DB code: D00043
| CATH domain | 2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3 | Catalytic domain |
|---|---|---|
| 3.40.50.80 : Rossmann fold | Catalytic domain | |
| E.C. | 1.6.2.2 | |
| CSA | 1ndh | |
| M-CSA | 1ndh | |
| MACiE | ||
| CATH domain | Related DB codes (homologues) |
|---|---|
| 2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3 | M00006 M00141 M00159 M00164 |
| 3.40.50.80 : Rossmann fold | M00006 M00141 M00159 M00164 |
| Uniprot Enzyme Name | UniprotKB | Protein name | Synonyms | Contains | Pfam | RefSeq |
|---|---|---|---|---|---|
| P83686 |
NADH-cytochrome b5 reductase 3
|
Cytochrome b5 reductase
B5R EC 1.6.2.2 Diaphorase-1 |
None |
PF00970
(FAD_binding_6)
PF00175 (NAD_binding_1) [Graphical View] |
|
| P20070 |
NADH-cytochrome b5 reductase 3
|
Cytochrome b5 reductase
B5R EC 1.6.2.2 Diaphorase-1 |
NADH-cytochrome b5 reductase 3 membrane-bound form
NADH-cytochrome b5 reductase 3 soluble form |
PF00970
(FAD_binding_6)
PF00175 (NAD_binding_1) [Graphical View] |
NP_620232.1
(Protein)
NM_138877.1 (DNA/RNA sequence) |
| P00387 |
NADH-cytochrome b5 reductase 3
|
Cytochrome b5 reductase
B5R EC 1.6.2.2 Diaphorase-1 |
NADH-cytochrome b5 reductase 3 membrane-bound form
NADH-cytochrome b5 reductase 3 soluble form |
PF00970
(FAD_binding_6)
PF00175 (NAD_binding_1) [Graphical View] |
NP_000389.1
(Protein)
NM_000398.6 (DNA/RNA sequence) NP_001123291.1 (Protein) NM_001129819.2 (DNA/RNA sequence) NP_001165131.1 (Protein) NM_001171660.1 (DNA/RNA sequence) NP_001165132.1 (Protein) NM_001171661.1 (DNA/RNA sequence) NP_015565.1 (Protein) NM_007326.4 (DNA/RNA sequence) |
| KEGG enzyme name |
|---|
|
cytochrome-b5 reductase
cytochrome b5 reductase dihydronicotinamide adenine dinucleotide-cytochrome b5 reductase reduced nicotinamide adeninedinucleotide-cytochrome b5 reductase NADH-ferricytochrome b5 oxidoreductase NADH-cytochrome b5 reductase NADH 5alpha-reductase NADH-cytochrome-b5 reductase |
| UniprotKB: Accession Number | Entry name | Activity | Subunit | Subcellular location | Cofactor |
|---|---|---|---|---|---|
| P83686 | NB5R3_PIG | NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5. | Component of a complex composed of cytochrome b5, NADH- cytochrome b5 reductase (CYB5R3) and MOSC2. | Endoplasmic reticulum membrane, Lipid- anchor, Cytoplasmic side (By similarity). Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side (By similarity). Cytoplasm (By similarity). Note=The enzyme exists in two forms, a membrane-bound form on the cytoplasmic side of the endoplasmic reticulum and also on the mitochondrial outer membrane and in soluble form in erythrocytes (By similarity). NADH-cytochrome b5 reductase 3 membrane-bound form: Endoplasmic reticulum membrane, Lipid-anchor, Cytoplasmic side (By similarity). Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side (By similarity). NADH-cytochrome b5 reductase 3 soluble form: Cytoplasm (By similarity). | FAD. |
| P20070 | NB5R3_RAT | NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5. | Component of a complex composed of cytochrome b5, NADH- cytochrome b5 reductase (CYB5R3) and MOSC2 (By similarity). | Isoform 1: Endoplasmic reticulum membrane, Lipid-anchor, Cytoplasmic side. Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side. Isoform 3: Cytoplasm. Note=Produces the soluble form found in erythrocytes. | FAD. |
| P00387 | NB5R3_HUMAN | NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5. | Component of a complex composed of cytochrome b5, NADH- cytochrome b5 reductase (CYB5R3) and MOSC2 (By similarity). | Isoform 1: Endoplasmic reticulum membrane, Lipid-anchor, Cytoplasmic side. Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side. Isoform 2: Cytoplasm. Note=Produces the soluble form found in erythrocytes. | FAD. |
| KEGG Pathways | Map code | Pathways | E.C. |
|---|---|---|
| MAP00530 | Aminosugars metabolism |
| Compound table | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cofactors | Substrates | Products | Intermediates | |||||||||
| KEGG-id | C00016 | C00004 | C00996 | C00080 | C00003 | C00999 | ||||||
| E.C. | ||||||||||||
| Compound | FAD | NADH | Ferricytochrome b5 | H+ | NAD+ | Ferrocytochrome b5 | ||||||
| Type | amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotide | amide group,amine group,nucleotide | aromatic ring (with nitrogen atoms),carbohydrate,heavy metal | others | amide group,amine group,nucleotide | aromatic ring (with nitrogen atoms),carbohydrate,heavy metal | ||||||
| ChEBI |
16238 16238 |
16908 16908 |
15378 15378 |
15846 15846 |
||||||||
| PubChem |
643975 643975 |
439153 439153 |
1038 1038 |
5893 5893 |
||||||||
| 1ndhA01 |
|
|
|
|
|
Bound:FAD | Unbound | Unbound | Unbound | Unbound | ||
| 1i7pA01 |
|
|
|
|
|
Bound:FAD | Unbound | Unbound | Unbound | Unbound | ||
| 1ib0A01 |
|
|
|
|
|
Bound:FAD | Unbound | Unbound | Bound:NAD | Unbound | ||
| 1qx4A01 |
|
|
|
|
|
Bound:FAD | Unbound | Unbound | Unbound | Unbound | ||
| 1qx4B01 |
|
|
|
|
|
Bound:FAD | Unbound | Unbound | Unbound | Unbound | ||
| 1umkA01 |
|
|
|
|
|
Bound:FAD | Unbound | Unbound | Unbound | Unbound | ||
| 1ndhA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | ||
| 1i7pA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | ||
| 1ib0A02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | ||
| 1qx4A02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | ||
| 1qx4B02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | ||
| 1umkA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | ||
| Reference for Active-site residues | ||
|---|---|---|
| resource | references | E.C. |
| Swissprot;P83686 & literature [17] | ||
| Active-site residues | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| PDB | Catalytic residues | Cofactor-binding residues | Modified residues | Main-chain involved in catalysis | Comment | |||||
| 1ndhA01 |
|
|
|
|
|
HIS 49;ARG 63;TYR 65 | ||||
| 1i7pA01 |
|
|
|
|
|
HIS 77;ARG 91;TYR 93 | ||||
| 1ib0A01 |
|
|
|
|
|
HIS 77;ARG 91;TYR 93 | ||||
| 1qx4A01 |
|
|
|
|
|
HIS 77;ARG 91;TYR 93 | mutant S127P | |||
| 1qx4B01 |
|
|
|
|
|
HIS 77;ARG 91;TYR 93 | mutant S127P | |||
| 1umkA01 |
|
|
|
|
|
HIS 77;ARG 91;TYR 93 | ||||
| 1ndhA02 |
|
|
|
|
|
PHE 272 | ||||
| 1i7pA02 |
|
|
|
|
|
PHE 300 | ||||
| 1ib0A02 |
|
|
|
|
|
PHE 300 | ||||
| 1qx4A02 |
|
|
|
|
|
PHE 300 | ||||
| 1qx4B02 |
|
|
|
|
|
PHE 300 | ||||
| 1umkA02 |
|
|
|
|
|
PHE 300 | ||||
| References for Catalytic Mechanism | ||
|---|---|---|
| References | Sections | No. of steps in catalysis |
|
[12]
|
p.39-40 | |
|
[14]
|
p.299-300 | |
|
[17]
|
||
|
[19]
|
Scheme II, p.3587-3588 | |
| References | |
|---|---|
| [1] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 3624234 |
| Journal | J Biol Chem |
| Year | 1987 |
| Volume | 262 |
| Pages | 11801-2 |
| Authors | Miki K, Kaida S, Kasai N, Iyanagi T, Kobayashi K, Hayashi K |
| Title | Crystallization and preliminary x-ray crystallographic study of NADH-cytochrome b5 reductase from pig liver microsomes. |
| Related PDB | |
| Related UniProtKB | |
| [2] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 3656431 |
| Journal | J Mol Biol |
| Year | 1987 |
| Volume | 195 |
| Pages | 749-50 |
| Authors | Takano T, Ogawa K, Sato M, Bando S, Yubisui T |
| Title | Preliminary X-ray data of NADH-cytochrome b5 reductase from human erythrocytes. |
| Related PDB | |
| Related UniProtKB | |
| [3] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 2831990 |
| Journal | Biochim Biophys Acta |
| Year | 1988 |
| Volume | 953 |
| Pages | 164-78 |
| Authors | Utecht RE, Kurtz DM Jr |
| Title | Cytochrome b5 and NADH-cytochrome-b5 reductase from sipunculan erythrocytes; a methemerythrin reduction system from Phascolopsis gouldii. |
| Related PDB | |
| Related UniProtKB | |
| [4] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 2494940 |
| Journal | Arch Biochem Biophys |
| Year | 1989 |
| Volume | 270 |
| Pages | 137-43 |
| Authors | Reif DW, Coulombe RA Jr, Aust SD |
| Title | Vanadate-dependent NAD(P)H oxidation by microsomal enzymes. |
| Related PDB | |
| Related UniProtKB | |
| [5] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 2189408 |
| Journal | Biochem Biophys Res Commun |
| Year | 1990 |
| Volume | 168 |
| Pages | 1285-91 |
| Authors | Hyde GE, Campbell WH |
| Title | High-level expression in Escherichia coli of the catalytically active flavin domain of corn leaf NADH:nitrate reductase and its comparison to human NADH:cytochrome B5 reductase. |
| Related PDB | |
| Related UniProtKB | |
| [6] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 2123873 |
| Journal | J Biol Chem |
| Year | 1990 |
| Volume | 265 |
| Pages | 21709-13 |
| Authors | Strittmatter P, Hackett CS, Korza G, Ozols J |
| Title | Characterization of the covalent cross-links of the active sites of amidinated cytochrome b5 and NADH:cytochrome b5 reductase. |
| Related PDB | |
| Related UniProtKB | |
| [7] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 2019583 |
| Journal | J Biol Chem |
| Year | 1991 |
| Volume | 266 |
| Pages | 7531-6 |
| Authors | Shirabe K, Yubisui T, Nishino T, Takeshita M |
| Title |
Role of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. |
| Related PDB | |
| Related UniProtKB | |
| [8] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 1898726 |
| Journal | J Biol Chem |
| Year | 1991 |
| Volume | 266 |
| Pages | 66-70 |
| Authors | Yubisui T, Shirabe K, Takeshita M, Kobayashi Y, Fukumaki Y, Sakaki Y, Takano T |
| Title | Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase. |
| Related PDB | |
| Related UniProtKB | |
| [9] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 1370824 |
| Journal | J Biol Chem |
| Year | 1992 |
| Volume | 267 |
| Pages | 2519-23 |
| Authors | Strittmatter P, Kittler JM, Coghill JE, Ozols J |
| Title | Characterization of lysyl residues of NADH-cytochrome b5 reductase implicated in charge-pairing with active-site carboxyl residues of cytochrome b5 by site-directed mutagenesis of an expression vector for the flavoprotein. |
| Related PDB | |
| Related UniProtKB | |
| [10] | |
| Resource | |
| Comments | X-ray crystallography |
| Medline ID | |
| PubMed ID | 7893687 |
| Journal | Biochemistry |
| Year | 1995 |
| Volume | 34 |
| Pages | 2763-7 |
| Authors | Nishida H, Inaka K, Yamanaka M, Kaida S, Kobayashi K, Miki K |
| Title | Crystal structure of NADH-cytochrome b5 reductase from pig liver at 2.4 A resolution. |
| Related PDB | 1ndh |
| Related UniProtKB | |
| [11] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 7890048 |
| Journal | FEBS Lett |
| Year | 1995 |
| Volume | 361 |
| Pages | 97-100 |
| Authors | Nishida H, Inaka K, Miki K |
| Title | Specific arrangement of three amino acid residues for flavin-binding barrel structures in NADH-cytochrome b5 reductase and the other flavin-dependent reductases. |
| Related PDB | |
| Related UniProtKB | |
| [12] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 8880927 |
| Journal | Proteins |
| Year | 1996 |
| Volume | 26 |
| Pages | 32-41 |
| Authors | Nishida H, Miki K |
| Title | Electrostatic properties deduced from refined structures of NADH-cytochrome b5 reductase and the other flavin-dependent reductases: pyridine nucleotide-binding and interaction with an electron-transfer partner. |
| Related PDB | |
| Related UniProtKB | |
| [13] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 9602031 |
| Journal | Biochim Biophys Acta |
| Year | 1998 |
| Volume | 1384 |
| Pages | 16-22 |
| Authors | Shirabe K, Nagai T, Yubisui T, Takeshita M |
| Title | Electrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5 studied by site-directed mutagenesis. |
| Related PDB | |
| Related UniProtKB | |
| [14] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 10082957 |
| Journal | Biochim Biophys Acta |
| Year | 1999 |
| Volume | 1430 |
| Pages | 290-301 |
| Authors | Kimura S, Emi Y, Ikushiro S, Iyanagi T |
| Title | Systematic mutations of highly conserved His49 and carboxyl-terminal of recombinant porcine liver NADH-cytochrome b5 reductase solubilized domain. |
| Related PDB | |
| Related UniProtKB | |
| [15] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 10622712 |
| Journal | FEBS Lett |
| Year | 1999 |
| Volume | 462 |
| Pages | 283-8 |
| Authors | Lamb DC, Kelly DE, Manning NJ, Kaderbhai MA, Kelly SL |
| Title | Biodiversity of the P450 catalytic cycle: yeast cytochrome b5/NADH cytochrome b5 reductase complex efficiently drives the entire sterol 14-demethylation (CYP51) reaction. |
| Related PDB | |
| Related UniProtKB | |
| [16] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 11695905 |
| Journal | Biochemistry |
| Year | 2001 |
| Volume | 40 |
| Pages | 13574-82 |
| Authors | Bewley MC, Marohnic CC, Barber MJ |
| Title | The structure and biochemistry of NADH-dependent cytochrome b5 reductase are now consistent. |
| Related PDB | 1i7p 1ib0 |
| Related UniProtKB | |
| [17] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 11574067 |
| Journal | J Biochem (Tokyo) |
| Year | 2001 |
| Volume | 130 |
| Pages | 481-90 |
| Authors | Kimura S, Nishida H, Iyanagi T |
| Title | Effects of flavin-binding motif amino acid mutations in the NADH-cytochrome b5 reductase catalytic domain on protein stability and catalysis. |
| Related PDB | |
| Related UniProtKB | |
| [18] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 14503867 |
| Journal | Biochemistry |
| Year | 2003 |
| Volume | 42 |
| Pages | 11170-82 |
| Authors | Marohnic CC, Bewley MC, Barber MJ |
| Title | Engineering and characterization of a NADPH-utilizing cytochrome b5 reductase. |
| Related PDB | |
| Related UniProtKB | |
| [19] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 12459552 |
| Journal | J Biol Chem |
| Year | 2003 |
| Volume | 278 |
| Pages | 3580-9 |
| Authors | Kimura S, Kawamura M, Iyanagi T |
| Title | Role of Thr(66) in porcine NADH-cytochrome b5 reductase in catalysis and control of the rate-limiting step in electron transfer. |
| Related PDB | |
| Related UniProtKB | |
| [20] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 14609324 |
| Journal | Biochemistry |
| Year | 2003 |
| Volume | 42 |
| Pages | 13145-51 |
| Authors | Bewley MC, Davis CA, Marohnic CC, Taormina D, Barber MJ |
| Title | The structure of the S127P mutant of cytochrome b5 reductase that causes methemoglobinemia shows the AMP moiety of the flavin occupying the substrate binding site. |
| Related PDB | 1qx4 |
| Related UniProtKB | |
| [21] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 15488472 |
| Journal | Arch Biochem Biophys |
| Year | 2004 |
| Volume | 431 |
| Pages | 233-44 |
| Authors | Davis CA, Crowley LJ, Barber MJ |
| Title |
Cytochrome b5 reductase: the roles of the recessive congenital methemoglobinemia mutants P144L, |
| Related PDB | |
| Related UniProtKB | |
| [22] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 15502298 |
| Journal | Acta Crystallogr D Biol Crystallogr |
| Year | 2004 |
| Volume | 60 |
| Pages | 1929-34 |
| Authors | Bando S, Takano T, Yubisui T, Shirabe K, Takeshita M, Nakagawa A |
| Title | Structure of human erythrocyte NADH-cytochrome b5 reductase. |
| Related PDB | 1umk |
| Related UniProtKB | |
| Comments |
|---|
| Created | Updated |
|---|---|
| 2004-12-20 | 2009-02-26 |