VASP_CANLF
ID VASP_CANLF Reviewed; 384 AA.
AC P50551;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 133.
DE RecName: Full=Vasodilator-stimulated phosphoprotein;
DE Short=VASP;
GN Name=VASP;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Cocker spaniel; TISSUE=Kidney;
RX PubMed=7828592; DOI=10.1002/j.1460-2075.1995.tb06971.x;
RA Haffner C., Jarchau T., Reinhard M., Hoppe J., Lohmann S.M., Walter U.;
RT "Molecular cloning, structural analysis and functional expression of the
RT proline-rich focal adhesion and microfilament-associated protein VASP.";
RL EMBO J. 14:19-27(1995).
RN [2]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-160 BY PKA.
RX PubMed=15096524; DOI=10.1083/jcb.200312118;
RA Koehler K., Louvard D., Zahraoui A.;
RT "Rab13 regulates PKA signaling during tight junction assembly.";
RL J. Cell Biol. 165:175-180(2004).
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, lamellipodial and filopodial dynamics,
CC platelet activation and cell migration. VASP promotes actin filament
CC elongation. It protects the barbed end of growing actin filaments
CC against capping and increases the rate of actin polymerization in the
CC presence of capping protein. VASP stimulates actin filament elongation
CC by promoting the transfer of profilin-bound actin monomers onto the
CC barbed end of growing actin filaments. Plays a role in actin-based
CC mobility of Listeria monocytogenes in host cells. Regulates actin
CC dynamics in platelets and plays an important role in regulating
CC platelet aggregation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homotetramer. Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1.
CC Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This
CC interaction is important for targeting to focal adhesions and the
CC formation of actin-rich structures at the apical surface of cells.
CC Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria
CC monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich
CC domain, with the C-terminal SH3 domain of DNMBP. Interacts weakly with
CC MEFV (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15096524}.
CC Cytoplasm, cytoskeleton {ECO:0000250}. Cell junction, focal adhesion
CC {ECO:0000250}. Cell junction, tight junction
CC {ECO:0000269|PubMed:15096524}. Cell projection, lamellipodium membrane
CC {ECO:0000250}. Cell projection, filopodium membrane {ECO:0000250}.
CC Note=Targeted to stress fibers and focal adhesions through interaction
CC with a number of proteins including MRL family members. Localizes to
CC the plasma membrane in protruding lamellipodia and filopodial tips.
CC Stimulation by thrombin or PMA, also translocates VASP to focal
CC adhesions. Localized along the sides of actin filaments throughout the
CC peripheral cytoplasm under basal conditions. In pre-apoptotic cells,
CC colocalizes with MEFV in large specks (pyroptosomes) (By similarity).
CC {ECO:0000250}.
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 -!- DOMAIN: The WH1 domain mediates interaction with XIRP1. {ECO:0000250}.
CC -!- PTM: Major substrate for cAMP-dependent (PKA) and cGMP-dependent
CC protein kinase (PKG) in platelets. The preferred site for PKA is Ser-
CC 160, the preferred site for PKG/PRKG1, Ser-242. In ADP-activated
CC platelets, phosphorylation by PKA or PKG on Ser-160 leads to fibrinogen
CC receptor inhibition. Phosphorylation on Thr-281 requires prior
CC phosphorylation on Ser-160 and Ser-242. In response to phorbol ester
CC (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to
CC thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-
CC 281 by AMPK does not require prior phosphorylation at Ser-160 or Ser-
CC 242. Phosphorylation at Ser-160 by PKA is required for localization to
CC the tight junctions in epithelial cells. Phosphorylation modulates F-
CC actin binding, actin filament elongation and platelet activation.
CC Phosphorylation at Ser-326 by AMPK also alters actin filament binding.
CC Carbon monoxide (CO) promotes phosphorylation at Ser-160, while nitric
CC oxide (NO) promotes phosphorylation at Ser-160, but also at Ser-242 (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Ena/VASP family. {ECO:0000305}.
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DR EMBL; Z46388; CAA86522.1; -; mRNA.
DR PIR; S51796; S51796.
DR RefSeq; NP_001003256.1; NM_001003256.1.
DR AlphaFoldDB; P50551; -.
DR SMR; P50551; -.
DR STRING; 9615.ENSCAFP00000064684; -.
DR iPTMnet; P50551; -.
DR PaxDb; P50551; -.
DR PRIDE; P50551; -.
DR GeneID; 403936; -.
DR KEGG; cfa:403936; -.
DR CTD; 7408; -.
DR eggNOG; KOG4590; Eukaryota.
DR InParanoid; P50551; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0031258; C:lamellipodium membrane; 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:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0001843; P:neural tube closure; IBA:GO_Central.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IBA:GO_Central.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR034367; VASP.
DR InterPro; IPR017354; VASP/EVL.
DR InterPro; IPR038023; VASP_sf.
DR InterPro; IPR014885; VASP_tetra.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR PANTHER; PTHR11202:SF12; PTHR11202:SF12; 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; SSF118370; SSF118370; 1.
DR PROSITE; PS50229; WH1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Cell junction; Cell membrane; Cell projection;
KW Coiled coil; Cytoplasm; Cytoskeleton; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; SH3-binding; Tight junction.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT CHAIN 2..384
FT /note="Vasodilator-stimulated phosphoprotein"
FT /id="PRO_0000065766"
FT DOMAIN 2..113
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REPEAT 348..362
FT /note="1"
FT REPEAT 363..377
FT /note="2"
FT REGION 112..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..381
FT /note="EVH2"
FT REGION 228..248
FT /note="EVH2 block A"
FT REGION 262..281
FT /note="EVH2 block B"
FT REGION 347..381
FT /note="EVH2 block C"
FT REGION 348..377
FT /note="2 X 15 AA tandem repeats of L-[EQ]-[KR] [MV]-K-[EQ]-
FT E-[IL]-[IL]-E-[AEV]-[FV]-[KRV]-[KQ]-E"
FT COILED 344..377
FT /evidence="ECO:0000255"
FT MOTIF 237..240
FT /note="KLKR"
FT COMPBIAS 115..130
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..145
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..192
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..297
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 39
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 160
FT /note="Phosphoserine; by PKA, PKG/PRKG1, PKC and ROCK1"
FT /evidence="ECO:0000269|PubMed:15096524"
FT MOD_RES 242
FT /note="Phosphoserine; by PKA and PKG/PRKG1"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 281
FT /note="Phosphothreonine; by PKA, PKG/PRKG1 and AMPK"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 286
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 320
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 326
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:P50552"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70460"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70460"
SQ SEQUENCE 384 AA; 40413 MW; 266BB3C46FB4397F CRC64;
MSETVICSSW ATVMLYDDSN KRWLPAGTGP QSFSRVQIYH NPTANSFRVV GWKMQPDQQV
VINCAIVRGI KYNQATPTFH QWRDARQVWG LNFGSKEDAT QFAAAMASAL EALEGGGPPP
PPPPAAPPTW SVQNGPASEE VEQQKRQQPG PPEHLERRVS NAGGPPAPPA GGPPPPPGPP
PPPGPPPPPG VSLSGGSAAG HGAGGGPPPA PPLPTAQGTS GGGTGAPGLA AAIAGAKLRK
VSKQEEASGG PPVPKAESTR STGGGLMEEM NAMLARRRKA TQVGEKPPKD ESANEEPEAR
VPVPAQSETV RRPWEKNSTT LPRMKSSSSV TTSEAHPSTP SSSDESDLER VKQELLEEVR
KELQKVKEEI IEAFVQELRK RGSP
