Q5R4H4 (EPS8_PONAB) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 58. History...
Names and origin
|Protein names||Recommended name:|
Epidermal growth factor receptor kinase substrate 8
|Organism||Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]|
|Taxonomic identifier||9601 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pongo|
|Sequence length||822 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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.
Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with BAIAP2. Interacts with SHB and LANCL1. Interacts with EGFR; mediates EPS8 phosphorylation. Interacts with MYO15A and DFNB31 By similarity.
Cytoplasm › cell cortex By similarity. Cell projection › ruffle membrane By similarity. Cell projection › growth cone By similarity. Cell projection › stereocilium By similarity. Note: Localizes to the midzone of dividing cells By similarity.
The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. It mediates both barbed-end actin capping and actin bundling activities. The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament By similarity.
The SH3 domain mediates interaction with SHB By similarity.
Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during G2 phase, leading to its transient degradation and subsequent cell shape changes required to allow mitotic progression. Reappears at the midzone of dividing cells By similarity.
Phosphorylation at Ser-625 and Thr-629 by MAPK following BDNF treatment promotes removal from actin and filopodia formation. Phosphorylated by several receptor tyrosine kinases By similarity.
Belongs to the EPS8 family.
Contains 1 PH domain.
Contains 1 SH3 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 822||822||Epidermal growth factor receptor kinase substrate 8||PRO_0000086996|
|Domain||69 – 129||61||PH; first part|
|Domain||381 – 414||34||PH; second part|
|Domain||531 – 590||60||SH3|
|Region||649 – 822||174||Effector region By similarity|
|Region||680 – 698||19||Amphipathic helix By similarity|
|Region||718 – 738||21||Helix bundle 1 By similarity|
|Region||752 – 757||6||Helix bundle 2 By similarity|
|Region||762 – 767||6||Helix bundle 3 By similarity|
|Region||766 – 785||20||Helix bundle 4 By similarity|
|Compositional bias||615 – 651||37||Pro-rich|
Amino acid modifications
|Modified residue||317||1||Phosphothreonine By similarity|
|Modified residue||476||1||Phosphoserine By similarity|
|Modified residue||625||1||Phosphoserine; by MAPK By similarity|
|Modified residue||629||1||Phosphothreonine; by MAPK By similarity|
|Modified residue||659||1||Phosphoserine By similarity|
|Sequence conflict||41||1||A → V in CAH90029. Ref.1|
|Sequence conflict||270||1||V → A in CAH90029. Ref.1|
|||The German cDNA consortium|
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain cortex and Kidney.
|||"A 6x draft sequence assembly of the Pongo pygmaeus abelii genome."|
Wilson R.K., Mardis E.
Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|CR857764 mRNA. Translation: CAH90029.1.|
CR861274 mRNA. Translation: CAH93342.1.
ABGA01225282 Genomic DNA. No translation available.
ABGA01225283 Genomic DNA. No translation available.
ABGA01225284 Genomic DNA. No translation available.
ABGA01225285 Genomic DNA. No translation available.
ABGA01225286 Genomic DNA. No translation available.
ABGA01225287 Genomic DNA. No translation available.
ABGA01225288 Genomic DNA. No translation available.
ABGA01225289 Genomic DNA. No translation available.
ABGA01225290 Genomic DNA. No translation available.
ABGA01225291 Genomic DNA. No translation available.
ABGA01225292 Genomic DNA. No translation available.
ABGA01225293 Genomic DNA. No translation available.
ABGA01225294 Genomic DNA. No translation available.
ABGA01225295 Genomic DNA. No translation available.
ABGA01225296 Genomic DNA. No translation available.
ABGA01225297 Genomic DNA. No translation available.
ABGA01225298 Genomic DNA. No translation available.
ABGA01225299 Genomic DNA. No translation available.
ABGA01225300 Genomic DNA. No translation available.
|RefSeq||NP_001127655.1. NM_001134183.1. |
3D structure databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSPPYT00000033390; ENSPPYP00000024127; ENSPPYG00000004333. |
Family and domain databases
|Gene3D||22.214.171.124. 1 hit. |
|InterPro||IPR011993. PH_like_dom. |
|Pfam||PF08416. PTB. 1 hit. |
PF00018. SH3_1. 1 hit.
|SMART||SM00462. PTB. 1 hit. |
SM00326. SH3. 1 hit.
|SUPFAM||SSF50044. SSF50044. 1 hit. |
|PROSITE||PS50003. PH_DOMAIN. False negative. |
PS50002. SH3. 1 hit.
|Accession||Primary (citable) accession number: Q5R4H4|
Secondary accession number(s): K7EUA3, Q5RDX8
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families