Reviewed, UniProtKB/Swiss-Prot Q68EJ0 (NB5R4_RAT)

Names and origin

Protein names

Recommended name:
    Cytochrome b5 reductase 4
    EC=1.6.2.2
Alternative name(s):
    Flavohemoprotein b5/b5R
      Short name=b5+b5R
    cb5/cb5R
    N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein

Gene names

Name:	Cyb5r4
Synonyms:	Ncb5or

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	520 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	NADH-cytochrome b5 reductase involved in endolasmic 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).
Catalytic activity	NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5. Ref.2
Cofactor	FAD.
Subcellular location	Endoplasmic reticulum. Note: Soluble protein By similarity.
Tissue specificity	Isoform 2 is expressed in testis, brain, skeletal muscle and in the male germline. Ref.3
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=28 µM for Ferricyanide KM=1 µM for NADPH KM=7 µM for cytochrome c

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing
Ligand	FAD Flavoprotein Heme Iron Metal-binding NAD
Molecular function	Oxidoreductase
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NADPH-hemoprotein reductase activity Ref.2 Inferred from direct assay. Source: RGD cytochrome-b5 reductase activity Inferred from electronic annotation. Source: EC heme binding Ref.2 Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q68EJ0-1)

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: Q68EJ0-2)

Also known as: cb5/cb5rDelta12;

The sequence of this isoform differs from the canonical sequence as follows:
     318-368: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 520	520	Cytochrome b5 reductase 4		PRO_0000287558
Regions
	Domain	54 – 130	77	Cytochrome b5 heme-binding
	Domain	164 – 255	92	CS
	Domain	272 – 384	113	FAD-binding FR-type
	Nucleotide binding	364 – 379	16	FAD By similarity
	Nucleotide binding	391 – 423	33	FAD By similarity
Sites
	Metal binding	89	1	Iron (heme axial ligand)
	Metal binding	112	1	Iron (heme axial ligand)
Natural variations
	Alternative sequence	318 – 368	51	Missing in isoform 2.		VSP_025563
Experimental info
	Mutagenesis	89	1	H → A or M: Abolishes heme-binding but does not affect reductase activity. Ref.2
	Mutagenesis	112	1	H → A or M: Abolishes heme-binding but does not affect reductase activity. Ref.2
	Sequence conflict	38	1	F → I in AAH80240. Ref.1
	Sequence conflict	244	1	Q → L in AAG45053. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 15, 2007. Version 2. Checksum: F0C0553206F7976A	FASTA	520	58,835
	10 20 30 40 50 60 MLNVPSQAFP APGSQQRVAS QGRSKVPLKQ GRSLMDWFRL TKSGKDFTGL KGGLIEVTEE 70 80 90 100 110 120 ELKKHNKKDD CWICIRGFVY NVSPYMEYHP GGEDELMRAA GADGTDLFNE VHRWVNYESM 130 140 150 160 170 180 LKECLVGRMA VKPAVPKDCH EGKRVLNGML PKSQVTDTLP REGPSSPSYD WFQTESSVTI 190 200 210 220 230 240 VIYTKQKNIN LDSVIVDLQD DSLRAEAVIK DHSYLIHIGL SHEVQENFSV RVIENVGKIE 250 260 270 280 290 300 IVLQKKETVS WKCLGDPLEK HDSFIPKKDT GLYYRQCQLI SKEDVTHDTR LFCLMLPPST 310 320 330 340 350 360 HLQVPVGQHV YLKLSVTGAE IVKPYTPVSE SLLSDFKEPV LSPNKYIYFL IKIYPAGLFT 370 380 390 400 410 420 PELDRLQIGD FVSVSGPEGN FKVSKLQEVE DLFLLAAGTG FTPMVTVLNH ALTHMSSLRK 430 440 450 460 470 480 VKLMFFNKTE DDIIWRCQLE KLALKDKRFH VEYVLSAPSP EWNGKQGHVS RALLSEFLQR 490 500 510 520 SLENSKVFLC ICGPTPFTDE GIRLLHDLNF SDDEIHGFTA
	Isoform 2 (cb5/cb5rDelta12). Checksum: F51B15B52318FFE2	FASTA	469	53,038
	10 20 30 40 50 60 MLNVPSQAFP APGSQQRVAS QGRSKVPLKQ GRSLMDWFRL TKSGKDFTGL KGGLIEVTEE 70 80 90 100 110 120 ELKKHNKKDD CWICIRGFVY NVSPYMEYHP GGEDELMRAA GADGTDLFNE VHRWVNYESM 130 140 150 160 170 180 LKECLVGRMA VKPAVPKDCH EGKRVLNGML PKSQVTDTLP REGPSSPSYD WFQTESSVTI 190 200 210 220 230 240 VIYTKQKNIN LDSVIVDLQD DSLRAEAVIK DHSYLIHIGL SHEVQENFSV RVIENVGKIE 250 260 270 280 290 300 IVLQKKETVS WKCLGDPLEK HDSFIPKKDT GLYYRQCQLI SKEDVTHDTR LFCLMLPPST 310 320 330 340 350 360 HLQVPVGQHV YLKLSVTGDF VSVSGPEGNF KVSKLQEVED LFLLAAGTGF TPMVTVLNHA 370 380 390 400 410 420 LTHMSSLRKV KLMFFNKTED DIIWRCQLEK LALKDKRFHV EYVLSAPSPE WNGKQGHVSR 430 440 450 460 ALLSEFLQRS LENSKVFLCI CGPTPFTDEG IRLLHDLNFS DDEIHGFTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 1). Tissue: Lung.
[2]	"Heterologous expression of an endogenous rat cytochrome b(5)/cytochrome b(5) reductase fusion protein: identification of histidines 62 and 85 as the heme axial ligands." Davis C.A., Dhawan I.K., Johnson M.K., Barber M.J. Arch. Biochem. Biophys. 400:63-75(2002) [PubMed: 11913972] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-520 (ISOFORM 1), ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FAD-BINDING, HEME-BINDING AT HIS-89 AND HIS-112, MUTAGENESIS OF HIS-89 AND HIS-112.
[3]	"Identification and characterization of a novel splice variant of mouse and rat cytochrome b5/cytochrome b5 reductase." Curry B.J., Roman S.D., Wallace C.A., Scott R., Miriami E., Aitken R.J. Genomics 83:425-438(2004) [PubMed: 14962668] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-520 (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Strain: Wistar. Tissue: Testis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC080240 mRNA. Translation: AAH80240.1. Different initiation. AF307840 mRNA. Translation: AAG45053.1. AY321370 mRNA. Translation: AAQ83902.1. AY321371 mRNA. Translation: AAQ83903.1.
IPI	IPI00189672. IPI00390401.
RefSeq	NP_596918.2.
UniGene	Rn.3334
3D structure databases
HSSP	HSSP built from PDB template 1QX4 based on UniProtKB P20070.
SMR	Q68EJ0. Positions 54-132, 162-257, 265-518.
ModBase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000013908; ENSRNOP00000013909; ENSRNOG00000010024; Rattus norvegicus. [Genome view]
GeneID	171015.
KEGG	rno:171015.
UCSC	NM_133427. rat.
Organism-specific databases
CTD	171015.
RGD	621834. Cyb5r4.
Phylogenomic databases
eggNOG	roNOG07055.
HOVERGEN	Q68EJ0.
InParanoid	Q68EJ0.
PhylomeDB	Q68EJ0.
Enzyme and pathway databases
BRENDA	1.6.2.2. 248.
Gene expression databases
ArrayExpress	Q68EJ0.
Genevestigator	Q68EJ0.
Family and domain databases
InterPro	IPR017447. CS. IPR007052. CS_domain. IPR001199. Cyt_B5. 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]
Gene3D	G3DSA:3.10.120.10. Cyt_B5. 1 hit.
Pfam	PF04969. CS. 1 hit. PF00173. Cyt-b5. 1 hit. PF00970. FAD_binding_6. 1 hit. PF00175. NAD_binding_1. 1 hit. [Graphical view]
PRINTS	PR00406. CYTB5RDTASE. PR00363. CYTOCHROMEB5.
PROSITE	PS51203. CS. 1 hit. PS00191. CYTOCHROME_B5_1. 1 hit. PS50255. CYTOCHROME_B5_2. 1 hit. PS51384. FAD_FR. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	621501.

Entry information

Entry name

NB5R4_RAT

Accession

Primary (citable) accession number: Q68EJ0
Secondary accession number(s): Q6VXY2, Q6VXY3, Q9EPZ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	May 15, 2007
Last modified:	January 19, 2010
This is version 51 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)