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Neural precursor cell expressed, developmentally down-regulated 9
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols NEDD9 ; CAS-L; CAS2; CASL; CASS2; HEF1
External IDs OMIM602265 MGI97302 HomoloGene4669 GeneCards: NEDD9 Gene
RNA expression pattern
PBB GE NEDD9 202149 at tn.png
PBB GE NEDD9 202150 s at tn.png
More reference expression data
Species Human Mouse
Entrez 4739 18003
Ensembl ENSG00000111859 ENSMUSG00000021365
UniProt Q14511 O35177
RefSeq (mRNA) NM_001142393 NM_001111324
RefSeq (protein) NP_001135865 NP_001104794
Location (UCSC) Chr 6:
11.18 – 11.38 Mb
Chr 13:
41.31 – 41.49 Mb
PubMed search [1] [2]

Enhancer of filamentation 1 is a protein that in humans is encoded by the NEDD9 gene.[1] Synonyms are CASL, HEF1, p105CAS. It is a member of the CAS (Crk-associated substrates) family. It is organized into domains, from N to C terminus: SH3 domain, SH2-binding substrate domain (which when phosphorylated binds SH2 domains), serine-rich domain, SBD (putative Src-binding domain), and a C-terminal domain that binds GEF (GDP-exchange factor) proteins of the NSP (Novel SH2 domain containing Protein) family such as BCAR3.[2] It is believed that when tyrosine in the SBD is phosphorylated by FAK, it binds to the inhibitory domain of c-Src which is thus activated and phosphorylates tyrosines in the substrate domain of NEDD9, creating a binding site for c-Crk and activating pathways leading the cells to survival, proliferation, motility,and invasion (promoting growth and metastasis).[3]


NEDD9 has been shown to interact with ID2,[4] LYN,[5] NCK1,[6] MICAL1,[7] CDH1,[8] Abl gene,[6][9] PTK2,[9] CRKL,[5][10][11][12] CRK[6][13] and Mothers against decapentaplegic homolog 3.[8][14][15]


  1. ^ "Entrez Gene: NEDD9 neural precursor cell expressed, developmentally down-regulated 9". 
  2. ^ Garron, Marie-Line (2009), "Structural Insights into the Association between BCAR3 and Cas Family Members, an Atypical Complex Implicated in Anti-Oestrogen Resistance", Journal of Molecular Biology 386 (1): 190–203, doi:10.1016/j.jmb.2008.12.010 
  3. ^ , PMID 19738060  Missing or empty |title= (help)
  4. ^ Law, S F; Zhang Y Z; Fashena S J; Toby G; Estojak J; Golemis E A (October 1999). "Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain". Exp. Cell Res. (UNITED STATES) 252 (1): 224–35. doi:10.1006/excr.1999.4609. ISSN 0014-4827. PMID 10502414. 
  5. ^ a b Manié, S N; Beck A R, Astier A, Law S F, Canty T, Hirai H, Druker B J, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin J D, Golemis E A, Freedman A S (February 1997). "Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells". J. Biol. Chem. (UNITED STATES) 272 (7): 4230–6. doi:10.1074/jbc.272.7.4230. ISSN 0021-9258. PMID 9020138. 
  6. ^ a b c Minegishi, M; Tachibana K; Sato T; Iwata S; Nojima Y; Morimoto C (October 1996). "Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes". J. Exp. Med. (UNITED STATES) 184 (4): 1365–75. doi:10.1084/jem.184.4.1365. ISSN 0022-1007. PMC 2192828. PMID 8879209. 
  7. ^ Suzuki, Takahiro; Nakamoto Tetsuya; Ogawa Seishi; Seo Sachiko; Matsumura Tomoko; Tachibana Kouichi; Morimoto Chikao; Hirai Hisamaru (April 2002). "MICAL, a novel CasL interacting molecule, associates with vimentin". J. Biol. Chem. (United States) 277 (17): 14933–41. doi:10.1074/jbc.M111842200. ISSN 0021-9258. PMID 11827972. 
  8. ^ a b Nourry, Claire; Maksumova Lola; Pang Mona; Liu Xiaohong; Wang Tongwen (May 2004). "Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation of HEF1". BMC Cell Biol. (England) 5 (1): 20. doi:10.1186/1471-2121-5-20. PMC 420458. PMID 15144564. 
  9. ^ a b Law, S F; Estojak J; Wang B; Mysliwiec T; Kruh G; Golemis E A (July 1996). "Human enhancer of filamentation 1, a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae". Mol. Cell. Biol. (UNITED STATES) 16 (7): 3327–37. ISSN 0270-7306. PMC 231327. PMID 8668148. 
  10. ^ Kyono, W T; de Jong R; Park R K; Liu Y; Heisterkamp N; Groffen J; Durden D L (November 1998). "Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI)". J. Immunol. (UNITED STATES) 161 (10): 5555–63. ISSN 0022-1767. PMID 9820532. 
  11. ^ Astier, A; Manié S N; Law S F; Canty T; Haghayghi N; Druker B J; Salgia R; Golemis E A; Freedman A S (December 1997). "Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells". Leuk. Lymphoma (SWITZERLAND) 28 (1–2): 65–72. doi:10.3109/10428199709058332. ISSN 1042-8194. PMID 9498705. 
  12. ^ Sattler, M; Salgia R; Shrikhande G; Verma S; Uemura N; Law S F; Golemis E A; Griffin J D (May 1997). "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". J. Biol. Chem. (UNITED STATES) 272 (22): 14320–6. doi:10.1074/jbc.272.22.14320. ISSN 0021-9258. PMID 9162067. 
  13. ^ Ohashi, Y; Tachibana K; Kamiguchi K; Fujita H; Morimoto C (March 1998). "T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G". J. Biol. Chem. (UNITED STATES) 273 (11): 6446–51. doi:10.1074/jbc.273.11.6446. ISSN 0021-9258. PMID 9497377. 
  14. ^ Feng, Libing; Guedes Susana; Wang Tongwen (July 2004). "Atrophin-1-interacting protein 4/human Itch is a ubiquitin E3 ligase for human enhancer of filamentation 1 in transforming growth factor-beta signaling pathways". J. Biol. Chem. (United States) 279 (28): 29681–90. doi:10.1074/jbc.M403221200. ISSN 0021-9258. PMID 15051726. 
  15. ^ Liu, X; Elia A E; Law S F; Golemis E A; Farley J; Wang T (December 2000). "A novel ability of Smad3 to regulate proteasomal degradation of a Cas family member HEF1". EMBO J. (ENGLAND) 19 (24): 6759–69. doi:10.1093/emboj/19.24.6759. ISSN 0261-4189. PMC 305889. PMID 11118211. 

Further reading[edit]