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Protein

Methionine synthase reductase

Gene

MTRR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state. Necessary for utilization of methylgroups from the folate cycle, thereby affecting transgenerational epigenetic inheritance. Folate pathway donates methyl groups necessary for cellular methylation and affects different pathways such as DNA methylation, possibly explaining the transgenerational epigenetic inheritance effects.1 Publication

Catalytic activityi

2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP+ = 2 [methionine synthase]-cob(II)alamin + NADPH + 2 S-adenosyl-L-methionine.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • FAD1 Publication
  • FMN1 Publication

Kineticsi

  1. KM=2.89 µM for NADPH1 Publication
  2. KM=3540 µM for NADH1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei318 – 3181NADP1 Publication
    Binding sitei686 – 6861NADP1 Publication
    Binding sitei724 – 7241FAD1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi120 – 15132FMNPROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi478 – 4814FAD1 Publication
    Nucleotide bindingi514 – 5174FAD1 Publication
    Nucleotide bindingi637 – 6382NADP1 Publication
    Nucleotide bindingi651 – 6533NADP1 Publication

    GO - Molecular functioni

    • [methionine synthase] reductase activity Source: UniProtKB
    • aquacobalamin reductase (NADPH) activity Source: CACAO
    • FAD binding Source: BHF-UCL
    • flavin adenine dinucleotide binding Source: UniProtKB
    • FMN binding Source: UniProtKB
    • iron ion binding Source: InterPro
    • NADP binding Source: UniProtKB
    • NADPH binding Source: BHF-UCL
    • NADPH-hemoprotein reductase activity Source: BHF-UCL
    • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen Source: GO_Central
    • oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor Source: UniProtKB

    GO - Biological processi

    • cellular nitrogen compound metabolic process Source: Reactome
    • cobalamin metabolic process Source: Reactome
    • DNA methylation Source: UniProtKB
    • folic acid metabolic process Source: UniProtKB
    • homocysteine catabolic process Source: BHF-UCL
    • methionine biosynthetic process Source: BHF-UCL
    • methionine metabolic process Source: UniProtKB
    • methylation Source: Reactome
    • negative regulation of cystathionine beta-synthase activity Source: BHF-UCL
    • oxidation-reduction process Source: UniProtKB
    • S-adenosylmethionine cycle Source: BHF-UCL
    • small molecule metabolic process Source: Reactome
    • sulfur amino acid metabolic process Source: Reactome
    • vitamin metabolic process Source: Reactome
    • water-soluble vitamin metabolic process Source: Reactome
    • xenobiotic metabolic process Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Amino-acid biosynthesis, Methionine biosynthesis

    Keywords - Ligandi

    FAD, Flavoprotein, FMN, NADP, S-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04756-MONOMER.
    BRENDAi1.16.1.8. 2681.
    ReactomeiREACT_115639. Sulfur amino acid metabolism.
    REACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
    REACT_169149. Defective MTR causes methylmalonic aciduria and homocystinuria type cblG.
    REACT_169439. Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE.
    REACT_6946. Methylation.
    SABIO-RKQ9UBK8.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Methionine synthase reductase (EC:1.16.1.8)
    Short name:
    MSR
    Gene namesi
    Name:MTRR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:7473. MTRR.

    Subcellular locationi

    Isoform A :

    GO - Cellular componenti

    • cytoplasm Source: HPA
    • cytosol Source: UniProtKB
    • intermediate filament cytoskeleton Source: HPA
    • nucleoplasm Source: HPA
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE)2 Publications

    The disease is caused by mutations affecting the gene represented in this entry.

    Disease descriptionAn autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia. Cells from patients with HMAE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent.

    See also OMIM:236270
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti81 – 811Missing in HMAE. 1 Publication
    VAR_012837
    Natural varianti83 – 831V → M in HMAE. 1 Publication
    VAR_012838
    Natural varianti156 – 1561A → T in HMAE. 1 Publication
    VAR_012839
    Natural varianti432 – 4321C → R in HMAE. 1 Publication
    VAR_012841
    Natural varianti514 – 5141G → R in HMAE. 1 Publication
    VAR_012842
    Natural varianti581 – 5811G → R in HMAE. 1 Publication
    VAR_015731
    Natural varianti603 – 6031Missing in HMAE. 1 Publication
    VAR_012843
    Neural tube defects, folate-sensitive (NTDFS)2 Publications

    Disease susceptibility is associated with variations affecting the gene represented in this entry.

    Disease descriptionThe most common NTDs are open spina bifida (myelomeningocele) and anencephaly.

    See also OMIM:601634

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi236270. phenotype.
    601634. phenotype.
    Orphaneti2169. Methylcobalamin deficiency type cblE.
    PharmGKBiPA31277.

    Chemistry

    DrugBankiDB00115. Cyanocobalamin.
    DB00200. Hydroxocobalamin.
    DB00134. L-Methionine.

    Polymorphism and mutation databases

    BioMutaiMTRR.
    DMDMi296439300.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 725725Methionine synthase reductasePRO_0000021785Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei198 – 1981Phosphoserine1 Publication
    Modified residuei216 – 2161Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9UBK8.
    PaxDbiQ9UBK8.
    PRIDEiQ9UBK8.

    PTM databases

    PhosphoSiteiQ9UBK8.

    Expressioni

    Tissue specificityi

    Found in all tissues tested, particularly abundant in skeletal muscle.

    Gene expression databases

    BgeeiQ9UBK8.
    CleanExiHS_MTRR.
    ExpressionAtlasiQ9UBK8. baseline and differential.
    GenevisibleiQ9UBK8. HS.

    Organism-specific databases

    HPAiHPA038113.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FLJ13057Q53SE73EBI-10319161,EBI-10172181

    Protein-protein interaction databases

    BioGridi110645. 6 interactions.
    DIPiDIP-61183N.
    IntActiQ9UBK8. 1 interaction.
    STRINGi9606.ENSP00000264668.

    Structurei

    Secondary structure

    1
    725
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi262 – 2643Combined sources
    Beta strandi277 – 2826Combined sources
    Beta strandi301 – 31010Combined sources
    Beta strandi320 – 3267Combined sources
    Beta strandi339 – 3435Combined sources
    Helixi348 – 35710Combined sources
    Helixi361 – 3633Combined sources
    Beta strandi366 – 3727Combined sources
    Helixi393 – 3997Combined sources
    Helixi409 – 4168Combined sources
    Helixi422 – 43211Combined sources
    Helixi437 – 4437Combined sources
    Turni444 – 4485Combined sources
    Helixi451 – 4577Combined sources
    Helixi465 – 4717Combined sources
    Beta strandi478 – 4814Combined sources
    Turni486 – 4883Combined sources
    Beta strandi492 – 4987Combined sources
    Beta strandi501 – 5033Combined sources
    Beta strandi510 – 5134Combined sources
    Helixi515 – 5239Combined sources
    Turni524 – 5274Combined sources
    Beta strandi546 – 5516Combined sources
    Beta strandi567 – 5704Combined sources
    Helixi573 – 5764Combined sources
    Helixi577 – 59216Combined sources
    Beta strandi601 – 6088Combined sources
    Turni610 – 6123Combined sources
    Helixi617 – 6259Combined sources
    Beta strandi631 – 6399Combined sources
    Helixi652 – 6587Combined sources
    Helixi660 – 66910Combined sources
    Beta strandi673 – 6797Combined sources
    Helixi681 – 69919Combined sources
    Helixi703 – 71513Combined sources
    Beta strandi718 – 7236Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2QTLX-ray1.90A192-725[»]
    2QTZX-ray1.90A192-725[»]
    ProteinModelPortaliQ9UBK8.
    SMRiQ9UBK8. Positions 19-725.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UBK8.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini32 – 174143Flavodoxin-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini298 – 560263FAD-binding FR-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni193 – 27482HingeAdd
    BLAST

    Sequence similaritiesi

    Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
    Contains 1 flavodoxin-like domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0369.
    GeneTreeiENSGT00620000087711.
    HOGENOMiHOG000007485.
    HOVERGENiHBG108376.
    InParanoidiQ9UBK8.
    KOiK00597.
    OMAiAKDVNDT.
    OrthoDBiEOG7NCV31.
    PhylomeDBiQ9UBK8.
    TreeFamiTF105716.

    Family and domain databases

    Gene3Di1.20.990.10. 1 hit.
    3.40.50.360. 1 hit.
    InterProiIPR003097. FAD-binding_1.
    IPR017927. Fd_Rdtase_FAD-bd.
    IPR001094. Flavdoxin.
    IPR008254. Flavodoxin/NO_synth.
    IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
    IPR029039. Flavoprotein-like.
    IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF00667. FAD_binding_1. 1 hit.
    PF00258. Flavodoxin_1. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00369. FLAVODOXIN.
    PR00371. FPNCR.
    SUPFAMiSSF52218. SSF52218. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS51384. FAD_FR. 1 hit.
    PS50902. FLAVODOXIN_LIKE. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform A (identifier: Q9UBK8-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MGAASVRAGA RLVEVALCSF TVTCLEVMRR FLLLYATQQG QAKAIAEEIC
    60 70 80 90 100
    EQAVVHGFSA DLHCISESDK YDLKTETAPL VVVVSTTGTG DPPDTARKFV
    110 120 130 140 150
    KEIQNQTLPV DFFAHLRYGL LGLGDSEYTY FCNGGKIIDK RLQELGARHF
    160 170 180 190 200
    YDTGHADDCV GLELVVEPWI AGLWPALRKH FRSSRGQEEI SGALPVASPA
    210 220 230 240 250
    SSRTDLVKSE LLHIESQVEL LRFDDSGRKD SEVLKQNAVN SNQSNVVIED
    260 270 280 290 300
    FESSLTRSVP PLSQASLNIP GLPPEYLQVH LQESLGQEES QVSVTSADPV
    310 320 330 340 350
    FQVPISKAVQ LTTNDAIKTT LLVELDISNT DFSYQPGDAF SVICPNSDSE
    360 370 380 390 400
    VQSLLQRLQL EDKREHCVLL KIKADTKKKG ATLPQHIPAG CSLQFIFTWC
    410 420 430 440 450
    LEIRAIPKKA FLRALVDYTS DSAEKRRLQE LCSKQGAADY SRFVRDACAC
    460 470 480 490 500
    LLDLLLAFPS CQPPLSLLLE HLPKLQPRPY SCASSSLFHP GKLHFVFNIV
    510 520 530 540 550
    EFLSTATTEV LRKGVCTGWL ALLVASVLQP NIHASHEDSG KALAPKISIS
    560 570 580 590 600
    PRTTNSFHLP DDPSIPIIMV GPGTGIAPFI GFLQHREKLQ EQHPDGNFGA
    610 620 630 640 650
    MWLFFGCRHK DRDYLFRKEL RHFLKHGILT HLKVSFSRDA PVGEEEAPAK
    660 670 680 690 700
    YVQDNIQLHG QQVARILLQE NGHIYVCGDA KNMAKDVHDA LVQIISKEVG
    710 720
    VEKLEAMKTL ATLKEEKRYL QDIWS
    Length:725
    Mass (Da):80,410
    Last modified:May 18, 2010 - v3
    Checksum:iC3EF82DAC388BAF1
    GO
    Isoform B (identifier: Q9UBK8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-27: Missing.

    Show »
    Length:698
    Mass (Da):77,674
    Checksum:iD4B394F0B24A07E5
    GO
    Isoform C (identifier: Q9UBK8-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-27: Missing.
         71-85: YDLKTETAPLVVVVS → VSVIQNTPTFAMGGR
         86-725: Missing.

    Show »
    Length:58
    Mass (Da):6,368
    Checksum:i5FDB3101DE6A9453
    GO

    Polymorphismi

    Variant Met-49 has been associated with an increased risk for spina bifida and may be associated with chromosomal non-disjunction and Down syndrome.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti49 – 491I → M Polymorphism; may increase risk for spina bifida. 1 Publication
    Corresponds to variant rs1801394 [ dbSNP | Ensembl ].
    VAR_012836
    Natural varianti81 – 811Missing in HMAE. 1 Publication
    VAR_012837
    Natural varianti83 – 831V → M in HMAE. 1 Publication
    VAR_012838
    Natural varianti156 – 1561A → T in HMAE. 1 Publication
    VAR_012839
    Natural varianti202 – 2021S → L.3 Publications
    Corresponds to variant rs1532268 [ dbSNP | Ensembl ].
    VAR_034595
    Natural varianti284 – 2841S → T.
    Corresponds to variant rs2303080 [ dbSNP | Ensembl ].
    VAR_034596
    Natural varianti360 – 3601L → V.1 Publication
    Corresponds to variant rs10064631 [ dbSNP | Ensembl ].
    VAR_012840
    Natural varianti377 – 3771K → R.
    Corresponds to variant rs162036 [ dbSNP | Ensembl ].
    VAR_034597
    Natural varianti432 – 4321C → R in HMAE. 1 Publication
    VAR_012841
    Natural varianti442 – 4421R → C.
    Corresponds to variant rs2287780 [ dbSNP | Ensembl ].
    VAR_034598
    Natural varianti477 – 4771P → R.
    Corresponds to variant rs16879334 [ dbSNP | Ensembl ].
    VAR_034599
    Natural varianti514 – 5141G → R in HMAE. 1 Publication
    VAR_012842
    Natural varianti542 – 5421A → V.
    Corresponds to variant rs16879355 [ dbSNP | Ensembl ].
    VAR_056947
    Natural varianti581 – 5811G → R in HMAE. 1 Publication
    VAR_015731
    Natural varianti603 – 6031Missing in HMAE. 1 Publication
    VAR_012843
    Natural varianti622 – 6221H → Y.
    Corresponds to variant rs10380 [ dbSNP | Ensembl ].
    VAR_014944

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2727Missing in isoform B and isoform C. 3 PublicationsVSP_003910Add
    BLAST
    Alternative sequencei71 – 8515YDLKT…VVVVS → VSVIQNTPTFAMGGR in isoform C. 2 PublicationsVSP_003911Add
    BLAST
    Alternative sequencei86 – 725640Missing in isoform C. 2 PublicationsVSP_003912Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF121213
    , AF121202, AF121203, AF121204, AF121205, AF121206, AF121207, AF121208, AF121209, AF121210, AF121211, AF121212 Genomic DNA. Translation: AAF17303.1.
    AF121214 mRNA. Translation: AAF16876.1.
    AF121213
    , AF121202, AF121203, AF121204, AF121205, AF121206, AF121207, AF121208, AF121209, AF121210, AF121211, AF121212 Genomic DNA. Translation: AAF17304.1.
    AF025794 mRNA. Translation: AAC39667.1.
    AC010346 Genomic DNA. No translation available.
    AC025174 Genomic DNA. No translation available.
    BC054816 mRNA. Translation: AAH54816.2.
    BC109216 mRNA. Translation: AAI09217.1.
    CCDSiCCDS3874.1. [Q9UBK8-1]
    CCDS47190.1. [Q9UBK8-2]
    RefSeqiNP_002445.2. NM_002454.2. [Q9UBK8-2]
    NP_076915.2. NM_024010.2. [Q9UBK8-1]
    UniGeneiHs.481551.

    Genome annotation databases

    EnsembliENST00000264668; ENSP00000264668; ENSG00000124275. [Q9UBK8-1]
    ENST00000440940; ENSP00000402510; ENSG00000124275. [Q9UBK8-2]
    ENST00000510279; ENSP00000427200; ENSG00000124275. [Q9UBK8-3]
    ENST00000514369; ENSP00000426132; ENSG00000124275. [Q9UBK8-3]
    GeneIDi4552.
    KEGGihsa:4552.
    UCSCiuc003jed.3. human. [Q9UBK8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    The hidden things - Issue 166 of December 2014

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF121213
    , AF121202, AF121203, AF121204, AF121205, AF121206, AF121207, AF121208, AF121209, AF121210, AF121211, AF121212 Genomic DNA. Translation: AAF17303.1.
    AF121214 mRNA. Translation: AAF16876.1.
    AF121213
    , AF121202, AF121203, AF121204, AF121205, AF121206, AF121207, AF121208, AF121209, AF121210, AF121211, AF121212 Genomic DNA. Translation: AAF17304.1.
    AF025794 mRNA. Translation: AAC39667.1.
    AC010346 Genomic DNA. No translation available.
    AC025174 Genomic DNA. No translation available.
    BC054816 mRNA. Translation: AAH54816.2.
    BC109216 mRNA. Translation: AAI09217.1.
    CCDSiCCDS3874.1. [Q9UBK8-1]
    CCDS47190.1. [Q9UBK8-2]
    RefSeqiNP_002445.2. NM_002454.2. [Q9UBK8-2]
    NP_076915.2. NM_024010.2. [Q9UBK8-1]
    UniGeneiHs.481551.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2QTLX-ray1.90A192-725[»]
    2QTZX-ray1.90A192-725[»]
    ProteinModelPortaliQ9UBK8.
    SMRiQ9UBK8. Positions 19-725.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi110645. 6 interactions.
    DIPiDIP-61183N.
    IntActiQ9UBK8. 1 interaction.
    STRINGi9606.ENSP00000264668.

    Chemistry

    DrugBankiDB00115. Cyanocobalamin.
    DB00200. Hydroxocobalamin.
    DB00134. L-Methionine.

    PTM databases

    PhosphoSiteiQ9UBK8.

    Polymorphism and mutation databases

    BioMutaiMTRR.
    DMDMi296439300.

    Proteomic databases

    MaxQBiQ9UBK8.
    PaxDbiQ9UBK8.
    PRIDEiQ9UBK8.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000264668; ENSP00000264668; ENSG00000124275. [Q9UBK8-1]
    ENST00000440940; ENSP00000402510; ENSG00000124275. [Q9UBK8-2]
    ENST00000510279; ENSP00000427200; ENSG00000124275. [Q9UBK8-3]
    ENST00000514369; ENSP00000426132; ENSG00000124275. [Q9UBK8-3]
    GeneIDi4552.
    KEGGihsa:4552.
    UCSCiuc003jed.3. human. [Q9UBK8-1]

    Organism-specific databases

    CTDi4552.
    GeneCardsiGC05P007851.
    GeneReviewsiMTRR.
    H-InvDBHIX0031952.
    HGNCiHGNC:7473. MTRR.
    HPAiHPA038113.
    MIMi236270. phenotype.
    601634. phenotype.
    602568. gene.
    neXtProtiNX_Q9UBK8.
    Orphaneti2169. Methylcobalamin deficiency type cblE.
    PharmGKBiPA31277.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0369.
    GeneTreeiENSGT00620000087711.
    HOGENOMiHOG000007485.
    HOVERGENiHBG108376.
    InParanoidiQ9UBK8.
    KOiK00597.
    OMAiAKDVNDT.
    OrthoDBiEOG7NCV31.
    PhylomeDBiQ9UBK8.
    TreeFamiTF105716.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04756-MONOMER.
    BRENDAi1.16.1.8. 2681.
    ReactomeiREACT_115639. Sulfur amino acid metabolism.
    REACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
    REACT_169149. Defective MTR causes methylmalonic aciduria and homocystinuria type cblG.
    REACT_169439. Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE.
    REACT_6946. Methylation.
    SABIO-RKQ9UBK8.

    Miscellaneous databases

    EvolutionaryTraceiQ9UBK8.
    GeneWikiiMTRR_(gene).
    GenomeRNAii4552.
    NextBioi17541.
    PROiQ9UBK8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9UBK8.
    CleanExiHS_MTRR.
    ExpressionAtlasiQ9UBK8. baseline and differential.
    GenevisibleiQ9UBK8. HS.

    Family and domain databases

    Gene3Di1.20.990.10. 1 hit.
    3.40.50.360. 1 hit.
    InterProiIPR003097. FAD-binding_1.
    IPR017927. Fd_Rdtase_FAD-bd.
    IPR001094. Flavdoxin.
    IPR008254. Flavodoxin/NO_synth.
    IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
    IPR029039. Flavoprotein-like.
    IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF00667. FAD_binding_1. 1 hit.
    PF00258. Flavodoxin_1. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00369. FLAVODOXIN.
    PR00371. FPNCR.
    SUPFAMiSSF52218. SSF52218. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS51384. FAD_FR. 1 hit.
    PS50902. FLAVODOXIN_LIKE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular cloning, expression and physical mapping of the human methionine synthase reductase gene."
      Leclerc D., Odievre M.-H., Wu Q., Wilson A., Huizenga J., Rozen R., Scherer S.W., Gravel R.A.
      Gene 240:75-88(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS A; B AND C), VARIANT LEU-202.
    2. "Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria."
      Leclerc D., Wilson A., Dumas R., Gafuik C., Song D., Watkins D., Heng H.H.Q., Rommens J.M., Scherer S.W., Rosenblatt D.S., Gravel R.A.
      Proc. Natl. Acad. Sci. U.S.A. 95:3059-3064(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), VARIANT LEU-202, VARIANT HMAE LEU-603 DEL.
    3. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
      Tissue: Lung.
    5. "Restricted role for methionine synthase reductase defined by subcellular localization."
      Froese D.S., Wu X., Zhang J., Dumas R., Schoel W.M., Amrein M., Gravel R.A.
      Mol. Genet. Metab. 94:68-77(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION (ISOFORM A).
    6. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    9. "Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry."
      Wolthers K.R., Lou X., Toogood H.S., Leys D., Scrutton N.S.
      Biochemistry 46:11833-11844(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 192-725 IN COMPLEX WITH FAD AND NADP, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, FUNCTION.
    10. "Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism."
      Wilson A., Leclerc D., Rosenblatt D.S., Gravel R.A.
      Hum. Mol. Genet. 8:2009-2016(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HMAE VAL-81 DEL; MET-83; THR-156; ARG-432; ARG-514 AND ARG-581, VARIANT VAL-360.
    11. "A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida."
      Wilson A., Platt R., Wu Q., Leclerc D., Christensen B., Yang H., Gravel R.A., Rozen R.
      Mol. Genet. Metab. 67:317-323(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO NTDFS, VARIANT MET-49.
    12. "Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida."
      Doolin M.-T., Barbaux S., McDonnell M., Hoess K., Whitehead A.S., Mitchell L.E.
      Am. J. Hum. Genet. 71:1222-1226(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO NTDFS, VARIANT MET-49.
    13. "Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association."
      O'Leary V.B., Mills J.L., Pangilinan F., Kirke P.N., Cox C., Conley M., Weiler A., Peng K., Shane B., Scott J.M., Parle-McDermott A., Molloy A.M., Brody L.C.
      Mol. Genet. Metab. 85:220-227(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MET-49; LEU-202 AND ARG-377.

    Entry informationi

    Entry nameiMTRR_HUMAN
    AccessioniPrimary (citable) accession number: Q9UBK8
    Secondary accession number(s): O60471, Q32MA9, Q7Z4M8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 27, 2002
    Last sequence update: May 18, 2010
    Last modified: June 24, 2015
    This is version 151 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.