CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-024781
UniProt Accession
Genbank Protein ID
  
Genbank Nucleotide ID
  
Protein Name
 Epidermal growth factor receptor kinase substrate 8 
Protein Synonyms/Alias
  
Gene Name
 Eps8 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Rattus norvegicus (Rat) 
NCBI Taxa ID
 10116 
Lysine Modification
Position
Peptide
Type
References
92DDGIRKLKLLDAKGKacetylation[1]
Reference
 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405] 
Functional Description
 Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac- specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2- dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with DFNB31 and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes (By similarity). 
Sequence Annotation
 DOMAIN 69 129 PH; first part.
 DOMAIN 381 414 PH; second part.
 DOMAIN 531 590 SH3.
 REGION 649 822 Effector region (By similarity).
 REGION 680 698 Amphipathic helix (By similarity).
 REGION 718 738 Helix bundle 1 (By similarity).
 REGION 752 757 Helix bundle 2 (By similarity).
 REGION 762 767 Helix bundle 3 (By similarity).
 REGION 766 785 Helix bundle 4 (By similarity).
 MOD_RES 317 317 Phosphothreonine.
 MOD_RES 476 476 Phosphoserine (By similarity).
 MOD_RES 625 625 Phosphoserine; by MAPK (By similarity).
 MOD_RES 629 629 Phosphothreonine; by MAPK (By  
Keyword
 Actin-binding; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Membrane; Phosphoprotein; Reference proteome; SH3 domain; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 822 AA 
Protein Sequence
MNGHMSNHSS GYGIYPSQMN GYGSSPPYSQ MDREHCSRTS AKALYEQRKN YARDSVSSVS 60
DVSQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV WTQDMILQVD DRAVSLIDLE 120
SKNELENFPL NTIQHCQAVA HTCSYDSILA LVCKEPTQNK PDLHLFQCDE VKANLISEDI 180
ESAISDSKGG KQKRRPEALR MIAKADPGIP PPPRAPAPVP PGTVTQVDVR SRVAAWSAWA 240
ADQGDFEKPR QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR 300
KKSKKSKRKG PGEGVLTLRA KPPPPDEFVD CFQKFKHGFN LLAKLKSHIQ NPSASDLVHF 360
LFTPLNMVVQ ATGGPELASS VLSPLLTKDT VDFLNYTVKA EERQLWMSLG ETWMKVRAEW 420
PKEQFIPPYV PRFRNGWEPP MLNFMGAPTE QDMYQLAESV ANAAEQQRKQ DSKRQSTEHS 480
SMSDYPPADG YTFSNSMYHR GPHVDQGEAA LALKSTPNRH VDRNYDPVKT QPKKYAKSKY 540
DFVARNSSEL SVMKDDVLEI LDDRKQWWKV RNASGDSGFV PNNILDIMRT PESGVGRTDP 600
PYTHTIQKQR TEYGPRSADT PSAPSPPPTP APVPVPLPPS APAPVPVPKV PANVTRQNSS 660
SSESGGSIAR DSQRYKQLPV DRRKSQMEEV QDELFQRLTI GRSAAQRKFH VPRQNVPVIN 720
ITYDSSPEEV KTWLQSKGFN PVTVSSLGVL NGAQLFSLNK DELRSVCPEG ARVFSQITVQ 780
KAALEDSSGS SELQEIMRRR QEKISAAASD SGVESFDEGS SH 822 
Gene Ontology
 GO:0005938; C:cell cortex; ISS:UniProtKB.
 GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
 GO:0017146; C:N-methyl-D-aspartate selective glutamate receptor complex; IEA:Compara.
 GO:0014069; C:postsynaptic density; IEA:Compara.
 GO:0032587; C:ruffle membrane; ISS:UniProtKB.
 GO:0032420; C:stereocilium; ISS:UniProtKB.
 GO:0003779; F:actin binding; ISS:UniProtKB.
 GO:0048365; F:Rac GTPase binding; ISS:UniProtKB.
 GO:0051764; P:actin crosslink formation; ISS:UniProtKB.
 GO:0031532; P:actin cytoskeleton reorganization; IEA:Compara.
 GO:0051017; P:actin filament bundle assembly; ISS:UniProtKB.
 GO:0070358; P:actin polymerization-dependent cell motility; ISS:UniProtKB.
 GO:0008344; P:adult locomotory behavior; IEA:Compara.
 GO:0051016; P:barbed-end actin filament capping; ISS:UniProtKB.
 GO:0048149; P:behavioral response to ethanol; IEA:Compara.
 GO:0036336; P:dendritic cell migration; ISS:UniProtKB.
 GO:0010458; P:exit from mitosis; ISS:UniProtKB.
 GO:0016601; P:Rac protein signal transduction; ISS:UniProtKB.
 GO:0008360; P:regulation of cell shape; ISS:UniProtKB. 
Interpro
 IPR011993; PH_like_dom.
 IPR013625; PTB.
 IPR006020; PTyr_interaction_dom.
 IPR001452; SH3_domain. 
Pfam
 PF08416; PTB
 PF00018; SH3_1 
SMART
 SM00462; PTB
 SM00326; SH3 
PROSITE
 PS50003; PH_DOMAIN
 PS50002; SH3 
PRINTS