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FLASH GENE

Symbol

CYB5R3

contributors: mct - updated : 02-06-2020

HGNC name	cytochrome b5 reductase 3
HGNC id	2873

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CYB5R3D methemoglobinemia, with CYB5R3 deficiency
Location	22q13.2      Physical location : 43.013.846 - 43.045.405
Synonym name	diaphorase-1
	diaphorase (NADH) (cytochrome b-5 reductase)
	NADH-cytochrome b5 reductase 3 membrane-bound form
Synonym symbol(s)	DIA1, B5R
EC.number	1.6.2.2

DNA

TYPE	functioning gene
STRUCTURE	30.59 kb     10 Exon(s)

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000398 9 splicing 2923 NP_000389 34 301 - 1992 1400360 also called DIA1-Vm membrane bound coding exon 1 M NM_007326 9 splicing 2922 NP_015565 - 278 late stage of erytroid maturation 1992 1400360 also called DIA1-Vs soluble isoform non-coding exon 1S NM_001129819 9 - 3167 NP_001123291 - 278 - 1992 1400360 NM_001171660 9 - 3063 NP_001165131 - 334 - 1992 1400360 NM_001171661 10 - 2983 NP_001165132 - 278 - 1992 1400360

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine small intestine     predominantly   liver       highly Nervous nerve cranial nerve     highly Reproductive female system uterus cervix     Skin/Tegument skin

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Muscular smooth vessel   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive hepatocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies	ortholog to murine Cyb5r3
	ortholog to rattus Dia1

Homologene

FAMILY

flavoprotein pyridine nucleotide cytochrome reductase family

CATEGORY

enzyme , transport

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,mitochondria,outer
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic,microsome
text	membrane-associated form (34kDa)

basic FUNCTION	desaturation and elongation of fatty acids
	drug metabolism
	methemoglobin reduction (erythrocyte form)
	decline in the activities of G6PD and CYB5R3 would indicate a decrease in the antioxidant response associated to Red blood cell (RBC) aging
	influences the NAD(+)/NADH ratio and may play a regulatory role that connects aerobic metabolism with aging
	contributes to regulate redox homeostasis, aerobic metabolism, and cellular senescence, suggesting that CYB5R3 might be a key effector of oxidative and nutritional stress pathways
	CYB5R3 involvement in the activation of redox cyclers in the outer mitochondrial membrane
	central role of CYB5R3 in extravasation/colonization of cancer cells
	is a flavoprotein known for its ability to transfer electrons from its NADH domain through the small heme protein partner cytochrome b5 (CYB5) to a final electron acceptor
	critical role for CYB5R3 in cGMP signaling

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

electron transport

text

iron

PATHWAY

metabolism

energetic , lipid/lipoprotein

signaling

hemoglobin metabolism

a component

INTERACTION

DNA

RNA

small molecule	cofactor, nucleotide,
	NADH

protein	cytochrome b5
	SCAI is a novel transcriptional cofactor that controls gene expression downstream of CYB5R3 to dictate changes in cell invasive behaviour
	CYB5R3 is an essential gene that appears as a final effector for both nutritional and oxidative stress responses through FOXO3a and NFE2L2, respectively, and their interaction promotes CYB5R3 expression
	CYB5R3 regulates alpha-globin heme redox state in small artery and arteriolar endothelial cells to control NO diffusion
	FOXO1 is unable to maintain expression of key differentiation markers in CYB5R3-deficient beta cells, suggesting that CYB5R3 is required for FOXO1-dependent lineage stability

cell & other

REGULATION

Other

expression of CYB5R3 is regulated by the cooperation of NFE2L2 and FOXO3

ASSOCIATED DISORDERS

corresponding disease(s)

CYB5R3D

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	prognostic marker of disease-free and overall survival in estrogen receptor-negative breast cancer
Therapy target

ANIMAL & CELL MODELS