Download Gene Section SPA17 (sperm autoantigenic protein 17) Atlas of Genetics and Cytogenetics

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SPA17 (sperm autoantigenic protein 17)
Leri S Faried, Ahmad Faried
Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University,
Maebashi, Japan
Published in Atlas Database: September 2007
Online updated version: http://AtlasGeneticsOncology.org/Genes/SPA17ID42360ch11q24.html
DOI: 10.4267/2042/38505
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2008 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Protein
Hugo: SPA17
Other names: SP17; SP17-1
Location: 11q24.2
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. SPA17's
central domain is necessary for heparin-binding and
exhibits the greatest sequence divergence of all three
domains. This region plays an important role in cellcell and/or cell matrix recognition process and/or cell
regulation, possibly via its interaction with extra
cellular heparin sulfate.
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.
Expression
Transcription
The SPA17 expression was originally found to be
expressed exclusively in the testis. Recently, this gene
also found in other somatic tissues.
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.
Localisation
SPA17 is present throughout the cytoplasm and is
particularly concentrated around the nucleus. It's also
present on the surface of B-lymphocytes and
granulocytes; T-lymphocytes and monocytes; most
malignant B and T lymphocytes cell lines.
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 fulllength SPA17 polypeptide.
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2)
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.
159
SPA17 (sperm autoantigenic protein 17)
Faried LS, Faried A
Chiriva-Internati M, Wang Z, Xue Y, Bumm K, Hahn AB, Lim
SH. Sperm protein 17 (Sp17) in multiple myeloma: opportunity
for myeloma-specific donor T cell infusion to enhance graftversus-myeloma effect without increasing graft-versus-host
disease risk. Eur J Immunol 2001;31:2277-2283.
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.
Lacy HM, Sanderson RD. Sperm protein 17 is expressed on
normal and malignant lymphocyte and promotes heparin
sulfate-mediated cell-cell adhesion. Blood 2001;98:2160-2165.
Implicated in
Lim SH, Wang Z, Chiriva-Internati M, Xue Y. Sperm protein 17
is a novel cancer-testis antigen in multiple myeloma. Blood
2001;97:1508-1510.
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).
Wen Y, Richardson RT, Widgren EE, O'Rand MG.
Characterization of Sp17: a ubiquitous three domain protein
that binds heparin. Biochem J 2001;357:25-31.
Buchli R, De Jong A, Robbins DL. Genomic organization of an
intron-containing sperm protein 17 gene (Sp17-1) and an
intronless pseudogene (Sp17-2) in humans: a new model.
Biochim Biophys Acta 2002;1578:29-42.
Chiriva-Internati M, Wang Z, Salati E, Bumm K, Barlogie B, Lim
SH. Sperm protein (Sp17) is a suitable target for
immunotherapy of multiple myeloma. Blood 2002;100:961-995.
Chiriva-Internati M, Wang Z, Salati E, Timmins P, Lim SH.
Tumor vaccine for ovarian carcinoma targeting sperm protein
17. Cancer 2002;94:2447-2453.
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.
Chiriva-Internati M, Wang Z, Salati E, Wroblewski D, Lim SH.
Successful 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.
Scan J Immunol 2002;56:429-433.
De Jong A, Buchli R, Robbins D. Characterization sperm
protein 17 in human somatic and neoplastic tissue. Cancer Lett
2002;186:201-209.
Straughn JM Jr, Shaw DR, Guerrero A, Bhoola SM, Racelis A,
Wang Z, Chiriva-Internati M, Grizzle WE, Alvarez RD, Lim SH,
Strong TV. Expression of sperm protein 17 (Sp17) in ovarian
cancer. Int J Cancer 2004;108:805-811.
Bumm K, Grizzi F, Franceschini B, Koch M, Iro H, Wurm J,
Ceva-Grimaldi G, Dimmler A, Cobos E, Dioguardi N, Sinha UK,
Kast WM, Chiriva-Internati M. Sperm protein 17 expression
defines 2 subsets of primary esthesioneuroblastoma. Hum
Pathol 2005;36:1289-1293.
References
Grizzi F, Gaetani P, Franceschini B, Di Ieva A, Colombo P,
Ceva-Grimaldi G, Bollati A, Frezza EE, Cobos E, Rodriguez y
Baena R, Dioguardi N, Chiriva-Internati M. Sperm protein 17 is
expressed in human nervous system tumors. BMC Cancer
2006;6:23.
O'Rand MG, Widgren EE, Fisher SJ. Characterization of the
rabbit sperm membrane autoantigen, RSA, as a lectin-like
zona binding protein. Dev Biol 1988;129:231-240.
Taylor SS, Buechler JA, Yonemoto W. cAMP dependent
protein kinase: framework for a diverse family of regulatory
enzymes. Annu Rev Biochem 1990;59:971-1005.
Gupta G, Sharma R, Chattopadhyay TK, Gupta SD, Ralhan R.
Clinical significance of sperm protein 17 expression and
immunogenicity in esophageal cancer. Int J Cancer
2007;120:1739-1748.
Lea IA, Richardson RT, Widgren EE, O'Rand MG. Cloning and
sequencing of cDNAs encoding the human sperm protein,
Sp17. Biochim Biophys Acta 1996;1307:263-266.
Lea IA, Adoyo P, O'Rand MG. Autoimmunity of the human
sperm protein Sp17 in vasectomized men and identification of
linear B epitopes. Fertil Steril 1997;67:355-361.
Nakazato T, Kanuma T, Tamura T, Faried LS, Aoki H,
Minegishi T. Sperm protein 17 influences the tissue-specific
malignancy of clear cell adenocarcinoma in human epithelial
ovarian cancer. Int J Gynecol Cancer 2007;17:426-432.
Lim SH, Bailey-Wood R. Idiotypic protein-pulsed dendritic cell
vaccination in multiple myeloma. Int J Cancer 1999;83:215222.
This article should be referenced as such:
Faried LS, Faried A. SPA17 (sperm autoantigenic protein 17).
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):159-160.
Wen Y, Richardson RT, O'rand MG. Processing of the sperm
protein Sp17 during the acrosome reaction and
characterization as a calmodulin binding protein. Dev Biol
1999;206:113-122.
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2)
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