BHMT1_MOUSE
ID BHMT1_MOUSE Reviewed; 407 AA.
AC O35490; Q3UEM1; Q3UL72; Q561N0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Betaine--homocysteine S-methyltransferase 1;
DE EC=2.1.1.5 {ECO:0000250|UniProtKB:Q93088};
GN Name=Bhmt;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvEv;
RX PubMed=10854776; DOI=10.1016/s0378-1119(00)00191-8;
RA Neece D.J., Griffiths M.A., Garrow T.A.;
RT "Isolation and characterization of a mouse betaine-homocysteine S-
RT methyltransferase gene and pseudogene.";
RL Gene 250:31-40(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129; TISSUE=Liver;
RA Sowden M.P., Smith H.C.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-40; LYS-93; LYS-98; LYS-232;
RP LYS-241; LYS-340 AND LYS-377, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Involved in the regulation of homocysteine metabolism.
CC Converts betaine and homocysteine to dimethylglycine and methionine,
CC respectively. This reaction is also required for the irreversible
CC oxidation of choline. {ECO:0000250|UniProtKB:Q93088}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine betaine + L-homocysteine = L-methionine + N,N-
CC dimethylglycine; Xref=Rhea:RHEA:22336, ChEBI:CHEBI:17750,
CC ChEBI:CHEBI:57844, ChEBI:CHEBI:58199, ChEBI:CHEBI:58251; EC=2.1.1.5;
CC Evidence={ECO:0000250|UniProtKB:Q93088};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22337;
CC Evidence={ECO:0000250|UniProtKB:Q93088};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q93088};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q93088};
CC -!- PATHWAY: Amine and polyamine degradation; betaine degradation;
CC sarcosine from betaine: step 1/2.
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-methionine from L-homocysteine (BhmT route): step 1/1.
CC {ECO:0000250|UniProtKB:Q93088}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q93088}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O09171}. Nucleus {ECO:0000250|UniProtKB:O09171}.
CC Note=Predominantly localized in the cytoplasm with a small fraction
CC detected in the nucleus. Translocates into the nucleus upon oxidative
CC stress. {ECO:0000250|UniProtKB:O09171}.
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DR EMBL; AH009623; AAF85944.1; -; Genomic_DNA.
DR EMBL; AF033381; AAB87501.1; -; mRNA.
DR EMBL; AK145668; BAE26578.1; -; mRNA.
DR EMBL; AK149457; BAE28890.1; -; mRNA.
DR EMBL; AK166754; BAE38995.1; -; mRNA.
DR EMBL; AK166818; BAE39044.1; -; mRNA.
DR EMBL; BC037004; AAH37004.1; -; mRNA.
DR EMBL; BC093510; AAH93510.1; -; mRNA.
DR EMBL; BC110307; AAI10308.1; -; mRNA.
DR CCDS; CCDS36748.1; -.
DR RefSeq; NP_057877.1; NM_016668.3.
DR AlphaFoldDB; O35490; -.
DR SMR; O35490; -.
DR BioGRID; 198347; 2.
DR IntAct; O35490; 1.
DR MINT; O35490; -.
DR STRING; 10090.ENSMUSP00000096912; -.
DR iPTMnet; O35490; -.
DR MetOSite; O35490; -.
DR PhosphoSitePlus; O35490; -.
DR SwissPalm; O35490; -.
DR REPRODUCTION-2DPAGE; O35490; -.
DR CPTAC; non-CPTAC-3450; -.
DR jPOST; O35490; -.
DR MaxQB; O35490; -.
DR PaxDb; O35490; -.
DR PeptideAtlas; O35490; -.
DR PRIDE; O35490; -.
DR ProteomicsDB; 265212; -.
DR DNASU; 12116; -.
DR Ensembl; ENSMUST00000091776; ENSMUSP00000135956; ENSMUSG00000069324.
DR Ensembl; ENSMUST00000099309; ENSMUSP00000096912; ENSMUSG00000074768.
DR GeneID; 12116; -.
DR KEGG; mmu:12116; -.
DR UCSC; uc007rli.1; mouse.
DR CTD; 635; -.
DR MGI; MGI:1339972; Bhmt.
DR VEuPathDB; HostDB:ENSMUSG00000069324; -.
DR VEuPathDB; HostDB:ENSMUSG00000074768; -.
DR eggNOG; KOG1579; Eukaryota.
DR GeneTree; ENSGT00390000003122; -.
DR HOGENOM; CLU_047457_0_0_1; -.
DR InParanoid; O35490; -.
DR OMA; IATRWDI; -.
DR OrthoDB; 731388at2759; -.
DR PhylomeDB; O35490; -.
DR TreeFam; TF329202; -.
DR BRENDA; 2.1.1.5; 3474.
DR Reactome; R-MMU-1614635; Sulfur amino acid metabolism.
DR Reactome; R-MMU-6798163; Choline catabolism.
DR UniPathway; UPA00051; UER00083.
DR UniPathway; UPA00291; UER00432.
DR BioGRID-ORCS; 12116; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Bhmt; mouse.
DR PRO; PR:O35490; -.
DR Proteomes; UP000000589; Chromosome 13.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; O35490; protein.
DR Bgee; ENSMUSG00000069324; Expressed in morula and 11 other tissues.
DR Genevisible; O35490; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0047150; F:betaine-homocysteine S-methyltransferase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008168; F:methyltransferase activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0071266; P:'de novo' L-methionine biosynthetic process; ISO:MGI.
DR GO; GO:0006579; P:amino-acid betaine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006577; P:amino-acid betaine metabolic process; ISO:MGI.
DR GO; GO:0071267; P:L-methionine salvage; ISO:MGI.
DR GO; GO:0009086; P:methionine biosynthetic process; IDA:MGI.
DR GO; GO:0006479; P:protein methylation; ISO:MGI.
DR Gene3D; 3.20.20.330; -; 1.
DR InterPro; IPR017226; Betaine-hCys_S-MeTrfase_BHMT.
DR InterPro; IPR003726; HCY_dom.
DR InterPro; IPR036589; HCY_dom_sf.
DR Pfam; PF02574; S-methyl_trans; 1.
DR PIRSF; PIRSF037505; Betaine_HMT; 1.
DR SUPFAM; SSF82282; SSF82282; 1.
DR PROSITE; PS50970; HCY; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..407
FT /note="Betaine--homocysteine S-methyltransferase 1"
FT /id="PRO_0000114622"
FT DOMAIN 11..314
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 217
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q93088,
FT ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q93088,
FT ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 300
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q93088,
FT ECO:0000255|PROSITE-ProRule:PRU00333"
FT MOD_RES 40
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 93
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 98
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 232
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 241
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O09171"
FT MOD_RES 340
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 377
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 7
FT /note="K -> E (in Ref. 3; BAE26578)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 407 AA; 45021 MW; 1C600BE9CC44EE32 CRC64;
MAPVAGKKAK KGILERLNAG EVVIGDGGFV FALEKRGYVK AGPWTPEAAV EHPEAVRQLH
REFLRAGSNV MQTFTFYASE DKLENRGNYV AEKISGQKVN EAACDIARQV ADEGDALVAG
GVSQTPSYLS CKSEVEVKKI FRQQLEVFMK KNVDFLIAEY FEHVEEAVWA VEALKASGKP
VAATMCIGPE GDLHGVPPGE CAVRLVKAGA SIVGVNCHFD PSVSLQTVKL MKEGLEAARL
KAYLMSQPLA YHTPDCGKQG FIDLPEFPFG LEPRVATRWD IQKYAREAYN LGVRYIGGCC
GFEPYHIRAI AEELAPERGF LPPASEKHGS WGSGLDMHTK PWIRARARKE YWQNLRIASG
RPYNPSMSRP DAWGVTKGAA ELMQQKEATT EQQLRELFEK QKFKSAQ
