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CYB5A cytochrome b5 type A [ Homo sapiens (human) ]

Gene ID: 1528, updated on 27-Nov-2024

Summary

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Official Symbol
CYB5Aprovided by HGNC
Official Full Name
cytochrome b5 type Aprovided by HGNC
Primary source
HGNC:HGNC:2570
See related
Ensembl:ENSG00000166347 MIM:613218; AllianceGenome:HGNC:2570
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CYB5; MCB5; METAG
Summary
The protein encoded by this gene is a membrane-bound cytochrome that reduces ferric hemoglobin (methemoglobin) to ferrous hemoglobin, which is required for stearyl-CoA-desaturase activity. Defects in this gene are a cause of type IV hereditary methemoglobinemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
Expression
Broad expression in liver (RPKM 226.1), kidney (RPKM 141.0) and 16 other tissues See more
Orthologs
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Genomic context

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See CYB5A in Genome Data Viewer
Location:
18q22.3
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (74250846..74291963, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (74478400..74519513, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (71918081..71959198, complement)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13491 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13492 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13493 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr18:71817752-71818951 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr18:71822138-71823337 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13494 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50247 Neighboring gene translocase of inner mitochondrial membrane 21 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:71864836-71865492 Neighboring gene RNA, 7SL, cytoplasmic 551, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:71904867-71905366 Neighboring gene Sharpr-MPRA regulatory region 12176 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr18:71917515-71918450 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:71935092-71935632 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50263 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50279 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:71948314-71948841 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50293 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:71957777-71958384 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50301 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13495 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50307 Neighboring gene MPRA-validated peak3184 silencer Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50330 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50334 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50341 Neighboring gene chromosome 18 open reading frame 63 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_50347 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_50353 and experimental_50354 Neighboring gene NANOG hESC enhancer GRCh37_chr18:72050693-72051551 Neighboring gene FAU pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A splicing mutation in the cytochrome b5 gene from a patient with congenital methemoglobinemia and pseudohermaphrodism. Giordano SJ, et al. Hum Genet, 1994 May. PMID 8168836
  2. CYB5A polymorphism increases androgens and reduces risk of rheumatoid arthritis in women. Stark K, et al. Arthritis Res Ther, 2015 Mar 11. PMID 25890314, Free PMC Article
  3. CYB5A and autophagy-mediated cell death in pancreatic cancer. Giovannetti E, et al. Autophagy, 2014 Apr. PMID 24448000, Free PMC Article
  4. Role of cytochrome b5 and α-tocopherol to microsomal and mitochondrial oxidation. Agadzhanyan ZS, et al. Bull Exp Biol Med, 2013 Dec. PMID 24319746
  5. Isolated 17,20-lyase deficiency due to the cytochrome b5 mutation W27X. Kok RC, et al. J Clin Endocrinol Metab, 2010 Mar. PMID 20080843

See all (103) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Proteomics, modeling, and fluorescence assays delineate cytochrome b5 residues involved in binding and stimulation of cytochrome P450 17A1 17,20-lyase.
    Title: Proteomics, modeling, and fluorescence assays delineate cytochrome b(5) residues involved in binding and stimulation of cytochrome P450 17A1 17,20-lyase.
  2. The N-terminal intrinsically disordered region of Ncb5or docks with the cytochrome b5 core to form a helical motif that is of ancient origin.
    Title: The N-terminal intrinsically disordered region of Ncb5or docks with the cytochrome b(5) core to form a helical motif that is of ancient origin.
  3. The association between CYB5A gene rs1790834 polymorphism and clinical improvement after 6 months of leflunomide treatment in women with rheumatoid arthritis.
    Title: The association between CYB5A gene rs1790834 polymorphism and clinical improvement after 6 months of leflunomide treatment in women with rheumatoid arthritis.
  4. Regulating Effect of Cytochrome b5 Overexpression on Human Breast Cancer Cells.
    Title: Regulating Effect of Cytochrome b(5) Overexpression on Human Breast Cancer Cells.
  5. An alternative CYB5A transcript is expressed in aneuploid ALL and enriched in relapse.
    Title: An alternative CYB5A transcript is expressed in aneuploid ALL and enriched in relapse.
  6. Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity.
    Title: Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity.
  7. Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with rheumatoid arthritis.
    Title: Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with rheumatoid arthritis.
  8. Isolated 17, 20 Lyase Deficiency Secondary to a Novel CYB5A Variant: Comparison of Steroid Metabolomic Findings with Published Cases Provides Diagnostic Guidelines and Greater Insight into Its Biological Role.
    Title: Isolated 17, 20 Lyase Deficiency Secondary to a Novel CYB5A Variant: Comparison of Steroid Metabolomic Findings with Published Cases Provides Diagnostic Guidelines and Greater Insight into Its Biological Role.
  9. A homodimer model can resolve the conundrum as to how cytochrome P450 oxidoreductase and cytochrome b5 compete for the same binding site on cytochrome P450c17. (Review)
    Title: A Homodimer Model Can Resolve the Conundrum as to How Cytochrome P450 Oxidoreductase and Cytochrome b5 Compete for the Same Binding Site on Cytochrome P450c17.
  10. Data suggest CYP17A1, with electron donor NADPH-P450 reductase, is inherently distributive enzyme but that some processivity is present; some 17alpha-hydroxy pregnenolone formed does not dissociate from CYP17A1 before conversion to dehydroepiandrosterone; CYB5A does not enhance reaction by decreasing k(off) of ligands of CYP17A1. (CYP17A1 = cytochrome P450, family 17, subfamily A, polypeptide 1; CYB5A = cytochrome b5)
    Title: Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1.
Submit: New GeneRIF Correction See all GeneRIFs (38)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Methemoglobinemia type 4
MedGen: C4285231 OMIM: 250790 GeneReviews: Not available
Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cytochrome-c oxidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables heme binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in proton transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in intracellular membrane-bounded organelle IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in membrane HDA PubMed 
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial outer membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
cytochrome b5
Names
cytochrome b5 type A (microsomal)
epididymis secretory sperm binding protein
type 1 cyt-b5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_023211.2 RefSeqGene

    Range
    5000..46117
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001190807.3 → NP_001177736.1  cytochrome b5 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AC090398, BG196223, CA771478, CB112646
    Consensus CDS
    CCDS54188.1
    UniProtKB/Swiss-Prot
    P00167
    Related
    ENSP00000381011.4, ENST00000397914.4
    Conserved Domains (1) summary
    pfam00173
    Location:13 → 85
    Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain

  2. NM_001914.4 → NP_001905.1  cytochrome b5 isoform 2

    See identical proteins and their annotated locations for NP_001905.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an additional exon in the 3' coding region, which introduces a stop codon, as compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus, as compared to isoform 1.
    Source sequence(s)
    AC090398, BG196223, CB112646, M60174
    Consensus CDS
    CCDS12005.1
    UniProtKB/Swiss-Prot
    P00167
    Related
    ENSP00000436461.2, ENST00000494131.6
    Conserved Domains (1) summary
    pfam00173
    Location:13 → 85
    Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain

  3. NM_148923.4 → NP_683725.1  cytochrome b5 isoform 1

    See identical proteins and their annotated locations for NP_683725.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC090398, BC015182, BG196223, CB112646
    Consensus CDS
    CCDS12004.1
    UniProtKB/Swiss-Prot
    A8MV91, F8WEU4, P00167, Q6IB14
    UniProtKB/TrEMBL
    A0A384ME44
    Related
    ENSP00000341625.4, ENST00000340533.9
    Conserved Domains (1) summary
    pfam00173
    Location:13 → 85
    Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    74250846..74291963 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011525835.3 → XP_011524137.1  cytochrome b5 isoform X1

    See identical proteins and their annotated locations for XP_011524137.1

    UniProtKB/Swiss-Prot
    P00167
    Conserved Domains (1) summary
    pfam00173
    Location:13 → 85
    Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    74478400..74519513 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054318223.1 → XP_054174198.1  cytochrome b5 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P00167.2 GenPept UniProtKB/Swiss-Prot:P00167

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