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Q7L1T6 (NB5R4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome b5 reductase 4

EC=1.6.2.2
Alternative name(s):
Flavohemoprotein b5/b5R
Short name=b5+b5R
N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein
cb5/cb5R
Gene names
Name:CYB5R4
Synonyms:NCB5OR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length521 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS). Reduces a variety of substrates in vitro, such as cytochrome c, feericyanide and methemoglobin.

Catalytic activity

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

Cofactor

FAD.

Subcellular location

Endoplasmic reticulum. Note: Soluble protein. Ref.4 Ref.8

Tissue specificity

Widely expressed. Ref.4

Polymorphism

Variants Arg-187 and Arg-223 do not influence the pathogenesis of non-autoimmune diabetes.

Sequence similarities

Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.

Contains 1 CS domain.

Contains 1 cytochrome b5 heme-binding domain.

Contains 1 FAD-binding FR-type domain.

Biophysicochemical properties

Kinetic parameters:

KM=25 mM for O2

Redox potential:

E0 is -108 mV.

Sequence caution

The sequence AAF04812.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAI19905.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI22326.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
   Coding sequence diversityPolymorphism
   LigandFAD
Flavoprotein
Heme
Iron
Metal-binding
NAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNADP metabolic process

Inferred from electronic annotation. Source: Ensembl

cell development

Inferred from sequence or structural similarity. Source: UniProtKB

detection of oxygen

Non-traceable author statement Ref.4. Source: UniProtKB

generation of precursor metabolites and energy

Inferred from direct assay Ref.4. Source: UniProtKB

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

insulin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

oxidation-reduction process

Inferred from direct assay Ref.8. Source: UniProtKB

response to antibiotic

Inferred from sequence or structural similarity. Source: UniProtKB

superoxide metabolic process

Inferred from direct assay Ref.4. Source: UniProtKB

   Cellular_componentendoplasmic reticulum

Inferred from direct assay Ref.8. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.4. Source: UniProtKB

   Molecular_functionNAD(P)H oxidase activity

Inferred from direct assay Ref.4. Source: UniProtKB

NADPH-hemoprotein reductase activity

Inferred from electronic annotation. Source: Ensembl

cytochrome-b5 reductase activity, acting on NAD(P)H

Inferred from direct assay Ref.4. Source: UniProtKB

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: Ensembl

heme binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 521521Cytochrome b5 reductase 4
PRO_0000287556

Regions

Domain54 – 13077Cytochrome b5 heme-binding
Domain165 – 25692CS
Domain273 – 385113FAD-binding FR-type
Nucleotide binding365 – 38016FAD By similarity
Nucleotide binding392 – 42433FAD By similarity

Sites

Metal binding891Iron (heme axial ligand)
Metal binding1121Iron (heme axial ligand)

Amino acid modifications

Modified residue11N-acetylmethionine Ref.5

Natural variations

Natural variant1401R → H. Ref.1
Corresponds to variant rs61762820 [ dbSNP | Ensembl ].
VAR_047967
Natural variant1871Q → R. Ref.7
VAR_032323
Natural variant2231H → R. Ref.7
Corresponds to variant rs141290525 [ dbSNP | Ensembl ].
VAR_032324
Natural variant2671P → A. Ref.1
Corresponds to variant rs61382555 [ dbSNP | Ensembl ].
VAR_047968
Natural variant2821S → P.
Corresponds to variant rs10080628 [ dbSNP | Ensembl ].
VAR_032325
Natural variant3161P → S. Ref.1
Corresponds to variant rs10080628 [ dbSNP | Ensembl ].
VAR_047969
Natural variant3711D → Y in a breast cancer sample; somatic mutation. Ref.9
VAR_036240
Natural variant3901L → M in a breast cancer sample; somatic mutation. Ref.9
VAR_036241

Secondary structure

........................ 521
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q7L1T6 [UniParc].

Last modified August 30, 2005. Version 1.
Checksum: 9D83BAB387E3B0F4

FASTA52159,474
        10         20         30         40         50         60 
MLNVPSQSFP APRSQQRVAS GGRSKVPLKQ GRSLMDWIRL TKSGKDLTGL KGRLIEVTEE 

        70         80         90        100        110        120 
ELKKHNKKDD CWICIRGFVY NVSPYMEYHP GGEDELMRAA GSDGTELFDQ VHRWVNYESM 

       130        140        150        160        170        180 
LKECLVGRMA IKPAVLKDYR EEEKKVLNGM LPKSQVTDTL AKEGPSYPSY DWFQTDSLVT 

       190        200        210        220        230        240 
IAIYTKQKDI NLDSIIVDHQ NDSFRAETII KDCLYLIHIG LSHEVQEDFS VRVVESVGKI 

       250        260        270        280        290        300 
EIVLQKKENT SWDFLGHPLK NHNSLIPRKD TGLYYRKCQL ISKEDVTHDT RLFCLMLPPS 

       310        320        330        340        350        360 
THLQVPIGQH VYLKLPITGT EIVKPYTPVS GSLLSEFKEP VLPNNKYIYF LIKIYPTGLF 

       370        380        390        400        410        420 
TPELDRLQIG DFVSVSSPEG NFKISKFQEL EDLFLLAAGT GFTPMVKILN YALTDIPSLR 

       430        440        450        460        470        480 
KVKLMFFNKT EDDIIWRSQL EKLAFKDKRL DVEFVLSAPI SEWNGKQGHI SPALLSEFLK 

       490        500        510        520 
RNLDKSKVLV CICGPVPFTE QGVRLLHDLN FSKNEIHSFT A 

« Hide

References

« Hide 'large scale' references
[1]SeattleSNPs variation discovery resource
Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-140; ALA-267 AND SER-316.
[2]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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].
Tissue: Testis.
[4]"Identification of a cytochrome b-type NAD(P)H oxidoreductase ubiquitously expressed in human cells."
Zhu H., Qiu H., Yoon H.-W., Huang S., Bunn H.F.
Proc. Natl. Acad. Sci. U.S.A. 96:14742-14747(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-521, SUBCELLULAR LOCATION, HEME-BINDING, FAD-BINDING, TISSUE SPECIFICITY.
[5]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain."
Deng B., Parthasarathy S., Wang W., Gibney B.R., Battaile K.P., Lovell S., Benson D.R., Zhu H.
J. Biol. Chem. 285:30181-30191(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 51-137, HEME-BINDING SITES.
[7]"Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus."
Andersen G., Wegner L., Rose C.S., Xie J., Zhu H., Larade K., Johansen A., Ek J., Lauenborg J., Drivsholm T., Borch-Johnsen K., Damm P., Hansen T., Bunn H.F., Pedersen O.
Diabetes 53:2992-2997(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-187 AND ARG-223.
[8]"NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum."
Zhu H., Larade K., Jackson T.A., Xie J., Ladoux A., Acker H., Berchner-Pfannschmidt U., Fandrey J., Cross A.R., Lukat-Rodgers G.S., Rodgers K.R., Bunn H.F.
J. Biol. Chem. 279:30316-30325(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] TYR-371 AND MET-390.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
EU448291 Genomic DNA. Translation: ACA06109.1.
AL139232, AL034347 Genomic DNA. Translation: CAI19904.2.
AL034347, AL139232 Genomic DNA. Translation: CAI22325.2.
AL034347, AL139232 Genomic DNA. Translation: CAI22326.1. Sequence problems.
AL139232, AL034347 Genomic DNA. Translation: CAI19905.1. Sequence problems.
BC025380 mRNA. Translation: AAH25380.2.
AF169803 mRNA. Translation: AAF04812.1. Different initiation.
CCDSCCDS5000.2.
RefSeqNP_057314.2. NM_016230.3.
UniGeneHs.5741.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3LF5X-ray1.25A/B51-137[»]
ProteinModelPortalQ7L1T6.
SMRQ7L1T6. Positions 51-137, 275-495.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119347. 2 interactions.
IntActQ7L1T6. 1 interaction.
MINTMINT-4714403.
STRING9606.ENSP00000358695.

PTM databases

PhosphoSiteQ7L1T6.

Proteomic databases

MaxQBQ7L1T6.
PaxDbQ7L1T6.
PRIDEQ7L1T6.

Protocols and materials databases

DNASU51167.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369681; ENSP00000358695; ENSG00000065615.
GeneID51167.
KEGGhsa:51167.
UCSCuc003pkf.3. human.

Organism-specific databases

CTD51167.
GeneCardsGC06P084569.
HGNCHGNC:20147. CYB5R4.
HPAHPA018992.
MIM608343. gene.
neXtProtNX_Q7L1T6.
PharmGKBPA134904907.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0543.
HOGENOMHOG000230826.
HOVERGENHBG108174.
InParanoidQ7L1T6.
OMAKDYHEEK.
OrthoDBEOG718KBZ.
PhylomeDBQ7L1T6.
TreeFamTF313874.

Gene expression databases

ArrayExpressQ7L1T6.
BgeeQ7L1T6.
CleanExHS_CYB5R4.
GenevestigatorQ7L1T6.

Family and domain databases

Gene3D2.60.40.790. 1 hit.
3.10.120.10. 1 hit.
InterProIPR007052. CS_dom.
IPR001199. Cyt_B5-like_heme/steroid-bd.
IPR018506. Cyt_B5_heme-BS.
IPR017927. Fd_Rdtase_FAD-bd.
IPR008978. HSP20-like_chaperone.
IPR001834. NADH-Cyt_B5_reductase.
IPR008333. OxRdtase_FAD-bd_dom.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamPF04969. CS. 1 hit.
PF00173. Cyt-b5. 1 hit.
PF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSPR00406. CYTB5RDTASE.
PR00363. CYTOCHROMEB5.
SUPFAMSSF49764. SSF49764. 1 hit.
SSF55856. SSF55856. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEPS51203. CS. 1 hit.
PS00191. CYTOCHROME_B5_1. 1 hit.
PS50255. CYTOCHROME_B5_2. 1 hit.
PS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ7L1T6.
GeneWikiCYB5R4.
GenomeRNAi51167.
NextBio54103.
PROQ7L1T6.
SOURCESearch...

Entry information

Entry nameNB5R4_HUMAN
AccessionPrimary (citable) accession number: Q7L1T6
Secondary accession number(s): B1AEM2 expand/collapse secondary AC list , Q5TGI9, Q9NUE4, Q9UHI9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: August 30, 2005
Last modified: July 9, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM