ID G3V8A4_RAT Unreviewed; 1253 AA. AC G3V8A4; DT 16-NOV-2011, integrated into UniProtKB/TrEMBL. DT 16-NOV-2011, sequence version 1. DT 17-JUN-2020, entry version 70. 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 methyl- CC cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and CC methionine. Subsequently, remethylates the cofactor using CC methyltetrahydrofolate. {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|PIRSR:PIRSR000381-1}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000256|PIRSR:PIRSR000381-1}; CC -!- COFACTOR: CC Name=methylcob(III)alamin; Xref=ChEBI:CHEBI:28115; CC Evidence={ECO:0000256|PIRNR:PIRNR000381, CC 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|PIRNR:PIRNR000381}. 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 eggNOG; KOG1579; Eukaryota. DR eggNOG; COG0646; LUCA. DR eggNOG; COG1410; LUCA. 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 8 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|PIRNR:PIRNR000381}; KW Cobalamin {ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-2}; KW Cobalt {ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1}; KW Metal-binding {ECO:0000256|PIRNR:PIRNR000381, KW ECO:0000256|PIRSR:PIRSR000381-1, ECO:0000256|PROSITE-ProRule:PRU00333}; KW Methionine biosynthesis {ECO:0000256|PIRNR:PIRNR000381}; KW Methyltransferase {ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE- KW ProRule:PRU00333, ECO:0000313|EMBL:EDM06981.1}; KW Proteomics identification {ECO:0000213|PeptideAtlas:G3V8A4}; KW Reference proteome {ECO:0000313|Proteomes:UP000002494}; KW S-adenosyl-L-methionine {ECO:0000256|PIRNR:PIRNR000381, KW ECO:0000256|PIRSR:PIRSR000381-2}; KW Transferase {ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PROSITE- KW ProRule:PRU00333, ECO:0000313|EMBL:EDM06981.1}; KW Zinc {ECO:0000256|PIRNR:PIRNR000381, ECO:0000256|PIRSR:PIRSR000381-1, KW 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 //