ID EVL_MOUSE Reviewed; 414 AA.
AC P70429; Q9ERU8;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-NOV-2002, sequence version 2.
DT 27-MAR-2024, entry version 183.
DE RecName: Full=Ena/VASP-like protein;
DE AltName: Full=Ena/vasodilator-stimulated phosphoprotein-like;
GN Name=Evl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH PFN2;
RP LYN; APBB1; ABL1 AND SRC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION BY PKA.
RC STRAIN=C57BL/6J;
RX PubMed=10945997; DOI=10.1074/jbc.m006274200;
RA Lambrechts A., Kwiatkowski A.V., Lanier L.M., Bear J.E., Vandekerckhove J.,
RA Ampe C., Gertler F.B.;
RT "cAMP-dependent protein kinase phosphorylation of EVL, a Mena/VASP
RT relative, regulates its interaction with actin and SH3 domains.";
RL J. Biol. Chem. 275:36143-36151(2000).
RN [3]
RP ROLE IN L.MONOCYTOGENES MOBILITY, MISCELLANEOUS, AND INTERACTION WITH
RP L.MONOCYTOGENES ACTA.
RX PubMed=10087267; DOI=10.1083/jcb.144.6.1245;
RA Laurent V., Loisel T.P., Harbeck B., Wehman A., Groebe L., Jockusch B.M.,
RA Wehland J., Gertler F.B., Carlier M.-F.;
RT "Role of proteins of the Ena/VASP family in actin-based motility of
RT Listeria monocytogenes.";
RL J. Cell Biol. 144:1245-1258(1999).
RN [4]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX 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., Macklis J.D.,
RA Kwiatkowski D., Soriano P., Gertler F.B.;
RT "Mena is required for neurulation and commissure formation.";
RL Neuron 22:313-325(1999).
RN [5]
RP INTERACTION WITH SEMA6A.
RX PubMed=10993894; DOI=10.1074/jbc.m006316200;
RA Klostermann A., Lutz B., Gertler F., Behl C.;
RT "The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-
RT 1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like
RT protein (EVL) via a novel carboxyl-terminal zyxin-like domain.";
RL J. Biol. Chem. 275:39647-39653(2000).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329 AND SER-367, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-130 IN COMPLEX WITH A SYNTHETIC
RP PRO-RICH PEPTIDE.
RX PubMed=10404224; DOI=10.1038/10717;
RA Fedorov A.A., Fedorov E., Gertler F., Almo S.C.;
RT "Structure of EVH1, a novel proline-rich ligand-binding module involved in
RT cytoskeletal dynamics and neural function.";
RL Nat. Struct. Biol. 6:661-665(1999).
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. EVL enhances actin nucleation and
CC polymerization. {ECO:0000269|PubMed:10087267,
CC ECO:0000269|PubMed:10945997}.
CC -!- SUBUNIT: Homotetramer (By similarity). Binds to the SH3 domains of
CC ABL1, LYN and SRC (PubMed:10945997). Also binds to profilin, with
CC preference for isoform IIa of PFN2, and the WW domain of APBB1/FE65
CC (PubMed:10945997). Binds to SEMA6A (PubMed:10993894). Interacts, via
CC the Pro-rich region, with the C-terminal SH3 domain of DNMBP
CC (PubMed:14506234). Interacts with RAPH1 (By similarity). Binds, via the
CC EVH1 domain, the Pro-rich domain of Listeria monocytogenes actA
CC (PubMed:10087267). Binds, via the EVH1 domain, the Pro-rich domain of
CC ZYX. Interacts with FYB1. Interacts with ZDHHC17 (By similarity).
CC {ECO:0000250|UniProtKB:Q9UI08, ECO:0000269|PubMed:10087267,
CC ECO:0000269|PubMed:10404224, ECO:0000269|PubMed:10945997,
CC ECO:0000269|PubMed:10993894, ECO:0000269|PubMed:14506234}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:10945997}. Cytoplasm, cytoskeleton, stress fiber
CC {ECO:0000269|PubMed:10945997}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:10945997}. Note=Targeted to the leading edge of
CC lamellipodia and the distal tip of stress fibers through interaction
CC with a number of proteins. In activated T-cells, localizes to the F-
CC actin collar and the distal tip of microspikes.
CC {ECO:0000269|PubMed:10945997}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=EVL-I;
CC IsoId=P70429-1; Sequence=Displayed;
CC Name=1;
CC IsoId=P70429-2; Sequence=VSP_004045;
CC -!- TISSUE SPECIFICITY: Highest expression in thymus and spleen (at protein
CC level). Low levels in placenta, ovary, testis, fat and lung (at protein
CC level). Isoform 1 and isoform 2 are expressed in cortical neurons and
CC glial cells. {ECO:0000269|PubMed:10069337,
CC ECO:0000269|PubMed:10945997}.
CC -!- DEVELOPMENTAL STAGE: At an early stage, highly expressed in the
CC branchial and pharyngeal arches, but not in the brain. Expression in
CC the brain starts at 15 dpc (at protein level).
CC {ECO:0000269|PubMed:10069337}.
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: Phosphorylated by PKA; phosphorylation abolishes binding to SH3
CC domains of ABL and SRC. {ECO:0000269|PubMed:10945997}.
CC -!- MISCELLANEOUS: Required to transform actin polymerization into active
CC movement for the propulsive force of Listeria monocytogenes.
CC -!- SIMILARITY: Belongs to the Ena/VASP family. {ECO:0000305}.
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DR EMBL; U72519; AAC52862.1; -; mRNA.
DR EMBL; AF279662; AAG23653.1; -; mRNA.
DR CCDS; CCDS26161.1; -. [P70429-2]
DR CCDS; CCDS49167.1; -. [P70429-1]
DR RefSeq; NP_001156866.1; NM_001163394.1. [P70429-1]
DR RefSeq; NP_031991.3; NM_007965.3. [P70429-2]
DR PDB; 1QC6; X-ray; 2.60 A; A/B=1-130.
DR PDBsum; 1QC6; -.
DR AlphaFoldDB; P70429; -.
DR SMR; P70429; -.
DR BioGRID; 199547; 17.
DR DIP; DIP-40886N; -.
DR ELM; P70429; -.
DR IntAct; P70429; 3.
DR MINT; P70429; -.
DR STRING; 10090.ENSMUSP00000021689; -.
DR GlyGen; P70429; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P70429; -.
DR PhosphoSitePlus; P70429; -.
DR EPD; P70429; -.
DR jPOST; P70429; -.
DR MaxQB; P70429; -.
DR PaxDb; 10090-ENSMUSP00000021689; -.
DR ProteomicsDB; 275699; -. [P70429-1]
DR ProteomicsDB; 275700; -. [P70429-2]
DR Pumba; P70429; -.
DR Antibodypedia; 14371; 172 antibodies from 33 providers.
DR DNASU; 14026; -.
DR Ensembl; ENSMUST00000021689.14; ENSMUSP00000021689.7; ENSMUSG00000021262.16. [P70429-1]
DR Ensembl; ENSMUST00000077735.13; ENSMUSP00000076916.6; ENSMUSG00000021262.16. [P70429-2]
DR GeneID; 14026; -.
DR KEGG; mmu:14026; -.
DR UCSC; uc007ozv.1; mouse. [P70429-2]
DR UCSC; uc007ozw.1; mouse. [P70429-1]
DR AGR; MGI:1194884; -.
DR MGI; MGI:1194884; Evl.
DR VEuPathDB; HostDB:ENSMUSG00000021262; -.
DR eggNOG; KOG4590; Eukaryota.
DR GeneTree; ENSGT00940000157826; -.
DR HOGENOM; CLU_017790_0_0_1; -.
DR InParanoid; P70429; -.
DR OMA; RTHFGIN; -.
DR OrthoDB; 2884005at2759; -.
DR PhylomeDB; P70429; -.
DR TreeFam; TF321411; -.
DR Reactome; R-MMU-376176; Signaling by ROBO receptors.
DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins.
DR BioGRID-ORCS; 14026; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Evl; mouse.
DR EvolutionaryTrace; P70429; -.
DR PRO; PR:P70429; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P70429; Protein.
DR Bgee; ENSMUSG00000021262; Expressed in peripheral lymph node and 257 other cell types or tissues.
DR ExpressionAtlas; P70429; baseline and differential.
DR Genevisible; P70429; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:MGI.
DR GO; GO:0001725; C:stress fiber; 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:UniProtKB.
DR GO; GO:0030048; P:actin filament-based movement; NAS:UniProtKB.
DR GO; GO:0045010; P:actin nucleation; NAS:UniProtKB.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; NAS:UniProtKB.
DR GO; GO:0051016; P:barbed-end actin filament capping; NAS:UniProtKB.
DR GO; GO:0071346; P:cellular response to type II interferon; IDA:MGI.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:1900028; P:negative regulation of ruffle assembly; ISO:MGI.
DR GO; GO:0030168; P:platelet activation; NAS:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR CDD; cd01207; EVH1_Ena_VASP-like; 1.
DR DisProt; DP02387; -.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 1.20.5.1160; Vasodilator-stimulated phosphoprotein; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR017354; VASP/EVL.
DR InterPro; IPR038023; VASP_sf.
DR InterPro; IPR014885; VASP_tetra.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR PANTHER; PTHR11202:SF4; ENA_VASP-LIKE PROTEIN; 1.
DR PANTHER; PTHR11202; SPROUTY-RELATED, EVH1 DOMAIN-CONTAINING PROTEIN FAMILY MEMBER; 1.
DR Pfam; PF08776; VASP_tetra; 1.
DR Pfam; PF00568; WH1; 1.
DR PIRSF; PIRSF038010; Vasodilator_Phospo; 1.
DR SMART; SM00461; WH1; 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF118370; Vasodilator-stimulated phosphoprotein, VASP, tetramerisation domain; 1.
DR PROSITE; PS50229; WH1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cell projection;
KW Cytoplasm; Cytoskeleton; Phosphoprotein; Reference proteome; SH3-binding.
FT CHAIN 1..414
FT /note="Ena/VASP-like protein"
FT /id="PRO_0000087105"
FT DOMAIN 1..112
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REGION 157..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..411
FT /note="EVH2"
FT REGION 220..240
FT /note="EVH2 block A"
FT REGION 263..280
FT /note="EVH2 block B"
FT REGION 340..360
FT /note="Required for interaction with ZDHHC17"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT REGION 377..411
FT /note="EVH2 block C"
FT MOTIF 229..232
FT /note="KLKR"
FT COMPBIAS 177..206
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..297
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08719"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08719"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UI08"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 339..359
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:8861907"
FT /id="VSP_004045"
FT STRAND 4..17
FT /evidence="ECO:0007829|PDB:1QC6"
FT TURN 18..21
FT /evidence="ECO:0007829|PDB:1QC6"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:1QC6"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:1QC6"
FT TURN 42..45
FT /evidence="ECO:0007829|PDB:1QC6"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:1QC6"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:1QC6"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:1QC6"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:1QC6"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:1QC6"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:1QC6"
FT HELIX 95..111
FT /evidence="ECO:0007829|PDB:1QC6"
SQ SEQUENCE 414 AA; 44337 MW; 146A018BCD6CA370 CRC64;
MSEQSICQAR ASVMVYDDTS KKWVPIKPGQ QGFSRINIYH NTASSTFRVV GVKLQDQQVV
INYSIVKGLK YNQATPTFHQ WRDARQVYGL NFASKEEATT FSNAMLFALN IMNSQEGGPS
TQRQVQNGPS PEEMDIQRRQ VMEQQHRQES LERRISATGP ILPPGHPSSA ASTTLSCSGP
PPPPPPPVPP PPTGSTPPPP PPLPAGGAQG TNHDESSASG LAAALAGAKL RRVQRPEDAS
GGSSPSGTSK SDANRASSGG GGGGLMEEMN KLLAKRRKAA SQTDKPADRK EDESQTEDPS
TSPSPGTRAT SQPPNSSEAG RKPWERSNSV EKPVSSLLSR TPSVAKSPEA KSPLQSQPHS
RVKPAGSVND VGLDALDLDR MKQEILEEVV RELHKVKEEI IDAIRQELSG ISTT
//
