Q93088 (BHMT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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 Reference proteome
Gene Ontology (GO)
Biological_process	amino-acid betaine catabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome methionine biosynthetic process Inferred from electronic annotation. Source: Compara protein methylation Non-traceable author statement Ref.2. Source: UniProtKB regulation of homocysteine metabolic process Non-traceable author statement Ref.2. Source: UniProtKB sulfur amino acid metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	betaine-homocysteine S-methyltransferase activity Non-traceable author statement Ref.2. Source: UniProtKB homocysteine S-methyltransferase activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 406

405

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

199

1

G → S.
Corresponds to variant rs59866108 [ dbSNP | Ensembl ].

VAR_061345

Natural variant

239

1

R → Q May decrease risk for coronary artery disease. Ref.1 Ref.7
Corresponds to variant rs3733890 [ dbSNP | Ensembl ].

VAR_015886

Secondary structure

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406

Helix Strand Turn

Details...

Helix

13 – 18

6

Helix

29 – 36

8

Turn

41 – 43

3

Helix

48 – 51

4

Helix

53 – 65

13

Beta strand

69 – 72

4

Helix

97 – 111

15

Turn

112 – 115

4

Beta strand

117 – 122

6

Helix

126 – 129

4

Helix

133 – 151

19

Beta strand

154 – 158

5

Helix

164 – 174

11

Helix

175 – 177

3

Beta strand

181 – 185

5

Helix

198 – 206

9

Turn

207 – 209

3

Beta strand

211 – 219

9

Helix

221 – 236

16

Turn

237 – 239

3

Beta strand

243 – 247

5

Helix

261 – 263

3

Turn

265 – 269

5

Helix

272 – 274

3

Helix

278 – 291

14

Beta strand

293 – 296

4

Helix

304 – 313

10

Helix

315 – 318

4

Helix

323 – 327

5

Helix

333 – 337

5

Helix

341 – 344

4

Helix

349 – 354

6

Sequences

	Sequence		Length	Mass (Da)
	Q93088 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: VARIANT GLN-239.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_001713.2.

UniGene

Hs.80756.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q93088.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q93088. 5 interactions.

MINT

MINT-246738.

STRING

9606.ENSP00000274353.

PTM databases

PhosphoSite

Q93088.

Polymorphism databases

DMDM

145559446.

Proteomic databases

PaxDb

Q93088.

PRIDE

Q93088.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000274353; ENSP00000274353; ENSG00000145692.

GeneID

635.

KEGG

hsa:635.

UCSC

uc003kfu.4. human.

Organism-specific databases

CTD

635.

GeneCards

GC05P078443.

HGNC

HGNC:1047. BHMT.

HPA

HPA038285.

MIM

602888. gene.

neXtProt

NX_Q93088.

PharmGKB

PA25350.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0646.

HOGENOM

HOG000231636.

HOVERGEN

HBG080367.

InParanoid

Q93088.

KO

K00544.

OMA

CNKQGFI.

OrthoDB

EOG4001JM.

PhylomeDB

Q93088.

Enzyme and pathway databases

BRENDA

2.1.1.5. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q93088.

UniPathway

UPA00051; UER00083.
UPA00291; UER00432.

Gene expression databases

ArrayExpress

Q93088.

Bgee

Q93088.

CleanEx

HS_BHMT.

Genevestigator

Q93088.

GermOnline

ENSG00000145692. Homo sapiens.

Family and domain databases

Gene3D

3.20.20.330. 1 hit.

InterPro

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

Pfam

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

PIRSF

PIRSF037505. Betaine_HMT. 1 hit.

SUPFAM

SSF82282. S_methyl_trans. 1 hit.

PROSITE

PS50970. HCY. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q93088.

ChEMBL

CHEMBL4328.

DrugBank

DB00134. L-Methionine.

EvolutionaryTrace

Q93088.

GenomeRNAi

635.

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:	May 1, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.