SIX6_HUMAN
ID SIX6_HUMAN Reviewed; 246 AA.
AC O95475; Q6NT42; Q9P1X8;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Homeobox protein SIX6;
DE AltName: Full=Homeodomain protein OPTX2;
DE AltName: Full=Optic homeobox 2;
DE AltName: Full=Sine oculis homeobox homolog 6;
GN Name=SIX6; Synonyms=OPTX2, SIX9;
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 [GENOMIC DNA], AND VARIANT ASN-141.
RC TISSUE=Eye;
RA Leppert G.S., Yang J.-M., Toy J., Sundin O.H.;
RT "OPTX2, a novel gene expressed in the eye, belongs to a cluster of sine
RT oculis-related homeobox genes.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASN-141.
RX PubMed=10381575; DOI=10.1016/s0925-4773(99)00017-9;
RA Lopez-Rios J., Gallardo E., Rodriguez de Cordoba S., Bovolenta P.;
RT "Six9 (Optx2), a new member of the Six gene family of transcription
RT factors, is expressed at early stages of vertebrate ocular and pituitary
RT development.";
RL Mech. Dev. 83:155-159(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-141.
RX PubMed=10512683; DOI=10.1006/geno.1999.5916;
RA Gallardo M.E., Lopez-Rios J., Fernaud-Espinosa I., Granadino B., Sanz R.,
RA Ramos C., Ayuso C., Seller M.J., Brunner H.G., Bovolenta P.,
RA Rodriguez de Cordoba S.;
RT "Genomic cloning and characterization of the human homeobox gene SIX6
RT reveals a cluster of SIX genes in chromosome 14 and associates SIX6
RT hemizygosity with bilateral anophthalmia and pituitary anomalies.";
RL Genomics 61:82-91(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-141.
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-165.
RX PubMed=15014171; DOI=10.1093/molbev/msh100;
RA Kitano T., Liu Y.-H., Ueda S., Saitou N.;
RT "Human-specific amino acid changes found in 103 protein-coding genes.";
RL Mol. Biol. Evol. 21:936-944(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-212; SER-221; SER-225;
RP SER-227 AND SER-228, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP INVOLVEMENT IN ODRMD.
RX PubMed=23167593; DOI=10.1111/cge.12046;
RA Aldahmesh M.A., Khan A.O., Hijazi H., Alkuraya F.S.;
RT "Homozygous truncation of SIX6 causes complex microphthalmia in humans.";
RL Clin. Genet. 84:198-199(2013).
RN [8]
RP VARIANTS ASN-141 AND ALA-165.
RX PubMed=15266624; DOI=10.1002/ajmg.a.30126;
RA Gallardo M.E., Rodriguez De Cordoba S., Schneider A.S., Dwyer M.A.,
RA Ayuso C., Bovolenta P.;
RT "Analysis of the developmental SIX6 homeobox gene in patients with
RT anophthalmia/microphthalmia.";
RL Am. J. Med. Genet. A 129:92-94(2004).
CC -!- FUNCTION: May be involved in eye development.
CC -!- SUBUNIT: Interacts with TLE4 and TLE5. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- TISSUE SPECIFICITY: Expressed in the developing and adult retina. Also
CC expressed in the hypothalamic and the pituitary regions.
CC -!- DISEASE: Optic disk anomalies with retinal and/or macular dystrophy
CC (ODRMD) [MIM:212550]: An ocular disorder characterized by optic nerve
CC dysplasia, optic disk anomalies, chorioretinal dystrophy and macular
CC atrophy. Some patients have microphthalmia.
CC {ECO:0000269|PubMed:23167593}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
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DR EMBL; AF031648; AAF04402.1; -; Genomic_DNA.
DR EMBL; AJ011785; CAA09773.1; -; mRNA.
DR EMBL; AF141651; AAD49844.1; -; Genomic_DNA.
DR EMBL; BC069413; AAH69413.2; -; mRNA.
DR EMBL; AB041399; BAA94484.1; -; Genomic_DNA.
DR CCDS; CCDS9747.1; -.
DR RefSeq; NP_031400.2; NM_007374.2.
DR AlphaFoldDB; O95475; -.
DR BMRB; O95475; -.
DR SMR; O95475; -.
DR BioGRID; 111034; 8.
DR IntAct; O95475; 1.
DR STRING; 9606.ENSP00000328596; -.
DR iPTMnet; O95475; -.
DR PhosphoSitePlus; O95475; -.
DR BioMuta; SIX6; -.
DR CPTAC; CPTAC-1185; -.
DR EPD; O95475; -.
DR MassIVE; O95475; -.
DR MaxQB; O95475; -.
DR PaxDb; O95475; -.
DR PeptideAtlas; O95475; -.
DR PRIDE; O95475; -.
DR ProteomicsDB; 50906; -.
DR Antibodypedia; 40; 166 antibodies from 29 providers.
DR DNASU; 4990; -.
DR Ensembl; ENST00000327720.6; ENSP00000328596.5; ENSG00000184302.7.
DR GeneID; 4990; -.
DR KEGG; hsa:4990; -.
DR MANE-Select; ENST00000327720.6; ENSP00000328596.5; NM_007374.3; NP_031400.2.
DR UCSC; uc001xfa.5; human.
DR CTD; 4990; -.
DR DisGeNET; 4990; -.
DR GeneCards; SIX6; -.
DR HGNC; HGNC:10892; SIX6.
DR HPA; ENSG00000184302; Tissue enhanced (brain, pituitary gland, retina).
DR MalaCards; SIX6; -.
DR MIM; 212550; phenotype.
DR MIM; 606326; gene.
DR neXtProt; NX_O95475; -.
DR OpenTargets; ENSG00000184302; -.
DR Orphanet; 98938; Colobomatous microphthalmia.
DR Orphanet; 435930; Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome.
DR Orphanet; 35612; Nanophthalmos.
DR PharmGKB; PA35792; -.
DR VEuPathDB; HostDB:ENSG00000184302; -.
DR eggNOG; KOG0775; Eukaryota.
DR GeneTree; ENSGT00940000160091; -.
DR HOGENOM; CLU_046914_0_1_1; -.
DR InParanoid; O95475; -.
DR OMA; GTPEMLG; -.
DR OrthoDB; 1575904at2759; -.
DR PhylomeDB; O95475; -.
DR TreeFam; TF315545; -.
DR PathwayCommons; O95475; -.
DR SignaLink; O95475; -.
DR SIGNOR; O95475; -.
DR BioGRID-ORCS; 4990; 11 hits in 1090 CRISPR screens.
DR GenomeRNAi; 4990; -.
DR Pharos; O95475; Tbio.
DR PRO; PR:O95475; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; O95475; protein.
DR Bgee; ENSG00000184302; Expressed in adenohypophysis and 21 other tissues.
DR Genevisible; O95475; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0001654; P:eye development; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR031701; SIX1_SD.
DR InterPro; IPR032947; SIX6.
DR PANTHER; PTHR10390:SF12; PTHR10390:SF12; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF16878; SIX1_SD; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Cataract; Developmental protein; Disease variant; DNA-binding; Homeobox;
KW Microphthalmia; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..246
FT /note="Homeobox protein SIX6"
FT /id="PRO_0000049307"
FT DNA_BIND 128..187
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 190..246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..246
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 212
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VARIANT 141
FT /note="H -> N (in dbSNP:rs33912345)"
FT /evidence="ECO:0000269|PubMed:10381575,
FT ECO:0000269|PubMed:10512683, ECO:0000269|PubMed:15266624,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1"
FT /id="VAR_031631"
FT VARIANT 165
FT /note="T -> A (found in a patient with bilateral asymmetric
FT microphthalmia, cataract and nystagmus; unknown
FT pathological significance; dbSNP:rs104894480)"
FT /evidence="ECO:0000269|PubMed:15266624"
FT /id="VAR_026241"
SQ SEQUENCE 246 AA; 27687 MW; 5378438C9DE8C597 CRC64;
MFQLPILNFS PQQVAGVCET LEESGDVERL GRFLWSLPVA PAACEALNKN ESVLRARAIV
AFHGGNYREL YHILENHKFT KESHAKLQAL WLEAHYQEAE KLRGRPLGPV DKYRVRKKFP
LPRTIWDGEQ KTHCFKERTR HLLREWYLQD PYPNPSKKRE LAQATGLTPT QVGNWFKNRR
QRDRAAAAKN RLQQQVLSQG SGRALRAEGD GTPEVLGVAT SPAASLSSKA ATSAISITSS
DSECDI
