This gene encodes a multipass membrane protein that functions as an iron transporter. The encoded protein can reduce both iron (Fe3+) and copper (Cu2+) cations. This protein may mediate downstream responses to p53, including promoting apoptosis. Deficiency in this gene can cause anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015] See more...

Aliases for STEAP3 Gene

Aliases for STEAP3 Gene

  • STEAP3 Metalloreductase 2 3 5
  • TSAP6 2 3 4
  • Six-Transmembrane Epithelial Antigen Of Prostate 3 3 4
  • Tumor Suppressor-Activated Pathway Protein 6 3 4
  • STEAP Family Member 3, Metalloreductase 2 3
  • Metalloreductase STEAP3 3 4
  • Dudulin-2 3 4
  • Dudlin-2 2 3
  • STMP3 2 3
  • PHyde 3 4
  • Tumor Suppressor PHyde 3
  • EC 1.16.1.- 4
  • AHMIO2 3
  • STEAP3 5
  • HTSAP6 4
  • HpHyde 4

External Ids for STEAP3 Gene

Previous GeneCards Identifiers for STEAP3 Gene

  • GC02P119698
  • GC02P119981
  • GC02P112313

Summaries for STEAP3 Gene

Entrez Gene Summary for STEAP3 Gene

  • This gene encodes a multipass membrane protein that functions as an iron transporter. The encoded protein can reduce both iron (Fe3+) and copper (Cu2+) cations. This protein may mediate downstream responses to p53, including promoting apoptosis. Deficiency in this gene can cause anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

GeneCards Summary for STEAP3 Gene

STEAP3 (STEAP3 Metalloreductase) is a Protein Coding gene. Diseases associated with STEAP3 include Anemia, Hypochromic Microcytic, With Iron Overload 2 and Hypochromic Microcytic Anemia. Among its related pathways are TP53 Regulates Transcription of Cell Death Genes and Copper homeostasis. Gene Ontology (GO) annotations related to this gene include cupric reductase activity and ferric-chelate reductase activity. An important paralog of this gene is STEAP2.

UniProtKB/Swiss-Prot Summary for STEAP3 Gene

  • Endosomal ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Participates in erythroid iron homeostasis by reducing Fe(3+) to Fe(2+). Can also reduce of Cu(2+) to Cu(1+), suggesting that it participates in copper homeostasis. Uses NADP(+) as acceptor. May play a role downstream of p53/TP53 to interface apoptosis and cell cycle progression. Indirectly involved in exosome secretion by facilitating the secretion of proteins such as TCTP.

Gene Wiki entry for STEAP3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for STEAP3 Gene

Genomics for STEAP3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for STEAP3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J119223 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 615.4 +1.7 1667 2.1 HNRNPL PRDM10 IKZF1 ZNF692 LARP7 ZNF143 RBFOX2 RXRB PATZ1 IRF2 STEAP3 HSALNG0018313 C2orf76
GH02J119251 Enhancer 1.2 Ensembl ENCODE dbSUPER 23.1 +33.2 33225 9 TEAD4 PRDM10 ZNF629 KDM1A ZIC2 HDAC1 ZNF600 SOX6 ZNF341 MNT STEAP3 STEAP3-AS1 HSALNG0018313 C2orf76
GH02J119218 Enhancer 1.2 Ensembl ENCODE dbSUPER 17.1 -3.6 -3575 3.4 GATAD2A CTCF PRDM10 ZNF692 ZIC2 PATZ1 REST RAD21 SP1 ESR1 STEAP3 LOC107985941 C1QL2
GH02J119229 Enhancer 1.4 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 12.3 +9.9 9857 5.9 CTCF KDM1A RELA REST DPF2 CEBPB RUNX3 CTBP1 ZNF444 FOS HSALNG0018313 STEAP3 MTATP6P26 STEAP3-AS1 C2orf76
GH02J119267 Enhancer 0.8 FANTOM5 Ensembl 22.2 +45.5 45525 1.2 PKNOX1 NFE2 ZNF316 USF1 MAFG MAFK ZNF384 ZEB2 EMSY STEAP3 DBI LOC105373581 STEAP3-AS1 HSALNG0018313 C2orf76
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around STEAP3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for STEAP3

Top Transcription factor binding sites by QIAGEN in the STEAP3 gene promoter:
  • AREB6
  • c-Ets-1
  • MyoD
  • p53
  • Spz1

Genomic Locations for STEAP3 Gene

Genomic Locations for STEAP3 Gene
chr2:119,222,476-119,265,652
(GRCh38/hg38)
Size:
43,177 bases
Orientation:
Plus strand
chr2:119,981,384-120,023,228
(GRCh37/hg19)
Size:
41,845 bases
Orientation:
Plus strand

Genomic View for STEAP3 Gene

Genes around STEAP3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
STEAP3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for STEAP3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for STEAP3 Gene

Proteins for STEAP3 Gene

  • Protein details for STEAP3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q658P3-STEA3_HUMAN
    Recommended name:
    Metalloreductase STEAP3
    Protein Accession:
    Q658P3
    Secondary Accessions:
    • A8K6E3
    • Q4VBR2
    • Q4ZG36
    • Q53SQ8
    • Q7Z389
    • Q86SF6
    • Q8NEW6
    • Q8TDP3
    • Q8TF03
    • Q9NVB5

    Protein attributes for STEAP3 Gene

    Size:
    488 amino acids
    Molecular mass:
    54601 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Cofactor:
    Name=heme; Xref=ChEBI:CHEBI:30413;
    Quaternary structure:
    • Homodimer. Interacts with BNIP3L, MYT1, RHBDL4/RHBDD1 and TCTP.

    Three dimensional structures from OCA and Proteopedia for STEAP3 Gene

    Alternative splice isoforms for STEAP3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for STEAP3 Gene

Post-translational modifications for STEAP3 Gene

  • Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage occurs at multiple sites in a glycosylation-independent manner.
  • Glycosylated.
  • Glycosylation at Asn256 and Asn344
  • Ubiquitination at Lys339, Lys472, and Lys484
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for STEAP3 Gene

Domains & Families for STEAP3 Gene

Gene Families for STEAP3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for STEAP3 Gene

Suggested Antigen Peptide Sequences for STEAP3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ14101 fis, clone MAMMA1000859 (Q9H7Y1_HUMAN)
  • pHyde (STEA3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q658P3

UniProtKB/Swiss-Prot:

STEA3_HUMAN :
  • Belongs to the STEAP family.
Family:
  • Belongs to the STEAP family.
genes like me logo Genes that share domains with STEAP3: view

Function for STEAP3 Gene

Molecular function for STEAP3 Gene

UniProtKB/Swiss-Prot Function:
Endosomal ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Participates in erythroid iron homeostasis by reducing Fe(3+) to Fe(2+). Can also reduce of Cu(2+) to Cu(1+), suggesting that it participates in copper homeostasis. Uses NADP(+) as acceptor. May play a role downstream of p53/TP53 to interface apoptosis and cell cycle progression. Indirectly involved in exosome secretion by facilitating the secretion of proteins such as TCTP.
UniProtKB/Swiss-Prot Induction:
By p53/TP53.

Enzyme Numbers (IUBMB) for STEAP3 Gene

Phenotypes From GWAS Catalog for STEAP3 Gene

Gene Ontology (GO) - Molecular Function for STEAP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 22624035
GO:0008823 cupric reductase activity IBA 21873635
GO:0016491 oxidoreductase activity IEA --
GO:0046872 metal ion binding IEA --
GO:0052851 ferric-chelate reductase (NADPH) activity IBA 21873635
genes like me logo Genes that share ontologies with STEAP3: view
genes like me logo Genes that share phenotypes with STEAP3: view

Human Phenotype Ontology for STEAP3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for STEAP3 Gene

MGI Knock Outs for STEAP3:

Animal Model Products

  • Taconic Biosciences Mouse Models for STEAP3

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for STEAP3

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for STEAP3 Gene

Localization for STEAP3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for STEAP3 Gene

Endosome membrane. Multi-pass membrane protein. Note=Localizes to vesicular-like structures at the plasma membrane and around the nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for STEAP3 gene
Compartment Confidence
endosome 5
plasma membrane 4
extracellular 2
mitochondrion 2
nucleus 2
cytosol 2
lysosome 2
cytoskeleton 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoli (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for STEAP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 25468996
GO:0005768 endosome IBA 21873635
GO:0005771 multivesicular body IDA 15319436
GO:0005886 plasma membrane IBA 21873635
GO:0010008 endosome membrane IEA,TAS --
genes like me logo Genes that share ontologies with STEAP3: view

Pathways & Interactions for STEAP3 Gene

genes like me logo Genes that share pathways with STEAP3: view

Gene Ontology (GO) - Biological Process for STEAP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006915 apoptotic process IEA --
GO:0007049 cell cycle IEA --
GO:0009306 protein secretion IDA,IMP 22624035
GO:0015677 copper ion import IBA 21873635
genes like me logo Genes that share ontologies with STEAP3: view

No data available for SIGNOR curated interactions for STEAP3 Gene

Drugs & Compounds for STEAP3 Gene

(5) Drugs for STEAP3 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma 249
FAD Approved Pharma 0
Iron Approved, Experimental Pharma 1560
NAD Experimental Pharma Agonist, Full agonist, Activator 0
heme Pharma Agonist 0
genes like me logo Genes that share compounds with STEAP3: view

Transcripts for STEAP3 Gene

mRNA/cDNA for STEAP3 Gene

4 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for STEAP3

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for STEAP3 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11
SP1: - - - - -
SP2: - - - - -
SP3: - - - - - -
SP4: - - - -
SP5: - - -
SP6: - - - -
SP7: - - -
SP8: - -
SP9:

Relevant External Links for STEAP3 Gene

GeneLoc Exon Structure for
STEAP3

Expression for STEAP3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for STEAP3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for STEAP3 Gene

This gene is overexpressed in Liver (x16.2).

Protein differential expression in normal tissues from HIPED for STEAP3 Gene

This gene is overexpressed in Breast (23.6), Bone (15.2), and Liver (7.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for STEAP3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for STEAP3

SOURCE GeneReport for Unigene cluster for STEAP3 Gene:

Hs.647822

mRNA Expression by UniProt/SwissProt for STEAP3 Gene:

Q658P3-STEA3_HUMAN
Tissue specificity: Expressed in adult bone marrow, placenta, liver, skeletal muscle and pancreas. Down-regulated in hepatocellular carcinoma.

Evidence on tissue expression from TISSUES for STEAP3 Gene

  • Liver(4.6)
  • Intestine(4.5)
  • Kidney(4.5)
  • Nervous system(3.6)
  • Blood(2.3)
  • Bone marrow(2.1)
  • Muscle(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for STEAP3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
Regions:
Head and neck:
  • brain
  • pituitary gland
Thorax:
  • breast
Abdomen:
  • liver
  • spleen
Pelvis:
  • ovary
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vulva
General:
  • blood
  • hair
  • red blood cell
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with STEAP3: view

No data available for Protein tissue co-expression partners for STEAP3 Gene

Orthologs for STEAP3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for STEAP3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia STEAP3 30 31
  • 99.04 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia STEAP3 30 31
  • 87.47 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia STEAP3 30 31
  • 86.56 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Steap3 30 17 31
  • 84.97 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Steap3 30
  • 84.56 (n)
Oppossum
(Monodelphis domestica)
Mammalia STEAP3 31
  • 73 (a)
OneToOne
Chicken
(Gallus gallus)
Aves STEAP3 30 31
  • 72.35 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia STEAP3 31
  • 63 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii steap3 30 31
  • 58.95 (n)
OneToOne
Species where no ortholog for STEAP3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for STEAP3 Gene

ENSEMBL:
Gene Tree for STEAP3 (if available)
TreeFam:
Gene Tree for STEAP3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for STEAP3: view image

Paralogs for STEAP3 Gene

Paralogs for STEAP3 Gene

(6) SIMAP similar genes for STEAP3 Gene using alignment to 2 proteins:

  • STEA3_HUMAN
  • B8ZZX6_HUMAN
genes like me logo Genes that share paralogs with STEAP3: view

Variants for STEAP3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for STEAP3 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
708749 Likely Benign: not provided 119,248,175(+) G/A MISSENSE_VARIANT
709721 Benign: not provided 119,247,691(+) G/A MISSENSE_VARIANT
712428 Benign: not provided 119,248,167(+) C/T SYNONYMOUS_VARIANT
719383 Likely Benign: not provided 119,247,833(+) C/T MISSENSE_VARIANT
723023 Likely Benign: not provided 119,254,829(+) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for STEAP3 Gene

Structural Variations from Database of Genomic Variants (DGV) for STEAP3 Gene

Variant ID Type Subtype PubMed ID
esv3893204 CNV loss 25118596
nsv1131501 CNV deletion 24896259
nsv459119 CNV gain 19166990
nsv519595 CNV loss 19592680
nsv582783 CNV gain 21841781
nsv582784 CNV gain 21841781
nsv582785 CNV gain 21841781

Variation tolerance for STEAP3 Gene

Residual Variation Intolerance Score: 92.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.68; 65.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for STEAP3 Gene

Human Gene Mutation Database (HGMD)
STEAP3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
STEAP3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for STEAP3 Gene

Disorders for STEAP3 Gene

MalaCards: The human disease database

(12) MalaCards diseases for STEAP3 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
anemia, hypochromic microcytic, with iron overload 2
  • ahmio2
hypochromic microcytic anemia
  • anemia, hypochromic microcytic
hypochromic microcytic anemia with iron overload
  • anemia, hypochromic microcytic, with iron overload 1
microcytic anemia
  • iron-refractory iron deficiency anemia
anemia, sideroblastic, 1
  • sidba1
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

STEA3_HUMAN
  • Anemia, hypochromic microcytic, with iron overload 2 (AHMIO2) [MIM:615234]: A hematologic disease characterized by abnormal hemoglobin content in the erythrocytes which are reduced in size, severe anemia, erythropoietic hyperplasia of bone marrow, massive hepatic iron deposition, and hepatosplenomegaly. {ECO:0000269 PubMed:22031863}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for STEAP3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with STEAP3: view

No data available for Genatlas for STEAP3 Gene

Publications for STEAP3 Gene

  1. The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase. (PMID: 12606722) Passer BJ … Telerman A (Proceedings of the National Academy of Sciences of the United States of America 2003) 2 3 4
  2. Exosome-related multi-pass transmembrane protein TSAP6 is a target of rhomboid protease RHBDD1-induced proteolysis. (PMID: 22624035) Wan C … Wang L (PloS one 2012) 3 4
  3. A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene. (PMID: 22031863) Grandchamp B … Heimpel H (Blood 2011) 3 4
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  5. Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection. (PMID: 20587610) Ucisik-Akkaya E … Dorak MT (Molecular human reproduction 2010) 3 41

Products for STEAP3 Gene

Sources for STEAP3 Gene