ES8L3_HUMAN
ID ES8L3_HUMAN Reviewed; 593 AA.
AC Q8TE67; A8K833; Q5T8Q6; Q5T8Q7; Q5T8Q8; Q96E47; Q9H719;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Epidermal growth factor receptor kinase substrate 8-like protein 3;
DE Short=EPS8-like protein 3;
DE AltName: Full=Epidermal growth factor receptor pathway substrate 8-related protein 3;
DE Short=EPS8-related protein 3;
GN Name=EPS8L3; Synonyms=EPS8R3;
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), AND VARIANT SER-163.
RX PubMed=12620401; DOI=10.1016/s0888-7543(03)00002-8;
RA Tocchetti A., Confalonieri S., Scita G., Di Fiore P.P., Betsholtz C.;
RT "In silico analysis of the EPS8 gene family: genomic organization,
RT expression profile, and protein structure.";
RL Genomics 81:234-244(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP TYR-293.
RC TISSUE=Colon;
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], AND ALTERNATIVE SPLICING.
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT TYR-293.
RC TISSUE=Colon;
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 [5]
RP IDENTIFICATION IN A COMPLEX WITH ABI1 AND SOS1, INTERACTION WITH ABI1,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14565974; DOI=10.1091/mbc.e03-06-0427;
RA Offenhaeuser N., Borgonovo A., Disanza A., Romano P., Ponzanelli I.,
RA Iannolo G., Di Fiore P.P., Scita G.;
RT "The eps8 family of proteins links growth factor stimulation to actin
RT reorganization generating functional redundancy in the Ras/Rac pathway.";
RL Mol. Biol. Cell 15:91-98(2004).
RN [6]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP STRUCTURE BY NMR OF 453-507.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SH3 domain of human hypothetical protein
RT FLJ21522.";
RL Submitted (JAN-2006) to the PDB data bank.
RN [9]
RP VARIANT HYPT5 THR-8, AND INVOLVEMENT IN HYPT5.
RX PubMed=23099647; DOI=10.1136/jmedgenet-2012-101134;
RA Zhang X., Guo B.R., Cai L.Q., Jiang T., Sun L.D., Cui Y., Hu J.C., Zhu J.,
RA Chen G., Tang X.F., Sun G.Q., Tang H.Y., Liu Y., Li M., Li Q.B., Cheng H.,
RA Gao M., Li P., Yang X., Zuo X.B., Zheng X.D., Wang P.G., Wang J., Wang J.,
RA Liu J.J., Yang S., Li Y.R., Zhang X.J.;
RT "Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna
RT hereditary hypotrichosis.";
RL J. Med. Genet. 49:727-730(2012).
CC -!- SUBUNIT: Interacts with ABI1. Part of a complex that contains SOS1,
CC ABI1 and EPS8L2. Interacts with FASLG. {ECO:0000269|PubMed:14565974,
CC ECO:0000269|PubMed:19807924}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14565974}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8TE67-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TE67-2; Sequence=VSP_019096;
CC Name=3; Synonyms=A;
CC IsoId=Q8TE67-3; Sequence=VSP_019095;
CC -!- DISEASE: Hypotrichosis 5 (HYPT5) [MIM:612841]: A form of hypotrichosis,
CC a condition characterized by the presence of less than the normal
CC amount of hair and abnormal hair follicles and shafts, which are thin
CC and atrophic. The extent of scalp and body hair involvement can be very
CC variable, within as well as between families. HYPT5 is an autosomal
CC dominant form characterized by little or no scalp hair at birth, wiry
CC and irregular scalp hair in childhood, and sparse or no forehead and
CC parietal hair at puberty. Eyebrows and eyelashes are thin, and pubic
CC and axillary hair fails to develop. Scarring alopecia is modest, and
CC vertex hair is normal. {ECO:0000269|PubMed:23099647}. Note=The disease
CC may be caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the EPS8 family. {ECO:0000305}.
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DR EMBL; AY074930; AAL76119.1; -; mRNA.
DR EMBL; AK025175; BAB15081.1; -; mRNA.
DR EMBL; AK292198; BAF84887.1; -; mRNA.
DR EMBL; AL158847; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012926; AAH12926.1; -; mRNA.
DR CCDS; CCDS813.1; -. [Q8TE67-2]
DR CCDS; CCDS814.1; -. [Q8TE67-1]
DR CCDS; CCDS815.1; -. [Q8TE67-3]
DR RefSeq; NP_001306881.1; NM_001319952.1.
DR RefSeq; NP_078802.2; NM_024526.3. [Q8TE67-2]
DR RefSeq; NP_573444.2; NM_133181.3. [Q8TE67-1]
DR RefSeq; NP_620641.1; NM_139053.2. [Q8TE67-3]
DR PDB; 1WXT; NMR; -; A=453-507.
DR PDBsum; 1WXT; -.
DR AlphaFoldDB; Q8TE67; -.
DR SMR; Q8TE67; -.
DR BioGRID; 122721; 4.
DR CORUM; Q8TE67; -.
DR IntAct; Q8TE67; 4.
DR MINT; Q8TE67; -.
DR STRING; 9606.ENSP00000358820; -.
DR GlyGen; Q8TE67; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TE67; -.
DR PhosphoSitePlus; Q8TE67; -.
DR BioMuta; EPS8L3; -.
DR DMDM; 108864727; -.
DR jPOST; Q8TE67; -.
DR MassIVE; Q8TE67; -.
DR MaxQB; Q8TE67; -.
DR PaxDb; Q8TE67; -.
DR PeptideAtlas; Q8TE67; -.
DR PRIDE; Q8TE67; -.
DR ProteomicsDB; 74404; -. [Q8TE67-1]
DR ProteomicsDB; 74405; -. [Q8TE67-2]
DR ProteomicsDB; 74406; -. [Q8TE67-3]
DR ABCD; Q8TE67; 5 sequenced antibodies.
DR Antibodypedia; 53746; 176 antibodies from 25 providers.
DR DNASU; 79574; -.
DR Ensembl; ENST00000361852.8; ENSP00000354551.4; ENSG00000198758.11. [Q8TE67-2]
DR Ensembl; ENST00000361965.9; ENSP00000355255.4; ENSG00000198758.11. [Q8TE67-1]
DR Ensembl; ENST00000369805.7; ENSP00000358820.3; ENSG00000198758.11. [Q8TE67-3]
DR GeneID; 79574; -.
DR KEGG; hsa:79574; -.
DR MANE-Select; ENST00000361965.9; ENSP00000355255.4; NM_133181.4; NP_573444.2.
DR UCSC; uc001dyq.3; human. [Q8TE67-1]
DR CTD; 79574; -.
DR DisGeNET; 79574; -.
DR GeneCards; EPS8L3; -.
DR HGNC; HGNC:21297; EPS8L3.
DR HPA; ENSG00000198758; Group enriched (gallbladder, intestine, stomach).
DR MalaCards; EPS8L3; -.
DR MIM; 612841; phenotype.
DR MIM; 614989; gene.
DR neXtProt; NX_Q8TE67; -.
DR OpenTargets; ENSG00000198758; -.
DR Orphanet; 444; Marie Unna hereditary hypotrichosis.
DR PharmGKB; PA134940846; -.
DR VEuPathDB; HostDB:ENSG00000198758; -.
DR eggNOG; KOG3557; Eukaryota.
DR GeneTree; ENSGT00940000158169; -.
DR HOGENOM; CLU_014510_0_1_1; -.
DR InParanoid; Q8TE67; -.
DR OMA; GYIPNNI; -.
DR OrthoDB; 1324479at2759; -.
DR PhylomeDB; Q8TE67; -.
DR TreeFam; TF313069; -.
DR PathwayCommons; Q8TE67; -.
DR SignaLink; Q8TE67; -.
DR BioGRID-ORCS; 79574; 41 hits in 1063 CRISPR screens.
DR EvolutionaryTrace; Q8TE67; -.
DR GeneWiki; EPS8L3; -.
DR GenomeRNAi; 79574; -.
DR Pharos; Q8TE67; Tbio.
DR PRO; PR:Q8TE67; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8TE67; protein.
DR Bgee; ENSG00000198758; Expressed in mucosa of transverse colon and 140 other tissues.
DR ExpressionAtlas; Q8TE67; baseline and differential.
DR Genevisible; Q8TE67; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; IBA:GO_Central.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; IBA:GO_Central.
DR GO; GO:0042634; P:regulation of hair cycle; IMP:UniProtKB.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR CDD; cd01210; PTB_EPS8; 1.
DR CDD; cd11764; SH3_Eps8; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR039801; EPS8-like.
DR InterPro; IPR033928; EPS8_PTB.
DR InterPro; IPR035462; Eps8_SH3.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR013625; PTB.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR041418; SAM_3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR12287; PTHR12287; 1.
DR Pfam; PF08416; PTB; 1.
DR Pfam; PF18016; SAM_3; 1.
DR Pfam; PF00018; SH3_1; 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; Cytoplasm; Disease variant;
KW Hypotrichosis; Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..593
FT /note="Epidermal growth factor receptor kinase substrate 8-
FT like protein 3"
FT /id="PRO_0000239087"
FT DOMAIN 450..509
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 149..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 374..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 153
FT /note="Q -> QS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019095"
FT VAR_SEQ 412..441
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019096"
FT VARIANT 8
FT /note="A -> T (in HYPT5; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23099647"
FT /id="VAR_083829"
FT VARIANT 35
FT /note="M -> I (in dbSNP:rs17598321)"
FT /id="VAR_050976"
FT VARIANT 163
FT /note="G -> S (in dbSNP:rs6693815)"
FT /evidence="ECO:0000269|PubMed:12620401"
FT /id="VAR_026580"
FT VARIANT 293
FT /note="H -> Y (in dbSNP:rs3818562)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_026581"
FT VARIANT 356
FT /note="P -> S (in dbSNP:rs11102001)"
FT /id="VAR_026582"
FT VARIANT 581
FT /note="R -> Q (in dbSNP:rs35072794)"
FT /id="VAR_050977"
FT STRAND 453..459
FT /evidence="ECO:0007829|PDB:1WXT"
FT STRAND 465..468
FT /evidence="ECO:0007829|PDB:1WXT"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:1WXT"
FT STRAND 483..490
FT /evidence="ECO:0007829|PDB:1WXT"
FT STRAND 496..500
FT /evidence="ECO:0007829|PDB:1WXT"
FT HELIX 501..503
FT /evidence="ECO:0007829|PDB:1WXT"
SQ SEQUENCE 593 AA; 66861 MW; 2BB9B52ADD338F88 CRC64;
MSRPSSRAIY LHRKEYSQNL TSEPTLLQHR VEHLMTCKQG SQRVQGPEDA LQKLFEMDAQ
GRVWSQDLIL QVRDGWLQLL DIETKEELDS YRLDSIQAMN VALNTCSYNS ILSITVQEPG
LPGTSTLLFQ CQEVGAERLK TSLQKALEEE LEQRPRLGGL QPGQDRWRGP AMERPLPMEQ
ARYLEPGIPP EQPHQRTLEH SLPPSPRPLP RHTSAREPSA FTLPPPRRSS SPEDPERDEE
VLNHVLRDIE LFMGKLEKAQ AKTSRKKKFG KKNKDQGGLT QAQYIDCFQK IKHSFNLLGR
LATWLKETSA PELVHILFKS LNFILARCPE AGLAAQVISP LLTPKAINLL QSCLSPPESN
LWMGLGPAWT TSRADWTGDE PLPYQPTFSD DWQLPEPSSQ APLGYQDPVS LRRGSHRLGS
TSHFPQEKTH NHDPQPGDPN SRPSSPKPAQ PALKMQVLYE FEARNPRELT VVQGEKLEVL
DHSKRWWLVK NEAGRSGYIP SNILEPLQPG TPGTQGQSPS RVPMLRLSSR PEEVTDWLQA
ENFSTATVRT LGSLTGSQLL RIRPGELQML CPQEAPRILS RLEAVRRMLG ISP
