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Protein

Epidermal growth factor receptor kinase substrate 8

Gene

EPS8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 WHRN 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.2 Publications

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • Rac GTPase binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionActin-binding

Enzyme and pathway databases

SignaLinkiQ12929

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor kinase substrate 8
Gene namesi
Name:EPS8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000151491.12
HGNCiHGNC:3420 EPS8
MIMi600206 gene
neXtProtiNX_Q12929

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 102 (DFNB102)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic deafness characterized by profound hearing loss affecting all frequencies. Vestibular function is unaffected.
See also OMIM:615974
Defects in EPS8 are associated with some cancers, such as pancreatic, oral squamous cell carcinomas or pituitary cancers. Contributes to cell transformation in response to growth factor treatment and is overexpressed in a number of tumors, indicating that EPS8 levels must be tightly regulated.5 Publications

Keywords - Diseasei

Deafness, Non-syndromic deafness

Organism-specific databases

DisGeNETi2059
MalaCardsiEPS8
MIMi615974 phenotype
OpenTargetsiENSG00000151491
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBiPA27839

Polymorphism and mutation databases

BioMutaiEPS8
DMDMi2833239

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000869941 – 822Epidermal growth factor receptor kinase substrate 8Add BLAST822

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei58PhosphoserineBy similarity1
Modified residuei223PhosphothreonineCombined sources1
Modified residuei317PhosphothreonineBy similarity1
Modified residuei476PhosphoserineCombined sources1
Modified residuei625PhosphoserineCombined sources1
Modified residuei629Phosphothreonine; by MAPKBy similarity1
Modified residuei659PhosphoserineBy similarity1
Modified residuei662PhosphoserineBy similarity1
Modified residuei685PhosphoserineBy similarity1
Modified residuei811PhosphoserineBy similarity1
Modified residuei815PhosphoserineBy similarity1

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 (By similarity). Phosphorylated by several receptor tyrosine kinases.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ12929
MaxQBiQ12929
PaxDbiQ12929
PeptideAtlasiQ12929
PRIDEiQ12929
ProteomicsDBi59033

PTM databases

iPTMnetiQ12929
PhosphoSitePlusiQ12929

Expressioni

Tissue specificityi

Expressed in all tissues analyzed, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed in all epithelial and fibroblastic lines examined and in some, but not all, hematopoietic cells.

Gene expression databases

BgeeiENSG00000151491 Expressed in 235 organ(s), highest expression level in caput epididymis
CleanExiHS_EPS8
ExpressionAtlasiQ12929 baseline and differential
GenevisibleiQ12929 HS

Organism-specific databases

HPAiHPA003897

Interactioni

Subunit structurei

Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with MYO15A and WHRN. Interacts with LANCL1 (By similarity). Interacts with EGFR; mediates EPS8 phosphorylation (By similarity). Interacts with BAIAP2. Interacts with SHB.By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108373, 62 interactors
CORUMiQ12929
DIPiDIP-32859N
IntActiQ12929, 59 interactors
MINTiQ12929
STRINGi9606.ENSP00000281172

Structurei

Secondary structure

1822
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ12929
SMRiQ12929
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ12929

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini69 – 129PH; first partAdd BLAST61
Domaini381 – 414PH; second partAdd BLAST34
Domaini531 – 590SH3PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni649 – 822Effector regionBy similarityAdd BLAST174
Regioni680 – 698Amphipathic helixBy similarityAdd BLAST19
Regioni718 – 738Helix bundle 1By similarityAdd BLAST21
Regioni752 – 757Helix bundle 2By similarity6
Regioni762 – 767Helix bundle 3By similarity6
Regioni766 – 785Helix bundle 4By similarityAdd BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi421 – 440Pro-richAdd BLAST20
Compositional biasi615 – 651Pro-richAdd BLAST37
Compositional biasi659 – 664Poly-Ser6

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.

Sequence similaritiesi

Belongs to the EPS8 family.Curated

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG3557 Eukaryota
ENOG410XT9R LUCA
GeneTreeiENSGT00390000003646
HOGENOMiHOG000060324
HOVERGENiHBG003090
InParanoidiQ12929
KOiK17277
OMAiAEWPKEQ
OrthoDBiEOG091G023T
PhylomeDBiQ12929
TreeFamiTF313069

Family and domain databases

CDDicd01210 PTB_EPS8, 1 hit
cd11764 SH3_Eps8, 1 hit
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR030222 EPS8
IPR033928 EPS8_PTB
IPR035462 Eps8_SH3
IPR011993 PH-like_dom_sf
IPR013625 PTB
IPR006020 PTB/PI_dom
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR12287:SF21 PTHR12287:SF21, 1 hit
PfamiView protein in Pfam
PF08416 PTB, 1 hit
PF00018 SH3_1, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS50002 SH3, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q12929-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MNGHISNHPS SFGMYPSQMN GYGSSPTFSQ TDREHGSKTS AKALYEQRKN
60 70 80 90 100
YARDSVSSVS DISQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV
110 120 130 140 150
WTQDMILQVD DRAVSLIDLE SKNELENFPL NTIQHCQAVM HSCSYDSVLA
160 170 180 190 200
LVCKEPTQNK PDLHLFQCDE VKANLISEDI ESAISDSKGG KQKRRPDALR
210 220 230 240 250
MISNADPSIP PPPRAPAPAP PGTVTQVDVR SRVAAWSAWA ADQGDFEKPR
260 270 280 290 300
QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR
310 320 330 340 350
KKNKKGKRKG PGEGVLTLRA KPPPPDEFLD CFQKFKHGFN LLAKLKSHIQ
360 370 380 390 400
NPSAADLVHF LFTPLNMVVQ ATGGPELASS VLSPLLNKDT IDFLNYTVNG
410 420 430 440 450
DERQLWMSLG GTWMKARAEW PKEQFIPPYV PRFRNGWEPP MLNFMGATME
460 470 480 490 500
QDLYQLAESV ANVAEHQRKQ EIKRLSTEHS SVSEYHPADG YAFSSNIYTR
510 520 530 540 550
GSHLDQGEAA VAFKPTSNRH IDRNYEPLKT QPKKYAKSKY DFVARNNSEL
560 570 580 590 600
SVLKDDILEI LDDRKQWWKV RNASGDSGFV PNNILDIVRP PESGLGRADP
610 620 630 640 650
PYTHTIQKQR MEYGPRPADT PPAPSPPPTP APVPVPLPPS TPAPVPVSKV
660 670 680 690 700
PANITRQNSS SSDSGGSIVR DSQRHKQLPV DRRKSQMEEV QDELIHRLTI
710 720 730 740 750
GRSAAQKKFH VPRQNVPVIN ITYDSTPEDV KTWLQSKGFN PVTVNSLGVL
760 770 780 790 800
NGAQLFSLNK DELRTVCPEG ARVYSQITVQ KAALEDSSGS SELQEIMRRR
810 820
QEKISAAASD SGVESFDEGS SH
Length:822
Mass (Da):91,882
Last modified:November 1, 1996 - v1
Checksum:iAC5EB1D28B784B3B
GO
Isoform 2 (identifier: Q12929-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-260: Missing.

Note: No experimental confirmation available.
Show »
Length:562
Mass (Da):62,871
Checksum:i8670D1025054D476
GO

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H0R8F5H0R8_HUMAN
Epidermal growth factor receptor ki...
EPS8
200Annotation score:
F5GYM8F5GYM8_HUMAN
Epidermal growth factor receptor ki...
EPS8
120Annotation score:
F5H3Q6F5H3Q6_HUMAN
Epidermal growth factor receptor ki...
EPS8
128Annotation score:
H0YFG1H0YFG1_HUMAN
Epidermal growth factor receptor ki...
EPS8
68Annotation score:
F5H2B8F5H2B8_HUMAN
Epidermal growth factor receptor ki...
EPS8
68Annotation score:
F5H1B5F5H1B5_HUMAN
Epidermal growth factor receptor ki...
EPS8
67Annotation score:
A0A2R8YE63A0A2R8YE63_HUMAN
Epidermal growth factor receptor ki...
EPS8
839Annotation score:
A0A2R8Y4W2A0A2R8Y4W2_HUMAN
Epidermal growth factor receptor ki...
EPS8
830Annotation score:
F5H714F5H714_HUMAN
Epidermal growth factor receptor ki...
EPS8
41Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti73F → S in BAF84466 (PubMed:14702039).Curated1
Sequence conflicti128F → S in BAF84466 (PubMed:14702039).Curated1
Sequence conflicti194R → G in BAF84466 (PubMed:14702039).Curated1
Sequence conflicti205A → S in BAF85620 (PubMed:14702039).Curated1
Sequence conflicti497I → V in BAF85620 (PubMed:14702039).Curated1
Sequence conflicti631A → V in AAH30010 (PubMed:15489334).Curated1
Sequence conflicti705A → T in BAF85620 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050971761D → E1 PublicationCorresponds to variant dbSNP:rs7137185EnsemblClinVar.1
Natural variantiVAR_050972806A → S. Corresponds to variant dbSNP:rs1802658Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564601 – 260Missing in isoform 2. 1 PublicationAdd BLAST260

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12535 mRNA Translation: AAA62280.1
AK291777 mRNA Translation: BAF84466.1
AK292931 mRNA Translation: BAF85620.1
AK301834 mRNA Translation: BAG63278.1
AK316134 mRNA Translation: BAH14505.1
AK316239 mRNA Translation: BAH14610.1
AC022073 Genomic DNA No translation available.
AC073651 Genomic DNA No translation available.
AC092753 Genomic DNA No translation available.
CH471094 Genomic DNA Translation: EAW96354.1
CH471094 Genomic DNA Translation: EAW96355.1
BC030010 mRNA Translation: AAH30010.1
CCDSiCCDS31753.1 [Q12929-1]
PIRiI38728
RefSeqiNP_004438.3, NM_004447.5 [Q12929-1]
UniGeneiHs.591160

Genome annotation databases

EnsembliENST00000281172; ENSP00000281172; ENSG00000151491 [Q12929-1]
ENST00000540613; ENSP00000441888; ENSG00000151491 [Q12929-2]
ENST00000542903; ENSP00000437806; ENSG00000151491 [Q12929-2]
ENST00000543523; ENSP00000441867; ENSG00000151491 [Q12929-1]
ENST00000543612; ENSP00000442388; ENSG00000151491 [Q12929-1]
ENST00000642278; ENSP00000494689; ENSG00000151491 [Q12929-1]
ENST00000644374; ENSP00000495956; ENSG00000151491 [Q12929-1]
ENST00000645775; ENSP00000495824; ENSG00000151491 [Q12929-1]
ENST00000646828; ENSP00000494842; ENSG00000151491 [Q12929-1]
ENST00000646918; ENSP00000495722; ENSG00000151491 [Q12929-1]
ENST00000647087; ENSP00000496406; ENSG00000151491 [Q12929-1]
ENST00000647224; ENSP00000496516; ENSG00000151491 [Q12929-1]
GeneIDi2059
KEGGihsa:2059
UCSCiuc001rdb.4 human [Q12929-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12535 mRNA Translation: AAA62280.1
AK291777 mRNA Translation: BAF84466.1
AK292931 mRNA Translation: BAF85620.1
AK301834 mRNA Translation: BAG63278.1
AK316134 mRNA Translation: BAH14505.1
AK316239 mRNA Translation: BAH14610.1
AC022073 Genomic DNA No translation available.
AC073651 Genomic DNA No translation available.
AC092753 Genomic DNA No translation available.
CH471094 Genomic DNA Translation: EAW96354.1
CH471094 Genomic DNA Translation: EAW96355.1
BC030010 mRNA Translation: AAH30010.1
CCDSiCCDS31753.1 [Q12929-1]
PIRiI38728
RefSeqiNP_004438.3, NM_004447.5 [Q12929-1]
UniGeneiHs.591160

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E8MNMR-A699-784[»]
ProteinModelPortaliQ12929
SMRiQ12929
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108373, 62 interactors
CORUMiQ12929
DIPiDIP-32859N
IntActiQ12929, 59 interactors
MINTiQ12929
STRINGi9606.ENSP00000281172

PTM databases

iPTMnetiQ12929
PhosphoSitePlusiQ12929

Polymorphism and mutation databases

BioMutaiEPS8
DMDMi2833239

Proteomic databases

EPDiQ12929
MaxQBiQ12929
PaxDbiQ12929
PeptideAtlasiQ12929
PRIDEiQ12929
ProteomicsDBi59033

Protocols and materials databases

DNASUi2059
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000281172; ENSP00000281172; ENSG00000151491 [Q12929-1]
ENST00000540613; ENSP00000441888; ENSG00000151491 [Q12929-2]
ENST00000542903; ENSP00000437806; ENSG00000151491 [Q12929-2]
ENST00000543523; ENSP00000441867; ENSG00000151491 [Q12929-1]
ENST00000543612; ENSP00000442388; ENSG00000151491 [Q12929-1]
ENST00000642278; ENSP00000494689; ENSG00000151491 [Q12929-1]
ENST00000644374; ENSP00000495956; ENSG00000151491 [Q12929-1]
ENST00000645775; ENSP00000495824; ENSG00000151491 [Q12929-1]
ENST00000646828; ENSP00000494842; ENSG00000151491 [Q12929-1]
ENST00000646918; ENSP00000495722; ENSG00000151491 [Q12929-1]
ENST00000647087; ENSP00000496406; ENSG00000151491 [Q12929-1]
ENST00000647224; ENSP00000496516; ENSG00000151491 [Q12929-1]
GeneIDi2059
KEGGihsa:2059
UCSCiuc001rdb.4 human [Q12929-1]

Organism-specific databases

CTDi2059
DisGeNETi2059
EuPathDBiHostDB:ENSG00000151491.12
GeneCardsiEPS8
HGNCiHGNC:3420 EPS8
HPAiHPA003897
MalaCardsiEPS8
MIMi600206 gene
615974 phenotype
neXtProtiNX_Q12929
OpenTargetsiENSG00000151491
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBiPA27839
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3557 Eukaryota
ENOG410XT9R LUCA
GeneTreeiENSGT00390000003646
HOGENOMiHOG000060324
HOVERGENiHBG003090
InParanoidiQ12929
KOiK17277
OMAiAEWPKEQ
OrthoDBiEOG091G023T
PhylomeDBiQ12929
TreeFamiTF313069

Enzyme and pathway databases

SignaLinkiQ12929

Miscellaneous databases

ChiTaRSiEPS8 human
EvolutionaryTraceiQ12929
GeneWikiiEPS8
GenomeRNAii2059
PROiPR:Q12929
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151491 Expressed in 235 organ(s), highest expression level in caput epididymis
CleanExiHS_EPS8
ExpressionAtlasiQ12929 baseline and differential
GenevisibleiQ12929 HS

Family and domain databases

CDDicd01210 PTB_EPS8, 1 hit
cd11764 SH3_Eps8, 1 hit
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR030222 EPS8
IPR033928 EPS8_PTB
IPR035462 Eps8_SH3
IPR011993 PH-like_dom_sf
IPR013625 PTB
IPR006020 PTB/PI_dom
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR12287:SF21 PTHR12287:SF21, 1 hit
PfamiView protein in Pfam
PF08416 PTB, 1 hit
PF00018 SH3_1, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEPS8_HUMAN
AccessioniPrimary (citable) accession number: Q12929
Secondary accession number(s): A6NMC3
, A8K6W2, A8KA66, B4DX66, Q8N6J0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 169 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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