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Heph hephaestin [ Mus musculus (house mouse) ]

Gene ID: 15203, updated on 27-Nov-2024

Summary

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Official Symbol
Hephprovided by MGI
Official Full Name
hephaestinprovided by MGI
Primary source
MGI:MGI:1332240
See related
Ensembl:ENSMUSG00000031209 AllianceGenome:MGI:1332240
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
Hp; Cpl; sla; mKIAA0698; C130006F04Rik
Summary
Enables ferroxidase activity. Involved in intestinal iron absorption; multicellular organismal-level iron ion homeostasis; and positive regulation of iron export across plasma membrane. Acts upstream of or within erythrocyte differentiation. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in basolateral plasma membrane. Orthologous to human HEPH (hephaestin). [provided by Alliance of Genome Resources, Nov 2024]
Expression
Broad expression in large intestine adult (RPKM 13.9), ovary adult (RPKM 10.4) and 15 other tissues See more
Orthologs
human all
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Genomic context

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See Heph in Genome Data Viewer
Location:
X C3; X 42.69 cM
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) X NC_000086.8 (95499042..95618091)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) X NC_000086.7 (96455436..96574485)

Chromosome X - NC_000086.8Genomic Context describing neighboring genes Neighboring gene predicted gene, 18171 Neighboring gene heat shock transcription factor 3 Neighboring gene STARR-seq mESC enhancer starr_47582 Neighboring gene cofilin 1, non-muscle pseudogene Neighboring gene STARR-seq mESC enhancer starr_47583 Neighboring gene ribosomal protein L17, pseudogene 8 Neighboring gene heat shock protein 1 (chaperonin) pseudogene 10 Neighboring gene STARR-seq mESC enhancer starr_47584 Neighboring gene G protein-coupled receptor 165 Neighboring gene STARR-seq mESC enhancer starr_47585 Neighboring gene STARR-seq mESC enhancer starr_47586 Neighboring gene predicted gene 14803

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Uptake of circulating iron by the duodenum of normal mice and mice with altered iron stores, including sex-linked anemia: high resolution radioautographic study. Bédard YC, et al. Lab Invest, 1976 Jun. PMID 180329
  2. Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency. Chen H, et al. J Nutr, 2006 May. PMID 16614410
  3. Age-dependent expression of hephaestin in the brain of ceruloplasmin-deficient mice. Cui R, et al. J Trace Elem Med Biol, 2009. PMID 19747625
  4. Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice. Chen H, et al. Blood, 2004 May 15. PMID 14751926
  5. Mislocalisation of hephaestin, a multicopper ferroxidase involved in basolateral intestinal iron transport, in the sex linked anaemia mouse. Kuo YM, et al. Gut, 2004 Feb. PMID 14724150, Free PMC Article

See all (58) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. HEPH and CP are not essential for intestinal iron absorption but are required for proper systemic iron distribution.
    Title: Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin.
  2. results suggest that ablation of hephaestin and ceruloplasmin could lead to severe systemic iron deficiency and local tissue iron overload, which disrupt the whole body iron homeostasis and impact on tissue functions
    Title: Deletion of hephaestin and ceruloplasmin induces a serious systemic iron deficiency and disrupts iron homeostasis.
  3. Results show that both HEPH and CP are expressed in subcutaneous adipose tissue. Ablation of either MCF leads to a compensatory increase in the other, which contributes to the balance of iron status. However, ablation of both induces severe iron deposition in adipocytes and displays disordered carbohydrate metabolism characterized as type 2 diabetes.
    Title: Ablation of hephaestin and ceruloplasmin results in iron accumulation in adipocytes and type 2 diabetes.
  4. We thus used hephaestin (Heph) and ceruloplasmin (Cp) single-knockout mice and Heph/Cp double-knockout mice to investigate the roles of multicopper ferroxidases(MCF) in pancreatic iron homeostasis. We found that both HEPH and CP were expressed in the mouse pancreas, and that ablation of either MCF had limited effect on the pancreatic iron levels.
    Title: Ceruloplasmin and hephaestin jointly protect the exocrine pancreas against oxidative damage by facilitating iron efflux.
  5. Hephaestin and ceruloplasmin have roles in facilitating iron metabolism in the mouse kidney
    Title: Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney.
  6. In mice with mutation of Cp and Heph, iron accumulates in glia, while neurons have low iron levels. Both neurons and glia degenerate and mice become ataxic unless given an iron chelator.
    Title: Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone.
  7. The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice.
    Title: The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice.
  8. Data (including data from studies in knockout mice) suggest that hephaestin and ceruloplasmin play distinct roles in regulation of gene expression in various regions of the brain and are involved in iron homeostasis.
    Title: Hephaestin and ceruloplasmin play distinct but interrelated roles in iron homeostasis in mouse brain.
  9. Cp and Heph are necessary for iron export from the retina but are not essential for iron import into the retina.
    Title: Ferroxidase hephaestin's cell-autonomous role in the retinal pigment epithelium.
  10. results show that Heph is expressed by oligodendrocytes and plays an important role in iron efflux from these cells.
    Title: Iron efflux from oligodendrocytes is differentially regulated in gray and white matter.
Submit: New GeneRIF Correction See all GeneRIFs (16)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Chemically induced (ENU) (1)  1 citation
  • Endonuclease-mediated (2) 
  • Radiation induced (1) 
  • Targeted (2)  1 citation

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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Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables copper ion binding IEA
Inferred from Electronic Annotation
more info
  
enables copper ion binding ISO
Inferred from Sequence Orthology
more info
  
enables ferrous iron binding ISO
Inferred from Sequence Orthology
more info
  
enables ferroxidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ferroxidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ferroxidase activity ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within erythrocyte differentiation IMP
Inferred from Mutant Phenotype
more info
  
involved_in intestinal iron absorption IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in iron ion transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in iron ion transport ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within iron ion transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in multicellular organismal-level iron ion homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of iron export across plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in basolateral plasma membrane ISO
Inferred from Sequence Orthology
more info
  
is_active_in basolateral plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in perinuclear region of cytoplasm ISO
Inferred from Sequence Orthology
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
hephaestin
Names
haphaestin
sex linked anemia
NP_001153099.1
NP_001153100.1
NP_034547.2
NP_851790.1

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.

mRNA and Protein(s)

  1. NM_001159627.1 → NP_001153099.1  hephaestin isoform 1 precursor

    See identical proteins and their annotated locations for NP_001153099.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) represents use of an alternate promoter, compared to variant 1, and enocdes the longest isoform (1). Both variants 1 and 3 encode the same isoform.
    Source sequence(s)
    AF082567, AK129194, CJ053588
    Consensus CDS
    CCDS30289.1
    UniProtKB/Swiss-Prot
    A2AI63, Q6ZQ65, Q80Y80, Q8C4S2, Q9Z0Z4
    Related
    ENSMUSP00000109469.2, ENSMUST00000113838.8
    Conserved Domains (5) summary
    cd04222
    Location:26 → 208
    CuRO_1_ceruloplasmin; The first cupredoxin domain of Ceruloplasmin
    cd04224
    Location:377 → 571
    CuRO_3_ceruloplasmin; The third cupredoxin domain of Ceruloplasmin
    cd04225
    Location:732 → 903
    CuRO_5_ceruloplasmin; The fifth cupredoxin domain of Ceruloplasmin
    cd11021
    Location:223 → 363
    CuRO_2_ceruloplasmin; The second cupredoxin domain of Ceruloplasmin
    cl19115
    Location:574 → 717
    Cupredoxin; Cupredoxin superfamily

  2. NM_001159628.1 → NP_001153100.1  hephaestin isoform 3 precursor

    See identical proteins and their annotated locations for NP_001153100.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) uses an alternate splice site in the 3' coding region, compared to variant 1. The resulting isoform (3) lacks one internal amino acid near the C-terminus, compared to isoform 1.
    Source sequence(s)
    AL732365
    UniProtKB/Swiss-Prot
    Q9Z0Z4
    Conserved Domains (5) summary
    cd04222
    Location:26 → 208
    CuRO_1_ceruloplasmin; The first cupredoxin domain of Ceruloplasmin
    cd04224
    Location:377 → 571
    CuRO_3_ceruloplasmin; The third cupredoxin domain of Ceruloplasmin
    cd04225
    Location:732 → 903
    CuRO_5_ceruloplasmin; The fifth cupredoxin domain of Ceruloplasmin
    cd11021
    Location:223 → 363
    CuRO_2_ceruloplasmin; The second cupredoxin domain of Ceruloplasmin
    cl19115
    Location:574 → 717
    Cupredoxin; Cupredoxin superfamily

  3. NM_010417.2 → NP_034547.2  hephaestin isoform 1 precursor

    See identical proteins and their annotated locations for NP_034547.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). Both variants 1 and 3 encode the same isoform.
    Source sequence(s)
    AF082567, AK129194, CJ067085
    Consensus CDS
    CCDS30289.1
    UniProtKB/Swiss-Prot
    A2AI63, Q6ZQ65, Q80Y80, Q8C4S2, Q9Z0Z4
    Related
    ENSMUSP00000033553.8, ENSMUST00000033553.14
    Conserved Domains (5) summary
    cd04222
    Location:26 → 208
    CuRO_1_ceruloplasmin; The first cupredoxin domain of Ceruloplasmin
    cd04224
    Location:377 → 571
    CuRO_3_ceruloplasmin; The third cupredoxin domain of Ceruloplasmin
    cd04225
    Location:732 → 903
    CuRO_5_ceruloplasmin; The fifth cupredoxin domain of Ceruloplasmin
    cd11021
    Location:223 → 363
    CuRO_2_ceruloplasmin; The second cupredoxin domain of Ceruloplasmin
    cl19115
    Location:574 → 717
    Cupredoxin; Cupredoxin superfamily

  4. NM_181273.4 → NP_851790.1  hephaestin isoform 2 precursor

    See identical proteins and their annotated locations for NP_851790.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) represents use of an alternate promoter and uses an alternate 3' splice pattern, compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AK081330, CJ053588
    Consensus CDS
    CCDS30290.1
    UniProtKB/TrEMBL
    A2AI62
    Related
    ENSMUSP00000078301.6, ENSMUST00000079322.12
    Conserved Domains (3) summary
    cd04222
    Location:26 → 208
    CuRO_1_ceruloplasmin; The first cupredoxin domain of Ceruloplasmin
    cd11021
    Location:223 → 363
    CuRO_2_ceruloplasmin; The second cupredoxin domain of Ceruloplasmin
    cl19115
    Location:377 → 529
    Cupredoxin; Cupredoxin superfamily

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000086.8 Reference GRCm39 C57BL/6J

    Range
    95499042..95618091
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Z0Z4.3 GenPept UniProtKB/Swiss-Prot:Q9Z0Z4

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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