CYB5R4
Cytochrome b5 reductase 4
Also known as: b5+b5R, dJ676J13.1, NB5R4_HUMAN, NCB5OR
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q7L1T6
- Gene
- CYB5R4
- Ensembl
- ENSG00000065615
- Chromosome
- 6
- Canonical length
- 521 aa
- Protein class
- Enzymes, Metabolic proteins, Predicted intracellular proteins
OverviewNCBI Gene
This locus represents naturally occurring readthrough transcription between the neighboring RIPPLY2 (ripply transcriptional repressor 2) and CYB5R4 (cytochrome b5 reductase 4) genes on chromosome 6. Multiple readthrough transcript variants exist for this readthrough gene. One variant encodes a protein that shares sequence identity with the downstream gene product but lacks the N-terminal region and initiates translation from an in-frame, downstream start codon. Additional readthrough transcript variants are candidates for nonsense-mediated mRNA decay (NMD), and are unlikely to produce a protein product. [provided by RefSeq, Jan 2022]
Canonical amino-acid sequenceUniProt
521 residues, UniProt reviewed canonical sequence.
>Q7L1T6|CYB5R4
1 MLNVPSQSFP APRSQQRVAS GGRSKVPLKQ GRSLMDWIRL TKSGKDLTGL KGRLIEVTEE
61 ELKKHNKKDD CWICIRGFVY NVSPYMEYHP GGEDELMRAA GSDGTELFDQ VHRWVNYESM
121 LKECLVGRMA IKPAVLKDYR EEEKKVLNGM LPKSQVTDTL AKEGPSYPSY DWFQTDSLVT
181 IAIYTKQKDI NLDSIIVDHQ NDSFRAETII KDCLYLIHIG LSHEVQEDFS VRVVESVGKI
241 EIVLQKKENT SWDFLGHPLK NHNSLIPRKD TGLYYRKCQL ISKEDVTHDT RLFCLMLPPS
301 THLQVPIGQH VYLKLPITGT EIVKPYTPVS GSLLSEFKEP VLPNNKYIYF LIKIYPTGLF
361 TPELDRLQIG DFVSVSSPEG NFKISKFQEL EDLFLLAAGT GFTPMVKILN YALTDIPSLR
421 KVKLMFFNKT EDDIIWRSQL EKLAFKDKRL DVEFVLSAPI SEWNGKQGHI SPALLSEFLK
481 RNLDKSKVLV CICGPVPFTE QGVRLLHDLN FSKNEIHSFT ALocalizationUniProt · AlphaFold · HPA
Whether an antibody against CYB5R4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.31
- Highest tissue expression
- 16 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 16 nTPM
- appendix: 11 nTPM
- testis: 11 nTPM
- lymph node: 9.1 nTPM
- spleen: 8.3 nTPM
- small intestine: 6.9 nTPM
Single-cell type
- neutrophils: 1,022 nCPM
- late spermatids: 652 nCPM
- neutrophil progenitors: 287 nCPM
- early spermatids: 287 nCPM
- monocytes: 229 nCPM
- microglia: 127 nCPM
Immune cell
- neutrophil: 200 nTPM
- eosinophil: 178 nTPM
- basophil: 104 nTPM
- classical monocyte: 59 nTPM
- non-classical monocyte: 59 nTPM
- intermediate monocyte: 51 nTPM
Brain region
- cerebellum: 38 nTPM
- white matter: 34 nTPM
- cerebral cortex: 32 nTPM
- pons: 29 nTPM
- basal ganglia: 28 nTPM
- medulla oblongata: 27 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.94
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.74
- DepMap mean gene effect
- -0.28
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- bicarbonate transport
- cell development
- detection of oxygen
- glucose homeostasis
- insulin secretion
- reactive oxygen species metabolic process
- response to antibiotic
- superoxide metabolic process
Molecular functions
- cytochrome-b5 reductase activity, acting on NAD(P)H
- cytochrome-b5 reductase activity, acting on NADH
- heme binding
- metal ion binding
- NAD(P)H oxidase H2O2-forming activity
- oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Cytochrome b5-like heme/steroid binding domain
- Oxidoreductase FAD/NAD(P)-binding
- CS domain
- Flavoprotein pyridine nucleotide cytochrome reductase-like, FAD-binding domain
- HSP20-like chaperone
- FAD-binding domain, ferredoxin reductase-type
- Riboflavin synthase-like beta-barrel
- Cytochrome b5, heme-binding site
- Cytochrome b5-like heme/steroid binding domain superfamily
- Ferredoxin-NADP reductase (FNR), nucleotide-binding domain
- Cytochrome b5-like Heme/Steroid binding domain
- Oxidoreductase NAD-binding domain
- Oxidoreductase FAD-binding domain
- CS domain
- Cytochrome b5 reductase 4, p23 domain
- Cytochrome b5/Flavoprotein Reductase
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CYB5R4 as an antibody target. Whether an autoantibody or antibody against CYB5R4 could matter depends on whether native CYB5R4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CYB5R4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CYB5R4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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