CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-019768
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Methionine synthase 
Protein Synonyms/Alias
 5-methyltetrahydrofolate--homocysteine methyltransferase; Vitamin-B12 dependent methionine synthase; MS 
Gene Name
 MTR 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
15LSQPEGLKKTLRDEIubiquitination[1]
16SQPEGLKKTLRDEINubiquitination[1, 2, 3]
28EINAILQKRIMVLDGubiquitination[1, 2, 3, 4]
45GTMIQREKLNEEHFRubiquitination[1]
57HFRGQEFKDHARPLKubiquitination[1]
64KDHARPLKGNNDILSubiquitination[1]
127CSAGVARKAAEEVTLubiquitination[1]
139VTLQTGIKRFVAGALubiquitination[1, 4]
151GALGPTNKTLSVSPSubiquitination[1]
231ISGTIVDKSGRTLSGubiquitination[1, 2, 3, 5]
306ETPSMMAKHLKDFAMubiquitination[1]
309SMMAKHLKDFAMDGLubiquitination[1]
339REIAEAVKNCKPRVPubiquitination[1]
385CNVAGSRKFAKLIMAubiquitination[1]
388AGSRKFAKLIMAGNYubiquitination[1]
466GLKCCQGKCIVNSISubiquitination[1]
475IVNSISLKEGEDDFLubiquitination[1]
484GEDDFLEKARKIKKYubiquitination[1]
526AYHLLVKKLGFNPNDubiquitination[1]
565IHATKVIKETLPGARubiquitination[1]
658QTQGTGGKKVIQTDEubiquitination[4]
659TQGTGGKKVIQTDEWubiquitination[1]
681RLEYALVKGIEKHIIubiquitination[1]
685ALVKGIEKHIIEDTEubiquitination[1, 2, 3, 4]
700EARLNQKKYPRPLNIubiquitination[1]
727GDLFGAGKMFLPQVIubiquitination[1, 2, 3]
735MFLPQVIKSARVMKKubiquitination[1]
742KSARVMKKAVGHLIPubiquitination[1]
753HLIPFMEKEREETRVubiquitination[1]
781TIVLATVKGDVHDIGubiquitination[1]
789GDVHDIGKNIVGVVLubiquitination[1, 2, 3, 4]
814GVMTPCDKILKAALDubiquitination[1, 2, 3, 4]
817TPCDKILKAALDHKAubiquitination[1, 2, 3]
823LKAALDHKADIIGLSubiquitination[1]
865IGGATTSKTHTAVKIubiquitination[1, 2, 3]
871SKTHTAVKIAPRYSAubiquitination[1, 4]
925QDHYESLKERRYLPLubiquitination[1]
995YPNRGFPKIFNDKTVubiquitination[1]
1000FPKIFNDKTVGGEARubiquitination[1, 2, 3]
1025NTLISQKKLRARGVVubiquitination[1]
1071GLRQQAEKDSASTEPubiquitination[1]
1127DYSSIMVKALGDRLAubiquitination[1]
1169DLRRLRYKGIRPAPGubiquitination[1]
1186SQPDHTEKLTMWRLAubiquitination[1]
1224GLYFSNLKSKYFAVGubiquitination[1]
1226YFSNLKSKYFAVGKIubiquitination[1]
1232SKYFAVGKISKDQVEubiquitination[1]
1235FAVGKISKDQVEDYAubiquitination[1]
1245VEDYALRKNISVAEVubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
Functional Description
 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). 
Sequence Annotation
 DOMAIN 19 338 Hcy-binding.
 DOMAIN 371 632 Pterin-binding.
 DOMAIN 662 759 B12-binding N-terminal.
 DOMAIN 772 907 B12-binding.
 DOMAIN 923 1265 AdoMet activation.
 REGION 860 861 Cobalamin-binding (By similarity).
 REGION 1227 1228 S-adenosyl-L-methionine binding (By
 METAL 260 260 Zinc (By similarity).
 METAL 323 323 Zinc (By similarity).
 METAL 324 324 Zinc (By similarity).
 METAL 785 785 Cobalt (cobalamin axial ligand) (By
 BINDING 830 830 Cobalamin (By similarity).
 BINDING 974 974 S-adenosyl-L-methionine (By similarity).
 BINDING 1172 1172 S-adenosyl-L-methionine; via carbonyl
 BINDING 1176 1176 Cobalamin; via carbonyl oxygen (By  
Keyword
 3D-structure; Amino-acid biosynthesis; Cobalamin; Cobalt; Complete proteome; Cytoplasm; Disease mutation; Metal-binding; Methionine biosynthesis; Methyltransferase; Polymorphism; Reference proteome; Repeat; S-adenosyl-L-methionine; Transferase; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1265 AA 
Protein Sequence
MSPALQDLSQ PEGLKKTLRD EINAILQKRI MVLDGGMGTM IQREKLNEEH FRGQEFKDHA 60
RPLKGNNDIL SITQPDVIYQ IHKEYLLAGA DIIETNTFSS TSIAQADYGL EHLAYRMNMC 120
SAGVARKAAE EVTLQTGIKR FVAGALGPTN KTLSVSPSVE RPDYRNITFD ELVEAYQEQA 180
KGLLDGGVDI LLIETIFDTA NAKAALFALQ NLFEEKYAPR PIFISGTIVD KSGRTLSGQT 240
GEGFVISVSH GEPLCIGLNC ALGAAEMRPF IEIIGKCTTA YVLCYPNAGL PNTFGDYDET 300
PSMMAKHLKD FAMDGLVNIV GGCCGSTPDH IREIAEAVKN CKPRVPPATA FEGHMLLSGL 360
EPFRIGPYTN FVNIGERCNV AGSRKFAKLI MAGNYEEALC VAKVQVEMGA QVLDVNMDDG 420
MLDGPSAMTR FCNLIASEPD IAKVPLCIDS SNFAVIEAGL KCCQGKCIVN SISLKEGEDD 480
FLEKARKIKK YGAAMVVMAF DEEGQATETD TKIRVCTRAY HLLVKKLGFN PNDIIFDPNI 540
LTIGTGMEEH NLYAINFIHA TKVIKETLPG ARISGGLSNL SFSFRGMEAI REAMHGVFLY 600
HAIKSGMDMG IVNAGNLPVY DDIHKELLQL CEDLIWNKDP EATEKLLRYA QTQGTGGKKV 660
IQTDEWRNGP VEERLEYALV KGIEKHIIED TEEARLNQKK YPRPLNIIEG PLMNGMKIVG 720
DLFGAGKMFL PQVIKSARVM KKAVGHLIPF MEKEREETRV LNGTVEEEDP YQGTIVLATV 780
KGDVHDIGKN IVGVVLGCNN FRVIDLGVMT PCDKILKAAL DHKADIIGLS GLITPSLDEM 840
IFVAKEMERL AIRIPLLIGG ATTSKTHTAV KIAPRYSAPV IHVLDASKSV VVCSQLLDEN 900
LKDEYFEEIM EEYEDIRQDH YESLKERRYL PLSQARKSGF QMDWLSEPHP VKPTFIGTQV 960
FEDYDLQKLV DYIDWKPFFD VWQLRGKYPN RGFPKIFNDK TVGGEARKVY DDAHNMLNTL 1020
ISQKKLRARG VVGFWPAQSI QDDIHLYAEA AVPQAAEPIA TFYGLRQQAE KDSASTEPYY 1080
CLSDFIAPLH SGIRDYLGLF AVACFGVEEL SKAYEDDGDD YSSIMVKALG DRLAEAFAEE 1140
LHERVRRELW AYCGSEQLDV ADLRRLRYKG IRPAPGYPSQ PDHTEKLTMW RLADIEQSTG 1200
IRLTESLAMA PASAVSGLYF SNLKSKYFAV GKISKDQVED YALRKNISVA EVEKWLGPIL 1260
GYDTD 1265 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
 GO:0008898; F:homocysteine S-methyltransferase activity; IEA:InterPro.
 GO:0008705; F:methionine synthase activity; IEA:EC.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome.
 GO:0032259; P:methylation; TAS:Reactome.
 GO:0007399; P:nervous system development; TAS:ProtInc.
 GO:0042558; P:pteridine-containing compound metabolic process; IEA:InterPro.
 GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
 GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. 
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. 
Pfam
 PF02310; B12-binding
 PF02607; B12-binding_2
 PF02965; Met_synt_B12
 PF00809; Pterin_bind
 PF02574; S-methyl_trans 
SMART
 SM01018; B12-binding_2 
PROSITE
 PS50974; ADOMET_ACTIVATION
 PS51332; B12_BINDING
 PS51337; B12_BINDING_NTER
 PS50970; HCY
 PS50972; PTERIN_BINDING 
PRINTS