ID G3V8A4_RAT Unreviewed; 1253 AA. AC G3V8A4; DT 16-NOV-2011, integrated into UniProtKB/TrEMBL. DT 16-NOV-2011, sequence version 1. DT 12-AUG-2020, entry version 71. DE RecName: Full=Methionine synthase {ECO:0000256|PIRNR:PIRNR000381}; DE EC=2.1.1.13 {ECO:0000256|PIRNR:PIRNR000381}; DE AltName: Full=5-methyltetrahydrofolate--homocysteine methyltransferase {ECO:0000256|PIRNR:PIRNR000381}; GN Name=Mtr {ECO:0000313|EMBL:EDM06981.1, GN ECO:0000313|Ensembl:ENSRNOP00000023973, ECO:0000313|RGD:621283}; GN ORFNames=rCG_30554 {ECO:0000313|EMBL:EDM06981.1}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000023973, ECO:0000313|Proteomes:UP000002494}; RN [1] {ECO:0000313|Ensembl:ENSRNOP00000023973, ECO:0000313|Proteomes:UP000002494} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000023973, RC ECO:0000313|Proteomes:UP000002494}; RX PubMed=15057822; DOI=10.1038/nature02426; RG Rat Genome Sequencing Project Consortium; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] {ECO:0000313|EMBL:EDM06981.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=BN {ECO:0000313|EMBL:EDM06981.1}; RX PubMed=15632090; DOI=10.1101/gr.2889405; RA Florea L., Di Francesco V., Miller J., Turner R., Yao A., Harris M., RA Walenz B., Mobarry C., Merkulov G.V., Charlab R., Dew I., Deng Z., RA Istrail S., Li P., Sutton G.; RT "Gene and alternative splicing annotation with AIR."; RL Genome Res. 15:54-66(2005). RN [3] {ECO:0000313|EMBL:EDM06981.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=BN {ECO:0000313|EMBL:EDM06981.1}; RA Mural R.J., Li P.W., Adams M.D., Amanatides P.G., Baden-Tillson H., RA Barnstead M., Chin S.H., Dew I., Evans C.A., Ferriera S., Flanigan M., RA Fosler C., Glodek A., Gu Z., Holt R.A., Jennings D., Kraft C.L., Lu F., RA Nguyen T., Nusskern D.R., Pfannkoch C.M., Sitter C., Sutton G.G., RA Venter J.C., Wang Z., Woodage T., Zheng X.H., Zhong F.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000313|Ensembl:ENSRNOP00000023973} RP IDENTIFICATION. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000023973}; RG Ensembl; RL Submitted (SEP-2011) to UniProtKB. RN [5] {ECO:0000213|PubMed:22673903} RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [6] {ECO:0000313|Ensembl:ENSRNOP00000071254} RP IDENTIFICATION. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000071254}; RG Ensembl; RL Submitted (JUN-2015) to UniProtKB. CC -!- FUNCTION: Catalyzes the transfer of a methyl group from CC methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound CC cob(I)alamin and methionine in the cytosol. MeCbl is an active form of CC cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. CC Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl CC group from 5-methyltetrahydrofolate. The processing of cobalamin in the CC cytosol occurs in a multiprotein complex composed of at least MMACHC, CC MMADHC, MTRR (methionine synthase reductase) and MTR which may CC contribute to shuttle safely and efficiently cobalamin towards MTR in CC order to produce methionine. {ECO:0000256|PIRNR:PIRNR000381}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = CC (6S)-5,6,7,8-tetrahydrofolate + L-methionine; Xref=Rhea:RHEA:11172, CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57453, ChEBI:CHEBI:57844, CC ChEBI:CHEBI:58199; EC=2.1.1.13; CC Evidence={ECO:0000256|PIRNR:PIRNR000381}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000256|ARBA:ARBA00001947, CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE-ProRule:PRU00333}; CC -!- COFACTOR: CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115; CC Evidence={ECO:0000256|ARBA:ARBA00001956, CC ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-2}; CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo CC pathway; L-methionine from L-homocysteine (MetH route): step 1/1. CC {ECO:0000256|ARBA:ARBA00005178, ECO:0000256|PIRNR:PIRNR000381}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|PIRNR:PIRNR000381}. CC -!- DOMAIN: Modular enzyme with four functionally distinct domains. The CC isolated Hcy-binding domain catalyzes methyl transfer from free CC methylcobalamin to homocysteine. The Hcy-binding domain in association CC with the pterin-binding domain catalyzes the methylation of CC cob(I)alamin by methyltetrahydrofolate and the methylation of CC homocysteine. The B12-binding domain binds the cofactor. The AdoMet CC activation domain binds S-adenosyl-L-methionine. Under aerobic CC conditions cob(I)alamin can be converted to inactive cob(II)alamin. CC Reductive methylation by S-adenosyl-L-methionine and flavodoxin CC regenerates methylcobalamin. {ECO:0000256|PIRNR:PIRNR000381}. CC -!- SIMILARITY: Belongs to the vitamin-B12 dependent methionine synthase CC family. {ECO:0000256|ARBA:ARBA00010398}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AABR07028348; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR07028349; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH474071; EDM06981.1; -; Genomic_DNA. DR Ensembl; ENSRNOT00000023974; ENSRNOP00000023973; ENSRNOG00000017593. DR Ensembl; ENSRNOT00000083172; ENSRNOP00000071254; ENSRNOG00000017593. DR RGD; 621283; Mtr. DR GeneTree; ENSGT00420000029824; -. DR HOGENOM; CLU_004914_2_0_1; -. DR OMA; ADCIAMS; -. DR TreeFam; TF312829; -. DR UniPathway; UPA00051; UER00081. DR Proteomes; UP000002494; Chromosome 17. DR Bgee; ENSRNOG00000017593; Expressed in adult mammalian kidney and 19 other tissues. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-UniRule. DR GO; GO:0008705; F:methionine synthase activity; IDA:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0031103; P:axon regeneration; IMP:BHF-UCL. DR GO; GO:0071732; P:cellular response to nitric oxide; IDA:BHF-UCL. DR GO; GO:0009235; P:cobalamin metabolic process; IEA:Ensembl. DR GO; GO:0006306; P:DNA methylation; IC:BHF-UCL. DR GO; GO:0042558; P:pteridine-containing compound metabolic process; IEA:InterPro. DR GO; GO:0048678; P:response to axon injury; IDA:BHF-UCL. DR CDD; cd02069; methionine_synthase_B12_BD; 1. DR Gene3D; 1.10.1240.10; -; 1. DR Gene3D; 3.10.196.10; -; 1. DR Gene3D; 3.20.20.20; -; 1. DR Gene3D; 3.20.20.330; -; 1. DR InterPro; IPR003759; Cbl-bd_cap. DR InterPro; IPR006158; Cobalamin-bd. DR InterPro; IPR036724; Cobalamin-bd_sf. DR InterPro; IPR011005; Dihydropteroate_synth-like. DR InterPro; IPR003726; HCY_dom. DR InterPro; IPR036589; HCY_dom_sf. DR InterPro; IPR033706; Met_synthase_B12-bd. DR InterPro; IPR011822; MetH. DR InterPro; IPR036594; Meth_synthase_dom. DR InterPro; IPR000489; Pterin-binding_dom. DR InterPro; IPR004223; VitB12-dep_Met_synth_activ_dom. DR InterPro; IPR037010; VitB12-dep_Met_synth_activ_sf. DR Pfam; PF02310; B12-binding; 1. DR Pfam; PF02607; B12-binding_2; 1. DR Pfam; PF02965; Met_synt_B12; 1. DR Pfam; PF00809; Pterin_bind; 1. DR Pfam; PF02574; S-methyl_trans; 1. DR PIRSF; PIRSF000381; MetH; 1. DR SMART; SM01018; B12-binding_2; 1. DR SUPFAM; SSF47644; SSF47644; 1. DR SUPFAM; SSF51717; SSF51717; 1. DR SUPFAM; SSF52242; SSF52242; 1. DR SUPFAM; SSF56507; SSF56507; 1. DR SUPFAM; SSF82282; SSF82282; 1. DR TIGRFAMs; TIGR02082; metH; 1. DR PROSITE; PS50974; ADOMET_ACTIVATION; 1. DR PROSITE; PS51332; B12_BINDING; 1. DR PROSITE; PS51337; B12_BINDING_NTER; 1. DR PROSITE; PS50970; HCY; 1. DR PROSITE; PS50972; PTERIN_BINDING; 1. PE 1: Evidence at protein level; KW Amino-acid biosynthesis {ECO:0000256|ARBA:ARBA00022605, KW ECO:0000256|PIRNR:PIRNR000381}; KW Cobalamin {ECO:0000256|ARBA:ARBA00022628, ECO:0000256|PIRNR:PIRNR000381, KW ECO:0000256|PIRSR:PIRSR000381-2}; KW Cobalt {ECO:0000256|ARBA:ARBA00023285, ECO:0000256|PIRNR:PIRNR000381, KW ECO:0000256|PIRSR:PIRSR000381-1}; KW Cytoplasm {ECO:0000256|PIRNR:PIRNR000381}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1, KW ECO:0000256|PROSITE-ProRule:PRU00333}; KW Methionine biosynthesis {ECO:0000256|ARBA:ARBA00023167, KW ECO:0000256|PIRNR:PIRNR000381}; KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603, KW ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE-ProRule:PRU00346, KW ECO:0000313|EMBL:EDM06981.1}; KW Proteomics identification {ECO:0000213|PeptideAtlas:G3V8A4}; KW Reference proteome {ECO:0000313|Proteomes:UP000002494}; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691, KW ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-2}; KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000381, KW ECO:0000256|PROSITE-ProRule:PRU00346, ECO:0000313|EMBL:EDM06981.1}; KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|PIRNR:PIRNR000381, KW ECO:0000256|PIRSR:PIRSR000381-1, ECO:0000256|PROSITE-ProRule:PRU00333}. FT DOMAIN 6..326 FT /note="Hcy-binding" FT /evidence="ECO:0000259|PROSITE:PS50970" FT DOMAIN 359..620 FT /note="Pterin-binding" FT /evidence="ECO:0000259|PROSITE:PS50972" FT DOMAIN 650..747 FT /note="B12-binding N-terminal" FT /evidence="ECO:0000259|PROSITE:PS51337" FT DOMAIN 760..895 FT /note="B12-binding" FT /evidence="ECO:0000259|PROSITE:PS51332" FT DOMAIN 911..1253 FT /note="AdoMet activation" FT /evidence="ECO:0000259|PROSITE:PS50974" FT REGION 848..849 FT /note="Cobalamin-binding" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT REGION 1215..1216 FT /note="S-adenosyl-L-methionine binding" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT METAL 248 FT /note="Zinc" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1, FT ECO:0000256|PROSITE-ProRule:PRU00333" FT METAL 311 FT /note="Zinc" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1, FT ECO:0000256|PROSITE-ProRule:PRU00333" FT METAL 312 FT /note="Zinc" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1, FT ECO:0000256|PROSITE-ProRule:PRU00333" FT METAL 773 FT /note="Cobalt (cobalamin axial ligand)" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-1" FT BINDING 818 FT /note="Cobalamin" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 962 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 1160 FT /note="S-adenosyl-L-methionine; via carbonyl oxygen" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" FT BINDING 1164 FT /note="Cobalamin; via carbonyl oxygen" FT /evidence="ECO:0000256|PIRSR:PIRSR000381-2" SQ SEQUENCE 1253 AA; 139191 MW; CFBD40BB66EBD75E CRC64; MKKTLQDEIE AILRKRIMVL DGGMGTMIQR YKLSEENFQG QEFKDHSRPL KGNNDILSIT QPDVIYQIHK EYLLAGADII ETNTFSSTSI AQADYGLEHL AYRMNKCSAD VARKAAEEIT LQTGVKRFVA GSLGPTNKTL SVSPSVERPD YRNITFDELV EAYQEQAKGL LDGGVDILLI ETIFDTANAK AALFALQKLF EENYASPRPI FISGTIVDKS GRTLSGQTGE AFVTSVSHSD PLCIGLNCAL GAAEMRPFIE TIGKCTTAYV LCYPNAGLPN TFGDYDETPA MMAMHLKDFA VDGLVNVVGG CCGSTPDHIR EIAEAVKNCK PRVPPDSVFE GHMLLSGLEP FRIGPYTNFV NIGERCNVAG SKKFAKLIMA GNYEEALSVA KVQVEMGAQV LDINMDDGML DGPSAMTKFC NFIASEPDIA KVPLCIDSSN FAVIEAGLKC CQGKCIVNSI SLKEGEEDFL EKARKIKKFG AAVVVMAFDE EGQATETDVK VSVCTRAYHL LVEKVGFNPN DIIFDPNILT IGTGMEEHNL YAINFIHATR VIKETLPGVR ISGGLSNLSF AFRGMDAIRE AMHGVFLYHA IKFGMDMGIV NAGSLPVYDD IHKDLLQLCE DLIWNRDAEA TEKLLRYAQT HGKGGKKVIQ TDEWRNGSIE ERLEYALVKG IEKHIVEDTE EARLNREKYP RPLNIIEGPL MNGMKVVGDL FGAGKMFLPQ VIKSARVMKK AVGHLIPFME KEREEARVLN GSVEEEDPYQ GTIVLATVKG DVHDIGKNIV GVVLGCNNFR VIDLGVMTPC DKILQAALDH KADIIGLSGL ITPSLDEMIF VAKEMERLAI KIPLLIGGAT TSRTHTAVKI APRYSAPVIH VLDASKSVVV CSQLLDENLK DDYFEEILEE YEDIRQDHYE SLKERKYLPL SQARKHSFHI DWLSEPHPVK PTFIGTQVFE DYNLQKLVDY IDWKPFFDVW QLRGKYPNRG FPKIFNDKAV GEEARKVYED AQNMLNILIS RKKLRARGVV GFWPAQSVQD DIHLYAEGAV PQAAEPIATF YGLRQQAEKD SSSTDPYHCL SDFVAPLHSG VRDYLGLFAV ACFGVEELSK AYEDDGDDYS SIMVKALGDR LAEAFAEELH ERVRRELWAY CGSEQLGVTD LRKLRYEGIR PAPGYPSQPD HTEKLTMWRL ANIEQATGIR LTESLAMAPA SAVSGLYFSN VKSKYFAVGK ISKDQIEDYA LRKNMSVAEV EKWLGPILGY DTD //