DDEF2 explained

Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 is a protein that in humans is encoded by the ASAP2 gene.^{[1] [2]}

This gene encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. The protein localizes in the Golgi apparatus and at the plasma membrane, where it colocalizes with protein tyrosine kinase 2-beta (PYK2). The encoded protein forms a stable complex with PYK2 in vivo. This interaction appears to be mediated by binding of its SH3 domain to the C-terminal proline-rich domain of PYK2. The encoded protein is tyrosine phosphorylated by activated PYK2. In vitro it shows strong GTPase-activating protein (GAP) activity towards the small GTPases ADP-ribosylation factor (ARF) 1 and ARF5 and weak activity towards ARF6. The encoded protein is believed to function as an ARF GAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport.^[3]

Interactions

DDEF2 has been shown to interact with PTK2B.^[4]

Further reading

• Brown MT, Andrade J, Radhakrishna H . ASAP1, a Phospholipid-Dependent Arf GTPase-Activating Protein That Associates with and Is Phosphorylated by Src . Mol. Cell. Biol. . 18 . 12 . 7038–51 . 1998 . 9819391 . 10.1128/MCB.18.12.7038. 109286 . etal.
• Kondo A, Hashimoto S, Yano H . A New Paxillin-binding Protein, PAG3/Papα/KIAA0400, Bearing an ADP-Ribosylation Factor GTPase-activating Protein Activity, Is Involved in Paxillin Recruitment to Focal Adhesions and Cell Migration . Mol. Biol. Cell . 11 . 4 . 1315–27 . 2000 . 10749932 . 10.1091/mbc.11.4.1315. 14849 . etal.
• Uchida H, Kondo A, Yoshimura Y . Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages . J. Exp. Med. . 193 . 8 . 955–66 . 2001 . 11304556 . 10.1084/jem.193.8.955 . 2193405 . etal.
• Kim H, Lee Y . Interaction of poly(A) polymerase with the 25-kDa subunit of cleavage factor I . Biochem. Biophys. Res. Commun. . 289 . 2 . 513–8 . 2002 . 11716503 . 10.1006/bbrc.2001.5992 .
• Oshiro T, Koyama S, Sugiyama S . Interaction of POB1, a downstream molecule of small G protein Ral, with PAG2, a paxillin-binding protein, is involved in cell migration . J. Biol. Chem. . 277 . 41 . 38618–26 . 2002 . 12149250 . 10.1074/jbc.M203453200 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . etal. 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Hashimoto S, Hashimoto A, Yamada A . A novel mode of action of an ArfGAP, AMAP2/PAG3/Papa lpha, in Arf6 function . J. Biol. Chem. . 279 . 36 . 37677–84 . 2004 . 15231847 . 10.1074/jbc.M404196200 . etal. free .
• Kojima C, Hashimoto A, Yabuta I . Regulation of Bin1 SH3 domain binding by phosphoinositides . EMBO J. . 23 . 22 . 4413–22 . 2005 . 15483625 . 10.1038/sj.emboj.7600442 . 526460 . etal.
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Onodera Y, Hashimoto S, Hashimoto A . Expression of AMAP1, an ArfGAP, provides novel targets to inhibit breast cancer invasive activities . EMBO J. . 24 . 5 . 963–73 . 2005 . 15719014 . 10.1038/sj.emboj.7600588 . 554134 . etal.
• Olsen JV, Blagoev B, Gnad F . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . etal. free .
• Ewing RM, Chu P, Elisma F . Large-scale mapping of human protein–protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 . etal.

Notes and References

1. Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J . Identification of a New Pyk2 Target Protein with Arf-GAP Activity . Mol Cell Biol . 19 . 3 . 2338–50 . Mar 1999 . 10022920 . 84026 . 10.1128/MCB.19.3.2338.
2. Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro . DNA Res . 4 . 5 . 307–13 . Feb 1998 . 9455477 . 10.1093/dnares/4.5.307 . free .
3. Web site: Entrez Gene: DDEF2 development and differentiation enhancing factor 2.
4. Andreev . J . Simon J P . Sabatini D D . Kam J . Plowman G . Randazzo P A . Schlessinger J . Mar 1999 . Identification of a New Pyk2 Target Protein with Arf-GAP Activity . Mol. Cell. Biol. . 19 . 3 . 2338–50 . 0270-7306. 10022920 . 84026 . 10.1128/MCB.19.3.2338 .