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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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