Reviewed, UniProtKB/Swiss-Prot Q93088 (BHMT1_HUMAN)

Names and origin

Protein names

Recommended name:
    Betaine--homocysteine S-methyltransferase 1
    EC=2.1.1.5

Gene names

Name:

BHMT

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline.
Catalytic activity	Trimethylammonioacetate + L-homocysteine = dimethylglycine + L-methionine.
Cofactor	Binds 1 zinc ion per subunit.
Pathway	Amine and polyamine degradation; betaine degradation; sarcosine from betaine: step 1/2. Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (BhmT route): step 1/1.
Subunit structure	Homotetramer. Ref.6
Subcellular location	Cytoplasm.
Tissue specificity	Found exclusively in liver and kidney. Ref.4
Sequence similarities	Contains 1 Hcy-binding domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Methyltransferase Transferase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid methylation Ref.2 Non-traceable author statement. Source: UniProtKB regulation of homocysteine metabolic process Ref.2 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	betaine-homocysteine S-methyltransferase activity Ref.2 Non-traceable author statement. Source: UniProtKB homocysteine S-methyltransferase activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 406

406

Betaine--homocysteine S-methyltransferase 1

PRO_0000114621

Regions

Domain

11 – 314

304

Hcy-binding

Sites

Metal binding

217

1

Zinc

Metal binding

299

1

Zinc

Metal binding

300

1

Zinc

Natural variations

Natural variant

239

1

R → Q May decrease risk for coronary artery disease. dbSNP rs3733890. Ref.1 Ref.7

VAR_015886

Secondary structure

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406

Helix Strand Turn

Details...

Helix

13 – 18

6

Helix

29 – 36

8

Helix

53 – 66

14

Beta strand

69 – 74

6

Helix

100 – 112

13

Turn

113 – 115

3

Beta strand

117 – 122

6

Helix

126 – 129

4

Helix

134 – 150

17

Beta strand

154 – 158

5

Helix

164 – 174

11

Helix

175 – 177

3

Beta strand

181 – 185

5

Helix

198 – 207

10

Beta strand

211 – 219

9

Helix

221 – 237

17

Beta strand

243 – 247

5

Helix

261 – 263

3

Turn

265 – 269

5

Helix

272 – 274

3

Helix

278 – 291

14

Helix

304 – 313

10

Helix

315 – 318

4

Helix

349 – 354

6

Sequences

	Sequence		Length	Mass (Da)
	Q93088-1 [UniParc]. Last modified April 17, 2007. Version 2. Checksum: 557855B8CEDD0D54	FASTA	406	44,998
	10 20 30 40 50 60 MPPVGGKKAK KGILERLNAG EIVIGDGGFV FALEKRGYVK AGPWTPEAAV EHPEAVRQLH 70 80 90 100 110 120 REFLRAGSNV MQTFTFYASE DKLENRGNYV LEKISGQEVN EAACDIARQV ADEGDALVAG 130 140 150 160 170 180 GVSQTPSYLS CKSETEVKKV FLQQLEVFMK KNVDFLIAEY FEHVEEAVWA VETLIASGKP 190 200 210 220 230 240 VAATMCIGPE GDLHGVPPGE CAVRLVKAGA SIIGVNCHFD PTISLKTVKL MKEGLEAARL 250 260 270 280 290 300 KAHLMSQPLA YHTPDCNKQG FIDLPEFPFG LEPRVATRWD IQKYAREAYN LGVRYIGGCC 310 320 330 340 350 360 GFEPYHIRAI AEELAPERGF LPPASEKHGS WGSGLDMHTK PWVRARARKE YWENLRIASG 370 380 390 400 RPYNPSMSKP DGWGVTKGTA ELMQQKEATT EQQLKELFEK QKFKSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification, kinetic properties, and cDNA cloning of mammalian betaine-homocysteine methyltransferase." Garrow T.A. J. Biol. Chem. 271:22831-22838(1996) [PubMed: 8798461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-239. Tissue: Liver.
[2]	"Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene." Park E.I., Garrow T.A. J. Biol. Chem. 274:7816-7824(1999) [PubMed: 10075673] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lung.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[4]	"Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene." Sunden S.L.F., Renduchintala M.S., Park E.I., Miklasz S.D., Garrow T.A. Arch. Biochem. Biophys. 345:171-174(1997) [PubMed: 9281325] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Human betaine-homocysteine methyltransferase is a zinc metalloenzyme." Millian N.S., Garrow T.A. Arch. Biochem. Biophys. 356:93-98(1998) [PubMed: 9681996] [Abstract] Cited for: CHARACTERIZATION, ZINC-BINDING. Tissue: Liver.
[6]	"Betaine-homocysteine methyltransferase: zinc in a distorted barrel." Evans J.C., Huddler D.P., Jiracek J., Castro C., Millian N.S., Garrow T.A., Ludwig M.L. Structure 10:1159-1171(2002) [PubMed: 12220488] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS), SUBUNIT.
[7]	"Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease." Weisberg I.S., Park E., Ballman K.V., Berger P., Nunn M., Suh D.S., Breksa A.P., Garrow T.A., Rozen R. Atherosclerosis 167:205-214(2003) [PubMed: 12818402] [Abstract] Cited for: VARIANT GLN-239.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U50929 mRNA. Translation: AAC50668.1.
AF118378 , AF118371, AF118372, AF118373, AF118374, AF118375, AF118376, AF118377 Genomic DNA. Translation: AAD22043.1.
BC012616 mRNA. Translation: AAH12616.1.

IPI

IPI00004101.

RefSeq

NP_001704.2.

UniGene

Hs.80756

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LT7	X-ray	2.15	A/B	3-406	[»]
1LT8	X-ray	2.05	A/B	3-406	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q93088. 4 interactions.

PTM databases

PhosphoSite

Q93088.

Proteomic databases

PRIDE

Q93088.

Genome annotation databases

Ensembl

ENSG00000145692. Homo sapiens. [Contig view]

GeneID

635.

KEGG

hsa:635.

NMPDR

fig|9606.3.peg.25450.

UCSC

uc003kfu.2. human.

Organism-specific databases

GeneCards

GC05P078443.

H-InvDB

HIX0004981.

HGNC

HGNC:1047. BHMT.

MIM

602888. gene.

PharmGKB

PA25350.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q93088.

OMA

Q93088. CKSEAEV.

Enzyme and pathway databases

BRENDA

2.1.1.5. 247.

Gene expression databases

ArrayExpress

Q93088.

Bgee

Q93088.

CleanEx

HS_BHMT.

GermOnline

ENSG00000145692. Homo sapiens.

Family and domain databases

InterPro

IPR017226. Betaine-hCys_S-MeTrfase_BHMT.
IPR003726. S_MeTrfase.
[Graphical view]

Gene3D

G3DSA:3.20.20.330. S_methyl_trans. 1 hit.

Pfam

PF02574. S-methyl_trans. 1 hit.
[Graphical view]

PIRSF

PIRSF037505. Betaine_HMT. 1 hit.

PROSITE

PS50970. HCY. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00134. L-Methionine.

NextBio

2568.

SOURCE

Search...

Entry information

Entry name

BHMT1_HUMAN

Accession

Primary (citable) accession number: Q93088
Secondary accession number(s): Q9UNI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 17, 2007
Last modified:	July 7, 2009
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)