Q4JIJ3 (METH_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methionine synthase
EC=2.1.1.13

Alternative name(s):
5-methyltetrahydrofolate--homocysteine methyltransferase
Vitamin-B12 dependent methionine synthase
Short name=MS

Gene names

Name:

MTR

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	1265 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate By similarity.
Catalytic activity	5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.
Cofactor	Methylcobalamin (MeCBL) By similarity. Binds 1 zinc ion per subunit By similarity.
Pathway	Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
Subcellular location	Cytoplasm By similarity.
Domain	Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin By similarity.
Miscellaneous	L-homocysteine is bound via the zinc atom By similarity.
Sequence similarities	Belongs to the vitamin-B12 dependent methionine synthase family. Contains 1 AdoMet activation domain. Contains 1 B12-binding domain. Contains 1 B12-binding N-terminal domain. Contains 1 Hcy-binding domain. Contains 1 pterin-binding domain.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Methionine biosynthesis
Cellular component	Cytoplasm
Domain	Repeat
Ligand	Cobalamin Cobalt Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	pteridine-containing compound metabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cobalamin binding Inferred from electronic annotation. Source: UniProtKB-KW homocysteine S-methyltransferase activity Inferred from electronic annotation. Source: InterPro methionine synthase activity Inferred from electronic annotation. Source: EC 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
	Chain	1 – 1265	1265	Methionine synthase		PRO_0000251734
Regions
	Domain	19 – 338	320	Hcy-binding
	Domain	371 – 632	262	Pterin-binding
	Domain	662 – 759	98	B12-binding N-terminal
	Domain	772 – 907	136	B12-binding
	Domain	923 – 1265	343	AdoMet activation
	Region	860 – 861	2	Cobalamin-binding By similarity
	Region	1227 – 1228	2	S-adenosyl-L-methionine binding By similarity
Sites
	Metal binding	260	1	Zinc By similarity
	Metal binding	323	1	Zinc By similarity
	Metal binding	324	1	Zinc By similarity
	Metal binding	785	1	Cobalt (cobalamin axial ligand) By similarity
	Binding site	830	1	Cobalamin By similarity
	Binding site	974	1	S-adenosyl-L-methionine By similarity
	Binding site	1172	1	S-adenosyl-L-methionine; via carbonyl oxygen By similarity
	Binding site	1176	1	Cobalamin; via carbonyl oxygen By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q4JIJ3 [UniParc]. Last modified August 2, 2005. Version 1. Checksum: 7E1E03AB95134529	FASTA	1,265	140,478
	10 20 30 40 50 60 MAPTLQDLTP SAGMKKTLQD EIEAILQERI MVLDGGMGTM IQRHKLSEED FRGQEFKDHA 70 80 90 100 110 120 RPLKGNNDIL SITQPNVIYQ IHKEYLLAGA DIIETNTFSS TSIAQADYGL EHLAYRMNMC 130 140 150 160 170 180 SAGVARKAAE DISLQTGIKR YVAGALGPTN KTLSVSPSVE RPDYRNITFD ELVEAYKEQA 190 200 210 220 230 240 KGLLDGGVDI LLIETIFDTA NAKAALFAVQ KLFEEEYVPR PVFISGTIVD KSGRTLSGQT 250 260 270 280 290 300 GEAFVISVSH ADPLCIGLNC ALGAAEMRPF IETIGKCTTA YVLCYPNAGL PNTFGDYDET 310 320 330 340 350 360 PHVMAMHLKD FAVDGLVNIV GGCCGTTPDH IREIAEAVKN CKPRVPPATV FEGHMLLSGL 370 380 390 400 410 420 EPFRIGPYTN FVNIGERCNV AGSRRFAKLI MAGNYEEALS VAKMQVEMGA QVLDINMDDG 430 440 450 460 470 480 MLDGPSAMTR FCNFIASEPD IAKVPLCIDS SNFAVIEAGL KCCQGKCIVN SISLKEGEDD 490 500 510 520 530 540 FLEKARKIKK FGAAVVVMAF DEEGQATETD PKIRVCTRAY HLLLKKLGFN PNDIIFDPNI 550 560 570 580 590 600 LTIGTGMEEH NLYAVNFINA TKVIKETLPG AKVSGGLSNL SFSFRGMEAI REAMHGVFLY 610 620 630 640 650 660 HAIKFGMDMG IVNAGSLPVY DDIHKELLQL CEDLIWNRDP EATEKLLHYA QTQGKGGKKV 670 680 690 700 710 720 IQTDEWRNGP LEERLEYALV KGIEKYIIED TEEARLNQEK YPRPLNIIEG PLMNGMKIVG 730 740 750 760 770 780 DLFGAGKMFL PQVIKSARVM KKAVGHLIPF MEKEREETKV LTGKIEDEDP YQGTIVLATV 790 800 810 820 830 840 KGDVHDIGKN IVGVVLGCNN FRVIDLGVMT PCDKILKAAL DHKADIIGLS GLITPSLDEM 850 860 870 880 890 900 IFVAKEMERL AIKIPLLIGG ATTSRTHTAV KIAPRYSAPV IHVLDASKSV VVCSQLLDEN 910 920 930 940 950 960 LKDEYFEEIL EEYEDIRQDH YESLKERRYL TLRQARENGF HIDWLSEPPP VKPTFLGTRV 970 980 990 1000 1010 1020 FEDYDLQKLV DYIDWKPFFD VWQLRGKYPN RGFPKIFDDK TVGEEAKKVY DDAQNMLQAL 1030 1040 1050 1060 1070 1080 ISQKKLQARG VVGFWPAQSI QDDIHLYAEG AVPQASEPIA TFYGLRQQAE KDSASSDPYL 1090 1100 1110 1120 1130 1140 CLSDFIAPLH SGIPDYLGLF AVACFGVEEL SKAYEEECDD YSSIMVKALG DRLAEAFAEE 1150 1160 1170 1180 1190 1200 LHERARRELW GYCSGEQLAV ADLRRLRYEG IRPAPGYPSQ PDHTEKLTVW RLADVEQRTG 1210 1220 1230 1240 1250 1260 IRLTESLAMA PASAVSGLYF SNLKSKYFAV GKISKDQIED YASRKNMSVA EVEKWLGPIL GYDTD

References

[1]	"Interactions of folic acid-vitamin B12-methionine: effects on liver metabolism and production of dairy cows." Palin M.-F., Beaudry D., Charest R., Girard C. Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ084519 mRNA. Translation: AAY86762.1.
IPI	IPI00711806.
RefSeq	NP_001025469.1. NM_001030298.1.
UniGene	Bt.47673.
3D structure databases
HSSP	HSSP built from PDB template 1MSK based on UniProtKB P13009.
ProteinModelPortal	Q4JIJ3.
SMR	Q4JIJ3. Positions 664-920, 926-1264.
ModBase	Search...
Protein-protein interaction databases
STRING	9913.ENSBTAP00000016262.
Proteomic databases
PRIDE	Q4JIJ3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	280869.
KEGG	bta:280869.
Organism-specific databases
CTD	4548.
Phylogenomic databases
eggNOG	COG1410.
HOGENOM	HOG000251409.
HOVERGEN	HBG006347.
InParanoid	Q4JIJ3.
KO	K00548.
OrthoDB	EOG41JZBC.
Enzyme and pathway databases
UniPathway	UPA00051; UER00081.
Family and domain databases
Gene3D	1.10.1240.10. 1 hit. 3.10.196.10. 1 hit. 3.20.20.20. 1 hit. 3.20.20.330. 1 hit. 3.40.50.280. 1 hit.
InterPro	IPR003759. Cbl-bd_cap. IPR006158. Cobalamin-bd. IPR011005. Dihydropteroate_synth-like. IPR011822. MetH. IPR000489. Pterin-binding. IPR003726. S_MeTrfase. IPR004223. VitB12-dep_Met_synth_activ_dom. [Graphical view]
PANTHER	PTHR21091:SF9. PTHR21091:SF9. 1 hit.
Pfam	PF02310. B12-binding. 1 hit. PF02607. B12-binding_2. 1 hit. PF02965. Met_synt_B12. 1 hit. PF00809. Pterin_bind. 1 hit. PF02574. S-methyl_trans. 1 hit. [Graphical view]
PIRSF	PIRSF000381. MetH. 1 hit.
SMART	SM01018. B12-binding_2. 1 hit. [Graphical view]
SUPFAM	SSF52242. Cbl-bd. 1 hit. SSF51717. DHP_synth_like. 1 hit. SSF56507. Met_synth_B12. 1 hit. SSF47644. Met_synth_Cbl-bd. 1 hit. SSF82282. S_methyl_trans. 1 hit.
TIGRFAMs	TIGR02082. metH. 1 hit.
PROSITE	PS50974. ADOMET_ACTIVATION. 1 hit. PS51332. B12_BINDING. 1 hit. PS51337. B12_BINDING_NTER. 1 hit. PS50970. HCY. 1 hit. PS50972. PTERIN_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	20805009.

Entry information

Entry name

METH_BOVIN

Accession

Primary (citable) accession number: Q4JIJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2006
Last sequence update:	August 2, 2005
Last modified:	April 3, 2013
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program