VANG2_HUMAN
ID VANG2_HUMAN Reviewed; 521 AA.
AC Q9ULK5; D3DVE9; Q5T212;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Vang-like protein 2;
DE AltName: Full=Loop-tail protein 1 homolog;
DE AltName: Full=Strabismus 1;
DE AltName: Full=Van Gogh-like protein 2;
GN Name=VANGL2; Synonyms=KIAA1215, STB1;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP VARIANTS NTD PHE-84; CYS-353 AND SER-437, AND CHARACTERIZATION OF VARIANTS
RP NTD CYS-353 AND SER-437.
RX PubMed=20558380; DOI=10.1056/nejmc0910820;
RA Lei Y.P., Zhang T., Li H., Wu B.L., Jin L., Wang H.Y.;
RT "VANGL2 mutations in human cranial neural-tube defects.";
RL N. Engl. J. Med. 362:2232-2235(2010).
CC -!- FUNCTION: Involved in the control of early morphogenesis and patterning
CC of both axial midline structures and the development of neural plate.
CC Plays a role in the regulation of planar cell polarity, particularly in
CC the orientation of stereociliary bundles in the cochlea. Required for
CC polarization and movement of myocardializing cells in the outflow tract
CC and seems to act via RHOA signaling to regulate this process. Required
CC for cell surface localization of FZD3 and FZD6 in the inner ear (By
CC similarity). {ECO:0000250|UniProtKB:Q91ZD4}.
CC -!- SUBUNIT: Homodimer and heterodimer with VANGL1. Interacts through its
CC C-terminal region with the N-terminal half of DVL1, DVL2 and DVL3. The
CC PDZ domain of DVL1, DVL2 and DVL3 is required for the interaction. Also
CC interacts with the PDZ domains of MAGI3, SCRIB/SCRB1 and FZD3 (By
CC similarity). Interacts with PRICKLE3 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q90X64}.
CC -!- INTERACTION:
CC Q9ULK5; Q12959: DLG1; NbExp=2; IntAct=EBI-1054279, EBI-357481;
CC Q9ULK5; P26045: PTPN3; NbExp=2; IntAct=EBI-1054279, EBI-1047946;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital
CC malformations of the central nervous system and adjacent structures
CC related to defective neural tube closure during the first trimester of
CC pregnancy. Failure of neural tube closure can occur at any level of the
CC embryonic axis. Common NTD forms include anencephaly, myelomeningocele
CC and spina bifida, which result from the failure of fusion in the
CC cranial and spinal region of the neural tube. NTDs have a
CC multifactorial etiology encompassing both genetic and environmental
CC components. {ECO:0000269|PubMed:20558380}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Vang family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86529.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB033041; BAA86529.1; ALT_INIT; mRNA.
DR EMBL; AL445230; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52718.1; -; Genomic_DNA.
DR EMBL; BC103920; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS30915.1; -.
DR RefSeq; NP_065068.1; NM_020335.2.
DR RefSeq; XP_005245414.1; XM_005245357.1.
DR RefSeq; XP_011508106.1; XM_011509804.1.
DR PDB; 6XA6; X-ray; 1.95 A; C/D=514-521.
DR PDB; 6XA7; X-ray; 2.50 A; E/F/G/H=514-521.
DR PDB; 6XA8; X-ray; 2.20 A; C/D=515-521.
DR PDBsum; 6XA6; -.
DR PDBsum; 6XA7; -.
DR PDBsum; 6XA8; -.
DR AlphaFoldDB; Q9ULK5; -.
DR SMR; Q9ULK5; -.
DR BioGRID; 121454; 173.
DR CORUM; Q9ULK5; -.
DR IntAct; Q9ULK5; 35.
DR MINT; Q9ULK5; -.
DR STRING; 9606.ENSP00000357040; -.
DR iPTMnet; Q9ULK5; -.
DR PhosphoSitePlus; Q9ULK5; -.
DR BioMuta; VANGL2; -.
DR DMDM; 38258849; -.
DR EPD; Q9ULK5; -.
DR jPOST; Q9ULK5; -.
DR MassIVE; Q9ULK5; -.
DR MaxQB; Q9ULK5; -.
DR PaxDb; Q9ULK5; -.
DR PeptideAtlas; Q9ULK5; -.
DR PRIDE; Q9ULK5; -.
DR ProteomicsDB; 85062; -.
DR Antibodypedia; 34278; 238 antibodies from 32 providers.
DR DNASU; 57216; -.
DR Ensembl; ENST00000368061.3; ENSP00000357040.2; ENSG00000162738.6.
DR GeneID; 57216; -.
DR KEGG; hsa:57216; -.
DR MANE-Select; ENST00000368061.3; ENSP00000357040.2; NM_020335.3; NP_065068.1.
DR UCSC; uc001fwc.3; human.
DR CTD; 57216; -.
DR DisGeNET; 57216; -.
DR GeneCards; VANGL2; -.
DR HGNC; HGNC:15511; VANGL2.
DR HPA; ENSG00000162738; Tissue enhanced (skin).
DR MalaCards; VANGL2; -.
DR MIM; 182940; phenotype.
DR MIM; 600533; gene.
DR neXtProt; NX_Q9ULK5; -.
DR OpenTargets; ENSG00000162738; -.
DR Orphanet; 268392; Cervical spina bifida aperta.
DR Orphanet; 268762; Cervical spina bifida cystica.
DR Orphanet; 268397; Cervicothoracic spina bifida aperta.
DR Orphanet; 268766; Cervicothoracic spina bifida cystica.
DR Orphanet; 563609; Isolated anencephaly.
DR Orphanet; 563612; Isolated exencephaly.
DR Orphanet; 268388; Lumbosacral spina bifida aperta.
DR Orphanet; 268758; Lumbosacral spina bifida cystica.
DR Orphanet; 268384; Thoracolumbosacral spina bifida aperta.
DR Orphanet; 268752; Thoracolumbosacral spina bifida cystica.
DR Orphanet; 268377; Total spina bifida aperta.
DR Orphanet; 268748; Total spina bifida cystica.
DR Orphanet; 268740; Upper thoracic spina bifida aperta.
DR Orphanet; 268770; Upper thoracic spina bifida cystica.
DR PharmGKB; PA37970; -.
DR VEuPathDB; HostDB:ENSG00000162738; -.
DR eggNOG; KOG3814; Eukaryota.
DR GeneTree; ENSGT00390000012496; -.
DR HOGENOM; CLU_015742_1_0_1; -.
DR InParanoid; Q9ULK5; -.
DR OMA; TRDMDNE; -.
DR OrthoDB; 1325060at2759; -.
DR PhylomeDB; Q9ULK5; -.
DR TreeFam; TF313467; -.
DR PathwayCommons; Q9ULK5; -.
DR Reactome; R-HSA-4086400; PCP/CE pathway.
DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696270; RND2 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; Q9ULK5; -.
DR BioGRID-ORCS; 57216; 8 hits in 1077 CRISPR screens.
DR ChiTaRS; VANGL2; human.
DR GenomeRNAi; 57216; -.
DR Pharos; Q9ULK5; Tbio.
DR PRO; PR:Q9ULK5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9ULK5; protein.
DR Bgee; ENSG00000162738; Expressed in ganglionic eminence and 145 other tissues.
DR Genevisible; Q9ULK5; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045176; P:apical protein localization; ISS:UniProtKB.
DR GO; GO:0035787; P:cell migration involved in kidney development; ISS:UniProtKB.
DR GO; GO:0001736; P:establishment of planar polarity; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB.
DR GO; GO:1905515; P:non-motile cilium assembly; ISS:UniProtKB.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IBA:GO_Central.
DR InterPro; IPR009539; VANGL.
DR PANTHER; PTHR20886; PTHR20886; 1.
DR Pfam; PF06638; Strabismus; 1.
DR PIRSF; PIRSF007991; Strabismus; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Developmental protein; Disease variant;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..521
FT /note="Vang-like protein 2"
FT /id="PRO_0000186195"
FT TOPO_DOM 1..108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..129
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..147
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..217
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 239..521
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..30
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 84
FT /note="S -> F (in NTD; dbSNP:rs1571244916)"
FT /evidence="ECO:0000269|PubMed:20558380"
FT /id="VAR_067221"
FT VARIANT 353
FT /note="R -> C (in NTD; the mutant protein has diminished
FT interaction with DVL1 compared to wild-type;
FT dbSNP:rs267607167)"
FT /evidence="ECO:0000269|PubMed:20558380"
FT /id="VAR_067222"
FT VARIANT 437
FT /note="F -> S (in NTD; the mutation protein completely
FT abrogates interaction with DVL1 compared to wild-type;
FT dbSNP:rs267607168)"
FT /evidence="ECO:0000269|PubMed:20558380"
FT /id="VAR_067223"
FT STRAND 518..521
FT /evidence="ECO:0007829|PDB:6XA6"
SQ SEQUENCE 521 AA; 59714 MW; 0E1FFE4ACC102560 CRC64;
MDTESQYSGY SYKSGHSRSS RKHRDRRDRH RSKSRDGGRG DKSVTIQAPG EPLLDNESTR
GDERDDNWGE TTTVVTGTSE HSISHDDLTR IAKDMEDSVP LDCSRHLGVA AGATLALLSF
LTPLAFLLLP PLLWREELEP CGTACEGLFI SVAFKLLILL LGSWALFFRR PKASLPRVFV
LRALLMVLVF LLVVSYWLFY 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
