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METF_HAEIN
ID   METF_HAEIN              Reviewed;         292 AA.
AC   P45208;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 127.
DE   RecName: Full=5,10-methylenetetrahydrofolate reductase;
DE            EC=1.5.1.20;
GN   Name=metF; OrderedLocusNames=HI_1444;
OS   Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Haemophilus.
OX   NCBI_TaxID=71421;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX   PubMed=7542800; DOI=10.1126/science.7542800;
RA   Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F.,
RA   Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M.,
RA   McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D.,
RA   Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F.,
RA   Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R.,
RA   Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D.,
RA   Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A.,
RA   Small K.V., Fraser C.M., Smith H.O., Venter J.C.;
RT   "Whole-genome random sequencing and assembly of Haemophilus influenzae
RT   Rd.";
RL   Science 269:496-512(1995).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-
CC         methylene-5,6,7,8-tetrahydrofolate + H(+) + NADPH;
CC         Xref=Rhea:RHEA:19817, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC         ChEBI:CHEBI:18608, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.20;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10-
CC         methylene-5,6,7,8-tetrahydrofolate + H(+) + NADH;
CC         Xref=Rhea:RHEA:19821, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC         ChEBI:CHEBI:18608, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.5.1.20;
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC   -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; L42023; AAC23094.1; -; Genomic_DNA.
DR   PIR; H64123; H64123.
DR   RefSeq; NP_439596.1; NC_000907.1.
DR   RefSeq; WP_005652747.1; NC_000907.1.
DR   PDB; 5UME; X-ray; 2.70 A; A/B/C/D/E/F=1-292.
DR   PDBsum; 5UME; -.
DR   AlphaFoldDB; P45208; -.
DR   SMR; P45208; -.
DR   STRING; 71421.HI_1444; -.
DR   EnsemblBacteria; AAC23094; AAC23094; HI_1444.
DR   KEGG; hin:HI_1444; -.
DR   PATRIC; fig|71421.8.peg.1506; -.
DR   eggNOG; COG0685; Bacteria.
DR   HOGENOM; CLU_025841_0_0_6; -.
DR   OMA; EMHPQAR; -.
DR   PhylomeDB; P45208; -.
DR   BioCyc; HINF71421:G1GJ1-1470-MON; -.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000000579; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR   GO; GO:0004489; F:methylenetetrahydrofolate reductase (NAD(P)H) activity; IBA:GO_Central.
DR   GO; GO:0106312; F:methylenetetrahydrofolate reductase NADH activity; IEA:RHEA.
DR   GO; GO:0106313; F:methylenetetrahydrofolate reductase NADPH activity; IEA:RHEA.
DR   GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central.
DR   GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR   CDD; cd00537; MTHFR; 1.
DR   InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR   InterPro; IPR003171; Mehydrof_redctse-like.
DR   InterPro; IPR004620; MTHF_reductase_bac.
DR   Pfam; PF02219; MTHFR; 1.
DR   SUPFAM; SSF51730; SSF51730; 1.
DR   TIGRFAMs; TIGR00676; fadh2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amino-acid biosynthesis; FAD; Flavoprotein;
KW   Methionine biosynthesis; NAD; NADP; Oxidoreductase; Reference proteome.
FT   CHAIN           1..292
FT                   /note="5,10-methylenetetrahydrofolate reductase"
FT                   /id="PRO_0000190263"
FT   ACT_SITE        26
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         26..31
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         57..60
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         57..58
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         86
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         116..118
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         118
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         129..130
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         150
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         154..157
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         163..170
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         181
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         217
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         273
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         277
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   HELIX           4..14
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          22..27
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           33..46
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           47..49
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          52..56
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           60..62
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           65..79
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          83..92
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           94..107
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          111..115
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           130..140
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          144..149
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           160..172
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          177..182
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           186..199
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          205..209
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           215..224
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           231..235
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   TURN            236..239
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           244..264
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   STRAND          269..273
FT                   /evidence="ECO:0007829|PDB:5UME"
FT   HELIX           279..288
FT                   /evidence="ECO:0007829|PDB:5UME"
SQ   SEQUENCE   292 AA;  33020 MW;  C6DCC9BC80CFF9B4 CRC64;
     MSYAKEIDTL NQHIADFNKK INVSFEFFPP KNEKMETLLW DSIHRLKVLK PKFVSVTYGA
     NSGERDRTHG IVKAIKQETG LEAAPHLTGI DATPEELKQI ARDYWDSGIR RIVALRGDEP
     KGYAKKPFYA SDLVELLRSV ADFDISVAAY PEVHPEAKSA QADLINLKRK IDAGANHVIT
     QFFFDIENYL RFRDRCASIG IDTEIVPGIL PVTNFKQLQK MASFTNVKIP AWLVKAYDGL
     DNDPTTRNLV AASVAMDMVK ILSREGVNDF HFYTLNRSEL TYAICHMLGV RP
 
 
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