ISX_MOUSE
ID ISX_MOUSE Reviewed; 240 AA.
AC A1A546; A1A545; Q9D2Z0;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Intestine-specific homeobox;
GN Name=Isx;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cecum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [3]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16971476; DOI=10.1242/dev.02537;
RA Choi M.Y., Romer A.I., Hu M., Lepourcelet M., Mechoor A., Yesilaltay A.,
RA Krieger M., Gray P.A., Shivdasani R.A.;
RT "A dynamic expression survey identifies transcription factors relevant in
RT mouse digestive tract development.";
RL Development 133:4119-4129(2006).
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18093975; DOI=10.1074/jbc.m707928200;
RA Seino Y., Miki T., Kiyonari H., Abe T., Fujimoto W., Kimura K.,
RA Takeuchi A., Takahashi Y., Oiso Y., Iwanaga T., Seino S.;
RT "Isx participates in the maintenance of vitamin A metabolism by regulation
RT of beta-carotene 15,15'-monooxygenase (Bcmo1) expression.";
RL J. Biol. Chem. 283:4905-4911(2008).
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.
CC {ECO:0000269|PubMed:16971476, ECO:0000269|PubMed:18093975}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A1A546-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A1A546-2; Sequence=VSP_025717;
CC -!- TISSUE SPECIFICITY: Expressed in intestinal epithelial cells from the
CC duodenum to the proximal colon. {ECO:0000269|PubMed:16971476,
CC ECO:0000269|PubMed:18093975}.
CC -!- DEVELOPMENTAL STAGE: Appears late in development, just before the
CC villus transition in intestine morphogenesis. Restricted to the
CC epithelial compartment in both adult and fetal intestine.
CC {ECO:0000269|PubMed:16971476}.
CC -!- DISRUPTION PHENOTYPE: Mice appear healthy for at least 1 year and
CC display normal histological features in the gut. They however show
CC defects in intestinal gene expression with a dysregulation of the
CC scavenger receptor Scarb1. {ECO:0000269|PubMed:16971476}.
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DR EMBL; AK018615; BAB31309.1; -; mRNA.
DR EMBL; BC128289; AAI28290.2; -; mRNA.
DR EMBL; BC128290; AAI28291.2; -; mRNA.
DR CCDS; CCDS40391.1; -. [A1A546-1]
DR CCDS; CCDS80899.1; -. [A1A546-2]
DR RefSeq; NP_001281207.1; NM_001294278.1. [A1A546-2]
DR RefSeq; NP_082113.2; NM_027837.3. [A1A546-1]
DR AlphaFoldDB; A1A546; -.
DR SMR; A1A546; -.
DR STRING; 10090.ENSMUSP00000034034; -.
DR iPTMnet; A1A546; -.
DR PhosphoSitePlus; A1A546; -.
DR PaxDb; A1A546; -.
DR PRIDE; A1A546; -.
DR Antibodypedia; 25329; 75 antibodies from 16 providers.
DR Ensembl; ENSMUST00000034034; ENSMUSP00000034034; ENSMUSG00000031621. [A1A546-1]
DR Ensembl; ENSMUST00000174427; ENSMUSP00000134368; ENSMUSG00000031621. [A1A546-2]
DR GeneID; 71597; -.
DR KEGG; mmu:71597; -.
DR UCSC; uc009mgv.1; mouse. [A1A546-1]
DR UCSC; uc012ggb.1; mouse. [A1A546-2]
DR CTD; 91464; -.
DR MGI; MGI:1918847; Isx.
DR VEuPathDB; HostDB:ENSMUSG00000031621; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000161702; -.
DR HOGENOM; CLU_079373_0_0_1; -.
DR InParanoid; A1A546; -.
DR OMA; WETQPLP; -.
DR OrthoDB; 1270742at2759; -.
DR PhylomeDB; A1A546; -.
DR TreeFam; TF315976; -.
DR BioGRID-ORCS; 71597; 2 hits in 74 CRISPR screens.
DR PRO; PR:A1A546; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; A1A546; protein.
DR Bgee; ENSMUSG00000031621; Expressed in small intestine Peyer's patch and 26 other tissues.
DR ExpressionAtlas; A1A546; baseline and differential.
DR Genevisible; A1A546; MM.
DR GO; GO:0005634; C:nucleus; IC:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IMP:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0048484; P:enteric nervous system development; IBA:GO_Central.
DR GO; GO:1904479; P:negative regulation of intestinal absorption; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:1901738; P:regulation of vitamin A metabolic process; IMP:MGI.
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 2: Evidence at transcript level;
KW Activator; Alternative splicing; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..240
FT /note="Intestine-specific homeobox"
FT /id="PRO_0000288603"
FT DNA_BIND 78..137
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 36..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 67..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 150..240
FT /note="EAGLALPSNMDVSGPVLTPTAMTTLVPPTECCLLSQTQLPSSWFPTQIPLVP
FT WHPWDLQPLPGPLTQHPCVPTFMFPPLHPKWGSICATST -> SCADTHCYDYIGTSHR
FT MLPTLSDSAPFKLVPYTDSPCPMAPMGPTAPAWPSHPASLCPYLHVPTPTPQVGQHLCN
FT FNIGTDFSLSKQATLLSQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025717"
FT CONFLICT 176
FT /note="P -> L (in Ref. 1; BAB31309)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 240 AA; 27169 MW; C7BFA37A5950FA1B CRC64;
MAGPTIHRDM EKSSGYCEAP ENLGLSFSIE AILKKPTERR SLPRPQSICK EDSRQTTIPG
SKLERPPQDQ PQEEKKNKRR VRTTFTTEQL QELEKLFHFT HYPDIHVRSQ LASRINLPEA
RVQIWFQNQR AKWRKQEKSG NLSAPQQPGE AGLALPSNMD VSGPVLTPTA MTTLVPPTEC
CLLSQTQLPS SWFPTQIPLV PWHPWDLQPL PGPLTQHPCV PTFMFPPLHP KWGSICATST