SPA17 (sperm autoantigenic protein 17)

2007-09-01   Leri S. Faried , Ahmad Faried 

Department of Gynecology, Reproductive Medicine, Graduate School of Medicine, Gunma University, Japan (FLS); Department of Surgery I, Gunma University, Japan (FA).

Identity

HGNC
LOCATION
11q24.2
LOCUSID
ALIAS
CT22,SP17,SP17-1

DNA/RNA

Description

The SPA17 gene contains 5 exons and 4 introns and was predicted to span over approximately 23 kb of the genomic DNA. The first exon is encodes solely the 5 untranslated sequence. The exon 2 encodes the first 51 amino acid residue. Exon 3 and 4 are only 71 and 87 bp length and contain coding region. Exon 5 contains stop codon and followed by 3 untranslated sequence. The size of introns 2, 3 and 4 were 5970, 10.235 and 2520 bp, respectively.

Transcription

Two transcript variants encoding the same protein have been identified for SP17-1 gene. This variant which was named SP17-1A and SP17-1B, both cDNA encodes identical protein sequence and only differed in 5 UTR part. One hundred percent homology can be detected from the poly A tail up to SP17-1 position -62 for variant A and -31 for variant B.

Pseudogene

There is one pseudogene, SP17-2 intronless gene has all the hallmark of retro-position giving rise to a pseudogene, located on chromosome 10. SP17-2 gene had 61 point mutations, 4 nucleotide insertions and 2 deletions leading to internal stop codons and frame shifts which do not result in ORF encoding a full-length SPA17 polypeptide.

Proteins

Description

The SPA17 consists of 151 amino acids corresponding to a molecular weight of 17.4 kDa. SPA17 protein indicated to have functional role in cell regulation by its calmodulin binding site located at its C-terminal end. The N-terminal end of SPA17, similar to human cyclic adenosine 3-5-monophosphate (cAMP)-dependent protein kinase type II regulatory subunits (RII), may facilitate dimmer formation. SPA17s central domain is necessary for heparin-binding and exhibits the greatest sequence divergence of all three domains. This region plays an important role in cell-cell and/or cell matrix recognition process and/or cell regulation, possibly via its interaction with extra cellular heparin sulfate.

Expression

The SPA17 expression was originally found to be expressed exclusively in the testis. Recently, this gene also found in other somatic tissues.

Localisation

SPA17 is present throughout the cytoplasm and is particularly concentrated around the nucleus. Its also present on the surface of B-lymphocytes and granulocytes; T-lymphocytes and monocytes; most malignant B and T lymphocytes cell lines.

Function

SPA17 is highly antigenic, testes specific antigen and known have function to bind sperm to the zona pellucida of the oocyte. In addition, SPA17 may also have an alternative role in highly proliferating and neoplastic cells, such as a mediator of signal transduction, protein synthesis and/or unregulated growth.

Homology

The homologues of SPA17 protein sequences were found from eutherian and marsupial mammals, including rat, mouse, macaque, baboon, human, marmoset, rabbit, Monodelphis and wallaby.

Implicated in

Entity name
Immune system
Disease
SPA17 is a highly immunogenic protein. More than 90% of male spontaneously developed B-cell immunity of SPA17 following vasectomy. SPA17 can be easily generated SPA17-specific cytotoxic T lymphocytes (CTLs) from peripheral blood of healthy donors and also from peripheral blood of cancer-bearing patients. SPA17 have been tested as tumor vaccines in a phase I study. In addition, SPA17 gene was described in human rheumatoid arthritis (RA).
Entity name
Malignancy
Disease
SPA17 reported to be over-expressed in female reproduction organ, multiple myeloma, esthesioneuroblastoma, nervous system tumors and esophageal cancer.
Prognosis
SPA17 expression closely related with poor prognosis in malignancy.
Oncogenesis
SPA17 was identified as a candidate gene related to chemoresistance of clear cell adenocarcinoma of the ovary, which has a poor prognosis due to its chemoresistancy and early metastasis to the lymph nodes.

Bibliography

Pubmed IDLast YearTitleAuthors
123931852002Genomic organization of an intron-containing sperm protein 17 gene (Sp17-1) and an intronless pseudogene (Sp17-2) in humans: a new model.Buchli R et al
163111222005Sperm protein 17 expression defines 2 subsets of primary esthesioneuroblastoma.Bumm K et al
122342642002Successful generation of sperm protein 17 (Sp17)-specific cytotoxic T lymphocytes from normal donors: implication for tumour-specific adoptive immunotherapy following allogeneic stem cell transplantation for Sp17-positive multiple myeloma.Chiriva-Internati M et al
122132902002Characterization of sperm protein 17 in human somatic and neoplastic tissue.De Jong A et al
164387282006Sperm protein 17 is expressed in human nervous system tumours.Grizzi F et al
172305142007Clinical significance of sperm protein 17 expression and immunogenicity in esophageal cancer.Gupta G et al
115680032001Sperm protein 17 is expressed on normal and malignant lymphocytes and promotes heparan sulfate-mediated cell-cell adhesion.Lacy HM et al
90226151997Autoimmunogenicity of the human sperm protein Sp17 in vasectomized men and identification of linear B cell epitopes.Lea IA et al
86884581996Cloning and sequencing of cDNAs encoding the human sperm protein, Sp17.Lea IA et al
104715301999Idiotypic protein-pulsed dendritic cell vaccination in multiple myeloma.Lim SH et al
112224012001Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma.Lim SH et al
173095632007Sperm protein 17 influences the tissue-specific malignancy of clear cell adenocarcinoma in human epithelial ovarian cancer.Nakazato T et al
34101591988Characterization of the rabbit sperm membrane autoantigen, RSA, as a lectin-like zona binding protein.O'Rand MG et al
147124802004Expression of sperm protein 17 (Sp17) in ovarian cancer.Straughn JM Jr et al
21653851990cAMP-dependent protein kinase: framework for a diverse family of regulatory enzymes.Taylor SS et al
114154322001Characterization of Sp17: a ubiquitous three domain protein that binds heparin.Wen Y et al

Other Information

Locus ID:

NCBI: 53340
MIM: 608621
HGNC: 11210
Ensembl: ENSG00000064199

Variants:

dbSNP: 53340
ClinVar: 53340
TCGA: ENSG00000064199
COSMIC: SPA17

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000064199ENST00000227135Q15506
ENSG00000064199ENST00000227135A0A172Q397
ENSG00000064199ENST00000532692Q15506
ENSG00000064199ENST00000532692A0A172Q397

Expression (GTEx)

0
5
10
15
20
25
30
35
40

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
147124802004Expression of sperm protein 17 (Sp17) in ovarian cancer.27
257391192015Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets.17
196043942009Sperm protein 17 is expressed in the sperm fibrous sheath.13
172305142007Clinical significance of sperm protein 17 expression and immunogenicity in esophageal cancer.10
187797502008Sperm protein 17 is a suitable target for adoptive T-cell-based immunotherapy in human ovarian cancer.10
197443472009Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells.10
207128742010Sperm protein 17 is highly expressed in endometrial and cervical cancers.10
239230792013Sperm protein 17, MAGE-C1 and NY-ESO-1 in hepatocellular carcinoma: expression frequency and their correlation with clinical parameters.9
122132902002Characterization of sperm protein 17 in human somatic and neoplastic tissue.8
241037812013Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma.8

Citation

Leri S. Faried ; Ahmad Faried

SPA17 (sperm autoantigenic protein 17)

Atlas Genet Cytogenet Oncol Haematol. 2007-09-01

Online version: http://atlasgeneticsoncology.org/gene/42360/spa17