ID   ISX_HUMAN               Reviewed;         245 AA.
AC   Q2M1V0; Q68DJ5;
DT   29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   29-MAY-2007, sequence version 2.
DT   03-AUG-2022, entry version 133.
DE   RecName: Full=Intestine-specific homeobox;
DE   AltName: Full=RAX-like homeobox;
GN   Name=ISX; Synonyms=RAXLX;
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 [LARGE SCALE MRNA].
RC   TISSUE=Colon carcinoma;
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).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLY-28 AND SER-57.
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).
CC   -!- FUNCTION: Transcription factor that regulates gene expression in
CC       intestine. May participate in vitamin A metabolism most likely by
CC       regulating BCO1 expression in the intestine (By similarity).
CC       {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q2M1V0; Q15038: DAZAP2; NbExp=3; IntAct=EBI-6426064, EBI-724310;
CC       Q2M1V0; O15499: GSC2; NbExp=3; IntAct=EBI-6426064, EBI-19954058;
CC       Q2M1V0; P78424: POU6F2; NbExp=3; IntAct=EBI-6426064, EBI-12029004;
CC       Q2M1V0; Q01974: ROR2; NbExp=3; IntAct=EBI-6426064, EBI-6422642;
CC       Q2M1V0; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-6426064, EBI-2514383;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
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DR   EMBL; CR749372; CAH18225.1; -; mRNA.
DR   EMBL; Z83853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL024494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC112212; AAI12213.1; -; mRNA.
DR   EMBL; BC113633; AAI13634.1; -; mRNA.
DR   CCDS; CCDS33640.1; -.
DR   RefSeq; NP_001290437.1; NM_001303508.1.
DR   AlphaFoldDB; Q2M1V0; -.
DR   SMR; Q2M1V0; -.
DR   BioGRID; 124838; 33.
DR   IntAct; Q2M1V0; 22.
DR   STRING; 9606.ENSP00000311492; -.
DR   PhosphoSitePlus; Q2M1V0; -.
DR   BioMuta; ISX; -.
DR   DMDM; 150387849; -.
DR   MassIVE; Q2M1V0; -.
DR   PaxDb; Q2M1V0; -.
DR   PeptideAtlas; Q2M1V0; -.
DR   PRIDE; Q2M1V0; -.
DR   Antibodypedia; 25329; 75 antibodies from 16 providers.
DR   DNASU; 91464; -.
DR   Ensembl; ENST00000308700.6; ENSP00000311492.6; ENSG00000175329.13.
DR   Ensembl; ENST00000404699.7; ENSP00000386037.1; ENSG00000175329.13.
DR   GeneID; 91464; -.
DR   KEGG; hsa:91464; -.
DR   MANE-Select; ENST00000404699.7; ENSP00000386037.1; NM_001303508.2; NP_001290437.1.
DR   UCSC; uc003anj.4; human.
DR   CTD; 91464; -.
DR   DisGeNET; 91464; -.
DR   GeneCards; ISX; -.
DR   HGNC; HGNC:28084; ISX.
DR   HPA; ENSG00000175329; Tissue enriched (intestine).
DR   MIM; 612019; gene.
DR   neXtProt; NX_Q2M1V0; -.
DR   OpenTargets; ENSG00000175329; -.
DR   PharmGKB; PA147357909; -.
DR   VEuPathDB; HostDB:ENSG00000175329; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000161702; -.
DR   HOGENOM; CLU_079373_0_0_1; -.
DR   InParanoid; Q2M1V0; -.
DR   OMA; WETQPLP; -.
DR   OrthoDB; 1270742at2759; -.
DR   PhylomeDB; Q2M1V0; -.
DR   TreeFam; TF315976; -.
DR   PathwayCommons; Q2M1V0; -.
DR   SignaLink; Q2M1V0; -.
DR   BioGRID-ORCS; 91464; 11 hits in 1087 CRISPR screens.
DR   GenomeRNAi; 91464; -.
DR   Pharos; Q2M1V0; Tbio.
DR   PRO; PR:Q2M1V0; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; Q2M1V0; protein.
DR   Bgee; ENSG00000175329; Expressed in ileal mucosa and 25 other tissues.
DR   Genevisible; Q2M1V0; HS.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0048484; P:enteric nervous system development; IBA:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd00086; homeodomain; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   Pfam; PF00046; Homeodomain; 1.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; SSF46689; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
PE   1: Evidence at protein level;
KW   Activator; DNA-binding; Homeobox; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..245
FT                   /note="Intestine-specific homeobox"
FT                   /id="PRO_0000288602"
FT   DNA_BIND        82..141
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          38..86
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        38..54
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        72..86
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         28
FT                   /note="S -> G (in dbSNP:rs361863)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_032448"
FT   VARIANT         57
FT                   /note="P -> S (in dbSNP:rs362090)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_032449"
FT   VARIANT         83
FT                   /note="R -> Q (in dbSNP:rs8140287)"
FT                   /id="VAR_032450"
FT   VARIANT         158
FT                   /note="A -> V (in dbSNP:rs7291048)"
FT                   /id="VAR_032451"
SQ   SEQUENCE   245 AA;  27011 MW;  361FB0447DC6C02D CRC64;
     MCAEVGPALC RGMERNSLGC CEAPKKLSLS FSIEAILKRP ARRSDMDRPE GPGEEGPGEA
     AASGSGLEKP PKDQPQEGRK SKRRVRTTFT TEQLHELEKI FHFTHYPDVH IRSQLAARIN
     LPEARVQIWF QNQRAKWRKQ EKIGNLGAPQ QLSEASVALP TNLDVAGPTW TSTALRRLAP
     PTSCCPSAQD QLASAWFPAW ITLLPAHPWE TQPVPGLPIH QTCIPVLCIL PPPHPKWGSI
     CATST