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Q03173 (ENAH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein enabled homolog
Alternative name(s):
NPC-derived proline-rich protein 1
Short name=NDPP-1
Gene names
Name:Enah
Synonyms:Mena, Ndpp1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length802 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.5 Ref.6 Ref.12

Subunit structure

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). Ref.2 Ref.4 Ref.7 Ref.8 Ref.9 Ref.10 Ref.13

Subcellular location

Cytoplasm. Cytoplasmcytoskeleton By similarity. Cell projectionlamellipodium By similarity. Cell projectionfilopodium By similarity. Cell junctionsynapse By similarity. Cell junctionfocal adhesion By similarity. Note: Targeted to the leading edge of lamellipodia and filopodia by MRL family members. Colocalizes at filopodial tips with a number of other proteins including vinculin and zyxlin. Colocalizes with N-WASP at the leading edge. Colocalizes with GPHN and PFN at synapses By similarity. Ref.2 Ref.5 Ref.6

Tissue specificity

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. Ref.1 Ref.2 Ref.5

Developmental stage

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). Ref.5

Domain

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.

Post-translational modification

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

Disruption phenotype

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. Ref.5

Miscellaneous

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

Sequence similarities

Belongs to the Ena/VASP family.

Contains 1 WH1 domain.

Sequence caution

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

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

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
   Cellular componentCell junction
Cell projection
Cytoplasm
Cytoskeleton
Synapse
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Repeat
SH3-binding
   LigandActin-binding
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from genetic interaction PubMed 15371503. Source: MGI

actin filament organization

Inferred from direct assay Ref.2. Source: UniProtKB

actin polymerization or depolymerization

Inferred from direct assay Ref.2. Source: MGI

axon guidance

Inferred from mutant phenotype Ref.5PubMed 15371503. Source: MGI

cellular component movement

Inferred from direct assay Ref.2. Source: UniProtKB

intracellular transport

Inferred from electronic annotation. Source: InterPro

neural tube closure

Inferred from genetic interaction Ref.5PubMed 15371503. Source: MGI

   Cellular_componentactin cytoskeleton

Traceable author statement Ref.5. Source: MGI

cytosol

Traceable author statement. Source: Reactome

filopodium

Inferred from direct assay Ref.5Ref.10. Source: MGI

focal adhesion

Inferred from direct assay Ref.2. Source: UniProtKB

lamellipodium

Inferred from direct assay Ref.8Ref.10. Source: MGI

stress fiber

Inferred from direct assay Ref.2. Source: MGI

synapse

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionSH3 domain binding

Inferred from direct assay PubMed 9126384. Source: MGI

profilin binding

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BAIAP2Q9UQB83EBI-6083294,EBI-525456From a different organism.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 5 (identifier: Q03173-1)

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.
Isoform 1 (identifier: Q03173-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-412: Missing.
Note: No experimental confirmation available.
Isoform 2 (identifier: Q03173-3)

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.
Isoform 3 (identifier: Q03173-4)

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.
Isoform 4 (identifier: Q03173-5)

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
Isoform 6 (identifier: Q03173-6)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 802802Protein enabled homolog
PRO_0000086972

Regions

Domain1 – 111111WH1
Repeat175 – 17951
Repeat180 – 18452
Repeat185 – 18953
Repeat190 – 19454
Repeat195 – 19955
Repeat200 – 20456
Repeat205 – 20957
Region175 – 209357 X 5 AA tandem repeats of [LM]-E-[QR]-[EQ]-[QR]
Region623 – 799177EVH2
Region623 – 64321EVH2 block A
Region674 – 69118EVH2 block B
Region765 – 79935EVH2 block C
Coiled coil154 – 258105 Potential
Coiled coil767 – 79731 Potential
Motif632 – 6354KLKR
Compositional bias269 – 605337Pro-rich

Amino acid modifications

Modified residue1441Phosphoserine Ref.11
Modified residue2551Phosphoserine; by PKA Ref.12
Modified residue5571Phosphotyrosine Ref.8
Modified residue7381Phosphoserine By similarity
Modified residue7401Phosphoserine By similarity

Natural variations

Alternative sequence1 – 412412Missing in isoform 1.
VSP_007255
Alternative sequence117 – 13519Missing in isoform 2, isoform 3 and isoform 6.
VSP_007259
Alternative sequence117 – 13115Missing in isoform 4.
VSP_007257
Alternative sequence132 – 1354CIFC → VFYL in isoform 4.
VSP_007258
Alternative sequence259 – 500242Missing in isoform 2 and isoform 6.
VSP_007260
Alternative sequence561 – 59434Missing in isoform 6.
VSP_010565

Experimental info

Mutagenesis2551S → 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. Ref.6
Mutagenesis2551S → 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. Ref.6
Mutagenesis6371S → 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. Ref.6
Mutagenesis6371S → 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. Ref.6
Sequence conflict5001G → A in BAA01570. Ref.1

Secondary structure

.................. 802
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 5 (Neural variant Mena+++) (140 kDa isoform) [UniParc].

Last modified April 23, 2003. Version 2.
Checksum: 592BB975EE20F77F

FASTA80285,844
        10         20         30         40         50         60 
MSEQSICQAR AAVMVYDDAN KKWVPAGGST GFSRVHIYHH TGNNTFRVVG RKIQDHQVVI 

        70         80         90        100        110        120 
NCAIPKGLKY NQATQTFHQW RDARQVYGLN FGSKEDANVF ASAMMHALEV LNSQEAAQSK 

       130        140        150        160        170        180 
VTATQDSTNL RCIFCGPTLP RQNSQLPAQV QNGPSQEELE IQRRQLQEQQ RQKELERERM 

       190        200        210        220        230        240 
ERERLERERL ERERLERERL EQEQLERQRQ EREHVERLER ERLERLERER QERERERLEQ 

       250        260        270        280        290        300 
LEREQVEWER ERRMSNAAPS SDSSLSSAPL PEYSSCQPPS APPPSYAKVI SAPVSDATPD 

       310        320        330        340        350        360 
YAVVTALPPT STPPTPPLRH AATRFATSLG SAFHPVLPHY ATVPRPLNKN SRPSSPVNTP 

       370        380        390        400        410        420 
SSQPPAAKSC AWPTSNFSPL PPSPPIMISS PPGKATGPRP VLPVCVSSPV PQMPPSPTAP 

       430        440        450        460        470        480 
NGSLDSVTYP VSPPPTSGPA APPPPPPPPP PPPPPPLPPP PLPPLASLSH CGSQASPPPG 

       490        500        510        520        530        540 
TPLASTPSSK PSVLPSPSAG APASAETPLN PELGDSSASE PGLQAASQPA ESPTPQGLVL 

       550        560        570        580        590        600 
GPPAPPPPPP LPSGPAYASA LPPPPGPPPP PPLPSTGPPP PPPPPPPLPN QAPPPPPPPP 

       610        620        630        640        650        660 
APPLPASGIF SGSTSEDNRP LTGLAAAIAG AKLRKVSRVE DGSFPGGGNT GSVSLASSKA 

       670        680        690        700        710        720 
DAGRGNGPLP LGGSGLMEEM SALLARRRRI AEKGSTIETE QKEDRNEDAE PITAKAPSTS 

       730        740        750        760        770        780 
TPEPTRKPWE RTNTMNGSKS PVISRPKSTP SSQPSANGVQ TEGLDYDRLK QDILDEMRKE 

       790        800 
LAKLKEELID AIRQELSKSN TA 

« Hide

Isoform 1 [UniParc].

Checksum: 1AA5DDB306450847
Show »

FASTA39039,306
Isoform 2 (Mena) (80 kDa isoform) [UniParc].

Checksum: 19B25FD175DF0451
Show »

FASTA54159,643
Isoform 3 (Neural variant Mena+) [UniParc].

Checksum: 5E610BE7FDDA97FE
Show »

FASTA78383,776
Isoform 4 (Neural variant Mena++) [UniParc].

Checksum: 18C228F070EDCCF2
Show »

FASTA78784,299
Isoform 6 (Mena(S)) [UniParc].

Checksum: FA0C43AAD240503C
Show »

FASTA50756,357

References

« Hide 'large scale' references
[1]"Identification of a developmentally regulated gene in the mouse central nervous system which encodes a novel proline rich protein."
Sazuka T., Tomooka Y., Kathju S., Ikawa Y., Noda M., Kumar S.
Biochim. Biophys. Acta 1132:240-248(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics."
Gertler F.B., Niebuhr K., Reinhard M., Wehland J., Soriano P.
Cell 87:227-239(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ROLE IN L.MONOCYTOGENES MOBILITY, MISCELLANEOUS, INTERACTION WITH PFN1.
Tissue: Brain.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6.
Tissue: Brain.
[4]"The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled."
Ermekova K.S., Zambrano N., Linn H., Minopoli G., Gertler F., Russo T., Sudol M.
J. Biol. Chem. 272:32869-32877(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APBB1; NEDD4 AND YAP1.
[5]"Mena is required for neurulation and commissure formation."
Lanier L.M., Gates M.A., Witke W., Menzies A.S., Wehman A.M., Macklis J.D., Kwiatkowski D., Soriano P., Gertler F.B.
Neuron 22:313-325(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[6]"Critical roles of phosphorylation and actin binding motifs, but not the central proline-rich region, for Ena/vasodilator-stimulated phosphoprotein (VASP) function during cell migration."
Loureiro J.J., Rubinson D.A., Bear J.E., Baltus G.A., Kwiatkowski A.V., Gertler F.B.
Mol. Biol. Cell 13:2533-2546(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-255 AND SER-637.
[7]"Robo4 is a vascular-specific receptor that inhibits endothelial migration."
Park K.W., Morrison C.M., Sorensen L.K., Jones C.A., Rao Y., Chien C.-B., Wu J.Y., Urness L.D., Li D.Y.
Dev. Biol. 261:251-267(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ROBO4.
Strain: FVB/N.
[8]"Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase."
Tani K., Sato S., Sukezane T., Kojima H., Hirose H., Hanafusa H., Shishido T.
J. Biol. Chem. 278:21685-21692(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 6), PHOSPHORYLATION AT TYR-557, INTERACTION WITH ABI1.
[9]"Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton."
Salazar M.A., Kwiatkowski A.V., Pellegrini L., Cestra G., Butler M.H., Rossman K.L., Serna D.M., Sondek J., Gertler F.B., De Camilli P.
J. Biol. Chem. 278:49031-49043(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNMBP.
[10]"Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact."
Tanoue T., Takeichi M.
J. Cell Biol. 165:517-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAT1.
[11]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-144, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[12]"Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1."
Lebrand C., Dent E.W., Strasser G.A., Lanier L.M., Krause M., Svitkina T.M., Borisy G.G., Gertler F.B.
Neuron 42:37-49(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-255.
[13]"PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins."
Jenzora A., Behrendt B., Small J.V., Wehland J., Stradal T.E.
FEBS Lett. 579:455-463(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APBB1IP.
[14]"Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly."
Prehoda K.E., Lee D.J., Lim W.A.
Cell 97:471-480(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-112 IN COMPLEX WITH PRO-RICH PEPTIDE OF L.MONOCYTOGENES ACTA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS27200.
RefSeqNP_001076590.1. NM_001083121.2.
UniGeneMm.389224.
Mm.87759.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EVHX-ray1.80A1-112[»]
4CC3X-ray1.97B/D/F/H547-558[»]
ProteinModelPortalQ03173.
SMRQ03173. Positions 1-113, 760-799.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199446. 10 interactions.
IntActQ03173. 6 interactions.
MINTMINT-1215621.

PTM databases

PhosphoSiteQ03173.

Proteomic databases

PaxDbQ03173.
PRIDEQ03173.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000111025; ENSMUSP00000106654; ENSMUSG00000022995. [Q03173-6]
GeneID13800.
KEGGmmu:13800.
UCSCuc007dxs.1. mouse. [Q03173-3]

Organism-specific databases

CTD55740.
MGIMGI:108360. Enah.

Phylogenomic databases

eggNOGNOG289321.
GeneTreeENSGT00730000110272.
HOGENOMHOG000013015.
HOVERGENHBG006655.
InParanoidQ03173.
KOK05746.
PhylomeDBQ03173.

Enzyme and pathway databases

ReactomeREACT_98458. Immune System.

Gene expression databases

ArrayExpressQ03173.
BgeeQ03173.
CleanExMM_ENAH.
GenevestigatorQ03173.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR000156. Ran_bind_dom.
IPR014885. VASP_tetra.
IPR000697. WH1/EVH1.
[Graphical view]
PfamPF08776. VASP_tetra. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
SMARTSM00160. RanBD. 1 hit.
SM00461. WH1. 1 hit.
[Graphical view]
PROSITEPS50229. WH1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSENAH. mouse.
EvolutionaryTraceQ03173.
NextBio284558.
PROQ03173.
SOURCESearch...

Entry information

Entry nameENAH_MOUSE
AccessionPrimary (citable) accession number: Q03173
Secondary accession number(s): P70430 expand/collapse secondary AC list , P70431, P70432, P70433, Q5D053
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 23, 2003
Last modified: April 16, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot