STEAP3 STEAP3 metalloreductase [Homo sapiens (human)] - Gene

Summary

Official Symbol: STEAP3provided by HGNC
Official Full Name: STEAP3 metalloreductaseprovided by HGNC
Primary source: HGNC:HGNC:24592
See related: Ensembl:ENSG00000115107 MIM:609671; AllianceGenome:HGNC:24592
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: STMP3; TSAP6; pHyde; AHMIO2; dudlin-2; dudulin-2
Summary: 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]
Expression: Ubiquitous expression in liver (RPKM 27.2), duodenum (RPKM 11.9) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q14.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (119223834..119265652)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (119657360..119699155)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (119981410..120023228)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

STEAP3 promotes colon cancer cell proliferation and migration via regulating histone acetylation.
Title: STEAP3 promotes colon cancer cell proliferation and migration via regulating histone acetylation.
STEAP3 Affects Ovarian Cancer Progression by Regulating Ferroptosis through the p53/SLC7A11 Pathway.
Title: STEAP3 Affects Ovarian Cancer Progression by Regulating Ferroptosis through the p53/SLC7A11 Pathway.
Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis.
Title: Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis.
STEAP3 Affects Ferroptosis and Progression of Renal Cell Carcinoma Through the p53/xCT Pathway.
Title: STEAP3 Affects Ferroptosis and Progression of Renal Cell Carcinoma Through the p53/xCT Pathway.
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.
STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma.
Title: STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma.
This article is the first report of a role of Steap3 in mature RBCs; it defines a new mechanism of redox biology in RBCs with a substantial effect upon RBC function and provides a novel mechanistic determinant of genetic variation of RBC storage.
Title: Differences in Steap3 expression are a mechanism of genetic variation of RBC storage and oxidative damage in mice.
this study identified oxidative stress-dependent upregulation of the iron-converting metalloreductase, STEAP3, as a key mediator of extracellular matrix production in wound healing
Title: Reduced Iron in Diabetic Wounds: An Oxidative Stress-Dependent Role for STEAP3 in Extracellular Matrix Deposition and Remodeling.
In hepatocellular carcinoma (HCC), lower expression of the STEAP3 copper reductase and heavy Cu isotope enrichment have been reported for the tumor mass, relative to the surrounding tissue
Title: Copper transporters are responsible for copper isotopic fractionation in eukaryotic cells.
TSAP6 over expression is associated with poor survival in metastatic high-grade serous carcinoma.
Title: TSAP6 is a novel candidate marker of poor survival in metastatic high-grade serous carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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

Associated conditions

Description	Tests
Severe congenital hypochromic anemia with ringed sideroblasts MedGen: C3808920 OMIM: 615234 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH99327 (e-PCR)
- UniSTS:84538

SHGC-86162 (e-PCR)
- UniSTS:104807

SHGC-54575 (e-PCR)
- UniSTS:55657

D2S2254 (e-PCR)
- UniSTS:35211

ha2302 (e-PCR)
- UniSTS:515518

SHGC-10888 (e-PCR)
- UniSTS:40898

RH98234 (e-PCR)
- UniSTS:89575

RH120128 (e-PCR)
- UniSTS:132333

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 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
enables oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in copper ion import	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within protein secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in protein secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transferrin transport	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in endosome membrane	TAS Traceable Author Statement more info
located_in multivesicular body	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: metalloreductase STEAP3

Names: STEAP family member 3, metalloreductase; ferrireductase; six-transmembrane epithelial antigen of prostate 3; tumor suppressor pHyde; tumor suppressor-activated pathway protein 6

NP_001008410.1

EC 1.16.1.-

NP_060704.2

EC 1.16.1.-

NP_619543.2

EC 1.16.1.-

NP_878919.2

EC 1.16.1.-

XP_011509705.1

EC 1.16.1.-

XP_047300851.1

EC 1.16.1.-

XP_054198754.1

EC 1.16.1.-

XP_054198755.1

EC 1.16.1.-

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.

Genomic

NG_042823.1 RefSeqGene

Range

5027..46845

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001008410.2 → NP_001008410.1 metalloreductase STEAP3 isoform b

See identical proteins and their annotated locations for NP_001008410.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an exon in the 5' region and initiates translation at a downstream start codon compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 2 and 3 both encode the same isoform (b).

Source sequence(s)

AC016736, AY214461, BM146930

Consensus CDS

CCDS2125.1

UniProtKB/Swiss-Prot

A8K6E3, Q4VBR2, Q4ZG36, Q53SQ8, Q658P3, Q7Z389, Q86SF6, Q8NEW6, Q8TDP3, Q8TF03, Q9NVB5

Related

ENSP00000376819.2, ENST00000393107.2

Conserved Domains (2) summary

COG2085
Location:29 → 209

COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]

pfam01794
Location:262 → 405

Ferric_reduct; Ferric reductase like transmembrane component
NM_018234.3 → NP_060704.2 metalloreductase STEAP3 isoform b

See identical proteins and their annotated locations for NP_060704.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon and contains an alternate exon in the 5' region, and initiates translation at a downstream start codon compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 2 and 3 both encode the same isoform (b).

Source sequence(s)

AC016736, AY214461

Consensus CDS

CCDS2125.1

UniProtKB/Swiss-Prot

A8K6E3, Q4VBR2, Q4ZG36, Q53SQ8, Q658P3, Q7Z389, Q86SF6, Q8NEW6, Q8TDP3, Q8TF03, Q9NVB5

Related

ENSP00000376818.2, ENST00000393106.6

Conserved Domains (2) summary

COG2085
Location:29 → 209

COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]

pfam01794
Location:262 → 405

Ferric_reduct; Ferric reductase like transmembrane component
NM_138637.3 → NP_619543.2 metalloreductase STEAP3 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an exon in the 5' region and contains an alternate exon in the 3' region, compared to variant 1. It initiates translation at a downstream start codon, and contains a frameshift in the 3' coding region. The resulting isoform (c) is shorter at the N-terminus and has a distinct C-terminus compared to isoform a.

Source sequence(s)

AC016736, AF262322, AF423424, AL833624

Consensus CDS

CCDS82504.1

UniProtKB/TrEMBL

B8ZZX6

Related

ENSP00000386510.1, ENST00000409811.5

Conserved Domains (3) summary

COG2085
Location:29 → 209

COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]

pfam01794
Location:262 → 394

Ferric_reduct; Ferric reductase like transmembrane component

pfam03807
Location:32 → 117

F420_oxidored; NADP oxidoreductase coenzyme F420-dependent
NM_182915.3 → NP_878919.2 metalloreductase STEAP3 isoform a

See identical proteins and their annotated locations for NP_878919.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

AC016736, AL833624, BX538047

Consensus CDS

CCDS42738.1

UniProtKB/Swiss-Prot

Q658P3

Related

ENSP00000376822.2, ENST00000393110.7

Conserved Domains (3) summary

COG2085
Location:39 → 219

COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]

pfam01794
Location:272 → 415

Ferric_reduct; Ferric reductase like transmembrane component

pfam03807
Location:42 → 127

F420_oxidored; NADP oxidoreductase coenzyme F420-dependent

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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

119223834..119265652

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011511403.2 → XP_011509705.1 metalloreductase STEAP3 isoform X2

See identical proteins and their annotated locations for XP_011509705.1

UniProtKB/Swiss-Prot

A8K6E3, Q4VBR2, Q4ZG36, Q53SQ8, Q658P3, Q7Z389, Q86SF6, Q8NEW6, Q8TDP3, Q8TF03, Q9NVB5

Conserved Domains (2) summary

COG2085
Location:29 → 209

COG2085; Predicted dinucleotide-binding enzyme [General function prediction only]

pfam01794
Location:262 → 405

Ferric_reduct; Ferric reductase like transmembrane component
XM_047444895.1 → XP_047300851.1 metalloreductase STEAP3 isoform X1