Q8TAA9 (VANG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vang-like protein 1

Alternative name(s):
Loop-tail protein 2 homolog
Short name=LPP2
Strabismus 2
Van Gogh-like protein 1

Gene names

Name:	VANGL1
Synonyms:	STB2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	524 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Accordiing to Ref.1, ubiquitously expressed. According to Ref.2, expressed specifically in testis and ovary. Ref.1 Ref.2
Involvement in disease	Defects in VANGL1 are a cause of neural tube defects (NTD) [MIM:182940]. NTD are congenital malformations. The most common forms of NTD are described as open defects (including anencephaly and myelomeningocele, or spina bifida), which result from the failure of fusion in the cranial and spinal region of the neural tube, respectively. Other open dysraphisms (including myeloschisis, hemimyelomeningocele, and hemimyelocele) are sometimes associated with a Chiari type 2 malformation. A number of skin-covered (closed) NTD are categorized clinically depending on the presence of a subcutaneous mass (lipomyeloschisis, lipomyelomeningocele, meningocele, and myelocystocele) or the absence of such a mass (complex dysraphic states, including split cord malformations, dermal sinus, caudal regression, and segmental spinal dysgenesis). Ref.9 Ref.10 Defects in VANGL1 are a cause of sacral defect with anterior meningocele (SDAM) [MIM:600145]. SDAM is a form of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, or meningitis. Inheritance is autosomal dominant. Ref.9
Sequence similarities	Belongs to the Vang family.
Sequence caution	The sequence AAH32773.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	multicellular organismal development Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD82	P27701	6	EBI-682393,EBI-682379

Alternative products

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

Isoform 1 (identifier: Q8TAA9-1)

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 2 (identifier: Q8TAA9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     67-68: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 524	524	Vang-like protein 1		PRO_0000186193
Regions
	Topological domain	1 – 117	117	Cytoplasmic Potential
	Transmembrane	118 – 138	21	Helical; Name=1; Potential
	Topological domain	139 – 151	13	Extracellular Potential
	Transmembrane	152 – 172	21	Helical; Name=2; Potential
	Topological domain	173 – 182	10	Cytoplasmic Potential
	Transmembrane	183 – 203	21	Helical; Name=3; Potential
	Topological domain	204 – 222	19	Extracellular Potential
	Transmembrane	223 – 243	21	Helical; Name=4; Potential
	Topological domain	244 – 524	281	Cytoplasmic Potential
Amino acid modifications
	Modified residue	96	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	67 – 68	2	Missing in isoform 2.		VSP_008742
	Natural variant	25	1	E → K. Ref.10		VAR_062321
	Natural variant	83	1	S → L in NTD; uncertain pathogenicity. Ref.10		VAR_062322
	Natural variant	116	1	A → T. Ref.8 Corresponds to variant rs4839469 [ dbSNP | Ensembl ].		VAR_027143
	Natural variant	153	1	F → S in NTD; uncertain pathogenicity. Ref.10		VAR_062323
	Natural variant	175	1	R → Q. Ref.10		VAR_062324
	Natural variant	181	1	R → Q in NTD; uncertain pathogenicity. Ref.10		VAR_062325
	Natural variant	202	1	L → F in NTD; uncertain pathogenicity. Ref.10		VAR_062326
	Natural variant	239	1	V → I in SDAM; abolishes ability to interact with DVL1, DVL2 and DVL3. Ref.9		VAR_035209
	Natural variant	251	1	T → M. Ref.10		VAR_062327
	Natural variant	274	1	R → Q in NTD; does not abolish ability to interact with DVL1, DVL2 and DVL3. Ref.9		VAR_035210
	Natural variant	290	1	Y → H. Ref.10		VAR_062328
	Natural variant	328	1	M → T in NTD; does not abolish ability to interact with DVL1, DVL2 and DVL3. Ref.9		VAR_035211
	Natural variant	347	1	E → A. Corresponds to variant rs34059106 [ dbSNP | Ensembl ].		VAR_035435
	Natural variant	404	1	A → S in NTD; uncertain pathogenicity. Ref.10		VAR_062329
	Natural variant	468	1	D → E. Ref.10		VAR_062330

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 65CB263D26274585	FASTA	524	59,975
	10 20 30 40 50 60 MDTESTYSGY SYYSSHSKKS HRQGERTRER HKSPRNKDGR GSEKSVTIQP PTGEPLLGND 70 80 90 100 110 120 STRTEEVQDD NWGETTTAIT GTSEHSISQE DIARISKDME DSVGLDCKRY LGLTVASFLG 130 140 150 160 170 180 LLVFLTPIAF ILLPPILWRD ELEPCGTICE GLFISMAFKL LILLIGTWAL FFRKRRADMP 190 200 210 220 230 240 RVFVFRALLL VLIFLFVVSY WLFYGVRILD SRDRNYQGIV QYAVSLVDAL LFIHYLAIVL 250 260 270 280 290 300 LELRQLQPMF TLQVVRSTDG ESRFYSLGHL SIQRAALVVL ENYYKDFTIY NPNLLTASKF 310 320 330 340 350 360 RAAKHMAGLK VYNVDGPSNN ATGQSRAMIA AAARRRDSSH NELYYEEAEH ERRVKKRKAR 370 380 390 400 410 420 LVVAVEEAFI HIQRLQAEEQ QKAPGEVMDP REAAQAIFPS MARALQKYLR ITRQQNYHSM 430 440 450 460 470 480 ESILQHLAFC ITNGMTPKAF LERYLSAGPT LQYDKDRWLS TQWRLVSDEA VTNGLRDGIV 490 500 510 520 FVLKCLDFSL VVNVKKIPFI ILSEEFIDPK SHKFVLRLQS ETSV
	Isoform 2 [UniParc]. Checksum: 8E06DD3BE2003F02	FASTA	522	59,748
	10 20 30 40 50 60 MDTESTYSGY SYYSSHSKKS HRQGERTRER HKSPRNKDGR GSEKSVTIQP PTGEPLLGND 70 80 90 100 110 120 STRTEEDDNW GETTTAITGT SEHSISQEDI ARISKDMEDS VGLDCKRYLG LTVASFLGLL 130 140 150 160 170 180 VFLTPIAFIL LPPILWRDEL EPCGTICEGL FISMAFKLLI LLIGTWALFF RKRRADMPRV 190 200 210 220 230 240 FVFRALLLVL IFLFVVSYWL FYGVRILDSR DRNYQGIVQY AVSLVDALLF IHYLAIVLLE 250 260 270 280 290 300 LRQLQPMFTL QVVRSTDGES RFYSLGHLSI QRAALVVLEN YYKDFTIYNP NLLTASKFRA 310 320 330 340 350 360 AKHMAGLKVY NVDGPSNNAT GQSRAMIAAA ARRRDSSHNE LYYEEAEHER RVKKRKARLV 370 380 390 400 410 420 VAVEEAFIHI QRLQAEEQQK APGEVMDPRE AAQAIFPSMA RALQKYLRIT RQQNYHSMES 430 440 450 460 470 480 ILQHLAFCIT NGMTPKAFLE RYLSAGPTLQ YDKDRWLSTQ WRLVSDEAVT NGLRDGIVFV 490 500 510 520 LKCLDFSLVV NVKKIPFIIL SEEFIDPKSH KFVLRLQSET SV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of Strabismus 2 (STB2)." Katoh M. Int. J. Oncol. 20:993-998(2002) [PubMed: 11956595] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]	"Isolation and characterization of a novel human gene, VANGL1, as a therapeutic target for hepatocellular carcinoma." Yagyu R., Hamamoto R., Furukawa Y., Okabe H., Yamamura T., Nakamura Y. Int. J. Oncol. 20:1173-1178(2002) [PubMed: 12011995] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	"Identification of LPP2, a second Vang-like protein." Doudney K., Paternotte C., Murdoch J.N., Copp A.J., Stanier P. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Prostate and Skin.
[7]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Analysis of the planar cell polarity gene Vangl2 and its co-expressed paralogue Vangl1 in neural tube defect patients." Doudney K., Ybot-Gonzalez P., Paternotte C., Stevenson R.E., Greene N.D., Moore G.E., Copp A.J., Stanier P. Am. J. Med. Genet. A 136:90-92(2005) [PubMed: 15952208] [Abstract] Cited for: VARIANT THR-116.
[9]	"Mutations in VANGL1 associated with neural-tube defects." Kibar Z., Torban E., McDearmid J.R., Reynolds A., Berghout J., Mathieu M., Kirillova I., De Marco P., Merello E., Hayes J.M., Wallingford J.B., Drapeau P., Capra V., Gros P. N. Engl. J. Med. 356:1432-1437(2007) [PubMed: 17409324] [Abstract] Cited for: VARIANT SDAM ILE-239, VARIANTS NTD GLN-274 AND THR-328, CHARACTERIZATION OF VARIANT SDAM ILE-239, CHARACTERIZATION OF VARIANTS NTD GLN-274 AND THR-328.
[10]	"Novel mutations in VANGL1 in neural tube defects." Kibar Z., Bosoi C.M., Kooistra M., Salem S., Finnell R.H., De Marco P., Merello E., Bassuk A.G., Capra V., Gros P. Hum. Mutat. 30:E706-E715(2009) [PubMed: 19319979] [Abstract] Cited for: VARIANTS NTD LEU-83; SER-153; GLN-181; PHE-202 AND SER-404, VARIANTS LYS-25; GLN-175; MET-251; HIS-290 AND GLU-468.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB075805 mRNA. Translation: BAB86362.1. AB057596 mRNA. Translation: BAB86334.1. AF481859 mRNA. Translation: AAO61751.1. AL450389 Genomic DNA. Translation: CAI23371.1. AL450389 Genomic DNA. Translation: CAI23372.1. CH471122 Genomic DNA. Translation: EAW56630.1. CH471122 Genomic DNA. Translation: EAW56631.1. BC032773 mRNA. Translation: AAH32773.1. Different initiation. BC065272 mRNA. Translation: AAH65272.1.
IPI	IPI00031195. IPI00386349.
RefSeq	NP_001165882.1. NM_001172411.1. NP_001165883.1. NM_001172412.1. NP_620409.1. NM_138959.2.
UniGene	Hs.515130.
3D structure databases
ProteinModelPortal	Q8TAA9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8TAA9. 6 interactions.
STRING	Q8TAA9.
PTM databases
PhosphoSite	Q8TAA9.
Polymorphism databases
DMDM	38258809.
Proteomic databases
PRIDE	Q8TAA9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310260; ENSP00000310800; ENSG00000173218. ENST00000355485; ENSP00000347672; ENSG00000173218. ENST00000369509; ENSP00000358522; ENSG00000173218.
GeneID	81839.
KEGG	hsa:81839.
UCSC	uc001efv.1. human. uc009wgy.1. human.
Organism-specific databases
CTD	81839.
GeneCards	GC01P116184.
H-InvDB	HIX0028502.
HGNC	HGNC:15512. VANGL1.
HPA	HPA025235.
MIM	182940. phenotype. 600145. phenotype. 610132. gene.
neXtProt	NX_Q8TAA9.
Orphanet	3027. Caudal regression sequence. 1768. Familial caudal dysgenesis.
PharmGKB	PA37971.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000012496.
HOGENOM	HBG716583.
HOVERGEN	HBG058215.
InParanoid	Q8TAA9.
OMA	GLDCRRY.
PhylomeDB	Q8TAA9.
Gene expression databases
ArrayExpress	Q8TAA9.
Bgee	Q8TAA9.
CleanEx	HS_VANGL1.
Genevestigator	Q8TAA9.
GermOnline	ENSG00000173218. Homo sapiens.
Family and domain databases
InterPro	IPR009539. Strabismus. [Graphical view]
KO	K04510.
PANTHER	PTHR20886. Strabismus. 1 hit.
Pfam	PF06638. Strabismus. 1 hit. [Graphical view]
PIRSF	PIRSF007991. Strabismus. 1 hit.
ProtoNet	Search...
Other
NextBio	72138.
SOURCE	Search...

Entry information

Entry name

VANG1_HUMAN

Accession

Primary (citable) accession number: Q8TAA9
Secondary accession number(s): Q5T1D3 , Q5T1D4, Q86WG8, Q8N559

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	June 1, 2002
Last modified:	January 25, 2012
This is version 75 of the entry and version 1 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.