Q9ULK5 (VANG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vang-like protein 2

Alternative name(s):
Loop-tail protein 1 homolog
Strabismus 1
Van Gogh-like protein 2

Gene names

Name:	VANGL2
Synonyms:	KIAA1215, STB1

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	521 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Subunit structure	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. Also interacts with the PDZ domains of MAGI3, SCRIB/SCRB1 and FZD3 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Involvement in disease	Neural tube defects (NTD) [MIM:182940]: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Belongs to the Vang family.
Sequence caution	The sequence BAA86529.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Membrane
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Rho protein signal transduction Inferred from electronic annotation. Source: Compara anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara apical protein localization Inferred from sequence or structural similarity. Source: UniProtKB cell migration involved in kidney development Inferred from sequence or structural similarity. Source: UniProtKB cochlea morphogenesis Inferred from electronic annotation. Source: Compara convergent extension involved in axis elongation Inferred from electronic annotation. Source: Compara convergent extension involved in neural plate elongation Inferred from electronic annotation. Source: Compara digestive tract morphogenesis Inferred from electronic annotation. Source: Compara establishment of body hair planar orientation Inferred from electronic annotation. Source: Compara establishment of planar polarity Inferred from sequence or structural similarity. Source: UniProtKB establishment of planar polarity involved in neural tube closure Inferred from electronic annotation. Source: Compara establishment or maintenance of epithelial cell apical/basal polarity Inferred from electronic annotation. Source: Compara hair follicle development Inferred from electronic annotation. Source: Compara heart looping Inferred from sequence or structural similarity. Source: UniProtKB inner ear receptor stereocilium organization Inferred from electronic annotation. Source: Compara lateral sprouting involved in lung morphogenesis Inferred from electronic annotation. Source: Compara membranous septum morphogenesis Inferred from electronic annotation. Source: Compara muscular septum morphogenesis Inferred from electronic annotation. Source: Compara neural tube closure Inferred from sequence or structural similarity. Source: UniProtKB nonmotile primary cilium assembly Inferred from sequence or structural similarity. Source: UniProtKB orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis Inferred from electronic annotation. Source: Compara planar cell polarity pathway involved in axis elongation Inferred from electronic annotation. Source: Compara planar cell polarity pathway involved in neural tube closure Inferred from electronic annotation. Source: Compara planar dichotomous subdivision of terminal units involved in lung branching morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of JUN kinase activity Inferred from electronic annotation. Source: Compara regulation of actin cytoskeleton organization Inferred from electronic annotation. Source: Compara somatic stem cell division Inferred from electronic annotation. Source: Compara somatic stem cell maintenance Inferred from electronic annotation. Source: Compara wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB basolateral plasma membrane Inferred from electronic annotation. Source: Compara cell pole Inferred from electronic annotation. Source: Compara cell-cell junction Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lateral plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 521	521	Vang-like protein 2		PRO_0000186195
Regions
	Topological domain	1 – 108	108	Cytoplasmic Potential
	Transmembrane	109 – 129	21	Helical; Name=1; Potential
	Topological domain	130 – 147	18	Extracellular Potential
	Transmembrane	148 – 168	21	Helical; Name=2; Potential
	Topological domain	169 – 178	10	Cytoplasmic Potential
	Transmembrane	179 – 199	21	Helical; Name=3; Potential
	Topological domain	200 – 217	18	Extracellular Potential
	Transmembrane	218 – 238	21	Helical; Name=4; Potential
	Topological domain	239 – 521	283	Cytoplasmic Potential
Natural variations
	Natural variant	84	1	S → F in NTD. Ref.5		VAR_067221
	Natural variant	353	1	R → C in NTD; the mutant protein has diminished interaction with DVL1 compared to wild-type. Ref.5		VAR_067222
	Natural variant	437	1	F → S in NTD; the mutation protein completely abrogates interaction with DVL1 compared to wild-type. Ref.5		VAR_067223

Sequences

	Sequence		Length	Mass (Da)
	Q9ULK5 [UniParc]. Last modified October 31, 2003. Version 2. Checksum: 0E1FFE4ACC102560	FASTA	521	59,714
	10 20 30 40 50 60 MDTESQYSGY SYKSGHSRSS RKHRDRRDRH RSKSRDGGRG DKSVTIQAPG EPLLDNESTR 70 80 90 100 110 120 GDERDDNWGE TTTVVTGTSE HSISHDDLTR IAKDMEDSVP LDCSRHLGVA AGATLALLSF 130 140 150 160 170 180 LTPLAFLLLP PLLWREELEP CGTACEGLFI SVAFKLLILL LGSWALFFRR PKASLPRVFV 190 200 210 220 230 240 LRALLMVLVF LLVVSYWLFY GVRILDARER SYQGVVQFAV SLVDALLFVH YLAVVLLELR 250 260 270 280 290 300 QLQPQFTLKV VRSTDGASRF YNVGHLSIQR VAVWILEKYY HDFPVYNPAL LNLPKSVLAK 310 320 330 340 350 360 KVSGFKVYSL GEENSTNNST GQSRAVIAAA ARRRDNSHNE YYYEEAEHER RVRKRRARLV 370 380 390 400 410 420 VAVEEAFTHI KRLQEEEQKN PREVMDPREA AQAIFASMAR AMQKYLRTTK QQPYHTMESI 430 440 450 460 470 480 LQHLEFCITH DMTPKAFLER YLAAGPTIQY HKERWLAKQW TLVSEEPVTN GLKDGIVFLL 490 500 510 520 KRQDFSLVVS TKKVPFFKLS EEFVDPKSHK FVMRLQSETS V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O. DNA Res. 6:337-345(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"VANGL2 mutations in human cranial neural-tube defects." Lei Y.P., Zhang T., Li H., Wu B.L., Jin L., Wang H.Y. N. Engl. J. Med. 362:2232-2235(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NTD PHE-84; CYS-353 AND SER-437, CHARACTERIZATION OF VARIANTS NTD CYS-353 AND SER-437.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB033041 mRNA. Translation: BAA86529.1. Different initiation. AL445230 Genomic DNA. Translation: CAI15015.1. CH471121 Genomic DNA. Translation: EAW52718.1. BC103920 mRNA. No translation available.
IPI	IPI00029449.
RefSeq	NP_065068.1. NM_020335.2.
UniGene	Hs.99477.
3D structure databases
ProteinModelPortal	Q9ULK5.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000357040.
PTM databases
PhosphoSite	Q9ULK5.
Polymorphism databases
DMDM	38258849.
Proteomic databases
PaxDb	Q9ULK5.
PRIDE	Q9ULK5.
Protocols and materials databases
DNASU	57216.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368061; ENSP00000357040; ENSG00000162738.
GeneID	57216.
KEGG	hsa:57216.
UCSC	uc001fwb.2. human.
Organism-specific databases
CTD	57216.
GeneCards	GC01P160370.
H-InvDB	HIX0001219.
HGNC	HGNC:15511. VANGL2.
HPA	HPA027043.
MIM	182940. phenotype. 600533. gene.
neXtProt	NX_Q9ULK5.
Orphanet	268357. Neural tube closure defect. 3388. Neural tube defect.
PharmGKB	PA37970.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG268286.
HOGENOM	HOG000230590.
HOVERGEN	HBG058215.
InParanoid	Q9ULK5.
KO	K04510.
OMA	DMTPKAF.
OrthoDB	EOG4FJ88V.
PhylomeDB	Q9ULK5.
Gene expression databases
Bgee	Q9ULK5.
CleanEx	HS_VANGL2.
Genevestigator	Q9ULK5.
GermOnline	ENSG00000162738. Homo sapiens.
Family and domain databases
InterPro	IPR009539. Strabismus. [Graphical view]
PANTHER	PTHR20886. PTHR20886. 1 hit.
Pfam	PF06638. Strabismus. 1 hit. [Graphical view]
PIRSF	PIRSF007991. Strabismus. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	VANGL2. human.
GenomeRNAi	57216.
NextBio	63337.
SOURCE	Search...

Entry information

Entry name

VANG2_HUMAN

Accession

Primary (citable) accession number: Q9ULK5
Secondary accession number(s): D3DVE9, Q5T212

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	October 31, 2003
Last modified:	May 1, 2013
This is version 85 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.