Q3TDX8 (NB5R4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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
N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein
cb5/cb5R

Gene names

Name:	Cyb5r4
Synonyms:	Ncb5or

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	528 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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). Ref.6
Catalytic activity	NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5.
Cofactor	FAD By similarity.
Subcellular location	Endoplasmic reticulum. Note: Soluble protein By similarity.
Tissue specificity	Ubiquitously expressed. Isoform 2 is expressed in testis, brain, skeletal muscle and in the male germline. Ref.5 Ref.7
Disruption phenotype	Mice display insulin-deficient diabetes. Embryos and fetus develop normally. At 4 weeks of age, mice show have normal blood glucose levels but impaired glucose tolerance. Isolated islets have markedly impaired glucose- or arginine-stimulated insulin secretion. By 7 weeks of age, they develop severe hyperglycemia with markedly decreased serum insulin levels and nearly normal insulin tolerance. As the animals age, there is a progressive loss of beta cells in pancreatic islets, but there is no loss of alpha, delta, or PP cells. 4 week-old mice have enhanced sensitivity to the diabetogenic agent streptozotocin. Ref.6
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.
Sequence caution	The sequence AAH25438.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAC41118.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAE34044.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAE42908.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	FAD Flavoprotein Heme Iron Metal-binding NAD
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell development Inferred from mutant phenotype Ref.6. Source: MGI generation of precursor metabolites and energy Inferred from electronic annotation. Source: Compara glucose homeostasis Inferred from mutant phenotype Ref.6. Source: MGI heme metabolic process Inferred from sequence alignment Ref.4. Source: MGI insulin secretion Inferred from mutant phenotype Ref.6. Source: MGI response to antibiotic Inferred from mutant phenotype PubMed 17343567. Source: MGI superoxide metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum Inferred from direct assay PubMed 15131110. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	NAD(P)H oxidase activity Inferred from electronic annotation. Source: Compara cytochrome-b5 reductase activity, acting on NAD(P)H Inferred from direct assay PubMed 15131110. Source: MGI heme binding Inferred from sequence alignment Ref.4. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q3TDX8-4)

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: Q3TDX8-5)

Also known as: cb5/cb5rDelta12;

The sequence of this isoform differs from the canonical sequence as follows:
     326-376: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 528	528	Cytochrome b5 reductase 4		PRO_0000410469
Regions
	Domain	54 – 130	77	Cytochrome b5 heme-binding
	Domain	172 – 263	92	CS
	Domain	280 – 392	113	FAD-binding FR-type
	Nucleotide binding	372 – 387	16	FAD By similarity
	Nucleotide binding	399 – 431	33	FAD By similarity
Sites
	Metal binding	89	1	Iron (heme axial ligand) By similarity
	Metal binding	112	1	Iron (heme axial ligand) By similarity
Natural variations
	Alternative sequence	326 – 376	51	Missing in isoform 2.		VSP_041453
	Natural variant	156	1	S → SDTLPRDVT.
Experimental info
	Sequence conflict	171	1	D → G in BAE34044. Ref.1
	Sequence conflict	171	1	D → G in BAE41470. Ref.1
	Sequence conflict	171	1	D → G in BAE42908. Ref.1
	Sequence conflict	171	1	D → G in AAK08116. Ref.4
	Sequence conflict	171	1	D → G in AAQ83900. Ref.5
	Sequence conflict	171	1	D → G in AAQ83901. Ref.5
	Sequence conflict	216	1	V → I in AAH25438. Ref.3
	Sequence conflict	300	1	F → L in BAE34044. Ref.1
	Sequence conflict	300	1	F → L in BAE41470. Ref.1
	Sequence conflict	300	1	F → L in BAE42908. Ref.1
	Sequence conflict	300	1	F → L in AAH02170. Ref.3
	Sequence conflict	300	1	F → L in AAK08116. Ref.4
	Sequence conflict	300	1	F → L in AAQ83900. Ref.5
	Sequence conflict	300	1	F → L in AAQ83901. Ref.5
	Sequence conflict	336	1	V → L in BAE34044. Ref.1
	Sequence conflict	339	1	S → P in BAE41470. Ref.1
	Sequence conflict	356	1	C → Y in BAE34044. Ref.1
	Sequence conflict	356	1	C → Y in BAE41470. Ref.1
	Sequence conflict	356	1	C → Y in BAE42908. Ref.1
	Sequence conflict	356	1	C → Y in AAH02170. Ref.3
	Sequence conflict	356	1	C → Y in AAH25438. Ref.3
	Sequence conflict	356	1	C → Y in AAK08116. Ref.4
	Sequence conflict	356	1	C → Y in AAQ83900. Ref.5
	Sequence conflict	388	1	D → N in BAE34044. Ref.1
	Sequence conflict	388	1	D → N in BAE41470. Ref.1
	Sequence conflict	388	1	D → N in BAE42908. Ref.1
	Sequence conflict	388	1	D → N in AAH02170. Ref.3
	Sequence conflict	388	1	D → N in AAH25438. Ref.3
	Sequence conflict	388	1	D → N in AAK08116. Ref.4
	Sequence conflict	388	1	D → N in AAQ83900. Ref.5
	Sequence conflict	388	1	D → N in AAQ83901. Ref.5
	Sequence conflict	393	1	K → T in AAH25438. Ref.3
	Sequence conflict	438	1	E → D in BAC37357. Ref.1
	Sequence conflict	504	1	P → Q in BAE39522. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 28, 2011. Version 3. Checksum: 8CF34CE865980A66	FASTA	528	59,716
	10 20 30 40 50 60 MLNVPSQAFP APGSQQRVSS QGRSKVPLKQ GRSLMDWIRL TKSGKDLTGL KGGLIEVTEE 70 80 90 100 110 120 ELKKHNKKED CWICIRGFVY NVSPYMEYHP GGEDELMRAA GADGTDLFNE VHRWVNYESM 130 140 150 160 170 180 LKECLVGRMA VKPAVPKDCH EGKRVLNGML PKSQMSDTLP RDVTDTLPRE DLSSPSYDWF 190 200 210 220 230 240 QTESSVTIVV YTKQKNISLD SVIVDLQDDS LRAEAVIKDH SYLVHVGLSH EVQENFSVRV 250 260 270 280 290 300 IENVGKIEIV LQKKESVSWQ CLGDHLEKHD SFIPKKDTGL YYRRCQLISK EDVTHDTRLF 310 320 330 340 350 360 CLMLPPSTHL QVPVGQHVYL KLSVTGAEIV KPYTPVSDSL LSDFKEPVLS PNKYICFLIK 370 380 390 400 410 420 IYPAGLFTPE LDRLQIGDFI SVSGPEGDFK VSKLQEVEDL FLLAAGTGFT PMVTVLNYAL 430 440 450 460 470 480 SHMSSLRKVK LMFFNKTEDD IIWRCQLEKL ALREKRFDVE FVLSAPSPEW NGKQGHISRA 490 500 510 520 LLSEFLQRSS ENSRAFLCIC GPTPFTDEGI RLLHDLNFSD DEIHGFTA
	Isoform 2 (cb5/cb5rDelta12) [UniParc]. Checksum: 4F809037109F6B5D	FASTA	477	53,994
	10 20 30 40 50 60 MLNVPSQAFP APGSQQRVSS QGRSKVPLKQ GRSLMDWIRL TKSGKDLTGL KGGLIEVTEE 70 80 90 100 110 120 ELKKHNKKED CWICIRGFVY NVSPYMEYHP GGEDELMRAA GADGTDLFNE VHRWVNYESM 130 140 150 160 170 180 LKECLVGRMA VKPAVPKDCH EGKRVLNGML PKSQMSDTLP RDVTDTLPRE DLSSPSYDWF 190 200 210 220 230 240 QTESSVTIVV YTKQKNISLD SVIVDLQDDS LRAEAVIKDH SYLVHVGLSH EVQENFSVRV 250 260 270 280 290 300 IENVGKIEIV LQKKESVSWQ CLGDHLEKHD SFIPKKDTGL YYRRCQLISK EDVTHDTRLF 310 320 330 340 350 360 CLMLPPSTHL QVPVGQHVYL KLSVTGDFIS VSGPEGDFKV SKLQEVEDLF LLAAGTGFTP 370 380 390 400 410 420 MVTVLNYALS HMSSLRKVKL MFFNKTEDDI IWRCQLEKLA LREKRFDVEF VLSAPSPEWN 430 440 450 460 470 GKQGHISRAL LSEFLQRSSE NSRAFLCICG PTPFTDEGIR LLHDLNFSDD EIHGFTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS. Strain: C57BL/6J and NOD. Tissue: Eye, Liver, Spinal cord and Spleen.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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] (ISOFORM 1), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS. Strain: Czech II and FVB/N. Tissue: Mammary tumor.
[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 35-528 (ISOFORM 1), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-528 (ISOFORMS 1 AND 2), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS, TISSUE SPECIFICITY. Strain: Swiss. Tissue: Testis.
[6]	"Absence of a reductase, NCB5OR, causes insulin-deficient diabetes." Xie J., Zhu H., Larade K., Ladoux A., Seguritan A., Chu M., Ito S., Bronson R.T., Leiter E.H., Zhang C.-Y., Rosen E.D., Bunn H.F. Proc. Natl. Acad. Sci. U.S.A. 101:10750-10755(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]	"Promoter characterization and transcriptional regulation of Ncb5or, a novel reductase necessary for pancreatic beta-cell maintenance." Larade K., Bunn H.F. Biochim. Biophys. Acta 1759:257-262(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK078682 mRNA. Translation: BAC37357.1. AK090159 mRNA. Translation: BAC41118.1. Different initiation. AK157312 mRNA. Translation: BAE34044.1. Different initiation. AK167436 mRNA. Translation: BAE39522.1. AK169937 mRNA. Translation: BAE41470.1. AK172252 mRNA. Translation: BAE42908.1. Different initiation. AC156793 Genomic DNA. No translation available. BC025438 mRNA. Translation: AAH25438.1. Different initiation. BC002170 mRNA. Translation: AAH02170.1. AF338818 mRNA. Translation: AAK08116.1. AY321368 mRNA. Translation: AAQ83900.1. AY321369 mRNA. Translation: AAQ83901.1.
IPI	IPI00988590. IPI01026790.
RefSeq	NP_077157.2. NM_024195.2.
UniGene	Mm.30166. Mm.394780.
3D structure databases
HSSP	HSSP built from PDB template 1SH4 based on UniProtKB P00171.
ProteinModelPortal	Q3TDX8.
SMR	Q3TDX8. Positions 51-137, 282-502.
ModBase	Search...
PTM databases
PhosphoSite	Q3TDX8.
Proteomic databases
PRIDE	Q3TDX8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000168529; ENSMUSP00000126119; ENSMUSG00000032872. ENSMUST00000173126; ENSMUSP00000134460; ENSMUSG00000032872.
GeneID	266690.
KEGG	mmu:266690.
UCSC	uc009qyc.2. mouse. uc009qyf.2. mouse.
Organism-specific databases
CTD	51167.
MGI	MGI:2386848. Cyb5r4.
Phylogenomic databases
eggNOG	COG0543.
GeneTree	ENSGT00390000008881.
HOVERGEN	HBG108174.
InParanoid	Q3TDX8.
OMA	DSVIVDH.
OrthoDB	EOG49CQ7B.
Gene expression databases
ArrayExpress	Q3TDX8.
Bgee	Q3TDX8.
CleanEx	MM_CYB5R4.
Genevestigator	Q3TDX8.
Family and domain databases
Gene3D	3.10.120.10. 1 hit.
InterPro	IPR007052. CS-like_domain. IPR017447. CS_domain. 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]
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.
SUPFAM	SSF55856. Cyt_B5. 1 hit. SSF49764. HSP20_chap. 1 hit. SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.
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
ChiTaRS	CYB5R4. mouse.
NextBio	392180.
SOURCE	Search...

Entry information

Entry name

NB5R4_MOUSE

Accession

Primary (citable) accession number: Q3TDX8
Secondary accession number(s): E9Q129 , Q3TJH3, Q3U012, Q6VXY4, Q6VXY5, Q8BJV8, Q8BTI5, Q8R3H8, Q99LY4, Q99P29

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	June 28, 2011
Last modified:	May 1, 2013
This is version 78 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program