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Hematopoietically-expressed homeobox protein HHEX (Homeobox protein HEX) (Homeobox protein PRH)

 HHEX_HUMAN              Reviewed;         270 AA.
Q03014; B1AQ17; Q96CE9;
01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
01-JUN-1994, sequence version 1.
31-JAN-2018, entry version 174.
RecName: Full=Hematopoietically-expressed homeobox protein HHEX;
Short=Homeobox protein HEX;
AltName: Full=Homeobox protein PRH;
Name=HHEX; Synonyms=HEX, PRH, PRHX;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=1360645; DOI=10.1093/nar/20.21.5661;
Crompton M.R., Bartlett T.J., Macgregor A.D., Manfioletti G.,
Buratti E., Giancotti V., Goodwin G.H.;
"Identification of a novel vertebrate homeobox gene expressed in
haematopoietic cells.";
Nucleic Acids Res. 20:5661-5667(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=Myeloid leukemia cell;
PubMed=8103988; DOI=10.1006/bbrc.1993.2140;
Hromas R.A., Collins S.J., Radich J.;
"PCR cloning of an orphan homeobox gene (PRH) preferentially expressed
in myeloid and liver cells.";
Biochem. Biophys. Res. Commun. 195:976-983(1993).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Mammary gland;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15164054; DOI=10.1038/nature02462;
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 10.";
Nature 429:375-381(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Bone marrow, and Uterus;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 122-270, AND TISSUE SPECIFICITY.
TISSUE=Leukemia, and Peripheral blood monocyte;
PubMed=8096636; DOI=10.1093/nar/21.5.1245;
Bedford F.K., Ashworth A., Enver T., Wiedemann L.M.;
"HEX: a novel homeobox gene expressed during haematopoiesis and
conserved between mouse and human.";
Nucleic Acids Res. 21:1245-1249(1993).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[9]
3D-STRUCTURE MODELING OF 136-196.
PubMed=7911091; DOI=10.1016/0014-5793(94)00446-3;
Neidle S., Goodwin G.H.;
"A homology-based molecular model of the proline-rich homeodomain
protein Prh, from haematopoietic cells.";
FEBS Lett. 345:93-98(1994).
[10]
STRUCTURE BY NMR OF 138-194.
RIKEN structural genomics initiative (RSGI);
"Solution structure of RSGI RUH-028, a homeobox domain from human.";
Submitted (NOV-2006) to the PDB data bank.
-!- FUNCTION: Recognizes the DNA sequence 5'-ATTAA-3'. Transcriptional
repressor. May play a role in hematopoietic differentiation.
Establishes anterior identity at two levels; acts early to enhance
canonical WNT-signaling by repressing expression of TLE4, and acts
later to inhibit NODAL-signaling by directly targeting NODAL (By
similarity). {ECO:0000250}.
-!- INTERACTION:
Q5VWX1:KHDRBS2; NbExp=4; IntAct=EBI-747421, EBI-742808;
P60370:KRTAP10-5; NbExp=3; IntAct=EBI-747421, EBI-10172150;
P60371:KRTAP10-6; NbExp=4; IntAct=EBI-747421, EBI-12012928;
P60409:KRTAP10-7; NbExp=3; IntAct=EBI-747421, EBI-10172290;
P60410:KRTAP10-8; NbExp=5; IntAct=EBI-747421, EBI-10171774;
O75690:KRTAP5-8; NbExp=4; IntAct=EBI-747421, EBI-12134621;
Q7Z3S9:NOTCH2NL; NbExp=4; IntAct=EBI-747421, EBI-945833;
Q05BL1:TP53BP2; NbExp=4; IntAct=EBI-747421, EBI-11952721;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
-!- TISSUE SPECIFICITY: Liver and promyelocytic leukemia cell line HL-
60. {ECO:0000269|PubMed:1360645, ECO:0000269|PubMed:8096636,
ECO:0000269|PubMed:8103988}.
-!- DEVELOPMENTAL STAGE: Expressed during hematopoiesis.
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EMBL; X67235; CAA47661.1; -; mRNA.
EMBL; L16499; AAA02988.1; -; mRNA.
EMBL; AK314891; BAG37405.1; -; mRNA.
EMBL; AL590080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471066; EAW50087.1; -; Genomic_DNA.
EMBL; CH471066; EAW50088.1; -; Genomic_DNA.
EMBL; BC014336; AAH14336.1; -; mRNA.
EMBL; BC015110; AAH15110.1; -; mRNA.
EMBL; BC050638; AAH50638.1; -; mRNA.
EMBL; Z21533; CAA79730.1; -; mRNA.
CCDS; CCDS7423.1; -.
PIR; JN0767; JN0767.
RefSeq; NP_002720.1; NM_002729.4.
UniGene; Hs.118651; -.
PDB; 2E1O; NMR; -; A=138-194.
PDBsum; 2E1O; -.
ProteinModelPortal; Q03014; -.
SMR; Q03014; -.
BioGrid; 109335; 10.
IntAct; Q03014; 25.
MINT; MINT-1439118; -.
STRING; 9606.ENSP00000282728; -.
iPTMnet; Q03014; -.
PhosphoSitePlus; Q03014; -.
BioMuta; HHEX; -.
DMDM; 547658; -.
EPD; Q03014; -.
MaxQB; Q03014; -.
PaxDb; Q03014; -.
PeptideAtlas; Q03014; -.
PRIDE; Q03014; -.
DNASU; 3087; -.
Ensembl; ENST00000282728; ENSP00000282728; ENSG00000152804.
GeneID; 3087; -.
KEGG; hsa:3087; -.
UCSC; uc001kid.4; human.
CTD; 3087; -.
DisGeNET; 3087; -.
EuPathDB; HostDB:ENSG00000152804.10; -.
GeneCards; HHEX; -.
HGNC; HGNC:4901; HHEX.
HPA; HPA051894; -.
HPA; HPA055460; -.
MIM; 604420; gene.
neXtProt; NX_Q03014; -.
OpenTargets; ENSG00000152804; -.
PharmGKB; PA29274; -.
eggNOG; KOG0483; Eukaryota.
eggNOG; ENOG410Z2UE; LUCA.
GeneTree; ENSGT00890000139333; -.
HOGENOM; HOG000049110; -.
HOVERGEN; HBG055460; -.
InParanoid; Q03014; -.
KO; K08024; -.
OMA; DNSCDQR; -.
OrthoDB; EOG091G0RNV; -.
PhylomeDB; Q03014; -.
TreeFam; TF325047; -.
EvolutionaryTrace; Q03014; -.
GeneWiki; HHEX; -.
GenomeRNAi; 3087; -.
PRO; PR:Q03014; -.
Proteomes; UP000005640; Chromosome 10.
Bgee; ENSG00000152804; -.
CleanEx; HS_HHEX; -.
ExpressionAtlas; Q03014; baseline and differential.
Genevisible; Q03014; HS.
GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
GO; GO:0032993; C:protein-DNA complex; IDA:BHF-UCL.
GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
GO; GO:0008301; F:DNA binding, bending; IDA:BHF-UCL.
GO; GO:0008190; F:eukaryotic initiation factor 4E binding; IDA:BHF-UCL.
GO; GO:0071837; F:HMG box domain binding; IEA:Ensembl.
GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
GO; GO:0070491; F:repressing transcription factor binding; IDA:BHF-UCL.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0017025; F:TBP-class protein binding; TAS:BHF-UCL.
GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL.
GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0009952; P:anterior/posterior pattern specification; ISS:UniProtKB.
GO; GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
GO; GO:0008283; P:cell proliferation; IDA:BHF-UCL.
GO; GO:0071103; P:DNA conformation change; IDA:BHF-UCL.
GO; GO:0035050; P:embryonic heart tube development; IEA:Ensembl.
GO; GO:0007492; P:endoderm development; IEA:Ensembl.
GO; GO:0048853; P:forebrain morphogenesis; IEA:Ensembl.
GO; GO:0061010; P:gall bladder development; IEA:Ensembl.
GO; GO:0061011; P:hepatic duct development; IEA:Ensembl.
GO; GO:0061017; P:hepatoblast differentiation; IEA:Ensembl.
GO; GO:0070365; P:hepatocyte differentiation; IEA:Ensembl.
GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
GO; GO:0022027; P:interkinetic nuclear migration; IEA:Ensembl.
GO; GO:0006406; P:mRNA export from nucleus; IDA:BHF-UCL.
GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
GO; GO:0002573; P:myeloid leukocyte differentiation; IEA:Ensembl.
GO; GO:0016525; P:negative regulation of angiogenesis; ISS:BHF-UCL.
GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; TAS:BHF-UCL.
GO; GO:0010621; P:negative regulation of transcription by transcription factor localization; IC:BHF-UCL.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; ISS:BHF-UCL.
GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
GO; GO:0031016; P:pancreas development; IEA:Ensembl.
GO; GO:0016973; P:poly(A)+ mRNA export from nucleus; IMP:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
GO; GO:0060431; P:primary lung bud formation; IEA:Ensembl.
GO; GO:0090009; P:primitive streak formation; IEA:Ensembl.
GO; GO:0034504; P:protein localization to nucleus; IDA:BHF-UCL.
GO; GO:0042127; P:regulation of cell proliferation; IEA:Ensembl.
GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
GO; GO:0009611; P:response to wounding; IEA:Ensembl.
GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
Pfam; PF00046; Homeobox; 1.
PRINTS; PR00024; HOMEOBOX.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Developmental protein;
Differentiation; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
Reference proteome; Repressor; Transcription;
Transcription regulation; Wnt signaling pathway.
CHAIN 1 270 Hematopoietically-expressed homeobox
protein HHEX.
/FTId=PRO_0000049074.
DNA_BIND 137 196 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
COMPBIAS 1 133 Pro-rich.
MOD_RES 53 53 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
CONFLICT 115 115 L -> V (in Ref. 2; AAA02988).
{ECO:0000305}.
CONFLICT 171 171 A -> T (in Ref. 6; AAH14336).
{ECO:0000305}.
HELIX 146 158 {ECO:0000244|PDB:2E1O}.
HELIX 164 173 {ECO:0000244|PDB:2E1O}.
HELIX 178 194 {ECO:0000244|PDB:2E1O}.
SEQUENCE 270 AA; 30022 MW; 9C16BB6D494475FC CRC64;
MQYPHPGPAA GAVGVPLYAP TPLLQPAHPT PFYIEDILGR GPAAPTPAPT LPSPNSSFTS
LVSPYRTPVY EPTPIHPAFS HHSAAALAAA YGPGGFGGPL YPFPRTVNDY THALLRHDPL
GKPLLWSPFL QRPLHKRKGG QVRFSNDQTI ELEKKFETQK YLSPPERKRL AKMLQLSERQ
VKTWFQNRRA KWRRLKQENP QSNKKEELES LDSSCDQRQD LPSEQNKGAS LDSSQCSPSP
ASQEDLESEI SEDSDQEVDI EGDKSYFNAG


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18-003-43167 Diencephalon_mesencephalon homeobox protein 1 - Diencephalon_mesencephalon-expressed brain homeobox gene 1 protein; Paired-like homeobox protein DMBX1; Paired-type homeobox Atx; Orthodenticle homolog 0.05 mg Aff Pur
EIAAB42542 Enteric neuron homeobox protein,Enx,Homeobox protein Hox-11L1,Homeobox TLX-2,Hox11L.1,Hox11l1,Mouse,Mus musculus,Ncx,PMUR10F,T-cell leukemia homeobox protein 2,Tlx1l1,Tlx2
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EIAAB27309 Cardiac-specific homeobox,Csx,Homeobox protein CSX,Homeobox protein NK-2 homolog E,Homeobox protein Nkx-2.5,Mouse,Mus musculus,Nkx-2.5,Nkx2-5,Nkx2e
GWB-63D05D Anti- HHEX (hematopoietically expressed homeobox) Antibody
EIAAB11459 Cdmx,Diencephalon_mesencephalon homeobox protein 1,Diencephalon_mesencephalon-expressed brain homeobox gene 1 protein,Dmbx1,Mbx,Mouse,Mus musculus,Orthodenticle homolog 3,Otx3,Paired-like homeobox pro
EIAAB31193 BFT,Hindlimb-expressed homeobox protein backfoot,Homeobox protein PITX1,Homo sapiens,Human,Paired-like homeodomain transcription factor 1,Pituitary homeobox 1,PITX1,PTX1
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EIAAB27310 Cardiac-specific homeobox,CSX,Homeobox protein CSX,Homeobox protein NK-2 homolog E,Homeobox protein Nkx-2.5,Homo sapiens,Human,NKX2.5,NKX2-5,NKX2E
EIAAB11440 Beta protein 1,BP1,DLX4,DLX7,DLX8,DLX9,Homeobox protein DLX-4,Homeobox protein DLX-7,Homeobox protein DLX-8,Homo sapiens,Human
E14429h Human Hematopoietically Expressed Homeobox Protein 96T
EIAAB42541 Homeobox protein Hox-11L1,Homo sapiens,HOX11L1,Human,NCX,Neural crest homeobox protein,T-cell leukemia homeobox protein 2,TLX2


 

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