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    STEAP4 STEAP4 metalloreductase [ Homo sapiens (human) ]

    Gene ID: 79689, updated on 11-Apr-2024

    Summary

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    Official Symbol
    STEAP4provided by HGNC
    Official Full Name
    STEAP4 metalloreductaseprovided by HGNC
    Primary source
    HGNC:HGNC:21923
    See related
    Ensembl:ENSG00000127954 MIM:611098; AllianceGenome:HGNC:21923
    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
    TIARP; STAMP2; SchLAH; TNFAIP9
    Summary
    The protein encoded by this gene belongs to the STEAP (six transmembrane epithelial antigen of prostate) family, and resides in the golgi apparatus. It functions as a metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+), using NAD(+) as acceptor. Studies in mice and human suggest that this gene maybe involved in adipocyte development and metabolism, and may contribute to the normal biology of the prostate cell, as well as prostate cancer progression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]
    Expression
    Broad expression in fat (RPKM 50.0), prostate (RPKM 32.8) and 17 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    7q21.12
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (88270892..88306894, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (89521348..89557349, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (87900207..87936209, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901691 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18355 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18356 Neighboring gene Sharpr-MPRA regulatory region 10982 Neighboring gene SRI antisense RNA 1 Neighboring gene sorcin Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:87894735-87895298 Neighboring gene uncharacterized LOC124901692 Neighboring gene uncharacterized LOC107986815 Neighboring gene eukaryotic translation initiation factor 4A1 pseudogene 13

    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. STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma. Tang Y, et al. Pathol Res Pract, 2022 May. PMID 35390632
    2. Cilostazol Improves HFD-Induced Hepatic Steatosis by Upregulating Hepatic STAMP2 Expression through AMPK. Oh YJ, et al. Mol Pharmacol, 2018 Dec. PMID 30366981
    3. Clinical and functional significance of STEAP4-splice variant in CD14(+) monocytes in patients with rheumatoid arthritis. Ebe H, et al. Clin Exp Immunol, 2018 Mar. PMID 29080328, Free PMC Article
    4. STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper. Scarl RT, et al. J Endocrinol, 2017 Sep. PMID 28576871, Free PMC Article
    5. STEAP4 expression in human islets is associated with differences in body mass index, sex, HbA1c, and inflammation. Gordon HM, et al. Endocrine, 2017 Jun. PMID 28405880, Free PMC Article

    See all (53) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. STEAP4 modulates cell proliferation and oxidative stress in benign prostatic hyperplasia.
      Title: STEAP4 modulates cell proliferation and oxidative stress in benign prostatic hyperplasia.
    2. STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma.
      Title: STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma.
    3. sSTEAP4 regulates cellular homeostasis and improves high-fat-diet-caused oxidative stress in hepatocytes.
      Title: sSTEAP4 regulates cellular homeostasis and improves high-fat-diet-caused oxidative stress in hepatocytes.
    4. Predictive potential of STEAP family for survival, immune microenvironment and therapy response in glioma.
      Title: Predictive potential of STEAP family for survival, immune microenvironment and therapy response in glioma.
    5. Stamp2 Protects From Maladaptive Structural Remodeling and Systolic Dysfunction in Post-Ischemic Hearts by Attenuating Neutrophil Activation.
      Title: Stamp2 Protects From Maladaptive Structural Remodeling and Systolic Dysfunction in Post-Ischemic Hearts by Attenuating Neutrophil Activation.
    6. The six-transmembrane protein Stamp2 ameliorates pulmonary vascular remodeling and pulmonary hypertension in mice.
      Title: The six-transmembrane protein Stamp2 ameliorates pulmonary vascular remodeling and pulmonary hypertension in mice.
    7. The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer.
      Title: The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer.
    8. Hepatic STAMP2 mediates recombinant FGF21-induced improvement of hepatic iron overload in nonalcoholic fatty liver disease.
      Title: Hepatic STAMP2 mediates recombinant FGF21-induced improvement of hepatic iron overload in nonalcoholic fatty liver disease.
    9. Enhancing STAMP2 expression with cilostazol represents a potential therapeutic avenue for treatment of NAFLD.
      Title: Cilostazol Improves HFD-Induced Hepatic Steatosis by Upregulating Hepatic STAMP2 Expression through AMPK.
    10. this study identified specific up-regulation of spliced variant STEAP4 in rheumatoid arthritis monocytes. This variant of STEAP4 might play a crucial role in the production of TNF-alpha and IL-6 through NF-kappaB and STAT-3 pathways, resulting in the generation of rheumatoid arthritis
      Title: Clinical and functional significance of STEAP4-splice variant in CD14(+) monocytes in patients with rheumatoid arthritis.
    Submit: New GeneRIF Correction See all GeneRIFs (41)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of STEAP family member 4 (STEAP4; TNFAIP9) in primary human brain microvascular endothelial cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Clone Names

    • FLJ23153, DKFZp666D049

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables FAD binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cupric reductase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables electron transfer activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ferric-chelate reductase (NADPH) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ferric-chelate reductase (NADPH) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables heme binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in copper ion import IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in fat cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in iron import into cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein homotrimerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in early endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    metalloreductase STEAP4
    Names
    STEAP family member 4
    seven chromosome locus associated with HCC
    six transmembrane prostate protein 2
    six-transmembrane epithelial antigen of prostate 4
    sixTransMembrane protein of prostate 2
    tumor necrosis factor, alpha-induced protein 9
    tumor necrosis-alpha-induced adipose-related protein
    NP_001192244.1
    NP_001192245.1
    NP_078912.2

    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_028313.2 RefSeqGene

      Range
      5000..41002
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001205315.2 → NP_001192244.1  metalloreductase STEAP4 isoform 1

      See identical proteins and their annotated locations for NP_001192244.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an additional 5' non-coding exon, and has a longer 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC003991, AF423422, AL833671, DB162772, DC333286
      Consensus CDS
      CCDS43611.1
      UniProtKB/Swiss-Prot
      Q658Q9, Q687X4, Q687X5, Q8WWB0, Q9H5R1
      Conserved Domains (2) summary
      COG2085
      Location:21 → 201
      COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]
      pfam01794
      Location:251 → 393
      Ferric_reduct; Ferric reductase like transmembrane component

    2. NM_001205316.2 → NP_001192245.1  metalloreductase STEAP4 isoform 2

      See identical proteins and their annotated locations for NP_001192245.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame coding exon compared to variant 1, resulting in a shorter isoform (2) missing an internal protein segment compared to isoform 1.
      Source sequence(s)
      AC003991, AK307644, AL833671, BC020600, DC333286
      Consensus CDS
      CCDS56494.1
      UniProtKB/Swiss-Prot
      Q687X5
      Related
      ENSP00000305545.5, ENST00000301959.9
      Conserved Domains (2) summary
      COG2085
      Location:21 → 155
      COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]
      pfam01794
      Location:163 → 217
      Ferric_reduct; Ferric reductase like transmembrane component

    3. NM_024636.4 → NP_078912.2  metalloreductase STEAP4 isoform 1

      See identical proteins and their annotated locations for NP_078912.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longer isoform (1). Variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AC003991, AF423422, AK307644, AL833671, DC333286
      Consensus CDS
      CCDS43611.1
      UniProtKB/Swiss-Prot
      Q658Q9, Q687X4, Q687X5, Q8WWB0, Q9H5R1
      Related
      ENSP00000369419.4, ENST00000380079.9
      Conserved Domains (2) summary
      COG2085
      Location:21 → 201
      COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]
      pfam01794
      Location:251 → 393
      Ferric_reduct; Ferric reductase like transmembrane component

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      88270892..88306894 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      89521348..89557349 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q687X5.1 GenPept UniProtKB/Swiss-Prot:Q687X5

    Gene LinkOut

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

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