PBX1_HUMAN
ID PBX1_HUMAN Reviewed; 430 AA.
AC P40424; B4DSC1; F5H4U9; Q5T488;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 219.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PBX1A).
RX PubMed=1682799; DOI=10.1128/mcb.11.12.6149-6157.1991;
RA Monica K., Galili N., Nourse J., Saltman D., Cleary M.L.;
RT "PBX2 and PBX3, new homeobox genes with extensive homology to the human
RT 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 Pima
RT Indians.";
RL Biochim. Biophys. Acta 1518:215-220(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 89-430, AND CHROMOSOMAL TRANSLOCATION WITH
RP 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., Cleary M.L.;
RT "The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding
RT sequences in acute lymphoblastic leukemias.";
RL Blood 77:687-693(1991).
RN [8]
RP FUNCTION, AND CHROMOSOMAL TRANSLOCATION WITH TCF3.
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 N-
RT terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6061-6065(1993).
RN [9]
RP CHARACTERIZATION.
RX PubMed=7910944; DOI=10.1128/mcb.14.6.3938-3948.1994;
RA Lu Q., Wright D.D., Kamps M.P.;
RT "Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive
RT transcriptional activator in human leukemias carrying the t(1;19)
RT translocation.";
RL Mol. Cell. Biol. 14:3938-3948(1994).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOXA5; HOXB7; HOXB8; HOXC8 AND HOXD4.
RX PubMed=7791786; DOI=10.1128/mcb.15.7.3786;
RA Lu Q., Knoepfler P.S., Scheele J., Wright D.D., Kamps M.P.;
RT "Both Pbx1 and E2A-Pbx1 bind the DNA motif ATCAATCAA cooperatively with the
RT products of multiple murine Hox genes, some of which are themselves
RT oncogenes.";
RL Mol. Cell. Biol. 15:3786-3795(1995).
RN [11]
RP FUNCTION, AND INTERACTION WITH HOXA1; HOXA5; HOXB7 AND HOXB8.
RX PubMed=9191052; DOI=10.1038/sj.onc.1201097;
RA Knoepfler P.S., Kamps M.P.;
RT "The highest affinity DNA element bound by Pbx complexes in t(1;19)
RT leukemic cells fails to mediate cooperative DNA-binding or cooperative
RT transactivation by E2a-Pbx1 and class I Hox proteins - evidence for
RT selective targetting of E2a-Pbx1 to a subset of Pbx-recognition elements.";
RL Oncogene 14:2521-2531(1997).
RN [12]
RP INTERACTION WITH PBXIP1.
RX PubMed=10825160; DOI=10.1074/jbc.m001323200;
RA Abramovich C., Shen W.-F., Pineault N., Imren S., Montpetit B., Largman C.,
RA Humphries R.K.;
RT "Functional cloning and characterization of a novel nonhomeodomain protein
RT that inhibits the binding of PBX1-HOX complexes to DNA.";
RL J. Biol. Chem. 275:26172-26177(2000).
RN [13]
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., 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 [14]
RP INTERACTION WITH FOXC1.
RX PubMed=15684392; DOI=10.1128/mcb.25.4.1415-1424.2005;
RA Berry F.B., O'Neill M.A., Coca-Prados M., Walter M.A.;
RT "FOXC1 transcriptional regulatory activity is impaired by PBX1 in a filamin
RT A-mediated manner.";
RL Mol. Cell. Biol. 25:1415-1424(2005).
RN [15]
RP INTERACTION WITH MEIS1.
RX PubMed=19799567; DOI=10.1042/bj20090694;
RA Mojsin M., Stevanovic M.;
RT "PBX1 and MEIS1 up-regulate SOX3 gene expression by direct interaction with
RT a consensus binding site within the basal promoter region.";
RL Biochem. J. 425:107-116(2009).
RN [16]
RP INTERACTION WITH MEIS2.
RX PubMed=20553494; DOI=10.1111/j.1742-4658.2010.07668.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 [17]
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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., Buerckstuemmer T.,
RA 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 [20]
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 [21]
RP SUBCELLULAR LOCATION, INVOLVEMENT IN CAKUTHED, AND TISSUE SPECIFICITY.
RX PubMed=28270404; DOI=10.1136/jmedgenet-2016-104435;
RA Le Tanno P., Breton J., Bidart M., Satre V., Harbuz R., Ray P.F.,
RA Bosson C., Dieterich K., Jaillard S., Odent S., Poke G., Beddow R.,
RA Digilio M.C., Novelli A., Bernardini L., Pisanti M.A., Mackenroth L.,
RA Hackmann K., Vogel I., Christensen R., Fokstuen S., Bena F., Amblard F.,
RA Devillard F., Vieville G., Apostolou A., Jouk P.S., Guebre-Egziabher F.,
RA Sartelet H., Coutton C.;
RT "PBX1 haploinsufficiency leads to syndromic congenital anomalies of the
RT kidney and urinary tract (CAKUT) in humans.";
RL J. Med. Genet. 54:502-510(2017).
RN [22]
RP INTERACTION WITH MN1.
RX PubMed=31839203; DOI=10.1016/j.ajhg.2019.11.011;
RA Miyake N., Takahashi H., Nakamura K., Isidor B., Hiraki Y., Koshimizu E.,
RA Shiina M., Sasaki K., Suzuki H., Abe R., Kimura Y., Akiyama T.,
RA Tomizawa S.I., Hirose T., Hamanaka K., Miyatake S., Mitsuhashi S.,
RA Mizuguchi T., Takata A., Obo K., Kato M., Ogata K., Matsumoto N.;
RT "Gain-of-function MN1 truncation variants cause a recognizable syndrome
RT with craniofacial and brain abnormalities.";
RL Am. J. Hum. Genet. 106:13-25(2020).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 233-319 IN COMPLEX WITH 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).
RN [24]
RP VARIANT CAKUTHED 184-ARG--ASN-430 DEL.
RX PubMed=28566479; DOI=10.1681/asn.2017010043;
RA Heidet L., Moriniere V., Henry C., De Tomasi L., Reilly M.L., Humbert C.,
RA Alibeu O., Fourrage C., Bole-Feysot C., Nitschke P., Tores F., Bras M.,
RA Jeanpierre M., Pietrement C., Gaillard D., Gonzales M., Novo R.,
RA Schaefer E., Roume J., Martinovic J., Malan V., Salomon R., Saunier S.,
RA Antignac C., Jeanpierre C.;
RT "Targeted exome sequencing identifies PBX1 as involved in monogenic
RT congenital anomalies of the kidney and urinary tract.";
RL J. Am. Soc. Nephrol. 28:2901-2914(2017).
CC -!- FUNCTION: Transcription factor which binds the DNA sequence 5'-
CC TGATTGAT-3' as part of a heterodimer with HOX proteins such as HOXA1,
CC HOXA5, HOXB7 and HOXB8 (PubMed:9191052). Binds to the DNA sequence 5'-
CC TGATTGAC-3' in complex with a nuclear factor which is not a class I HOX
CC protein (PubMed:9191052). Has also been shown to bind the DNA sequence
CC 5'-ATCAATCAA-3' cooperatively with HOXA5, HOXB7, HOXB8, HOXC8 and HOXD4
CC (PubMed:8327485, PubMed:7791786). Acts as a transcriptional activator
CC of PF4 in complex with MEIS1 (PubMed:12609849). Also activates
CC transcription of SOX3 in complex with MEIS1 by binding to the 5'-
CC TGATTGAC-3' consensus sequence (By similarity). In natural killer
CC cells, binds to the NFIL3 promoter and acts as a transcriptional
CC activator of NFIL3, promoting natural killer cell development (By
CC similarity). Plays a role in the cAMP-dependent regulation of CYP17A1
CC gene expression via its cAMP-regulatory sequence (CRS1) (By
CC similarity). Probably in complex with MEIS2, involved in
CC transcriptional regulation by KLF4 (PubMed:21746878). Acts as a
CC transcriptional activator of NKX2-5 and a transcriptional repressor of
CC CDKN2B (By similarity). Together with NKX2-5, required for spleen
CC development through a mechanism that involves CDKN2B repression (By
CC similarity). {ECO:0000250|UniProtKB:P41778,
CC ECO:0000269|PubMed:12609849, ECO:0000269|PubMed:21746878,
CC ECO:0000269|PubMed:7791786, ECO:0000269|PubMed:8327485,
CC ECO:0000269|PubMed:9191052}.
CC -!- FUNCTION: [Isoform PBX1b]: As part of a PDX1:PBX1b:MEIS2B complex in
CC pancreatic acinar cells, is involved in the transcriptional activation
CC of the ELA1 enhancer; the complex binds to the enhancer B element and
CC cooperates with the transcription factor 1 complex (PTF1) bound to the
CC enhancer A element. {ECO:0000250|UniProtKB:P41778}.
CC -!- SUBUNIT: Forms a heterodimer with MEIS1 which binds DNA
CC (PubMed:19799567). The PBX1-MEIS1 heterodimer binds a cAMP-responsive
CC sequence in CYP17 (By similarity). It also binds a consensus region in
CC the SOX3 promoter (PubMed:19799567). PBX1 forms heterotrimers with
CC MEIS1 and a number of HOX proteins including HOXA9, HOXD4, HOXD9 and
CC HOXD10 (By similarity). Forms heterodimers with HOXA1, HOXA5, HOXB7 and
CC HOXB8 which bind the 5'-TGATTGAT-3' consensus sequence
CC (PubMed:9191052). Also forms heterodimers with HOXA5, HOXB7, HOXB8,
CC HOXC8 and HOXD4 which bind the 5'-ATCAATCAA-3' consensus sequence
CC (PubMed:7791786). Interacts with PBXIP1 (PubMed:10825160). Interacts
CC with TLX1 (PubMed:19559479). Interacts with FOXC1 (PubMed:15684392).
CC Interacts with MN1 (PubMed:31839203). {ECO:0000250|UniProtKB:P41778,
CC ECO:0000269|PubMed:10052460, ECO:0000269|PubMed:10825160,
CC ECO:0000269|PubMed:12609849, ECO:0000269|PubMed:15684392,
CC ECO:0000269|PubMed:19559479, ECO:0000269|PubMed:19799567,
CC ECO:0000269|PubMed:20553494, ECO:0000269|PubMed:31839203,
CC ECO:0000269|PubMed:7791786, ECO:0000269|PubMed:9191052}.
CC -!- SUBUNIT: [Isoform PBX1a]: Interacts with MEIS2 isoform 4, SP1, SP3 and
CC KLF4. {ECO:0000269|PubMed:21746878}.
CC -!- SUBUNIT: [Isoform PBX1b]: Part of a PDX1:PBX1b:MEIS2B complex; PBX1b
CC recruits MEIS2B to the complex. {ECO:0000250|UniProtKB:P41778}.
CC -!- INTERACTION:
CC P40424; Q5PSV4: BRMS1L; NbExp=3; IntAct=EBI-301611, EBI-5666615;
CC P40424; Q96GN5: CDCA7L; NbExp=3; IntAct=EBI-301611, EBI-5278764;
CC P40424; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-301611, EBI-743105;
CC P40424; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-301611, EBI-6658203;
CC P40424; Q12948: FOXC1; NbExp=5; IntAct=EBI-301611, EBI-1175253;
CC P40424; P09067: HOXB5; NbExp=3; IntAct=EBI-301611, EBI-3893317;
CC P40424; Q00444: HOXC5; NbExp=3; IntAct=EBI-301611, EBI-11955357;
CC P40424; P31273: HOXC8; NbExp=3; IntAct=EBI-301611, EBI-1752118;
CC P40424; O00470: MEIS1; NbExp=3; IntAct=EBI-301611, EBI-1210694;
CC P40424; O14770-4: MEIS2; NbExp=9; IntAct=EBI-301611, EBI-8025850;
CC P40424; Q13526: PIN1; NbExp=3; IntAct=EBI-301611, EBI-714158;
CC P40424; P55347: PKNOX1; NbExp=10; IntAct=EBI-301611, EBI-1373569;
CC P40424-2; P31314: TLX1; NbExp=2; IntAct=EBI-6390251, EBI-2820655;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28270404}.
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 -!- TISSUE SPECIFICITY: Expressed in the kidney. Expressed in the
CC endothelial cells of the glomeruli and interstitium (at protein level)
CC (PubMed:28270404). Expressed in all tissues except in cells of the B
CC and T lineage. Expressed strongly in kidney and brain
CC (PubMed:28270404). {ECO:0000269|PubMed:28270404}.
CC -!- DOMAIN: The homeobox is required for PBX1 nuclear localization and for
CC transcriptional activation of NFIL3. {ECO:0000250|UniProtKB:P41778}.
CC -!- DISEASE: Congenital anomalies of kidney and urinary tract syndrome with
CC or without hearing loss, abnormal ears, or developmental delay
CC (CAKUTHED) [MIM:617641]: An autosomal dominant disorder characterized
CC by variable congenital anomalies of the kidney and urinary tract,
CC sometimes resulting in renal dysfunction or failure, dysmorphic facial
CC features, and abnormalities of the outer ear. Most patients have
CC hearing loss, and some may have global developmental delay.
CC {ECO:0000269|PubMed:28270404, ECO:0000269|PubMed:28566479}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=A chromosomal aberration involving PBX1 is a cause of
CC 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 or
CC by other members of the PBX protein family. TCF3-PBX1 binds the DNA
CC sequence 5'-ATCAATCAA-3'. {ECO:0000269|PubMed:1671560,
CC ECO:0000269|PubMed:1967983, ECO:0000269|PubMed:8327485}.
CC -!- SIMILARITY: Belongs to the TALE/PBX homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36764.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PBX1ID2.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; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390119; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357568; -; NOT_ANNOTATED_CDS; 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 CCDS; CCDS1246.1; -. [P40424-1]
DR CCDS; CCDS55653.1; -. [P40424-3]
DR CCDS; CCDS55654.1; -. [P40424-2]
DR PIR; B34734; B34734.
DR RefSeq; NP_001191892.1; NM_001204963.1. [P40424-3]
DR RefSeq; NP_002576.1; NM_002585.3. [P40424-1]
DR RefSeq; XP_005245286.1; XM_005245229.3. [P40424-1]
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 AlphaFoldDB; P40424; -.
DR BMRB; P40424; -.
DR SASBDB; P40424; -.
DR SMR; P40424; -.
DR BioGRID; 111120; 64.
DR IntAct; P40424; 30.
DR MINT; P40424; -.
DR STRING; 9606.ENSP00000405890; -.
DR iPTMnet; P40424; -.
DR MetOSite; P40424; -.
DR PhosphoSitePlus; P40424; -.
DR BioMuta; PBX1; -.
DR DMDM; 730279; -.
DR EPD; P40424; -.
DR jPOST; P40424; -.
DR MassIVE; P40424; -.
DR MaxQB; P40424; -.
DR PaxDb; P40424; -.
DR PeptideAtlas; P40424; -.
DR PRIDE; P40424; -.
DR ProteomicsDB; 26680; -.
DR ProteomicsDB; 55367; -. [P40424-1]
DR ProteomicsDB; 55368; -. [P40424-2]
DR Antibodypedia; 1079; 424 antibodies from 37 providers.
DR DNASU; 5087; -.
DR Ensembl; ENST00000367897.5; ENSP00000356872.1; ENSG00000185630.19. [P40424-2]
DR Ensembl; ENST00000420696.7; ENSP00000405890.2; ENSG00000185630.19. [P40424-1]
DR Ensembl; ENST00000627490.2; ENSP00000485692.1; ENSG00000185630.19. [P40424-3]
DR GeneID; 5087; -.
DR KEGG; hsa:5087; -.
DR MANE-Select; ENST00000420696.7; ENSP00000405890.2; NM_002585.4; NP_002576.1.
DR UCSC; uc001gct.4; human. [P40424-1]
DR CTD; 5087; -.
DR DisGeNET; 5087; -.
DR GeneCards; PBX1; -.
DR HGNC; HGNC:8632; PBX1.
DR HPA; ENSG00000185630; Low tissue specificity.
DR MalaCards; PBX1; -.
DR MIM; 176310; gene.
DR MIM; 617641; phenotype.
DR neXtProt; NX_P40424; -.
DR OpenTargets; ENSG00000185630; -.
DR Orphanet; 585877; B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality.
DR Orphanet; 97362; Renal hypoplasia, bilateral.
DR PharmGKB; PA32970; -.
DR VEuPathDB; HostDB:ENSG00000185630; -.
DR eggNOG; KOG0774; Eukaryota.
DR GeneTree; ENSGT00940000154374; -.
DR HOGENOM; CLU_041153_1_0_1; -.
DR InParanoid; P40424; -.
DR OMA; LAHHMTA; -.
DR OrthoDB; 804740at2759; -.
DR PhylomeDB; P40424; -.
DR TreeFam; TF314340; -.
DR PathwayCommons; P40424; -.
DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR SignaLink; P40424; -.
DR SIGNOR; P40424; -.
DR BioGRID-ORCS; 5087; 17 hits in 1092 CRISPR screens.
DR ChiTaRS; PBX1; human.
DR EvolutionaryTrace; P40424; -.
DR GeneWiki; PBX1; -.
DR GenomeRNAi; 5087; -.
DR Pharos; P40424; Tbio.
DR PRO; PR:P40424; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P40424; protein.
DR Bgee; ENSG00000185630; Expressed in cortical plate and 210 other tissues.
DR ExpressionAtlas; P40424; baseline and differential.
DR Genevisible; P40424; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:NTNU_SB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
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:0048568; P:embryonic organ development; IBA:GO_Central.
DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR GO; GO:0001654; P:eye development; IBA:GO_Central.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0001779; P:natural killer cell differentiation; ISS:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IBA:GO_Central.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR IDEAL; IID00149; -.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR005542; PBX.
DR Pfam; PF00046; Homeodomain; 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.
DR PROSITE; PS51978; PBC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Chromosomal rearrangement;
KW Developmental protein; Differentiation; Disease variant; DNA-binding;
KW Homeobox; Nucleus; Proto-oncogene; Reference proteome; Repressor;
KW Sexual differentiation; Steroidogenesis; Transcription;
KW Transcription regulation.
FT CHAIN 1..430
FT /note="Pre-B-cell leukemia transcription factor 1"
FT /id="PRO_0000049235"
FT DOMAIN 38..232
FT /note="PBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01322"
FT DNA_BIND 233..295
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 45..124
FT /note="PBC-A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01322"
FT REGION 127..232
FT /note="PBC-B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01322"
FT REGION 317..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 88..89
FT /note="Breakpoint for translocation to form TCF3-PBX1
FT oncogene"
FT SITE 286
FT /note="Required for binding to the NFIL3 promoter"
FT /evidence="ECO:0000250|UniProtKB:P41778"
FT VAR_SEQ 334..347
FT /note="SSSSFNMSNSGDLF -> GYPSPCYQPDRRIQ (in isoform PBX1b)"
FT /evidence="ECO:0000305"
FT /id="VSP_002271"
FT VAR_SEQ 348..430
FT /note="Missing (in isoform PBX1b)"
FT /evidence="ECO:0000305"
FT /id="VSP_002272"
FT VAR_SEQ 401..430
FT /note="ANGGWQDATTPSSVTSPTEGPGSVHSDTSN -> HLPRHPRQAHYHFRLPTW
FT HP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044499"
FT VARIANT 31
FT /note="G -> S (in dbSNP:rs2275558)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_068904"
FT VARIANT 184..430
FT /note="Missing (in CAKUTHED; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28566479"
FT /id="VAR_079369"
FT CONFLICT 351
FT /note="Q -> H (in Ref. 3; BAG61583)"
FT /evidence="ECO:0000305"
FT HELIX 242..254
FT /evidence="ECO:0007829|PDB:1PUF"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:1PUF"
FT HELIX 263..273
FT /evidence="ECO:0007829|PDB:1PUF"
FT HELIX 277..293
FT /evidence="ECO:0007829|PDB:1PUF"
FT TURN 295..300
FT /evidence="ECO:0007829|PDB:1PUF"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:1PUF"
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
