ID EFS_HUMAN Reviewed; 561 AA. AC O43281; B2RAJ7; B4DJ56; E9PGU2; O43282; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 25-MAY-2022, entry version 180. DE RecName: Full=Embryonal Fyn-associated substrate; DE Short=hEFS; DE AltName: Full=Cas scaffolding protein family member 3; GN Name=EFS; Synonyms=CASS3; 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] (ISOFORMS EFS1 AND EFS2). RC TISSUE=Hippocampus; RX PubMed=9349509; DOI=10.1038/sj.onc.1201346; RA Ishino M., Ohba T., Inazawa J., Sasaki H., Ariyama Y., Sasaki T.; RT "Identification of an Efs isoform that lacks the SH3 domain and chromosomal RT mapping of human Efs."; RL Oncogene 15:1741-1745(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS EFS1 AND 3). RC TISSUE=Amygdala, and Substantia nigra; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [4] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM EFS2). RC TISSUE=Brain; 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 [6] RP VARIANT [LARGE SCALE ANALYSIS] ILE-361. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Docking protein which plays a central coordinating role for CC tyrosine-kinase-based signaling related to cell adhesion. May serve as CC an activator of SRC and a downstream effector. Interacts with the SH3 CC domain of FYN and with CRK, SRC, and YES (By similarity). CC {ECO:0000250}. CC -!- INTERACTION: CC O43281; Q9NYB9: ABI2; NbExp=6; IntAct=EBI-718488, EBI-743598; CC O43281; P51451: BLK; NbExp=5; IntAct=EBI-718488, EBI-2105445; CC O43281; P06241: FYN; NbExp=4; IntAct=EBI-718488, EBI-515315; CC O43281; O75694: NUP155; NbExp=3; IntAct=EBI-718488, EBI-1050769; CC O43281; Q92882: OSTF1; NbExp=3; IntAct=EBI-718488, EBI-1051152; CC O43281; O94875: SORBS2; NbExp=3; IntAct=EBI-718488, EBI-311323; CC O43281; Q9BXA7: TSSK1B; NbExp=3; IntAct=EBI-718488, EBI-6423734; CC O43281; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-718488, EBI-740727; CC O43281-2; Q9NYB9-2: ABI2; NbExp=5; IntAct=EBI-11525448, EBI-11096309; CC O43281-2; P21549: AGXT; NbExp=3; IntAct=EBI-11525448, EBI-727098; CC O43281-2; P51451: BLK; NbExp=3; IntAct=EBI-11525448, EBI-2105445; CC O43281-2; P06241-3: FYN; NbExp=5; IntAct=EBI-11525448, EBI-10691738; CC O43281-2; Q92990: GLMN; NbExp=3; IntAct=EBI-11525448, EBI-726150; CC O43281-2; O95872: GPANK1; NbExp=3; IntAct=EBI-11525448, EBI-751540; CC O43281-2; Q68G74: LHX8; NbExp=3; IntAct=EBI-11525448, EBI-8474075; CC O43281-2; Q8IVT4: MGC50722; NbExp=3; IntAct=EBI-11525448, EBI-14086479; CC O43281-2; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-11525448, EBI-5662487; CC O43281-2; A0A0S2Z4D7: NCK1; NbExp=3; IntAct=EBI-11525448, EBI-16429340; CC O43281-2; A0A0S2Z4E4: NCK1; NbExp=3; IntAct=EBI-11525448, EBI-16432934; CC O43281-2; E7ERP6: NCK2; NbExp=3; IntAct=EBI-11525448, EBI-16429362; CC O43281-2; Q13526: PIN1; NbExp=3; IntAct=EBI-11525448, EBI-714158; CC O43281-2; Q8TEC5: SH3RF2; NbExp=3; IntAct=EBI-11525448, EBI-2130111; CC O43281-2; O94875-10: SORBS2; NbExp=3; IntAct=EBI-11525448, EBI-12037893; CC O43281-2; O75865-2: TRAPPC6A; NbExp=3; IntAct=EBI-11525448, EBI-8451480; CC O43281-2; Q9BXA7: TSSK1B; NbExp=3; IntAct=EBI-11525448, EBI-6423734; CC O43281-2; Q8TF42: UBASH3B; NbExp=3; IntAct=EBI-11525448, EBI-1380492; CC O43281-2; P07947: YES1; NbExp=5; IntAct=EBI-11525448, EBI-515331; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=Efs1; CC IsoId=O43281-1; Sequence=Displayed; CC Name=Efs2; CC IsoId=O43281-2; Sequence=VSP_004232; CC Name=3; CC IsoId=O43281-3; Sequence=VSP_004232, VSP_054584; CC -!- TISSUE SPECIFICITY: The protein has been detected in lung and placenta. CC -!- DOMAIN: Contains a central domain (substrate domain) containing CC multiple potential SH2-binding sites and a C-terminal domain containing CC a divergent helix-loop-helix (HLH) motif. The SH2-binding sites CC putatively bind CRK, NCK and ABL SH2 domains. CC -!- DOMAIN: The SH3-binding sites that bind to the SRC SH3 domain are CC required for interaction with CRK and are implicated in promotion of CC serum response element (SRE) activation. The SH3 domain interacts with CC PTK2/FAK1. CC -!- PTM: Phosphorylated on multiple tyrosine residues. Phosphorylated on CC tyrosines by FYN and SRC (By similarity). {ECO:0000250}. 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; AB001466; BAA24588.1; -; mRNA. DR EMBL; AB001467; BAA24589.1; -; mRNA. DR EMBL; AK295933; BAG58718.1; -; mRNA. DR EMBL; AK314221; BAG36894.1; -; mRNA. DR EMBL; AL049829; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471078; EAW66164.1; -; Genomic_DNA. DR EMBL; BC034246; AAH34246.1; -; mRNA. DR CCDS; CCDS61404.1; -. [O43281-3] DR CCDS; CCDS9595.1; -. [O43281-1] DR CCDS; CCDS9596.1; -. [O43281-2] DR RefSeq; NP_001264103.1; NM_001277174.1. [O43281-3] DR RefSeq; NP_005855.1; NM_005864.3. [O43281-1] DR RefSeq; NP_115835.1; NM_032459.2. [O43281-2] DR AlphaFoldDB; O43281; -. DR SMR; O43281; -. DR BioGRID; 115567; 37. DR IntAct; O43281; 37. DR MINT; O43281; -. DR STRING; 9606.ENSP00000216733; -. DR iPTMnet; O43281; -. DR PhosphoSitePlus; O43281; -. DR BioMuta; EFS; -. DR EPD; O43281; -. DR jPOST; O43281; -. DR MassIVE; O43281; -. DR MaxQB; O43281; -. DR PaxDb; O43281; -. DR PeptideAtlas; O43281; -. DR PRIDE; O43281; -. DR ProteomicsDB; 4348; -. DR ProteomicsDB; 48850; -. [O43281-1] DR ProteomicsDB; 48851; -. [O43281-2] DR Antibodypedia; 22453; 72 antibodies from 22 providers. DR DNASU; 10278; -. DR Ensembl; ENST00000216733.8; ENSP00000216733.3; ENSG00000100842.13. DR Ensembl; ENST00000351354.3; ENSP00000340607.3; ENSG00000100842.13. [O43281-2] DR Ensembl; ENST00000429593.6; ENSP00000416684.2; ENSG00000100842.13. [O43281-3] DR GeneID; 10278; -. DR KEGG; hsa:10278; -. DR MANE-Select; ENST00000216733.8; ENSP00000216733.3; NM_005864.4; NP_005855.1. DR UCSC; uc001wjo.5; human. [O43281-1] DR CTD; 10278; -. DR DisGeNET; 10278; -. DR GeneCards; EFS; -. DR HGNC; HGNC:16898; EFS. DR HPA; ENSG00000100842; Low tissue specificity. DR MIM; 609906; gene. DR neXtProt; NX_O43281; -. DR OpenTargets; ENSG00000100842; -. DR PharmGKB; PA134887136; -. DR VEuPathDB; HostDB:ENSG00000100842; -. DR eggNOG; ENOG502QUFB; Eukaryota. DR GeneTree; ENSGT00950000183008; -. DR HOGENOM; CLU_012582_1_0_1; -. DR InParanoid; O43281; -. DR OMA; LHNEYEG; -. DR OrthoDB; 1086228at2759; -. DR PhylomeDB; O43281; -. DR TreeFam; TF328782; -. DR PathwayCommons; O43281; -. DR SignaLink; O43281; -. DR BioGRID-ORCS; 10278; 16 hits in 1064 CRISPR screens. DR ChiTaRS; EFS; human. DR GenomeRNAi; 10278; -. DR Pharos; O43281; Tbio. DR PRO; PR:O43281; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; O43281; protein. DR Bgee; ENSG00000100842; Expressed in amniotic fluid and 229 other tissues. DR Genevisible; O43281; HS. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005925; C:focal adhesion; IBA:GO_Central. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0090527; P:actin filament reorganization; IBA:GO_Central. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd12003; SH3_EFS; 1. DR InterPro; IPR021901; CAS_C. DR InterPro; IPR037362; CAS_fam. DR InterPro; IPR035747; EFS_SH3. 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; PF14604; SH3_9; 1. DR PRINTS; PR00452; SH3DOMAIN. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50044; SSF50044; 1. DR PROSITE; PS50002; SH3; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Phosphoprotein; Reference proteome; KW SH3 domain; SH3-binding. FT CHAIN 1..561 FT /note="Embryonal Fyn-associated substrate" FT /id="PRO_0000086940" FT DOMAIN 5..68 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 68..123 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 171..215 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 240..372 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 390..422 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 438..488 FT /note="Divergent helix-loop-helix motif" FT MOTIF 305..311 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT MOTIF 335..341 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 71..88 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 104..123 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 184..198 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 309..325 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 333..347 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 353..372 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 253 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000250|UniProtKB:Q64355" FT VAR_SEQ 7..99 FT /note="Missing (in isoform Efs2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9349509" FT /id="VSP_004232" FT VAR_SEQ 186..261 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054584" FT VARIANT 7 FT /note="T -> A (in dbSNP:rs2231798)" FT /id="VAR_054088" FT VARIANT 100 FT /note="V -> M (in dbSNP:rs2231801)" FT /id="VAR_054089" FT VARIANT 361 FT /note="M -> I (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs1463886157)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035912" SQ SEQUENCE 561 AA; 58815 MW; 30FFF1AD4C9D1C4A CRC64; MAIATSTQLA RALYDNTAES PQELSFRRGD VLRVLQREGA GGLDGWCLCS LHGQQGIVPA NRVKLLPAGP APKPSLSPAS PAQPGSPYPA PDHSNEDQEV YVVPPPARPC PTSGPPAGPC PPSPDLIYKI PRASGTQLAA PRDALEVYDV PPTALRVPSS GPYDCPASFS HPLTRVAPQP PGEDDAPYDV PLTPKPPAEL EPDLEWEGGR EPGPPIYAAP SNLKRASALL NLYEAPEELL ADGEGGGTDE GIYDVPLLGP EAPPSPEPPG ALASHDQDTL AQLLARSPPP PHRPRLPSAE SLSRRPLPAL PVPEAPSPSP VPSPAPGRKG SIQDRPLPPP PPRLPGYGGP KVEGDPEGRE MEDDPAGHHN EYEGIPMAEE YDYVHLKGMD KAQGSRPPDQ ACTGDPELPE RGMPAPQEAL SPGEPLVVST GDLQLLYFYA GQCQSHYSAL QAAVAALMSS TQANQPPRLF VPHSKRVVVA AHRLVFVGDT LGRLAASAPL RAQVRAAGTA LGQALRATVL AVKGAALGYP SSPAIQEMVQ CVTELAGQAL QFTTLLTSLA P //