Full text data of PBX1
PBX1
(PRL)
[Confidence: low (only semi-automatic identification from reviews)]
Pre-B-cell leukemia transcription factor 1 (Homeobox protein PBX1; Homeobox protein PRL)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Pre-B-cell leukemia transcription factor 1 (Homeobox protein PBX1; Homeobox protein PRL)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P40424
ID PBX1_HUMAN Reviewed; 430 AA.
AC P40424; B4DSC1; F5H4U9; Q5T488;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Pre-B-cell leukemia transcription factor 1;
DE AltName: Full=Homeobox protein PBX1;
DE AltName: Full=Homeobox protein PRL;
GN Name=PBX1; Synonyms=PRL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PBX1A).
RX PubMed=1682799;
RA Monica K., Galili N., Nourse J., Saltman D., Cleary M.L.;
RT "PBX2 and PBX3, new homeobox genes with extensive homology to the
RT human proto-oncogene PBX1.";
RL Mol. Cell. Biol. 11:6149-6157(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM PBX1A).
RX PubMed=11267683; DOI=10.1016/S0167-4781(01)00189-0;
RA Thameem F., Wolford J.K., Bogardus C., Prochazka M.;
RT "Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in
RT Pima Indians.";
RL Biochim. Biophys. Acta 1518:215-220(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT
RP SER-31.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PBX1A).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 89-430, AND CHROMOSOMAL TRANSLOCATION
RP WITH TCF3.
RX PubMed=1967983; DOI=10.1016/0092-8674(90)90658-2;
RA Kamps M.P., Murre C., Sun X.-H., Baltimore D.;
RT "A new homeobox gene contributes the DNA binding domain of the t(1;19)
RT translocation protein in pre-B ALL.";
RL Cell 60:547-555(1990).
RN [7]
RP CHROMOSOMAL TRANSLOCATION WITH TCF3.
RX PubMed=1671560;
RA Hunger S.P., Galili N., Carroll A.J., Crist W.M., Link M.P.,
RA Cleary M.L.;
RT "The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1
RT coding sequences in acute lymphoblastic leukemias.";
RL Blood 77:687-693(1991).
RN [8]
RP CHARACTERIZATION.
RX PubMed=8327485; DOI=10.1073/pnas.90.13.6061;
RA van Dijk M.A., Voorhoeve P.M., Murre C.;
RT "Pbx1 is converted into a transcriptional activator upon acquiring the
RT N-terminal region of E2A in pre-B-cell acute lymphoblastoid
RT leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6061-6065(1993).
RN [9]
RP CHARACTERIZATION.
RX PubMed=7910944;
RA Lu Q., Wright D.D., Kamps M.P.;
RT "Fusion with E2A converts the Pbx1 homeodomain protein into a
RT constitutive transcriptional activator in human leukemias carrying the
RT t(1;19) translocation.";
RL Mol. Cell. Biol. 14:3938-3948(1994).
RN [10]
RP INTERACTION WITH PBXIP1.
RX PubMed=10825160; DOI=10.1074/jbc.M001323200;
RA Abramovich C., Shen W.-F., Pineault N., Imren S., Montpetit B.,
RA Largman C., Humphries R.K.;
RT "Functional cloning and characterization of a novel nonhomeodomain
RT protein that inhibits the binding of PBX1-HOX complexes to DNA.";
RL J. Biol. Chem. 275:26172-26177(2000).
RN [11]
RP FUNCTION, AND INTERACTION WITH MEIS1.
RX PubMed=12609849; DOI=10.1182/blood-2002-02-0380;
RA Okada Y., Nagai R., Sato T., Matsuura E., Minami T., Morita I.,
RA Doi T.;
RT "Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific
RT transcription of the platelet factor 4 gene.";
RL Blood 101:4748-4756(2003).
RN [12]
RP INTERACTION WITH MEIS2.
RX PubMed=20553494; DOI=10.1111/j.1742-464X.2010.07668.x;
RA Hyman-Walsh C., Bjerke G.A., Wotton D.;
RT "An autoinhibitory effect of the homothorax domain of Meis2.";
RL FEBS J. 277:2584-2597(2010).
RN [13]
RP INTERACTION WITH TLX1.
RX PubMed=19559479; DOI=10.1016/j.leukres.2009.06.003;
RA Milech N., Gottardo N.G., Ford J., D'Souza D., Greene W.K., Kees U.R.,
RA Watt P.M.;
RT "MEIS proteins as partners of the TLX1/HOX11 oncoprotein.";
RL Leuk. Res. 34:358-363(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH SP1; SP3 AND KLF4.
RX PubMed=21746878; DOI=10.1128/MCB.01456-10;
RA Bjerke G.A., Hyman-Walsh C., Wotton D.;
RT "Cooperative transcriptional activation by Klf4, Meis2, and Pbx1.";
RL Mol. Cell. Biol. 31:3723-3733(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 233-319 IN COMPLEX WITH
RP HOXB1.
RX PubMed=10052460; DOI=10.1016/S0092-8674(00)80662-5;
RA Piper D.E., Batchelor A.H., Chang C.-P., Cleary M.L., Wolberger C.;
RT "Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the
RT hexapeptide and a fourth homeodomain helix in complex formation.";
RL Cell 96:587-597(1999).
CC -!- FUNCTION: Binds the sequence 5'-ATCAATCAA-3'. Acts as a
CC transcriptional activator of PF4 in complex with MEIS1. Converted
CC into a potent transcriptional activator by the (1;19)
CC translocation. May have a role in steroidogenesis and,
CC subsequently, sexual development and differentiation. Isoform
CC PBX1b as part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar
CC cells is involved in the transcriptional activation of the ELA1
CC enhancer; the complex binds to the enhancer B element and
CC cooperates with the transcription factor 1 complex (PTF1) bound to
CC the enhancer A element. Probably in complex with MEIS2, is
CC involved in transcriptional regulation by KLF4. Acts as a
CC transcriptional activator of NKX2-5 and a transcriptional
CC repressor of CDKN2B. Together with NKX2-5, it is required for
CC spleen development through a mechanism that involves CDKN2B
CC repression (By similarity).
CC -!- SUBUNIT: Forms a heterodimer with MEIS1 which binds DNA including
CC a cAMP-responsive sequence in CYP17. Also forms heterotrimers with
CC MEIS1 and a number of HOX proteins including HOXA9, HOXD4, HOXD9
CC and HOXD10. Interacts with PBXIP1 and TLX1. Isoform PBX1a
CC interacts with MEIS2 isoform 4, SP1, SP3 and KLF4. Isoform PBX1b
CC is part of a PDX1:PBX1b:MEIS2b complex; PBX1b recruits Meis2B to
CC the complex.
CC -!- INTERACTION:
CC Q12948:FOXC1; NbExp=4; IntAct=EBI-301611, EBI-1175253;
CC O14770-4:MEIS2; NbExp=6; IntAct=EBI-301611, EBI-8025850;
CC P31314:TLX1; NbExp=2; IntAct=EBI-6390251, EBI-2820655;
CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=PBX1a;
CC IsoId=P40424-1; Sequence=Displayed;
CC Name=PBX1b;
CC IsoId=P40424-2; Sequence=VSP_002271, VSP_002272;
CC Name=3;
CC IsoId=P40424-3; Sequence=VSP_044499;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues except in cells of
CC the B and T lineage.
CC -!- DISEASE: Note=A chromosomal aberration involving PBX1 is a cause
CC of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation
CC t(1;19)(q23;p13.3) with TCF3. TCF3-PBX1 transforms cells by
CC constitutively activating transcription of genes regulated by PBX1
CC or by other members of the PBX protein family.
CC -!- SIMILARITY: Belongs to the TALE/PBX homeobox family.
CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36764.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PBX1.html";
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DR EMBL; M86546; AAA60031.1; -; mRNA.
DR EMBL; AF313404; AAG30941.1; -; Genomic_DNA.
DR EMBL; AF313396; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313397; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313398; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313399; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313400; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313401; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313402; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313403; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AK299673; BAG61583.1; -; mRNA.
DR EMBL; AL359255; CAI14854.1; -; Genomic_DNA.
DR EMBL; AL357568; CAI14854.1; JOINED; Genomic_DNA.
DR EMBL; AL390119; CAI14854.1; JOINED; Genomic_DNA.
DR EMBL; AL390119; CAH73499.1; -; Genomic_DNA.
DR EMBL; AL359255; CAH73499.1; JOINED; Genomic_DNA.
DR EMBL; AL357568; CAH73499.1; JOINED; Genomic_DNA.
DR EMBL; AL357568; CAI14908.1; -; Genomic_DNA.
DR EMBL; AL390119; CAI14908.1; JOINED; Genomic_DNA.
DR EMBL; AL359255; CAI14908.1; JOINED; Genomic_DNA.
DR EMBL; AL391001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101578; AAI01579.1; -; mRNA.
DR EMBL; M31522; AAA36764.1; ALT_INIT; mRNA.
DR PIR; B34734; B34734.
DR RefSeq; NP_001191892.1; NM_001204963.1.
DR RefSeq; NP_002576.1; NM_002585.3.
DR RefSeq; XP_005245286.1; XM_005245229.1.
DR UniGene; Hs.557097; -.
DR PDB; 1B72; X-ray; 2.35 A; B=233-319.
DR PDB; 1PUF; X-ray; 1.90 A; B=233-305.
DR PDBsum; 1B72; -.
DR PDBsum; 1PUF; -.
DR ProteinModelPortal; P40424; -.
DR SMR; P40424; 233-305.
DR IntAct; P40424; 7.
DR MINT; MINT-1532549; -.
DR STRING; 9606.ENSP00000405890; -.
DR BindingDB; P40424; -.
DR PhosphoSite; P40424; -.
DR DMDM; 730279; -.
DR PaxDb; P40424; -.
DR PRIDE; P40424; -.
DR DNASU; 5087; -.
DR Ensembl; ENST00000367897; ENSP00000356872; ENSG00000185630.
DR Ensembl; ENST00000401534; ENSP00000384856; ENSG00000185630.
DR Ensembl; ENST00000420696; ENSP00000405890; ENSG00000185630.
DR Ensembl; ENST00000540236; ENSP00000439943; ENSG00000185630.
DR GeneID; 5087; -.
DR KEGG; hsa:5087; -.
DR UCSC; uc001gct.3; human.
DR CTD; 5087; -.
DR GeneCards; GC01P164524; -.
DR HGNC; HGNC:8632; PBX1.
DR HPA; CAB018768; -.
DR HPA; HPA003505; -.
DR HPA; HPA003881; -.
DR MIM; 176310; gene.
DR neXtProt; NX_P40424; -.
DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia.
DR PharmGKB; PA32970; -.
DR eggNOG; NOG248144; -.
DR HOGENOM; HOG000266972; -.
DR HOVERGEN; HBG000122; -.
DR InParanoid; P40424; -.
DR KO; K09355; -.
DR OMA; NIQSQVD; -.
DR PhylomeDB; P40424; -.
DR SignaLink; P40424; -.
DR ChiTaRS; PBX1; human.
DR EvolutionaryTrace; P40424; -.
DR GeneWiki; PBX1; -.
DR GenomeRNAi; 5087; -.
DR NextBio; 19618; -.
DR PRO; PR:P40424; -.
DR ArrayExpress; P40424; -.
DR Bgee; P40424; -.
DR CleanEx; HS_PBX1; -.
DR CleanEx; HS_PRL; -.
DR Genevestigator; P40424; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IEA:Ensembl.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0035162; P:embryonic hemopoiesis; IEA:Ensembl.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IEA:Ensembl.
DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0009887; P:organ morphogenesis; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR Gene3D; 1.10.10.60; -; 1.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR005542; PBX.
DR Pfam; PF00046; Homeobox; 1.
DR Pfam; PF03792; PBC; 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 3D-structure; Activator; Alternative splicing;
KW Chromosomal rearrangement; Complete proteome; Developmental protein;
KW Differentiation; DNA-binding; Homeobox; Nucleus; Polymorphism;
KW Proto-oncogene; Reference proteome; Repressor; Sexual differentiation;
KW Steroidogenesis; Transcription; Transcription regulation.
FT CHAIN 1 430 Pre-B-cell leukemia transcription factor
FT 1.
FT /FTId=PRO_0000049235.
FT DNA_BIND 233 295 Homeobox; TALE-type.
FT COMPBIAS 127 135 Poly-Ala.
FT SITE 88 89 Breakpoint for translocation to form
FT TCF3-PBX1 oncogene.
FT VAR_SEQ 334 347 SSSSFNMSNSGDLF -> GYPSPCYQPDRRIQ (in
FT isoform PBX1b).
FT /FTId=VSP_002271.
FT VAR_SEQ 348 430 Missing (in isoform PBX1b).
FT /FTId=VSP_002272.
FT VAR_SEQ 401 430 ANGGWQDATTPSSVTSPTEGPGSVHSDTSN -> HLPRHPR
FT QAHYHFRLPTWHP (in isoform 3).
FT /FTId=VSP_044499.
FT VARIANT 31 31 G -> S (in dbSNP:rs2275558).
FT /FTId=VAR_068904.
FT CONFLICT 351 351 Q -> H (in Ref. 3; BAG61583).
FT HELIX 242 254
FT TURN 255 257
FT HELIX 263 273
FT HELIX 277 293
FT TURN 295 300
FT HELIX 301 304
SQ SEQUENCE 430 AA; 46626 MW; AD3FFACBC5A9E715 CRC64;
MDEQPRLMHS HAGVGMAGHP GLSQHLQDGA GGTEGEGGRK QDIGDILQQI MTITDQSLDE
AQARKHALNC HRMKPALFNV LCEIKEKTVL SIRGAQEEEP TDPQLMRLDN MLLAEGVAGP
EKGGGSAAAA AAAAASGGAG SDNSVEHSDY RAKLSQIRQI YHTELEKYEQ ACNEFTTHVM
NLLREQSRTR PISPKEIERM VSIIHRKFSS IQMQLKQSTC EAVMILRSRF LDARRKRRNF
NKQATEILNE YFYSHLSNPY PSEEAKEELA KKCGITVSQV SNWFGNKRIR YKKNIGKFQE
EANIYAAKTA VTATNVSAHG SQANSPSTPN SAGSSSSFNM SNSGDLFMSV QSLNGDSYQG
AQVGANVQSQ VDTLRHVISQ TGGYSDGLAA SQMYSPQGIS ANGGWQDATT PSSVTSPTEG
PGSVHSDTSN
//
ID PBX1_HUMAN Reviewed; 430 AA.
AC P40424; B4DSC1; F5H4U9; Q5T488;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Pre-B-cell leukemia transcription factor 1;
DE AltName: Full=Homeobox protein PBX1;
DE AltName: Full=Homeobox protein PRL;
GN Name=PBX1; Synonyms=PRL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PBX1A).
RX PubMed=1682799;
RA Monica K., Galili N., Nourse J., Saltman D., Cleary M.L.;
RT "PBX2 and PBX3, new homeobox genes with extensive homology to the
RT human proto-oncogene PBX1.";
RL Mol. Cell. Biol. 11:6149-6157(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM PBX1A).
RX PubMed=11267683; DOI=10.1016/S0167-4781(01)00189-0;
RA Thameem F., Wolford J.K., Bogardus C., Prochazka M.;
RT "Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in
RT Pima Indians.";
RL Biochim. Biophys. Acta 1518:215-220(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT
RP SER-31.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PBX1A).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 89-430, AND CHROMOSOMAL TRANSLOCATION
RP WITH TCF3.
RX PubMed=1967983; DOI=10.1016/0092-8674(90)90658-2;
RA Kamps M.P., Murre C., Sun X.-H., Baltimore D.;
RT "A new homeobox gene contributes the DNA binding domain of the t(1;19)
RT translocation protein in pre-B ALL.";
RL Cell 60:547-555(1990).
RN [7]
RP CHROMOSOMAL TRANSLOCATION WITH TCF3.
RX PubMed=1671560;
RA Hunger S.P., Galili N., Carroll A.J., Crist W.M., Link M.P.,
RA Cleary M.L.;
RT "The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1
RT coding sequences in acute lymphoblastic leukemias.";
RL Blood 77:687-693(1991).
RN [8]
RP CHARACTERIZATION.
RX PubMed=8327485; DOI=10.1073/pnas.90.13.6061;
RA van Dijk M.A., Voorhoeve P.M., Murre C.;
RT "Pbx1 is converted into a transcriptional activator upon acquiring the
RT N-terminal region of E2A in pre-B-cell acute lymphoblastoid
RT leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6061-6065(1993).
RN [9]
RP CHARACTERIZATION.
RX PubMed=7910944;
RA Lu Q., Wright D.D., Kamps M.P.;
RT "Fusion with E2A converts the Pbx1 homeodomain protein into a
RT constitutive transcriptional activator in human leukemias carrying the
RT t(1;19) translocation.";
RL Mol. Cell. Biol. 14:3938-3948(1994).
RN [10]
RP INTERACTION WITH PBXIP1.
RX PubMed=10825160; DOI=10.1074/jbc.M001323200;
RA Abramovich C., Shen W.-F., Pineault N., Imren S., Montpetit B.,
RA Largman C., Humphries R.K.;
RT "Functional cloning and characterization of a novel nonhomeodomain
RT protein that inhibits the binding of PBX1-HOX complexes to DNA.";
RL J. Biol. Chem. 275:26172-26177(2000).
RN [11]
RP FUNCTION, AND INTERACTION WITH MEIS1.
RX PubMed=12609849; DOI=10.1182/blood-2002-02-0380;
RA Okada Y., Nagai R., Sato T., Matsuura E., Minami T., Morita I.,
RA Doi T.;
RT "Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific
RT transcription of the platelet factor 4 gene.";
RL Blood 101:4748-4756(2003).
RN [12]
RP INTERACTION WITH MEIS2.
RX PubMed=20553494; DOI=10.1111/j.1742-464X.2010.07668.x;
RA Hyman-Walsh C., Bjerke G.A., Wotton D.;
RT "An autoinhibitory effect of the homothorax domain of Meis2.";
RL FEBS J. 277:2584-2597(2010).
RN [13]
RP INTERACTION WITH TLX1.
RX PubMed=19559479; DOI=10.1016/j.leukres.2009.06.003;
RA Milech N., Gottardo N.G., Ford J., D'Souza D., Greene W.K., Kees U.R.,
RA Watt P.M.;
RT "MEIS proteins as partners of the TLX1/HOX11 oncoprotein.";
RL Leuk. Res. 34:358-363(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH SP1; SP3 AND KLF4.
RX PubMed=21746878; DOI=10.1128/MCB.01456-10;
RA Bjerke G.A., Hyman-Walsh C., Wotton D.;
RT "Cooperative transcriptional activation by Klf4, Meis2, and Pbx1.";
RL Mol. Cell. Biol. 31:3723-3733(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 233-319 IN COMPLEX WITH
RP HOXB1.
RX PubMed=10052460; DOI=10.1016/S0092-8674(00)80662-5;
RA Piper D.E., Batchelor A.H., Chang C.-P., Cleary M.L., Wolberger C.;
RT "Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the
RT hexapeptide and a fourth homeodomain helix in complex formation.";
RL Cell 96:587-597(1999).
CC -!- FUNCTION: Binds the sequence 5'-ATCAATCAA-3'. Acts as a
CC transcriptional activator of PF4 in complex with MEIS1. Converted
CC into a potent transcriptional activator by the (1;19)
CC translocation. May have a role in steroidogenesis and,
CC subsequently, sexual development and differentiation. Isoform
CC PBX1b as part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar
CC cells is involved in the transcriptional activation of the ELA1
CC enhancer; the complex binds to the enhancer B element and
CC cooperates with the transcription factor 1 complex (PTF1) bound to
CC the enhancer A element. Probably in complex with MEIS2, is
CC involved in transcriptional regulation by KLF4. Acts as a
CC transcriptional activator of NKX2-5 and a transcriptional
CC repressor of CDKN2B. Together with NKX2-5, it is required for
CC spleen development through a mechanism that involves CDKN2B
CC repression (By similarity).
CC -!- SUBUNIT: Forms a heterodimer with MEIS1 which binds DNA including
CC a cAMP-responsive sequence in CYP17. Also forms heterotrimers with
CC MEIS1 and a number of HOX proteins including HOXA9, HOXD4, HOXD9
CC and HOXD10. Interacts with PBXIP1 and TLX1. Isoform PBX1a
CC interacts with MEIS2 isoform 4, SP1, SP3 and KLF4. Isoform PBX1b
CC is part of a PDX1:PBX1b:MEIS2b complex; PBX1b recruits Meis2B to
CC the complex.
CC -!- INTERACTION:
CC Q12948:FOXC1; NbExp=4; IntAct=EBI-301611, EBI-1175253;
CC O14770-4:MEIS2; NbExp=6; IntAct=EBI-301611, EBI-8025850;
CC P31314:TLX1; NbExp=2; IntAct=EBI-6390251, EBI-2820655;
CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=PBX1a;
CC IsoId=P40424-1; Sequence=Displayed;
CC Name=PBX1b;
CC IsoId=P40424-2; Sequence=VSP_002271, VSP_002272;
CC Name=3;
CC IsoId=P40424-3; Sequence=VSP_044499;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues except in cells of
CC the B and T lineage.
CC -!- DISEASE: Note=A chromosomal aberration involving PBX1 is a cause
CC of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation
CC t(1;19)(q23;p13.3) with TCF3. TCF3-PBX1 transforms cells by
CC constitutively activating transcription of genes regulated by PBX1
CC or by other members of the PBX protein family.
CC -!- SIMILARITY: Belongs to the TALE/PBX homeobox family.
CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36764.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PBX1.html";
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DR EMBL; M86546; AAA60031.1; -; mRNA.
DR EMBL; AF313404; AAG30941.1; -; Genomic_DNA.
DR EMBL; AF313396; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313397; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313398; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313399; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313400; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313401; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313402; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AF313403; AAG30941.1; JOINED; Genomic_DNA.
DR EMBL; AK299673; BAG61583.1; -; mRNA.
DR EMBL; AL359255; CAI14854.1; -; Genomic_DNA.
DR EMBL; AL357568; CAI14854.1; JOINED; Genomic_DNA.
DR EMBL; AL390119; CAI14854.1; JOINED; Genomic_DNA.
DR EMBL; AL390119; CAH73499.1; -; Genomic_DNA.
DR EMBL; AL359255; CAH73499.1; JOINED; Genomic_DNA.
DR EMBL; AL357568; CAH73499.1; JOINED; Genomic_DNA.
DR EMBL; AL357568; CAI14908.1; -; Genomic_DNA.
DR EMBL; AL390119; CAI14908.1; JOINED; Genomic_DNA.
DR EMBL; AL359255; CAI14908.1; JOINED; Genomic_DNA.
DR EMBL; AL391001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101578; AAI01579.1; -; mRNA.
DR EMBL; M31522; AAA36764.1; ALT_INIT; mRNA.
DR PIR; B34734; B34734.
DR RefSeq; NP_001191892.1; NM_001204963.1.
DR RefSeq; NP_002576.1; NM_002585.3.
DR RefSeq; XP_005245286.1; XM_005245229.1.
DR UniGene; Hs.557097; -.
DR PDB; 1B72; X-ray; 2.35 A; B=233-319.
DR PDB; 1PUF; X-ray; 1.90 A; B=233-305.
DR PDBsum; 1B72; -.
DR PDBsum; 1PUF; -.
DR ProteinModelPortal; P40424; -.
DR SMR; P40424; 233-305.
DR IntAct; P40424; 7.
DR MINT; MINT-1532549; -.
DR STRING; 9606.ENSP00000405890; -.
DR BindingDB; P40424; -.
DR PhosphoSite; P40424; -.
DR DMDM; 730279; -.
DR PaxDb; P40424; -.
DR PRIDE; P40424; -.
DR DNASU; 5087; -.
DR Ensembl; ENST00000367897; ENSP00000356872; ENSG00000185630.
DR Ensembl; ENST00000401534; ENSP00000384856; ENSG00000185630.
DR Ensembl; ENST00000420696; ENSP00000405890; ENSG00000185630.
DR Ensembl; ENST00000540236; ENSP00000439943; ENSG00000185630.
DR GeneID; 5087; -.
DR KEGG; hsa:5087; -.
DR UCSC; uc001gct.3; human.
DR CTD; 5087; -.
DR GeneCards; GC01P164524; -.
DR HGNC; HGNC:8632; PBX1.
DR HPA; CAB018768; -.
DR HPA; HPA003505; -.
DR HPA; HPA003881; -.
DR MIM; 176310; gene.
DR neXtProt; NX_P40424; -.
DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia.
DR PharmGKB; PA32970; -.
DR eggNOG; NOG248144; -.
DR HOGENOM; HOG000266972; -.
DR HOVERGEN; HBG000122; -.
DR InParanoid; P40424; -.
DR KO; K09355; -.
DR OMA; NIQSQVD; -.
DR PhylomeDB; P40424; -.
DR SignaLink; P40424; -.
DR ChiTaRS; PBX1; human.
DR EvolutionaryTrace; P40424; -.
DR GeneWiki; PBX1; -.
DR GenomeRNAi; 5087; -.
DR NextBio; 19618; -.
DR PRO; PR:P40424; -.
DR ArrayExpress; P40424; -.
DR Bgee; P40424; -.
DR CleanEx; HS_PBX1; -.
DR CleanEx; HS_PRL; -.
DR Genevestigator; P40424; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IEA:Ensembl.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0035162; P:embryonic hemopoiesis; IEA:Ensembl.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IEA:Ensembl.
DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0009887; P:organ morphogenesis; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR Gene3D; 1.10.10.60; -; 1.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR005542; PBX.
DR Pfam; PF00046; Homeobox; 1.
DR Pfam; PF03792; PBC; 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 3D-structure; Activator; Alternative splicing;
KW Chromosomal rearrangement; Complete proteome; Developmental protein;
KW Differentiation; DNA-binding; Homeobox; Nucleus; Polymorphism;
KW Proto-oncogene; Reference proteome; Repressor; Sexual differentiation;
KW Steroidogenesis; Transcription; Transcription regulation.
FT CHAIN 1 430 Pre-B-cell leukemia transcription factor
FT 1.
FT /FTId=PRO_0000049235.
FT DNA_BIND 233 295 Homeobox; TALE-type.
FT COMPBIAS 127 135 Poly-Ala.
FT SITE 88 89 Breakpoint for translocation to form
FT TCF3-PBX1 oncogene.
FT VAR_SEQ 334 347 SSSSFNMSNSGDLF -> GYPSPCYQPDRRIQ (in
FT isoform PBX1b).
FT /FTId=VSP_002271.
FT VAR_SEQ 348 430 Missing (in isoform PBX1b).
FT /FTId=VSP_002272.
FT VAR_SEQ 401 430 ANGGWQDATTPSSVTSPTEGPGSVHSDTSN -> HLPRHPR
FT QAHYHFRLPTWHP (in isoform 3).
FT /FTId=VSP_044499.
FT VARIANT 31 31 G -> S (in dbSNP:rs2275558).
FT /FTId=VAR_068904.
FT CONFLICT 351 351 Q -> H (in Ref. 3; BAG61583).
FT HELIX 242 254
FT TURN 255 257
FT HELIX 263 273
FT HELIX 277 293
FT TURN 295 300
FT HELIX 301 304
SQ SEQUENCE 430 AA; 46626 MW; AD3FFACBC5A9E715 CRC64;
MDEQPRLMHS HAGVGMAGHP GLSQHLQDGA GGTEGEGGRK QDIGDILQQI MTITDQSLDE
AQARKHALNC HRMKPALFNV LCEIKEKTVL SIRGAQEEEP TDPQLMRLDN MLLAEGVAGP
EKGGGSAAAA AAAAASGGAG SDNSVEHSDY RAKLSQIRQI YHTELEKYEQ ACNEFTTHVM
NLLREQSRTR PISPKEIERM VSIIHRKFSS IQMQLKQSTC EAVMILRSRF LDARRKRRNF
NKQATEILNE YFYSHLSNPY PSEEAKEELA KKCGITVSQV SNWFGNKRIR YKKNIGKFQE
EANIYAAKTA VTATNVSAHG SQANSPSTPN SAGSSSSFNM SNSGDLFMSV QSLNGDSYQG
AQVGANVQSQ VDTLRHVISQ TGGYSDGLAA SQMYSPQGIS ANGGWQDATT PSSVTSPTEG
PGSVHSDTSN
//
MIM
176310
*RECORD*
*FIELD* NO
176310
*FIELD* TI
*176310 PRE-B-CELL LEUKEMIA TRANSCRIPTION FACTOR 1; PBX1
PRE-B-CELL LEUKEMIA TRANSCRIPTION FACTOR PSEUDOGENE 1, INCLUDED; PBXP1,
read moreINCLUDED;;
PBX1/E2A FUSION GENE, INCLUDED
*FIELD* TX
DESCRIPTION
The PBX1 gene encodes a transcription factor that plays a role in the
development of several organ systems (summary by Koss et al., 2012).
CYTOGENETICS
Human pre-B-cell acute lymphoblastic leukemias are frequently associated
with a t(1;19)(q23;p13.3) chromosomal rearrangement. Kamps et al. (1990)
and Nourse et al. (1990) demonstrated that several cell lines carrying
this translocation synthesize chimeric mRNAs with 5-prime sequences
encoded by the E2A transcription factor gene (147141) on chromosome 19
and 3-prime sequences encoded by a homeobox-related sequence, called Prl
or PBX1, on chromosome 1. In the chimeric transcription factor, the DNA
binding domain of E2A is replaced by a putative DNA binding domain of
PBX1. In 3 cell lines reported by Nourse et al. (1990), identical
E2A-Prl mRNA junctions were observed, suggesting that the fusion
transcripts are a consistent feature of this translocation.
MAPPING
Monica et al. (1991) confirmed the mapping of PBX1 to 1q23 by in situ
hybridization.
- Pseudogenes
Sugaya et al. (1994) conducted a chromosome walk in the class III region
of the major histocompatibility complex (MHC) near the junction with
class II. There they found a gene with the characteristics of PBX2
(176311), which, however, had been mapped to chromosome 3 (Monica et
al., 1991). Fluorescence in situ hybridization confirmed the location of
the 'new' gene at 6p21.3. The PBX gene on chromosome 3 was later found
to be a pseudogene and the PBX gene on chromosome 6 was designated PBX2.
GENE FUNCTION
Kamps et al. (1991) discussed the chimeric genes created by the human
t(1;19) translocation in pre-B-cell acute lymphoblastic leukemias. The
authors cloned 2 different E2A-PBX1 fusion transcripts (which differed
only in the PBX1 sequences they contained) and showed that NIH-3T3 cells
transfected with cDNAs encoding the fusion proteins were able to cause
malignant tumors in nude mice. They discussed subtle differences in the
transforming ability of the 2 fusion proteins with respect to the
regions of the PBX1 gene they contained.
Mercader et al. (1999) described the role of homeobox genes Meis1
(601739), Meis2 (601740), and Pbx1 in the development of mouse, chicken,
and Drosophila limbs. Mercader et al. (1999) found that Meis1 and Meis2
expression is restricted to the proximal domain, coincident with the
previously reported domain in which Pbx1 is localized to the nucleus.
Meis1 regulates Pbx1 activity by promoting nuclear import of the Pbx1
protein. Mercader et al. (1999) also demonstrated that ectopic
expression of Meis1 in chicken disrupts distal limb development and
induces distal-to-proximal transformations. Mercader et al. (1999)
concluded that the restriction of Meis1 to proximal regions of the
vertebrate limb is essential to specify cell fates and differentiation
patterns along the proximodistal axis of the limb.
Wiemels et al. (2002) sequenced the genomic fusion between the PBX1 and
E2A genes in 22 pre-B acute lymphoblastic leukemias and 2 cell lines.
The prenatal origin of the leukemia was assessed in 15 pediatric
patients by screening for the clonotypic PBX1-E2A translocation in
neonatal blood spots, or Guthrie cards, obtained from the children at
birth. Two patients were weakly positive for the fusion at birth, in
contrast to previously studied childhood leukemia fusions, t(12;21),
t(8;21), and t(4;11), which are predominantly prenatal. The presence of
extensive N-nucleotides at the point of fusion in the PBX1-E2A
translocation as well as specific characteristics of the IGH
(147100)/TCR (see 186880) rearrangements provided additional evidence
for a postnatal, pre-B cell origin. Sixteen of 24 breakpoints on the
3.2-kb E2A intron 14 were located within 5 bp, providing evidence for a
site-specific recombination mechanism. Breakpoints on the 232-kb PBX1
intron 1 were more dispersed, but were highly clustered proximal to exon
2. Thus, the translocation breakpoints displayed evidence of unique
temporal, ontologic, and mechanistic formation in contrast to the
previously analyzed pediatric leukemia translocation breakpoints,
emphasizing the need to differentiate cytogenetic and molecular
subgroups for studies of leukemia causality.
Cheung et al. (2009) showed that PBX1 mRNA was constitutively expressed
in both human bone-derived cells (HBDC) and murine preosteoblasts.
Immunostaining revealed that PBX1 was localized in the nucleus
compartment. RNAi knockdown of PBX1 murine preosteoblasts resulted in
decreased expression of Runx2 (600211) and osterix (SP7; 606633), the
critical transcription factors for osteogenesis, but accelerated cell
proliferation and bone nodule formation.
MOLECULAR GENETICS
For discussion of an association between variation in the PBX1 gene and
bone mineral density, see BMND2 (605833).
ANIMAL MODEL
Selleri et al. (2001) showed that Pbx1 is required in skeletal
patterning and programming. Pbx1 -/- mice died by embryonic day 15 or 16
with severe hypoplasia or aplasia of multiple organs and widespread
patterning defects of the axial and appendicular skeleton. Pbx1 -/-
embryos had thinning compressions and fusions of the vertebral bodies
and neural arches, as well as defects in the proximal forelimbs and
hindlimbs.
In vitro studies have shown that PBX1 regulates the activity of IPF1, a
Para-Hox homeodomain transcription factor required for the development
and function of the pancreas in mice and humans. To investigate in vivo
roles of PBX1 in pancreatic development and function, Kim et al. (2002)
examined pancreatic Pbx1 expression, and morphogenesis, cell
differentiation, and function in mice deficient for Pbx1. Pbx1 -/-
embryos had pancreatic hypoplasia and marked defects in exocrine and
endocrine cell differentiation prior to death at embryonic day 15 or 16.
In these embryos, expression of Isl1 (600366) and Atoh5 (604882),
essential regulators of pancreatic morphogenesis and differentiation,
was severely reduced. Pbx1 +/- adults had pancreatic islet
malformations, impaired glucose tolerance, and hypoinsulinemia. Thus,
Kim et al. (2002) concluded that PBX1 is essential for normal pancreatic
development and function. Analysis of trans-heterozygous Pbx1 +/- and
Ipf1 +/- mice revealed in vivo genetic interactions between Pbx1 and
Ipf1 that are essential for postnatal pancreatic function.
Trans-heterozygous mice developed age-dependent overt diabetes mellitus,
unlike Pbx1 +/- or Ipf1 +/- mice. Mutations affecting the Ipf1 protein
promote diabetes mellitus in mice and humans. Kim et al. (2002)
concluded that perturbation of PBX1 activity may also promote
susceptibility to diabetes mellitus.
Koss et al. (2012) found that conditional knockout of Pbx1 in splenic
mesoderm of mouse embryos resulted in hyposplenia and fragmented
splenules due to a defect in mesenchymal cell proliferation. Conditional
knockout of Pbx1, which controls Nkx2-5 (600584) expression, resulted in
decreased expression of Nkx2-5 and hyposplenia, indicating that Nkx2-5
is critical for splenic growth. Pbx1 was found to repress the cell cycle
inhibitor CDKN2B (600431) in the spleen anlage; loss of Pbx1 in cultured
spleen mesenchymal cells caused upregulation of Cdkn2b and reduced
proliferation of these cells. Splenic expansion could be partially
rescued by genetic ablation of Cdkn2b. Thus, repression of Cdkn2b by
Pbx1 is required for proper organ morphogenesis and growth in vivo.
Nkx2-5 was also shown to bind to and repress Cdkn2b. The findings
delineated a regulatory module governing mammalian spleen organogenesis
that involves Pbx1, Nkx2-5, and Cdkn2b.
*FIELD* RF
1. Cheung, C.-L.; Chan, B. Y. Y.; Chan, V.; Ikegawa, S.; Kou, I.;
Ngai, H.; Smith, D.; Luk, K. D. K.; Huang, Q.-Y.; Mori, S.; Sham,
P.-C.; Kung, A. W. C.: Pre-B-cell leukemia homeobox 1 (PBX1) shows
functional and possible genetic association with bone mineral density
variation. Hum. Molec. Genet. 18: 679-687, 2009.
2. Kamps, M. P.; Look, A. T.; Baltimore, D.: The human t(1:19) translocation
in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with
differing transforming potentials. Genes Dev. 5: 358-368, 1991.
3. Kamps, M. P.; Murre, C.; Sun, X.; Baltimore, D.: A new homeobox
gene contributes the DNA binding domain of the t(1;19) translocation
protein in pre-B ALL. Cell 60: 547-555, 1990.
4. Kim, S. K.; Selleri, L.; Lee, J. S.; Zhang, A. Y.; Gu, X.; Jacobs,
Y.; Cleary, M. L.: Pbx1 inactivation disrupts pancreas development
and in Ipf1-deficient mice promotes diabetes mellitus. Nature Genet. 30:
430-435, 2002.
5. Koss, M.; Bolze, A.; Brendolan, A.; Saggese, M.; Capellini, T.
D.; Bojilova, E.; Boisson, B.; Prall, O. W. J.; Elliott, D. A.; Solloway,
M.; Lenti, E.; Hidaka, C.; Chang, C.-P.; Mahlaoui, N.; Harvey, R.
P.; Casanova, J.-L.; Selleri, L.: Congenital asplenia in mice and
humans with mutations in a Pbx/Nkx2-5/p15 module. Dev. Cell 22:
913-926, 2012.
6. Mercader, N.; Leonardo, E.; Azpiazu, N.; Serrano, A.; Morata, G.;
Martinez-A, C.; Torres, M.: Conserved regulation of proximodistal
limb axis development by Meis1/Hth. Nature 402: 425-429, 1999.
7. Monica, K.; Galili, N.; Nourse, J.; Saltman, D.; Cleary, M. L.
: PBX2 and PBX3, new homeobox genes with extensive homology to the
human proto-oncogene PBX1. Molec. Cell. Biol. 11: 6149-6157, 1991.
8. Nourse, J.; Mellentin, J. D.; Galili, N.; Wilkinson, J.; Stanbridge,
E.; Smith, S. D.; Cleary, M. L.: Chromosomal translocation t(1;19)
results in synthesis of a homeobox fusion mRNA that codes for a potential
chimeric transcription factor. Cell 60: 535-545, 1990.
9. Selleri, L.; Depew, M. J.; Jacobs, Y.; Chanda, S. K.; Tsang, K.
Y.; Cheah, K. S. E.; Rubenstein, J. L. R.; O'Gorman, S.; Cleary, M.
L.: Requirement for Pbx1 in skeletal patterning and programming of
chondrocyte proliferation and differentiation. Development 128:
3543-3557, 2001.
10. Sugaya, K.; Fukagawa, T.; Matsumoto, K.; Mita, K.; Takahashi,
E.; Ando, A.; Inoko, H.; Ikemura, T.: Three genes in the human MHC
class III region near the junction with the class II: gene for receptor
of advanced glycosylation end products, PBX2 homeobox gene and a Notch
homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 23:
408-419, 1994.
11. Wiemels, J. L.; Leonard, B. C.; Wang, Y.; Segal, M. R.; Hunger,
S. P.; Smith, M. T.; Crouse, V.; Ma, X.; Buffler, P. A.; Pine, S.
R.: Site-specific translocation and evidence of postnatal origin
of the t(1;19) E2A-PBX1 fusion in childhood acute lymphoblastic leukemia. Proc.
Nat. Acad. Sci. 99: 15101-15106, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 2/4/2013
George E. Tiller - updated: 8/10/2009
Victor A. McKusick - updated: 12/9/2002
Ada Hamosh - updated: 3/29/2002
Ada Hamosh - updated: 2/10/2000
Victor A. McKusick - edited: 3/3/1997
Mark H. Paalman - updated: 4/29/1996
*FIELD* CD
Victor A. McKusick: 9/9/1990
*FIELD* ED
carol: 02/04/2013
ckniffin: 2/4/2013
mgross: 11/16/2010
terry: 11/16/2010
terry: 10/21/2009
wwang: 8/20/2009
terry: 8/10/2009
terry: 3/18/2004
carol: 11/14/2003
carol: 12/10/2002
tkritzer: 12/9/2002
alopez: 4/2/2002
terry: 3/29/2002
carol: 9/20/2001
alopez: 2/10/2000
dkim: 7/7/1998
mark: 3/3/1997
terry: 1/17/1997
mark: 4/29/1996
mimadm: 2/25/1995
supermim: 3/16/1992
carol: 1/22/1992
supermim: 9/28/1990
carol: 9/9/1990
*RECORD*
*FIELD* NO
176310
*FIELD* TI
*176310 PRE-B-CELL LEUKEMIA TRANSCRIPTION FACTOR 1; PBX1
PRE-B-CELL LEUKEMIA TRANSCRIPTION FACTOR PSEUDOGENE 1, INCLUDED; PBXP1,
read moreINCLUDED;;
PBX1/E2A FUSION GENE, INCLUDED
*FIELD* TX
DESCRIPTION
The PBX1 gene encodes a transcription factor that plays a role in the
development of several organ systems (summary by Koss et al., 2012).
CYTOGENETICS
Human pre-B-cell acute lymphoblastic leukemias are frequently associated
with a t(1;19)(q23;p13.3) chromosomal rearrangement. Kamps et al. (1990)
and Nourse et al. (1990) demonstrated that several cell lines carrying
this translocation synthesize chimeric mRNAs with 5-prime sequences
encoded by the E2A transcription factor gene (147141) on chromosome 19
and 3-prime sequences encoded by a homeobox-related sequence, called Prl
or PBX1, on chromosome 1. In the chimeric transcription factor, the DNA
binding domain of E2A is replaced by a putative DNA binding domain of
PBX1. In 3 cell lines reported by Nourse et al. (1990), identical
E2A-Prl mRNA junctions were observed, suggesting that the fusion
transcripts are a consistent feature of this translocation.
MAPPING
Monica et al. (1991) confirmed the mapping of PBX1 to 1q23 by in situ
hybridization.
- Pseudogenes
Sugaya et al. (1994) conducted a chromosome walk in the class III region
of the major histocompatibility complex (MHC) near the junction with
class II. There they found a gene with the characteristics of PBX2
(176311), which, however, had been mapped to chromosome 3 (Monica et
al., 1991). Fluorescence in situ hybridization confirmed the location of
the 'new' gene at 6p21.3. The PBX gene on chromosome 3 was later found
to be a pseudogene and the PBX gene on chromosome 6 was designated PBX2.
GENE FUNCTION
Kamps et al. (1991) discussed the chimeric genes created by the human
t(1;19) translocation in pre-B-cell acute lymphoblastic leukemias. The
authors cloned 2 different E2A-PBX1 fusion transcripts (which differed
only in the PBX1 sequences they contained) and showed that NIH-3T3 cells
transfected with cDNAs encoding the fusion proteins were able to cause
malignant tumors in nude mice. They discussed subtle differences in the
transforming ability of the 2 fusion proteins with respect to the
regions of the PBX1 gene they contained.
Mercader et al. (1999) described the role of homeobox genes Meis1
(601739), Meis2 (601740), and Pbx1 in the development of mouse, chicken,
and Drosophila limbs. Mercader et al. (1999) found that Meis1 and Meis2
expression is restricted to the proximal domain, coincident with the
previously reported domain in which Pbx1 is localized to the nucleus.
Meis1 regulates Pbx1 activity by promoting nuclear import of the Pbx1
protein. Mercader et al. (1999) also demonstrated that ectopic
expression of Meis1 in chicken disrupts distal limb development and
induces distal-to-proximal transformations. Mercader et al. (1999)
concluded that the restriction of Meis1 to proximal regions of the
vertebrate limb is essential to specify cell fates and differentiation
patterns along the proximodistal axis of the limb.
Wiemels et al. (2002) sequenced the genomic fusion between the PBX1 and
E2A genes in 22 pre-B acute lymphoblastic leukemias and 2 cell lines.
The prenatal origin of the leukemia was assessed in 15 pediatric
patients by screening for the clonotypic PBX1-E2A translocation in
neonatal blood spots, or Guthrie cards, obtained from the children at
birth. Two patients were weakly positive for the fusion at birth, in
contrast to previously studied childhood leukemia fusions, t(12;21),
t(8;21), and t(4;11), which are predominantly prenatal. The presence of
extensive N-nucleotides at the point of fusion in the PBX1-E2A
translocation as well as specific characteristics of the IGH
(147100)/TCR (see 186880) rearrangements provided additional evidence
for a postnatal, pre-B cell origin. Sixteen of 24 breakpoints on the
3.2-kb E2A intron 14 were located within 5 bp, providing evidence for a
site-specific recombination mechanism. Breakpoints on the 232-kb PBX1
intron 1 were more dispersed, but were highly clustered proximal to exon
2. Thus, the translocation breakpoints displayed evidence of unique
temporal, ontologic, and mechanistic formation in contrast to the
previously analyzed pediatric leukemia translocation breakpoints,
emphasizing the need to differentiate cytogenetic and molecular
subgroups for studies of leukemia causality.
Cheung et al. (2009) showed that PBX1 mRNA was constitutively expressed
in both human bone-derived cells (HBDC) and murine preosteoblasts.
Immunostaining revealed that PBX1 was localized in the nucleus
compartment. RNAi knockdown of PBX1 murine preosteoblasts resulted in
decreased expression of Runx2 (600211) and osterix (SP7; 606633), the
critical transcription factors for osteogenesis, but accelerated cell
proliferation and bone nodule formation.
MOLECULAR GENETICS
For discussion of an association between variation in the PBX1 gene and
bone mineral density, see BMND2 (605833).
ANIMAL MODEL
Selleri et al. (2001) showed that Pbx1 is required in skeletal
patterning and programming. Pbx1 -/- mice died by embryonic day 15 or 16
with severe hypoplasia or aplasia of multiple organs and widespread
patterning defects of the axial and appendicular skeleton. Pbx1 -/-
embryos had thinning compressions and fusions of the vertebral bodies
and neural arches, as well as defects in the proximal forelimbs and
hindlimbs.
In vitro studies have shown that PBX1 regulates the activity of IPF1, a
Para-Hox homeodomain transcription factor required for the development
and function of the pancreas in mice and humans. To investigate in vivo
roles of PBX1 in pancreatic development and function, Kim et al. (2002)
examined pancreatic Pbx1 expression, and morphogenesis, cell
differentiation, and function in mice deficient for Pbx1. Pbx1 -/-
embryos had pancreatic hypoplasia and marked defects in exocrine and
endocrine cell differentiation prior to death at embryonic day 15 or 16.
In these embryos, expression of Isl1 (600366) and Atoh5 (604882),
essential regulators of pancreatic morphogenesis and differentiation,
was severely reduced. Pbx1 +/- adults had pancreatic islet
malformations, impaired glucose tolerance, and hypoinsulinemia. Thus,
Kim et al. (2002) concluded that PBX1 is essential for normal pancreatic
development and function. Analysis of trans-heterozygous Pbx1 +/- and
Ipf1 +/- mice revealed in vivo genetic interactions between Pbx1 and
Ipf1 that are essential for postnatal pancreatic function.
Trans-heterozygous mice developed age-dependent overt diabetes mellitus,
unlike Pbx1 +/- or Ipf1 +/- mice. Mutations affecting the Ipf1 protein
promote diabetes mellitus in mice and humans. Kim et al. (2002)
concluded that perturbation of PBX1 activity may also promote
susceptibility to diabetes mellitus.
Koss et al. (2012) found that conditional knockout of Pbx1 in splenic
mesoderm of mouse embryos resulted in hyposplenia and fragmented
splenules due to a defect in mesenchymal cell proliferation. Conditional
knockout of Pbx1, which controls Nkx2-5 (600584) expression, resulted in
decreased expression of Nkx2-5 and hyposplenia, indicating that Nkx2-5
is critical for splenic growth. Pbx1 was found to repress the cell cycle
inhibitor CDKN2B (600431) in the spleen anlage; loss of Pbx1 in cultured
spleen mesenchymal cells caused upregulation of Cdkn2b and reduced
proliferation of these cells. Splenic expansion could be partially
rescued by genetic ablation of Cdkn2b. Thus, repression of Cdkn2b by
Pbx1 is required for proper organ morphogenesis and growth in vivo.
Nkx2-5 was also shown to bind to and repress Cdkn2b. The findings
delineated a regulatory module governing mammalian spleen organogenesis
that involves Pbx1, Nkx2-5, and Cdkn2b.
*FIELD* RF
1. Cheung, C.-L.; Chan, B. Y. Y.; Chan, V.; Ikegawa, S.; Kou, I.;
Ngai, H.; Smith, D.; Luk, K. D. K.; Huang, Q.-Y.; Mori, S.; Sham,
P.-C.; Kung, A. W. C.: Pre-B-cell leukemia homeobox 1 (PBX1) shows
functional and possible genetic association with bone mineral density
variation. Hum. Molec. Genet. 18: 679-687, 2009.
2. Kamps, M. P.; Look, A. T.; Baltimore, D.: The human t(1:19) translocation
in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with
differing transforming potentials. Genes Dev. 5: 358-368, 1991.
3. Kamps, M. P.; Murre, C.; Sun, X.; Baltimore, D.: A new homeobox
gene contributes the DNA binding domain of the t(1;19) translocation
protein in pre-B ALL. Cell 60: 547-555, 1990.
4. Kim, S. K.; Selleri, L.; Lee, J. S.; Zhang, A. Y.; Gu, X.; Jacobs,
Y.; Cleary, M. L.: Pbx1 inactivation disrupts pancreas development
and in Ipf1-deficient mice promotes diabetes mellitus. Nature Genet. 30:
430-435, 2002.
5. Koss, M.; Bolze, A.; Brendolan, A.; Saggese, M.; Capellini, T.
D.; Bojilova, E.; Boisson, B.; Prall, O. W. J.; Elliott, D. A.; Solloway,
M.; Lenti, E.; Hidaka, C.; Chang, C.-P.; Mahlaoui, N.; Harvey, R.
P.; Casanova, J.-L.; Selleri, L.: Congenital asplenia in mice and
humans with mutations in a Pbx/Nkx2-5/p15 module. Dev. Cell 22:
913-926, 2012.
6. Mercader, N.; Leonardo, E.; Azpiazu, N.; Serrano, A.; Morata, G.;
Martinez-A, C.; Torres, M.: Conserved regulation of proximodistal
limb axis development by Meis1/Hth. Nature 402: 425-429, 1999.
7. Monica, K.; Galili, N.; Nourse, J.; Saltman, D.; Cleary, M. L.
: PBX2 and PBX3, new homeobox genes with extensive homology to the
human proto-oncogene PBX1. Molec. Cell. Biol. 11: 6149-6157, 1991.
8. Nourse, J.; Mellentin, J. D.; Galili, N.; Wilkinson, J.; Stanbridge,
E.; Smith, S. D.; Cleary, M. L.: Chromosomal translocation t(1;19)
results in synthesis of a homeobox fusion mRNA that codes for a potential
chimeric transcription factor. Cell 60: 535-545, 1990.
9. Selleri, L.; Depew, M. J.; Jacobs, Y.; Chanda, S. K.; Tsang, K.
Y.; Cheah, K. S. E.; Rubenstein, J. L. R.; O'Gorman, S.; Cleary, M.
L.: Requirement for Pbx1 in skeletal patterning and programming of
chondrocyte proliferation and differentiation. Development 128:
3543-3557, 2001.
10. Sugaya, K.; Fukagawa, T.; Matsumoto, K.; Mita, K.; Takahashi,
E.; Ando, A.; Inoko, H.; Ikemura, T.: Three genes in the human MHC
class III region near the junction with the class II: gene for receptor
of advanced glycosylation end products, PBX2 homeobox gene and a Notch
homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 23:
408-419, 1994.
11. Wiemels, J. L.; Leonard, B. C.; Wang, Y.; Segal, M. R.; Hunger,
S. P.; Smith, M. T.; Crouse, V.; Ma, X.; Buffler, P. A.; Pine, S.
R.: Site-specific translocation and evidence of postnatal origin
of the t(1;19) E2A-PBX1 fusion in childhood acute lymphoblastic leukemia. Proc.
Nat. Acad. Sci. 99: 15101-15106, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 2/4/2013
George E. Tiller - updated: 8/10/2009
Victor A. McKusick - updated: 12/9/2002
Ada Hamosh - updated: 3/29/2002
Ada Hamosh - updated: 2/10/2000
Victor A. McKusick - edited: 3/3/1997
Mark H. Paalman - updated: 4/29/1996
*FIELD* CD
Victor A. McKusick: 9/9/1990
*FIELD* ED
carol: 02/04/2013
ckniffin: 2/4/2013
mgross: 11/16/2010
terry: 11/16/2010
terry: 10/21/2009
wwang: 8/20/2009
terry: 8/10/2009
terry: 3/18/2004
carol: 11/14/2003
carol: 12/10/2002
tkritzer: 12/9/2002
alopez: 4/2/2002
terry: 3/29/2002
carol: 9/20/2001
alopez: 2/10/2000
dkim: 7/7/1998
mark: 3/3/1997
terry: 1/17/1997
mark: 4/29/1996
mimadm: 2/25/1995
supermim: 3/16/1992
carol: 1/22/1992
supermim: 9/28/1990
carol: 9/9/1990