STEAP2 (six transmembrane epithelial antigen of the prostate 2)
2010-05-01 Cláudio Maia , Sílvia Socorro , Cecília Santos AffiliationUniversidade da Beira Interior, Research Centre of Health Sciences, Av. Infante D. Henrique, 6200-506, Covilha, Portugal
Identity
HGNC
LOCATION
7q21.13
LOCUSID
ALIAS
IPCA1,PCANAP1,PUMPCn,STAMP1,STMP
FUSION GENES
DNA/RNA
Figure 1. Genomic organization of STEAP2 and its transcripts.
Description
Human STEAP2 gene was identified by using subtraction and cDNA arrays hybridizations in benign prostate hyperplasia and PC-3 prostate cancer cell line (Porkka et al., 2002). This gene is a member of the STEAP family and encodes a multi-pass membrane protein.
Transcription
The main STEAP2 transcript (variant 1) contains 5 exons and encodes a protein with 490 amino acids. The variant 2 differs from variant 1 in the 5 UTR, but encodes the same protein. The variant 3 differs in the 5 UTR, 3 UTR and 3 coding region compared to variant 1, resulting in a protein (isoform B) with unique C-terminus.
The lengths of these transcripts are:
- Variant 1: 6932 kb transcript; 1470 bp ORF,
- Variant 2: 6708 kb transcript; 1470 bp ORF,
- Variant 3: 2320 kb transcript; 1362 bp ORF.
The lengths of these transcripts are:
- Variant 1: 6932 kb transcript; 1470 bp ORF,
- Variant 2: 6708 kb transcript; 1470 bp ORF,
- Variant 3: 2320 kb transcript; 1362 bp ORF.
Proteins
Note
Members of this family are characterized by a six transmembrane helical domains.
Figure 2. Amino acids sequence of STEAP2 isoform A and B (Korkmaz et al., 2002).
Description
The main isoform (STEAP2 isoform A) is encoded by variant 1 and variant 2 mRNA. This isoform contains 490 amino acids (NCBI: NP_694544.2), 60 kDa and contains six transmembrane helical domains (figure 2).
The variant 3 mRNA encodes a protein (STEAP2 isoform B) that is shorter and has a unique C-terminus, compared to isoform A. However, none study has identified this isoform in in vitro or in vivo, yet. This putative isoform contains 454 amino acids (NCBI: NP_001035756.1), a 52 kDa and six transmembrane helical domains (figure 2).
The variant 3 mRNA encodes a protein (STEAP2 isoform B) that is shorter and has a unique C-terminus, compared to isoform A. However, none study has identified this isoform in in vitro or in vivo, yet. This putative isoform contains 454 amino acids (NCBI: NP_001035756.1), a 52 kDa and six transmembrane helical domains (figure 2).
Expression
STEAP2 is expressed exclusively in the epithelial cells of the prostate. In relation to prostate cell lines, STEAP2 is highly expressed in androgen receptor-positive cancer cell line LNCaP, CWR22 and CWR22R (Korkmaz et al., 2002).
Regarding to human tissues, STEAP2 is mainly expressed in prostate, but also in heart, brain, kidney, pancreas, ovary, fetal liver, colon, duodenum, ileum, liver, lung, stomach, thymus, choroid plexus and mesenchymal stem cells (Korkmaz et al., 2002; Ohgami et al., 2006; Vaghjiani et al., 2009).
Regarding to human tissues, STEAP2 is mainly expressed in prostate, but also in heart, brain, kidney, pancreas, ovary, fetal liver, colon, duodenum, ileum, liver, lung, stomach, thymus, choroid plexus and mesenchymal stem cells (Korkmaz et al., 2002; Ohgami et al., 2006; Vaghjiani et al., 2009).
Localisation
STEAP2 is localized mainly at plasma membrane, but also in trans-Golgi network and vesicular tubular structures (Korkmaz et al., 2002).
Function
Recently, it was demonstrated that STEAP2 acts as ferrireductase and cupric reductase, stimulating cellular uptake of both iron and copper (Ohgami et al., 2006). Moreover, its localization also suggests an important role in secretory/endocytic pathways (Korkmaz et al., 2002).
Furthermore, it was demonstrated that STEAP2 contains a domain associated to apoptosis and cancer, suggesting its involvement in cell cycle regulation (Sanchez-Pulido et al., 2004).
Furthermore, it was demonstrated that STEAP2 contains a domain associated to apoptosis and cancer, suggesting its involvement in cell cycle regulation (Sanchez-Pulido et al., 2004).
Homology
STEAP2 is known to have orthologs in chimpanzees, dogs, cows, mice, rats, chickens and even fish (NCBI: Homologene). Additional putative orthologs are likely in a variety of different species and can be viewed via Ensembl.
Mutations
Note
A great variety of single nucleotide polymorphisms (SNPs) have been identified, but its clinical significance remains unknown (NCBI: SNPs).
No STEAP2 mutations have been collected in the COSMIC database.
No STEAP2 mutations have been collected in the COSMIC database.
Implicated in
Entity name
Prostate cancer
Note
STEAP2 is highly expressed in androgen receptor-positive prostate cancer cell line LNCaP, but not in the androgen receptor-negative prostate cancer cell lines PC-3 and DU-145. However, STEAP2 expression is not significantly regulated by androgens in prostate cancer cells (Korkmaz et al., 2002). In human prostate tissues, STEAP2 is expressed exclusively in the epithelial cells of the prostate and its expression is significantly increased in prostate tumours compared with normal glands (Korkmaz et al., 2002). Moreover, STEAP2 expression is higher in both untreated primary and hormone-refractory prostate carcinomas than in benign prostate hyperplasias, suggesting an important role in prostate cancer progression. As a cell-surface antigen, STEAP2 is a potential diagnostic or therapeutic target in prostate cancer (Porkka et al., 2002).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12095985 | 2002 | Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer. | Korkmaz KS et al |
| 16609065 | 2006 | The Steap proteins are metalloreductases. | Ohgami RS et al |
| 12429817 | 2002 | Cloning and characterization of a novel six-transmembrane protein STEAP2, expressed in normal and malignant prostate. | Porkka KP et al |
| 15623366 | 2004 | ACRATA: a novel electron transfer domain associated to apoptosis and cancer. | Sanchez-Pulido L et al |
| 19196137 | 2009 | Six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2)-differentially expressed by murine and human mesenchymal stem cells. | Vaghjiani RJ et al |
Other Information
Locus ID:
NCBI: 261729
MIM: 605094
HGNC: 17885
Ensembl: ENSG00000157214
Variants:
dbSNP: 261729
ClinVar: 261729
TCGA: ENSG00000157214
COSMIC: STEAP2
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 35436987 | 2022 | METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition. | 27 |
| 36316642 | 2022 | STEAP2 promotes osteosarcoma progression by inducing epithelial-mesenchymal transition via the PI3K/AKT/mTOR signaling pathway and is regulated by EFEMP2. | 3 |
| 35436987 | 2022 | METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition. | 27 |
| 36316642 | 2022 | STEAP2 promotes osteosarcoma progression by inducing epithelial-mesenchymal transition via the PI3K/AKT/mTOR signaling pathway and is regulated by EFEMP2. | 3 |
| 34649092 | 2021 | Predictive potential of STEAP family for survival, immune microenvironment and therapy response in glioma. | 10 |
| 34649092 | 2021 | Predictive potential of STEAP family for survival, immune microenvironment and therapy response in glioma. | 10 |
| 31696760 | 2020 | STEAP2 is down-regulated in breast cancer tissue and suppresses PI3K/AKT signaling and breast cancer cell invasion in vitro and in vivo. | 16 |
| 32802887 | 2020 | The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer. | 20 |
| 31696760 | 2020 | STEAP2 is down-regulated in breast cancer tissue and suppresses PI3K/AKT signaling and breast cancer cell invasion in vitro and in vivo. | 16 |
| 32802887 | 2020 | The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer. | 20 |
| 29674723 | 2018 | STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells. | 24 |
| 29940176 | 2018 | Membrane cholesterol modulates STEAP2 conformation during dynamic intracellular trafficking processes leading to broad subcellular distribution. | 4 |
| 29674723 | 2018 | STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells. | 24 |
| 29940176 | 2018 | Membrane cholesterol modulates STEAP2 conformation during dynamic intracellular trafficking processes leading to broad subcellular distribution. | 4 |
| 25248617 | 2014 | A role for STEAP2 in prostate cancer progression. | 29 |
Citation
Cláudio Maia ; Sílvia Socorro ; Cecília Santos
STEAP2 (six transmembrane epithelial antigen of the prostate 2)
Atlas Genet Cytogenet Oncol Haematol. 2010-05-01
Online version: http://atlasgeneticsoncology.org/gene/42435/steap2
