Heph hephaestin [Mus musculus (house mouse)] - Gene

Summary

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

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_000086.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
Hephaestin and ceruloplasmin have roles in facilitating iron metabolism in the mouse kidney
Title: Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney.
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.
The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice.
Title: The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice.
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.
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.
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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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

EC 1.16.3.1

NP_001153100.1

EC 1.16.3.1

NP_034547.2

EC 1.16.3.1

NP_851790.1

EC 1.16.3.1

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)

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
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
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
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