CASL_MOUSE
ID CASL_MOUSE Reviewed; 833 AA.
AC O35177; Q8BJL8; Q8BK90; Q8BL52; Q8BM94; Q8BMI9; Q99KE7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Enhancer of filamentation 1;
DE Short=mEF1;
DE AltName: Full=CRK-associated substrate-related protein;
DE Short=CAS-L;
DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 9;
DE Short=NEDD-9;
DE AltName: Full=p105;
GN Name=Nedd9; Synonyms=Casl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Harvey K.F., Fitter S., Kumar S.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum, Corpora quadrigemina, Oviduct, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hematopoietic, and Mammary gland;
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 [4]
RP INTERACTION WITH SH2D3C.
RX PubMed=10692442; DOI=10.1074/jbc.275.9.6404;
RA Sakakibara A., Hattori S.;
RT "Chat, a Cas/HEF1-associated adaptor protein that integrates multiple
RT signaling pathways.";
RL J. Biol. Chem. 275:6404-6410(2000).
RN [5]
RP INTERACTION WITH BCAR3.
RX PubMed=12517963; DOI=10.4049/jimmunol.170.2.969;
RA Cai D., Felekkis K.N., Near R.I., O'Neill G.M., van Seventer J.M.,
RA Golemis E.A., Lerner A.;
RT "The GDP exchange factor AND-34 is expressed in B cells, associates with
RT HEF1, and activates Cdc42.";
RL J. Immunol. 170:969-978(2003).
RN [6]
RP FUNCTION, AND INTERACTION WITH SH2D3C.
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 [7]
RP TISSUE SPECIFICITY.
RX PubMed=19365570;
RA Near R.I., Smith R.S., Toselli P.A., Freddo T.F., Bloom A.B.,
RA Vanden Borre P., Seldin D.C., Lerner A.;
RT "Loss of AND-34/BCAR3 expression in mice results in rupture of the adult
RT lens.";
RL Mol. Vis. 15:685-699(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity). Required for correct
CC adhesion and migration of T-cells (PubMed:17174122).
CC {ECO:0000250|UniProtKB:Q14511, 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 (By similarity). Interacts with
CC BCAR3 (via Ras-GEF domain) (PubMed:12517963). Interacts with SH2D3C
CC isoform 1 and isoform 2 (PubMed:10692442, PubMed:17174122).
CC {ECO:0000250|UniProtKB:Q14511, ECO:0000269|PubMed:10692442,
CC ECO:0000269|PubMed:12517963, ECO:0000269|PubMed:17174122}.
CC -!- INTERACTION:
CC O35177; Q9QZS8: Sh2d3c; NbExp=2; IntAct=EBI-2642891, EBI-7964037;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex {ECO:0000250}. Nucleus
CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Note=Localizes to
CC both the cell nucleus and the cell periphery. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in splenic lymphocytes (at protein
CC level). {ECO:0000269|PubMed:19365570}.
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-368 induces
CC proteasomal degradation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CAS family. {ECO:0000305}.
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DR EMBL; AF009366; AAB71663.1; -; mRNA.
DR EMBL; AK030985; BAC27203.1; -; mRNA.
DR EMBL; AK033729; BAC28451.1; -; mRNA.
DR EMBL; AK046357; BAC32689.1; -; mRNA.
DR EMBL; AK054179; BAC35682.1; -; mRNA.
DR EMBL; AK083374; BAC38890.1; -; mRNA.
DR EMBL; BC004696; AAH04696.1; -; mRNA.
DR EMBL; BC053713; AAH53713.1; -; mRNA.
DR CCDS; CCDS49247.1; -.
DR RefSeq; NP_001104794.1; NM_001111324.2.
DR RefSeq; NP_059492.3; NM_017464.5.
DR AlphaFoldDB; O35177; -.
DR SMR; O35177; -.
DR BioGRID; 201726; 7.
DR DIP; DIP-57058N; -.
DR IntAct; O35177; 6.
DR STRING; 10090.ENSMUSP00000021794; -.
DR iPTMnet; O35177; -.
DR PhosphoSitePlus; O35177; -.
DR EPD; O35177; -.
DR MaxQB; O35177; -.
DR PaxDb; O35177; -.
DR PeptideAtlas; O35177; -.
DR PRIDE; O35177; -.
DR ProteomicsDB; 279912; -.
DR Antibodypedia; 10092; 365 antibodies from 38 providers.
DR DNASU; 18003; -.
DR Ensembl; ENSMUST00000021794; ENSMUSP00000021794; ENSMUSG00000021365.
DR GeneID; 18003; -.
DR KEGG; mmu:18003; -.
DR UCSC; uc007qfd.2; mouse.
DR CTD; 4739; -.
DR MGI; MGI:97302; Nedd9.
DR VEuPathDB; HostDB:ENSMUSG00000021365; -.
DR eggNOG; ENOG502QQHE; Eukaryota.
DR GeneTree; ENSGT00950000183008; -.
DR InParanoid; O35177; -.
DR OrthoDB; 1086228at2759; -.
DR PhylomeDB; O35177; -.
DR TreeFam; TF328782; -.
DR BioGRID-ORCS; 18003; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Nedd9; mouse.
DR PRO; PR:O35177; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; O35177; protein.
DR Bgee; ENSMUSG00000021365; Expressed in cumulus cell and 316 other tissues.
DR ExpressionAtlas; O35177; baseline and differential.
DR Genevisible; O35177; MM.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000922; C:spindle pole; IDA:MGI.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0090527; P:actin filament reorganization; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; IGI:MGI.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0007611; P:learning or memory; IMP:UniProtKB.
DR GO; GO:0097021; P:lymphocyte migration into lymphoid organs; IMP:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:1902952; P:positive regulation of dendritic spine maintenance; IMP:UniProtKB.
DR GO; GO:2000522; P:positive regulation of immunological synapse formation; IMP:UniProtKB.
DR GO; GO:0140131; P:positive regulation of lymphocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IMP:UniProtKB.
DR GO; GO:1903829; P:positive regulation of protein localization; IMP:UniProtKB.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
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 Cell adhesion; Cell cycle; Cell division; Cytoplasm; Cytoskeleton;
KW Growth regulation; Mitosis; Nucleus; Phosphoprotein; Reference proteome;
KW SH3 domain.
FT CHAIN 1..833
FT /note="Enhancer of filamentation 1"
FT /id="PRO_0000089329"
FT DOMAIN 3..65
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 237..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..403
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 709..759
FT /note="Divergent helix-loop-helix motif"
FT MOTIF 359..362
FT /note="Caspase cleavage related site"
FT /evidence="ECO:0000250"
FT COMPBIAS 237..256
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 364..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 564..583
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14511"
FT CONFLICT 2..4
FT /note="WAR -> KYK (in Ref. 2; BAC35682/BAC32689/BAC28451)"
FT /evidence="ECO:0000305"
FT CONFLICT 55
FT /note="V -> A (in Ref. 2; BAC32689)"
FT /evidence="ECO:0000305"
FT CONFLICT 126..127
FT /note="PE -> QN (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="V -> F (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="L -> V (in Ref. 2; BAC32689)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="H -> L (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="S -> N (in Ref. 2; BAC27203)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="K -> S (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
FT CONFLICT 504..506
FT /note="DLN -> ELD (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="D -> G (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
FT CONFLICT 604
FT /note="P -> A (in Ref. 2; BAC35682)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="P -> Q (in Ref. 2; BAC32689)"
FT /evidence="ECO:0000305"
FT CONFLICT 650
FT /note="E -> A (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
FT CONFLICT 685
FT /note="K -> R (in Ref. 2; BAC32689)"
FT /evidence="ECO:0000305"
FT CONFLICT 733..734
FT /note="SS -> TP (in Ref. 1; AAB71663)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 833 AA; 93052 MW; 78AA1B042775DC01 CRC64;
MWARNLMARA LYDNVPECAE ELAFRKGDIL TVIEQNTGGL EGWWLCSLHG RQGIVPGNRV
KLLIGPVQET PGHEQPTPGP MHQTFGQQKL YQVPNSQAAS RDTIYQVPPS YQNQGIYQVP
TGHGTPEQDV YQVPPSVQRN IGGTNGPLLS KKVITPVRTG HGYVYEYPSR YQKDVYDVPP
SHSTQGVYDI PPSSVKGPVF SVPVGEIKPQ GVYDIPPTQG VYAIPPSACR DEAGLREKEY
DFPPPMKQDG KPDTRPEGVY DIPPTSTKTA GKDLHIKFPC DAPGGVEPMA RRHQSFSLHH
APSQLGQSGD TQSDAYDVPR GVQFLEVPTE TSEKANPEER DGVYDVPLHN PADAKGSRDV
VDGINRLSFS STGSTRSNMS TSSTSSKESS LSASPSQDKR LRLDPDTAIE KLYRLQQTLE
MGVCSLMSLV TTDWRCYGYM ERHINEIRTA VDKVELFLRE YLHFAKGALA NASCLPELVL
HNKMKRELQR VEDSHQILSQ TSHDLNECSW SLNILAINKP QNKCDDLDRF VMVAKTVPDD
AKQLTTTIST YAETLFRADP ANSHLKNGPN SIMNSSEYTH PGSQMQPLHP GDYKAQVHSK
PLPPSLSKDQ PPDCGSSDGS ERSWMDDYDY VHLQGKEEFE RQQKELLEKE NIMKQSKAQL
EHHQLSQFQL LEQEITKPVE NDISKWKPSQ SLPTTNNSVG AQDRQLLCFY YDQCETHFIS
LLNAIDALFS CVSSAQPPRI FVAHSKFVIL SAHKLVFIGD TLTRQVAAQD IRNKVRNSSN
QLCEQLKTIV MATKMAALHY PSTTALQEMV HQVTDLSRNA QLFKRSLLEM ATF
