Reviewed, UniProtKB/Swiss-Prot Q9UI36 (DACH1_HUMAN)

Names and origin

Protein names

Recommended name:
    Dachshund homolog 1
      Short name=Dach1

Gene names

Name:	DACH1
Synonyms:	DACH

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	758 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transcription factor that is involved in regulation of organogenesis. Seems to be a regulator of SIX1, SIX6 and probably SIX5. Corepression of precursor cell proliferation in myoblasts by SIX1 is switched to coactivation through recruitment of EYA3 to the SIX1-DACH1 complex. Transcriptional activation seems also to involve association of CREBBP. Seems to act as a corepressor of SIX6 in regulating proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter By similarity. Inhibits TGF-beta signaling through interaction with SMAD4 and NCOR1. Binds to chromatin DNA via its DACHbox-N domain By similarity. Ref.7
Subunit structure	Interacts with SIX1, SIX6 and EYA3. Interacts with NCOR1 and HDAC3 through its N-terminus. Interacts with SIN3A through its C-terminus By similarity. Interacts with SMAD3 and SMAD4. Ref.7
Subcellular location	Nucleus Ref.7.
Tissue specificity	Widely expressed. Isoform 2 is found in brain, heart, kidney, liver, leukocytes and spleen. Isoform 3 is found in liver and heart. Isoform 4 is found in spleen. Ref.2
Domain	The DACHbox-N/DD1 domain forms a structure containing a DNA binding motif similar to that of the forkhead/winged helix domain.
Sequence similarities	Belongs to the DACH/dachshund family.
Sequence caution	The sequence CAC12840.2 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH73005.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH73006.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH73303.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH73304.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI14979.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI14980.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI16673.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Ligand	DNA-binding
Molecular function	Activator Developmental protein Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Ref.7 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCOR1	O75376	2	EBI-347111,EBI-347233
SIN3A	Q96ST3	1	EBI-347111,EBI-347218
SMAD3	P84022	1	EBI-347111,EBI-347161
SMAD4	Q13485	3	EBI-347111,EBI-347263

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q9UI36-1)

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.

Note: Derived from EST data. No experimental confirmation available.

Isoform 2 (identifier: Q9UI36-2)

The sequence of this isoform differs from the canonical sequence as follows:
     376-427: Missing.

Note: Major.

Isoform 3 (identifier: Q9UI36-3)

The sequence of this isoform differs from the canonical sequence as follows:
     376-427: Missing.
     428-575: Missing.

Isoform 4 (identifier: Q9UI36-4)

The sequence of this isoform differs from the canonical sequence as follows:
     322-575: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 758

758

Dachshund homolog 1

PRO_0000095597

Regions

Region

189 – 384

196

Interaction with SIX6 and HDAC3 By similarity

Region

189 – 275

87

DACHbox-N

Region

616 – 696

81

DACHbox-C

Region

627 – 706

80

Interaction with SIN3A By similarity

Coiled coil

630 – 718

89

Potential

Compositional bias

61 – 68

8

Poly-Ala

Compositional bias

74 – 87

14

Poly-Gly

Compositional bias

90 – 101

12

Poly-Gly

Compositional bias

114 – 121

8

Poly-Gly

Compositional bias

140 – 163

24

Poly-Ser

Compositional bias

325 – 333

9

Poly-Ala

Compositional bias

467 – 470

4

Poly-Ala

Amino acid modifications

Modified residue

578

1

Phosphothreonine Ref.8

Modified residue

581

1

Phosphoserine Ref.8

Modified residue

582

1

Phosphothreonine Ref.8

Modified residue

584

1

Phosphothreonine Ref.8

Natural variations

Alternative sequence

322 – 575

254

Missing in isoform 4.

VSP_009486

Alternative sequence

376 – 427

52

Missing in isoform 2 and isoform 3.

VSP_009872

Alternative sequence

428 – 575

148

Missing in isoform 3.

VSP_009873

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

758

Helix Strand Turn

Details...

Helix

184 – 186

3

Beta strand

189 – 193

5

Beta strand

196 – 203

8

Beta strand

206 – 210

5

Helix

211 – 218

8

Turn

219 – 223

5

Helix

226 – 235

10

Helix

245 – 253

9

Beta strand

265 – 268

4

Helix

269 – 280

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: DFB5054D7EC5FF11	FASTA	758	78,562
	10 20 30 40 50 60 MAVPAALIPP TQLVPPQPPI STSASSSGTT TSTSSATSSP APSIGPPASS GPTLFRPEPI 70 80 90 100 110 120 ASAAAAAATV TSTGGGGGGG GSGGGGGSSG NGGGGGGGGG GSNCNPNLAA ASNGSGGGGG 130 140 150 160 170 180 GISAGGGVAS STPINASTGS SSSSSSSSSS SSSSSSSSSS SSSCGPLPGK PVYSTPSPVE 190 200 210 220 230 240 NTPQNNECKM VDLRGAKVAS FTVEGCELIC LPQAFDLFLK HLVGGLHTVY TKLKRLEITP 250 260 270 280 290 300 VVCNVEQVRI LRGLGAIQPG VNRCKLISRK DFETLYNDCT NASSRPGRPP KRTQSVTSPE 310 320 330 340 350 360 NSHIMPHSVP GLMSPGIIPP TGLTAAAAAA AAATNAAIAE AMKVKKIKLE AMSNYHASNN 370 380 390 400 410 420 QHGADSENGD MNSSVGSSDG SWDKETLPSS PSQGPQASIT HPRMPGARSL PLSHPLNHLQ 430 440 450 460 470 480 QSHLLPNGLE LPFMMMPHPL IPVSLPPASV TMAMSQMNHL STIANMAAAA QVQSPPSRVE 490 500 510 520 530 540 TSVIKERVPD SPSPAPSLEE GRRPGSHPSS HRSSSVSSSP ARTESSSDRI PVHQNGLSMN 550 560 570 580 590 600 QMLMGLSPNV LPGPKEGDLA GHDMGHESKR MHIEKDETPL STPTARDSLD KLSLTGHGQP 610 620 630 640 650 660 LPPGFPSPFL FPDGLSSIET LLTNIQGLLK VAIDNARAQE KQVQLEKTEL KMDFLREREL 670 680 690 700 710 720 RETLEKQLAM EQKNRAIVQK RLKKEKKAKR KLQEALEFET KRREQAEQTL KQAASTDSLR 730 740 750 VLNDSLTPEI EADRSGGRTD AERTIQDGRL YLKTTVMY
	Isoform 2. Checksum: B9D6BA5058CC23DF	FASTA	706	73,030
	10 20 30 40 50 60 MAVPAALIPP TQLVPPQPPI STSASSSGTT TSTSSATSSP APSIGPPASS GPTLFRPEPI 70 80 90 100 110 120 ASAAAAAATV TSTGGGGGGG GSGGGGGSSG NGGGGGGGGG GSNCNPNLAA ASNGSGGGGG 130 140 150 160 170 180 GISAGGGVAS STPINASTGS SSSSSSSSSS SSSSSSSSSS SSSCGPLPGK PVYSTPSPVE 190 200 210 220 230 240 NTPQNNECKM VDLRGAKVAS FTVEGCELIC LPQAFDLFLK HLVGGLHTVY TKLKRLEITP 250 260 270 280 290 300 VVCNVEQVRI LRGLGAIQPG VNRCKLISRK DFETLYNDCT NASSRPGRPP KRTQSVTSPE 310 320 330 340 350 360 NSHIMPHSVP GLMSPGIIPP TGLTAAAAAA AAATNAAIAE AMKVKKIKLE AMSNYHASNN 370 380 390 400 410 420 QHGADSENGD MNSSVGLELP FMMMPHPLIP VSLPPASVTM AMSQMNHLST IANMAAAAQV 430 440 450 460 470 480 QSPPSRVETS VIKERVPDSP SPAPSLEEGR RPGSHPSSHR SSSVSSSPAR TESSSDRIPV 490 500 510 520 530 540 HQNGLSMNQM LMGLSPNVLP GPKEGDLAGH DMGHESKRMH IEKDETPLST PTARDSLDKL 550 560 570 580 590 600 SLTGHGQPLP PGFPSPFLFP DGLSSIETLL TNIQGLLKVA IDNARAQEKQ VQLEKTELKM 610 620 630 640 650 660 DFLRERELRE TLEKQLAMEQ KNRAIVQKRL KKEKKAKRKL QEALEFETKR REQAEQTLKQ 670 680 690 700 AASTDSLRVL NDSLTPEIEA DRSGGRTDAE RTIQDGRLYL KTTVMY
	Isoform 3. Checksum: 2671E7C3B8906122	FASTA	558	57,262
	10 20 30 40 50 60 MAVPAALIPP TQLVPPQPPI STSASSSGTT TSTSSATSSP APSIGPPASS GPTLFRPEPI 70 80 90 100 110 120 ASAAAAAATV TSTGGGGGGG GSGGGGGSSG NGGGGGGGGG GSNCNPNLAA ASNGSGGGGG 130 140 150 160 170 180 GISAGGGVAS STPINASTGS SSSSSSSSSS SSSSSSSSSS SSSCGPLPGK PVYSTPSPVE 190 200 210 220 230 240 NTPQNNECKM VDLRGAKVAS FTVEGCELIC LPQAFDLFLK HLVGGLHTVY TKLKRLEITP 250 260 270 280 290 300 VVCNVEQVRI LRGLGAIQPG VNRCKLISRK DFETLYNDCT NASSRPGRPP KRTQSVTSPE 310 320 330 340 350 360 NSHIMPHSVP GLMSPGIIPP TGLTAAAAAA AAATNAAIAE AMKVKKIKLE AMSNYHASNN 370 380 390 400 410 420 QHGADSENGD MNSSVDETPL STPTARDSLD KLSLTGHGQP LPPGFPSPFL FPDGLSSIET 430 440 450 460 470 480 LLTNIQGLLK VAIDNARAQE KQVQLEKTEL KMDFLREREL RETLEKQLAM EQKNRAIVQK 490 500 510 520 530 540 RLKKEKKAKR KLQEALEFET KRREQAEQTL KQAASTDSLR VLNDSLTPEI EADRSGGRTD 550 AERTIQDGRL YLKTTVMY
	Isoform 4. Checksum: D5B52F8AB9A9F05D	FASTA	504	51,891
	10 20 30 40 50 60 MAVPAALIPP TQLVPPQPPI STSASSSGTT TSTSSATSSP APSIGPPASS GPTLFRPEPI 70 80 90 100 110 120 ASAAAAAATV TSTGGGGGGG GSGGGGGSSG NGGGGGGGGG GSNCNPNLAA ASNGSGGGGG 130 140 150 160 170 180 GISAGGGVAS STPINASTGS SSSSSSSSSS SSSSSSSSSS SSSCGPLPGK PVYSTPSPVE 190 200 210 220 230 240 NTPQNNECKM VDLRGAKVAS FTVEGCELIC LPQAFDLFLK HLVGGLHTVY TKLKRLEITP 250 260 270 280 290 300 VVCNVEQVRI LRGLGAIQPG VNRCKLISRK DFETLYNDCT NASSRPGRPP KRTQSVTSPE 310 320 330 340 350 360 NSHIMPHSVP GLMSPGIIPP TDETPLSTPT ARDSLDKLSL TGHGQPLPPG FPSPFLFPDG 370 380 390 400 410 420 LSSIETLLTN IQGLLKVAID NARAQEKQVQ LEKTELKMDF LRERELRETL EKQLAMEQKN 430 440 450 460 470 480 RAIVQKRLKK EKKAKRKLQE ALEFETKRRE QAEQTLKQAA STDSLRVLND SLTPEIEADR 490 500 SGGRTDAERT IQDGRLYLKT TVMY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene." Kozmik Z., Pfeffer P., Kralova J., Paces J., Paces V., Kalousova A., Cvekl A. Dev. Genes Evol. 209:537-545(1999) [PubMed: 10502110] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Dach: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homolog." Ayres J.A., Shum L., Akarsu A.N., Dashner R., Takahashi K., Ikura T., Slavkin H.C., Nuckolls G.H. Genomics 77:18-26(2001) [PubMed: 11543628] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORMS 3; 4 AND 5), TISSUE SPECIFICITY.
[3]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	The European IMAGE consortium Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 108-758 (ISOFORM 2). Tissue: Retina.
[5]	"Mammalian and Drosophila dachshund genes are related to the Ski proto-oncogene and are expressed in eye and limb." Hammond K.L., Hanson I.M., Brown A.G., Lettice L.A., Hill R.E. Mech. Dev. 74:121-131(1998) [PubMed: 9651501] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 109-758 (ISOFORM 2).
[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] OF 186-758 (ISOFORM 2). Tissue: Uterus.
[7]	"DACH1 inhibits transforming growth factor-beta signaling through binding Smad4." Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K., Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G. J. Biol. Chem. 278:51673-51684(2003) [PubMed: 14525983] [Abstract] Cited for: FUNCTION IN TGF-BETA SIGNALING, INTERACTION WITH HDAC3; SMAD3; SMAD4; NCOR1 AND SIN3A, SUBCELLULAR LOCATION.
[8]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-578; SER-581; THR-582 AND THR-584, MASS SPECTROMETRY.
[9]	"Structure of the retinal determination protein dachshund reveals a DNA binding motif." Kim S.-S., Zhang R.-G., Braunstein S.E., Joachimiak A., Cvekl A., Hegde R.S. Structure 10:787-795(2002) [PubMed: 12057194] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 184-282.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF102546 mRNA. Translation: AAF01351.1.
AF069509 mRNA. Translation: AAC33466.1.
AF356492 mRNA. Translation: AAL08487.1.
AL138698 , AL139186, AL163542, AL354995 Genomic DNA. Translation: CAH73303.1. Sequence problems.
AL138698 , AL139186, AL163542, AL354995 Genomic DNA. Translation: CAH73304.1. Sequence problems.
AL139186 , AL138698, AL163542, AL354995 Genomic DNA. Translation: CAC12840.2. Sequence problems.
AL139186 , AL138698, AL163542, AL354995 Genomic DNA. Translation: CAI16673.1. Sequence problems.
AL163542 , AL138698, AL139186, AL354995 Genomic DNA. Translation: CAH73005.1. Sequence problems.
AL163542 , AL138698, AL139186, AL354995 Genomic DNA. Translation: CAH73006.1. Sequence problems.
AL354995 , AL138698, AL139186, AL163542 Genomic DNA. Translation: CAI14979.1. Sequence problems.
AL354995 , AL138698, AL139186, AL163542 Genomic DNA. Translation: CAI14980.1. Sequence problems.
AL079278 mRNA. Translation: CAB45153.1.
AJ005670 mRNA. Translation: CAA06666.1. Different initiation.
BC021219 mRNA. Translation: AAH21219.2.

IPI

IPI00854705.
IPI00936290.
IPI00953918.
IPI00953943.

RefSeq

NP_004383.3.
NP_542937.2.
NP_542938.2.

UniGene

Hs.129452

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1L8R	X-ray	1.65	A/B	184-282	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UI36. 6 interactions.

STRING

Q9UI36.

PTM databases

PhosphoSite

Q9UI36.

Proteomic databases

PRIDE

Q9UI36.

Genome annotation databases

Ensembl

ENST00000359684; ENSP00000352712; ENSG00000165659; Homo sapiens. [Genome view]

GeneID

1602.

UCSC

uc010ael.1. human.
uc010aem.1. human.

Organism-specific databases

CTD

1602.

GeneCards

GC13M070910.

H-InvDB

HIX0011360.
HIX0025348.

HGNC

HGNC:2663. DACH1.

HPA

HPA012672.

MIM

603803. gene.

PharmGKB

PA27134.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08548.

HOVERGEN

Q9UI36.

InParanoid

Q9UI36.

Gene expression databases

ArrayExpress

Q9UI36.

Bgee

Q9UI36.

Genevestigator

Q9UI36.

GermOnline

ENSG00000165659. Homo sapiens.

Family and domain databases

InterPro

IPR009061. DNA-bd_dom_put.
IPR003380. Transform_Ski.
[Graphical view]

Gene3D

G3DSA:3.10.260.20. Transform_Ski. 1 hit.

Pfam

PF02437. Ski_Sno. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

6570.

SOURCE

Search...

Entry information

Entry name

DACH1_HUMAN

Accession

Primary (citable) accession number: Q9UI36
Secondary accession number(s): O75523 , O75687, Q5VYY3, Q5VYY4, Q96SG3, Q96SG4, Q9H524, Q9UMH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2004
Last modified:	February 9, 2010
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.