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STEAP2 (six transmembrane epithelial antigen of the prostate 2)

Written2010-05Cláudio Maia, Sílvia Socorro, Cecília Santos
Universidade da Beira Interior, Research Centre of Health Sciences, Av. Infante D. Henrique, 6200-506, Covilha, Portugal

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPCANAP1
prostate cancer associated protein 1
six transmembrane epithelial antigen of the prostate 2
STEAP family member 2, metalloreductase
Alias_symbol (synonym)IPCA-1
STAMP1
STMP
Other aliasIPCA1
PUMPCn
HGNC (Hugo) STEAP2
LocusID (NCBI) 261729
Atlas_Id 42435
Location 7q21.13  [Link to chromosome band 7q21]
Location_base_pair Starts at 90211860 and ends at 90237678 bp from pter ( according to hg19-Feb_2009)  [Mapping STEAP2.png]
Fusion genes
(updated 2016)
RNF185 (22q12.2) / STEAP2 (7q21.13)SETDB2 (13q14.2) / STEAP2 (7q21.13)STEAP2 (7q21.13) / COL6A2 (21q22.3)
STEAP2 (7q21.13) / PDCD4 (10q25.2)STEAP2 (7q21.13) / SEC23A (14q21.1)STEAP2 (7q21.13) / STEAP2 (7q21.13)

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.

Protein

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).
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

Note
  
Entity 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

Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer.
Korkmaz KS, Elbi C, Korkmaz CG, Loda M, Hager GL, Saatcioglu F.
J Biol Chem. 2002 Sep 27;277(39):36689-96. Epub 2002 Jul 2.
PMID 12095985
 
The Steap proteins are metalloreductases.
Ohgami RS, Campagna DR, McDonald A, Fleming MD.
Blood. 2006 Aug 15;108(4):1388-94. Epub 2006 Apr 11.
PMID 16609065
 
Cloning and characterization of a novel six-transmembrane protein STEAP2, expressed in normal and malignant prostate.
Porkka KP, Helenius MA, Visakorpi T.
Lab Invest. 2002 Nov;82(11):1573-82.
PMID 12429817
 
ACRATA: a novel electron transfer domain associated to apoptosis and cancer.
Sanchez-Pulido L, Rojas AM, Valencia A, Martinez-A C, Andrade MA.
BMC Cancer. 2004 Dec 29;4:98.
PMID 15623366
 
Six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2)-differentially expressed by murine and human mesenchymal stem cells.
Vaghjiani RJ, Talma S, Murphy CL.
Tissue Eng Part A. 2009 Aug;15(8):2073-83.
PMID 19196137
 

Citation

This paper should be referenced as such :
Maia, C ; Socorro, S ; Santos, C
STEAP2 (six transmembrane epithelial antigen of the prostate 2)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(2):217-219.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/STEAP2ID42435ch7q21.html


External links

Nomenclature
HGNC (Hugo)STEAP2   17885
Cards
AtlasSTEAP2ID42435ch7q21
Entrez_Gene (NCBI)STEAP2  261729  STEAP2 metalloreductase
AliasesIPCA1; PCANAP1; PUMPCn; STAMP1; 
STMP
GeneCards (Weizmann)STEAP2
Ensembl hg19 (Hinxton)ENSG00000157214 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000157214 [Gene_View]  chr7:90211860-90237678 [Contig_View]  STEAP2 [Vega]
ICGC DataPortalENSG00000157214
TCGA cBioPortalSTEAP2
AceView (NCBI)STEAP2
Genatlas (Paris)STEAP2
WikiGenes261729
SOURCE (Princeton)STEAP2
Genetics Home Reference (NIH)STEAP2
Genomic and cartography
GoldenPath hg38 (UCSC)STEAP2  -     chr7:90211860-90237678 +  7q21.13   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)STEAP2  -     7q21.13   [Description]    (hg19-Feb_2009)
EnsemblSTEAP2 - 7q21.13 [CytoView hg19]  STEAP2 - 7q21.13 [CytoView hg38]
Mapping of homologs : NCBISTEAP2 [Mapview hg19]  STEAP2 [Mapview hg38]
OMIM605094   
Gene and transcription
Genbank (Entrez)AF455138 AF526382 AK026813 AK092666 AK094568
RefSeq transcript (Entrez)NM_001040665 NM_001040666 NM_001244944 NM_001244945 NM_001244946 NM_152999
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)STEAP2
Cluster EST : UnigeneHs.489051 [ NCBI ]
CGAP (NCI)Hs.489051
Alternative Splicing GalleryENSG00000157214
Gene ExpressionSTEAP2 [ NCBI-GEO ]   STEAP2 [ EBI - ARRAY_EXPRESS ]   STEAP2 [ SEEK ]   STEAP2 [ MEM ]
Gene Expression Viewer (FireBrowse)STEAP2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)261729
GTEX Portal (Tissue expression)STEAP2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8NFT2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8NFT2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8NFT2
Splice isoforms : SwissVarQ8NFT2
Catalytic activity : Enzyme1.16.1.- [ Enzyme-Expasy ]   1.16.1.-1.16.1.- [ IntEnz-EBI ]   1.16.1.- [ BRENDA ]   1.16.1.- [ KEGG ]   
PhosPhoSitePlusQ8NFT2
Domains : Interpro (EBI)Fe3_Rdtase_TM_dom    NAD(P)-bd_dom    P5C_Rdtase_cat_N   
Domain families : Pfam (Sanger)F420_oxidored (PF03807)    Ferric_reduct (PF01794)   
Domain families : Pfam (NCBI)pfam03807    pfam01794   
Conserved Domain (NCBI)STEAP2
DMDM Disease mutations261729
Blocks (Seattle)STEAP2
SuperfamilyQ8NFT2
Human Protein AtlasENSG00000157214
Peptide AtlasQ8NFT2
HPRD05481
IPIIPI00168894   IPI00885092   IPI00434815   IPI00795250   IPI00794626   IPI00877962   
Protein Interaction databases
DIP (DOE-UCLA)Q8NFT2
IntAct (EBI)Q8NFT2
FunCoupENSG00000157214
BioGRIDSTEAP2
STRING (EMBL)STEAP2
ZODIACSTEAP2
Ontologies - Pathways
QuickGOQ8NFT2
Ontology : AmiGOtransporter activity  early endosome  cytosol  plasma membrane  integral component of plasma membrane  Golgi to plasma membrane transport  endocytosis  cupric reductase activity  response to hormone  endosome membrane  copper ion import  trans-Golgi network transport vesicle  integral component of Golgi membrane  regulated exocytosis  metal ion binding  ferric-chelate reductase (NADPH) activity  iron ion homeostasis  oxidation-reduction process  
Ontology : EGO-EBItransporter activity  early endosome  cytosol  plasma membrane  integral component of plasma membrane  Golgi to plasma membrane transport  endocytosis  cupric reductase activity  response to hormone  endosome membrane  copper ion import  trans-Golgi network transport vesicle  integral component of Golgi membrane  regulated exocytosis  metal ion binding  ferric-chelate reductase (NADPH) activity  iron ion homeostasis  oxidation-reduction process  
Pathways : KEGGMineral absorption   
REACTOMEQ8NFT2 [protein]
REACTOME PathwaysR-HSA-917977 [pathway]   
NDEx NetworkSTEAP2
Atlas of Cancer Signalling NetworkSTEAP2
Wikipedia pathwaysSTEAP2
Orthology - Evolution
OrthoDB261729
GeneTree (enSembl)ENSG00000157214
Phylogenetic Trees/Animal Genes : TreeFamSTEAP2
HOVERGENQ8NFT2
HOGENOMQ8NFT2
Homologs : HomoloGeneSTEAP2
Homology/Alignments : Family Browser (UCSC)STEAP2
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSTEAP2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)STEAP2
dbVarSTEAP2
ClinVarSTEAP2
1000_GenomesSTEAP2 
Exome Variant ServerSTEAP2
ExAC (Exome Aggregation Consortium)STEAP2 (select the gene name)
Genetic variants : HAPMAP261729
Genomic Variants (DGV)STEAP2 [DGVbeta]
DECIPHERSTEAP2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSTEAP2 
Mutations
ICGC Data PortalSTEAP2 
TCGA Data PortalSTEAP2 
Broad Tumor PortalSTEAP2
OASIS PortalSTEAP2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSTEAP2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSTEAP2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch STEAP2
DgiDB (Drug Gene Interaction Database)STEAP2
DoCM (Curated mutations)STEAP2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)STEAP2 (select a term)
intoGenSTEAP2
NCG5 (London)STEAP2
Cancer3DSTEAP2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605094   
Orphanet
MedgenSTEAP2
Genetic Testing Registry STEAP2
NextProtQ8NFT2 [Medical]
TSGene261729
GENETestsSTEAP2
Target ValidationSTEAP2
Huge Navigator STEAP2 [HugePedia]
snp3D : Map Gene to Disease261729
BioCentury BCIQSTEAP2
ClinGenSTEAP2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD261729
Chemical/Pharm GKB GenePA38473
Clinical trialSTEAP2
Miscellaneous
canSAR (ICR)STEAP2 (select the gene name)
Probes
Litterature
PubMed13 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSTEAP2
EVEXSTEAP2
GoPubMedSTEAP2
iHOPSTEAP2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon May 22 09:24:21 CEST 2017

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