CASL_HUMAN
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 03-AUG-2022, entry version 218.
DE RecName: Full=Enhancer of filamentation 1;
DE Short=hEF1;
DE AltName: Full=CRK-associated substrate-related protein;
DE Short=CAS-L;
DE Short=CasL;
DE AltName: Full=Cas scaffolding protein family member 2;
DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 9;
DE Short=NEDD-9;
DE AltName: Full=Renal carcinoma antigen NY-REN-12;
DE AltName: Full=p105;
DE Contains:
DE RecName: Full=Enhancer of filamentation 1 p55;
GN Name=NEDD9; Synonyms=CASL, CASS2;
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).
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).
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 INCREASED TYROSINE PHOSPHORYLATION BY LIGATION OF INTEGRIN-B1 AND BCR.
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 PHOSPHORYLATION AT TYROSINE RESIDUES BY PTK2/FAK1.
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 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 PHOSPHORYLATION AT TYROSINE RESIDUES UPON CD3 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 CHARACTERIZATION OF 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.
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 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 [18]
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 [19]
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 [20]
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.
CC -!- FUNCTION: Docking protein which plays a central coordinating role for
CC tyrosine-kinase-based signaling related to cell adhesion. May function
CC in transmitting growth control signals between focal adhesions at the
CC cell periphery and the mitotic spindle in response to adhesion or
CC growth factor signals initiating cell proliferation. May play an
CC important role in integrin beta-1 or B cell antigen receptor (BCR)
CC mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads
CC to recruitment of various proteins including CRK, NCK and SHPTP2 to the
CC tyrosine phosphorylated form. Required for correct adhesion and
CC migration of T-cells (PubMed:17174122). {ECO:0000269|PubMed:17174122}.
CC -!- SUBUNIT: Homodimer. Can heterodimerize with HLH proteins ID2, E12, E47
CC and also with p130cas. Forms complexes in vivo with related adhesion
CC focal tyrosine kinase (RAFTK), adapter protein CRKL and LYN kinase.
CC Interacts with MICAL and TXNL4/DIM1. Interacts with BCAR3 (via Ras-GEF
CC domain) (By similarity). Interacts with SH2D3C isoform 1 and isoform 2
CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O35177,
CC ECO:0000269|PubMed:11054566, ECO:0000269|PubMed:11827972}.
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; O75381: PEX14; NbExp=2; IntAct=EBI-2108053, EBI-594898;
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; 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; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-11746523, EBI-11976299;
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; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-11746523, EBI-371922;
CC Q14511-2; Q5T9C2-3: FAM102A; NbExp=3; IntAct=EBI-11746523, EBI-11980989;
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. Nucleus. Golgi apparatus.
CC Cell projection, lamellipodium. Cytoplasm. Cell junction, focal
CC adhesion. Note=Localizes to both the cell nucleus and the cell
CC periphery and is differently localized in fibroblasts and epithelial
CC cells. In fibroblasts is predominantly nuclear and in some cells is
CC present in the Golgi apparatus. In epithelial cells localized
CC predominantly in the cell periphery with particular concentration in
CC lamellipodia but is also found in the nucleus. Isoforms p105 and p115
CC are predominantly cytoplasmic and associate with focal adhesions while
CC p55 associates with mitotic spindle.
CC -!- SUBCELLULAR LOCATION: [Enhancer of filamentation 1 p55]: Cytoplasm,
CC cytoskeleton, spindle.
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: Widely expressed. Higher levels detected in kidney,
CC lung, and placenta. Also detected in T-cells, B-cells and diverse cell
CC lines. The protein has been detected in lymphocytes, in diverse cell
CC lines, and in lung tissues.
CC -!- INDUCTION: Activated upon induction of cell growth.
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. The SH2-binding sites putatively bind CRK, NCK
CC and ABL SH2 domains. The HLH motif confers specific interaction with
CC the HLH proteins ID2, E12 and E47. It is absolutely required for the
CC induction of pseudohyphal growth in yeast and mediates homodimerization
CC and heterodimerization with p130cas.
CC -!- DOMAIN: The SH3 domain interacts with two proline-rich regions of
CC PTK2/FAK1.
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: PTK2/FAK1 phosphorylates the protein at the YDYVHL motif
CC (conserved among all cas proteins). The SRC family kinases (FYN, SRC,
CC LCK and CRK) are recruited to the phosphorylated sites and can
CC phosphorylate other tyrosine residues. Ligation of either integrin
CC beta-1 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. In
CC fibroblasts transformation with oncogene v-ABL results in an increase
CC in tyrosine phosphorylation. Transiently phosphorylated following CD3
CC cross-linking and this phosphorylated form binds to CRK and C3G. A
CC mutant lacking the SH3 domain is phosphorylated upon CD3 cross-linking
CC but not upon integrin beta-1 cross-linking. Tyrosine phosphorylation
CC occurs upon stimulation of the G-protein coupled C1a calcitonin
CC receptor. Calcitonin-stimulated tyrosine phosphorylation is mediated by
CC calcium- and protein kinase C-dependent mechanisms and requires the
CC integrity of the actin cytoskeleton. Phosphorylation at Ser-369 induces
CC proteasomal degradation. {ECO:0000269|PubMed:19539609}.
CC -!- SIMILARITY: Belongs to the CAS family. {ECO:0000305}.
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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; 77.
DR CORUM; Q14511; -.
DR ELM; Q14511; -.
DR IntAct; Q14511; 52.
DR MINT; Q14511; -.
DR STRING; 9606.ENSP00000368759; -.
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; Q14511; -.
DR PeptideAtlas; Q14511; -.
DR PRIDE; Q14511; -.
DR ProteomicsDB; 34087; -.
DR ProteomicsDB; 60015; -. [Q14511-1]
DR ProteomicsDB; 60016; -. [Q14511-2]
DR Antibodypedia; 10092; 365 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 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; QRCIDGP; -.
DR PhylomeDB; Q14511; -.
DR TreeFam; TF328782; -.
DR PathwayCommons; Q14511; -.
DR SignaLink; Q14511; -.
DR SIGNOR; Q14511; -.
DR BioGRID-ORCS; 4739; 19 hits in 1072 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 187 other tissues.
DR ExpressionAtlas; Q14511; baseline and differential.
DR Genevisible; Q14511; HS.
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; IEA:Ensembl.
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:0090527; P:actin filament reorganization; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; IEA:Ensembl.
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:0040008; P:regulation of growth; IEA:UniProtKB-KW.
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; cd12002; SH3_NEDD9; 1.
DR Gene3D; 1.20.120.830; -; 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; PTHR10654; 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; SSF50044; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell cycle;
KW Cell division; Cell junction; Cell projection; Cytoplasm; Cytoskeleton;
KW Golgi apparatus; Growth regulation; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; SH3 domain.
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 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 560..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 710..760
FT /note="Divergent helix-loop-helix motif"
FT MOTIF 360..363
FT /note="Caspase cleavage related site"
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 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19539609"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19539609"
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 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
