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Gene Review

SSFA2  -  sperm specific antigen 2

Homo sapiens

Synonyms: CS-1, CS1, Cleavage signal-1 protein, KIAA1927, KRAP, ...
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Disease relevance of SSFA2


High impact information on SSFA2

  • Here we report that day-12 colony-forming-unit spleen (CFU-S12)5 cells and reconstituting haematopoietic stem cells attach to the C-terminal, heparin-binding fragment of fibronectin by recognizing the CS-1 peptide of the alternatively spliced non-type III connecting segment (IIICS) of human plasma fibronectin [6].
  • Moreover, eosinophil migration over FN-preincubated or HUVEC-covered filters was significantly inhibited by anti-connecting segment 1 (CS-1) mAbs, as well as the soluble CS-1 peptide (unlike migration across bare untreated filters) [7].
  • (c) Both primitive LTBMC-IC and clonogenic progenitors adhere to the three known cell-attachment sites in the 33/66 kD cell-adhesion promoting fragment, FN-C/H I, FN-C/H II and CS1 [8].
  • Finally, the ability to block adhesion of LTBMC-IC to intact irradiated stroma with peptides FN-C/H II, FN-C/H I and CS1 suggests that receptors responsible for this interaction may be important in the homing of primitive progenitors to the bone marrow [8].
  • Furthermore, mAb's specific for CD49d and CD106, or the synthetic CS1 fibronectin peptide, could inhibit B-cell pseudoemperipolesis [9].

Chemical compound and disease context of SSFA2

  • Importantly, when melanoma cells were cultured on substrata coated with CS1 and then stimulated with 9.2.27-conjugated microsphere beads, formation of focal contacts and stress fibers was also observed, indicating that NG2 can collaborate with alpha 4 beta 1 integrin when each receptor is engaged on distinct and separate substrata [10].
  • When RGDS peptide homologues were tested for their ability to inhibit spreading of melanoma cells on CS1- and CS5-IgG conjugates, GRGDS, GRGES, and REDV were found to be inhibitory, while GRDGS had no effect [11].
  • When N-terminal cysteine derivatives of the CS peptides were conjugated to IgG by covalent cross-linking with N-succinimidyl-3(2-pyridyldithio)propionate, both the CS1 and CS5 conjugates promoted B16-F10 melanoma cell spreading [12].
  • These results indicate that the C-terminal cell- and heparin-binding domain of fibronectin mediates HL-60 cell binding by direct interaction independently of RGD, CS1, and melanoma cell adhesion domains in this fragment [13].
  • These results indicate that CS1 peptide of fibronectin, lacking the Arg-Gly-Asp-containing domain, actively inhibits tumor metastases in spontaneous and experimental metastasis models [14].

Biological context of SSFA2


Anatomical context of SSFA2


Associations of SSFA2 with chemical compounds

  • Binding was abrogated by both anti-alpha 4 integrin and CS1 peptides [17].
  • Both anti-CS-1 and an antibody to activated beta1 showed increased staining on the luminal endothelium of human coronary lesions with active monocyte entry [18].
  • Monoclonal antibodies against both the alpha 5 and the beta 1 subunits of the classical fibronectin receptor as well as an Arg-Gly-Asp (RGD) peptide inhibited attachment, whereas anti-alpha 4 monoclonal antibodies and the CS1 peptide did not [19].
  • Two nonadjacent CS peptides, designated CS1 and CS5, were inhibitory [12].
  • Triiodothyronine treatment of transiently transfected GC cells had little effect on CAT activity from the hGH-1 gene hybrid but increased CAT activity from the hCS-1 gene hybrid [20].

Other interactions of SSFA2


Analytical, diagnostic and therapeutic context of SSFA2

  • The ability of a synthetic peptidomimetic of connecting segment-1 (CS-1 peptide) to block the recruitment of leukocytes and the accumulation of lipid in the aortic sinus of either wild-type mice (strain C57BL/6J) or mice with a low-density lipoprotein null mutation (LDLR-/-) maintained on an atherogenic diet was assessed [21].
  • Examination by PCR of 17 other unrelated CS1 ETEC strains with a variety of serotypes demonstrated that all contained at least parts of both replicons of pCoo and that strains of the O6 genotype appear to contain a cointegrate very similar to pCoo [22].
  • METHODS--The effect of the synthetic peptide CS1 on lymphocyte binding to human synovial and peripheral lymph node high endothelial venules (HEVs) was measured in an in vitro frozen section assay [23].
  • A total of 370 patients (63%) had early clinical stages (CS) of disease; 295 (50%) had CS1, 32 (5%) had CS1Mk+ (CS1 with pathological serum tumor marker patterns after orchiectomy) and 43 (7%) had CS2A disease [24].
  • Pathological staging with retroperitoneal lymph node dissection (RPLND) of the retroperitoneum was performed in 345 (93%) of the early CS patients and 128 (37%) had pathological stage 2 (PS2) disease; 27% of the CS1, 100% of the CS1Mk+ and 66% of the CS2A patients [24].


  1. Deregulated expression of KRAP, a novel gene encoding actin-interacting protein, in human colon cancer cells. Inokuchi, J., Komiya, M., Baba, I., Naito, S., Sasazuki, T., Shirasawa, S. J. Hum. Genet. (2004) [Pubmed]
  2. Coordinate role for cell surface chondroitin sulfate proteoglycan and alpha 4 beta 1 integrin in mediating melanoma cell adhesion to fibronectin. Iida, J., Skubitz, A.P., Furcht, L.T., Wayner, E.A., McCarthy, J.B. J. Cell Biol. (1992) [Pubmed]
  3. A conserved residue in the tip proteins of CS1 and CFA/I pili of enterotoxigenic Escherichia coli that is essential for adherence. Sakellaris, H., Munson, G.P., Scott, J.R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Coordinate oncodevelopmental modulation of alternative splicing of fibronectin pre-messenger RNA at ED-A, ED-B, and CS1 regions in human liver tumors. Oyama, F., Hirohashi, S., Sakamoto, M., Titani, K., Sekiguchi, K. Cancer Res. (1993) [Pubmed]
  5. New tools in an old trade: CS1 pilus morphogenesis. Sakellaris, H., Scott, J.R. Mol. Microbiol. (1998) [Pubmed]
  6. Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions. Williams, D.A., Rios, M., Stephens, C., Patel, V.P. Nature (1991) [Pubmed]
  7. Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration. Kuijpers, T.W., Mul, E.P., Blom, M., Kovach, N.L., Gaeta, F.C., Tollefson, V., Elices, M.J., Harlan, J.M. J. Exp. Med. (1993) [Pubmed]
  8. Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin. Verfaillie, C.M., McCarthy, J.B., McGlave, P.B. J. Exp. Med. (1991) [Pubmed]
  9. Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism. Burger, J.A., Zvaifler, N.J., Tsukada, N., Firestein, G.S., Kipps, T.J. J. Clin. Invest. (2001) [Pubmed]
  10. Spreading and focal contact formation of human melanoma cells in response to the stimulation of both melanoma-associated proteoglycan (NG2) and alpha 4 beta 1 integrin. Iida, J., Meijne, A.M., Spiro, R.C., Roos, E., Furcht, L.T., McCarthy, J.B. Cancer Res. (1995) [Pubmed]
  11. The CS5 peptide is a second site in the IIICS region of fibronectin recognized by the integrin alpha 4 beta 1. Inhibition of alpha 4 beta 1 function by RGD peptide homologues. Mould, A.P., Komoriya, A., Yamada, K.M., Humphries, M.J. J. Biol. Chem. (1991) [Pubmed]
  12. Identification of two distinct regions of the type III connecting segment of human plasma fibronectin that promote cell type-specific adhesion. Humphries, M.J., Komoriya, A., Akiyama, S.K., Olden, K., Yamada, K.M. J. Biol. Chem. (1987) [Pubmed]
  13. Binding site in human plasma fibronectin to HL-60 cells localizes in the C-terminal heparin-binding region independently of RGD and CS1. Fujita, H., Mohri, H., Kanamori, H., Iwamatsu, A., Okubo, T. Exp. Cell Res. (1995) [Pubmed]
  14. Inhibition of lung metastasis by synthetic and recombinant fragments of human fibronectin with functional domains. Saiki, I., Murata, J., Makabe, T., Matsumoto, Y., Ohdate, Y., Kawase, Y., Taguchi, Y., Shimojo, T., Kimizuka, F., Kato, I. Jpn. J. Cancer Res. (1990) [Pubmed]
  15. Human cleavage signal-1 protein; cDNA cloning, transcription and immunological analysis. Javed, A.A., Naz, R.K. Gene (1992) [Pubmed]
  16. Attachment, spreading and locomotion of avian neural crest cells are mediated by multiple adhesion sites on fibronectin molecules. Dufour, S., Duband, J.L., Humphries, M.J., Obara, M., Yamada, K.M., Thiery, J.P. EMBO J. (1988) [Pubmed]
  17. Expression and functional significance of alternatively spliced CS1 fibronectin in rheumatoid arthritis microvasculature. Elices, M.J., Tsai, V., Strahl, D., Goel, A.S., Tollefson, V., Arrhenius, T., Wayner, E.A., Gaeta, F.C., Fikes, J.D., Firestein, G.S. J. Clin. Invest. (1994) [Pubmed]
  18. Minimally modified low-density lipoprotein induces monocyte adhesion to endothelial connecting segment-1 by activating beta1 integrin. Shih, P.T., Elices, M.J., Fang, Z.T., Ugarova, T.P., Strahl, D., Territo, M.C., Frank, J.S., Kovach, N.L., Cabanas, C., Berliner, J.A., Vora, D.K. J. Clin. Invest. (1999) [Pubmed]
  19. HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression. Weeks, B.S., Klotman, M.E., Dhawan, S., Kibbey, M., Rappaport, J., Kleinman, H.K., Yamada, K.M., Klotman, P.E. J. Cell Biol. (1991) [Pubmed]
  20. Regulated expression of chimaeric genes containing the 5'-flanking regions of human growth hormone-related genes in transiently transfected rat anterior pituitary tumor cells. Cattini, P.A., Eberhardt, N.L. Nucleic Acids Res. (1987) [Pubmed]
  21. Blocking very late antigen-4 integrin decreases leukocyte entry and fatty streak formation in mice fed an atherogenic diet. Shih, P.T., Brennan, M.L., Vora, D.K., Territo, M.C., Strahl, D., Elices, M.J., Lusis, A.J., Berliner, J.A. Circ. Res. (1999) [Pubmed]
  22. The pCoo plasmid of enterotoxigenic Escherichia coli is a mosaic cointegrate. Froehlich, B., Parkhill, J., Sanders, M., Quail, M.A., Scott, J.R. J. Bacteriol. (2005) [Pubmed]
  23. Role of the CS1 adhesion motif of fibronectin in T cell adhesion to synovial membrane and peripheral lymph node endothelium. van Dinther-Janssen, A.C., Pals, S.T., Scheper, R.J., Meijer, C.J. Ann. Rheum. Dis. (1993) [Pubmed]
  24. Early clinical stages (CS1, CS1Mk+ and CS2A) of non-seminomatous testis cancer. Value of pre- and post-orchiectomy serum tumor marker information in prediction of retroperitoneal lymph node metastases. Swedish-Norwegian Testicular Cancer Project (SWENOTECA). Klepp, O., Flodgren, P., Maartman-Moe, H., Lindholm, C.E., Unsgaard, B., Teigum, H., Fosså, S.D., Paus, E. Ann. Oncol. (1990) [Pubmed]
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