CYTH1 explained

Cytohesin-1 formerly known as Pleckstrin homology, Sec7 and coiled/coil domains 1 (PSCD1) is a protein that in humans is encoded by the CYTH1 gene.^{[1] [2] [3]}

Function

Cytohesin-1 (CYTH1) is a member of the cytohesin family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of CYTHs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. The CYTH1 is highly expressed in natural killer and peripheral T cells, and regulates the adhesiveness of integrins at the plasma membrane of lymphocytes. CYTH1 protein is 83% homologous to CYTH2.^[3]

Interactions

CYTH1 has been shown to interact with:

• ARFRP1,^[4]
• CD18,^{[5] [6]} and
• TRIM23.^[7]

Further reading

• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Kolanus W, Nagel W, Schiller B, Zeitlmann L, Godar S, Stockinger H, Seed B . Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule . Cell . 86 . 2 . 233–42 . 1996 . 8706128 . 10.1016/S0092-8674(00)80095-1 . 18390795 . free .
• Meacci E, Tsai SC, Adamik R, Moss J, Vaughan M . Cytohesin-1, a cytosolic guanine nucleotide-exchange protein for ADP-ribosylation factor . Proc. Natl. Acad. Sci. U.S.A. . 94 . 5 . 1745–8 . 1997 . 9050849 . 19987 . 10.1073/pnas.94.5.1745 . 1997PNAS...94.1745M . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Nagel W, Zeitlmann L, Schilcher P, Geiger C, Kolanus J, Kolanus W . Phosphoinositide 3-OH kinase activates the beta2 integrin adhesion pathway and induces membrane recruitment of cytohesin-1 . J. Biol. Chem. . 273 . 24 . 14853–61 . 1998 . 9614087 . 10.1074/jbc.273.24.14853 . free .
• Betz SF, Schnuchel A, Wang H, Olejniczak ET, Meadows RP, Lipsky BP, Harris EA, Staunton DE, Fesik SW . Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1 . Proc. Natl. Acad. Sci. U.S.A. . 95 . 14 . 7909–14 . 1998 . 9653114 . 20903 . 10.1073/pnas.95.14.7909 . 1998PNAS...95.7909B . free .
• Nagel W, Schilcher P, Zeitlmann L, Kolanus W . The PH domain and the polybasic c domain of cytohesin-1 cooperate specifically in plasma membrane association and cellular function . Mol. Biol. Cell . 9 . 8 . 1981–94 . 1998 . 9693361 . 25450 . 10.1091/mbc.9.8.1981 .
• Pacheco-Rodriguez G, Meacci E, Vitale N, Moss J, Vaughan M . Guanine nucleotide exchange on ADP-ribosylation factors catalyzed by cytohesin-1 and its Sec7 domain . J. Biol. Chem. . 273 . 41 . 26543–8 . 1998 . 9756891 . 10.1074/jbc.273.41.26543 . free .
• Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B . The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins . J. Biol. Chem. . 273 . 42 . 27459–66 . 1998 . 9765275 . 10.1074/jbc.273.42.27459 . free .
• Schürmann A, Schmidt M, Asmus M, Bayer S, Fliegert F, Koling S, Massmann S, Schilf C, Subauste MC, Voss M, Jakobs KH, Joost HG . The ADP-ribosylation factor (ARF)-related GTPase ARF-related protein binds to the ARF-specific guanine nucleotide exchange factor cytohesin and inhibits the ARF-dependent activation of phospholipase D . J. Biol. Chem. . 274 . 14 . 9744–51 . 1999 . 10092663 . 10.1074/jbc.274.14.9744 . free .
• Pacheco-Rodriguez G, Patton WA, Adamik R, Yoo HS, Lee FJ, Zhang GF, Moss J, Vaughan M . Structural elements of ADP-ribosylation factor 1 required for functional interaction with cytohesin-1 . J. Biol. Chem. . 274 . 18 . 12438–44 . 1999 . 10212218 . 10.1074/jbc.274.18.12438 . free .
• Venkateswarlu K, Gunn-Moore F, Tavaré JM, Cullen PJ . EGF-and NGF-stimulated translocation of cytohesin-1 to the plasma membrane of PC12 cells requires PI 3-kinase activation and a functional cytohesin-1 PH domain . J. Cell Sci. . 112 (Pt 12) . 12 . 1957–65 . 1999 . 10.1242/jcs.112.12.1957 . 10341214 .
• Ogasawara M, Kim SC, Adamik R, Togawa A, Ferrans VJ, Takeda K, Kirby M, Moss J, Vaughan M . Similarities in function and gene structure of cytohesin-4 and cytohesin-1, guanine nucleotide-exchange proteins for ADP-ribosylation factors . J. Biol. Chem. . 275 . 5 . 3221–30 . 2000 . 10652308 . 10.1074/jbc.275.5.3221 . free .
• Vitale N, Pacheco-Rodriguez G, Ferrans VJ, Riemenschneider W, Moss J, Vaughan M . Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1) . J. Biol. Chem. . 275 . 28 . 21331–9 . 2000 . 10748148 . 10.1074/jbc.M909642199 . free .
• Lee SY, Mansour M, Pohajdak B . B2-1, a Sec7- and pleckstrin homology domain-containing protein, localizes to the Golgi complex . Exp. Cell Res. . 256 . 2 . 515–21 . 2000 . 10772823 . 10.1006/excr.2000.4845 .
• Geiger C, Nagel W, Boehm T, van Kooyk Y, Figdor CG, Kremmer E, Hogg N, Zeitlmann L, Dierks H, Weber KS, Kolanus W . Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1 . EMBO J. . 19 . 11 . 2525–36 . 2000 . 10835351 . 212768 . 10.1093/emboj/19.11.2525 .
• Dierks H, Kolanus J, Kolanus W . Actin cytoskeletal association of cytohesin-1 is regulated by specific phosphorylation of its carboxyl-terminal polybasic domain . J. Biol. Chem. . 276 . 40 . 37472–81 . 2001 . 11438522 . 10.1074/jbc.M101502200 . free .
• Tang P, Cheng TP, Agnello D, Wu CY, Hissong BD, Watford WT, Ahn HJ, Galon J, Moss J, Vaughan M, O'Shea JJ, Gadina M . Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates its activity . Proc. Natl. Acad. Sci. U.S.A. . 99 . 5 . 2625–9 . 2002 . 11867758 . 122398 . 10.1073/pnas.052712999 . 2002PNAS...99.2625T . free .

Notes and References

1. Liu L, Pohajdak B . Cloning and sequencing of a human cDNA from cytolytic NK/T cells with homology to yeast SEC7 . Biochim. Biophys. Acta . 1132 . 1 . 75–8 . September 1992 . 1511013 . 10.1016/0167-4781(92)90055-5 .
2. Dixon B, Mansour M, Pohajdak B . Assignment of human B2-1 gene (D17S811E) to chromosome 17qter by PCR analysis of somatic cell hybrids and fluorescence in situ hybridization . Cytogenet. Cell Genet. . 63 . 1 . 42–4 . April 1993 . 8449036 . 10.1159/000133498 .
3. Web site: Entrez Gene: PSCD1 pleckstrin homology, Sec7 and coiled-coil domains 1(cytohesin 1).
4. Schürmann A, Schmidt M, Asmus M, Bayer S, Fliegert F, Koling S, Massmann S, Schilf C, Subauste MC, Voss M, Jakobs KH, Joost HG . The ADP-ribosylation factor (ARF)-related GTPase ARF-related protein binds to the ARF-specific guanine nucleotide exchange factor cytohesin and inhibits the ARF-dependent activation of phospholipase D . J. Biol. Chem. . 274 . 14 . 9744–51 . April 1999 . 10092663 . 10.1074/jbc.274.14.9744 . free .
5. Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B . The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins . J. Biol. Chem. . 273 . 42 . 27459–66 . October 1998 . 9765275 . 10.1074/jbc.273.42.27459 . free .
6. Geiger C, Nagel W, Boehm T, van Kooyk Y, Figdor CG, Kremmer E, Hogg N, Zeitlmann L, Dierks H, Weber KS, Kolanus W . Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1 . EMBO J. . 19 . 11 . 2525–36 . June 2000 . 10835351 . 212768 . 10.1093/emboj/19.11.2525 .
7. Vitale N, Pacheco-Rodriguez G, Ferrans VJ, Riemenschneider W, Moss J, Vaughan M . Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1) . J. Biol. Chem. . 275 . 28 . 21331–9 . July 2000 . 10748148 . 10.1074/jbc.M909642199 . free .