Q9UI08 (EVL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ena/VASP-like protein

Alternative name(s):
Ena/vasodilator-stimulated phosphoprotein-like

Gene names

Name:	EVL
Synonyms:	RNB6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Protein existence	Evidence 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. EVL enhances actin nucleation and polymerization.
Subunit structure	Homotetramer By similarity. Binds to the SH3 domains of ABL1, LYN and SRC. Also binds to profilin, with preference for isoform IIa of PFN2, and the WW domain of APBB1/FE65. Binds to SEMA6A. Interacts, via the Pro-rich region, with the C-terminal SH3 domain of DNMBP. Interacts with RAPH1. Binds, via the EVH1 domain, the Pro-rich domain of Listeria monocytogenes actA By similarity. Binds, via the EVH1 domain, the Pro-rich domain of ZYX. Ref.9 Ref.10 Ref.11
Subcellular location	Cytoplasm › cytoskeleton By similarity. Cell projection › lamellipodium By similarity. Note: Targeted to the leading edge of lamellipodia and the dital tip of stress fibers through interaction with a number of proteins. In activated T-cells, localizes to the F-actin collar and the distal tip of microspikes By similarity.
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	Phosphorylated by PKA; phosphorylation abolishes binding to SH3 domains of ABL and SRC By similarity.
Miscellaneous	Required to transform actin polymerization into active movement for the propulsive force of Listeria monocytogenes By similarity.
Sequence similarities	Belongs to the Ena/VASP family. Contains 1 WH1 domain.

Ontologies

Keywords
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3-binding
Ligand	Actin-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin polymerization or depolymerization Inferred from sequence or structural similarity. Source: UniProtKB axon guidance Traceable author statement. Source: Reactome cell surface receptor signaling pathway Non-traceable author statement Ref.9. Source: UniProtKB organ morphogenesis Non-traceable author statement Ref.9. Source: UniProtKB protein homotetramerization Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome focal adhesion Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	SH3 domain binding Inferred from sequence or structural similarity. Source: UniProtKB profilin binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HTT	P42858	2	EBI-6448852,EBI-466029

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q9UI08-1)

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: Q9UI08-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAT

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 416	416	Ena/VASP-like protein		PRO_0000087104
Regions
	Domain	1 – 112	112	WH1
	Region	222 – 413	192	EVH2
	Region	222 – 242	21	EVH2 block A
	Region	265 – 282	18	EVH2 block B
	Region	379 – 413	35	EVH2 block C
	Motif	231 – 234	4	KLKR
	Compositional bias	162 – 206	45	Pro-rich
Amino acid modifications
	Modified residue	246	1	Phosphoserine Ref.13
	Modified residue	304	1	Phosphoserine Ref.13 Ref.14
	Modified residue	306	1	Phosphoserine Ref.13
	Modified residue	329	1	Phosphoserine Ref.13
	Modified residue	331	1	Phosphoserine Ref.13
	Modified residue	341	1	Phosphoserine Ref.14
	Modified residue	345	1	Phosphoserine By similarity
	Modified residue	349	1	Phosphoserine Ref.12 Ref.13
	Modified residue	354	1	Phosphoserine Ref.14
	Modified residue	369	1	Phosphoserine Ref.12
Natural variations
	Alternative sequence	1	1	M → MAT in isoform 1.		VSP_004044
	Natural variant	188	1	P → L in a colorectal cancer sample; somatic mutation. Ref.18		VAR_036464
	Natural variant	247	1	P → L in a colorectal cancer sample; somatic mutation. Ref.18		VAR_036465
Experimental info
	Sequence conflict	201	1	P → S in AAF17197. Ref.3
	Sequence conflict	329	1	S → N in AAP97156. Ref.2
	Sequence conflict	364	1	M → Y in CAB63763. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified November 15, 2002. Version 2. Checksum: AD5B67458755D659	FASTA	416	44,620
	10 20 30 40 50 60 MSEQSICQAR ASVMVYDDTS KKWVPIKPGQ QGFSRINIYH NTASNTFRVV GVKLQDQQVV 70 80 90 100 110 120 INYSIVKGLK YNQATPTFHQ WRDARQVYGL NFASKEEATT FSNAMLFALN IMNSQEGGPS 130 140 150 160 170 180 SQRQVQNGPS PDEMDIQRRQ VMEQHQQQRQ ESLERRTSAT GPILPPGHPS SAASAPVSCS 190 200 210 220 230 240 GPPPPPPPPV PPPPTGATPP PPPPLPAGGA QGSSHDESSM SGLAAAIAGA KLRRVQRPED 250 260 270 280 290 300 ASGGSSPSGT SKSDANRASS GGGGGGLMEE MNKLLAKRRK AASQSDKPAE KKEDESQMED 310 320 330 340 350 360 PSTSPSPGTR AASQPPNSSE AGRKPWERSN SVEKPVSSIL SRTPSVAKSP EAKSPLQSQP 370 380 390 400 410 HSRMKPAGSV NDMALDAFDL DRMKQEILEE VVRELHKVKE EIIDAIRQEL SGISTT
	Isoform 1 [UniParc]. Checksum: BFCCF68CF923720C	FASTA	418	44,792
	10 20 30 40 50 60 MATSEQSICQ ARASVMVYDD TSKKWVPIKP GQQGFSRINI YHNTASNTFR VVGVKLQDQQ 70 80 90 100 110 120 VVINYSIVKG LKYNQATPTF HQWRDARQVY GLNFASKEEA TTFSNAMLFA LNIMNSQEGG 130 140 150 160 170 180 PSSQRQVQNG PSPDEMDIQR RQVMEQHQQQ RQESLERRTS ATGPILPPGH PSSAASAPVS 190 200 210 220 230 240 CSGPPPPPPP PVPPPPTGAT PPPPPPLPAG GAQGSSHDES SMSGLAAAIA GAKLRRVQRP 250 260 270 280 290 300 EDASGGSSPS GTSKSDANRA SSGGGGGGLM EEMNKLLAKR RKAASQSDKP AEKKEDESQM 310 320 330 340 350 360 EDPSTSPSPG TRAASQPPNS SEAGRKPWER SNSVEKPVSS ILSRTPSVAK SPEAKSPLQS 370 380 390 400 410 QPHSRMKPAG SVNDMALDAF DLDRMKQEIL EEVVRELHKV KEEIIDAIRQ ELSGISTT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Ohta S., Mineta T., Kimoto M., Tabuchi K. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Cloning of a new human cDNA homologous to R.norvegicus RNB6 mRNA." Wan Y.Z., Yu L., Yue P., Tu Q., Fu S.N., Zhao S.Y. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Adrenal gland.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 2). Tissue: Lung and Pancreas.
[7]	Mei G., Yu W., Gibbs R.A. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 55-416. Tissue: Brain.
[8]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 163-364. Tissue: Uterus.
[9]	"The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like protein (EVL) via a novel carboxyl-terminal zyxin-like domain." Klostermann A., Lutz B., Gertler F., Behl C. J. Biol. Chem. 275:39647-39653(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SEMA6A.
[10]	"Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics." Krause M., Leslie J.D., Stewart M., Lafuente E.M., Valderrama F., Jagannathan R., Strasser G.A., Rubinson D.A., Liu H., Way M., Yaffe M.B., Boussiotis V.A., Gertler F.B. Dev. Cell 7:571-583(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAPH1.
[11]	"Tes, a specific Mena interacting partner, breaks the rules for EVH1 binding." Boeda B., Briggs D.C., Higgins T., Garvalov B.K., Fadden A.J., McDonald N.Q., Way M. Mol. Cell 28:1071-1082(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZYX.
[12]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349 AND SER-369, MASS SPECTROMETRY. Tissue: T-cell.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-304; SER-306; SER-329; SER-331 AND SER-349, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304; SER-341 AND SER-354, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-188 AND LEU-247.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF052504 mRNA. Translation: AAF21709.1. AF087843 mRNA. Translation: AAP97156.1. AF112209 mRNA. Translation: AAF17197.1. AK289720 mRNA. Translation: BAF82409.1. CH471061 Genomic DNA. Translation: EAW81684.1. BC023997 mRNA. Translation: AAH23997.1. BC032358 mRNA. Translation: AAH32358.1. AF131766 mRNA. Translation: AAD20040.1. AL133642 mRNA. Translation: CAB63763.2.
IPI	IPI00170979. IPI00218245.
RefSeq	NP_057421.1. NM_016337.2.
UniGene	Hs.125867.
3D structure databases
ProteinModelPortal	Q9UI08.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UI08. 4 interactions.
MINT	MINT-3080348.
STRING	9606.ENSP00000376652.
PTM databases
PhosphoSite	Q9UI08.
Polymorphism databases
DMDM	25090276.
Proteomic databases
PaxDb	Q9UI08.
PRIDE	Q9UI08.
Protocols and materials databases
DNASU	51466.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000392920; ENSP00000376652; ENSG00000196405. ENST00000402714; ENSP00000384720; ENSG00000196405.
GeneID	51466.
KEGG	hsa:51466.
UCSC	uc001ygt.3. human. uc001ygu.3. human.
Organism-specific databases
CTD	51466.
GeneCards	GC14P101073.
H-InvDB	HIX0011964.
HGNC	HGNC:20234. EVL.
HPA	HPA018849.
neXtProt	NX_Q9UI08.
PharmGKB	PA134890866.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG265043.
HOVERGEN	HBG006655.
OMA	TQRQVQN.
OrthoDB	EOG4BVRV3.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9UI08.
Bgee	Q9UI08.
CleanEx	HS_EVL.
Genevestigator	Q9UI08.
GermOnline	ENSG00000196405. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR000697. EVH1. IPR011993. PH_like_dom. IPR017354. Vasodilator_phosphoprotein. IPR014885. VASP_tetra. [Graphical view]
Pfam	PF08776. VASP_tetra. 1 hit. PF00568. WH1. 1 hit. [Graphical view]
PIRSF	PIRSF038010. Vasodilator_Phospo. 1 hit.
SMART	SM00461. WH1. 1 hit. [Graphical view]
PROSITE	PS50229. WH1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	EVL. human.
GenomeRNAi	51466.
NextBio	55097.

Entry information

Entry name

EVL_HUMAN

Accession

Primary (citable) accession number: Q9UI08
Secondary accession number(s): A8K105 , O95884, Q7Z522, Q8TBV1, Q9UF25, Q9UIC2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	November 15, 2002
Last modified:	May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.