CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011606
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
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
683QLPVDRRKSQMEEVQubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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. 
Sequence Annotation
 DOMAIN 69 129 PH; first part.
 DOMAIN 381 414 PH; second part.
 DOMAIN 532 591 SH3.
 REGION 648 821 Effector region.
 REGION 679 697 Amphipathic helix.
 REGION 717 737 Helix bundle 1.
 REGION 751 756 Helix bundle 2.
 REGION 761 766 Helix bundle 3.
 REGION 765 784 Helix bundle 4.
 MOD_RES 317 317 Phosphothreonine (By similarity).
 MOD_RES 475 475 Phosphoserine (By similarity).
 MOD_RES 624 624 Phosphoserine; by MAPK.
 MOD_RES 628 628 Phosphothreonine; by MAPK.  
Keyword
 3D-structure; 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
 821 AA 
Protein Sequence
MNGHMSNRSS GYGVYPSQLN GYGSSPPYSQ MDREHSSRTS AKALYEQRKN YARDSVSSVS 60
DVSQYRVEHL TTFVLDRKDA MITVEDGIRK LKLLDAKGKV WTQDMILQVD DRAVSLIDLE 120
SKNELENFPL NTISHCQAVV HACSYDSILA LVCKEPTQSK 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 VDFLNYTATA EERKLWMSLG DSWVKVRAEW 420
PKEQFIPPYV PRFRNGWEPP MLNFMGAPTE QDMYQLAESV ANAEHQRKQD SKRLSTEHSN 480
VSDYPPADGY AYSSSMYHRG PHADHGEAAM PFKSTPNHQV DRNYDAVKTQ PKKYAKSKYD 540
FVARNSSELS VMKDDVLEIL DDRRQWWKVR NASGDSGFVP NNILDIMRTP ESGVGRADPP 600
YTHTIQKQRT EYGLRSADTP SAPSPPPTPA PVPVPLPPSV PAPVSVPKVP ANVTRQNSSS 660
SDSGGSIVRD SQRYKQLPVD RRKSQMEEVQ DELFQRLTIG RSAAQRKFHV PRQNVPVINI 720
TYDSSPEEVK TWLQSKGFNP VTVNSLGVLN GAQLFSLNKD ELRSVCPEGA RVFNQITVQK 780
AALEDSNGSS ELQEIMRRRQ EKISAAASDS GVESFDEGSS H 821 
Gene Ontology
 GO:0005938; C:cell cortex; IDA:UniProtKB.
 GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
 GO:0017146; C:N-methyl-D-aspartate selective glutamate receptor complex; IDA:MGI.
 GO:0014069; C:postsynaptic density; IDA:MGI.
 GO:0032587; C:ruffle membrane; IDA:UniProtKB.
 GO:0032420; C:stereocilium; IDA:UniProtKB.
 GO:0003779; F:actin binding; IDA:UniProtKB.
 GO:0048365; F:Rac GTPase binding; IDA:UniProtKB.
 GO:0051764; P:actin crosslink formation; IDA:UniProtKB.
 GO:0031532; P:actin cytoskeleton reorganization; IMP:MGI.
 GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
 GO:0070358; P:actin polymerization-dependent cell motility; IDA:UniProtKB.
 GO:0008344; P:adult locomotory behavior; IMP:MGI.
 GO:0051016; P:barbed-end actin filament capping; IDA:UniProtKB.
 GO:0048149; P:behavioral response to ethanol; IMP:MGI.
 GO:0036336; P:dendritic cell migration; IMP:UniProtKB.
 GO:0010458; P:exit from mitosis; IMP:UniProtKB.
 GO:0016601; P:Rac protein signal transduction; IDA:UniProtKB.
 GO:0008360; P:regulation of cell shape; IMP: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