STEAP2 (six transmembrane epithelial antigen of the prostate 2)

2010-05-01   Cláudio Maia , Sílvia Socorro , Cecília Santos 

Universidade 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

Atlas Image
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.

Proteins

Note

Members of this family are characterized by a six transmembrane helical domains.
Atlas Image
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).

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).

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).

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.

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).

Bibliography

Pubmed IDLast YearTitleAuthors
120959852002Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer.Korkmaz KS et al
166090652006The Steap proteins are metalloreductases.Ohgami RS et al
124298172002Cloning and characterization of a novel six-transmembrane protein STEAP2, expressed in normal and malignant prostate.Porkka KP et al
156233662004ACRATA: a novel electron transfer domain associated to apoptosis and cancer.Sanchez-Pulido L et al
191961372009Six-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

Gene IDTranscript IDUniprot
ENSG00000157214ENST00000287908Q8NFT2
ENSG00000157214ENST00000394621Q8NFT2
ENSG00000157214ENST00000394622Q8NFT2
ENSG00000157214ENST00000394626Q8NFT2
ENSG00000157214ENST00000394626Q6YPB2
ENSG00000157214ENST00000394629Q8NFT2
ENSG00000157214ENST00000394629Q6YPB2
ENSG00000157214ENST00000394632Q8NFT2
ENSG00000157214ENST00000402625B5MC02
ENSG00000157214ENST00000426158C9JHX5
ENSG00000157214ENST00000428074C9JLP2

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Mineral absorptionKEGGko04978
Mineral absorptionKEGGhsa04978
Transmembrane transport of small moleculesREACTOMER-HSA-382551
Iron uptake and transportREACTOMER-HSA-917937
Transferrin endocytosis and recyclingREACTOMER-HSA-917977

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
191961372009Six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2)-differentially expressed by murine and human mesenchymal stem cells.4
120959852002Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer.0
124298172002Cloning and characterization of a novel six-transmembrane protein STEAP2, expressed in normal and malignant prostate.0
158978942005Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer.0
166090652006The Steap proteins are metalloreductases.0
205875172010STAMP1 is both a proliferative and an antiapoptotic factor in prostate cancer.0
252486172014A role for STEAP2 in prostate cancer progression.0
296747232018STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells.0
299401762018Membrane cholesterol modulates STEAP2 conformation during dynamic intracellular trafficking processes leading to broad subcellular distribution.0

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