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Protein

Homeobox protein SIX5

Gene

SIX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi201 – 26060HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. sequence-specific DNA binding Source: Ensembl

GO - Biological processi

  1. lens development in camera-type eye Source: Ensembl
  2. negative regulation of skeletal muscle satellite cell proliferation Source: Ensembl
  3. negative regulation of transcription, DNA-templated Source: Ensembl
  4. spermatid development Source: Ensembl
  5. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein SIX5
Alternative name(s):
DM locus-associated homeodomain protein
Sine oculis homeobox homolog 5
Gene namesi
Name:SIX5
Synonyms:DMAHP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:10891. SIX5.

Subcellular locationi

  1. Cytoplasm 1 Publication
  2. Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. Golgi apparatus Source: HPA
  3. intracellular membrane-bounded organelle Source: HPA
  4. nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Branchiootorenal syndrome 2 (BOR2)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations.

See also OMIM:610896
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti158 – 1581A → T in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 Publication
VAR_032941
Natural varianti296 – 2961A → T in BOR2. 1 Publication
VAR_032942
Natural varianti365 – 3651G → R in BOR2. 1 Publication
VAR_032943
Natural varianti552 – 5521T → M in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 Publication
Corresponds to variant rs80356464 [ dbSNP | Ensembl ].
VAR_032944

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

MIMi610896. phenotype.
Orphaneti107. BOR syndrome.
PharmGKBiPA35791.

Polymorphism and mutation databases

BioMutaiSIX5.
DMDMi150421671.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 739739Homeobox protein SIX5PRO_0000049305Add
BLAST

Proteomic databases

MaxQBiQ8N196.
PaxDbiQ8N196.
PRIDEiQ8N196.

PTM databases

PhosphoSiteiQ8N196.

Expressioni

Tissue specificityi

Expressed in adult but not in fetal eyes. Found in corneal epithelium and endothelium, lens epithelium, ciliary body epithelia, cellular layers of the retina and the sclera.1 Publication

Developmental stagei

At the begin of fourth week of development detected in cytoplasm of somite cells, and at the end of fourth week is accumulated in the nucleus. Between the sixth and eighth week of development detected in the nucleus of limb bud cells.1 Publication

Gene expression databases

BgeeiQ8N196.
CleanExiHS_SIX5.
ExpressionAtlasiQ8N196. baseline and differential.
GenevestigatoriQ8N196.

Organism-specific databases

HPAiHPA042068.

Interactioni

Subunit structurei

Probably binds DNA dimer. Interacts with EYA3, and probably EYA1 and EYA2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ATXN1P542534EBI-946167,EBI-930964

Protein-protein interaction databases

BioGridi127096. 4 interactions.
IntActiQ8N196. 4 interactions.
MINTiMINT-2855964.
STRINGi9606.ENSP00000316842.

Structurei

3D structure databases

ProteinModelPortaliQ8N196.
SMRiQ8N196. Positions 86-259.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the SIX/Sine oculis homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG244874.
GeneTreeiENSGT00540000070251.
HOGENOMiHOG000154329.
HOVERGENiHBG050139.
InParanoidiQ8N196.
OMAiAAQGSIF.
OrthoDBiEOG7C5M8Z.
PhylomeDBiQ8N196.
TreeFamiTF315545.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8N196-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATLPAEPSA GPAAGGEAVA AAAATEEEEE EARQLLQTLQ AAEGEAAAAA
60 70 80 90 100
GAGAGAAAAG AEGPGSPGVP GSPPEAASEP PTGLRFSPEQ VACVCEALLQ
110 120 130 140 150
AGHAGRLSRF LGALPPAERL RGSDPVLRAR ALVAFQRGEY AELYRLLESR
160 170 180 190 200
PFPAAHHAFL QDLYLRARYH EAERARGRAL GAVDKYRLRK KFPLPKTIWD
210 220 230 240 250
GEETVYCFKE RSRAALKACY RGNRYPTPDE KRRLATLTGL SLTQVSNWFK
260 270 280 290 300
NRRQRDRTGA GGGAPCKSES DGNPTTEDES SRSPEDLERG AAPVSAEAAA
310 320 330 340 350
QGSIFLAGTG PPAPCPASSS ILVNGSFLAA SGSPAVLLNG GPVIINGLAL
360 370 380 390 400
GEASSLGPLL LTGGGGAPPP QPSPQGASET KTSLVLDPQT GEVRLEEAQS
410 420 430 440 450
EAPETKGAQV AAPGPALGEE VLGPLAQVVP GPPTAATFPL PPGPVPAVAA
460 470 480 490 500
PQVVPLSPPP GYPTGLSPTS PLLNLPQVVP TSQVVTLPQA VGPLQLLAAG
510 520 530 540 550
PGSPVKVAAA AGPANVHLIN SGVGVTALQL PSATAPGNFL LANPVSGSPI
560 570 580 590 600
VTGVALQQGK IILTATFPTS MLVSQVLPPA PGLALPLKPE TAISVPEGGL
610 620 630 640 650
PVAPSPALPE AHALGTLSAQ QPPPAAATTS STSLPFSPDS PGLLPNFPAP
660 670 680 690 700
PPEGLMLSPA AVPVWSAGLE LSAGTEGLLE AEKGLGTQAP HTVLRLPDPD
710 720 730
PEGLLLGATA GGEVDEGLEA EAKVLTQLQS VPVEEPLEL
Length:739
Mass (Da):74,562
Last modified:June 26, 2007 - v3
Checksum:iD8A2E8DBBBA263A2
GO

Sequence cautioni

The sequence AAH33204.1 differs from that shown.Aberrant splicing.Curated
The sequence AK074826 differs from that shown. Reason: Erroneous termination at position 721. Translated as Glu.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti158 – 1581A → T in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 Publication
VAR_032941
Natural varianti296 – 2961A → T in BOR2. 1 Publication
VAR_032942
Natural varianti365 – 3651G → R in BOR2. 1 Publication
VAR_032943
Natural varianti552 – 5521T → M in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 Publication
Corresponds to variant rs80356464 [ dbSNP | Ensembl ].
VAR_032944
Natural varianti556 – 5561L → V.
Corresponds to variant rs2014377 [ dbSNP | Ensembl ].
VAR_032945
Natural varianti635 – 6351P → S.
Corresponds to variant rs2014576 [ dbSNP | Ensembl ].
VAR_032946
Natural varianti693 – 6931V → M.
Corresponds to variant rs2341097 [ dbSNP | Ensembl ].
VAR_032947

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X84813 Genomic DNA. No translation available.
AC074212 Genomic DNA. No translation available.
BC033204 mRNA. Translation: AAH33204.1. Sequence problems.
BU859227 mRNA. No translation available.
AK074826 mRNA. No translation available.
CCDSiCCDS12673.1.
RefSeqiNP_787071.2. NM_175875.4.
UniGeneiHs.43314.

Genome annotation databases

EnsembliENST00000317578; ENSP00000316842; ENSG00000177045.
GeneIDi147912.
KEGGihsa:147912.
UCSCiuc002pdb.3. human.

Polymorphism and mutation databases

BioMutaiSIX5.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X84813 Genomic DNA. No translation available.
AC074212 Genomic DNA. No translation available.
BC033204 mRNA. Translation: AAH33204.1. Sequence problems.
BU859227 mRNA. No translation available.
AK074826 mRNA. No translation available.
CCDSiCCDS12673.1.
RefSeqiNP_787071.2. NM_175875.4.
UniGeneiHs.43314.

3D structure databases

ProteinModelPortaliQ8N196.
SMRiQ8N196. Positions 86-259.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127096. 4 interactions.
IntActiQ8N196. 4 interactions.
MINTiMINT-2855964.
STRINGi9606.ENSP00000316842.

PTM databases

PhosphoSiteiQ8N196.

Polymorphism and mutation databases

BioMutaiSIX5.
DMDMi150421671.

Proteomic databases

MaxQBiQ8N196.
PaxDbiQ8N196.
PRIDEiQ8N196.

Protocols and materials databases

DNASUi147912.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000317578; ENSP00000316842; ENSG00000177045.
GeneIDi147912.
KEGGihsa:147912.
UCSCiuc002pdb.3. human.

Organism-specific databases

CTDi147912.
GeneCardsiGC19M046268.
GeneReviewsiSIX5.
H-InvDBHIX0202857.
HGNCiHGNC:10891. SIX5.
HPAiHPA042068.
MIMi600963. gene.
610896. phenotype.
neXtProtiNX_Q8N196.
Orphaneti107. BOR syndrome.
PharmGKBiPA35791.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG244874.
GeneTreeiENSGT00540000070251.
HOGENOMiHOG000154329.
HOVERGENiHBG050139.
InParanoidiQ8N196.
OMAiAAQGSIF.
OrthoDBiEOG7C5M8Z.
PhylomeDBiQ8N196.
TreeFamiTF315545.

Miscellaneous databases

GeneWikiiSIX5.
GenomeRNAii147912.
NextBioi85758.
PROiQ8N196.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N196.
CleanExiHS_SIX5.
ExpressionAtlasiQ8N196. baseline and differential.
GenevestigatoriQ8N196.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat."
    Boucher C.A., King S.K., Carey N., Krahe R., Winchester C.L., Rahman S., Creavin T., Meghji P., Bailey M.E., Chartier F.L., Brown S.D., Sicilliano M.J., Johnson K.J.
    Hum. Mol. Genet. 4:1919-1925(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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].
    Tissue: Eye.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 185-739.
  5. "Characterization of the expression of DMPK and SIX5 in the human eye and implications for pathogenesis in myotonic dystrophy."
    Winchester C.L., Ferrier R.K., Sermoni A., Clark B.J., Johnson K.J.
    Hum. Mol. Genet. 8:481-492(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  6. "Functional analysis of the homeodomain protein SIX5."
    Harris S.E., Winchester C.L., Johnson K.J.
    Nucleic Acids Res. 28:1871-1878(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: DNA-BINDING.
  7. Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
  8. Cited for: VARIANTS BOR2 THR-158; THR-296; ARG-365 AND MET-552, CHARACTERIZATION OF VARIANTS BOR2 THR-158 AND MET-552.

Entry informationi

Entry nameiSIX5_HUMAN
AccessioniPrimary (citable) accession number: Q8N196
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: June 26, 2007
Last modified: April 29, 2015
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.