ID   IRX6_HUMAN              Reviewed;         446 AA.
AC   P78412; B2RN06; Q7Z2K0;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 3.
DT   24-JAN-2024, entry version 167.
DE   RecName: Full=Iroquois-class homeodomain protein IRX-6;
DE   AltName: Full=Homeodomain protein IRXB3;
DE   AltName: Full=Iroquois homeobox protein 6;
GN   Name=IRX6; Synonyms=IRX7, IRXB3;
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 / MRNA].
RA   Hansen L., Wu Q., Tommerup N.;
RT   "Characterization of the human homeobox two-cluster Iroquois gene family.";
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Thalamus;
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].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [MRNA] OF 1-195.
RA   Lewis M.T., Strickland P.A., Ross S., Snyder C.J., Daniel C.W.;
RT   "IRX: a new family of human homeobox genes from the breast.";
RL   Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Transcription factor. Binds to the iroquois binding site
CC       (IBS) motif of target genes to regulate gene expression; functions as a
CC       transcriptional activator or repressor. Modulates expression of RCVRN,
CC       VSX1, BHLHE22/BHLHB5 and TACR3/Nk3r. Required downstream of retinal
CC       bipolar cell specification for the terminal differentiation of type 2,
CC       type 3a and possibly type 6 bipolar cells.
CC       {ECO:0000250|UniProtKB:Q9ER75}.
CC   -!- INTERACTION:
CC       P78412; Q03989: ARID5A; NbExp=3; IntAct=EBI-12100506, EBI-948603;
CC       P78412; O43186: CRX; NbExp=3; IntAct=EBI-12100506, EBI-748171;
CC       P78412; O76003: GLRX3; NbExp=5; IntAct=EBI-12100506, EBI-374781;
CC       P78412; P49639: HOXA1; NbExp=3; IntAct=EBI-12100506, EBI-740785;
CC       P78412; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-12100506, EBI-10241353;
CC       P78412; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12100506, EBI-16439278;
CC       P78412; P10916: MYL2; NbExp=3; IntAct=EBI-12100506, EBI-725770;
CC       P78412; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-12100506, EBI-10271199;
CC       P78412; Q99471: PFDN5; NbExp=3; IntAct=EBI-12100506, EBI-357275;
CC       P78412; O60806: TBX19; NbExp=3; IntAct=EBI-12100506, EBI-12096770;
CC       P78412; Q08117-2: TLE5; NbExp=5; IntAct=EBI-12100506, EBI-11741437;
CC       P78412; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-12100506, EBI-492476;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the TALE/IRO homeobox family. {ECO:0000305}.
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DR   EMBL; AY335937; AAQ16543.1; -; mRNA.
DR   EMBL; AY335946; AAQ16552.1; -; Genomic_DNA.
DR   EMBL; AK125053; BAC86033.1; -; mRNA.
DR   EMBL; CH471092; EAW82823.1; -; Genomic_DNA.
DR   EMBL; BC136573; AAI36574.1; -; mRNA.
DR   EMBL; BC136576; AAI36577.1; -; mRNA.
DR   EMBL; U90305; AAB50003.1; -; mRNA.
DR   CCDS; CCDS32449.1; -.
DR   RefSeq; NP_077311.2; NM_024335.2.
DR   RefSeq; XP_005256194.1; XM_005256137.2.
DR   AlphaFoldDB; P78412; -.
DR   SMR; P78412; -.
DR   BioGRID; 122602; 11.
DR   IntAct; P78412; 12.
DR   STRING; 9606.ENSP00000290552; -.
DR   GlyGen; P78412; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P78412; -.
DR   PhosphoSitePlus; P78412; -.
DR   BioMuta; IRX6; -.
DR   DMDM; 116242594; -.
DR   jPOST; P78412; -.
DR   MassIVE; P78412; -.
DR   MaxQB; P78412; -.
DR   PaxDb; 9606-ENSP00000290552; -.
DR   PeptideAtlas; P78412; -.
DR   ProteomicsDB; 57617; -.
DR   Antibodypedia; 14626; 185 antibodies from 19 providers.
DR   DNASU; 79190; -.
DR   Ensembl; ENST00000290552.8; ENSP00000290552.8; ENSG00000159387.8.
DR   GeneID; 79190; -.
DR   KEGG; hsa:79190; -.
DR   MANE-Select; ENST00000290552.8; ENSP00000290552.8; NM_024335.3; NP_077311.2.
DR   UCSC; uc002ehy.4; human.
DR   AGR; HGNC:14675; -.
DR   CTD; 79190; -.
DR   DisGeNET; 79190; -.
DR   GeneCards; IRX6; -.
DR   HGNC; HGNC:14675; IRX6.
DR   HPA; ENSG00000159387; Tissue enhanced (adipose tissue, heart muscle, skin).
DR   MIM; 606196; gene.
DR   neXtProt; NX_P78412; -.
DR   OpenTargets; ENSG00000159387; -.
DR   PharmGKB; PA29929; -.
DR   VEuPathDB; HostDB:ENSG00000159387; -.
DR   eggNOG; KOG0773; Eukaryota.
DR   GeneTree; ENSGT00940000159909; -.
DR   HOGENOM; CLU_042927_1_0_1; -.
DR   InParanoid; P78412; -.
DR   OMA; EPAVQCQ; -.
DR   OrthoDB; 2915644at2759; -.
DR   PhylomeDB; P78412; -.
DR   TreeFam; TF319371; -.
DR   PathwayCommons; P78412; -.
DR   SignaLink; P78412; -.
DR   BioGRID-ORCS; 79190; 27 hits in 1168 CRISPR screens.
DR   ChiTaRS; IRX6; human.
DR   GeneWiki; IRX6; -.
DR   GenomeRNAi; 79190; -.
DR   Pharos; P78412; Tbio.
DR   PRO; PR:P78412; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; P78412; Protein.
DR   Bgee; ENSG00000159387; Expressed in apex of heart and 74 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; 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; IBA:GO_Central.
DR   GO; GO:0048468; P:cell development; IBA:GO_Central.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IBA:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR008422; Homeobox_KN_domain.
DR   InterPro; IPR003893; Iroquois_homeo.
DR   PANTHER; PTHR11211; IROQUOIS-CLASS HOMEODOMAIN PROTEIN IRX; 1.
DR   PANTHER; PTHR11211:SF11; IROQUOIS-CLASS HOMEODOMAIN PROTEIN IRX-6; 1.
DR   Pfam; PF05920; Homeobox_KN; 1.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00548; IRO; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
PE   1: Evidence at protein level;
KW   DNA-binding; Homeobox; Nucleus; Reference proteome.
FT   CHAIN           1..446
FT                   /note="Iroquois-class homeodomain protein IRX-6"
FT                   /id="PRO_0000049162"
FT   DNA_BIND        146..208
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          208..273
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          362..394
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        208..229
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        257..273
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        117
FT                   /note="S -> G (in Ref. 5; AAB50003)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        444
FT                   /note="Missing (in Ref. 1)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   446 AA;  48240 MW;  4E542FEDD5D06912 CRC64;
     MSFPHFGHPY RGASQFLASA SSSTTCCEST QRSVSDVASG STPAPALCCA PYDSRLLGSA
     RPELGAALGI YGAPYAAAAA AQSYPGYLPY SPEPPSLYGA LNPQYEFKEA AGSFTSSLAQ
     PGAYYPYERT LGQYQYERYG AVELSGAGRR KNATRETTST LKAWLNEHRK NPYPTKGEKI
     MLAIITKMTL TQVSTWFANA RRRLKKENKM TWAPKNKGGE ERKAEGGEED SLGCLTADTK
     EVTASQEARG LRLSDLEDLE EEEEEEEEAE DEEVVATAGD RLTEFRKGAQ SLPGPCAAAR
     EGRLERRECG LAAPRFSFND PSGSEEADFL SAETGSPRLT MHYPCLEKPR IWSLAHTATA
     SAVEGAPPAR PRPRSPECRM IPGQPPASAR RLSVPRDSAC DESSCIPKAF GNPKFALQGL
     PLNCAPCPRR SEPVVQCQYP SGAEAG
//