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Q5R4H4

- EPS8_PONAB

UniProt

Q5R4H4 - EPS8_PONAB

Protein

Epidermal growth factor receptor kinase substrate 8

Gene

EPS8

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 61 (01 Oct 2014)
      Sequence version 2 (03 Apr 2013)
      Previous versions | rss
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    Functioni

    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.By similarity

    GO - Molecular functioni

    1. actin binding Source: UniProtKB
    2. Rac GTPase binding Source: UniProtKB

    GO - Biological processi

    1. actin crosslink formation Source: UniProtKB
    2. actin filament bundle assembly Source: UniProtKB
    3. actin polymerization-dependent cell motility Source: UniProtKB
    4. barbed-end actin filament capping Source: UniProtKB
    5. dendritic cell migration Source: UniProtKB
    6. exit from mitosis Source: UniProtKB
    7. Rac protein signal transduction Source: UniProtKB
    8. regulation of actin filament length Source: UniProtKB
    9. regulation of cell shape Source: UniProtKB

    Keywords - Ligandi

    Actin-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Epidermal growth factor receptor kinase substrate 8
    Gene namesi
    Name:EPS8
    OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
    Taxonomic identifieri9601 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
    ProteomesiUP000001595: Chromosome 12

    Subcellular locationi

    Cytoplasmcell cortex By similarity. Cell projectionruffle membrane By similarity. Cell projectiongrowth cone By similarity. Cell projectionstereocilium By similarity. Cell junctionsynapsesynaptosome By similarity
    Note: Localizes to the midzone of dividing cells.By similarity

    GO - Cellular componenti

    1. cell cortex Source: UniProtKB
    2. cell junction Source: UniProtKB-KW
    3. growth cone Source: UniProtKB-SubCell
    4. ruffle membrane Source: UniProtKB
    5. stereocilium Source: UniProtKB
    6. synapse Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Synapse, Synaptosome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 822822Epidermal growth factor receptor kinase substrate 8PRO_0000086996Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei317 – 3171PhosphothreonineBy similarity
    Modified residuei476 – 4761PhosphoserineBy similarity
    Modified residuei625 – 6251Phosphoserine; by MAPKBy similarity
    Modified residuei629 – 6291Phosphothreonine; by MAPKBy similarity
    Modified residuei659 – 6591PhosphoserineBy similarity

    Post-translational modificationi

    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.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.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ5R4H4.

    Interactioni

    Subunit structurei

    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.By similarity

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini69 – 12961PH; first partAdd
    BLAST
    Domaini381 – 41434PH; second partAdd
    BLAST
    Domaini531 – 59060SH3PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni649 – 822174Effector regionBy similarityAdd
    BLAST
    Regioni680 – 69819Amphipathic helixBy similarityAdd
    BLAST
    Regioni718 – 73821Helix bundle 1By similarityAdd
    BLAST
    Regioni752 – 7576Helix bundle 2By similarity
    Regioni762 – 7676Helix bundle 3By similarity
    Regioni766 – 78520Helix bundle 4By similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi615 – 65137Pro-richAdd
    BLAST

    Domaini

    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.By similarity
    The SH3 domain mediates interaction with SHB.By similarity

    Sequence similaritiesi

    Belongs to the EPS8 family.Curated
    Contains 1 PH domain.Curated
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH3 domain

    Phylogenomic databases

    GeneTreeiENSGT00390000003646.
    HOVERGENiHBG003090.
    InParanoidiQ5R4H4.
    KOiK17277.
    OrthoDBiEOG7TMZR9.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    InterProiIPR011993. PH_like_dom.
    IPR013625. PTB.
    IPR006020. PTB/PI_dom.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF08416. PTB. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    SMARTiSM00462. PTB. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    PROSITEiPS50002. SH3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q5R4H4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNGHISNHPS SFEMYPSQMN GYGSSPTFSQ MDREHGSKTS AKALYEQRKN    50
    YARDSVSSVS DISQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV 100
    WTQDMILQVD DRAVSLIDLE SKNELENFPL NTIQHCQAVM HSCSYDSVLA 150
    LVCKEPTQNK PDLHLFQCDE VKANLISEDI ESAISDSKGG KQKRRPDALR 200
    MISNADPGIP PPPRAPAPAP PGTVTQVDVR SRVAAWSAWA ADQGDFEKPR 250
    QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR 300
    KKNKKGKRKG PGEGVLTLRA KPPPPDEFLD CFQKFKHGFN LLAKLKSHIQ 350
    NPSAADLVHF LFTPLNMVVQ ATGGPELASS VLSPLLNKDT IDFLNYTVNG 400
    DERQLWMSLG GTWTKARAEW PKEQFIPPYV PRFRNGWEPP MLNFMGATME 450
    QDLYQLAESV ANVAEHQRKQ EIKRLSTEHS SVSEYHPADG YAFSSNIYTR 500
    GSHLDQGEAA VAFKPTSNRH IDRNYEPLKT QPKKYAKSKY DFVARNNSEL 550
    SVLKDDILEI LDDRKQWWKV RNASGDSGFV PNNILDIVRP PESGLGRADP 600
    PYTHTIQKQR MEYGPRPADT PPAPSPPPTP APVPVPLPPS TPAPVPVSKF 650
    PANITRQNSS SSDSGGSIVR DSQRHKQLPV DRRKSQMEEV QDELIHRLTI 700
    GRSAAQKKFH VPRQNVPVIN ITYDSTPEDV KTWLQSKGFN PVTVNSLGVL 750
    NGAQLFSLNK DELRTVCPEG ARVYSQITVQ KAALEDSSGS SELQEIMRRR 800
    QEKISAAASD SGVESFDEGS SH 822
    Length:822
    Mass (Da):91,972
    Last modified:April 3, 2013 - v2
    Checksum:i32ABBCDE17505774
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti41 – 411A → V in CAH90029. 1 PublicationCurated
    Sequence conflicti270 – 2701V → A in CAH90029. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    RefSeqiNP_001127655.1. NM_001134183.1.
    UniGeneiPab.1694.

    Genome annotation databases

    EnsembliENSPPYT00000033390; ENSPPYP00000024127; ENSPPYG00000004333.
    GeneIDi100174737.
    KEGGipon:100174737.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    RefSeqi NP_001127655.1. NM_001134183.1.
    UniGenei Pab.1694.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Proteomic databases

    PRIDEi Q5R4H4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSPPYT00000033390 ; ENSPPYP00000024127 ; ENSPPYG00000004333 .
    GeneIDi 100174737.
    KEGGi pon:100174737.

    Organism-specific databases

    CTDi 2059.

    Phylogenomic databases

    GeneTreei ENSGT00390000003646.
    HOVERGENi HBG003090.
    InParanoidi Q5R4H4.
    KOi K17277.
    OrthoDBi EOG7TMZR9.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    InterProi IPR011993. PH_like_dom.
    IPR013625. PTB.
    IPR006020. PTB/PI_dom.
    IPR001452. SH3_domain.
    [Graphical view ]
    Pfami PF08416. PTB. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    SMARTi SM00462. PTB. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    PROSITEi PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
    2. "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].

    Entry informationi

    Entry nameiEPS8_PONAB
    AccessioniPrimary (citable) accession number: Q5R4H4
    Secondary accession number(s): K7EUA3, Q5RDX8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 30, 2005
    Last sequence update: April 3, 2013
    Last modified: October 1, 2014
    This is version 61 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3