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Protein

NADH-cytochrome b5 reductase 3

Gene

CYB5R3

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

Functioni

Desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction.

Catalytic activityi

NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5.

Cofactori

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi132 – 14716FADBy similarityAdd
BLAST
Nucleotide bindingi171 – 20636FADBy similarityAdd
BLAST

GO - Molecular functioni

  1. ADP binding Source: Ensembl
  2. AMP binding Source: Ensembl
  3. cytochrome-b5 reductase activity, acting on NAD(P)H Source: Reactome
  4. FAD binding Source: UniProtKB
  5. flavin adenine dinucleotide binding Source: Ensembl
  6. NAD binding Source: Ensembl

GO - Biological processi

  1. blood circulation Source: ProtInc
  2. cholesterol biosynthetic process Source: UniProtKB-KW
  3. L-ascorbic acid metabolic process Source: Reactome
  4. small molecule metabolic process Source: Reactome
  5. vitamin metabolic process Source: Reactome
  6. water-soluble vitamin metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Keywords - Ligandi

FAD, Flavoprotein, NAD

Enzyme and pathway databases

BioCyciMetaCyc:HS02015-MONOMER.
BRENDAi1.6.2.2. 2681.
ReactomeiREACT_11202. Vitamin C (ascorbate) metabolism.
SABIO-RKP00387.

Names & Taxonomyi

Protein namesi
Recommended name:
NADH-cytochrome b5 reductase 3 (EC:1.6.2.2)
Short name:
B5R
Short name:
Cytochrome b5 reductase
Alternative name(s):
Diaphorase-1
Cleaved into the following 2 chains:
Gene namesi
Name:CYB5R3
Synonyms:DIA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 22

Organism-specific databases

HGNCiHGNC:2873. CYB5R3.

Subcellular locationi

Isoform 2 : Cytoplasm
Note: Produces the soluble form found in erythrocytes.

GO - Cellular componenti

  1. cytoplasm Source: ProtInc
  2. endoplasmic reticulum Source: HPA
  3. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  4. extracellular vesicular exosome Source: UniProtKB
  5. hemoglobin complex Source: ProtInc
  6. lipid particle Source: UniProtKB
  7. membrane Source: UniProtKB
  8. mitochondrial inner membrane Source: Ensembl
  9. mitochondrial outer membrane Source: Reactome
  10. mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

Methemoglobinemia CYB5R3-related10 Publications

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

Disease descriptionA form of methemoglobinemia, a hematologic disease characterized by the presence of excessive amounts of methemoglobin in blood cells, resulting in decreased oxygen carrying capacity of the blood, cyanosis and hypoxia. There are two types of methemoglobinemia CYB5R3-related. In type 1, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type 2, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes and all body tissues. Type 2 methemoglobinemia is associated with mental deficiency and other neurologic symptoms.

See also OMIM:250800
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti58 – 581R → Q in METHB-CYB5R3; type 1; 62% of activity. 3 Publications
VAR_004619
Natural varianti73 – 731L → P in METHB-CYB5R3; type 1. 2 Publications
VAR_010750
Natural varianti106 – 1061V → M in METHB-CYB5R3; type 1; 77% of activity. 1 Publication
Corresponds to variant rs121965009 [ dbSNP | Ensembl ].
VAR_004620
Natural varianti128 – 1281S → P in METHB-CYB5R3; type 2; Hiroshima. 1 Publication
VAR_004621
Natural varianti149 – 1491L → P in METHB-CYB5R3. 1 Publication
VAR_004622
Natural varianti179 – 1791A → V in METHB-CYB5R3; type 1. 1 Publication
Corresponds to variant rs201232518 [ dbSNP | Ensembl ].
VAR_010752
Natural varianti204 – 2041C → R in METHB-CYB5R3; type 2. 1 Publication
VAR_010753
Natural varianti204 – 2041C → Y in METHB-CYB5R3; type 1. 2 Publications
VAR_010754
Natural varianti256 – 2561Missing in METHB-CYB5R3; type 1; retains approximately 38% of residual diaphorase activity. 2 Publications
VAR_037315
Natural varianti273 – 2731Missing in METHB-CYB5R3; type 2. 1 Publication
VAR_010755
Natural varianti292 – 2921G → D in METHB-CYB5R3; type 1; retains approximately 58% of residual diaphorase activity. 2 Publications
VAR_037316
Natural varianti299 – 2991Missing in METHB-CYB5R3; type2; almost complete loss of activity. 1 Publication
VAR_004623

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi250800. phenotype.
Orphaneti139373. Recessive hereditary methemoglobinemia type 1.
139380. Recessive hereditary methemoglobinemia type 2.
PharmGKBiPA27331.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 301300NADH-cytochrome b5 reductase 3 membrane-bound formPRO_0000019392Add
BLAST
Chaini27 – 301275NADH-cytochrome b5 reductase 3 soluble formPRO_0000019394Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei42 – 421N6-acetyllysine1 Publication
Modified residuei43 – 431Phosphotyrosine1 Publication
Modified residuei120 – 1201N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiP00387.
PaxDbiP00387.
PRIDEiP00387.

2D gel databases

REPRODUCTION-2DPAGEIPI00446235.

PTM databases

PhosphoSiteiP00387.

Expressioni

Tissue specificityi

Isoform 2 is expressed at late stages of erythroid maturation.

Gene expression databases

BgeeiP00387.
CleanExiHS_CYB5R3.
ExpressionAtlasiP00387. baseline and differential.
GenevestigatoriP00387.

Organism-specific databases

HPAiHPA001566.

Interactioni

Subunit structurei

Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MOSC2.By similarity

Protein-protein interaction databases

BioGridi108071. 19 interactions.
DIPiDIP-50463N.
IntActiP00387. 2 interactions.
MINTiMINT-5003981.

Structurei

Secondary structure

1
301
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi43 – 5210Combined sources
Beta strandi54 – 6310Combined sources
Beta strandi78 – 858Combined sources
Beta strandi88 – 947Combined sources
Beta strandi104 – 1118Combined sources
Beta strandi115 – 1184Combined sources
Helixi126 – 1338Combined sources
Beta strandi139 – 1468Combined sources
Beta strandi148 – 1536Combined sources
Beta strandi156 – 1594Combined sources
Beta strandi168 – 1714Combined sources
Beta strandi173 – 1808Combined sources
Helixi181 – 1833Combined sources
Helixi184 – 19512Combined sources
Beta strandi203 – 21210Combined sources
Helixi213 – 2153Combined sources
Helixi219 – 22810Combined sources
Turni230 – 2323Combined sources
Beta strandi233 – 2419Combined sources
Beta strandi247 – 2526Combined sources
Helixi255 – 2617Combined sources
Helixi265 – 2673Combined sources
Beta strandi270 – 2756Combined sources
Helixi277 – 2826Combined sources
Helixi285 – 2917Combined sources
Helixi295 – 2973Combined sources
Beta strandi298 – 3003Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M91model-A1-301[»]
1UMKX-ray1.75A27-301[»]
ProteinModelPortaliP00387.
SMRiP00387. Positions 31-301.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00387.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 152113FAD-binding FR-typePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0543.
GeneTreeiENSGT00390000008881.
HOGENOMiHOG000175005.
HOVERGENiHBG052580.
InParanoidiP00387.
KOiK00326.
OrthoDBiEOG7CZK69.
PhylomeDBiP00387.
TreeFamiTF314333.

Family and domain databases

InterProiIPR017927. Fd_Rdtase_FAD-bd.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR001834. NADH-Cyt_B5_reductase.
IPR008333. OxRdtase_FAD-bd_dom.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00406. CYTB5RDTASE.
PR00371. FPNCR.
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: P00387-1) [UniParc]FASTAAdd to basket

Also known as: M

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
MGAQLSTLGH MVLFPVWFLY SLLMKLFQRS TPAITLESPD IKYPLRLIDR
60 70 80 90 100
EIISHDTRRF RFALPSPQHI LGLPVGQHIY LSARIDGNLV VRPYTPISSD
110 120 130 140 150
DDKGFVDLVI KVYFKDTHPK FPAGGKMSQY LESMQIGDTI EFRGPSGLLV
160 170 180 190 200
YQGKGKFAIR PDKKSNPIIR TVKSVGMIAG GTGITPMLQV IRAIMKDPDD
210 220 230 240 250
HTVCHLLFAN QTEKDILLRP ELEELRNKHS ARFKLWYTLD RAPEAWDYGQ
260 270 280 290 300
GFVNEEMIRD HLPPPEEEPL VLMCGPPPMI QYACLPNLDH VGHPTERCFV

F
Length:301
Mass (Da):34,235
Last modified:January 23, 2007 - v3
Checksum:iFDCDCDC4EC3570B4
GO
Isoform 2 (identifier: P00387-2) [UniParc]FASTAAdd to basket

Also known as: S

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Show »
Length:278
Mass (Da):31,629
Checksum:i229597F14FA6582E
GO
Isoform 3 (identifier: P00387-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MGAQLST → MNRSLLVGCMQSKDIWGREESICERLKQDGLDVERAESWE

Note: No experimental confirmation available.

Show »
Length:334
Mass (Da):38,226
Checksum:i91CCE3D9A18621E8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti28 – 325QRSTP → RWPRA in AAA52307 (PubMed:3035541).Curated
Sequence conflicti29 – 291R → G in AAA59900 (PubMed:2479590).Curated
Sequence conflicti31 – 311T → K in CAA09006 (Ref. 4) Curated
Sequence conflicti31 – 311T → K in CAA09007 (Ref. 4) Curated
Sequence conflicti31 – 311T → K in CAA09008 (Ref. 4) Curated
Sequence conflicti34 – 352IT → LA in AAA52307 (PubMed:3035541).Curated
Sequence conflicti187 – 1882ML → IV in CAA09006 (Ref. 4) Curated
Sequence conflicti187 – 1882ML → IV in CAA09007 (Ref. 4) Curated
Sequence conflicti191 – 1922IR → MS in CAA09006 (Ref. 4) Curated
Sequence conflicti191 – 1922IR → MS in CAA09007 (Ref. 4) Curated
Sequence conflicti192 – 1921R → G in AAA52306 (PubMed:3035541).Curated
Sequence conflicti233 – 2342FK → CN in CAA09006 (Ref. 4) Curated
Sequence conflicti233 – 2342FK → CN in CAA09007 (Ref. 4) Curated
Sequence conflicti280 – 2801I → N in AAL87744 (Ref. 3) Curated

Polymorphismi

Ser-117 seems to only be found in persons of African origin. The allele frequency is 0.23 in African Americans. It was not found in Caucasians, Asians, Indo-Aryans, or Arabs. There seems to be no effect on the enzyme activity.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti58 – 581R → Q in METHB-CYB5R3; type 1; 62% of activity. 3 Publications
VAR_004619
Natural varianti66 – 661S → P.3 Publications
Corresponds to variant rs1130706 [ dbSNP | Ensembl ].
VAR_018419
Natural varianti73 – 731L → P in METHB-CYB5R3; type 1. 2 Publications
VAR_010750
Natural varianti106 – 1061V → M in METHB-CYB5R3; type 1; 77% of activity. 1 Publication
Corresponds to variant rs121965009 [ dbSNP | Ensembl ].
VAR_004620
Natural varianti117 – 1171T → S.2 Publications
Corresponds to variant rs1800457 [ dbSNP | Ensembl ].
VAR_010751
Natural varianti128 – 1281S → P in METHB-CYB5R3; type 2; Hiroshima. 1 Publication
VAR_004621
Natural varianti149 – 1491L → P in METHB-CYB5R3. 1 Publication
VAR_004622
Natural varianti179 – 1791A → V in METHB-CYB5R3; type 1. 1 Publication
Corresponds to variant rs201232518 [ dbSNP | Ensembl ].
VAR_010752
Natural varianti204 – 2041C → R in METHB-CYB5R3; type 2. 1 Publication
VAR_010753
Natural varianti204 – 2041C → Y in METHB-CYB5R3; type 1. 2 Publications
VAR_010754
Natural varianti256 – 2561Missing in METHB-CYB5R3; type 1; retains approximately 38% of residual diaphorase activity. 2 Publications
VAR_037315
Natural varianti273 – 2731Missing in METHB-CYB5R3; type 2. 1 Publication
VAR_010755
Natural varianti292 – 2921G → D in METHB-CYB5R3; type 1; retains approximately 58% of residual diaphorase activity. 2 Publications
VAR_037316
Natural varianti299 – 2991Missing in METHB-CYB5R3; type2; almost complete loss of activity. 1 Publication
VAR_004623

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2323Missing in isoform 2. CuratedVSP_010200Add
BLAST
Alternative sequencei1 – 77MGAQLST → MNRSLLVGCMQSKDIWGREE SICERLKQDGLDVERAESWE in isoform 3. 1 PublicationVSP_042827

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M28713
, M28705, M28706, M28707, M28708, M28709, M28710, M28711 Genomic DNA. Translation: AAA59900.1.
Y09501 mRNA. Translation: CAA70696.1.
AF361370 mRNA. Translation: AAL87744.1.
AJ010116 mRNA. Translation: CAA09006.1.
AJ010117 mRNA. Translation: CAA09007.1.
AJ010118 mRNA. Translation: CAA09008.1.
AY341030 Genomic DNA. Translation: AAP88936.1.
BT009821 mRNA. Translation: AAP88823.1.
CR456435 mRNA. Translation: CAG30321.1.
AF061830 Genomic DNA. Translation: AAF06818.1.
AF061831 Genomic DNA. Translation: AAF06819.1.
AK302204 mRNA. Translation: BAH13649.1.
Z93241 Genomic DNA. Translation: CAB42843.1.
Z93241 Genomic DNA. Translation: CAQ08414.1.
BC004821 mRNA. Translation: AAH04821.1.
AJ310899 mRNA. Translation: CAC84523.1.
AJ310900 mRNA. Translation: CAC84524.1.
M16461 mRNA. Translation: AAA52306.1.
M16462 mRNA. Translation: AAA52307.1.
CCDSiCCDS14040.1. [P00387-2]
CCDS33658.1. [P00387-1]
CCDS54535.1. [P00387-3]
PIRiJS0468. RDHUB5.
RefSeqiNP_000389.1. NM_000398.6. [P00387-1]
NP_001123291.1. NM_001129819.2. [P00387-2]
NP_001165131.1. NM_001171660.1. [P00387-3]
NP_001165132.1. NM_001171661.1. [P00387-2]
NP_015565.1. NM_007326.4. [P00387-2]
UniGeneiHs.561064.

Genome annotation databases

EnsembliENST00000352397; ENSP00000338461; ENSG00000100243. [P00387-1]
ENST00000361740; ENSP00000354468; ENSG00000100243. [P00387-3]
ENST00000402438; ENSP00000385679; ENSG00000100243. [P00387-2]
ENST00000407332; ENSP00000384457; ENSG00000100243. [P00387-2]
ENST00000407623; ENSP00000384834; ENSG00000100243. [P00387-2]
GeneIDi1727.
KEGGihsa:1727.
UCSCiuc003bcx.3. human. [P00387-1]
uc011aps.2. human. [P00387-3]

Polymorphism databases

DMDMi127846.

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M28713
, M28705, M28706, M28707, M28708, M28709, M28710, M28711 Genomic DNA. Translation: AAA59900.1.
Y09501 mRNA. Translation: CAA70696.1.
AF361370 mRNA. Translation: AAL87744.1.
AJ010116 mRNA. Translation: CAA09006.1.
AJ010117 mRNA. Translation: CAA09007.1.
AJ010118 mRNA. Translation: CAA09008.1.
AY341030 Genomic DNA. Translation: AAP88936.1.
BT009821 mRNA. Translation: AAP88823.1.
CR456435 mRNA. Translation: CAG30321.1.
AF061830 Genomic DNA. Translation: AAF06818.1.
AF061831 Genomic DNA. Translation: AAF06819.1.
AK302204 mRNA. Translation: BAH13649.1.
Z93241 Genomic DNA. Translation: CAB42843.1.
Z93241 Genomic DNA. Translation: CAQ08414.1.
BC004821 mRNA. Translation: AAH04821.1.
AJ310899 mRNA. Translation: CAC84523.1.
AJ310900 mRNA. Translation: CAC84524.1.
M16461 mRNA. Translation: AAA52306.1.
M16462 mRNA. Translation: AAA52307.1.
CCDSiCCDS14040.1. [P00387-2]
CCDS33658.1. [P00387-1]
CCDS54535.1. [P00387-3]
PIRiJS0468. RDHUB5.
RefSeqiNP_000389.1. NM_000398.6. [P00387-1]
NP_001123291.1. NM_001129819.2. [P00387-2]
NP_001165131.1. NM_001171660.1. [P00387-3]
NP_001165132.1. NM_001171661.1. [P00387-2]
NP_015565.1. NM_007326.4. [P00387-2]
UniGeneiHs.561064.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M91model-A1-301[»]
1UMKX-ray1.75A27-301[»]
ProteinModelPortaliP00387.
SMRiP00387. Positions 31-301.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108071. 19 interactions.
DIPiDIP-50463N.
IntActiP00387. 2 interactions.
MINTiMINT-5003981.

Chemistry

ChEMBLiCHEMBL2146.
DrugBankiDB03147. Flavin adenine dinucleotide.

PTM databases

PhosphoSiteiP00387.

Polymorphism databases

DMDMi127846.

2D gel databases

REPRODUCTION-2DPAGEIPI00446235.

Proteomic databases

MaxQBiP00387.
PaxDbiP00387.
PRIDEiP00387.

Protocols and materials databases

DNASUi1727.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000352397; ENSP00000338461; ENSG00000100243. [P00387-1]
ENST00000361740; ENSP00000354468; ENSG00000100243. [P00387-3]
ENST00000402438; ENSP00000385679; ENSG00000100243. [P00387-2]
ENST00000407332; ENSP00000384457; ENSG00000100243. [P00387-2]
ENST00000407623; ENSP00000384834; ENSG00000100243. [P00387-2]
GeneIDi1727.
KEGGihsa:1727.
UCSCiuc003bcx.3. human. [P00387-1]
uc011aps.2. human. [P00387-3]

Organism-specific databases

CTDi1727.
GeneCardsiGC22M043014.
HGNCiHGNC:2873. CYB5R3.
HPAiHPA001566.
MIMi250800. phenotype.
613213. gene.
neXtProtiNX_P00387.
Orphaneti139373. Recessive hereditary methemoglobinemia type 1.
139380. Recessive hereditary methemoglobinemia type 2.
PharmGKBiPA27331.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0543.
GeneTreeiENSGT00390000008881.
HOGENOMiHOG000175005.
HOVERGENiHBG052580.
InParanoidiP00387.
KOiK00326.
OrthoDBiEOG7CZK69.
PhylomeDBiP00387.
TreeFamiTF314333.

Enzyme and pathway databases

BioCyciMetaCyc:HS02015-MONOMER.
BRENDAi1.6.2.2. 2681.
ReactomeiREACT_11202. Vitamin C (ascorbate) metabolism.
SABIO-RKP00387.

Miscellaneous databases

EvolutionaryTraceiP00387.
GeneWikiiCYB5R3.
GenomeRNAii1727.
NextBioi6983.
PROiP00387.
SOURCEiSearch...

Gene expression databases

BgeeiP00387.
CleanExiHS_CYB5R3.
ExpressionAtlasiP00387. baseline and differential.
GenevestigatoriP00387.

Family and domain databases

InterProiIPR017927. Fd_Rdtase_FAD-bd.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR001834. NADH-Cyt_B5_reductase.
IPR008333. OxRdtase_FAD-bd_dom.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00406. CYTB5RDTASE.
PR00371. FPNCR.
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The organization and the complete nucleotide sequence of the human NADH-cytochrome b5 reductase gene."
    Tomatsu S., Kobayashi Y., Fukumaki Y., Yubisui T., Orii T., Sakaki Y.
    Gene 80:353-361(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-66.
    Tissue: Placenta.
  2. Voice M.W.
    Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Liver.
  3. Yoon B., Chung H., Ko E., Lee D.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. Lan F.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-66, VARIANTS HM GLN-58; PRO-73 AND TYR-204.
    Tissue: Leukocyte.
  5. NIEHS SNPs program
    Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-117.
  6. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  8. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Testis.
  9. "The DNA sequence of human chromosome 22."
    Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M.
    , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
    Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "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] (ISOFORM 1).
    Tissue: Placenta.
  11. "Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase."
    Yubisui T., Naitoh Y., Zenno S., Tamura M., Takeshita M., Sakaki Y.
    Proc. Natl. Acad. Sci. U.S.A. 84:3609-3613(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-301 (ISOFORM 1), VARIANT PRO-66.
    Tissue: Liver.
  12. "Upregulation of voltage-gated Na+ channel expression and metastatic potential in human breast cancer: correlative studies on cell lines and biopsy tissues."
    Diss J.K.J., Fraser S.P., Coombes R.C., Djamgoz M.B.A.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 101-250 (ISOFORM 1).
  13. "The NH2-terminal structures of human and rat liver microsomal NADH-cytochrome b5 reductases."
    Murakami K., Yubisui T., Takeshita M., Miyata T.
    J. Biochem. 105:312-317(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-25, MYRISTOYLATION AT GLY-2.
  14. "Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes."
    Yubisui T., Miyata T., Iwanaga S., Tamura M., Takeshita M.
    J. Biochem. 99:407-422(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 27-301.
    Tissue: Erythrocyte.
  15. "Amino acid sequence of NADH-cytochrome b5 reductase of human erythrocytes."
    Yubisui T., Miyata T., Iwanaga S., Tamura M., Yoshida S., Takeshita M., Nakajima H.
    J. Biochem. 96:579-582(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 27-301.
    Tissue: Erythrocyte.
  16. "An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5 reductase in humans."
    Bulbarelli A., Valentini A., De Silvestris M., Cappellini M.D., Borgese N.
    Blood 92:310-319(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE PROMOTER USAGE.
  17. "Role of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. Cys-273 and Cys-283 are located close to the NADH-binding site but are not catalytically essential."
    Shirabe K., Yubisui T., Nishino T., Takeshita M.
    J. Biol. Chem. 266:7531-7536(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF CYSTEINE RESIDUES.
  18. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-43, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  19. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  21. "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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  22. Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 31-301.
  23. "Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase."
    Yubisui T., Shirabe K., Takeshita M., Kobayashi Y., Fukumaki Y., Sakaki Y., Takano T.
    J. Biol. Chem. 266:66-70(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT METHB-CYB5R3 PRO-128.
  24. "Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency."
    Katsube T., Sakamoto N., Kobayashi Y., Seki R., Hirano M., Tanishima K., Tomoda A., Takazakura E., Yubisui T., Takeshita M., Sakaki Y., Fukumaki Y.
    Am. J. Hum. Genet. 48:799-808(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS METHB-CYB5R3 GLN-58 AND PRO-149.
  25. "Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type)."
    Shirabe K., Yubisui T., Borgese N., Tang C.-Y., Hultquist D.E., Takeshita M.
    J. Biol. Chem. 267:20416-20421(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT METHB-CYB5R3 MET-106.
  26. "An in-frame deletion of codon 298 of the NADH-cytochrome b5 reductase gene results in hereditary methemoglobinemia type II (generalized type). A functional implication for the role of the COOH-terminal region of the enzyme."
    Shirabe K., Fujimoto Y., Yubisui T., Takeshita M.
    J. Biol. Chem. 269:5952-5957(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT METHB-CYB5R3 PHE-299 DEL.
  27. "Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II."
    Vieira L.M., Kaplan J.-C., Kahn A., Leroux A.
    Blood 85:2254-2262(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS METHB-CYB5R3 ARG-204 AND MET-273 DEL.
  28. "A high-frequency polymorphism of NADH-cytochrome b5 reductase in African-Americans."
    Jenkins M.M., Prchal J.T.
    Hum. Genet. 99:248-250(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SER-117.
  29. "Identification of a novel point mutation (Leu72-to-Pro) in the NADH-cytochrome b5 reductase gene of a patient with hereditary methaemoglobinaemia type I."
    Wu Y.-S., Huang C.-H., Wan Y., Huang Q.-J., Zhu Z.-Y.
    Br. J. Haematol. 102:575-577(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT METHB-CYB5R3 PRO-73.
  30. "Molecular basis of hereditary methaemoglobinaemia, types I and II: two novel mutations in the NADH-cytochrome b5 reductase gene."
    Higasa K., Manabe J.I., Yubisui T., Sumimoto H., Pung-Amritt P., Tanphaichitr V.S., Fukumaki Y.
    Br. J. Haematol. 103:922-930(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 76-83 AND 171-187, VARIANT METHB-CYB5R3 VAL-179.
  31. "A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia."
    Wang Y., Wu Y.-S., Zheng P.-Z., Yang W.-X., Fang G.-A., Tang Y.-C., Xie F., Lan F.-H., Zhu Z.-Y.
    Blood 95:3250-3255(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT METHB-CYB5R3 TYR-204.
  32. "Arginine-glutamine replacement at residue 57 of NADH-cytochrome b5 reductase in Chinese hereditary methemoglobinemia."
    Huang C.-H., Xie Y., Wang Y., Wu Y.-S.
    Zhonghua Xue Ye Xue Za Zhi 18:200-203(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT METHB-CYB5R3 GLN-58.
  33. "Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADH-cytochrome b5 reductase."
    Percy M.J., Gillespie M.J.S., Savage G., Hughes A.E., McMullin M.F., Lappin T.R.J.
    Blood 100:3447-3449(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS METHB-CYB5R3 GLU-256 DEL AND ASP-292.
  34. "Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase."
    Percy M.J., Crowley L.J., Davis C.A., McMullin M.F., Savage G., Hughes J., McMahon C., Quinn R.J.M., Smith O., Barber M.J., Lappin T.R.J.
    Br. J. Haematol. 129:847-853(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS METHB-CYB5R3 GLU-256 DEL AND ASP-292.

Entry informationi

Entry nameiNB5R3_HUMAN
AccessioniPrimary (citable) accession number: P00387
Secondary accession number(s): B1AHF2
, B7Z7L3, O75675, Q8TDL8, Q8WTS8, Q9UEN4, Q9UEN5, Q9UL55, Q9UL56
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: March 4, 2015
This is version 201 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: 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. 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.