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 24-JAN-2024, entry version 163. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9606-ENSP00000255192; -. DR PeptideAtlas; Q9H2M3; -. DR ProteomicsDB; 80567; -. [Q9H2M3-1] DR ProteomicsDB; 80568; -. [Q9H2M3-2] DR Antibodypedia; 24546; 129 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 AGR; HGNC:1048; -. 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; ENMESKW; -. DR OrthoDB; 66796at2759; -. DR PhylomeDB; Q9H2M3; -. DR TreeFam; TF329202; -. DR BioCyc; MetaCyc:HS05696-MONOMER; -. DR PathwayCommons; Q9H2M3; -. DR Reactome; R-HSA-1614635; Sulfur amino acid metabolism. DR SignaLink; Q9H2M3; -. DR UniPathway; UPA00051; UER00083. DR BioGRID-ORCS; 23743; 107 hits in 1146 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 165 other cell types or 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:0008898; F:S-adenosylmethionine-homocysteine S-methyltransferase activity; IEA:UniProtKB-EC. 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: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; Homocysteine-binding-like domain; 1. DR InterPro; IPR017226; Betaine-hCys_S-MeTrfase_BHMT. DR InterPro; IPR003726; HCY_dom. DR InterPro; IPR036589; HCY_dom_sf. DR PANTHER; PTHR46120; BETAINE--HOMOCYSTEINE S-METHYLTRANSFERASE 1; 1. DR PANTHER; PTHR46120:SF3; S-METHYLMETHIONINE--HOMOCYSTEINE S-METHYLTRANSFERASE BHMT2; 1. DR Pfam; PF02574; S-methyl_trans; 1. DR PIRSF; PIRSF037505; Betaine_HMT; 1. DR SUPFAM; SSF82282; Homocysteine S-methyltransferase; 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 PDF //