HHEX_XENLA
ID HHEX_XENLA Reviewed; 272 AA.
AC O13023;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Hematopoietically-expressed homeobox protein hhex;
DE Short=Homeobox protein hex;
DE Short=XHex;
DE AltName: Full=Hhex-A protein;
GN Name=hhex {ECO:0000250|UniProtKB:P43120};
GN Synonyms=hex {ECO:0000303|PubMed:9376326}, hhex-a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB82335.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Heart {ECO:0000312|EMBL:AAB82335.1};
RX PubMed=9376326; DOI=10.1016/s0925-4773(97)00092-0;
RA Newman C.S., Chia F., Krieg P.A.;
RT "The XHex homeobox gene is expressed during development of the vascular
RT endothelium: overexpression leads to an increase in vascular endothelial
RT cell number.";
RL Mech. Dev. 66:83-93(1997).
RN [2] {ECO:0000312|EMBL:AAH59320.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen {ECO:0000312|EMBL:AAH59320.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10508583; DOI=10.1016/s0960-9822(99)80421-7;
RA Jones C.M., Broadbent J., Thomas P.Q., Smith J.C., Beddington R.S.P.;
RT "An anterior signalling centre in Xenopus revealed by the homeobox gene
RT XHex.";
RL Curr. Biol. 9:946-954(1999).
RN [4] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10328921; DOI=10.1006/dbio.1999.9257;
RA Zorn A.M., Butler K., Gurdon J.B.;
RT "Anterior endomesoderm specification in Xenopus by Wnt/beta-catenin and
RT TGF-beta signalling pathways.";
RL Dev. Biol. 209:282-297(1999).
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=11335125; DOI=10.1016/s0925-4773(01)00341-0;
RA Zorn A.M., Mason J.;
RT "Gene expression in the embryonic Xenopus liver.";
RL Mech. Dev. 103:153-157(2001).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=12464432; DOI=10.1016/s0925-4773(02)00361-1;
RA Smithers L.E., Jones C.M.;
RT "Xhex-expressing endodermal tissues are essential for anterior patterning
RT in Xenopus.";
RL Mech. Dev. 119:191-200(2002).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=15687261; DOI=10.1101/gad.1279405;
RA Foley A.C., Mercola M.;
RT "Heart induction by Wnt antagonists depends on the homeodomain
RT transcription factor Hex.";
RL Genes Dev. 19:387-396(2005).
RN [8] {ECO:0000305}
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).
CC -!- FUNCTION: Recognizes the DNA sequence 5'-ATTAA-3'. Transcriptional
CC repressor. Regulates the differentiation of both endothelial and blood
CC cells (By similarity). Probably plays a role in the proliferation of
CC vascular endothelial cells during blood vessel development. 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/nr1 and nodal2/nr2. May
CC play a role in liver development. Induces heart development.
CC {ECO:0000250|UniProtKB:Q05502, ECO:0000250|UniProtKB:Q9IAV3,
CC ECO:0000269|PubMed:10328921, ECO:0000269|PubMed:10508583,
CC ECO:0000269|PubMed:12464432, ECO:0000269|PubMed:15687261,
CC ECO:0000269|PubMed:16936074, ECO:0000269|PubMed:9376326}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: First expressed in the dorsal endomesoderm of the
CC gastrula stage embryo. The dorsal endomesoderm contributes to forming
CC the embryonic liver, and expression continues in the liver throughout
CC development. Also expressed in precursors of the developing thyroid
CC gland, and beginning at the tailbud stage, expressed in the ventral
CC region of the head. Also transiently expressed in the endothelial layer
CC of developing vascular tissues of the embryo, beginning at the tailbud
CC stages. {ECO:0000269|PubMed:10328921, ECO:0000269|PubMed:10508583,
CC ECO:0000269|PubMed:11335125, ECO:0000269|PubMed:9376326}.
CC -!- DEVELOPMENTAL STAGE: Expressed zygotically. During gastrulation,
CC expression levels rise rapidly to peak at about stage 10.5. Following
CC gastrulation, levels decrease slightly and then increase again during
CC early tailbud stages, with expression continuing throughout embryonic
CC development. {ECO:0000269|PubMed:9376326}.
CC -!- INDUCTION: By maternal wnt-beta-catenin signaling and tgf-beta
CC signaling. {ECO:0000269|PubMed:10328921, ECO:0000269|PubMed:10508583}.
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DR EMBL; U94837; AAB82335.1; -; mRNA.
DR EMBL; BC059320; AAH59320.1; -; mRNA.
DR RefSeq; NP_001079059.1; NM_001085590.1.
DR AlphaFoldDB; O13023; -.
DR SMR; O13023; -.
DR GeneID; 373590; -.
DR KEGG; xla:373590; -.
DR CTD; 373590; -.
DR Xenbase; XB-GENE-865680; hhex.L.
DR OMA; AGPLYPF; -.
DR OrthoDB; 1596695at2759; -.
DR Proteomes; UP000186698; Chromosome 7L.
DR Bgee; 373590; Expressed in liver and 15 other tissues.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:UniProtKB.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0001889; P:liver development; IEP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IMP:UniProtKB.
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 2: Evidence at transcript level;
KW Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Wnt signaling pathway.
FT CHAIN 1..272
FT /note="Hematopoietically-expressed homeobox protein hhex"
FT /id="PRO_0000326220"
FT DNA_BIND 137..196
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 222..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 234..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 272 AA; 30576 MW; 15FC2FDBBCAFFF6E CRC64;
MQYQHPSSSA LGLSVPLFAP TPLQHPTPFY IDDILGRNSA SNGTPALPTP TLPSPNSSFT
SLVATYRTPI YEPTPIHPAF THPGAALAAS YGASTYASPL YPFSRPVSDY THALIRHDSL
GKPLLWSPFI QRPLHKRKGG QVRFSNDQTI ELEKKFETQK YLSPPERKRL AKMLQLSERQ
VKTWFQNRRA KWRRLKQENP QGNKKDETES LENICEESQE RCLSAEQKSR ESSLDDPTSS
PTSQGNLDSE VSDDSDQEVD IEGDKGYYNC AH
