ID CASL_HUMAN Reviewed; 834 AA. AC Q14511; A8K9G7; A8MSJ9; G5E9Y9; Q5T9R4; Q5XKI0; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 227. DE RecName: Full=Enhancer of filamentation 1 {ECO:0000303|PubMed:9584194}; DE Short=hEF1 {ECO:0000303|PubMed:9584194}; DE AltName: Full=CRK-associated substrate-related protein {ECO:0000303|PubMed:9497377}; DE Short=CAS-L {ECO:0000303|PubMed:9497377}; DE Short=CasL {ECO:0000303|PubMed:11827972}; DE AltName: Full=Cas scaffolding protein family member 2 {ECO:0000312|HGNC:HGNC:7733}; DE Short=CASS2 {ECO:0000312|HGNC:HGNC:7733}; DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 9 {ECO:0000312|HGNC:HGNC:7733}; DE Short=NEDD-9 {ECO:0000312|HGNC:HGNC:7733}; DE AltName: Full=Renal carcinoma antigen NY-REN-12 {ECO:0000303|PubMed:10508479}; DE AltName: Full=p105 {ECO:0000303|PubMed:8879209}; DE Contains: DE RecName: Full=Enhancer of filamentation 1 p55; GN Name=NEDD9 {ECO:0000312|HGNC:HGNC:7733}; GN Synonyms=CASL {ECO:0000303|PubMed:11827972}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PTK2, SUBCELLULAR RP LOCATION, AND DOMAIN. RC TISSUE=Placenta; RX PubMed=8668148; DOI=10.1128/mcb.16.7.3327; RA Law S.F., Estojak J., Wang B., Mysliwiec T., Kruh G., Golemis E.A.; RT "Human enhancer of filamentation 1, a novel p130cas-like docking protein, RT associates with focal adhesion kinase and induces pseudohyphal growth in RT Saccharomyces cerevisiae."; RL Mol. Cell. Biol. 16:3327-3337(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH PTK2. RC TISSUE=Lymphoma; RX PubMed=8879209; DOI=10.1084/jem.184.4.1365; RA Minegishi M., Tachibana K., Sato T., Iwata S., Nojima Y., Morimoto C.; RT "Structure and function of Cas-L, a 105-kD Crk-associated substrate-related RT protein that is involved in beta 1 integrin-mediated signaling in RT lymphocytes."; RL J. Exp. Med. 184:1365-1375(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, INTERACTION WITH CRKL AND PTK2B, TISSUE SPECIFICITY, RP PHOSPHORYLATION, INCREASED TYROSINE PHOSPHORYLATION BY LIGATION OF RP INTEGRIN-B1 AND BCR, AND DOMAIN. RX PubMed=9020138; DOI=10.1074/jbc.272.7.4230; RA Manie S.N., Beck A.R.P., Astier A., Law S.F., Canty T., Hirai H., RA Druker B.J., Avraham H., Haghayeghi N., Sattler M., Salgia R., RA Griffin J.D., Golemis E.A., Freedman A.S.; RT "Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, RT in a cytoskeleton-dependent signaling pathway initiated by ligation of RT integrin or antigen receptor on human B cells."; RL J. Biol. Chem. 272:4230-4236(1997). RN [8] RP INTERACTION WITH PTK2; LYN AND FYN, AND PHOSPHORYLATION AT TYROSINE RP RESIDUES BY PTK2. RX PubMed=9360983; DOI=10.1074/jbc.272.46.29083; RA Tachibana K., Urano T., Fujita H., Ohashi Y., Kamiguchi K., Iwata S., RA Hirai H., Morimoto C.; RT "Tyrosine phosphorylation of Crk-associated substrates by focal adhesion RT kinase. A putative mechanism for the integrin-mediated tyrosine RT phosphorylation of Crk-associated substrates."; RL J. Biol. Chem. 272:29083-29090(1997). RN [9] RP SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND RP PROTEOLYTIC PROCESSING. RX PubMed=9584194; DOI=10.1128/mcb.18.6.3540; RA Law S.F., Zhang Y.-Z., Klein-Szanto A.J.P., Golemis E.A.; RT "Cell cycle-regulated processing of HEF1 to multiple protein forms RT differentially targeted to multiple subcellular compartments."; RL Mol. Cell. Biol. 18:3540-3551(1998). RN [10] RP TISSUE SPECIFICITY, AND PHOSPHORYLATION AT TYROSINE RESIDUES UPON CD3 RP CROSS-LINKING. RX PubMed=9497377; DOI=10.1074/jbc.273.11.6446; RA Ohashi Y., Tachibana K., Kamiguchi K., Fujita H., Morimoto C.; RT "T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk- RT associated substrate-related protein, and its association of Crk and C3G."; RL J. Biol. Chem. 273:6446-6451(1998). RN [11] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [12] RP SUBUNIT, INTERACTION WITH BCAR1 AND ID2, AND CHARACTERIZATION OF RP CARBOXY-TERMINAL DOMAIN. RX PubMed=10502414; DOI=10.1006/excr.1999.4609; RA Law S.F., Zhang Y.-Z., Fashena S.J., Toby G., Estojak J., Golemis E.A.; RT "Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal RT helix-loop-helix domain."; RL Exp. Cell Res. 252:224-235(1999). RN [13] RP INTERACTION WITH TXNL4. RX PubMed=11054566; DOI=10.1016/s0378-1119(00)00372-3; RA Zhang Y.-Z., Lindblom T., Chang A., Sudol M., Sluder A.E., Golemis E.A.; RT "Evidence that Dim1 associates with proteins involved in pre-mRNA splicing, RT and delineation of residues essential for Dim1 interactions with hnRNP F RT and Npw38/PQBP-1."; RL Gene 257:33-43(2000). RN [14] RP INTERACTION WITH MICAL, AND SUBCELLULAR LOCATION. RX PubMed=11827972; DOI=10.1074/jbc.m111842200; RA Suzuki T., Nakamoto T., Ogawa S., Seo S., Matsumura T., Tachibana K., RA Morimoto C., Hirai H.; RT "MICAL, a novel CasL interacting molecule, associates with vimentin."; RL J. Biol. Chem. 277:14933-14941(2002). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=12522270; DOI=10.1073/pnas.2436191100; RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., RA Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.; RT "Profiling of tyrosine phosphorylation pathways in human cells using mass RT spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [17] RP IDENTIFICATION IN A COMPLEX WITH SMAD3 AND ITCH, INTERACTION WITH SMAD3 AND RP ITCH, AND UBIQUITINATION. RX PubMed=15051726; DOI=10.1074/jbc.m403221200; RA Feng L., Guedes S., Wang T.; RT "Atrophin-1-interacting protein 4/human Itch is a ubiquitin E3 ligase for RT human enhancer of filamentation 1 in transforming growth factor-beta RT signaling pathways."; RL J. Biol. Chem. 279:29681-29690(2004). RN [18] RP FUNCTION. RX PubMed=17174122; DOI=10.1016/j.immuni.2006.09.014; RA Regelmann A.G., Danzl N.M., Wanjalla C., Alexandropoulos K.; RT "The hematopoietic isoform of Cas-Hef1-associated signal transducer RT regulates chemokine-induced inside-out signaling and T cell trafficking."; RL Immunity 25:907-918(2006). RN [19] RP INTERACTION WITH ECT2, AND SUBCELLULAR LOCATION. RX PubMed=16394104; DOI=10.1091/mbc.e05-03-0237; RA Dadke D., Jarnik M., Pugacheva E.N., Singh M.K., Golemis E.A.; RT "Deregulation of HEF1 impairs M-phase progression by disrupting the RhoA RT activation cycle."; RL Mol. Biol. Cell 17:1204-1217(2006). RN [20] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17604723; DOI=10.1016/j.cell.2007.04.035; RA Pugacheva E.N., Jablonski S.A., Hartman T.R., Henske E.P., Golemis E.A.; RT "HEF1-dependent Aurora A activation induces disassembly of the primary RT cilium."; RL Cell 129:1351-1363(2007). RN [21] RP INTERACTION WITH PTPN11, AND SUBCELLULAR LOCATION. RX PubMed=19275884; DOI=10.1016/j.bbrc.2009.03.010; RA Yo K., Iwata S., Hashizume Y., Kondo S., Nomura S., Hosono O., Kawasaki H., RA Tanaka H., Dang N.H., Morimoto C.; RT "SHP-2 inhibits tyrosine phosphorylation of Cas-L and regulates cell RT migration."; RL Biochem. Biophys. Res. Commun. 382:210-214(2009). RN [22] RP PHOSPHORYLATION AT SER-296 AND SER-369. RX PubMed=19539609; DOI=10.1016/j.bcp.2009.06.005; RA Hivert V., Pierre J., Raingeaud J.; RT "Phosphorylation of human enhancer of filamentation (HEF1) on serine 369 RT induces its proteasomal degradation."; RL Biochem. Pharmacol. 78:1017-1025(2009). RN [23] RP INTERACTION WITH BCAR3, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-751; RP HIS-754; PHE-758 AND MET-796. RX PubMed=19103205; DOI=10.1016/j.jmb.2008.12.010; RA Garron M.L., Arsenieva D., Zhong J., Bloom A.B., Lerner A., O'Neill G.M., RA Arold S.T.; RT "Structural insights into the association between BCAR3 and Cas family RT members, an atypical complex implicated in anti-oestrogen resistance."; RL J. Mol. Biol. 386:190-203(2009). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [25] RP INTERACTION WITH ABL1, AND PHOSPHORYLATION AT TYR-92; TYR-164; TYR-166; RP TYR-177; TYR-189; TYR-214; TYR-223; TYR-279 AND TYR-317. RX PubMed=22810897; DOI=10.1126/scisignal.2002632; RA Gu J.J., Lavau C.P., Pugacheva E., Soderblom E.J., Moseley M.A., RA Pendergast A.M.; RT "Abl family kinases modulate T cell-mediated inflammation and chemokine- RT induced migration through the adaptor HEF1 and the GTPase Rap1."; RL Sci. Signal. 5:ra51-ra51(2012). RN [26] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH CTTN AND AURKA, AND INTERACTION RP WITH CTTN. RX PubMed=24574519; DOI=10.1158/1541-7786.mcr-13-0654; RA Kozyreva V.K., McLaughlin S.L., Livengood R.H., Calkins R.A., Kelley L.C., RA Rajulapati A., Ice R.J., Smolkin M.B., Weed S.A., Pugacheva E.N.; RT "NEDD9 regulates actin dynamics through cortactin deacetylation in an RT AURKA/HDAC6-dependent manner."; RL Mol. Cancer Res. 12:681-693(2014). RN [27] RP INTERACTION WITH SMAD3 AND NKX2-5, SUBCELLULAR LOCATION, INDUCTION BY RP OXIDANT STRESS, AND MUTAGENESIS OF CYS-18. RX PubMed=29899023; DOI=10.1126/scitranslmed.aap7294; RA Samokhin A.O., Stephens T., Wertheim B.M., Wang R.S., Vargas S.O., RA Yung L.M., Cao M., Brown M., Arons E., Dieffenbach P.B., Fewell J.G., RA Matar M., Bowman F.P., Haley K.J., Alba G.A., Marino S.M., Kumar R., RA Rosas I.O., Waxman A.B., Oldham W.M., Khanna D., Graham B.B., Seo S., RA Gladyshev V.N., Yu P.B., Fredenburgh L.E., Loscalzo J., Leopold J.A., RA Maron B.A.; RT "NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary RT arterial hypertension."; RL Sci. Transl. Med. 10:0-0(2018). RN [28] RP STRUCTURE BY NMR OF 399-563. RG Northeast structural genomics consortium (NESG); RT "Northeast structural genomics consortium target HR5554A."; RL Submitted (FEB-2011) to the PDB data bank. RN [29] {ECO:0007744|PDB:5X3S} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 799-809 IN COMPLEX WITH PLK1, RP INTERACTION WITH PLK1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-780 AND RP THR-804, AND MUTAGENESIS OF SER-735; SER-780 AND THR-804. RX PubMed=29191835; DOI=10.1074/jbc.m117.802587; RA Lee K.H., Hwang J.A., Kim S.O., Kim J.H., Shin S.C., Kim E.E., Lee K.S., RA Rhee K., Jeon B.H., Bang J.K., Cha-Molstad H., Soung N.K., Jang J.H., RA Ko S.K., Lee H.G., Ahn J.S., Kwon Y.T., Kim B.Y.; RT "Phosphorylation of human enhancer filamentation 1 (HEF1) stimulates RT interaction with Polo-like kinase 1 leading to HEF1 localization to focal RT adhesions."; RL J. Biol. Chem. 293:847-862(2018). CC -!- FUNCTION: Scaffolding protein which plays a central coordinating role CC for tyrosine-kinase-based signaling related to cell adhesion CC (PubMed:24574519). As a focal adhesion protein, plays a role in CC embryonic fibroblast migration (By similarity). May play an important CC role in integrin beta-1 or B cell antigen receptor (BCR) mediated CC signaling in B- and T-cells. Integrin beta-1 stimulation leads to CC recruitment of various proteins including CRKL and SHPTP2 to the CC tyrosine phosphorylated form (PubMed:9020138). Promotes adhesion and CC migration of lymphocytes; as a result required for the correct CC migration of lymphocytes to the spleen and other secondary lymphoid CC organs (PubMed:17174122). Plays a role in the organization of T-cell F- CC actin cortical cytoskeleton and the centralization of T-cell receptor CC microclusters at the immunological synapse (By similarity). Negatively CC regulates cilia outgrowth in polarized cysts (By similarity). Modulates CC cilia disassembly via activation of AURKA-mediated phosphorylation of CC HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723). CC Positively regulates RANKL-induced osteoclastogenesis (By similarity). CC Required for the maintenance of hippocampal dendritic spines in the CC dentate gyrus and CA1 regions, thereby involved in spatial learning and CC memory (By similarity). {ECO:0000250|UniProtKB:A0A8I3PDQ1, CC ECO:0000250|UniProtKB:O35177, ECO:0000269|PubMed:17174122, CC ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:24574519, CC ECO:0000269|PubMed:9020138}. CC -!- SUBUNIT: Homodimer (PubMed:9584194, PubMed:10502414). Forms CC heterodimers with BCAR1/p130cas (PubMed:10502414). Forms complexes with CC PTK2B/RAFTK, adapter protein CRKL and LYN kinase (PubMed:9020138). Part CC of a complex composed of NEDD9, AURKA and CTTN; within the complex CC NEDD9 acts as a scaffold protein and is required for complex formation CC (PubMed:24574519). Part of a ternary complex composed of SMAD3, CC ITCH/AIP4 and NEDD9/HEF1; within the complex NEDD9/HEF1 interacts (via CC N-terminus) with ITCH/AIP4 (via WW domains); the complex mediates CC ubiquitination and proteasomal degradation of NEDD9/HEF1 CC (PubMed:15051726). Interacts with SMAD3; the interaction promotes NEDD9 CC ubiquitination and proteasomal degradation (PubMed:24574519). Interacts CC with ID2 (PubMed:10502414). Interacts with CTTN (via N-terminus) CC (PubMed:24574519). Interacts with MICAL (PubMed:11827972). Interacts CC with TXNL4/DIM1 (PubMed:11054566). Interacts with BCAR3 (via Ras-GEF CC domain) (PubMed:19103205). Interacts with SH2D3C isoform 1 and isoform CC 2 (By similarity). Interacts with ECT2 (PubMed:16394104). Interacts CC with PTPN11/SHP-2 (via SH2 domains); the interaction is enhanced when CC NEDD9/CAS-L is tyrosine phosphorylated (PubMed:19275884). Interacts CC (via C-terminus) with PLK1 (via polo box domains) (PubMed:29191835). CC Interacts with NKX2-5 (PubMed:29899023). Interacts with SMAD3; the CC interaction is inhibited by oxidation of NEDD9 (PubMed:15051726, CC PubMed:29899023). Interacts with NEDD9/HEF1; interaction is induced by CC CXCL12 promotion of ABL-mediated phosphorylation of NEDD9/HEF1 CC (PubMed:22810897). Interacts (via SH3 domain) with PTK2/FAK CC (PubMed:8668148, PubMed:8879209, PubMed:9360983). Interacts with FYN; CC in the presence of PTK2 (PubMed:9360983). Interacts with INPPL1/SHIP2 CC (By similarity). {ECO:0000250|UniProtKB:A0A8I3PDQ1, CC ECO:0000250|UniProtKB:O35177, ECO:0000269|PubMed:10502414, CC ECO:0000269|PubMed:11054566, ECO:0000269|PubMed:11827972, CC ECO:0000269|PubMed:15051726, ECO:0000269|PubMed:16394104, CC ECO:0000269|PubMed:19103205, ECO:0000269|PubMed:19275884, CC ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:24574519, CC ECO:0000269|PubMed:29191835, ECO:0000269|PubMed:29899023, CC ECO:0000269|PubMed:8668148, ECO:0000269|PubMed:8879209, CC ECO:0000269|PubMed:9020138, ECO:0000269|PubMed:9360983, CC ECO:0000269|PubMed:9584194}. CC -!- INTERACTION: CC Q14511; Q8N9N5: BANP; NbExp=4; IntAct=EBI-2108053, EBI-744695; CC Q14511; O75815: BCAR3; NbExp=4; IntAct=EBI-2108053, EBI-702336; CC Q14511; Q15742: NAB2; NbExp=4; IntAct=EBI-2108053, EBI-8641936; CC Q14511; P25963: NFKBIA; NbExp=3; IntAct=EBI-2108053, EBI-307386; CC Q14511; P86479: PRR20C; NbExp=3; IntAct=EBI-2108053, EBI-10172814; CC Q14511; Q93062: RBPMS; NbExp=3; IntAct=EBI-2108053, EBI-740322; CC Q14511; Q04864: REL; NbExp=3; IntAct=EBI-2108053, EBI-307352; CC Q14511; Q8HWS3: RFX6; NbExp=3; IntAct=EBI-2108053, EBI-746118; CC Q14511; P14373: TRIM27; NbExp=4; IntAct=EBI-2108053, EBI-719493; CC Q14511; Q15654: TRIP6; NbExp=3; IntAct=EBI-2108053, EBI-742327; CC Q14511-2; Q5BKX5-3: ACTMAP; NbExp=3; IntAct=EBI-11746523, EBI-11976299; CC Q14511-2; Q49AR9: ANKS1A; NbExp=6; IntAct=EBI-11746523, EBI-11954519; CC Q14511-2; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-11746523, EBI-11524452; CC Q14511-2; O14613: CDC42EP2; NbExp=3; IntAct=EBI-11746523, EBI-3438291; CC Q14511-2; Q7L190: DPPA4; NbExp=3; IntAct=EBI-11746523, EBI-710457; CC Q14511-2; Q5T9C2-3: EEIG1; NbExp=3; IntAct=EBI-11746523, EBI-11980989; CC Q14511-2; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-11746523, EBI-371922; CC Q14511-2; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-11746523, EBI-12193763; CC Q14511-2; P53539: FOSB; NbExp=3; IntAct=EBI-11746523, EBI-2806743; CC Q14511-2; P49639: HOXA1; NbExp=3; IntAct=EBI-11746523, EBI-740785; CC Q14511-2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-11746523, EBI-6509505; CC Q14511-2; Q9BS75: KLHL20; NbExp=3; IntAct=EBI-11746523, EBI-10693436; CC Q14511-2; Q14532: KRT32; NbExp=3; IntAct=EBI-11746523, EBI-1044146; CC Q14511-2; Q68G74: LHX8; NbExp=3; IntAct=EBI-11746523, EBI-8474075; CC Q14511-2; A0JLT2-2: MED19; NbExp=3; IntAct=EBI-11746523, EBI-13288755; CC Q14511-2; Q15742: NAB2; NbExp=3; IntAct=EBI-11746523, EBI-8641936; CC Q14511-2; P25963: NFKBIA; NbExp=3; IntAct=EBI-11746523, EBI-307386; CC Q14511-2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-11746523, EBI-22310682; CC Q14511-2; Q92569: PIK3R3; NbExp=3; IntAct=EBI-11746523, EBI-79893; CC Q14511-2; Q96QH2: PRAM1; NbExp=4; IntAct=EBI-11746523, EBI-2860740; CC Q14511-2; Q8HWS3: RFX6; NbExp=3; IntAct=EBI-11746523, EBI-746118; CC Q14511-2; O60806: TBX19; NbExp=3; IntAct=EBI-11746523, EBI-12096770; CC Q14511-2; Q12933: TRAF2; NbExp=3; IntAct=EBI-11746523, EBI-355744; CC Q14511-2; P36406: TRIM23; NbExp=3; IntAct=EBI-11746523, EBI-740098; CC Q14511-2; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-11746523, EBI-12040603; CC Q14511-2; P36508: ZNF76; NbExp=3; IntAct=EBI-11746523, EBI-7254550; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex CC {ECO:0000269|PubMed:11827972}. Nucleus {ECO:0000269|PubMed:29899023, CC ECO:0000269|PubMed:8668148, ECO:0000269|PubMed:9584194}. Golgi CC apparatus {ECO:0000269|PubMed:8668148}. Cell projection, lamellipodium CC {ECO:0000269|PubMed:24574519, ECO:0000269|PubMed:8668148}. Cytoplasm CC {ECO:0000269|PubMed:11827972, ECO:0000269|PubMed:9584194}. Cell CC junction, focal adhesion {ECO:0000269|PubMed:19103205, CC ECO:0000269|PubMed:19275884, ECO:0000269|PubMed:29191835, CC ECO:0000269|PubMed:8668148}. Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:11827972}. Cytoplasm, cytoskeleton, spindle pole CC {ECO:0000269|PubMed:16394104, ECO:0000269|PubMed:9584194}. Cell CC projection, cilium {ECO:0000269|PubMed:17604723}. Cytoplasm, CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:17604723}. CC Basolateral cell membrane {ECO:0000250|UniProtKB:A0A8I3PDQ1}. CC -!- SUBCELLULAR LOCATION: [Enhancer of filamentation 1 p55]: Cytoplasm, CC cytoskeleton, spindle {ECO:0000269|PubMed:9584194}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q14511-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14511-2; Sequence=VSP_042835, VSP_042836; CC Name=3; CC IsoId=Q14511-3; Sequence=VSP_044579; CC -!- TISSUE SPECIFICITY: Expressed in B-cells (at protein level) CC (PubMed:9020138). Expressed in the respiratory epithelium of the main CC bronchi to the bronchioles in the lungs (at protein level) CC (PubMed:9584194). High levels detected in kidney, lung, and placenta CC (PubMed:9584194). Expressed in lymphocytes (PubMed:9497377). CC {ECO:0000269|PubMed:9020138, ECO:0000269|PubMed:9497377, CC ECO:0000269|PubMed:9584194}. CC -!- DEVELOPMENTAL STAGE: initially expressed in the fetus (at protein CC level). {ECO:0000269|PubMed:9584194}. CC -!- INDUCTION: Induced by oxidant stress in pulmonary artery endothelial CC cells. {ECO:0000269|PubMed:29899023}. CC -!- DOMAIN: Contains a central domain containing multiple potential SH2- CC binding sites and a C-terminal domain containing a divergent helix- CC loop-helix (HLH) motif (PubMed:10502414). The SH2-binding sites CC putatively bind CRKL SH2 domains (PubMed:9020138). The HLH motif CC confers specific interaction with the HLH protein ID2 CC (PubMed:10502414). It is absolutely required for the induction of CC pseudohyphal growth in yeast and mediates homodimerization and CC heterodimerization with BCAR1/p130cas (PubMed:8668148, CC PubMed:10502414). {ECO:0000269|PubMed:10502414, CC ECO:0000269|PubMed:8668148, ECO:0000269|PubMed:9020138}. CC -!- PTM: Cell cycle-regulated processing produces four isoforms: p115, CC p105, p65, and p55. Isoform p115 arises from p105 phosphorylation and CC appears later in the cell cycle. Isoform p55 arises from p105 as a CC result of cleavage at a caspase cleavage-related site and it appears CC specifically at mitosis. The p65 isoform is poorly detected. CC {ECO:0000269|PubMed:9584194}. CC -!- PTM: Polyubiquitinated by ITCH/AIP4, leading to proteasomal CC degradation. {ECO:0000269|PubMed:15051726}. CC -!- PTM: PTK2/FAK1 phosphorylates the protein at the YDYVHL motif CC (conserved among all cas proteins) following integrin stimulation CC (PubMed:9360983). The SRC family kinases (FYN, SRC, LCK and CRK) are CC recruited to the phosphorylated sites and can phosphorylate other CC tyrosine residues (PubMed:9020138). Ligation of either integrin beta-1 CC or B-cell antigen receptor on tonsillar B-cells and B-cell lines CC promotes tyrosine phosphorylation and both integrin and BCR-mediated CC tyrosine phosphorylation requires an intact actin network CC (PubMed:9020138). Phosphorylation is required to recruit NEDD9 to T- CC cell receptor microclusters at the periphery of newly formed CC immunological synapses (By similarity). In fibroblasts transformation CC with oncogene v-ABL results in an increase in tyrosine phosphorylation. CC Transiently phosphorylated following CD3 cross-linking and this CC phosphorylated form binds to CRKL and C3G (PubMed:9497377). A mutant CC lacking the SH3 domain is phosphorylated upon CD3 cross-linking but not CC upon integrin beta-1 cross-linking (PubMed:9497377). Tyrosine CC phosphorylation occurs upon stimulation of the G-protein coupled C1a CC calcitonin receptor. Calcitonin-stimulated tyrosine phosphorylation is CC mediated by calcium- and protein kinase C-dependent mechanisms and CC requires the integrity of the actin cytoskeleton. Phosphorylation at CC Ser-369 induces proteasomal degradation (PubMed:19539609). CC Phosphorylated by LYN (PubMed:9020138). Phosphorylation at Ser-780 by CC CSNK1D or CSNK1E, or phosphorylation of Thr-804 by CSNK1E enhances the CC interaction of NEDD9 with PLK1 (PubMed:29191835). CC {ECO:0000250|UniProtKB:O35177, ECO:0000269|PubMed:19539609, CC ECO:0000269|PubMed:29191835, ECO:0000269|PubMed:9020138, CC ECO:0000269|PubMed:9360983, ECO:0000269|PubMed:9497377}. CC -!- SIMILARITY: Belongs to the CAS family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L43821; AAA98770.1; -; mRNA. DR EMBL; U64317; AAB53696.1; -; mRNA. DR EMBL; AK292682; BAF85371.1; -; mRNA. DR EMBL; AL022098; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL136139; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL139807; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL512382; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471087; EAW55299.1; -; Genomic_DNA. DR EMBL; CH471087; EAW55301.1; -; Genomic_DNA. DR EMBL; BC020686; AAH20686.1; -; mRNA. DR EMBL; BC040207; AAH40207.1; -; mRNA. DR CCDS; CCDS34340.1; -. [Q14511-2] DR CCDS; CCDS4520.1; -. [Q14511-1] DR CCDS; CCDS47373.1; -. [Q14511-3] DR RefSeq; NP_001135865.1; NM_001142393.1. [Q14511-3] DR RefSeq; NP_001257962.1; NM_001271033.1. DR RefSeq; NP_006394.1; NM_006403.3. [Q14511-1] DR RefSeq; NP_892011.2; NM_182966.3. [Q14511-2] DR PDB; 2L81; NMR; -; A=399-563. DR PDB; 5X3S; X-ray; 2.90 A; C/D=799-809. DR PDBsum; 2L81; -. DR PDBsum; 5X3S; -. DR AlphaFoldDB; Q14511; -. DR BMRB; Q14511; -. DR SMR; Q14511; -. DR BioGRID; 110816; 79. DR CORUM; Q14511; -. DR ELM; Q14511; -. DR IntAct; Q14511; 52. DR MINT; Q14511; -. DR STRING; 9606.ENSP00000368759; -. DR GlyCosmos; Q14511; 1 site, 2 glycans. DR GlyGen; Q14511; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; Q14511; -. DR PhosphoSitePlus; Q14511; -. DR BioMuta; NEDD9; -. DR DMDM; 8134360; -. DR jPOST; Q14511; -. DR MassIVE; Q14511; -. DR MaxQB; Q14511; -. DR PaxDb; 9606-ENSP00000368759; -. DR PeptideAtlas; Q14511; -. DR ProteomicsDB; 34087; -. DR ProteomicsDB; 60015; -. [Q14511-1] DR ProteomicsDB; 60016; -. [Q14511-2] DR Antibodypedia; 10092; 418 antibodies from 38 providers. DR DNASU; 4739; -. DR Ensembl; ENST00000379433.5; ENSP00000368745.5; ENSG00000111859.17. [Q14511-2] DR Ensembl; ENST00000379446.10; ENSP00000368759.5; ENSG00000111859.17. [Q14511-1] DR Ensembl; ENST00000504387.5; ENSP00000422871.1; ENSG00000111859.17. [Q14511-3] DR GeneID; 4739; -. DR KEGG; hsa:4739; -. DR MANE-Select; ENST00000379446.10; ENSP00000368759.5; NM_006403.4; NP_006394.1. DR UCSC; uc003mzv.2; human. [Q14511-1] DR AGR; HGNC:7733; -. DR CTD; 4739; -. DR DisGeNET; 4739; -. DR GeneCards; NEDD9; -. DR HGNC; HGNC:7733; NEDD9. DR HPA; ENSG00000111859; Low tissue specificity. DR MIM; 602265; gene. DR neXtProt; NX_Q14511; -. DR OpenTargets; ENSG00000111859; -. DR PharmGKB; PA31538; -. DR VEuPathDB; HostDB:ENSG00000111859; -. DR eggNOG; ENOG502QQHE; Eukaryota. DR GeneTree; ENSGT00950000183008; -. DR HOGENOM; CLU_017000_1_0_1; -. DR InParanoid; Q14511; -. DR OMA; GHSVRPE; -. DR OrthoDB; 2902504at2759; -. DR PhylomeDB; Q14511; -. DR TreeFam; TF328782; -. DR PathwayCommons; Q14511; -. DR SignaLink; Q14511; -. DR SIGNOR; Q14511; -. DR BioGRID-ORCS; 4739; 23 hits in 1146 CRISPR screens. DR ChiTaRS; NEDD9; human. DR GeneWiki; NEDD9; -. DR GenomeRNAi; 4739; -. DR Pharos; Q14511; Tbio. DR PRO; PR:Q14511; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q14511; Protein. DR Bgee; ENSG00000111859; Expressed in right lung and 189 other cell types or tissues. DR ExpressionAtlas; Q14511; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0001772; C:immunological synapse; ISS:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell. DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005819; C:spindle; TAS:ProtInc. DR GO; GO:0000922; C:spindle pole; ISS:UniProtKB. DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB. DR GO; GO:0051017; P:actin filament bundle assembly; NAS:UniProtKB. DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0061523; P:cilium disassembly; IMP:UniProtKB. DR GO; GO:0007010; P:cytoskeleton organization; NAS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; NAS:UniProtKB. DR GO; GO:0007611; P:learning or memory; ISS:UniProtKB. DR GO; GO:0097021; P:lymphocyte migration into lymphoid organs; ISS:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB. DR GO; GO:1902952; P:positive regulation of dendritic spine maintenance; ISS:UniProtKB. DR GO; GO:2000522; P:positive regulation of immunological synapse formation; ISS:UniProtKB. DR GO; GO:0140131; P:positive regulation of lymphocyte chemotaxis; ISS:UniProtKB. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISS:UniProtKB. DR GO; GO:1903829; P:positive regulation of protein localization; ISS:UniProtKB. DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd11570; FAT-like_NEDD9_C; 1. DR CDD; cd11550; Serine_rich_NEDD9; 1. DR CDD; cd12002; SH3_NEDD9; 1. DR Gene3D; 1.20.120.230; Alpha-catenin/vinculin-like; 1. DR Gene3D; 1.20.120.830; Serine-rich domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR021901; CAS_C. DR InterPro; IPR037362; CAS_fam. DR InterPro; IPR035746; NEDD9_SH3. DR InterPro; IPR014928; Serine_rich_dom. DR InterPro; IPR038319; Serine_rich_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR10654; CAS SCAFFOLDING PROTEIN; 1. DR PANTHER; PTHR10654:SF20; ENHANCER OF FILAMENTATION 1; 1. DR Pfam; PF12026; CAS_C; 1. DR Pfam; PF08824; Serine_rich; 1. DR Pfam; PF14604; SH3_9; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q14511; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; Cell cycle; KW Cell division; Cell junction; Cell membrane; Cell projection; Cytoplasm; KW Cytoskeleton; Golgi apparatus; Growth regulation; Membrane; Mitosis; KW Nucleus; Phosphoprotein; Reference proteome; SH3 domain; Ubl conjugation. FT CHAIN 1..834 FT /note="Enhancer of filamentation 1" FT /id="PRO_0000089328" FT CHAIN 1..? FT /note="Enhancer of filamentation 1 p55" FT /id="PRO_0000296242" FT DOMAIN 3..65 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 1..505 FT /note="Required for interaction with ITCH" FT /evidence="ECO:0000269|PubMed:15051726" FT REGION 102..229 FT /note="Interacts strongly with spindle-regulatory protein FT D1M1" FT REGION 238..260 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 291..316 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 328..398 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 351..834 FT /note="Interacts with CTTN" FT /evidence="ECO:0000269|PubMed:24574519" FT REGION 560..623 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 710..834 FT /note="Required for interaction with PLK1" FT /evidence="ECO:0000269|PubMed:29191835" FT REGION 710..760 FT /note="Divergent helix-loop-helix motif" FT MOTIF 360..363 FT /note="Caspase cleavage related site" FT /evidence="ECO:0000269|PubMed:9584194" FT COMPBIAS 298..315 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 365..397 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 569..583 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 92 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 164 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 166 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 177 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 189 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 214 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 223 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 279 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 296 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19539609" FT MOD_RES 317 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:22810897" FT MOD_RES 369 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19539609" FT MOD_RES 780 FT /note="Phosphoserine; by CSNK1D and CSNK1E" FT /evidence="ECO:0000269|PubMed:29191835" FT MOD_RES 804 FT /note="Phosphothreonine; by CSNK1E" FT /evidence="ECO:0000269|PubMed:29191835" FT VAR_SEQ 1..4 FT /note="MKYK -> MWTR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044579" FT VAR_SEQ 155..174 FT /note="ITPVRTGHGYVYEYPSRYQK -> FQRDGQVSYFLVRASKQTSL (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042835" FT VAR_SEQ 175..834 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042836" FT VARIANT 178 FT /note="D -> N (in dbSNP:rs11546959)" FT /id="VAR_054082" FT VARIANT 304 FT /note="P -> L (in dbSNP:rs34184473)" FT /id="VAR_054083" FT VARIANT 577 FT /note="T -> M (in dbSNP:rs3734401)" FT /id="VAR_021857" FT MUTAGEN 18 FT /note="C->A: Abolishes the oxidation-mediated reduction in FT interaction with SMAD3." FT /evidence="ECO:0000269|PubMed:29899023" FT MUTAGEN 735 FT /note="S->A: No effect on interaction with PLK1." FT /evidence="ECO:0000269|PubMed:29191835" FT MUTAGEN 751 FT /note="L->D: Abolishes interaction with BCAR3." FT /evidence="ECO:0000269|PubMed:19103205" FT MUTAGEN 754 FT /note="H->D: No effect on interaction with BCAR3." FT /evidence="ECO:0000269|PubMed:19103205" FT MUTAGEN 758 FT /note="F->D: No effect on interaction with BCAR3." FT /evidence="ECO:0000269|PubMed:19103205" FT MUTAGEN 780 FT /note="S->A: Reduces interaction with PLK1. Reduces protein FT phosphorylation by CSNK1D; when associated with A-804." FT /evidence="ECO:0000269|PubMed:29191835" FT MUTAGEN 780 FT /note="S->D: Reduces interaction with PLK1. Abolishes FT interaction with PLK1; when associated with D-804." FT /evidence="ECO:0000269|PubMed:29191835" FT MUTAGEN 780 FT /note="S->E: Abolishes interaction with PLK1." FT /evidence="ECO:0000269|PubMed:29191835" FT MUTAGEN 796 FT /note="M->D: No effect on interaction with BCAR3." FT /evidence="ECO:0000269|PubMed:19103205" FT MUTAGEN 804 FT /note="T->A: Reduces interaction with PLK1. Reduces protein FT phosphorylation by CSNK1D; when associated with A-780." FT /evidence="ECO:0000269|PubMed:29191835" FT MUTAGEN 804 FT /note="T->D: Reduces interaction with PLK1. Abolishes FT interaction with PLK1; when associated with D-780." FT /evidence="ECO:0000269|PubMed:29191835" FT MUTAGEN 804 FT /note="T->E: No effect on interaction with PLK1." FT /evidence="ECO:0000269|PubMed:29191835" FT CONFLICT 139 FT /note="Q -> R (in Ref. 3; BAF85371)" FT /evidence="ECO:0000305" FT HELIX 406..430 FT /evidence="ECO:0007829|PDB:2L81" FT HELIX 438..442 FT /evidence="ECO:0007829|PDB:2L81" FT TURN 443..446 FT /evidence="ECO:0007829|PDB:2L81" FT HELIX 447..473 FT /evidence="ECO:0007829|PDB:2L81" FT HELIX 480..508 FT /evidence="ECO:0007829|PDB:2L81" FT TURN 509..511 FT /evidence="ECO:0007829|PDB:2L81" FT HELIX 513..516 FT /evidence="ECO:0007829|PDB:2L81" FT HELIX 527..535 FT /evidence="ECO:0007829|PDB:2L81" FT HELIX 538..551 FT /evidence="ECO:0007829|PDB:2L81" FT HELIX 553..556 FT /evidence="ECO:0007829|PDB:2L81" SQ SEQUENCE 834 AA; 92861 MW; C54DEC36C8C8E9E6 CRC64; MKYKNLMARA LYDNVPECAE ELAFRKGDIL TVIEQNTGGL EGWWLCSLHG RQGIVPGNRV KLLIGPMQET ASSHEQPASG LMQQTFGQQK LYQVPNPQAA PRDTIYQVPP SYQNQGIYQV PTGHGTQEQE VYQVPPSVQR SIGGTSGPHV GKKVITPVRT GHGYVYEYPS RYQKDVYDIP PSHTTQGVYD IPPSSAKGPV FSVPVGEIKP QGVYDIPPTK GVYAIPPSAC RDEAGLREKD YDFPPPMRQA GRPDLRPEGV YDIPPTCTKP AGKDLHVKYN CDIPGAAEPV ARRHQSLSPN HPPPQLGQSV GSQNDAYDVP RGVQFLEPPA ETSEKANPQE RDGVYDVPLH NPPDAKGSRD LVDGINRLSF SSTGSTRSNM STSSTSSKES SLSASPAQDK RLFLDPDTAI ERLQRLQQAL EMGVSSLMAL VTTDWRCYGY MERHINEIRT AVDKVELFLK EYLHFVKGAV ANAACLPELI LHNKMKRELQ RVEDSHQILS QTSHDLNECS WSLNILAINK PQNKCDDLDR FVMVAKTVPD DAKQLTTTIN TNAEALFRPG PGSLHLKNGP ESIMNSTEYP HGGSQGQLLH PGDHKAQAHN KALPPGLSKE QAPDCSSSDG SERSWMDDYD YVHLQGKEEF ERQQKELLEK ENIMKQNKMQ LEHHQLSQFQ LLEQEITKPV ENDISKWKPS QSLPTTNSGV SAQDRQLLCF YYDQCETHFI SLLNAIDALF SCVSSAQPPR IFVAHSKFVI LSAHKLVFIG DTLTRQVTAQ DIRNKVMNSS NQLCEQLKTI VMATKMAALH YPSTTALQEM VHQVTDLSRN AQLFKRSLLE MATF //