Q54P92 (METH_DICDI) 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
ORF Names:	DDB_G0284699

Organism

Dictyostelium discoideum (Slime mold) [Reference proteome]

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	1260 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

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.
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
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	intracellular Inferred from electronic annotation. Source: InterPro
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 sequence or structural similarity. Source: UniProtKB 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 – 1260	1260	Methionine synthase		PRO_0000327799
Regions
	Domain	13 – 333	321	Hcy-binding
	Domain	364 – 625	262	Pterin-binding
	Domain	655 – 749	95	B12-binding N-terminal
	Domain	766 – 883	118	B12-binding
	Domain	916 – 1256	341	AdoMet activation
	Region	853 – 854	2	Cobalamin-binding By similarity
	Region	1218 – 1219	2	S-adenosyl-L-methionine binding By similarity
Sites
	Metal binding	255	1	Zinc By similarity
	Metal binding	318	1	Zinc By similarity
	Metal binding	319	1	Zinc By similarity
	Metal binding	778	1	Cobalt (cobalamin axial ligand) By similarity
	Binding site	823	1	Cobalamin By similarity
	Binding site	966	1	S-adenosyl-L-methionine By similarity
	Binding site	1163	1	S-adenosyl-L-methionine; via carbonyl oxygen By similarity
	Binding site	1167	1	Cobalamin; via carbonyl oxygen By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q54P92 [UniParc]. Last modified May 24, 2005. Version 1. Checksum: 095402C1F5889CF0	FASTA	1,260	140,122
	10 20 30 40 50 60 MINSNDKNES DTFGIIRKIL SERIMVLDGA MGTEIQKFKL KDNDYRGEEF KDFPHELGGN 70 80 90 100 110 120 NDLLSLTQPH IIREIHCKYL EAGADFIETN TFNGNIFSQA DYKMEHLVKR INIESARLAK 130 140 150 160 170 180 SACEEYTKKD PSRPRFVCGA VGPTNKTASI SPSVERPEAR NVLFDELVSG YLEQVEALVE 190 200 210 220 230 240 GGIDVILVET VFDSLNCKAA LFAIEEFFKT YSPRLPVFVS GTIVDKSGRT LSGQTGEAFY 250 260 270 280 290 300 TSVASANLMV FGLNCALGAQ EMRPFLQNIS KCSECYVSCY PNAGLPNTFG GYDETPEMMA 310 320 330 340 350 360 EQIKEFAESG LLNIVGGCCG TSPDHIRAFC NAIEGIAPRA IPTLVPNTTL SGLEPLVFTK 370 380 390 400 410 420 ELNFVNVGER CNVSGSRRFA NLIKANKYEE ALSVARQQVE AGAQIIDINM DEGMIDAVAA 430 440 450 460 470 480 IQKFLFFIGS EPEISKVPIM LDSSNFDVVE AGLKCVQGKC IVNSISLKVG EELFIKQAKI 490 500 510 520 530 540 VKQYGASVVV MAFDENGQAT SKEEKVRICY RSYKILTEQV GFYPQDIIFD PNILTIATGL 550 560 570 580 590 600 EEHNNYGVEF IEATREIKAL MPLTRVSGGV SNLSFSFRGN EPLREAMHSA FLYYAIAAGM 610 620 630 640 650 660 DMGIVNAGAL PIYDDIPKDL LKLVEDAILN RTNDATEKLL EYAQANNKSE KANVEVEEWR 670 680 690 700 710 720 NKPVSERIAH ALVKGITTYI IEDTEEARNT LPSSLSVIEG PLMGGMNVVG DLFGAGKMFL 730 740 750 760 770 780 PQVIKSARVM KKAVAHLIPF MEEEKRLKRL EKGNDEAAED EPDNAGVVVL ATVKGDVHDI 790 800 810 820 830 840 GKNIVGVVLG CNNYKVIDIG VMTPCEKIVE AIIANKADVV GLSGLITPSL DEMIYVASEL 850 860 870 880 890 900 ERLKFKIPLM IGGATTSQIH TAVKISPHYS QPTVHVLDAS RSVTVVQSLL DPNNKEVFAE 910 920 930 940 950 960 DVSQQYAELR EKHYASLKDR KYTSLEKARQ HCVKVNWKTI QPVKPTFLGT QVFKEYSLEK 970 980 990 1000 1010 1020 LVTKIDWNPF FVTWQLRGKY PNRGYPRIFN DETVGAEAKK LFDDAQTMLK EIVDKKLLNA 1030 1040 1050 1060 1070 1080 RGVIGFYPAN SIDEDIIIYD HNDDETRSKP IATLFGLRQQ NEKETDEPYI AIGDYIAPVS 1090 1100 1110 1120 1130 1140 SGVKDYIGLF AVSSGFGLED MVEKYKKEND DYSSIMAKAL ADRLAEALAE AVHEDVRREH 1150 1160 1170 1180 1190 1200 WAYEKDQALS NEDLFKIKYK GIRPAPGYPA QPDHTEMKTI WSLMNVNENT SIELTDHMAM 1210 1220 1230 1240 1250 1260 LPGAAVCGVY FSHEHAKYFS VGKITKEQIE SYASRKQITK EEAERWLSSI LSYDRLPLVK

References

[1]

"The genome of the social amoeba Dictyostelium discoideum." Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A. Nature 435:43-57(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.

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Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AAFI02000070 Genomic DNA. Translation: EAL65119.1.
RefSeq	XP_638483.1. XM_633391.1.
3D structure databases
HSSP	HSSP built from PDB template 1BMT based on UniProtKB P13009.
ProteinModelPortal	Q54P92.
SMR	Q54P92. Positions 657-913, 919-1254.
ModBase	Search...
Protein-protein interaction databases
STRING	44689.DDB_0230138.
Proteomic databases
PRIDE	Q54P92.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblProtists	DDB0230138; DDB0230138; DDB_G0284699.
GeneID	8624734.
KEGG	ddi:DDB_G0284699.
Organism-specific databases
dictyBase	DDB_G0284699. mtr.
Phylogenomic databases
eggNOG	COG1410.
KO	K00548.
OMA	VRKEFWG.
ProtClustDB	CLSZ2430243.
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...

Entry information

Entry name

METH_DICDI

Accession

Primary (citable) accession number: Q54P92

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	May 24, 2005
Last modified:	May 1, 2013
This is version 57 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)