S., Yoshikawa,Y., Matsunawa,H., Ichihara,T.,
Shiohata,N., Sano,S., Moriya,S., Momiyama,H., Satoh,N., Takami,S.,
Terashima,Y., Suzuki,O., Nakagawa,S., Senoh,A., Mizoguchi,H.,
Goto,Y., Shimizu,F., Wakebe,H., Hishigaki,H., Watanabe,T.,
Sugiyama,A., Takemoto,M., Kawakami,B., Yamazaki,M., Watanabe,K.,
Kumagai,A., Itakura,S., Fukuzumi,Y., Fujimori,Y., Komiyama,M.,
Tashiro,H., Tanigami,A., Fujiwara,T., Ono,T., Yamada,K., Fujii,Y.,
Ozaki,K., Hirao,M., Ohmori,Y., Kawabata,A., Hikiji,T., Kobatake,N.,
Inagaki,H., Ikema,Y., Okamoto,S., Okitani,R., Kawakami,T.,
Noguchi,S., Itoh,T., Shigeta,K., Senba,T., Matsumura,K.,
Nakajima,Y., Mizuno,T., Morinaga,M., Sasaki,M., Togashi,T.,
Oyama,M., Hata,H., Watanabe,M., Komatsu,T., Mizushima-Sugano,J.,
Satoh,T., Shirai,Y., Takahashi,Y., Nakagawa,K., Okumura,K.,
Nagase,T., Nomura,N., Kikuchi,H., Masuho,Y., Yamashita,R.,
Nakai,K., Yada,T., Nakamura,Y., Ohara,O., Isogai,T. and Sugano,S.
TITLE Complete sequencing and characterization of 21,243 full-length
human cDNAs
JOURNAL Nat Genet 36 (1), 40-45 (2004)
PUBMED 14702039
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
VARIANT MET-75.;
TISSUE=Testis
REFERENCE 2 (residues 1 to 233)
AUTHORS Schmutz,J., Martin,J., Terry,A., Couronne,O., Grimwood,J.,
Lowry,S., Gordon,L.A., Scott,D., Xie,G., Huang,W., Hellsten,U.,
Tran-Gyamfi,M., She,X., Prabhakar,S., Aerts,A., Altherr,M.,
Bajorek,E., Black,S., Branscomb,E., Caoile,C., Challacombe,J.F.,
Chan,Y.M., Denys,M., Detter,J.C., Escobar,J., Flowers,D.,
Fotopulos,D., Glavina,T., Gomez,M., Gonzales,E., Goodstein,D.,
Grigoriev,I., Groza,M., Hammon,N., Hawkins,T., Haydu,L., Israni,S.,
Jett,J., Kadner,K., Kimball,H., Kobayashi,A., Lopez,F., Lou,Y.,
Martinez,D., Medina,C., Morgan,J., Nandkeshwar,R., Noonan,J.P.,
Pitluck,S., Pollard,M., Predki,P., Priest,J., Ramirez,L.,
Retterer,J., Rodriguez,A., Rogers,S., Salamov,A., Salazar,A.,
Thayer,N., Tice,H., Tsai,M., Ustaszewska,A., Vo,N., Wheeler,J.,
Wu,K., Yang,J., Dickson,M., Cheng,J.F., Eichler,E.E., Olsen,A.,
Pennacchio,L.A., Rokhsar,D.S., Richardson,P., Lucas,S.M.,
Myers,R.M. and Rubin,E.M.
TITLE The DNA sequence and comparative analysis of human chromosome 5
JOURNAL Nature 431 (7006), 268-274 (2004)
PUBMED 15372022
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
REFERENCE 3 (residues 1 to 233)
AUTHORS Mural,R.J., Istrail,S., Sutton,G.G., Florea,L., Halpern,A.L.,
Mobarry,C.M., Lippert,R., Walenz,B., Shatkay,H., Dew,I.,
Miller,J.R., Flanigan,M.J., Edwards,N.J., Bolanos,R., Fasulo,D.,
Halldorsson,B.V., Hannenhalli,S., Turner,R., Yooseph,S., Lu,F.,
Nusskern,D.R., Shue,B.C., Zheng,X.H., Zhong,F., Delcher,A.L.,
Huson,D.H., Kravitz,S.A., Mouchard,L., Reinert,K., Remington,K.A.,
Clark,A.G., Waterman,M.S., Eichler,E.E., Adams,M.D.,
Hunkapiller,M.W., Myers,E.W. and Venter,J.C.
TITLE Direct Submission
JOURNAL Submitted (??-SEP-2005) to the EMBL/GenBank/DDBJ databases
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
REFERENCE 4 (residues 1 to 233)
AUTHORS Gerhard,D.S., Wagner,L., Feingold,E.A., Shenmen,C.M., Grouse,L.H.,
Schuler,G., Klein,S.L., Old,S., Rasooly,R., Good,P., Guyer,M.,
Peck,A.M., Derge,J.G., Lipman,D., Collins,F.S., Jang,W., Sherry,S.,
Feolo,M., Misquitta,L., Lee,E., Rotmistrovsky,K., Greenhut,S.F.,
Schaefer,C.F., Buetow,K., Bonner,T.I., Haussler,D., Kent,J.,
Kiekhaus,M., Furey,T., Brent,M., Prange,C., Schreiber,K.,
Shapiro,N., Bhat,N.K., Hopkins,R.F., Hsie,F., Driscoll,T.,
Soares,M.B., Casavant,T.L., Scheetz,T.E., Brown-stein,M.J.,
Usdin,T.B., Toshiyuki,S., Carninci,P., Piao,Y., Dudekula,D.B.,
Ko,M.S., Kawakami,K., Suzuki,Y., Sugano,S., Gruber,C.E.,
Smith,M.R., Simmons,B., Moore,T., Waterman,R., Johnson,S.L.,
Ruan,Y., Wei,C.L., Mathavan,S., Gunaratne,P.H., Wu,J., Garcia,A.M.,
Hulyk,S.W., Fuh,E., Yuan,Y., Sneed,A., Kowis,C., Hodgson,A.,
Muzny,D.M., McPherson,J., Gibbs,R.A., Fahey,J., Helton,E.,
Ketteman,M., Madan,A., Rodrigues,S., Sanchez,A., Whiting,M.,
Madari,A., Young,A.C., Wetherby,K.D., Granite,S.J., Kwong,P.N.,
Brinkley,C.P., Pearson,R.L., Bouffard,G.G., Blakesly,R.W.,
Green,E.D., Dickson,M.C., Rodriguez,A.C., Grimwood,J., Schmutz,J.,
Myers,R.M., Butterfield,Y.S., Griffith,M., Griffith,O.L.,
Krzywinski,M.I., Liao,N., Morin,R., Palmquist,D., Petrescu,A.S.,
Skalska,U., Smailus,D.E., Stott,J.M., Schnerch,A., Schein,J.E.,
Jones,S.J., Holt,R.A., Baross,A., Marra,M.A., Clifton,S.,
Makowski,K.A., Bosak,S. and Malek,J.
CONSRTM MGC Project Team
TITLE The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC)
JOURNAL Genome Res 14 (10B), 2121-2127 (2004)
PUBMED 15489334
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
MET-75.;
TISSUE=Colon
Erratum:[Genome Res. 2006 Jun;16(6):804. Morrin, Ryan [corrected to
Morin, Ryan]]
REFERENCE 5 (residues 1 to 233)
AUTHORS Van Damme,P., Lasa,M., Polevoda,B., Gazquez,C., Elosegui-Artola,A.,
Kim,D.S., De Juan-Pardo,E., Demeyer,K., Hole,K., Larrea,E.,
Timmerman,E., Prieto,J., Arnesen,T., Sherman,F., Gevaert,K. and
Aldabe,R.
TITLE N-terminal acetylome analyses and functional insights of the
N-terminal acetyltransferase NatB
JOURNAL Proc Natl Acad Sci U S A 109 (31), 12449-12454 (2012)
PUBMED 22814378
REMARK ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
REFERENCE 6 (residues 1 to 233)
AUTHORS Willemen,H.L.D.M., Kavelaars,A., Prado,J., Maas,M., Versteeg,S.,
Nellissen,L.J.J., Tromp,J., Gonzalez Cano,R., Zhou,W.,
Jakobsson,M.E., Malecki,J., Posthuma,G., Habib,A.M., Heijnen,C.J.,
Falnes,P.O. and Eijkelkamp,N.
TITLE Identification of FAM173B as a protein methyltransferase promoting
chronic pain
JOURNAL PLoS Biol 16 (2), e2003452 (2018)
PUBMED 29444090
REMARK FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS
OF ASP-94.
Publication Status: Online-Only
REFERENCE 7 (residues 1 to 233)
AUTHORS Malecki,J.M., Willemen,H.L.D.M., Pinto,R., Ho,A.Y.Y., Moen,A.,
Kjonstad,I.F., Burgering,B.M.T., Zwartkruis,F., Eijkelkamp,N. and
Falnes,P.O.
TITLE Lysine methylation by the mitochondrial methyltransferase FAM173B
optimizes the function of mitochondrial ATP synthase
JOURNAL J Biol Chem 294 (4), 1128-1141 (2019)
PUBMED 30530489
REMARK FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, DOMAIN, AND
MUTAGENESIS OF GLU-117.
COMMENT On Jun 14, 2008 this sequence version replaced gi:74758272.
[FUNCTION] 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).
{ECO:0000269|PubMed:29444090, ECO:0000269|PubMed:30530489}.
[CATALYTIC ACTIVITY] Reaction=L-lysyl-[protein] + 3
S-adenosyl-L-methionine =
N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3
S-adenosyl-L-homocysteine + 3 H(+); Xref=Rhea:RHEA:54192,
Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13826, ChEBI:CHEBI:15378,
ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
ChEBI:CHEBI:61961; Evidence={ECO:0000269|PubMed:29444090,
ECO:0000269|PubMed:30530489}; PhysiologicalDirection=left-to-right;
Xref=Rhea:RHEA:54193; Evidence={ECO:0000269|PubMed:29444090,
ECO:0000269|PubMed:30530489}.
[INTERACTION] Q6P4H8; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12382465,
EBI-16439278.
[SUBCELLULAR LOCATION] Mitochondrion membrane
{ECO:0000269|PubMed:30530489, ECO:0000305|PubMed:29444090};
Single-pass membrane protein {ECO:0000255}. Note=Localizes to
mitochondrial cristae. {ECO:0000269|PubMed:29444090}.
[ALTERNATIVE PRODUCTS] Event=Alternative splicing; Named
isoforms=2; Name=1; IsoId=Q6P4H8-1; Sequence=Displayed; Name=2;
IsoId=Q6P4H8-2; Sequence=VSP_044724.
[TISSUE SPECIFICITY] Ubiquitously expressed.
{ECO:0000269|PubMed:29444090}.
[DOMAIN] Contains an atypical, non-cleavable mitochondrial
targeting sequence responsible for its localization to
mitochondria. {ECO:0000269|PubMed:30530489}.
[SIMILARITY] Belongs to the ANT/ATPSC lysine N-methyltransferase
family. {ECO:0000305}.
FEATURES Location/Qualifiers
source 1..233
/organism="Homo sapiens"
/db_xref="taxon:9606"
gene 1..233
/gene="ATPSCKMT"
/gene_synonym="FAM173B"
Protein 1..233
/product="ATP synthase subunit C lysine
N-methyltransferase"
/EC_number="2.1.1.-"
/note="Protein N-lysine methyltransferase FAM173B;
hFAM173B"
/UniProtKB_evidence="Evidence at protein level"
Region 1..233
/region_name="Mature chain"
/note="ATP synthase subunit C lysine N-methyltransferase.
/id=PRO_0000321536."
Site 1
/site_type="acetylation"
/note="N-acetylmethionine.
/evidence=ECO:0007744|PubMed:22814378."
Region 38..58
/region_name="Transmembrane region"
/note="Helical. /evidence=ECO:0000255."
Region 56..90
/region_name="Region of interest in the sequence"
/note="Required for mitochondrial location.
/evidence=ECO:0000269|PubMed:30530489."
Region 75
/region_name="Variant"
/note="T -> M (in dbSNP:rs2438652).
/evidence=ECO:0000269|PubMed:14702039,
ECO:0000269|PubMed:15489334. /id=VAR_039345."
Region 76..>136
/region_name="UbiG"
/note="2-polyprenyl-3-methyl-5-hydroxy-6-metoxy-1,
4-benzoquinol methylase [Coenzyme transport and
metabolism]; COG2227"
/db_xref="CDD:441829"
Site 94
/site_type="mutagenized"
/note="D->A: Abolished protein-lysine N-methyltransferase
activity and ability to promote chronic pain.
/evidence=ECO:0000269|PubMed:29444090."
Region 105
/region_name="Variant"
/note="A -> V (in dbSNP:rs16884350). /id=VAR_039346."
Region 114
/region_name="Variant"
/note="V -> A (in dbSNP:rs17360625). /id=VAR_039347."
Site 117
/site_type="mutagenized"
/note="E->A: Abolished protein-lysine N-methyltransferase
activity. /evidence=ECO:0000269|PubMed:30530489."
Region 149..165
/region_name="Splicing variant"
/note="Missing (in isoform 2).
/evidence=ECO:0000303|PubMed:14702039. /id=VSP_044724."
Region 229
/region_name="Variant"
/note="L -> M (in dbSNP:rs15757). /id=VAR_039348."
ORIGIN
1 meggggiple tlkeesqsrh vlpasfevns lqksnwgfll tglvggtlva vyavatpfvt
61 palrkvclpf vpattkqien vvkmlrcrrg slvdigsgdg riviaaakkg ftavgyelnp
121 wlvwysryra wregvhgsak fyisdlwkvt fsqysnvvif gvpqmmlqle kklereledd
181 arviacrfpf phwtpdhvtg egidtvwayd astfrgrekr pctsmhfqlp iqa
//