CMKMT_HUMAN
ID CMKMT_HUMAN Reviewed; 323 AA.
AC Q7Z624; Q4ZG15; Q53SS6; Q8N6P5; Q9H5G8;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Calmodulin-lysine N-methyltransferase;
DE Short=CLNMT;
DE Short=CaM KMT;
DE EC=2.1.1.60;
GN Name=CAMKMT; Synonyms=C2orf34, CLNMT;
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] (ISOFORM 1).
RC TISSUE=Small intestine;
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=15913950; DOI=10.1016/j.ygeno.2005.04.001;
RA Parvari R., Gonen Y., Alshafee I., Buriakovsky S., Regev K.,
RA Hershkovitz E.;
RT "The 2p21 deletion syndrome: characterization of the transcription
RT content.";
RL Genomics 86:195-211(2005).
RN [5]
RP INVOLVEMENT IN HCS.
RX PubMed=21686663; DOI=10.1136/bcr.08.2008.0719;
RA Chabrol B., Martens K., Meulemans S., Cano A., Jaeken J., Matthijs G.,
RA Creemers J.W.;
RT "Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria
RT syndrome.";
RL BMJ Case Rep. 2009:0-0(2009).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20975703; DOI=10.1038/ncomms1044;
RA Magnani R., Dirk L.M., Trievel R.C., Houtz R.L.;
RT "Calmodulin methyltransferase is an evolutionarily conserved enzyme that
RT trimethylates Lys-115 in calmodulin.";
RL Nat. Commun. 1:43-43(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH HSP90.
RX PubMed=23285036; DOI=10.1371/journal.pone.0052425;
RA Magen S., Magnani R., Haziza S., Hershkovitz E., Houtz R., Cambi F.,
RA Parvari R.;
RT "Human calmodulin methyltransferase: expression, activity on calmodulin,
RT and Hsp90 dependence.";
RL PLoS ONE 7:E52425-E52425(2012).
CC -!- FUNCTION: Catalyzes the trimethylation of 'Lys-116' in calmodulin.
CC {ECO:0000269|PubMed:20975703}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[calmodulin]-L-lysine + S-adenosyl-L-methionine =
CC [calmodulin]-N(6)-methyl-L-lysine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:21556, Rhea:RHEA-COMP:11360, Rhea:RHEA-COMP:11361,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.60;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00942,
CC ECO:0000269|PubMed:20975703};
CC -!- SUBUNIT: Monomer (By similarity). Interacts with HSP90, probably as a
CC client. {ECO:0000250, ECO:0000269|PubMed:23285036}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:23285036}. Nucleus {ECO:0000269|PubMed:23285036}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Golgi apparatus
CC {ECO:0000269|PubMed:23285036}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7Z624-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z624-2; Sequence=VSP_027784, VSP_027785;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in brain, liver, muscle
CC colon and lung. Isoform 2 is expressed in colon, testis, kidney and
CC brain. Isoform 1 and isoform 2 are expressed in normal lymphoblastoid
CC cells but not in lymphoblastoid cells from patients with hypotonia-
CC cystinuria syndrome. {ECO:0000269|PubMed:15913950}.
CC -!- DISEASE: Hypotonia-cystinuria syndrome (HCS) [MIM:606407]:
CC Characterized generalized hypotonia at birth, nephrolithiasis, growth
CC hormone deficiency, minor facial dysmorphism, failure to thrive,
CC followed by hyperphagia and rapid weight gain in late childhood.
CC {ECO:0000269|PubMed:21686663}. Note=The gene represented in this entry
CC is involved in disease pathogenesis. A homozygous 77.4-kb deletion that
CC disrupts the gene represented in this entry, PREPL, and SLC3A1, causes
CC atypical hypotonia-cystinuria syndrome, characterized by mild to
CC moderate intellectual disability and respiratory chain complex IV
CC deficiency. {ECO:0000269|PubMed:21686663}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. CLNMT methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00942}.
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DR EMBL; AK027104; BAB15658.1; -; mRNA.
DR EMBL; AC016703; AAX93163.1; -; Genomic_DNA.
DR EMBL; AC067957; AAX88866.1; -; Genomic_DNA.
DR EMBL; BC029359; AAH29359.1; -; mRNA.
DR EMBL; BC053733; AAH53733.1; -; mRNA.
DR CCDS; CCDS1820.1; -. [Q7Z624-1]
DR RefSeq; NP_079042.1; NM_024766.4. [Q7Z624-1]
DR PDB; 4PWY; X-ray; 1.90 A; A=61-323.
DR PDBsum; 4PWY; -.
DR AlphaFoldDB; Q7Z624; -.
DR SMR; Q7Z624; -.
DR BioGRID; 122917; 37.
DR IntAct; Q7Z624; 7.
DR STRING; 9606.ENSP00000367755; -.
DR GlyGen; Q7Z624; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7Z624; -.
DR PhosphoSitePlus; Q7Z624; -.
DR BioMuta; CAMKMT; -.
DR DMDM; 158563944; -.
DR EPD; Q7Z624; -.
DR jPOST; Q7Z624; -.
DR MassIVE; Q7Z624; -.
DR MaxQB; Q7Z624; -.
DR PaxDb; Q7Z624; -.
DR PeptideAtlas; Q7Z624; -.
DR PRIDE; Q7Z624; -.
DR ProteomicsDB; 69369; -. [Q7Z624-1]
DR ProteomicsDB; 69370; -. [Q7Z624-2]
DR Antibodypedia; 53862; 21 antibodies from 13 providers.
DR DNASU; 79823; -.
DR Ensembl; ENST00000378494.8; ENSP00000367755.3; ENSG00000143919.15. [Q7Z624-1]
DR Ensembl; ENST00000403853.7; ENSP00000385124.3; ENSG00000143919.15. [Q7Z624-2]
DR GeneID; 79823; -.
DR KEGG; hsa:79823; -.
DR MANE-Select; ENST00000378494.8; ENSP00000367755.3; NM_024766.5; NP_079042.1.
DR UCSC; uc002rul.3; human. [Q7Z624-1]
DR CTD; 79823; -.
DR DisGeNET; 79823; -.
DR GeneCards; CAMKMT; -.
DR HGNC; HGNC:26276; CAMKMT.
DR HPA; ENSG00000143919; Low tissue specificity.
DR MalaCards; CAMKMT; -.
DR MIM; 606407; phenotype.
DR MIM; 609559; gene.
DR neXtProt; NX_Q7Z624; -.
DR OpenTargets; ENSG00000143919; -.
DR Orphanet; 163693; 2p21 microdeletion syndrome.
DR Orphanet; 369881; 2p21 microdeletion syndrome without cystinuria.
DR Orphanet; 238523; Atypical hypotonia-cystinuria syndrome.
DR PharmGKB; PA142672380; -.
DR VEuPathDB; HostDB:ENSG00000143919; -.
DR eggNOG; KOG3201; Eukaryota.
DR GeneTree; ENSGT00390000002168; -.
DR HOGENOM; CLU_153311_1_0_1; -.
DR InParanoid; Q7Z624; -.
DR OMA; FQDECVA; -.
DR OrthoDB; 1161502at2759; -.
DR PhylomeDB; Q7Z624; -.
DR TreeFam; TF316589; -.
DR BRENDA; 2.1.1.60; 2681.
DR PathwayCommons; Q7Z624; -.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR Reactome; R-HSA-8876725; Protein methylation.
DR SignaLink; Q7Z624; -.
DR BioGRID-ORCS; 79823; 13 hits in 1082 CRISPR screens.
DR ChiTaRS; CAMKMT; human.
DR GenomeRNAi; 79823; -.
DR Pharos; Q7Z624; Tbio.
DR PRO; PR:Q7Z624; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q7Z624; protein.
DR Bgee; ENSG00000143919; Expressed in nucleus accumbens and 147 other tissues.
DR ExpressionAtlas; Q7Z624; baseline and differential.
DR Genevisible; Q7Z624; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0018025; F:calmodulin-lysine N-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR GO; GO:0018022; P:peptidyl-lysine methylation; IEA:Ensembl.
DR GO; GO:0006479; P:protein methylation; TAS:Reactome.
DR GO; GO:0022400; P:regulation of rhodopsin mediated signaling pathway; TAS:Reactome.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025800; CaM-Lys-N-MeTrfase.
DR InterPro; IPR019410; Methyltransf_16.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR13539; PTHR13539; 1.
DR Pfam; PF10294; Methyltransf_16; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51610; SAM_CLNMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Golgi apparatus;
KW Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..323
FT /note="Calmodulin-lysine N-methyltransferase"
FT /id="PRO_0000300115"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 126..132
FT /note="CIWPSEE -> WEATRGK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027784"
FT VAR_SEQ 133..323
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027785"
FT CONFLICT 209
FT /note="V -> F (in Ref. 3; AAH53733)"
FT /evidence="ECO:0000305"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 88..95
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 112..117
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 129..140
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:4PWY"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 160..168
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 181..196
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 215..219
FT /evidence="ECO:0007829|PDB:4PWY"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 225..232
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 240..250
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 251..261
FT /evidence="ECO:0007829|PDB:4PWY"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 267..277
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 290..302
FT /evidence="ECO:0007829|PDB:4PWY"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:4PWY"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:4PWY"
FT STRAND 315..321
FT /evidence="ECO:0007829|PDB:4PWY"
SQ SEQUENCE 323 AA; 36128 MW; 0B2C0D4E2C7B10FB CRC64;
MESRVADAGT GETARAAGGS PAVGCTTRGP VVSAPLGAAR WKLLRQVLKQ KHLDDCLRHV
SVRRFESFNL FSVTEGKERE TEEEVGAWVQ YTSIFCPEYS ISLRHNSGSL NVEDVLTSFD
NTGNVCIWPS EEVLAYYCLK HNNIFRALAV CELGGGMTCL AGLMVAISAD VKEVLLTDGN
EKAIRNVQDI ITRNQKAGVF KTQKISSCVL RWDNETDVSQ LEGHFDIVMC ADCLFLDQYR
ASLVDAIKRL LQPRGKAMVF APRRGNTLNQ FCNLAEKAGF CIQRHENYDE HISNFHSKLK
KENPDIYEEN LHYPLLLILT KHG
