Reviewed, UniProtKB/Swiss-Prot Q6BCY4 (NB5R2_HUMAN)

Names and origin

Protein names

Recommended name:
    NADH-cytochrome b5 reductase 2
      Short name=b5R.2
    EC=1.6.2.2

Gene names

Name:

CYB5R2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	276 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction By similarity. Responsible for NADH-dependent lucigenin chemiluminescence in spermatozoa by reducing both lucigenin and 2-[4-iodophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H tetrazolium monosodium salt (WST-1). Ref.2
Catalytic activity	NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5.
Cofactor	FAD By similarity.
Tissue specificity	Restricted expression. Ref.1
Sequence similarities	Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family. Contains 1 FAD-binding FR-type domain.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	FAD Flavoprotein NAD
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	oxidation reduction Ref.1 Inferred from direct assay. Source: UniProtKB sterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	membrane Ref.1 Inferred from direct assay. Source: UniProtKB soluble fraction Ref.1 Non-traceable author statement. Source: UniProtKB
Molecular function	cytochrome-b5 reductase activity Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6BCY4-1)

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.

Isoform 2 (identifier: Q6BCY4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     221-276: WKYSSGFVTADMIKEHLPPPAKSTLILVCGPPPLIQTAAHPNLEKLGYTQDMIFTY → PWSAEGATLLSNSAQFH

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 276	276	NADH-cytochrome b5 reductase 2		PRO_0000287548
Regions
	Domain	15 – 127	113	FAD-binding FR-type
	Nucleotide binding	107 – 137	31	FAD By similarity
	Nucleotide binding	146 – 181	36	FAD By similarity
Amino acid modifications
	Modified residue	177	1	Phosphothreonine Ref.5
Natural variations
	Alternative sequence	221 – 276	56	WKYSS…MIFTY → PWSAEGATLLSNSAQFH in isoform 2.		VSP_025559
	Natural variant	15	1	E → A: dbSNP rs11041525.		VAR_032321
	Natural variant	209	1	N → D: dbSNP rs12801394. Ref.1 Ref.3 Ref.4		VAR_032322
Experimental info
	Sequence conflict	130	1	G → R in AAF04811. Ref.1
	Sequence conflict	253	1	P → T in AAF04811. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 13, 2004. Version 1. Checksum: A475039D1E56ABDA	FASTA	276	31,458
	10 20 30 40 50 60 MNSRRREPIT LQDPEAKYPL PLIEKEKISH NTRRFRFGLP SPDHVLGLPV GNYVQLLAKI 70 80 90 100 110 120 DNELVVRAYT PVSSDDDRGF VDLIIKIYFK NVHPQYPEGG KMTQYLENMK IGETIFFRGP 130 140 150 160 170 180 RGRLFYHGPG NLGIRPDQTS EPKKTLADHL GMIAGGTGIT PMLQLIRHIT KDPSDRTRMS 190 200 210 220 230 240 LIFANQTEED ILVRKELEEI ARTHPDQFNL WYTLDRPPIG WKYSSGFVTA DMIKEHLPPP 250 260 270 AKSTLILVCG PPPLIQTAAH PNLEKLGYTQ DMIFTY
	Isoform 2. Checksum: 54044C015E5D4CA0	FASTA	237	27,043
	10 20 30 40 50 60 MNSRRREPIT LQDPEAKYPL PLIEKEKISH NTRRFRFGLP SPDHVLGLPV GNYVQLLAKI 70 80 90 100 110 120 DNELVVRAYT PVSSDDDRGF VDLIIKIYFK NVHPQYPEGG KMTQYLENMK IGETIFFRGP 130 140 150 160 170 180 RGRLFYHGPG NLGIRPDQTS EPKKTLADHL GMIAGGTGIT PMLQLIRHIT KDPSDRTRMS 190 200 210 220 230 LIFANQTEED ILVRKELEEI ARTHPDQFNL WYTLDRPPIG PWSAEGATLL SNSAQFH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 10611283] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT ASP-209.
[2]	"Identification of cytochrome-b5 reductase as the enzyme responsible for NADH-dependent lucigenin chemiluminescence in human spermatozoa." Baker M.A., Krutskikh A., Curry B.J., Hetherington L., Aitken R.J. Biol. Reprod. 73:334-342(2005) [PubMed: 15858218] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ASP-209. Tissue: Placenta.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 7-276 (ISOFORM 1), VARIANT ASP-209. Tissue: Testis.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-177, MASS SPECTROMETRY. Tissue: Epithelium.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF169802 mRNA. Translation: AAF04811.1. AY665398 mRNA. Translation: AAT75296.1. BC001346 mRNA. Translation: AAH01346.1. AL133582 mRNA. Translation: CAB63726.1.
IPI	IPI00008234. IPI00332396.
PIR	T43491.
RefSeq	NP_057313.2.
UniGene	Hs.414362
3D structure databases
HSSP	HSSP built from PDB template 1QX4 based on UniProtKB P20070.
SMR	Q6BCY4. Positions 9-276.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6BCY4. 2 interactions.
2-D gel databases
REPRODUCTION-2DPAGE	IPI00332396.
Proteomic databases
PRIDE	Q6BCY4.
Genome annotation databases
Ensembl	ENST00000299498; ENSP00000299498; ENSG00000166394; Homo sapiens. [Genome view]
GeneID	51700.
KEGG	hsa:51700.
UCSC	uc001mfm.1. human.
Organism-specific databases
CTD	51700.
GeneCards	GC11M007642.
H-InvDB	HIX0009418.
HGNC	HGNC:24376. CYB5R2.
MIM	608342. gene.
PharmGKB	PA142672060.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05213.
HOGENOM	HBG591994.
HOVERGEN	Q6BCY4.
InParanoid	Q6BCY4.
OMA	DDDQGFV.
OrthoDB	EOG9KM1NT.
PhylomeDB	Q6BCY4.
Enzyme and pathway databases
BRENDA	1.6.2.2. 247.
Gene expression databases
ArrayExpress	Q6BCY4.
Bgee	Q6BCY4.
CleanEx	HS_CYB5R2.
Genevestigator	Q6BCY4.
Family and domain databases
InterPro	IPR017927. 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]
Pfam	PF00970. FAD_binding_6. 1 hit. PF00175. NAD_binding_1. 1 hit. [Graphical view]
PRINTS	PR00406. CYTB5RDTASE. PR00371. FPNCR.
PROSITE	PS51384. FAD_FR. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	55720.
SOURCE	Search...

Entry information

Entry name

NB5R2_HUMAN

Accession

Primary (citable) accession number: Q6BCY4
Secondary accession number(s): Q9BVA3, Q9UF68, Q9UHJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	September 13, 2004
Last modified:	January 19, 2010
This is version 45 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.