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Q9NZR4 (VSX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Visual system homeobox 1
Alternative name(s):
Homeodomain protein RINX
Retinal inner nuclear layer homeobox protein
Transcription factor VSX1
Gene names
Name:VSX1
Synonyms:RINX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length365 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to the 37-bp core of the locus control region (LCR) of the red/green visual pigment gene cluster. May regulate the activity of the LCR and the cone opsin genes at earlier stages of development.

Subcellular location

Nucleus By similarity.

Tissue specificity

In the adult eye, expressed in lens, iris, ciliary body, choroid, optical nerve head and, most strongly, in retina, but not expressed in sclera and cornea. According to PubMed 11978762, expressed in adult retina but not in lens and cornea. Within adult retina, found exclusively in the inner nuclear layer. Isoform 1, isoform 2, isoform 3 and isoform 4 expressed in adult retina, but not in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. Not expressed in thymus and spleen. Expressed in embryonic craniofacial tissue. Expressed in fetal (week 14) retina. Strongly expressed in neonatal retina (day 0), weakly in neonatal lens (day 0), choroid (day 0) and cornea (day 0, 4; month 9). Ref.1 Ref.2 Ref.3 Ref.7

Involvement in disease

Corneal dystrophy, posterior polymorphous, 1 (PPCD1) [MIM:122000]: A rare corneal disorder characterized by small aggregates of apparent vesicles bordered by a gray haze at the level of Descemet membrane, an altered corneal endothelial cell structure, and an unusual proliferation of endothelial cells. Symptoms can range from very aggressive to asymptomatic and non-progressive, even within the same family.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Keratoconus 1 (KTCN1) [MIM:148300]: Frequent corneal dystrophy with an incidence that varies from 50 to 230 per 100'000. The cornea assumes a conical shape as a result of a progressive non-inflammatory thinning of the corneal stroma. Keratoconus is most often an isolated sporadic condition with cases of autosomal dominant and autosomal recessive transmission.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.9

Craniofacial anomalies and anterior segment dysgenesis syndrome (CAASDS) [MIM:614195]: A disorder with extremely variable expressivity. Clinical features include wide interpupillary distance, abnormal corneal endothelium, unusual pinnae, partially to completely empty sella turcica, posterior fossa cyst, anterior encephalocele, and/or hydrocephalus.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the paired homeobox family.

Contains 1 CVC domain.

Contains 1 homeobox DNA-binding domain.

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9NZR4-1)

Also known as: L1;

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.
Note: Major form.
Isoform 2 (identifier: Q9NZR4-2)

Also known as: S1; L3;

The sequence of this isoform differs from the canonical sequence as follows:
     211-239: WFQNRRAKWRKREKRWGGSSVMAEYGLYG → SGVPFLRSKDTTENVSFPHSVSQSAVPSL
     240-365: Missing.
Note: Major form.
Isoform 3 (identifier: Q9NZR4-3)

Also known as: S2;

The sequence of this isoform differs from the canonical sequence as follows:
     141-141: S → SGNQARAFRS...PVVVTSSTEQ
     211-239: WFQNRRAKWRKREKRWGGSSVMAEYGLYG → SGVPFLRSKDTTENVSFPHSVSQSAVPSL
     240-365: Missing.
Note: Minor form.
Isoform 4 (identifier: Q9NZR4-4)

Also known as: S3;

The sequence of this isoform differs from the canonical sequence as follows:
     142-143: DE → AM
     144-365: Missing.
Note: Minor form.
Isoform 5 (identifier: Q9NZR4-5)

The sequence of this isoform differs from the canonical sequence as follows:
     270-280: GMHKKSMGMIR → EGETLGCREMK
     281-365: Missing.
Isoform 6 (identifier: Q9NZR4-6)

The sequence of this isoform differs from the canonical sequence as follows:
     210-218: VWFQNRRAK → RVRHWAAEK
     219-365: Missing.
Isoform 7 (identifier: Q9NZR4-7)

The sequence of this isoform differs from the canonical sequence as follows:
     210-236: VWFQNRRAKWRKREKRWGGSSVMAEYG → CKLLLLEAPVHWTLQETHRLPRPRGGA
     237-365: Missing.
Isoform 8 (identifier: Q9NZR4-8)

The sequence of this isoform differs from the canonical sequence as follows:
     270-301: GMHKKSMGMIRKPGSEDKLAGLWGSDHFKEGS → VQTSAPGGSRSLDFAGDTQAPQTPWWCLMTFS
     302-365: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 365365Visual system homeobox 1
PRO_0000049355

Regions

Domain224 – 27754CVC
DNA binding164 – 22360Homeobox
Motif31 – 388Octapeptide motif
Motif161 – 1666Nuclear localization signal Potential
Compositional bias44 – 12784Pro-rich
Compositional bias76 – 8914Gly/Leu-rich
Compositional bias142 – 15211Asp/Glu-rich (acidic)

Natural variations

Alternative sequence1411S → SGNQARAFRSCPCPLGSEPR RGHRPSPHRTPGPSGPDLGG EPRARPRRGRGIRGAAPPAP CCILNPCLSSGVLFPQRCET ATTWFRVEPFDETLGSSTTI SRGPFFPPAPGASLRLWQLR GSGRPGPVVVTSSTEQ in isoform 3.
VSP_002299
Alternative sequence142 – 1432DE → AM in isoform 4.
VSP_002300
Alternative sequence144 – 365222Missing in isoform 4.
VSP_002301
Alternative sequence210 – 23627VWFQN…MAEYG → CKLLLLEAPVHWTLQETHRL PRPRGGA in isoform 7.
VSP_039141
Alternative sequence210 – 2189VWFQNRRAK → RVRHWAAEK in isoform 6.
VSP_039140
Alternative sequence211 – 23929WFQNR…YGLYG → SGVPFLRSKDTTENVSFPHS VSQSAVPSL in isoform 2 and isoform 3.
VSP_002302
Alternative sequence219 – 365147Missing in isoform 6.
VSP_039142
Alternative sequence237 – 365129Missing in isoform 7.
VSP_039143
Alternative sequence240 – 365126Missing in isoform 2 and isoform 3.
VSP_002303
Alternative sequence270 – 30132GMHKK…FKEGS → VQTSAPGGSRSLDFAGDTQA PQTPWWCLMTFS in isoform 8.
VSP_039145
Alternative sequence270 – 28011GMHKKSMGMIR → EGETLGCREMK in isoform 5.
VSP_039144
Alternative sequence281 – 36585Missing in isoform 5.
VSP_039146
Alternative sequence302 – 36564Missing in isoform 8.
VSP_039147
Natural variant171L → P in KTCN1. Ref.9
VAR_066670
Natural variant1311R → S. Ref.8
Corresponds to variant rs6050307 [ dbSNP | Ensembl ].
VAR_066671
Natural variant1441D → E in PPCD1 and KTCN1. Ref.7 Ref.9
Corresponds to variant rs140122268 [ dbSNP | Ensembl ].
VAR_014243
Natural variant1591L → M in KTCN1. Ref.7
VAR_014244
Natural variant1601G → D in PPCD1; also in a patient with keratoconus; unknown pathological significance. Ref.7 Ref.9
Corresponds to variant rs74315433 [ dbSNP | Ensembl ].
VAR_014245
Natural variant1661R → W in KTCN1; sporadic. Ref.7
VAR_014246
Natural variant1751Q → H in KTCN1. Ref.6
VAR_063100
Natural variant2441H → R in KTCN1; unknown pathological significance. Ref.7
Corresponds to variant rs148957473 [ dbSNP | Ensembl ].
VAR_014247
Natural variant2471P → R in KTCN1; unknown pathological significance; also in a patient with retinal dysfunction. Ref.7 Ref.9
VAR_014248
Natural variant2561A → S in CAASDS. Ref.8
Corresponds to variant rs74315435 [ dbSNP | Ensembl ].
VAR_066672

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (L1) [UniParc].

Last modified March 1, 2001. Version 2.
Checksum: C58BE94767D66FCB

FASTA36538,431
        10         20         30         40         50         60 
MTGRDSLSDG RTSSRALVPG GSPRGSRPRG FAITDLLGLE AELPAPAGPG QGSGCEGPAV 

        70         80         90        100        110        120 
APCPGPGLDG SSLARGALPL GLGLLCGFGT QPPAAARAPC LLLADVPFLP PRGPEPAAPL 

       130        140        150        160        170        180 
APSRPPPALG RQKRSDSVST SDEDSQSEDR NDLKASPTLG KRKKRRHRTV FTAHQLEELE 

       190        200        210        220        230        240 
KAFSEAHYPD VYAREMLAVK TELPEDRIQV WFQNRRAKWR KREKRWGGSS VMAEYGLYGA 

       250        260        270        280        290        300 
MVRHCIPLPD SVLNSAEGGL LGSCAPWLLG MHKKSMGMIR KPGSEDKLAG LWGSDHFKEG 

       310        320        330        340        350        360 
SSQSESGSQR GSDKVSPENG LEDVAIDLSS SARQETKKVH PGAGAQGGSN STALEGPQPG 


KVGAT 

« Hide

Isoform 2 (S1) (L3) [UniParc].

Checksum: 8F16E19365A59829
Show »

FASTA23924,996
Isoform 3 (S2) [UniParc].

Checksum: 999B9D725C347B0B
Show »

FASTA37439,343
Isoform 4 (S3) [UniParc].

Checksum: 4B1228D8FBF47C95
Show »

FASTA14314,049
Isoform 5 [UniParc].

Checksum: 93F50A50D1724EE9
Show »

FASTA28029,863
Isoform 6 [UniParc].

Checksum: C4EEBE486A79C4FF
Show »

FASTA21822,975
Isoform 7 [UniParc].

Checksum: E8D71E1D7C478E32
Show »

FASTA23624,915
Isoform 8 [UniParc].

Checksum: 2D092C371A74D9DD
Show »

FASTA30132,054

References

« Hide 'large scale' references
[1]"Isolation and characterization of a novel human paired-like homeodomain-containing transcription factor gene, VSX1, expressed in ocular tissues."
Semina E.V., Mintz-Hittner H.A., Murray J.C.
Genomics 63:289-293(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Craniofacial.
[2]"RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the adult retina."
Hayashi T., Huang J., Deeb S.S.
Genomics 67:128-139(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), TISSUE SPECIFICITY.
Tissue: Retina.
[3]"Genetic analysis of chromosome 20-related posterior polymorphous corneal dystrophy: genetic heterogeneity and exclusion of three candidate genes."
Hosseini S.M., Herd S., Vincent A.L., Heon E.
Mol. Vis. 14:71-80(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 5; 6; 7 AND 8), TISSUE SPECIFICITY.
Tissue: Retina.
[4]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 1).
[6]"A novel VSX1 mutation identified in an individual with keratoconus in India."
Paliwal P., Singh A., Tandon R., Titiyal J.S., Sharma A.
Mol. Vis. 15:2475-2479(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 168-186 (ISOFORMS 1/2/3/5/6/7/8), VARIANT KTCN1 HIS-175.
[7]"VSX1: a gene for posterior polymorphous dystrophy and keratoconus."
Heon E., Greenberg A., Kopp K.K., Rootman D., Vincent A.L., Billingsley G., Priston M., Dorval K.M., Chow R.L., McInnes R.R., Heathcote G., Westall C., Sutphin J.E., Semina E., Bremner R., Stone E.M.
Hum. Mol. Genet. 11:1029-1036(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANTS PPCD1 GLU-144 AND ASP-160, VARIANTS KTCN1 GLU-144; MET-159; TRP-166 AND ARG-244, VARIANT ARG-247.
[8]"VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells."
Mintz-Hittner H.A., Semina E.V., Frishman L.J., Prager T.C., Murray J.C.
Ophthalmology 111:828-836(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CAASDS SER-256, VARIANT SER-131.
[9]"VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation."
Bisceglia L., Ciaschetti M., De Bonis P., Campo P.A., Pizzicoli C., Scala C., Grifa M., Ciavarella P., Delle Noci N., Vaira F., Macaluso C., Zelante L.
Invest. Ophthalmol. Vis. Sci. 46:39-45(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS KTCN1 PRO-17; GLU-144; ASP-160 AND ARG-247.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF176797 mRNA. Translation: AAF37425.2.
AF251033 mRNA. Translation: AAF99656.1.
AF251034 mRNA. Translation: AAF99657.1.
DQ854807 mRNA. Translation: ABI23973.1.
DQ854808 mRNA. Translation: ABI23974.1.
DQ854809 mRNA. Translation: ABI23975.1.
DQ854810 mRNA. Translation: ABI23976.1.
DQ854811 mRNA. Translation: ABI23977.1.
DQ854812 mRNA. Translation: ABI23978.1.
AL080312 Genomic DNA. Translation: CAI18918.1.
AL080312 Genomic DNA. Translation: CAX15203.1.
AL080312 Genomic DNA. Translation: CAX15204.1.
AL080312 Genomic DNA. Translation: CAX15205.1.
BC126228 mRNA. Translation: AAI26229.1.
BC136497 mRNA. Translation: AAI36498.1.
GU138372 Genomic DNA. Translation: ACZ01961.1.
CCDSCCDS13168.1. [Q9NZR4-1]
CCDS13169.1. [Q9NZR4-2]
CCDS58766.1. [Q9NZR4-7]
CCDS58767.1. [Q9NZR4-8]
RefSeqNP_001243200.1. NM_001256271.1. [Q9NZR4-7]
NP_001243201.1. NM_001256272.1. [Q9NZR4-8]
NP_055403.2. NM_014588.5. [Q9NZR4-1]
NP_955457.1. NM_199425.2. [Q9NZR4-2]
UniGeneHs.274264.

3D structure databases

ProteinModelPortalQ9NZR4.
SMRQ9NZR4. Positions 171-220.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000365899.

PTM databases

PhosphoSiteQ9NZR4.

Polymorphism databases

DMDM25009572.

Proteomic databases

PaxDbQ9NZR4.
PRIDEQ9NZR4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000376707; ENSP00000365897; ENSG00000100987. [Q9NZR4-2]
ENST00000376709; ENSP00000365899; ENSG00000100987. [Q9NZR4-1]
ENST00000398332; ENSP00000381376; ENSG00000100987. [Q9NZR4-4]
ENST00000409285; ENSP00000386612; ENSG00000100987. [Q9NZR4-5]
ENST00000409958; ENSP00000387069; ENSG00000100987. [Q9NZR4-6]
ENST00000424574; ENSP00000399496; ENSG00000100987. [Q9NZR4-5]
ENST00000429762; ENSP00000401690; ENSG00000100987. [Q9NZR4-8]
ENST00000444511; ENSP00000387720; ENSG00000100987. [Q9NZR4-7]
ENST00000451258; ENSP00000389654; ENSG00000100987. [Q9NZR4-6]
GeneID30813.
KEGGhsa:30813.
UCSCuc002wuf.4. human. [Q9NZR4-1]
uc002wug.2. human. [Q9NZR4-2]
uc010gdd.3. human. [Q9NZR4-8]
uc010gdf.3. human. [Q9NZR4-7]

Organism-specific databases

CTD30813.
GeneCardsGC20M025051.
HGNCHGNC:12723. VSX1.
MIM122000. phenotype.
148300. phenotype.
605020. gene.
614195. phenotype.
neXtProtNX_Q9NZR4.
Orphanet2335. Isolated keratoconus.
98973. Posterior polymorphous corneal dystrophy.
PharmGKBPA37334.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG237888.
HOVERGENHBG036251.
InParanoidQ9NZR4.
KOK09335.
OMAWGSDHLK.
OrthoDBEOG76474B.
PhylomeDBQ9NZR4.
TreeFamTF350743.

Gene expression databases

BgeeQ9NZR4.
CleanExHS_VSX1.
GenevestigatorQ9NZR4.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR023339. CVC.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS51496. CVC. 1 hit.
PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiVSX1.
GenomeRNAi30813.
NextBio52864.
PROQ9NZR4.
SOURCESearch...

Entry information

Entry nameVSX1_HUMAN
AccessionPrimary (citable) accession number: Q9NZR4
Secondary accession number(s): B9EGJ4 expand/collapse secondary AC list , D1MF28, Q0GM60, Q0GM61, Q0GM62, Q0GM63, Q0GM64, Q0GM65, Q5TF40, Q5TF41, Q9HCU3, Q9NU27
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM