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Vang-like protein 2 (Loop-tail protein 1) (Loop-tail-associated protein) (Van Gogh-like protein 2)

 VANG2_MOUSE             Reviewed;         521 AA.
Q91ZD4; Q923Z8;
31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
01-JUN-2002, sequence version 3.
27-SEP-2017, entry version 118.
RecName: Full=Vang-like protein 2;
AltName: Full=Loop-tail protein 1;
AltName: Full=Loop-tail-associated protein;
AltName: Full=Van Gogh-like protein 2;
Name=Vangl2; Synonyms=Lpp1, Ltap;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT LP
ASN-464.
STRAIN=C57BL/6J;
PubMed=11709546; DOI=10.1093/hmg/10.22.2593;
Murdoch J.N., Doudney K., Paternotte C., Copp A.J., Stanier P.;
"Severe neural tube defects in the loop-tail mouse result from
mutation of Lpp1, a novel gene involved in floor plate
specification.";
Hum. Mol. Genet. 10:2593-2601(2001).
[2]
NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, TISSUE SPECIFICITY,
AND VARIANTS LP GLU-255 AND ASN-464.
STRAIN=C57BL/6J;
PubMed=11431695; DOI=10.1038/90081;
Kibar Z., Vogan K.J., Groulx N., Justice M.J., Underhill D.A.,
Gros P.;
"Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is
altered in the mouse neural tube mutant loop-tail.";
Nat. Genet. 28:251-255(2001).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Limb;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
DISEASE.
PubMed=11440971; DOI=10.1161/hh1301.092497;
Henderson D.J., Conway S.J., Greene N.D.E., Gerrelli D., Murdoch J.N.,
Anderson R.H., Copp A.J.;
"Cardiovascular defects associated with abnormalities in midline
development in the loop-tail mouse mutant.";
Circ. Res. 89:6-12(2001).
[5]
FUNCTION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
PubMed=12724779; DOI=10.1038/nature01618;
Montcouquiol M., Rachel R.A., Lanford P.J., Copeland N.G.,
Jenkins N.A., Kelley M.W.;
"Identification of Vangl2 and Scrb1 as planar polarity genes in
mammals.";
Nature 423:173-177(2003).
[6]
INTERACTION WITH DVL1; DVL2 AND DVL3.
PubMed=15456783; DOI=10.1074/jbc.M408675200;
Torban E., Wang H.-J., Groulx N., Gros P.;
"Independent mutations in mouse Vangl2 that cause neural tube defects
in looptail mice impair interaction with members of the Dishevelled
family.";
J. Biol. Chem. 279:52703-52713(2004).
[7]
INTERACTION WITH MAGI3.
PubMed=15195140; DOI=10.1038/sj.onc.1207817;
Yao R., Natsume Y., Noda T.;
"MAGI-3 is involved in the regulation of the JNK signaling pathway as
a scaffold protein for frizzled and Ltap.";
Oncogene 23:6023-6030(2004).
[8]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=15637299; DOI=10.1161/01.RES.0000154912.08695.88;
Phillips H.M., Murdoch J.N., Chaudhry B., Copp A.J., Henderson D.J.;
"Vangl2 acts via RhoA signaling to regulate polarized cell movements
during development of the proximal outflow tract.";
Circ. Res. 96:292-299(2005).
[9]
FUNCTION.
PubMed=16495441; DOI=10.1523/JNEUROSCI.4698-05.2005;
Wang Y., Guo N., Nathans J.;
"The role of Frizzled3 and Frizzled6 in neural tube closure and in the
planar polarity of inner-ear sensory hair cells.";
J. Neurosci. 26:2147-2156(2006).
[10]
INTERACTION WITH FZD3 AND SCRIB, AND TISSUE SPECIFICITY.
PubMed=16687519; DOI=10.1523/JNEUROSCI.4680-05.2006;
Montcouquiol M., Sans N., Huss D., Kach J., Dickman J.D., Forge A.,
Rachel R.A., Copeland N.G., Jenkins N.A., Bogani D., Murdoch J.,
Warchol M.E., Wenthold R.J., Kelley M.W.;
"Asymmetric localization of Vangl2 and Fz3 indicate novel mechanisms
for planar cell polarity in mammals.";
J. Neurosci. 26:5265-5275(2006).
[11]
SUBCELLULAR LOCATION, AND SUBUNIT.
PubMed=23029439; DOI=10.1371/journal.pone.0046213;
Belotti E., Puvirajesinghe T.M., Audebert S., Baudelet E., Camoin L.,
Pierres M., Lasvaux L., Ferracci G., Montcouquiol M., Borg J.P.;
"Molecular characterisation of endogenous Vangl2/Vangl1 heteromeric
protein complexes.";
PLoS ONE 7:E46213-E46213(2012).
-!- FUNCTION: Involved in the control of early morphogenesis and
patterning of both axial midline structures and the development of
neural plate. Plays a role in the regulation of planar cell
polarity, particularly in the orientation of stereociliary bundles
in the cochlea. Required for polarization and movement of
myocardializing cells in the outflow tract and seems to act via
RHOA signaling to regulate this process. Required for cell surface
localization of FZD3 and FZD6 in the inner ear (PubMed:16495441).
{ECO:0000269|PubMed:12724779, ECO:0000269|PubMed:15637299,
ECO:0000269|PubMed:16495441}.
-!- SUBUNIT: Homodimer and heterodimer with Vangl1. Interacts through
its C-terminal region with the N-terminal half of DVL1, DVL2 and
DVL3. The PDZ domain of DVL1, DVL2 and DVL3 is required for the
interaction. Variants Glu-255 and Asn-464 impair interaction with
the DVL proteins. Also interacts with the PDZ domains of MAGI3,
SCRIB/SCRB1 and FZD3. {ECO:0000269|PubMed:15195140,
ECO:0000269|PubMed:15456783, ECO:0000269|PubMed:16687519,
ECO:0000269|PubMed:23029439}.
-!- INTERACTION:
Q8R4A3:Dact1; NbExp=3; IntAct=EBI-1750744, EBI-3870250;
P31016:Dlg4 (xeno); NbExp=6; IntAct=EBI-1750744, EBI-375655;
P51141:Dvl1; NbExp=2; IntAct=EBI-1750744, EBI-1538407;
Q60838:Dvl2; NbExp=4; IntAct=EBI-1750744, EBI-641940;
Q61062:Dvl3; NbExp=2; IntAct=EBI-1750744, EBI-1538450;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23029439};
Multi-pass membrane protein {ECO:0000269|PubMed:23029439}.
-!- TISSUE SPECIFICITY: Primarily expressed in the brain and
epididymis. Not detected in the cochlea of Lp mice.
{ECO:0000269|PubMed:11431695, ECO:0000269|PubMed:11709546,
ECO:0000269|PubMed:12724779, ECO:0000269|PubMed:16687519}.
-!- DEVELOPMENTAL STAGE: In the embryo, strongly expressed in the
neuroectoderm from the earliest stages of neural induction through
the late stages of neural tube closure. Detected in the dorso-
ventral axis of the neural tube, but not in the floor plate.
Expression is low at day E7; it peaks at E11, and it remains
strong at E15 and E17. Also expressed in the cochlear epithelium
at days E14.5 and E16.5. Detected at low levels in the outflow
tract myocardium from E9.5 with levels increasing by E11.5.
{ECO:0000269|PubMed:11431695, ECO:0000269|PubMed:12724779,
ECO:0000269|PubMed:15637299}.
-!- DISEASE: Note=Defects in Vangl2 are a cause of the loop-tail (Lp)
mutant phenotype. Heterozygous Lp mice exhibit a characteristic
looped tail, while homozygous embryos show a completely open
neural tube in the hindbrain and spinal region, a condition
similar to the severe craniorachischisis defect in humans.
Homozygotes also have complex cardiovascular defects including
double-outlet right ventricle, perimembranous ventricular defects,
double-sided aortic arch and associated abnormalities in the
aortic arch arteries. Homozygotes show cytoplasmic accumulation of
Vangl2 instead of the normal membrane localization, and Rhoa
expression, which is detected in the mesenchymal cushion cells
adjacent to the outflow tract, is lost in homozygotes. Homozygous
embryos typically die shortly before or at birth.
{ECO:0000269|PubMed:11440971}.
-!- SIMILARITY: Belongs to the Vang family. {ECO:0000305}.
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EMBL; AY035370; AAK63188.3; -; mRNA.
EMBL; AF365875; AAK91927.1; -; mRNA.
EMBL; BC052195; AAH52195.1; -; mRNA.
CCDS; CCDS15505.1; -.
RefSeq; NP_277044.1; NM_033509.4.
RefSeq; XP_006497114.1; XM_006497051.3.
RefSeq; XP_006497115.1; XM_006497052.3.
RefSeq; XP_006497116.1; XM_006497053.3.
RefSeq; XP_006497117.1; XM_006497054.3.
RefSeq; XP_017168497.1; XM_017313008.1.
UniGene; Mm.36148; -.
UniGene; Mm.392110; -.
ProteinModelPortal; Q91ZD4; -.
BioGrid; 220314; 6.
CORUM; Q91ZD4; -.
IntAct; Q91ZD4; 11.
MINT; MINT-8416698; -.
STRING; 10090.ENSMUSP00000027837; -.
iPTMnet; Q91ZD4; -.
PhosphoSitePlus; Q91ZD4; -.
SwissPalm; Q91ZD4; -.
MaxQB; Q91ZD4; -.
PaxDb; Q91ZD4; -.
PRIDE; Q91ZD4; -.
Ensembl; ENSMUST00000027837; ENSMUSP00000027837; ENSMUSG00000026556.
Ensembl; ENSMUST00000111263; ENSMUSP00000106894; ENSMUSG00000026556.
GeneID; 93840; -.
KEGG; mmu:93840; -.
UCSC; uc007dpi.1; mouse.
CTD; 57216; -.
MGI; MGI:2135272; Vangl2.
eggNOG; KOG3814; Eukaryota.
eggNOG; ENOG410XPVT; LUCA.
GeneTree; ENSGT00390000012496; -.
HOVERGEN; HBG058215; -.
InParanoid; Q91ZD4; -.
KO; K04510; -.
TreeFam; TF313467; -.
Reactome; R-MMU-4086400; PCP/CE pathway.
Reactome; R-MMU-4608870; Asymmetric localization of PCP proteins.
PRO; PR:Q91ZD4; -.
Proteomes; UP000000589; Chromosome 1.
Bgee; ENSMUSG00000026556; -.
CleanEx; MM_VANGL2; -.
ExpressionAtlas; Q91ZD4; baseline and differential.
Genevisible; Q91ZD4; MM.
GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
GO; GO:0071944; C:cell periphery; IDA:MGI.
GO; GO:0060187; C:cell pole; IDA:MGI.
GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IDA:MGI.
GO; GO:0016021; C:integral component of membrane; ISS:MGI.
GO; GO:0016328; C:lateral plasma membrane; IDA:MGI.
GO; GO:0005886; C:plasma membrane; IDA:MGI.
GO; GO:0001725; C:stress fiber; IDA:MGI.
GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
GO; GO:0045176; P:apical protein localization; IMP:MGI.
GO; GO:0001569; P:branching involved in blood vessel morphogenesis; TAS:DFLAT.
GO; GO:0060947; P:cardiac vascular smooth muscle cell differentiation; TAS:DFLAT.
GO; GO:0035787; P:cell migration involved in kidney development; IMP:UniProtKB.
GO; GO:0090102; P:cochlea development; IGI:MGI.
GO; GO:0090103; P:cochlea morphogenesis; IMP:MGI.
GO; GO:0060028; P:convergent extension involved in axis elongation; IMP:MGI.
GO; GO:0022007; P:convergent extension involved in neural plate elongation; IMP:MGI.
GO; GO:0060029; P:convergent extension involved in organogenesis; IGI:MGI.
GO; GO:0048546; P:digestive tract morphogenesis; IGI:MGI.
GO; GO:0036514; P:dopaminergic neuron axon guidance; IMP:ParkinsonsUK-UCL.
GO; GO:0003347; P:epicardial cell to mesenchymal cell transition; TAS:DFLAT.
GO; GO:0048105; P:establishment of body hair planar orientation; IMP:MGI.
GO; GO:0090162; P:establishment of epithelial cell polarity; TAS:DFLAT.
GO; GO:0001736; P:establishment of planar polarity; IMP:UniProtKB.
GO; GO:0090177; P:establishment of planar polarity involved in neural tube closure; IMP:MGI.
GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IMP:MGI.
GO; GO:0032835; P:glomerulus development; IMP:MGI.
GO; GO:0001942; P:hair follicle development; IMP:MGI.
GO; GO:0001947; P:heart looping; IMP:UniProtKB.
GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:MGI.
GO; GO:0060119; P:inner ear receptor cell development; IGI:MGI.
GO; GO:0060122; P:inner ear receptor stereocilium organization; IMP:MGI.
GO; GO:0060993; P:kidney morphogenesis; IMP:MGI.
GO; GO:0060490; P:lateral sprouting involved in lung morphogenesis; IMP:MGI.
GO; GO:0003149; P:membranous septum morphogenesis; IGI:MGI.
GO; GO:0003150; P:muscular septum morphogenesis; IGI:MGI.
GO; GO:0001843; P:neural tube closure; IMP:MGI.
GO; GO:0035567; P:non-canonical Wnt signaling pathway; IMP:MGI.
GO; GO:1905515; P:non-motile cilium assembly; IGI:MGI.
GO; GO:0060488; P:orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis; IMP:MGI.
GO; GO:0003148; P:outflow tract septum morphogenesis; TAS:DFLAT.
GO; GO:0003402; P:planar cell polarity pathway involved in axis elongation; IGI:MGI.
GO; GO:1904938; P:planar cell polarity pathway involved in axon guidance; IMP:ParkinsonsUK-UCL.
GO; GO:0061346; P:planar cell polarity pathway involved in heart morphogenesis; IMP:MGI.
GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IMP:MGI.
GO; GO:0060489; P:planar dichotomous subdivision of terminal units involved in lung branching morphogenesis; IMP:MGI.
GO; GO:0043507; P:positive regulation of JUN kinase activity; IGI:MGI.
GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:MGI.
GO; GO:0090175; P:regulation of establishment of planar polarity; IGI:MGI.
GO; GO:0030111; P:regulation of Wnt signaling pathway; IMP:MGI.
GO; GO:0007266; P:Rho protein signal transduction; IMP:MGI.
GO; GO:0036515; P:serotonergic neuron axon guidance; IMP:ParkinsonsUK-UCL.
GO; GO:0048103; P:somatic stem cell division; IMP:MGI.
GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IMP:MGI.
GO; GO:0042060; P:wound healing; IGI:MGI.
InterPro; IPR009539; VANGL.
PANTHER; PTHR20886; PTHR20886; 1.
Pfam; PF06638; Strabismus; 1.
PIRSF; PIRSF007991; Strabismus; 1.
1: Evidence at protein level;
Cell membrane; Complete proteome; Developmental protein;
Disease mutation; Membrane; Reference proteome; Transmembrane;
Transmembrane helix.
CHAIN 1 521 Vang-like protein 2.
/FTId=PRO_0000186196.
TOPO_DOM 1 108 Cytoplasmic. {ECO:0000255}.
TRANSMEM 109 129 Helical; Name=1. {ECO:0000255}.
TOPO_DOM 130 147 Extracellular. {ECO:0000255}.
TRANSMEM 148 168 Helical; Name=2. {ECO:0000255}.
TOPO_DOM 169 178 Cytoplasmic. {ECO:0000255}.
TRANSMEM 179 199 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 200 217 Extracellular. {ECO:0000255}.
TRANSMEM 218 238 Helical; Name=4. {ECO:0000255}.
TOPO_DOM 239 521 Cytoplasmic. {ECO:0000255}.
VARIANT 255 255 D -> E (in Lp).
{ECO:0000269|PubMed:11431695}.
VARIANT 464 464 S -> N (in Lp).
{ECO:0000269|PubMed:11431695,
ECO:0000269|PubMed:11709546}.
SEQUENCE 521 AA; 59771 MW; 94ECEF3EE63DF5BC CRC64;
MDTESQYSGY SYKSGHSRSS RKHRDRRDRH RSKSRDGSRG DKSVTIQAPG EPLLDNESTR
GDERDDNWGE TTTVVTGTSE HSISHDDLTR IAKDMEDSVP LDCSRHLGVA AGAILALLSF
LTPLAFLLLP PLLWREELEP CGTACEGLFI SVAFKLLILL LGSWALFFRR PKASLPRVFV
LRALLMVLVF LLVISYWLFY GVRILDARER SYQGVVQFAV SLVDALLFVH YLAVVLLELR
QLQPQFTLKV VRSTDGASRF YNVGHLSIQR VAVWILEKYY HDFPVYNPAL LNLPKSVLAK
KVSGFKVYSL GEENSTNNST GQSRAVIAAA ARRRDNSHNE YYYEEAEHER RVRKRRARLV
VAVEEAFTHI KRLQEEEQKN PREVMDPREA AQAIFASMAR AMQKYLRTTK QQPYHTMESI
LQHLEFCITH DMTPKAFLER YLAAGPTIQY HKERWLAKQW TLVSEEPVTN GLKDGIVFLL
KRQDFSLVVS TKKVPFFKLS EEFVDPKSHK FVMRLQSETS V


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