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Protein

S-methylmethionine--homocysteine S-methyltransferase BHMT2

Gene

BHMT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the regulation of homocysteine metabolism. Converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor.1 Publication

Catalytic activityi

S-methyl-L-methionine + L-homocysteine = 2 L-methionine.1 Publication

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Pathway: L-methionine biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes L-methionine from L-homocysteine (BhmT route).
Proteins known to be involved in this subpathway in this organism are:
  1. cDNA, FLJ96222, highly similar to Homo sapiens betaine-homocysteine methyltransferase (BHMT), mRNA, Betaine-homocysteine methyltransferase, isoform CRA_a (HEL-S-61p), cDNA FLJ54604, highly similar to Betaine--homocysteine S-methyltransferase (EC 2.1.1.5), S-methylmethionine--homocysteine S-methyltransferase BHMT2 (BHMT2), Betaine--homocysteine S-methyltransferase 1 (BHMT), cDNA, FLJ96586, highly similar to Homo sapiens betaine-homocysteine methyltransferase 2 (BHMT2), mRNA, Betaine-homocysteine methyltransferase 2, isoform CRA_c (BHMT2)
This subpathway is part of the pathway L-methionine biosynthesis via de novo pathway, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-methionine from L-homocysteine (BhmT route), the pathway L-methionine biosynthesis via de novo pathway and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi208 – 2081ZincPROSITE-ProRule annotation
Metal bindingi290 – 2901ZincPROSITE-ProRule annotation
Metal bindingi291 – 2911ZincPROSITE-ProRule annotation

GO - Molecular functioni

  • S-adenosylmethionine-homocysteine S-methyltransferase activity Source: BHF-UCL
  • S-methylmethionine-homocysteine S-methyltransferase activity Source: BHF-UCL
  • zinc ion binding Source: BHF-UCL

GO - Biological processi

  • L-methionine salvage Source: BHF-UCL
  • S-adenosylmethionine metabolic process Source: BHF-UCL
  • S-methylmethionine cycle Source: GO_Central
  • S-methylmethionine metabolic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS05696-MONOMER.
UniPathwayiUPA00051; UER00083.

Names & Taxonomyi

Protein namesi
Recommended name:
S-methylmethionine--homocysteine S-methyltransferase BHMT2 (EC:2.1.1.10)
Short name:
SMM-hcy methyltransferase
Alternative name(s):
Betaine--homocysteine S-methyltransferase 2
Gene namesi
Name:BHMT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:1048. BHMT2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: GO_Central
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA25351.

Chemistry

DrugBankiDB00134. L-Methionine.

Polymorphism and mutation databases

BioMutaiBHMT2.
DMDMi74733563.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 363363S-methylmethionine--homocysteine S-methyltransferase BHMT2PRO_0000273224Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei321 – 3211Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9H2M3.
PRIDEiQ9H2M3.

PTM databases

PhosphoSiteiQ9H2M3.

Expressioni

Tissue specificityi

Expressed in liver and kidney and at reduced levels in the brain, heart, and skeletal muscle.1 Publication

Gene expression databases

BgeeiQ9H2M3.
CleanExiHS_BHMT2.
ExpressionAtlasiQ9H2M3. baseline and differential.
GenevisibleiQ9H2M3. HS.

Organism-specific databases

HPAiHPA044573.

Interactioni

Subunit structurei

Homotetramer (By similarity). May interact with PRNP.By similarity

Protein-protein interaction databases

BioGridi117245. 4 interactions.
STRINGi9606.ENSP00000255192.

Structurei

3D structure databases

ProteinModelPortaliQ9H2M3.
SMRiQ9H2M3. Positions 10-362.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini11 – 305295Hcy-bindingPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 Hcy-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0646.
GeneTreeiENSGT00390000003122.
HOGENOMiHOG000231636.
HOVERGENiHBG080367.
InParanoidiQ9H2M3.
OMAiPEGDMHD.
OrthoDBiEOG79GT7C.
PhylomeDBiQ9H2M3.
TreeFamiTF329202.

Family and domain databases

Gene3Di3.20.20.330. 1 hit.
InterProiIPR017226. Betaine-hCys_S-MeTrfase_BHMT.
IPR003726. S_MeTrfase.
[Graphical view]
PfamiPF02574. S-methyl_trans. 1 hit.
[Graphical view]
PIRSFiPIRSF037505. Betaine_HMT. 1 hit.
SUPFAMiSSF82282. SSF82282. 1 hit.
PROSITEiPS50970. HCY. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H2M3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAPAGRPGAK KGILERLESG EVVIGDGSFL ITLEKRGYVK AGLWTPEAVI
60 70 80 90 100
EHPDAVRQLH MEFLRAGSNV MQTFTFSASE DNMESKWEDV NAAACDLARE
110 120 130 140 150
VAGKGDALVA GGICQTSIYK YQKDEARIKK LFRQQLEVFA WKNVDFLIAE
160 170 180 190 200
YFEHVEEAVW AVEVLKESDR PVAVTMCIGP EGDMHDITPG ECAVRLVKAG
210 220 230 240 250
ASIVGVNCRF GPDTSLKTME LMKEGLEWAG LKAHLMVQPL GFHAPDCGKE
260 270 280 290 300
GFVDLPEYPF GLESRVATRW DIQKYAREAY NLGVRYIGGC CGFEPYHIRA
310 320 330 340 350
IAEELAPERG FLPPASEKHG SWGSGLDMHT KPWIRARARR EYWENLLPAS
360
GRPFCPSLSK PDF
Length:363
Mass (Da):40,354
Last modified:March 1, 2001 - v1
Checksum:i92D35414D2D56003
GO
Isoform 2 (identifier: Q9H2M3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-150: Missing.

Note: No experimental confirmation available.
Show »
Length:299
Mass (Da):33,167
Checksum:i763335314695E79E
GO

Sequence cautioni

The sequence BAA90880.1 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei87 – 15064Missing in isoform 2. 1 PublicationVSP_042938Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF257473 mRNA. Translation: AAG41356.1.
AK000008 mRNA. Translation: BAA90880.1. Different initiation.
AK298298 mRNA. Translation: BAH12752.1.
AC008502 Genomic DNA. No translation available.
BC020665 mRNA. Translation: AAH20665.1.
CCDSiCCDS4045.1. [Q9H2M3-1]
CCDS54871.1. [Q9H2M3-2]
RefSeqiNP_001171476.1. NM_001178005.1. [Q9H2M3-2]
NP_060084.2. NM_017614.4. [Q9H2M3-1]
UniGeneiHs.114172.

Genome annotation databases

EnsembliENST00000255192; ENSP00000255192; ENSG00000132840. [Q9H2M3-1]
ENST00000521567; ENSP00000430278; ENSG00000132840. [Q9H2M3-2]
GeneIDi23743.
KEGGihsa:23743.
UCSCiuc003kft.3. human. [Q9H2M3-1]
uc011cth.2. human. [Q9H2M3-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF257473 mRNA. Translation: AAG41356.1.
AK000008 mRNA. Translation: BAA90880.1. Different initiation.
AK298298 mRNA. Translation: BAH12752.1.
AC008502 Genomic DNA. No translation available.
BC020665 mRNA. Translation: AAH20665.1.
CCDSiCCDS4045.1. [Q9H2M3-1]
CCDS54871.1. [Q9H2M3-2]
RefSeqiNP_001171476.1. NM_001178005.1. [Q9H2M3-2]
NP_060084.2. NM_017614.4. [Q9H2M3-1]
UniGeneiHs.114172.

3D structure databases

ProteinModelPortaliQ9H2M3.
SMRiQ9H2M3. Positions 10-362.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117245. 4 interactions.
STRINGi9606.ENSP00000255192.

Chemistry

BindingDBiQ9H2M3.
ChEMBLiCHEMBL2163167.
DrugBankiDB00134. L-Methionine.

PTM databases

PhosphoSiteiQ9H2M3.

Polymorphism and mutation databases

BioMutaiBHMT2.
DMDMi74733563.

Proteomic databases

PaxDbiQ9H2M3.
PRIDEiQ9H2M3.

Protocols and materials databases

DNASUi23743.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000255192; ENSP00000255192; ENSG00000132840. [Q9H2M3-1]
ENST00000521567; ENSP00000430278; ENSG00000132840. [Q9H2M3-2]
GeneIDi23743.
KEGGihsa:23743.
UCSCiuc003kft.3. human. [Q9H2M3-1]
uc011cth.2. human. [Q9H2M3-2]

Organism-specific databases

CTDi23743.
GeneCardsiGC05P078366.
HGNCiHGNC:1048. BHMT2.
HPAiHPA044573.
MIMi605932. gene.
neXtProtiNX_Q9H2M3.
PharmGKBiPA25351.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0646.
GeneTreeiENSGT00390000003122.
HOGENOMiHOG000231636.
HOVERGENiHBG080367.
InParanoidiQ9H2M3.
OMAiPEGDMHD.
OrthoDBiEOG79GT7C.
PhylomeDBiQ9H2M3.
TreeFamiTF329202.

Enzyme and pathway databases

UniPathwayiUPA00051; UER00083.
BioCyciMetaCyc:HS05696-MONOMER.

Miscellaneous databases

ChiTaRSiBHMT2. human.
GenomeRNAii23743.
NextBioi46663.
PROiQ9H2M3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9H2M3.
CleanExiHS_BHMT2.
ExpressionAtlasiQ9H2M3. baseline and differential.
GenevisibleiQ9H2M3. HS.

Family and domain databases

Gene3Di3.20.20.330. 1 hit.
InterProiIPR017226. Betaine-hCys_S-MeTrfase_BHMT.
IPR003726. S_MeTrfase.
[Graphical view]
PfamiPF02574. S-methyl_trans. 1 hit.
[Graphical view]
PIRSFiPIRSF037505. Betaine_HMT. 1 hit.
SUPFAMiSSF82282. SSF82282. 1 hit.
PROSITEiPS50970. HCY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Betaine-homocysteine methyltransferase-2: cDNA cloning, gene sequence, physical mapping, and expression of the human and mouse genes."
    Chadwick L.H., McCandless S.E., Silverman G.L., Schwartz S., Westaway D., Nadeau J.H.
    Genomics 70:66-73(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, POSSIBLE INTERACTION WITH PRNP.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-363 (ISOFORM 1).
    Tissue: Adipose tissue and Kidney.
  3. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Liver.
  5. "Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase."
    Szegedi S.S., Castro C.C., Koutmos M., Garrow T.A.
    J. Biol. Chem. 283:8939-8945(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ZINC-BINDING.
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiBHMT2_HUMAN
AccessioniPrimary (citable) accession number: Q9H2M3
Secondary accession number(s): B7Z516, Q9NXX7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: March 1, 2001
Last modified: June 24, 2015
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.