BHMT2_HUMAN
ID BHMT2_HUMAN Reviewed; 363 AA.
AC Q9H2M3; B7Z516; Q9NXX7;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=S-methylmethionine--homocysteine S-methyltransferase BHMT2;
DE Short=SMM-hcy methyltransferase;
DE EC=2.1.1.10;
DE AltName: Full=Betaine--homocysteine S-methyltransferase 2;
GN Name=BHMT2;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND POSSIBLE
RP INTERACTION WITH PRNP.
RX PubMed=11087663; DOI=10.1006/geno.2000.6319;
RA Chadwick L.H., McCandless S.E., Silverman G.L., Schwartz S., Westaway D.,
RA Nadeau J.H.;
RT "Betaine-homocysteine methyltransferase-2: cDNA cloning, gene sequence,
RT physical mapping, and expression of the human and mouse genes.";
RL Genomics 70:66-73(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 11-363 (ISOFORM 1).
RC TISSUE=Adipose tissue, and Kidney;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ZINC-BINDING.
RX PubMed=18230605; DOI=10.1074/jbc.m710449200;
RA Szegedi S.S., Castro C.C., Koutmos M., Garrow T.A.;
RT "Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-
RT homocysteine methyltransferase.";
RL J. Biol. Chem. 283:8939-8945(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Involved in the regulation of homocysteine metabolism.
CC Converts homocysteine to methionine using S-methylmethionine (SMM) as a
CC methyl donor. {ECO:0000269|PubMed:18230605}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homocysteine + S-methyl-L-methionine = H(+) + 2 L-
CC methionine; Xref=Rhea:RHEA:26337, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57844, ChEBI:CHEBI:58199, ChEBI:CHEBI:58252; EC=2.1.1.10;
CC Evidence={ECO:0000269|PubMed:18230605};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18230605};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18230605};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-methionine from L-homocysteine (BhmT route): step 1/1.
CC -!- SUBUNIT: Homotetramer (By similarity). May interact with PRNP.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H2M3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2M3-2; Sequence=VSP_042938;
CC -!- TISSUE SPECIFICITY: Expressed in liver and kidney and at reduced levels
CC in the brain, heart, and skeletal muscle.
CC {ECO:0000269|PubMed:11087663}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA90880.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF257473; AAG41356.1; -; mRNA.
DR EMBL; AK000008; BAA90880.1; ALT_INIT; mRNA.
DR EMBL; AK298298; BAH12752.1; -; mRNA.
DR EMBL; AC008502; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020665; AAH20665.1; -; mRNA.
DR CCDS; CCDS4045.1; -. [Q9H2M3-1]
DR CCDS; CCDS54871.1; -. [Q9H2M3-2]
DR RefSeq; NP_001171476.1; NM_001178005.1. [Q9H2M3-2]
DR RefSeq; NP_060084.2; NM_017614.4. [Q9H2M3-1]
DR AlphaFoldDB; Q9H2M3; -.
DR SMR; Q9H2M3; -.
DR BioGRID; 117245; 7.
DR IntAct; Q9H2M3; 3.
DR STRING; 9606.ENSP00000255192; -.
DR BindingDB; Q9H2M3; -.
DR ChEMBL; CHEMBL2163167; -.
DR DrugBank; DB00134; Methionine.
DR iPTMnet; Q9H2M3; -.
DR PhosphoSitePlus; Q9H2M3; -.
DR BioMuta; BHMT2; -.
DR DMDM; 74733563; -.
DR jPOST; Q9H2M3; -.
DR MassIVE; Q9H2M3; -.
DR MaxQB; Q9H2M3; -.
DR PaxDb; Q9H2M3; -.
DR PeptideAtlas; Q9H2M3; -.
DR PRIDE; Q9H2M3; -.
DR ProteomicsDB; 80567; -. [Q9H2M3-1]
DR ProteomicsDB; 80568; -. [Q9H2M3-2]
DR Antibodypedia; 24546; 120 antibodies from 21 providers.
DR DNASU; 23743; -.
DR Ensembl; ENST00000255192.8; ENSP00000255192.3; ENSG00000132840.10. [Q9H2M3-1]
DR Ensembl; ENST00000521567.1; ENSP00000430278.1; ENSG00000132840.10. [Q9H2M3-2]
DR GeneID; 23743; -.
DR KEGG; hsa:23743; -.
DR MANE-Select; ENST00000255192.8; ENSP00000255192.3; NM_017614.5; NP_060084.2.
DR UCSC; uc003kft.4; human. [Q9H2M3-1]
DR CTD; 23743; -.
DR DisGeNET; 23743; -.
DR GeneCards; BHMT2; -.
DR HGNC; HGNC:1048; BHMT2.
DR HPA; ENSG00000132840; Group enriched (kidney, liver).
DR MIM; 605932; gene.
DR neXtProt; NX_Q9H2M3; -.
DR OpenTargets; ENSG00000132840; -.
DR PharmGKB; PA25351; -.
DR VEuPathDB; HostDB:ENSG00000132840; -.
DR eggNOG; KOG1579; Eukaryota.
DR GeneTree; ENSGT00390000003122; -.
DR HOGENOM; CLU_047457_0_0_1; -.
DR InParanoid; Q9H2M3; -.
DR OMA; CRFGPRT; -.
DR PhylomeDB; Q9H2M3; -.
DR TreeFam; TF329202; -.
DR BioCyc; MetaCyc:HS05696-MON; -.
DR PathwayCommons; Q9H2M3; -.
DR Reactome; R-HSA-1614635; Sulfur amino acid metabolism.
DR SignaLink; Q9H2M3; -.
DR UniPathway; UPA00051; UER00083.
DR BioGRID-ORCS; 23743; 104 hits in 1068 CRISPR screens.
DR ChiTaRS; BHMT2; human.
DR GenomeRNAi; 23743; -.
DR Pharos; Q9H2M3; Tchem.
DR PRO; PR:Q9H2M3; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9H2M3; protein.
DR Bgee; ENSG00000132840; Expressed in renal medulla and 163 other tissues.
DR ExpressionAtlas; Q9H2M3; baseline and differential.
DR Genevisible; Q9H2M3; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0061627; F:S-methylmethionine-homocysteine S-methyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL.
DR GO; GO:0071267; P:L-methionine salvage; IDA:BHF-UCL.
DR GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; IDA:BHF-UCL.
DR GO; GO:0033477; P:S-methylmethionine metabolic process; IDA:BHF-UCL.
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 Alternative splicing; Metal-binding; Methyltransferase; Phosphoprotein;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..363
FT /note="S-methylmethionine--homocysteine S-methyltransferase
FT BHMT2"
FT /id="PRO_0000273224"
FT DOMAIN 11..305
FT /note="Hcy-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT BINDING 291
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00333"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 87..150
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042938"
SQ SEQUENCE 363 AA; 40354 MW; 92D35414D2D56003 CRC64;
MAPAGRPGAK KGILERLESG EVVIGDGSFL ITLEKRGYVK AGLWTPEAVI EHPDAVRQLH
MEFLRAGSNV MQTFTFSASE DNMESKWEDV NAAACDLARE VAGKGDALVA GGICQTSIYK
YQKDEARIKK LFRQQLEVFA WKNVDFLIAE YFEHVEEAVW AVEVLKESDR PVAVTMCIGP
EGDMHDITPG ECAVRLVKAG ASIVGVNCRF GPDTSLKTME LMKEGLEWAG LKAHLMVQPL
GFHAPDCGKE GFVDLPEYPF GLESRVATRW DIQKYAREAY NLGVRYIGGC CGFEPYHIRA
IAEELAPERG FLPPASEKHG SWGSGLDMHT KPWIRARARR EYWENLLPAS GRPFCPSLSK
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