Gene: Mtrr

Basic information

Tag Content
Uniprot ID Q498R1; D3ZDG8;
Entrez ID 290947
Genbank protein ID EDL87600.1; AAI00108.1;
Genbank nucleotide ID NM_001039003.1; XM_006227813.3;
Ensembl protein ID ENSRNOP00000058505; ENSRNOP00000024041;
Ensembl nucleotide ID ENSRNOG00000017826
Gene name Methionine synthase reductase
Gene symbol Mtrr
Organism Rattus norvegicus
NCBI taxa ID 10116
Cleft type
Developmental stage
Data sources Homology search
Reference
Functional description Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin. Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (By similarity). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (By similarity). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme. Also serves as an aquacobalamin reductase by reducing aquacobalamin to cob(II)alamin in the presence of NADPH, and this reduction leads to stimulation of the conversion of apoMTR and aquacobalamin to MTR holoenzyme (By similarity).
Sequence
MRRFLLLYAT QRGQAKAIAE EISEQALSHG FSADLHCVSE SEKYDLKTET GPLVMVVSTT 60
GTGDPPDTAR KFVKEIHNKT LPTDFFAHLW YGLLGLGDSE YTYFCNGGKV IDKRLQELGA 120
QHFYDTGHAD DCVGLELVVE PWIDGLWPAL TKHFKSLGGQ EDMSDSDTLA QASDAPLSMA 180
MKPELLHIQS QVELLSLEDV GKRDSELQEQ NETNKNQPSR IEDFDSSLVN SVPPLSQSSL 240
SIPAVSPEYL EVYLQESLGQ DENQASVPPS VDPIFQVPIS KAVELTTNDA IKTTLLLELD 300
ISKVEFSHQP GDSFNVICPN SGSEVEDLLQ RLQLADKQAH RVILKIKMDT KKKGASLPQH 360
VPEGSSLQFI FTWCLEIRAV PKKAFLRALS DYTSDATEKR RLQELCSKQG AADYNRFIRD 420
ASVCLLDLLL TFPSCQPPLN LLLEHLPKLQ PRPYSCASSS LLHPDKLHFV FNIVELPSNT 480
TAASLRKGVC TGWLATLVAP FLQPNTEVLT ADHSDALAPE ILISPRATNS FHLPDDLSAP 540
IIMVGPGTGV APFVGFLQHR EKLQEQHPDG NFGAMWLFFG CRHKDRDYLF REELRHFLKT 600
GVLTHLKVSF SRDAAPEEEE EAPAKYVQDN LQHHSQQVAR TLLQENGYIY VCGDAKNMAK 660
DVHDALVEII SKEAGVDKLE AMKTLATLKQ EKRYLQDIWS

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Protein disorder information

Orthologous information

Relation Gene symbol Entrez ID UniProt ID Cleft type Developmental stage Species Evidence Details
1:1 orthologMTRR507991F1MGP5Bos taurusPredictionMore>>
1:1 orthologMTRR102171193A0A452F9C4Capra hircusPredictionMore>>
1:1 orthologMTRR4552Q9UBK8CPO,CL/PHomo sapiensPublicationMore>>
1:1 orthologMtrr210009A0A0R4J0G9Mus musculusPredictionMore>>
1:1 orthologMTRR461717H2QQM3Pan troglodytesPredictionMore>>
1:1 orthologMTRRF1S0T1Sus scrofaPredictionMore>>
1:1 orthologMtrr290947Q498R1Rattus norvegicusPredictionMore>>
1:1 orthologmtrr560667F1RE28Danio rerioPredictionMore>>

Gene ontology

GO ID GO Term
GO:0005829 cytosol
GO:0030586 [methionine synthase] reductase activity
GO:0050444 aquacobalamin reductase (NADPH) activity
GO:0071949 FAD binding
GO:0050660 flavin adenine dinucleotide binding
GO:0010181 FMN binding
GO:0070402 NADPH binding
GO:0003958 NADPH-hemoprotein reductase activity
GO:0016491 oxidoreductase activity
GO:0016709 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
GO:0016723 oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor
GO:0006306 DNA methylation
GO:0046655 folic acid metabolic process
GO:0043418 homocysteine catabolic process
GO:0050667 homocysteine metabolic process
GO:0009086 methionine biosynthetic process
GO:1904042 negative regulation of cystathionine beta-synthase activity
GO:0055114 oxidation-reduction process
GO:0033353 S-adenosylmethionine cycle

Functional annotations

Keywords

Keyword ID Keyword Term
KW-0025 Alternative splicing
KW-0028 Amino-acid biosynthesis
KW-0963 Cytoplasm
KW-0274 FAD
KW-0285 Flavoprotein
KW-0288 FMN
KW-0486 Methionine biosynthesis
KW-0521 NADP
KW-0560 Oxidoreductase
KW-0597 Phosphoprotein
KW-1185 Reference proteome
KW-0949 S-adenosyl-L-methionine

Interpro

InterPro ID InterPro Term
IPR003097 CysJ-like_FAD-binding
IPR017927 FAD-bd_FR_type
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR039261 FNR_nucleotide-bd
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR001433 OxRdtase_FAD/NAD-bd
IPR017938 Riboflavin_synthase-like_b-brl

PROSITE

PROSITE ID PROSITE Term
PS51384 FAD_FR
PS50902 FLAVODOXIN_LIKE

Pfam

Pfam ID Pfam Term
PF00667 FAD_binding_1
PF00258 Flavodoxin_1
PF00175 NAD_binding_1