HHEX_MOUSE
ID HHEX_MOUSE Reviewed; 271 AA.
AC P43120; Q544N6; Q9CRV1; Q9R1X2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Hematopoietically-expressed homeobox protein Hhex;
DE Short=Homeobox protein HEX;
DE Short=mHex;
DE AltName: Full=Homeobox protein PRH;
GN Name=Hhex; Synonyms=Prh, Prhx;
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 [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=8096636; DOI=10.1093/nar/21.5.1245;
RA Bedford F.K., Ashworth A., Enver T., Wiedemann L.M.;
RT "HEX: a novel homeobox gene expressed during haematopoiesis and conserved
RT between mouse and human.";
RL Nucleic Acids Res. 21:1245-1249(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RX PubMed=10101294; DOI=10.1093/oxfordjournals.jbchem.a022351;
RA Myint Z., Inazu T., Tanaka T., Yamada K., Keng V.W., Inoue Y., Kuriyama M.,
RA Noguchi T.;
RT "Genomic organization and promoter analysis of a mouse homeobox gene,
RT Hex.";
RL J. Biochem. 125:795-802(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RX PubMed=10501975; DOI=10.1007/s003359901152;
RA Ghosh B., Jacobs H.C., Wiedemann L.M., Brown A., Bedford F.K.,
RA Nimmakayalu M.A., Ward D.C., Bogue C.W.;
RT "Genomic structure, cDNA mapping, and chromosomal localization of the mouse
RT homeobox gene, Hex.";
RL Mamm. Genome 10:1023-1025(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum, and Head;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [6]
RP FUNCTION.
RX PubMed=10804173; DOI=10.1242/dev.127.11.2303;
RA Brickman J.M., Jones C.M., Clements M., Smith J.C., Beddington R.S.P.;
RT "Hex is a transcriptional repressor that contributes to anterior identity
RT and suppresses Spemann organiser function.";
RL Development 127:2303-2315(2000).
RN [7]
RP FUNCTION.
RX PubMed=16936074; DOI=10.1242/dev.02516;
RA Zamparini A.L., Watts T., Gardner C.E., Tomlinson S.R., Johnston G.I.,
RA Brickman J.M.;
RT "Hex acts with beta-catenin to regulate anteroposterior patterning via a
RT Groucho-related co-repressor and Nodal.";
RL Development 133:3709-3722(2006).
RN [8]
RP INTERACTION WITH SOX13.
RX PubMed=20028982; DOI=10.1074/jbc.m109.046649;
RA Marfil V., Moya M., Pierreux C.E., Castell J.V., Lemaigre F.P., Real F.X.,
RA Bort R.;
RT "Interaction between Hhex and SOX13 modulates Wnt/TCF activity.";
RL J. Biol. Chem. 285:5726-5737(2010).
RN [9]
RP INTERACTION WITH CD81, AND SUBCELLULAR LOCATION.
RX PubMed=23665349; DOI=10.1016/j.ajpath.2013.03.013;
RA Bhave V.S., Mars W., Donthamsetty S., Zhang X., Tan L., Luo J., Bowen W.C.,
RA Michalopoulos G.K.;
RT "Regulation of liver growth by glypican 3, CD81, hedgehog, and Hhex.";
RL Am. J. Pathol. 183:153-159(2013).
CC -!- FUNCTION: Recognizes the DNA sequence 5'-ATTAA-3' (PubMed:10804173).
CC Transcriptional repressor (PubMed:10804173). Activator of WNT-mediated
CC transcription in conjunction with CTNNB1 (PubMed:16936074). Establishes
CC anterior identity at two levels; acts early to enhance canonical WNT-
CC signaling by repressing expression of TLE4, and acts later to inhibit
CC NODAL-signaling by directly targeting NODAL (PubMed:16936074). May play
CC a role in hematopoietic differentiation (PubMed:8096636).
CC {ECO:0000269|PubMed:10804173, ECO:0000269|PubMed:16936074,
CC ECO:0000269|PubMed:8096636}.
CC -!- SUBUNIT: Interacts with CD81; the interaction prevents nuclear
CC translocation of HHEX (PubMed:23665349). Interacts (via N-terminus)
CC with SOX13; abolishes the SOX13-mediated inhibition of WNT-mediated
CC transcriptional activity via competitive inhibition of the SOX13-TCF7
CC complex (PubMed:20028982). {ECO:0000269|PubMed:20028982,
CC ECO:0000269|PubMed:23665349}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23665349}.
CC -!- DEVELOPMENTAL STAGE: Expressed during hematopoiesis.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB29163.1; Type=Frameshift; Evidence={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; Z21524; CAA79729.1; -; Genomic_DNA.
DR EMBL; AB017132; BAA76714.1; -; Genomic_DNA.
DR EMBL; AF132550; AAF04349.1; -; Genomic_DNA.
DR EMBL; AK014111; BAB29163.1; ALT_FRAME; mRNA.
DR EMBL; AK033664; BAC28416.1; -; mRNA.
DR EMBL; BC057986; AAH57986.1; -; mRNA.
DR CCDS; CCDS29778.1; -.
DR PIR; S30230; S30230.
DR RefSeq; NP_032271.1; NM_008245.3.
DR AlphaFoldDB; P43120; -.
DR SMR; P43120; -.
DR BioGRID; 200297; 7.
DR IntAct; P43120; 2.
DR STRING; 10090.ENSMUSP00000025944; -.
DR iPTMnet; P43120; -.
DR PhosphoSitePlus; P43120; -.
DR MaxQB; P43120; -.
DR PaxDb; P43120; -.
DR PRIDE; P43120; -.
DR ProteomicsDB; 273338; -.
DR DNASU; 15242; -.
DR Ensembl; ENSMUST00000025944; ENSMUSP00000025944; ENSMUSG00000024986.
DR GeneID; 15242; -.
DR KEGG; mmu:15242; -.
DR UCSC; uc008hio.1; mouse.
DR CTD; 3087; -.
DR MGI; MGI:96086; Hhex.
DR VEuPathDB; HostDB:ENSMUSG00000024986; -.
DR eggNOG; KOG0483; Eukaryota.
DR GeneTree; ENSGT00940000164435; -.
DR HOGENOM; CLU_081944_0_0_1; -.
DR InParanoid; P43120; -.
DR OMA; AGPLYPF; -.
DR OrthoDB; 1596695at2759; -.
DR PhylomeDB; P43120; -.
DR TreeFam; TF325047; -.
DR BioGRID-ORCS; 15242; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Ccdc39; mouse.
DR PRO; PR:P43120; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P43120; protein.
DR Bgee; ENSMUSG00000024986; Expressed in foregut-midgut junction and 141 other tissues.
DR ExpressionAtlas; P43120; baseline and differential.
DR Genevisible; P43120; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032993; C:protein-DNA complex; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0008301; F:DNA binding, bending; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; ISO:MGI.
DR GO; GO:0071837; F:HMG box domain binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IMP:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; ISO:MGI.
DR GO; GO:0061009; P:common bile duct development; IMP:MGI.
DR GO; GO:0071103; P:DNA conformation change; ISO:MGI.
DR GO; GO:0035050; P:embryonic heart tube development; IMP:MGI.
DR GO; GO:0048568; P:embryonic organ development; IMP:MGI.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0048853; P:forebrain morphogenesis; IMP:MGI.
DR GO; GO:0061010; P:gall bladder development; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0061011; P:hepatic duct development; IMP:MGI.
DR GO; GO:0061017; P:hepatoblast differentiation; IMP:MGI.
DR GO; GO:0070365; P:hepatocyte differentiation; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0022027; P:interkinetic nuclear migration; IMP:MGI.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IMP:MGI.
DR GO; GO:0006406; P:mRNA export from nucleus; ISO:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0002573; P:myeloid leukocyte differentiation; IMP:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0031016; P:pancreas development; IMP:MGI.
DR GO; GO:0016973; P:poly(A)+ mRNA export from nucleus; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0060431; P:primary lung bud formation; IMP:MGI.
DR GO; GO:0090009; P:primitive streak formation; IMP:MGI.
DR GO; GO:0034504; P:protein localization to nucleus; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0070663; P:regulation of leukocyte proliferation; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IMP:MGI.
DR GO; GO:0030878; P:thyroid gland development; IMP:MGI.
DR GO; GO:0048729; P:tissue morphogenesis; IMP:MGI.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
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 Developmental protein; Differentiation; DNA-binding; Homeobox; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Wnt signaling pathway.
FT CHAIN 1..271
FT /note="Hematopoietically-expressed homeobox protein Hhex"
FT /id="PRO_0000049075"
FT DNA_BIND 138..197
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..138
FT /note="Interaction with SOX13"
FT /evidence="ECO:0000250|UniProtKB:Q03014"
FT REGION 138..271
FT /note="Required for WNT signaling induction"
FT /evidence="ECO:0000250|UniProtKB:Q03014"
FT REGION 195..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..212
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..246
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03014"
FT CONFLICT 10
FT /note="A -> L (in Ref. 4; BAB29163)"
FT /evidence="ECO:0000305"
FT CONFLICT 33
FT /note="F -> L (in Ref. 2; BAA76714)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 271 AA; 29987 MW; 376765557A71C962 CRC64;
MQFPHPGPAA APAVGVPLYA PTPLLQPAHP TPFYIDDILG RGPAAPTPTP TLPSPNSSFT
SLVSSYRTPV YEPTPVHPAF SHHPAAALAA AYGPSGFGGP LYPFPRTVND YTHALLRHDP
LGKPLLWSPF LQRPLHKRKG GQVRFSNDQT VELEKKFETQ KYLSPPERKR LAKMLQLSER
QVKTWFQNRR AKWRRLKQEN PQSNKKDALD SLDTSCEQGQ DLPSEQNKGA SLDRSQCSPS
PASQEDPDSE ISEDSDQEVD IEGDKGYFNA G
