ENAH_HUMAN
ID ENAH_HUMAN Reviewed; 591 AA.
AC Q8N8S7; D0PQI2; Q502W5; Q5T5M7; Q5VTQ9; Q5VTR0; Q9NVF3; Q9UFB8;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Protein enabled homolog;
GN Name=ENAH; Synonyms=MENA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Urbanelli L.;
RT "Human Mena: cDNA cloning, expression and promoter characterization.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Mammary tumor;
RX PubMed=15027125; DOI=10.1002/ijc.20094;
RA Di Modugno F., Bronzi G., Scanlan M.J., Del Bello D., Cascioli S.,
RA Venturo I., Botti C., Nicotra M.R., Mottolese M., Natali P.G., Santoni A.,
RA Jager E., Nistico P.;
RT "Human Mena protein, a serex-defined antigen overexpressed in breast cancer
RT eliciting both humoral and CD8+ T-cell immune response.";
RL Int. J. Cancer 109:909-918(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=23129656; DOI=10.1073/pnas.1214394109;
RA Di Modugno F., Iapicca P., Boudreau A., Mottolese M., Terrenato I.,
RA Perracchio L., Carstens R.P., Santoni A., Bissell M.J., Nistico P.;
RT "Splicing program of human MENA produces a previously undescribed isoform
RT associated with invasive, mesenchymal-like breast tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:19280-19285(2012).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 44-591 (ISOFORM 2).
RC TISSUE=Placenta, and Skin;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 85-591 (ISOFORM 2).
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 393-591 (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP PROTEIN SEQUENCE OF 23-47; 70-81; 123-145; 403-427; 484-499 AND 573-587,
RP FUNCTION, AND INTERACTION WITH BAIAP2.
RX PubMed=11696321; DOI=10.1016/s0960-9822(01)00506-1;
RA Krugmann S., Jordens I., Gevaert K., Driessens M., Vandekerckhove J.,
RA Hall A.;
RT "Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena
RT complex.";
RL Curr. Biol. 11:1645-1655(2001).
RN [9]
RP INTERACTION WITH VCL; ZYX AND L.MONOCYTOGENES ACTA.
RX PubMed=9312002; DOI=10.1093/emboj/16.17.5433;
RA Niebuhr K., Ebel F., Frank R., Reinhard M., Domann E., Carl U.D.,
RA Walter U., Gertler F.B., Wehland J., Chakraborty T.;
RT "A novel proline-rich motif present in ActA of Listeria monocytogenes and
RT cytoskeletal proteins is the ligand for the EVH1 domain, a protein module
RT present in the Ena/VASP family.";
RL EMBO J. 16:5433-5444(1997).
RN [10]
RP INTERACTION WITH ZYX.
RX PubMed=10801818; DOI=10.1074/jbc.m001698200;
RA Drees B., Friederich E., Fradelizi J., Louvard D., Beckerle M.C.,
RA Golsteyn R.M.;
RT "Characterization of the interaction between zyxin and members of the
RT Ena/vasodilator-stimulated phosphoprotein family of proteins.";
RL J. Biol. Chem. 275:22503-22511(2000).
RN [11]
RP INTERACTION WITH ROBO4.
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., Chien C.-B.,
RA 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 [12]
RP INTERACTION WITH APBB1IP.
RC TISSUE=T-cell;
RX PubMed=15469846; DOI=10.1016/j.devcel.2004.07.021;
RA Lafuente E.M., van Puijenbroek A.A., Krause M., Carman C.V., Freeman G.J.,
RA Berezovskaya A., Constantine E., Springer T.A., Gertler F.B.,
RA Boussiotis V.A.;
RT "RIAM, an Ena/VASP and profilin ligand, interacts with Rap1-GTP and
RT mediates Rap1-induced adhesion.";
RL Dev. Cell 7:585-595(2004).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=15469845; DOI=10.1016/j.devcel.2004.07.024;
RA Krause M., Leslie J.D., Stewart M., Lafuente E.M., Valderrama F.,
RA Jagannathan R., Strasser G.A., Rubinson D.A., Liu H., Way M., Yaffe M.B.,
RA Boussiotis V.A., Gertler F.B.;
RT "Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of
RT lamellipodial dynamics.";
RL Dev. Cell 7:571-583(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-506 AND SER-508,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-502 (ISOFORM 2),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-465 (ISOFORM 3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-506 AND SER-508, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512 (ISOFORM 2),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-475 (ISOFORM 3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508 (ISOFORM 2),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471 (ISOFORM 3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 347-356 IN COMPLEX WITH APBB1.
RX PubMed=17686488; DOI=10.1016/j.jmb.2007.06.064;
RA Meiyappan M., Birrane G., Ladias J.A.A.;
RT "Structural basis for polyproline recognition by the FE65 WW domain.";
RL J. Mol. Biol. 372:970-980(2007).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-113 IN COMPLEX WITH TES,
RP INTERACTION WITH ZYX, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18158903; DOI=10.1016/j.molcel.2007.10.033;
RA Boeda B., Briggs D.C., Higgins T., Garvalov B.K., Fadden A.J.,
RA McDonald N.Q., Way M.;
RT "Tes, a specific Mena interacting partner, breaks the rules for EVH1
RT binding.";
RL Mol. Cell 28:1071-1082(2007).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 1-116 IN COMPLEX WITH TES AND
RP ACTL7A.
RX PubMed=21278383; DOI=10.1074/jbc.m110.171264;
RA Boeda B., Knowles P.P., Briggs D.C., Murray-Rust J., Soriano E.,
RA Garvalov B.K., McDonald N.Q., Way M.;
RT "Molecular recognition of the Tes LIM2-3 domains by the actin-related
RT protein Arp7A.";
RL J. Biol. Chem. 286:11543-11554(2011).
CC -!- FUNCTION: Ena/VASP proteins are actin-associated proteins involved in a
CC range of processes dependent on cytoskeleton remodeling and cell
CC polarity such as axon guidance and lamellipodial and filopodial
CC dynamics in migrating cells. ENAH induces the formation of F-actin rich
CC outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and
CC downstream of NTN1 to promote filipodia formation (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:11696321,
CC ECO:0000269|PubMed:18158903}.
CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with APBB1IP, APBB1,
CC PFN1 and ROBO4 (PubMed:12941633, PubMed:15469846, PubMed:17686488).
CC Isoforms, containing the polyproline-rich regions with PPLP motifs,
CC bind the WW domain of APBB1IP (PubMed:15469846). Isoforms, containing
CC the PPSY motif, bind, in vitro, to the WW2 and WW3 domains of NEDD4 and
CC to the WW1 domain of YAP1 (By similarity). Binds the SH3 domain of
CC BAIAP2-alpha but only after the autoinhibitory region of BAIAP2-alpha
CC has been blocked by interaction with CDC42 (PubMed:11696321,
CC PubMed:18158903). Interacts, via the EVH1/WH1 domain, with the Pro-rich
CC domains from VCL, ZYX and Listeria monocytogenes actA and with TES (via
CC LIM domains) (PubMed:9312002, PubMed:18158903, PubMed:21278383). The
CC TES LIM domain and the Pro-rich domains from VCL or ZYX compete for the
CC same binding site (PubMed:9312002). Interaction with ZYX is important
CC for targeting ENAH to focal adhesions and enhances production of actin-
CC rich structures at the apical surface of cells (PubMed:10801818).
CC Interacts, through the Pro-rich region, with the C-terminal SH3 domain
CC of DNMPB (By similarity). Binds GPHN (By similarity). Interacts with
CC FAT1 (via EVH1 domains) (By similarity). Heterotrimer with TES and
CC ACTL7A (PubMed:21278383). Interacts with PRPF40A (By similarity).
CC {ECO:0000250|UniProtKB:Q03173, ECO:0000269|PubMed:10801818,
CC ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:12941633,
CC ECO:0000269|PubMed:15469846, ECO:0000269|PubMed:17686488,
CC ECO:0000269|PubMed:18158903, ECO:0000269|PubMed:21278383,
CC ECO:0000269|PubMed:9312002}.
CC -!- INTERACTION:
CC Q8N8S7; Q14517: FAT1; NbExp=2; IntAct=EBI-2834410, EBI-1171918;
CC Q8N8S7; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-2834410, EBI-750109;
CC Q8N8S7; Q9UGI8: TES; NbExp=2; IntAct=EBI-2834410, EBI-2561654;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cell projection, lamellipodium {ECO:0000250}. Cell projection,
CC filopodium {ECO:0000250}. Synapse {ECO:0000250}. Cell junction, focal
CC adhesion. Note=Targeted to the leading edge of lamellipodia and
CC filopodia by MRL family members. Colocalizes at filopodial tips with a
CC number of other proteins including vinculin and zyxlin. Colocalizes
CC with N-WASP at the leading edge. Colocalizes with GPHN and PFN at
CC synapses (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N8S7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N8S7-2; Sequence=VSP_010564;
CC Name=3; Synonyms=Deltav6;
CC IsoId=Q8N8S7-3; Sequence=VSP_053772, VSP_053773;
CC -!- TISSUE SPECIFICITY: Expressed in myoepithelia of parotid, breast,
CC bronchial glands and sweat glands. Expressed in colon-rectum muscolaris
CC mucosae epithelium, pancreas acinar ductal epithelium, endometrium
CC epithelium, prostate fibromuscolar stroma and placenta vascular media.
CC Overexpressed in a majority of breast cancer cell lines and primary
CC breast tumor lesions. {ECO:0000269|PubMed:15027125}.
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 actin
CC polymerization. Block B is required for F-actin binding and subcellular
CC location, and Block C for tetramerization.
CC -!- PTM: NTN1-induced PKA phosphorylation on Ser-265 directly parallels the
CC formation of filopodial protrusions. {ECO:0000250}.
CC -!- MISCELLANEOUS: Required to transform actin polymerization into active
CC movement for the propulsive force of Listeria monocytogenes.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 3]: Expression restricted to invasive cancer
CC cells. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the Ena/VASP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91799.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC04736.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ENAHID44148ch1q42.html";
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DR EMBL; AY345143; AAR04685.1; -; mRNA.
DR EMBL; AF519769; AAQ08487.1; -; mRNA.
DR EMBL; EU255274; ABY78022.1; -; mRNA.
DR EMBL; AC092811; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356216; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC065238; AAH65238.1; -; mRNA.
DR EMBL; BC095481; AAH95481.1; -; mRNA.
DR EMBL; AK001635; BAA91799.1; ALT_INIT; mRNA.
DR EMBL; AK096246; BAC04736.1; ALT_INIT; mRNA.
DR EMBL; AL133059; CAB61384.1; -; mRNA.
DR CCDS; CCDS31040.1; -. [Q8N8S7-2]
DR CCDS; CCDS31041.1; -. [Q8N8S7-1]
DR PIR; T42661; T42661.
DR RefSeq; NP_001008493.1; NM_001008493.2. [Q8N8S7-1]
DR RefSeq; NP_060682.2; NM_018212.5. [Q8N8S7-2]
DR PDB; 2HO2; X-ray; 1.33 A; B=347-356.
DR PDB; 2IYB; X-ray; 2.35 A; A/B/C/D=1-113.
DR PDB; 2XQN; X-ray; 2.62 A; M=1-116.
DR PDB; 4MY6; X-ray; 1.70 A; A/B=1-111.
DR PDB; 5N91; X-ray; 1.49 A; A/B=1-111.
DR PDB; 5N9C; X-ray; 1.16 A; A/B=1-111.
DR PDB; 5N9P; X-ray; 1.80 A; A/B=1-111.
DR PDB; 5NAJ; X-ray; 1.46 A; A/B/C/D=1-111.
DR PDB; 5NBF; X-ray; 1.15 A; A=1-111.
DR PDB; 5NBX; X-ray; 1.65 A; A/B=1-111.
DR PDB; 5NC2; X-ray; 1.58 A; A/B=1-111.
DR PDB; 5NC7; X-ray; 2.70 A; A/B/C/D=1-111.
DR PDB; 5NCF; X-ray; 1.40 A; A/B=1-111.
DR PDB; 5NCG; X-ray; 1.02 A; A/B=1-111.
DR PDB; 5NCP; X-ray; 1.65 A; A=1-111.
DR PDB; 5ND0; X-ray; 1.45 A; A/B=1-111.
DR PDB; 5NDU; X-ray; 1.42 A; A/B=1-111.
DR PDB; 5NEG; X-ray; 1.29 A; A/B=1-111.
DR PDB; 6RCF; X-ray; 1.10 A; A=1-111.
DR PDB; 6RCJ; X-ray; 1.35 A; A=1-111.
DR PDB; 6RD2; X-ray; 1.00 A; A/B=1-111.
DR PDB; 6XVT; X-ray; 1.40 A; A/B=1-111.
DR PDB; 6XXR; X-ray; 1.48 A; A/B=1-111.
DR PDB; 7A5M; X-ray; 0.78 A; A=1-111.
DR PDB; 7AKI; X-ray; 1.36 A; A=1-111.
DR PDBsum; 2HO2; -.
DR PDBsum; 2IYB; -.
DR PDBsum; 2XQN; -.
DR PDBsum; 4MY6; -.
DR PDBsum; 5N91; -.
DR PDBsum; 5N9C; -.
DR PDBsum; 5N9P; -.
DR PDBsum; 5NAJ; -.
DR PDBsum; 5NBF; -.
DR PDBsum; 5NBX; -.
DR PDBsum; 5NC2; -.
DR PDBsum; 5NC7; -.
DR PDBsum; 5NCF; -.
DR PDBsum; 5NCG; -.
DR PDBsum; 5NCP; -.
DR PDBsum; 5ND0; -.
DR PDBsum; 5NDU; -.
DR PDBsum; 5NEG; -.
DR PDBsum; 6RCF; -.
DR PDBsum; 6RCJ; -.
DR PDBsum; 6RD2; -.
DR PDBsum; 6XVT; -.
DR PDBsum; 6XXR; -.
DR PDBsum; 7A5M; -.
DR PDBsum; 7AKI; -.
DR AlphaFoldDB; Q8N8S7; -.
DR SMR; Q8N8S7; -.
DR BioGRID; 120858; 123.
DR CORUM; Q8N8S7; -.
DR ELM; Q8N8S7; -.
DR IntAct; Q8N8S7; 35.
DR MINT; Q8N8S7; -.
DR STRING; 9606.ENSP00000355809; -.
DR CarbonylDB; Q8N8S7; -.
DR GlyGen; Q8N8S7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8N8S7; -.
DR MetOSite; Q8N8S7; -.
DR PhosphoSitePlus; Q8N8S7; -.
DR SwissPalm; Q8N8S7; -.
DR BioMuta; ENAH; -.
DR DMDM; 48428086; -.
DR EPD; Q8N8S7; -.
DR jPOST; Q8N8S7; -.
DR MassIVE; Q8N8S7; -.
DR MaxQB; Q8N8S7; -.
DR PaxDb; Q8N8S7; -.
DR PeptideAtlas; Q8N8S7; -.
DR PRIDE; Q8N8S7; -.
DR ProteomicsDB; 72457; -. [Q8N8S7-1]
DR ProteomicsDB; 72458; -. [Q8N8S7-2]
DR Antibodypedia; 34644; 215 antibodies from 33 providers.
DR DNASU; 55740; -.
DR Ensembl; ENST00000366843.7; ENSP00000355808.2; ENSG00000154380.18. [Q8N8S7-2]
DR Ensembl; ENST00000366844.7; ENSP00000355809.2; ENSG00000154380.18. [Q8N8S7-1]
DR GeneID; 55740; -.
DR KEGG; hsa:55740; -.
DR MANE-Select; ENST00000366843.7; ENSP00000355808.2; NM_018212.6; NP_060682.2. [Q8N8S7-2]
DR UCSC; uc001hpc.2; human. [Q8N8S7-1]
DR CTD; 55740; -.
DR DisGeNET; 55740; -.
DR GeneCards; ENAH; -.
DR HGNC; HGNC:18271; ENAH.
DR HPA; ENSG00000154380; Low tissue specificity.
DR MIM; 609061; gene.
DR neXtProt; NX_Q8N8S7; -.
DR OpenTargets; ENSG00000154380; -.
DR PharmGKB; PA38517; -.
DR VEuPathDB; HostDB:ENSG00000154380; -.
DR eggNOG; KOG4590; Eukaryota.
DR GeneTree; ENSGT00940000157376; -.
DR HOGENOM; CLU_017790_1_1_1; -.
DR InParanoid; Q8N8S7; -.
DR OrthoDB; 972128at2759; -.
DR PhylomeDB; Q8N8S7; -.
DR TreeFam; TF321411; -.
DR PathwayCommons; Q8N8S7; -.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-376176; Signaling by ROBO receptors.
DR SignaLink; Q8N8S7; -.
DR SIGNOR; Q8N8S7; -.
DR BioGRID-ORCS; 55740; 35 hits in 1076 CRISPR screens.
DR ChiTaRS; ENAH; human.
DR EvolutionaryTrace; Q8N8S7; -.
DR GeneWiki; ENAH_(gene); -.
DR GenomeRNAi; 55740; -.
DR Pharos; Q8N8S7; Tbio.
DR PRO; PR:Q8N8S7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8N8S7; protein.
DR Bgee; ENSG00000154380; Expressed in saphenous vein and 205 other tissues.
DR ExpressionAtlas; Q8N8S7; baseline and differential.
DR Genevisible; Q8N8S7; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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; IBA:GO_Central.
DR GO; GO:0017124; F:SH3 domain binding; IBA:GO_Central.
DR GO; GO:0050699; F:WW domain binding; IPI:UniProtKB.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IBA:GO_Central.
DR GO; GO:0070358; P:actin polymerization-dependent cell motility; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR038023; VASP_sf.
DR InterPro; IPR014885; VASP_tetra.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR Pfam; PF08776; VASP_tetra; 1.
DR Pfam; PF00568; WH1; 1.
DR SMART; SM00461; WH1; 1.
DR SUPFAM; SSF118370; SSF118370; 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; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Phosphoprotein; Reference proteome; Repeat;
KW SH3-binding; Synapse.
FT CHAIN 1..591
FT /note="Protein enabled homolog"
FT /id="PRO_0000086971"
FT DOMAIN 1..111
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REPEAT 156..160
FT /note="1"
FT REPEAT 161..165
FT /note="2"
FT REPEAT 166..170
FT /note="3"
FT REPEAT 171..175
FT /note="4"
FT REPEAT 176..180
FT /note="5"
FT REPEAT 181..185
FT /note="6"
FT REPEAT 186..190
FT /note="7"
FT REPEAT 191..195
FT /note="8"
FT REPEAT 196..200
FT /note="9"
FT REGION 115..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 156..200
FT /note="9 X 5 AA tandem repeats of [LMQ]-E-[QR]-E-[QR]"
FT REGION 221..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..588
FT /note="EVH2"
FT REGION 391..411
FT /note="EVH2 block A"
FT REGION 405..549
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..459
FT /note="EVH2 block B"
FT REGION 554..588
FT /note="EVH2 block C"
FT COILED 135..265
FT /evidence="ECO:0000255"
FT COILED 557..587
FT /evidence="ECO:0000255"
FT MOTIF 400..403
FT /note="KLKR"
FT COMPBIAS 115..141
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..264
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..303
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..374
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..432
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..479
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..511
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 265
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q03173"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT VAR_SEQ 268..304
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:23129656"
FT /id="VSP_053772"
FT VAR_SEQ 513..533
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:23129656"
FT /id="VSP_053773"
FT VAR_SEQ 514..534
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005,
FT ECO:0000303|Ref.1"
FT /id="VSP_010564"
FT CONFLICT 493
FT /note="T -> I (in Ref. 5; AAH95481)"
FT /evidence="ECO:0000305"
FT STRAND 3..17
FT /evidence="ECO:0007829|PDB:7A5M"
FT TURN 18..21
FT /evidence="ECO:0007829|PDB:7A5M"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:7A5M"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:7A5M"
FT STRAND 32..40
FT /evidence="ECO:0007829|PDB:7A5M"
FT TURN 41..44
FT /evidence="ECO:0007829|PDB:7A5M"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:7A5M"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:7A5M"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:7A5M"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:7A5M"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:7A5M"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:7A5M"
FT HELIX 94..110
FT /evidence="ECO:0007829|PDB:7A5M"
FT MOD_RES Q8N8S7-2:502
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q8N8S7-2:508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q8N8S7-2:512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES Q8N8S7-3:465
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q8N8S7-3:471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q8N8S7-3:475
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
SQ SEQUENCE 591 AA; 66510 MW; BF3252F6FCD1988B CRC64;
MSEQSICQAR AAVMVYDDAN KKWVPAGGST GFSRVHIYHH TGNNTFRVVG RKIQDHQVVI
NCAIPKGLKY NQATQTFHQW RDARQVYGLN FGSKEDANVF ASAMMHALEV LNSQETGPTL
PRQNSQLPAQ VQNGPSQEEL EIQRRQLQEQ QRQKELERER LERERMERER LERERLERER
LERERLEQEQ LERERQERER QERLERQERL ERQERLERQE RLDRERQERQ ERERLERLER
ERQERERQEQ LEREQLEWER ERRISSAAAP ASVETPLNSV LGDSSASEPG LQAASQPAET
PSQQGIVLGP LAPPPPPPLP PGPAQASVAL PPPPGPPPPP PLPSTGPPPP PPPPPLPNQV
PPPPPPPPAP PLPASGFFLA SMSEDNRPLT GLAAAIAGAK LRKVSRMEDT SFPSGGNAIG
VNSASSKTDT GRGNGPLPLG GSGLMEEMSA LLARRRRIAE KGSTIETEQK EDKGEDSEPV
TSKASSTSTP EPTRKPWERT NTMNGSKSPV ISRRDSPRKN QIVFDNRSYD SLHRPKSTPL
SQPSANGVQT EGLDYDRLKQ DILDEMRKEL TKLKEELIDA IRQELSKSNT A
