The Human Transcription Factors

Conclusion

Assessment	Binding Mode	Motif Status	Notes	Comments
Known motif	1 Monomer or homomultimer	In vivo/Misc source	Only known motifs are from Transfac or HocoMoco - origin is uncertain

Description

Description:

SIX homeobox 5 [Source:HGNC Symbol;Acc:HGNC:10891]

Entrez Summary

The protein encoded by this gene is a homeodomain-containing transcription factor that appears to function in the regulation of organogenesis. This gene is located downstream of the dystrophia myotonica-protein kinase gene. Mutations in this gene are a cause of branchiootorenal syndrome type 2. [provided by RefSeq, Jul 2009]

Ensembl ID:

ENSG00000177045

External Link:

CisBP

Interpro

IPR001356; IPR009057; IPR017970; ;

Protein Domain:

ENSP00000316842

Protein Domain:

ENSP00000453239

Protein Domain:

ENSP00000453189

Protein Domain:

ENSP00000481365

Domain:

Protein: ENSP00000316842	DBD: Homeodomain	Other: SIX1_SD
Protein: ENSP00000453239	DBD: Homeodomain	Other: SIX1_SD
Protein: ENSP00000453189	DBD: Homeodomain	Other:
Protein: ENSP00000481365	DBD: Homeodomain	Other:

Previous Annotations

Source	Annotation
TF-CAT classification	No PMIDS:
Vaquerizas 2009 TF classification "a" Has direct evidence of TF function; "b" Has evidence for an orthologous TF; "c" contains likely DBDs, but has no functional evidence; "x" is an unlikely TF such as predicted gene, genes with likely non-specific DBDs or that have function outside transcription; "other" category contains proteins without clear DBDs they curated from external sources.	a
CisBP considers it as a TF?	Yes
TFclass considers it as a TF?	Yes
Has GO:0003700 "transcription factor activity, sequence-specific DNA binding"	No
GO-Info
Initial Assessment 1a1 Protein has a high confidence PWM (HT-SELEX, PBM or B1H model) or there is a crystal structure that supports sequence specific DNA binding; 1a2 There is high confidence data for a close ortholog (as defined in CisBP); 2a1 There is lower confidence direct evidence, such as a Jaspar, Hocomoco or Transfac model; 2a2 There is lower confidence evidence for an close ortholog; 3a There is decent circumstantial evidence for its role as a TF or not; 4a Two or more datasets predict it as a TF; 5a One of the source datasets predicts is as a TF	1a1, Direct HQ evidence
TF has conditional DNA-binding requirements

DNA-Binding

Published Motif Data

Source	Annotation	Motif	Evidence
ChIP-seq	modENCODE		Direct
ChIP-seq	modENCODE		Direct
Transfac	Transfac	License required	Direct
Transfac	Transfac	License required	Direct
Transfac	Transfac	License required	Direct
PBM	BusserDevelopment2012		Inferred - Six4 (81% AA Identity, Drosophila melanogaster)
B1H	JASPAR		Inferred - Six4 (81% AA Identity, Drosophila melanogaster)
HT-SELEX	Yin2017		Inferred - SIX4 (77% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - SIX4 (77% AA Identity, Homo sapiens)
PBM	Berger08		Inferred - Six4 (77% AA Identity, Mus musculus)
Transfac	Transfac	License required	Inferred - SIX4 (77% AA Identity, Homo sapiens)
HT-SELEX	Yin2017		Inferred - SIX1 (65% AA Identity, Homo sapiens)
HT-SELEX	Yin2017		Inferred - SIX1 (65% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - SIX1 (65% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - SIX1 (65% AA Identity, Homo sapiens)
PBM	Berger08		Inferred - Six1 (65% AA Identity, Mus musculus)
HT-SELEX	Yin2017		Inferred - SIX2 (65% AA Identity, Homo sapiens)
HT-SELEX	Yin2017		Inferred - SIX2 (65% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - SIX2 (65% AA Identity, Homo sapiens)
Methyl-HT-SELEX	Yin2017		Inferred - SIX2 (65% AA Identity, Homo sapiens)
PBM	Berger08		Inferred - Six2 (65% AA Identity, Mus musculus)
B1H	JASPAR		Inferred - so (65% AA Identity, Drosophila melanogaster)
HT-SELEX	Nitta2015		Inferred - so (65% AA Identity, Drosophila melanogaster)
HT-SELEX	Nitta2015		Inferred - so (65% AA Identity, Drosophila melanogaster)
HT-SELEX	Nitta2015		Inferred - so (65% AA Identity, Drosophila melanogaster)
HT-SELEX	Nitta2015		Inferred - so (65% AA Identity, Drosophila melanogaster)
PBM	Zoo_01		Inferred - so (65% AA Identity, Drosophila melanogaster)
Transfac	Transfac	License required	Inferred - SIX1 (65% AA Identity, Homo sapiens)
Transfac	Transfac	License required	Inferred - SIX1 (65% AA Identity, Homo sapiens)
Misc	HOMER		Inferred - Six1 (65% AA Identity, Mus musculus)

Structure

Structure	PDB	Not_Covered

Experimental History

Method	Constructs
Tried in PBM? (Whether the protein was tried in PBM or not)
Tried in HT-SELEX (Whether the protein was tried in HT-SELEX or not, and if so, then what kind of clones were tested)
Other Information? (Tried with another method and failed?)

External Contribution

Name
Email
Comment
Reference

{"regions": [{"startStyle": "jagged", "end": 258, "endStyle": "curved", "aliStart": 208, "text": "HD", "colour": "#228B22", "aliEnd": 257, "start": 206, "href": "http://pfam.xfam.org/family/PF00046.27", "type": "pfama", "display": "true", "metadata": {"end": 258, "description": "The homeobox domain or homeodomain was first identified in a number of drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates [PUBMED:2568852, PUBMED:1357790]. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies [PUBMED:12445403]. The domain binds DNA through a helix-turn-helix (HTH) structure. ", "database": "PfamA", "aliStart": 208, "scoreName": "E-value", "accession": "PF00046.27", "start": 206, "score": 5.6e-13, "identifier": "Homeobox domain", "type": "DBD", "aliEnd": 257}}, {"startStyle": "straight", "end": 196, "endStyle": "straight", "aliStart": 86, "text": "SIX1_SD", "colour": "#9999ff", "aliEnd": 196, "start": 86, "href": "http://pfam.xfam.org/family/PF16878.3", "type": "pfama", "display": "true", "metadata": {"end": 196, "description": "SIX1_SD is a family of eukaryotic proteins, and it is found N-terminal to the Homeobox domain. As a transcription factor it lacks intrinsic activation domains and thus needs to bind to the EYA family of co-factors in order to mediate transcriptional activation. It is the SD domain that is necessary for this protein-protein interaction, binding to the C-terminal region of EYA - Eyes absent homologue proteins [1].", "database": "PfamA", "aliStart": 86, "scoreName": "E-value", "accession": "PF16878.3", "start": 86, "score": 9.199999999999998e-41, "identifier": "Transcriptional regulator, SIX1, N-terminal SD domain", "type": "DBD", "aliEnd": 196}}], "length": 740}

{"regions": [{"startStyle": "jagged", "end": 186, "endStyle": "curved", "aliStart": 136, "text": "HD", "colour": "#228B22", "aliEnd": 185, "start": 134, "href": "http://pfam.xfam.org/family/PF00046.27", "type": "pfama", "display": "true", "metadata": {"end": 186, "description": "The homeobox domain or homeodomain was first identified in a number of drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates [PUBMED:2568852, PUBMED:1357790]. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies [PUBMED:12445403]. The domain binds DNA through a helix-turn-helix (HTH) structure. ", "database": "PfamA", "aliStart": 136, "scoreName": "E-value", "accession": "PF00046.27", "start": 134, "score": 1.1e-13, "identifier": "Homeobox domain", "type": "DBD", "aliEnd": 185}}, {"startStyle": "straight", "end": 124, "endStyle": "straight", "aliStart": 14, "text": "SIX1_SD", "colour": "#9999ff", "aliEnd": 124, "start": 14, "href": "http://pfam.xfam.org/family/PF16878.3", "type": "pfama", "display": "true", "metadata": {"end": 124, "description": "SIX1_SD is a family of eukaryotic proteins, and it is found N-terminal to the Homeobox domain. As a transcription factor it lacks intrinsic activation domains and thus needs to bind to the EYA family of co-factors in order to mediate transcriptional activation. It is the SD domain that is necessary for this protein-protein interaction, binding to the C-terminal region of EYA - Eyes absent homologue proteins [1].", "database": "PfamA", "aliStart": 14, "scoreName": "E-value", "accession": "PF16878.3", "start": 14, "score": 7.3e-42, "identifier": "Transcriptional regulator, SIX1, N-terminal SD domain", "type": "DBD", "aliEnd": 124}}], "length": 256}

TF Info Page for SIX5 (Homeodomain)

Conclusion

Description

Previous Annotations

DNA-Binding

Published Motif Data

Structure

Experimental History

External Contribution