EFS_HUMAN
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 03-AUG-2022, entry version 181.
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}.
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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; 71 antibodies from 21 providers.
DR DNASU; 10278; -.
DR Ensembl; ENST00000216733.8; ENSP00000216733.3; ENSG00000100842.13. [O43281-1]
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 ganglionic eminence and 187 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
