BHMT1_RAT
ID BHMT1_RAT Reviewed; 407 AA.
AC O09171; Q6AZ06;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Betaine--homocysteine S-methyltransferase 1 {ECO:0000303|PubMed:12487625};
DE EC=2.1.1.5 {ECO:0000269|PubMed:12487625, ECO:0000269|PubMed:28288879};
GN Name=Bhmt {ECO:0000303|PubMed:12487625};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8753772; DOI=10.1006/bbrc.1996.1183;
RA Forestier M., Reichen J., Solioz M.;
RT "Application of mRNA differential display to liver cirrhosis: reduced
RT fetuin expression in biliary cirrhosis in the rat.";
RL Biochem. Biophys. Res. Commun. 225:377-383(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10417327; DOI=10.1042/bj3410639;
RA Sowden M.P., Collins H.L., Smith H.C., Garrow T.A., Sparks J.D.,
RA Sparks C.E.;
RT "Apolipoprotein B mRNA and lipoprotein secretion are increased in McArdle
RT RH-7777 cells by expression of betaine-homocysteine S-methyltransferase.";
RL Biochem. J. 341:639-645(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-21; ASP-26; THR-73; PHE-74;
RP TYR-77; ALA-119; GLU-159; THR-184 AND CYS-186.
RX PubMed=12487625; DOI=10.1042/bj20021510;
RA Gonzalez B., Campillo N., Garrido F., Gasset M., Sanz-Aparicio J.,
RA Pajares M.A.;
RT "Active-site-mutagenesis study of rat liver betaine-homocysteine S-
RT methyltransferase.";
RL Biochem. J. 370:945-952(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-330, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF LYS-7; LYS-8; LYS-10 AND ARG-11.
RX PubMed=28288879; DOI=10.1016/j.bbamcr.2017.03.004;
RA Perez-Miguelsanz J., Vallecillo N., Garrido F., Reytor E., Perez-Sala D.,
RA Pajares M.A.;
RT "Betaine homocysteine S-methyltransferase emerges as a new player of the
RT nuclear methionine cycle.";
RL Biochim. Biophys. Acta 1864:1165-1182(2017).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT.
RX PubMed=15099744; DOI=10.1016/j.jmb.2004.03.005;
RA Gonzalez B., Pajares M.A., Martinez-Ripoll M., Blundell T.L.,
RA Sanz-Aparicio J.;
RT "Crystal structure of rat liver betaine homocysteine S-methyltransferase
RT reveals new oligomerization features and conformational changes upon
RT substrate binding.";
RL J. Mol. Biol. 338:771-782(2004).
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:0000269|PubMed:12487625,
CC ECO:0000269|PubMed:28288879}.
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:0000269|PubMed:12487625, ECO:0000269|PubMed:28288879};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22337;
CC Evidence={ECO:0000305|PubMed:12487625, ECO:0000305|PubMed:28288879};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=106.4 uM for L-homocysteine {ECO:0000269|PubMed:12487625};
CC KM=333.3 uM for glycine betaine {ECO:0000269|PubMed:12487625};
CC Vmax=18.67 nmol/min/mg enzyme (L-methionine biosynthesis)
CC {ECO:0000269|PubMed:12487625};
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:0000305|PubMed:12487625}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15099744,
CC ECO:0000269|PubMed:28288879}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12487625,
CC ECO:0000269|PubMed:28288879}. Nucleus {ECO:0000269|PubMed:28288879}.
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:0000269|PubMed:28288879}.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver and kidney (at protein
CC level). Expressed at lower levels in testis, lung, cerebellum, skeletal
CC muscle and pancreas (at protein level). {ECO:0000269|PubMed:28288879}.
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DR EMBL; U96133; AAB53763.1; -; mRNA.
DR EMBL; AF038870; AAB95481.1; -; mRNA.
DR EMBL; BC078811; AAH78811.1; -; mRNA.
DR RefSeq; NP_110477.1; NM_030850.1.
DR PDB; 1UMY; X-ray; 2.50 A; A/B/C/D=1-407.
DR PDBsum; 1UMY; -.
DR AlphaFoldDB; O09171; -.
DR SMR; O09171; -.
DR IntAct; O09171; 2.
DR STRING; 10116.ENSRNOP00000015336; -.
DR iPTMnet; O09171; -.
DR PhosphoSitePlus; O09171; -.
DR PaxDb; O09171; -.
DR PRIDE; O09171; -.
DR GeneID; 81508; -.
DR KEGG; rno:81508; -.
DR UCSC; RGD:621496; rat.
DR CTD; 635; -.
DR RGD; 621496; Bhmt.
DR eggNOG; KOG1579; Eukaryota.
DR InParanoid; O09171; -.
DR OrthoDB; 731388at2759; -.
DR PhylomeDB; O09171; -.
DR TreeFam; TF329202; -.
DR BioCyc; MetaCyc:MON-9241; -.
DR BRENDA; 2.1.1.10; 5301.
DR BRENDA; 2.1.1.5; 5301.
DR Reactome; R-RNO-1614635; Sulfur amino acid metabolism.
DR Reactome; R-RNO-6798163; Choline catabolism.
DR UniPathway; UPA00051; UER00083.
DR UniPathway; UPA00291; UER00432.
DR EvolutionaryTrace; O09171; -.
DR PRO; PR:O09171; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0047150; F:betaine-homocysteine S-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0071266; P:'de novo' L-methionine biosynthetic process; ISO:RGD.
DR GO; GO:0006579; P:amino-acid betaine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006577; P:amino-acid betaine metabolic process; ISO:RGD.
DR GO; GO:0071267; P:L-methionine salvage; ISO:RGD.
DR GO; GO:0009086; P:methionine biosynthetic process; IDA:RGD.
DR GO; GO:0006479; P:protein methylation; IDA:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
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 3D-structure; Cytoplasm; Metal-binding; Methyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Zinc.
FT CHAIN 1..407
FT /note="Betaine--homocysteine S-methyltransferase 1"
FT /id="PRO_0000114624"
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:0000250|UniProtKB:O35490"
FT MOD_RES 93
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35490"
FT MOD_RES 98
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35490"
FT MOD_RES 232
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35490"
FT MOD_RES 241
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35490"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 340
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35490"
FT MOD_RES 377
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35490"
FT MUTAGEN 7
FT /note="K->A: Has no effect on tetramer assembly or
FT catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:28288879"
FT MUTAGEN 8
FT /note="K->A: Has no effect on tetramer assembly. Decreases
FT the catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:28288879"
FT MUTAGEN 10
FT /note="K->A: Has no effect on tetramer assembly. Decreases
FT the catalytic efficiency. Alters nucleocytoplasmic
FT distribution."
FT /evidence="ECO:0000269|PubMed:28288879"
FT MUTAGEN 11
FT /note="R->A: Has no effect on tetramer assembly."
FT /evidence="ECO:0000269|PubMed:28288879"
FT MUTAGEN 21
FT /note="E->A,K: Decreases the catalytic efficiency.
FT Increases the affinity for L-homocysteine."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 26
FT /note="D->A,I: Decreases the catalytic efficiency.
FT Decreases the affinity for glycine betaine."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 73
FT /note="T->G: Decreases the catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 74
FT /note="F->A: Decreases the catalytic efficiency. Decreases
FT the affinity for glycine betaine."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 77
FT /note="Y->A: Decreases the catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 119
FT /note="A->G: Decreases the catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 159
FT /note="E->G,K: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 184
FT /note="T->G: Decreases the catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:12487625"
FT MUTAGEN 186
FT /note="C->A,S: Decreases the catalytic efficiency.
FT Increases the affinity for L-homocysteine."
FT /evidence="ECO:0000269|PubMed:12487625"
FT CONFLICT 247..248
FT /note="HA -> QP (in Ref. 3; AAH78811)"
FT /evidence="ECO:0000305"
FT HELIX 13..18
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 29..35
FT /evidence="ECO:0007829|PDB:1UMY"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 53..66
FT /evidence="ECO:0007829|PDB:1UMY"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 96..112
FT /evidence="ECO:0007829|PDB:1UMY"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:1UMY"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 134..150
FT /evidence="ECO:0007829|PDB:1UMY"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 164..175
FT /evidence="ECO:0007829|PDB:1UMY"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 198..207
FT /evidence="ECO:0007829|PDB:1UMY"
FT STRAND 211..219
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 221..236
FT /evidence="ECO:0007829|PDB:1UMY"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:1UMY"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:1UMY"
FT TURN 265..269
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 278..291
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 304..313
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 315..318
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 323..327
FT /evidence="ECO:0007829|PDB:1UMY"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 341..344
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 349..354
FT /evidence="ECO:0007829|PDB:1UMY"
FT HELIX 378..397
FT /evidence="ECO:0007829|PDB:1UMY"
SQ SEQUENCE 407 AA; 44976 MW; 36E1D04A8E425887 CRC64;
MAPIAGKKAK RGILERLNAG EVVIGDGGFV FALEKRGYVK AGPWTPEAAV EHPEAVRQLH
REFLRAGSNV MQTFTFYASE DKLENRGNYV AEKISGQKVN EAACDIARQV ADEGDALVAG
GVSQTPSYLS CKSETEVKKI FHQQLEVFMK KNVDFLIAEY FEHVEEAVWA VEALKTSGKP
IAATMCIGPE GDLHGVSPGE CAVRLVKAGA AIVGVNCHFD PSTSLQTIKL MKEGLEAARL
KAYLMSHALA YHTPDCGKQG FIDLPEFPFG LEPRVATRWD IQKYAREAYN LGVRYIGGCC
GFEPYHIRAI AEELAPERGF LPPASEKHGS WGSGLDMHTK PWIRARARKE YWQNLRIASG
RPYNPSMSKP DAWGVTKGAA ELMQQKEATT EQQLRALFEK QKFKSAQ
