ID   DACH2_HUMAN             Reviewed;         599 AA.
AC   Q96NX9; B1AJV3; B4DQG3; Q8NAY3; Q8ND17; Q96N55;
DT   01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 156.
DE   RecName: Full=Dachshund homolog 2;
DE            Short=Dach2;
GN   Name=DACH2;
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 [MRNA] (ISOFORM 1).
RA   Prueitt R.L., Barnes R., Zinn A.R.;
RT   "Human Dachshund 2.";
RL   Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC   TISSUE=Lung, and Neuron;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 414-599 (ISOFORMS 1/3/4).
RC   TISSUE=Brain;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
CC   -!- FUNCTION: Transcription factor that is involved in regulation of
CC       organogenesis. Seems to be a regulator for SIX1 and SIX6. Seems to act
CC       as a corepressor of SIX6 in regulating proliferation by directly
CC       repressing cyclin-dependent kinase inhibitors, including the p27Kip1
CC       promoter. Is recruited with SIX6 to the p27Kip1 promoter in embryonal
CC       retina. SIX6 corepression seems also to involve NCOR1, TBL1, HDAC1 and
CC       HDAC3. May be involved together with PAX3, SIX1, and EYA2 in regulation
CC       of myogenesis. In the developing somite, expression of DACH2 and PAX3
CC       is regulated by the overlying ectoderm, and DACH2 and PAX3 positively
CC       regulate each other's expression (By similarity). Probably binds to DNA
CC       via its DACHbox-N domain. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with SIX6 and EYA2. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q96NX9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96NX9-2; Sequence=VSP_009490, VSP_009491;
CC       Name=3;
CC         IsoId=Q96NX9-3; Sequence=VSP_009492;
CC       Name=4;
CC         IsoId=Q96NX9-4; Sequence=VSP_044275;
CC   -!- DOMAIN: The DACHbox-N/DD1 domain forms a structure containing a DNA
CC       binding motif similar to that of the forkhead/winged helix domain.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the DACH/dachshund family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF428101; AAL26561.1; -; mRNA.
DR   EMBL; AK055953; BAB71054.1; -; mRNA.
DR   EMBL; AK091842; BAC03761.1; -; mRNA.
DR   EMBL; AK298787; BAG60925.1; -; mRNA.
DR   EMBL; AL390058; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL023095; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL109752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL034406; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL138747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL157381; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL591465; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; Z95124; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; Z95325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL834456; CAD39116.1; -; mRNA.
DR   CCDS; CCDS14455.1; -. [Q96NX9-1]
DR   CCDS; CCDS48140.1; -. [Q96NX9-2]
DR   CCDS; CCDS55457.1; -. [Q96NX9-4]
DR   RefSeq; NP_001132986.1; NM_001139514.1. [Q96NX9-2]
DR   RefSeq; NP_001132987.1; NM_001139515.1. [Q96NX9-4]
DR   RefSeq; NP_444511.1; NM_053281.3. [Q96NX9-1]
DR   RefSeq; XP_016884745.1; XM_017029256.1.
DR   AlphaFoldDB; Q96NX9; -.
DR   SMR; Q96NX9; -.
DR   BioGRID; 125560; 13.
DR   IntAct; Q96NX9; 9.
DR   MINT; Q96NX9; -.
DR   STRING; 9606.ENSP00000362217; -.
DR   GlyGen; Q96NX9; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q96NX9; -.
DR   PhosphoSitePlus; Q96NX9; -.
DR   BioMuta; DACH2; -.
DR   DMDM; 44887818; -.
DR   EPD; Q96NX9; -.
DR   jPOST; Q96NX9; -.
DR   MassIVE; Q96NX9; -.
DR   PaxDb; 9606-ENSP00000362217; -.
DR   PeptideAtlas; Q96NX9; -.
DR   ProteomicsDB; 4870; -.
DR   ProteomicsDB; 77573; -. [Q96NX9-1]
DR   ProteomicsDB; 77574; -. [Q96NX9-2]
DR   ProteomicsDB; 77575; -. [Q96NX9-3]
DR   Antibodypedia; 417; 184 antibodies from 30 providers.
DR   DNASU; 117154; -.
DR   Ensembl; ENST00000373125.9; ENSP00000362217.4; ENSG00000126733.22. [Q96NX9-1]
DR   Ensembl; ENST00000373131.5; ENSP00000362223.1; ENSG00000126733.22. [Q96NX9-2]
DR   Ensembl; ENST00000508860.5; ENSP00000420896.1; ENSG00000126733.22. [Q96NX9-4]
DR   Ensembl; ENST00000510272.5; ENSP00000421919.1; ENSG00000126733.22. [Q96NX9-3]
DR   GeneID; 117154; -.
DR   KEGG; hsa:117154; -.
DR   MANE-Select; ENST00000373125.9; ENSP00000362217.4; NM_053281.3; NP_444511.1.
DR   UCSC; uc004eew.3; human. [Q96NX9-1]
DR   AGR; HGNC:16814; -.
DR   CTD; 117154; -.
DR   DisGeNET; 117154; -.
DR   GeneCards; DACH2; -.
DR   HGNC; HGNC:16814; DACH2.
DR   HPA; ENSG00000126733; Group enriched (brain, epididymis, fallopian tube, retina).
DR   MIM; 300608; gene.
DR   neXtProt; NX_Q96NX9; -.
DR   OpenTargets; ENSG00000126733; -.
DR   PharmGKB; PA27135; -.
DR   VEuPathDB; HostDB:ENSG00000126733; -.
DR   eggNOG; KOG3915; Eukaryota.
DR   GeneTree; ENSGT00390000001134; -.
DR   HOGENOM; CLU_027923_0_0_1; -.
DR   InParanoid; Q96NX9; -.
DR   OMA; MAMNSIH; -.
DR   OrthoDB; 2881800at2759; -.
DR   PhylomeDB; Q96NX9; -.
DR   TreeFam; TF316697; -.
DR   PathwayCommons; Q96NX9; -.
DR   SignaLink; Q96NX9; -.
DR   SIGNOR; Q96NX9; -.
DR   BioGRID-ORCS; 117154; 18 hits in 776 CRISPR screens.
DR   ChiTaRS; DACH2; human.
DR   GeneWiki; DACH2; -.
DR   GenomeRNAi; 117154; -.
DR   Pharos; Q96NX9; Tbio.
DR   PRO; PR:Q96NX9; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q96NX9; Protein.
DR   Bgee; ENSG00000126733; Expressed in endothelial cell and 93 other cell types or tissues.
DR   ExpressionAtlas; Q96NX9; baseline and differential.
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; IBA:GO_Central.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0046545; P:development of primary female sexual characteristics; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd21081; DHD_Dac; 1.
DR   Gene3D; 3.10.260.20; Ski; 1.
DR   InterPro; IPR009061; DNA-bd_dom_put_sf.
DR   InterPro; IPR003380; SKI/SNO/DAC.
DR   InterPro; IPR037000; Ski_DNA-bd_sf.
DR   PANTHER; PTHR12577; DACHSHUND; 1.
DR   PANTHER; PTHR12577:SF7; DACHSHUND HOMOLOG 2; 1.
DR   Pfam; PF02437; Ski_Sno; 1.
DR   SUPFAM; SSF46955; Putative DNA-binding domain; 1.
DR   Genevisible; Q96NX9; HS.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Coiled coil; Developmental protein; DNA-binding;
KW   Nucleus; Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..599
FT                   /note="Dachshund homolog 2"
FT                   /id="PRO_0000095599"
FT   REGION          69..155
FT                   /note="DACHbox-N"
FT   REGION          166..186
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          237..280
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          370..409
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          453..533
FT                   /note="DACHbox-C"
FT   COILED          459..554
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        237..267
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        383..406
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..219
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_009492"
FT   VAR_SEQ         1..167
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_044275"
FT   VAR_SEQ         163..175
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_009490"
FT   VAR_SEQ         584..599
FT                   /note="GGNYYCLEMAQQLYSA -> A (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_009491"
SQ   SEQUENCE   599 AA;  65323 MW;  4EE435720A83BAA0 CRC64;
     MAVSASPVIS ATSSGAGVPG GLFRAEPLYS TPREPPRLTP NMINSFVVNN HSNSAGGGGR
     GNTNTNECRM VDMHGMKVAS FLMDGQELIC LPQVFDLFLK HLVGGLHTVY TKLKRLDISP
     VVCTVEQVRI LRGLGAIQPG VNRCKLITRK DFETLFTDCT NARRKRQMTR KQAVNSSRPG
     RPPKRSLGVL QENARLLTHA VPGLLSPGLI TPTGITAAAM AEAMKLQKMK LMAMNTLQGN
     GSQNGTESEP DDLNSNTGGS ESSWDKDKMQ SPFAAPGPQH GIAHAALAGQ PGIGGAPTLN
     PLQQNHLLTN RLDLPFMMMP HPLLPVSLPP ASVAMAMNQM NHLNTIANMA AAAQIHSPLS
     RAGTSVIKER IPESPSPAPS LEENHRPGSQ TSSHTSSSVS SSPSQMDHHL ERMEEVPVQI
     PIMKSPLDKI QLTPGQALPA GFPGPFIFAD SLSSVETLLT NIQGLLKVAL DNARIQEKQI
     QQEKKELRLE LYREREIREN LERQLAVELQ SRTTMQKRLK KEKKTKRKLQ EALEFESKRR
     EQVEQALKQA TTSDSGLRML KDTGIPDIEI ENNGTPHDSA AMQGGNYYCL EMAQQLYSA
//