Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein enabled homolog

Gene

Enah

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation.4 Publications

GO - Molecular functioni

  • profilin binding Source: UniProtKB
  • SH3 domain binding Source: MGI
  • WW domain binding Source: MGI

GO - Biological processi

  • actin cytoskeleton organization Source: MGI
  • actin filament organization Source: UniProtKB
  • actin polymerization or depolymerization Source: MGI
  • axon guidance Source: MGI
  • movement of cell or subcellular component Source: UniProtKB
  • neural tube closure Source: MGI
  • T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Keywords - Ligandi

Actin-binding

Enzyme and pathway databases

ReactomeiR-MMU-202433. Generation of second messenger molecules.
R-MMU-376176. Signaling by Robo receptor.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein enabled homolog
Alternative name(s):
NPC-derived proline-rich protein 1
Short name:
NDPP-1
Gene namesi
Name:Enah
Synonyms:Mena, Ndpp1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:108360. Enah.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: MGI
  • cell junction Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: Reactome
  • filopodium Source: MGI
  • focal adhesion Source: UniProtKB
  • lamellipodium Source: MGI
  • plasma membrane Source: MGI
  • stress fiber Source: MGI
  • synapse Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Cytoskeleton, Synapse

Pathology & Biotechi

Disruption phenotypei

Mutant animals are viable and recovered in the appropriate Mendelian ratios. they are smaller than their littermates until adulthood and exhibit abnormal cage behavior, including reduced activity.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi255S → A: No change in subcellular location nor colocalization with vinculin at focal adhesions nor with N-WASP at the leading edge. Loss of cell mobility function; when associated with A-637. 1 Publication1
Mutagenesisi255S → D: No change in subcellular location nor colocalization with vinculin at focal adhesions nor with N-WASP at the leading edge. No loss of cell mobility function; when associated with D-637. 1 Publication1
Mutagenesisi637S → A: No change in subcellular location nor colocalization with vinculin at focal adhesions nor with N-WASP at the leading edge. No loss of cell mobility function. when associated with A-255. 1 Publication1
Mutagenesisi637S → D: No change in subcellular location nor colocalization with vinculin at focal adhesions nor with N-WASP at the leading edge. No loss of cell mobility function. when associated with D-255. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000869721 – 802Protein enabled homologAdd BLAST802

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei144PhosphoserineCombined sources1
Modified residuei255Phosphoserine; by PKACombined sources1 Publication1
Modified residuei383PhosphoserineCombined sources1
Modified residuei557Phosphotyrosine1 Publication1
Modified residuei738PhosphoserineBy similarity1
Modified residuei740PhosphoserineBy similarity1

Post-translational modificationi

NTN1-induced PKA phosphorylation on Ser-255 directly parallels the formation of filopodial protrusions.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ03173.
PaxDbiQ03173.
PeptideAtlasiQ03173.
PRIDEiQ03173.

PTM databases

iPTMnetiQ03173.
PhosphoSitePlusiQ03173.

Expressioni

Tissue specificityi

Expressed in heart and testis, lower levels in lung, skeletal muscle, kidney, pancreas and brain. Isoform 5 is expressed exclusively in the brain. Isoform 2 is expressed predominantly in brain, testis, ovary and fat. In the brain, isoforms 2 and 5 are expressed at highest levels in the hippocampus, cortex and midbrain, and at lowest levels in the striatum and cerebellum. Isoform 6 is expressed in brain and spleen.3 Publications

Developmental stagei

At 8.5 dpc, particularly enriched in the neuroepithelium, the forebrain and the somites. Highly expressed in the edges of the neural folds. By 10.5 dpc, detected in the brain, dorsal root ganglia (DRG), somites and limb buds. Highly expressed in the branchial and pharyngeal arches, neural crest-derived structures that give rise to portions of the face and neck. At 11 dpc, isoform 2, isoform 3 and isoform 5 are expressed in embryonic brain (at protein level). Expression of isoform 3 decreases steadily and becomes almost undetectable by 16 dpc, while expression of isoform 5 begins to increase from 13 dpc and peaks between 16 and 18 dpc (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000022995.
CleanExiMM_ENAH.
ExpressionAtlasiQ03173. baseline and differential.
GenevisibleiQ03173. MM.

Interactioni

Subunit structurei

Homotetramer (By similarity). Interacts with APBB1IP, APBB1, PFN1 and ROBO4. Isoforms, containing the polyproline-rich regions with PPLP motifs, bind the WW domain of APBB1IP. Isoforms, containing the PPSY motif, bind, in vitro, to the WW2 and WW3 domains of NEDD4 and to the WW1 domain of YAP1. Binds the SH3 domain of BAIAP2-alpha but only after the autoinhibitory region of BAIAP2-alpha has been blocked by interaction with CDC42. Interacts, via the EVH1/WH1 domain, with the Pro-rich domains from VCL, ZYX and Listeria monocytogenes actA and with TES (via LIM domain). The TES LIM domain and the Pro-rich domains from VCL or ZYX compete for the same binding site. Interaction with ZYX is important for targeting ENAH to focal adhesions and enhances production of actin-rich structures at the apical surface of cells. Interacts, through the Pro-rich region, with the C-terminal SH3 domain of DNMPB. Binds GPHN. Heterotrimer with TES and ACTL7A (By similarity). Interacts with FAT1 (via EVH1 domains).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BAIAP2Q9UQB83EBI-6083294,EBI-525456From a different organism.

GO - Molecular functioni

  • profilin binding Source: UniProtKB
  • SH3 domain binding Source: MGI
  • WW domain binding Source: MGI

Protein-protein interaction databases

BioGridi199446. 12 interactors.
DIPiDIP-29359N.
IntActiQ03173. 7 interactors.
MINTiMINT-1215621.
STRINGi10090.ENSMUSP00000077781.

Structurei

Secondary structure

1802
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 17Combined sources15
Turni18 – 21Combined sources4
Beta strandi22 – 25Combined sources4
Helixi26 – 28Combined sources3
Beta strandi33 – 40Combined sources8
Turni41 – 44Combined sources4
Beta strandi45 – 52Combined sources8
Turni53 – 55Combined sources3
Beta strandi58 – 64Combined sources7
Beta strandi74 – 81Combined sources8
Beta strandi86 – 93Combined sources8
Helixi94 – 111Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EVHX-ray1.80A1-112[»]
4CC3X-ray1.97B/D/F/H547-558[»]
ProteinModelPortaliQ03173.
SMRiQ03173.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ03173.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 111WH1PROSITE-ProRule annotationAdd BLAST111
Repeati175 – 17915
Repeati180 – 18425
Repeati185 – 18935
Repeati190 – 19445
Repeati195 – 19955
Repeati200 – 20465
Repeati205 – 20975

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 2097 X 5 AA tandem repeats of [LM]-E-[QR]-[EQ]-[QR]Add BLAST35
Regioni623 – 799EVH2Add BLAST177
Regioni623 – 643EVH2 block AAdd BLAST21
Regioni674 – 691EVH2 block BAdd BLAST18
Regioni765 – 799EVH2 block CAdd BLAST35

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili154 – 258Sequence analysisAdd BLAST105
Coiled coili767 – 797Sequence analysisAdd BLAST31

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi632 – 635KLKR4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi269 – 605Pro-richAdd BLAST337

Domaini

The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.

Sequence similaritiesi

Belongs to the Ena/VASP family.Curated
Contains 1 WH1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, SH3-binding

Phylogenomic databases

eggNOGiKOG4590. Eukaryota.
ENOG41101TS. LUCA.
GeneTreeiENSGT00730000110272.
HOGENOMiHOG000013015.
HOVERGENiHBG006655.
InParanoidiQ03173.
KOiK05746.
PhylomeDBiQ03173.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR014885. VASP_tetra.
IPR000697. WH1/EVH1_dom.
[Graphical view]
PfamiPF08776. VASP_tetra. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
SMARTiSM00461. WH1. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50229. WH1. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 5 (identifier: Q03173-1) [UniParc]FASTAAdd to basket
Also known as: Neural variant Mena+++, 140 kDa isoform

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
MSEQSICQAR AAVMVYDDAN KKWVPAGGST GFSRVHIYHH TGNNTFRVVG
60 70 80 90 100
RKIQDHQVVI NCAIPKGLKY NQATQTFHQW RDARQVYGLN FGSKEDANVF
110 120 130 140 150
ASAMMHALEV LNSQEAAQSK VTATQDSTNL RCIFCGPTLP RQNSQLPAQV
160 170 180 190 200
QNGPSQEELE IQRRQLQEQQ RQKELERERM ERERLERERL ERERLERERL
210 220 230 240 250
EQEQLERQRQ EREHVERLER ERLERLERER QERERERLEQ LEREQVEWER
260 270 280 290 300
ERRMSNAAPS SDSSLSSAPL PEYSSCQPPS APPPSYAKVI SAPVSDATPD
310 320 330 340 350
YAVVTALPPT STPPTPPLRH AATRFATSLG SAFHPVLPHY ATVPRPLNKN
360 370 380 390 400
SRPSSPVNTP SSQPPAAKSC AWPTSNFSPL PPSPPIMISS PPGKATGPRP
410 420 430 440 450
VLPVCVSSPV PQMPPSPTAP NGSLDSVTYP VSPPPTSGPA APPPPPPPPP
460 470 480 490 500
PPPPPPLPPP PLPPLASLSH CGSQASPPPG TPLASTPSSK PSVLPSPSAG
510 520 530 540 550
APASAETPLN PELGDSSASE PGLQAASQPA ESPTPQGLVL GPPAPPPPPP
560 570 580 590 600
LPSGPAYASA LPPPPGPPPP PPLPSTGPPP PPPPPPPLPN QAPPPPPPPP
610 620 630 640 650
APPLPASGIF SGSTSEDNRP LTGLAAAIAG AKLRKVSRVE DGSFPGGGNT
660 670 680 690 700
GSVSLASSKA DAGRGNGPLP LGGSGLMEEM SALLARRRRI AEKGSTIETE
710 720 730 740 750
QKEDRNEDAE PITAKAPSTS TPEPTRKPWE RTNTMNGSKS PVISRPKSTP
760 770 780 790 800
SSQPSANGVQ TEGLDYDRLK QDILDEMRKE LAKLKEELID AIRQELSKSN

TA
Length:802
Mass (Da):85,844
Last modified:April 23, 2003 - v2
Checksum:i592BB975EE20F77F
GO
Isoform 1 (identifier: Q03173-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-412: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:390
Mass (Da):39,306
Checksum:i1AA5DDB306450847
GO
Isoform 2 (identifier: Q03173-3) [UniParc]FASTAAdd to basket
Also known as: Mena, 80 kDa isoform

The sequence of this isoform differs from the canonical sequence as follows:
     117-135: Missing.
     259-500: Missing.

Show »
Length:541
Mass (Da):59,643
Checksum:i19B25FD175DF0451
GO
Isoform 3 (identifier: Q03173-4) [UniParc]FASTAAdd to basket
Also known as: Neural variant Mena+

The sequence of this isoform differs from the canonical sequence as follows:
     117-135: Missing.

Note: Phosphorylated during neural development.
Show »
Length:783
Mass (Da):83,776
Checksum:i5E610BE7FDDA97FE
GO
Isoform 4 (identifier: Q03173-5) [UniParc]FASTAAdd to basket
Also known as: Neural variant Mena++

The sequence of this isoform differs from the canonical sequence as follows:
     117-131: Missing.
     132-135: CIFC → VFYL

Show »
Length:787
Mass (Da):84,299
Checksum:i18C228F070EDCCF2
GO
Isoform 6 (identifier: Q03173-6) [UniParc]FASTAAdd to basket
Also known as: Mena(S)

The sequence of this isoform differs from the canonical sequence as follows:
     117-135: Missing.
     259-500: Missing.
     561-594: Missing.

Show »
Length:507
Mass (Da):56,357
Checksum:iFA0C43AAD240503C
GO

Sequence cautioni

The sequence BAA01570 differs from that shown. Reason: Frameshift at several positions.Curated
Isoform 1 : The sequence BAA01570 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti500G → A in BAA01570 (PubMed:1420303).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0072551 – 412Missing in isoform 1. 1 PublicationAdd BLAST412
Alternative sequenceiVSP_007259117 – 135Missing in isoform 2, isoform 3 and isoform 6. 2 PublicationsAdd BLAST19
Alternative sequenceiVSP_007257117 – 131Missing in isoform 4. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_007258132 – 135CIFC → VFYL in isoform 4. 1 Publication4
Alternative sequenceiVSP_007260259 – 500Missing in isoform 2 and isoform 6. 2 PublicationsAdd BLAST242
Alternative sequenceiVSP_010565561 – 594Missing in isoform 6. CuratedAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10727 mRNA. Translation: BAA01570.1. Frameshift.
U72520 mRNA. Translation: AAC52863.1.
U72521 mRNA. Translation: AAC52864.1.
U72522 mRNA. Translation: AAC52865.1.
U72523 mRNA. Translation: AAC52866.1.
BC062927 mRNA. Translation: AAH62927.1.
CCDSiCCDS78764.1. [Q03173-3]
PIRiS27200.
RefSeqiNP_001076590.1. NM_001083121.2. [Q03173-3]
UniGeneiMm.389224.
Mm.87759.

Genome annotation databases

EnsembliENSMUST00000111025; ENSMUSP00000106654; ENSMUSG00000022995. [Q03173-6]
ENSMUST00000193703; ENSMUSP00000141462; ENSMUSG00000022995. [Q03173-3]
GeneIDi13800.
KEGGimmu:13800.
UCSCiuc007dxs.2. mouse. [Q03173-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10727 mRNA. Translation: BAA01570.1. Frameshift.
U72520 mRNA. Translation: AAC52863.1.
U72521 mRNA. Translation: AAC52864.1.
U72522 mRNA. Translation: AAC52865.1.
U72523 mRNA. Translation: AAC52866.1.
BC062927 mRNA. Translation: AAH62927.1.
CCDSiCCDS78764.1. [Q03173-3]
PIRiS27200.
RefSeqiNP_001076590.1. NM_001083121.2. [Q03173-3]
UniGeneiMm.389224.
Mm.87759.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EVHX-ray1.80A1-112[»]
4CC3X-ray1.97B/D/F/H547-558[»]
ProteinModelPortaliQ03173.
SMRiQ03173.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199446. 12 interactors.
DIPiDIP-29359N.
IntActiQ03173. 7 interactors.
MINTiMINT-1215621.
STRINGi10090.ENSMUSP00000077781.

PTM databases

iPTMnetiQ03173.
PhosphoSitePlusiQ03173.

Proteomic databases

MaxQBiQ03173.
PaxDbiQ03173.
PeptideAtlasiQ03173.
PRIDEiQ03173.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000111025; ENSMUSP00000106654; ENSMUSG00000022995. [Q03173-6]
ENSMUST00000193703; ENSMUSP00000141462; ENSMUSG00000022995. [Q03173-3]
GeneIDi13800.
KEGGimmu:13800.
UCSCiuc007dxs.2. mouse. [Q03173-3]

Organism-specific databases

CTDi55740.
MGIiMGI:108360. Enah.

Phylogenomic databases

eggNOGiKOG4590. Eukaryota.
ENOG41101TS. LUCA.
GeneTreeiENSGT00730000110272.
HOGENOMiHOG000013015.
HOVERGENiHBG006655.
InParanoidiQ03173.
KOiK05746.
PhylomeDBiQ03173.

Enzyme and pathway databases

ReactomeiR-MMU-202433. Generation of second messenger molecules.
R-MMU-376176. Signaling by Robo receptor.

Miscellaneous databases

ChiTaRSiEnah. mouse.
EvolutionaryTraceiQ03173.
PROiQ03173.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022995.
CleanExiMM_ENAH.
ExpressionAtlasiQ03173. baseline and differential.
GenevisibleiQ03173. MM.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR014885. VASP_tetra.
IPR000697. WH1/EVH1_dom.
[Graphical view]
PfamiPF08776. VASP_tetra. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
SMARTiSM00461. WH1. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50229. WH1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiENAH_MOUSE
AccessioniPrimary (citable) accession number: Q03173
Secondary accession number(s): P70430
, P70431, P70432, P70433, Q5D053
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 23, 2003
Last modified: November 2, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Required to transform actin polymerization into active movement for the propulsive force of Listeria monocytogenes.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.