Q9H2M3 (BHMT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
S-methylmethionine--homocysteine S-methyltransferase BHMT2
Short name=SMM-hcy methyltransferase
EC=2.1.1.5

Alternative name(s):
Betaine--homocysteine S-methyltransferase 2

Gene names

Name:

BHMT2

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	363 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the regulation of homocysteine metabolism. Converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor. Ref.5
Catalytic activity	Trimethylammonioacetate + L-homocysteine = dimethylglycine + L-methionine. Ref.5
Cofactor	Binds 1 zinc ion per subunit. Ref.5
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 By similarity. May interact with PRNP.
Tissue specificity	Expressed in liver and kidney and at reduced levels in the brain, heart, and skeletal muscle. Ref.1
Sequence similarities	Contains 1 Hcy-binding domain.
Sequence caution	The sequence BAA90880.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding Zinc
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amino-acid betaine catabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway methionine biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: InterPro
Molecular_function	betaine-homocysteine S-methyltransferase activity Inferred from electronic annotation. Source: EC homocysteine S-methyltransferase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H2M3-1)

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.

Isoform 2 (identifier: Q9H2M3-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 363	363	S-methylmethionine--homocysteine S-methyltransferase BHMT2		PRO_0000273224
Regions
	Domain	11 – 305	295	Hcy-binding
Sites
	Metal binding	208	1	Zinc By similarity
	Metal binding	290	1	Zinc By similarity
	Metal binding	291	1	Zinc By similarity
Natural variations
	Alternative sequence	87 – 150	64	Missing in isoform 2.		VSP_042938

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 92D35414D2D56003	FASTA	363	40,354
	10 20 30 40 50 60 MAPAGRPGAK KGILERLESG EVVIGDGSFL ITLEKRGYVK AGLWTPEAVI EHPDAVRQLH 70 80 90 100 110 120 MEFLRAGSNV MQTFTFSASE DNMESKWEDV NAAACDLARE VAGKGDALVA GGICQTSIYK 130 140 150 160 170 180 YQKDEARIKK LFRQQLEVFA WKNVDFLIAE YFEHVEEAVW AVEVLKESDR PVAVTMCIGP 190 200 210 220 230 240 EGDMHDITPG ECAVRLVKAG ASIVGVNCRF GPDTSLKTME LMKEGLEWAG LKAHLMVQPL 250 260 270 280 290 300 GFHAPDCGKE GFVDLPEYPF GLESRVATRW DIQKYAREAY NLGVRYIGGC CGFEPYHIRA 310 320 330 340 350 360 IAEELAPERG FLPPASEKHG SWGSGLDMHT KPWIRARARR EYWENLLPAS GRPFCPSLSK PDF
	Isoform 2 [UniParc]. Checksum: 763335314695E79E	FASTA	299	33,167
	10 20 30 40 50 60 MAPAGRPGAK KGILERLESG EVVIGDGSFL ITLEKRGYVK AGLWTPEAVI EHPDAVRQLH 70 80 90 100 110 120 MEFLRAGSNV MQTFTFSASE DNMESKYFEH VEEAVWAVEV LKESDRPVAV TMCIGPEGDM 130 140 150 160 170 180 HDITPGECAV RLVKAGASIV GVNCRFGPDT SLKTMELMKE GLEWAGLKAH LMVQPLGFHA 190 200 210 220 230 240 PDCGKEGFVD LPEYPFGLES RVATRWDIQK YAREAYNLGV RYIGGCCGFE PYHIRAIAEE 250 260 270 280 290 LAPERGFLPP ASEKHGSWGS GLDMHTKPWI RARARREYWE NLLPASGRPF CPSLSKPDF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00014363. IPI00922635.
RefSeq	NP_001171476.1. NM_001178005.1. NP_060084.2. NM_017614.4.
UniGene	Hs.114172.
3D structure databases
HSSP	HSSP built from PDB template 1LT7 based on UniProtKB Q93088.
ProteinModelPortal	Q9H2M3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000255192.
PTM databases
PhosphoSite	Q9H2M3.
Polymorphism databases
DMDM	74733563.
Proteomic databases
PaxDb	Q9H2M3.
PRIDE	Q9H2M3.
Protocols and materials databases
DNASU	23743.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000255192; ENSP00000255192; ENSG00000132840. ENST00000521567; ENSP00000430278; ENSG00000132840.
GeneID	23743.
KEGG	hsa:23743.
UCSC	uc003kft.3. human.
Organism-specific databases
CTD	23743.
GeneCards	GC05P078401.
HGNC	HGNC:1048. BHMT2.
HPA	HPA044573.
MIM	605932. gene.
neXtProt	NX_Q9H2M3.
PharmGKB	PA25351.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0646.
HOGENOM	HOG000231636.
HOVERGEN	HBG080367.
InParanoid	Q9H2M3.
OMA	GFHTPDC.
OrthoDB	EOG4001JM.
PhylomeDB	Q9H2M3.
Enzyme and pathway databases
UniPathway	UPA00051; UER00083. UPA00291; UER00432.
Gene expression databases
ArrayExpress	Q9H2M3.
Bgee	Q9H2M3.
CleanEx	HS_BHMT2.
Genevestigator	Q9H2M3.
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
ChiTaRS	BHMT2. human.
DrugBank	DB00134. L-Methionine.
GenomeRNAi	23743.
NextBio	46663.
SOURCE	Search...

Entry information

Entry name

BHMT2_HUMAN

Accession

Primary (citable) accession number: Q9H2M3
Secondary accession number(s): B7Z516, Q9NXX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2007
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 89 of the entry and version 1 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.