ID ENAH_MOUSE Reviewed; 802 AA. AC Q03173; P70430; P70431; P70432; P70433; Q5D053; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-APR-2003, sequence version 2. DT 19-OCT-2011, entry version 103. DE RecName: Full=Protein enabled homolog; DE AltName: Full=NPC-derived proline-rich protein 1; DE Short=NDPP-1; GN Name=Enah; Synonyms=Mena, Ndpp1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX MEDLINE=93041923; PubMed=1420303; DOI=10.1016/0167-4781(92)90156-T; RA Sazuka T., Tomooka Y., Kathju S., Ikawa Y., Noda M., Kumar S.; RT "Identification of a developmentally regulated gene in the mouse RT central nervous system which encodes a novel proline rich protein."; RL Biochim. Biophys. Acta 1132:240-248(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5), FUNCTION, TISSUE RP SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH PFN1. RC TISSUE=Brain; RX MEDLINE=97015079; PubMed=8861907; DOI=10.1016/S0092-8674(00)81341-0; RA Gertler F.B., Niebuhr K., Reinhard M., Wehland J., Soriano P.; RT "Mena, a relative of VASP and Drosophila Enabled, is implicated in the RT control of microfilament dynamics."; RL Cell 87:227-239(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6; TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH APBB1; NEDD4 AND YAP1. RX MEDLINE=98070482; PubMed=9407065; DOI=10.1074/jbc.272.52.32869; RA Ermekova K.S., Zambrano N., Linn H., Minopoli G., Gertler F., RA Russo T., Sudol M.; RT "The WW domain of neural protein FE65 interacts with proline-rich RT motifs in Mena, the mammalian homolog of Drosophila enabled."; RL J. Biol. Chem. 272:32869-32877(1997). RN [5] RP FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX MEDLINE=99166867; PubMed=10069337; DOI=10.1016/S0896-6273(00)81092-2; RA Lanier L.M., Gates M.A., Witke W., Menzies A.S., Wehman A.M., RA Macklis J.D., Kwiatkowski D., Soriano P., Gertler F.B.; RT "Mena is required for neurulation and commissure formation."; RL Neuron 22:313-325(1999). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-255 AND RP SER-637. RX PubMed=12134088; DOI=10.1091/mbc.E01-10-0102; RA Loureiro J.J., Rubinson D.A., Bear J.E., Baltus G.A., RA Kwiatkowski A.V., Gertler F.B.; RT "Critical roles of phosphorylation and actin binding motifs, but not RT the central proline-rich region, for Ena/vasodilator-stimulated RT phosphoprotein (VASP) function during cell migration."; RL Mol. Biol. Cell 13:2533-2546(2002). RN [7] RP INTERACTION WITH ROBO4. RC STRAIN=FVB/N; RX PubMed=12941633; DOI=10.1016/S0012-1606(03)00258-6; RA Park K.W., Morrison C.M., Sorensen L.K., Jones C.A., Rao Y., RA Chien C.-B., Wu J.Y., Urness L.D., Li D.Y.; RT "Robo4 is a vascular-specific receptor that inhibits endothelial RT migration."; RL Dev. Biol. 261:251-267(2003). RN [8] RP ALTERNATIVE SPLICING (ISOFORM 6), PHOSPHORYLATION AT TYR-557, AND RP INTERACTION WITH ABI1. RX PubMed=12672821; DOI=10.1074/jbc.M301447200; RA Tani K., Sato S., Sukezane T., Kojima H., Hirose H., Hanafusa H., RA Shishido T.; RT "Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian RT enabled (Mena) by c-Abl kinase."; RL J. Biol. Chem. 278:21685-21692(2003). RN [9] RP INTERACTION WITH DNMBP. RX PubMed=14506234; DOI=10.1074/jbc.M308104200; RA Salazar M.A., Kwiatkowski A.V., Pellegrini L., Cestra G., Butler M.H., RA Rossman K.L., Serna D.M., Sondek J., Gertler F.B., De Camilli P.; RT "Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology RT domains, links dynamin to regulation of the actin cytoskeleton."; RL J. Biol. Chem. 278:49031-49043(2003). RN [10] RP INTERACTION WITH FAT1. RX PubMed=15148305; DOI=10.1083/jcb.200403006; RA Tanoue T., Takeichi M.; RT "Mammalian Fat1 cadherin regulates actin dynamics and cell-cell RT contact."; RL J. Cell Biol. 165:517-528(2004). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-144, AND MASS RP SPECTROMETRY. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.M400085-MCP200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [12] RP FUNCTION, AND PHOSPHORYLATION AT SER-255. RX PubMed=15066263; DOI=10.1016/S0896-6273(04)00108-4; RA Lebrand C., Dent E.W., Strasser G.A., Lanier L.M., Krause M., RA Svitkina T.M., Borisy G.G., Gertler F.B.; RT "Critical role of Ena/VASP proteins for filopodia formation in neurons RT and in function downstream of netrin-1."; RL Neuron 42:37-49(2004). RN [13] RP INTERACTION WITH APBB1IP. RX PubMed=15642358; DOI=10.1016/j.febslet.2004.10.110; RA Jenzora A., Behrendt B., Small J.V., Wehland J., Stradal T.E.; RT "PREL1 provides a link from Ras signalling to the actin cytoskeleton RT via Ena/VASP proteins."; RL FEBS Lett. 579:455-463(2005). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-112 IN COMPLEX WITH RP PRO-RICH PEPTIDE OF L.MONOCYTOGENES ACTA. RX MEDLINE=99268533; PubMed=10338211; DOI=10.1016/S0092-8674(00)80757-6; RA Prehoda K.E., Lee D.J., Lim W.A.; RT "Structure of the enabled/VASP homology 1 domain-peptide complex: a RT key component in the spatial control of actin assembly."; RL Cell 97:471-480(1999). CC -!- FUNCTION: Ena/VASP proteins are actin-associated proteins involved CC in a range of processes dependent on cytoskeleton remodeling and CC cell polarity such as axon guidance and lamellipodial and CC filopodial dynamics in migrating cells. ENAH induces the formation CC of F-actin rich outgrowths in fibroblasts. Acts synergistically CC with BAIAP2-alpha and downstream of NTN1 to promote filipodia CC formation. Required for actin-based mobility of Listeria CC monocytogenes. CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with APBB1IP, CC APBB1, PFN1 and ROBO4. Isoforms, containing the polyproline-rich CC regions with PPLP motifs, bind the WW domain of APBB1IP. Isoforms, CC containing the PPSY motif, bind, in vitro, to the WW2 and WW3 CC domains of NEDD4 and to the WW1 domain of YAP1. Binds the SH3 CC domain of BAIAP2-alpha but only after the autoinhibitory region of CC BAIAP2-alpha has been blocked by interaction with CDC42. CC Interacts, via the EVH1/WH1 domain, with the Pro-rich domains from CC VCL, ZYX and Listeria monocytogenes actA and with TES (via LIM CC domain). The TES LIM domain and the Pro-rich domains from VCL or CC ZYX compete for the same binding site. Interaction with ZYX is CC important for targeting ENAH to focal adhesions and enhances CC production of actin-rich structures at the apical surface of CC cells. Interacts, through the Pro-rich region, with the C-terminal CC SH3 domain of DNMPB. Binds GPHN. Heterotrimer with TES and ACTL7A CC (By similarity). Interacts with FAT1 (via EVH1 domains). CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton (By CC similarity). Cell projection, lamellipodium (By similarity). Cell CC projection, filopodium (By similarity). Cell junction, synapse (By CC similarity). Cell junction, focal adhesion (By similarity). CC Note=Targeted to the leading edge of lamellipodia and filopodia by CC MRL family members. Colocalizes at filopodial tips with a number CC of other proteins including vinculin and zyxlin. Colocalizes with CC N-WASP at the leading edge. Colocalizes with GPHN and PFN at CC synapses (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=5; Synonyms=Neural variant Mena+++, 140 kDa isoform; CC IsoId=Q03173-1; Sequence=Displayed; CC Name=1; CC IsoId=Q03173-2; Sequence=VSP_007255; CC Note=No experimental confirmation available. Ref.1 (BAA01570) CC sequence differs from that shown due to several frameshifts; CC Name=2; Synonyms=Mena, 80 kDa isoform; CC IsoId=Q03173-3; Sequence=VSP_007259, VSP_007260; CC Name=3; Synonyms=Neural variant Mena+; CC IsoId=Q03173-4; Sequence=VSP_007259; CC Note=Phosphorylated during neural development; CC Name=4; Synonyms=Neural variant Mena++; CC IsoId=Q03173-5; Sequence=VSP_007257, VSP_007258; CC Name=6; Synonyms=Mena(S); CC IsoId=Q03173-6; Sequence=VSP_007259, VSP_007260, VSP_010565; CC -!- TISSUE SPECIFICITY: Expressed in heart and testis, lower levels in CC lung, skeletal muscle, kidney, pancreas and brain. Isoform 5 is CC expressed exclusively in the brain. Isoform 2 is expressed CC predominantly in brain, testis, ovary and fat. In the brain, both CC of these isoforms are more highly expressed in the hippocampus, CC cortex and midbrain, lowest levels in the striatum and cerebellum. CC Isoform 6 is expressed in brain and spleen. CC -!- DEVELOPMENTAL STAGE: In embryonic brains, isoform 2, isoform 3 and CC isoform 5 are expressed from E11. Expression of isoform 3 CC decreases steadily and becomes almost undetectable by E16, while CC expression of isoform 5 begins to increase from E13 and peaks CC between E16 and E18. During brain development, isoform 2 is CC particularly expressed in the neuroepithelium, forebrain and CC somites at E8.5. By E10.5, expression is detected in the brain, CC dorsal root ganglia, branchial and pharyngeal arches, somites and CC limb buds. Isoform 5 is detected at this stage in regions of the CC developing CNS. CC -!- DOMAIN: The EVH2 domain is comprised of 3 regions. Block A is a CC thymosin-like domain required for G-actin binding. The KLKR motif CC within this block is essential for the G-actin binding and for CC actin polymerization. Block B is required for F-actin binding and CC subcellular location, and Block C for tetramerization. CC -!- PTM: NTN1-induced PKA phosphorylation on Ser-255 directly CC parallels the formation of filopodial protrusions. CC -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR (By CC similarity). CC -!- SIMILARITY: Belongs to the Ena/VASP family. CC -!- SIMILARITY: Contains 1 WH1 domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D10727; BAA01570.1; ALT_FRAME; mRNA. DR EMBL; U72520; AAC52863.1; -; mRNA. DR EMBL; U72521; AAC52864.1; -; mRNA. DR EMBL; U72522; AAC52865.1; -; mRNA. DR EMBL; U72523; AAC52866.1; -; mRNA. DR EMBL; BC062927; AAH62927.1; -; mRNA. DR IPI; IPI00284242; -. DR IPI; IPI00284246; -. DR IPI; IPI00417165; -. DR IPI; IPI00468225; -. DR IPI; IPI00470077; -. DR IPI; IPI01008259; -. DR PIR; S27200; S27200. DR RefSeq; NP_001076589.1; NM_001083120.1. DR RefSeq; NP_001076590.1; NM_001083121.1. DR RefSeq; NP_032706.2; NM_008680.2. DR RefSeq; NP_034265.2; NM_010135.2. DR UniGene; Mm.389224; -. DR UniGene; Mm.87759; -. DR PDB; 1EVH; X-ray; 1.80 A; A=1-112. DR PDBsum; 1EVH; -. DR ProteinModelPortal; Q03173; -. DR SMR; Q03173; 1-113, 760-800. DR MINT; MINT-1215621; -. DR STRING; Q03173; -. DR PhosphoSite; Q03173; -. DR PRIDE; Q03173; -. DR Ensembl; ENSMUST00000111025; ENSMUSP00000106654; ENSMUSG00000022995. DR GeneID; 13800; -. DR KEGG; mmu:13800; -. DR UCSC; uc007dxp.1; mouse. DR UCSC; uc007dxq.1; mouse. DR UCSC; uc007dxr.1; mouse. DR UCSC; uc007dxs.1; mouse. DR CTD; 55740; -. DR MGI; MGI:108360; Enah. DR eggNOG; roNOG07783; -. DR GeneTree; ENSGT00440000039080; -. DR HOGENOM; HBG282727; -. DR HOVERGEN; HBG006655; -. DR InParanoid; Q03173; -. DR OrthoDB; EOG437RF0; -. DR Reactome; REACT_98458; Immune System. DR NextBio; 284558; -. DR ArrayExpress; Q03173; -. DR Bgee; Q03173; -. DR CleanEx; MM_ENAH; -. DR Genevestigator; Q03173; -. DR GermOnline; ENSMUSG00000022995; Mus musculus. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030175; C:filopodium; IDA:MGI. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IDA:MGI. DR GO; GO:0001725; C:stress fiber; IDA:MGI. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell. DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW. DR GO; GO:0005522; F:profilin binding; IDA:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IDA:MGI. DR GO; GO:0008154; P:actin polymerization or depolymerization; IDA:MGI. DR GO; GO:0007411; P:axon guidance; IMP:MGI. DR GO; GO:0006928; P:cellular component movement; IDA:UniProtKB. DR GO; GO:0046907; P:intracellular transport; IEA:InterPro. DR GO; GO:0001843; P:neural tube closure; IGI:MGI. DR InterPro; IPR000697; EVH1. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000156; RanBP. DR InterPro; IPR024669; VASP/Enah. DR InterPro; IPR014885; VASP_tetra. DR Gene3D; G3DSA:2.30.29.30; PH_type; 1. DR Pfam; PF11643; VASP; 1. DR Pfam; PF08776; VASP_tetra; 1. DR Pfam; PF00568; WH1; 1. DR SMART; SM00160; RanBD; 1. DR SMART; SM00461; WH1; 1. DR PROSITE; PS50229; WH1; 1. PE 1: Evidence at protein level; KW 3D-structure; Actin-binding; Alternative splicing; Cell junction; KW Cell projection; Coiled coil; Complete proteome; Cytoplasm; KW Cytoskeleton; Developmental protein; Differentiation; Neurogenesis; KW Phosphoprotein; Reference proteome; Repeat; SH3-binding; Synapse. FT CHAIN 1 802 Protein enabled homolog. FT /FTId=PRO_0000086972. FT DOMAIN 1 111 WH1. FT REPEAT 175 179 1. FT REPEAT 180 184 2. FT REPEAT 185 189 3. FT REPEAT 190 194 4. FT REPEAT 195 199 5. FT REPEAT 200 204 6. FT REPEAT 205 209 7. FT REGION 175 209 7 X 5 AA tandem repeats of [LM]-E-[QR]- FT [EQ]-[QR]. FT REGION 623 799 EVH2. FT REGION 623 643 EVH2 block A. FT REGION 674 691 EVH2 block B. FT REGION 765 799 EVH2 block C. FT COILED 154 258 Potential. FT COILED 767 797 Potential. FT MOTIF 632 635 KLKR. FT COMPBIAS 269 605 Pro-rich. FT MOD_RES 144 144 Phosphoserine. FT MOD_RES 255 255 Phosphoserine; by PKA. FT MOD_RES 557 557 Phosphotyrosine. FT MOD_RES 637 637 Phosphoserine (By similarity). FT MOD_RES 721 721 Phosphothreonine (By similarity). FT MOD_RES 734 734 Phosphothreonine (By similarity). FT MOD_RES 738 738 Phosphoserine (By similarity). FT MOD_RES 740 740 Phosphoserine (By similarity). FT VAR_SEQ 1 412 Missing (in isoform 1). FT /FTId=VSP_007255. FT VAR_SEQ 117 135 Missing (in isoform 2, isoform 3 and FT isoform 6). FT /FTId=VSP_007259. FT VAR_SEQ 117 131 Missing (in isoform 4). FT /FTId=VSP_007257. FT VAR_SEQ 132 135 CIFC -> VFYL (in isoform 4). FT /FTId=VSP_007258. FT VAR_SEQ 259 500 Missing (in isoform 2 and isoform 6). FT /FTId=VSP_007260. FT VAR_SEQ 561 594 Missing (in isoform 6). FT /FTId=VSP_010565. FT MUTAGEN 255 255 S->A: No change in subcellular location FT nor colocalization with vinculin at focal FT adhesions nor with N-WASP at the leading FT edge. Loss of cell mobility function; FT when associated with A-637. FT MUTAGEN 255 255 S->D: No change in subcellular location FT nor colocalization with vinculin at focal FT adhesions nor with N-WASP at the leading FT edge. No loss of cell mobility function; FT when associated with D-637. FT MUTAGEN 637 637 S->A: No change in subcellular location FT nor colocalization with vinculin at focal FT adhesions nor with N-WASP at the leading FT edge. No loss of cell mobility function. FT when associated with A-255. FT MUTAGEN 637 637 S->D: No change in subcellular location FT nor colocalization with vinculin at focal FT adhesions nor with N-WASP at the leading FT edge. No loss of cell mobility function. FT when associated with D-255. FT CONFLICT 500 500 G -> A (in Ref. 1; BAA01570). FT STRAND 3 17 FT TURN 18 21 FT STRAND 22 25 FT HELIX 26 28 FT STRAND 33 40 FT TURN 41 44 FT STRAND 45 52 FT TURN 53 55 FT STRAND 58 64 FT STRAND 74 81 FT STRAND 86 93 FT HELIX 94 111 SQ SEQUENCE 802 AA; 85844 MW; 592BB975EE20F77F CRC64; MSEQSICQAR AAVMVYDDAN KKWVPAGGST GFSRVHIYHH TGNNTFRVVG RKIQDHQVVI NCAIPKGLKY NQATQTFHQW RDARQVYGLN FGSKEDANVF ASAMMHALEV LNSQEAAQSK VTATQDSTNL RCIFCGPTLP RQNSQLPAQV QNGPSQEELE IQRRQLQEQQ RQKELERERM ERERLERERL ERERLERERL EQEQLERQRQ EREHVERLER ERLERLERER QERERERLEQ LEREQVEWER ERRMSNAAPS SDSSLSSAPL PEYSSCQPPS APPPSYAKVI SAPVSDATPD YAVVTALPPT STPPTPPLRH AATRFATSLG SAFHPVLPHY ATVPRPLNKN SRPSSPVNTP SSQPPAAKSC AWPTSNFSPL PPSPPIMISS PPGKATGPRP VLPVCVSSPV PQMPPSPTAP NGSLDSVTYP VSPPPTSGPA APPPPPPPPP PPPPPPLPPP PLPPLASLSH CGSQASPPPG TPLASTPSSK PSVLPSPSAG APASAETPLN PELGDSSASE PGLQAASQPA ESPTPQGLVL GPPAPPPPPP LPSGPAYASA LPPPPGPPPP PPLPSTGPPP PPPPPPPLPN QAPPPPPPPP APPLPASGIF SGSTSEDNRP LTGLAAAIAG AKLRKVSRVE DGSFPGGGNT GSVSLASSKA DAGRGNGPLP LGGSGLMEEM SALLARRRRI AEKGSTIETE QKEDRNEDAE PITAKAPSTS TPEPTRKPWE RTNTMNGSKS PVISRPKSTP SSQPSANGVQ TEGLDYDRLK QDILDEMRKE LAKLKEELID AIRQELSKSN TA //