{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P40424","secondaryAccessions":["B4DSC1","F5H4U9","Q5T488"],"uniProtkbId":"PBX1_HUMAN","entryAudit":{"firstPublicDate":"1995-02-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1995-02-01","entryVersion":238,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Pre-B-cell leukemia transcription factor 1"}},"alternativeNames":[{"fullName":{"value":"Homeobox protein PBX1"}},{"fullName":{"value":"Homeobox protein PRL"}}]},"genes":[{"geneName":{"value":"PBX1"},"synonyms":[{"value":"PRL"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P41778"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12609849"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21746878"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7791786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8327485"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9191052"}],"value":"Transcription factor which binds the DNA sequence 5'-TGATTGAT-3' as part of a heterodimer with HOX proteins such as HOXA1, HOXA5, HOXB7 and HOXB8 (PubMed:9191052). Binds to the DNA sequence 5'-TGATTGAC-3' in complex with a nuclear factor which is not a class I HOX protein (PubMed:9191052). Has also been shown to bind the DNA sequence 5'-ATCAATCAA-3' cooperatively with HOXA5, HOXB7, HOXB8, HOXC8 and HOXD4 (PubMed:7791786, PubMed:8327485). Acts as a transcriptional activator of PF4 in complex with MEIS1 (PubMed:12609849). Also activates transcription of SOX3 in complex with MEIS1 by binding to the 5'-TGATTGAC-3' consensus sequence (By similarity). In natural killer cells, binds to the NFIL3 promoter and acts as a transcriptional activator of NFIL3, promoting natural killer cell development (By similarity). Plays a role in the cAMP-dependent regulation of CYP17A1 gene expression via its cAMP-regulatory sequence (CRS1) (By similarity). Probably in complex with MEIS2, involved in transcriptional regulation by KLF4 (PubMed:21746878). Acts as a transcriptional activator of NKX2-5 and a transcriptional repressor of CDKN2B (By similarity). Together with NKX2-5, required for spleen development through a mechanism that involves CDKN2B repression (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P41778"}],"value":"As part of a PDX1:PBX1b:MEIS2B complex in pancreatic acinar cells, is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element"}],"commentType":"FUNCTION","molecule":"Isoform PBX1b"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P41778"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10052460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10825160"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12609849"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15684392"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19559479"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19799567"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20553494"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31839203"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7791786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9191052"}],"value":"Forms a heterodimer with MEIS1 which binds DNA (PubMed:19799567). The PBX1-MEIS1 heterodimer binds a cAMP-responsive sequence in CYP17 (By similarity). It also binds a consensus region in the SOX3 promoter (PubMed:19799567). PBX1 forms heterotrimers with MEIS1 and a number of HOX proteins including HOXA9, HOXD4, HOXD9 and HOXD10 (By similarity). Forms heterodimers with HOXA1, HOXA5, HOXB7 and HOXB8 which bind the 5'-TGATTGAT-3' consensus sequence (PubMed:9191052). Also forms heterodimers with HOXA5, HOXB7, HOXB8, HOXC8 and HOXD4 which bind the 5'-ATCAATCAA-3' consensus sequence (PubMed:7791786). Interacts with PBXIP1 (PubMed:10825160). Interacts with TLX1 (PubMed:19559479). Interacts with FOXC1 (PubMed:15684392). Interacts with MN1 (PubMed:31839203)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21746878"}],"value":"Interacts with MEIS2 isoform 4, SP1, SP3 and KLF4"}],"commentType":"SUBUNIT","molecule":"Isoform PBX1a"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P41778"}],"value":"Part of a PDX1:PBX1b:MEIS2B complex; PBX1b recruits MEIS2B to the complex"}],"commentType":"SUBUNIT","molecule":"Isoform PBX1b"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q5PSV4","geneName":"BRMS1L","intActId":"EBI-5666615"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q96GN5","geneName":"CDCA7L","intActId":"EBI-5278764"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q5JVL4","geneName":"EFHC1","intActId":"EBI-743105"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q86YD7","geneName":"FAM90A1","intActId":"EBI-6658203"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q12948","geneName":"FOXC1","intActId":"EBI-1175253"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"P09067","geneName":"HOXB5","intActId":"EBI-3893317"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q00444","geneName":"HOXC5","intActId":"EBI-11955357"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"P31273","geneName":"HOXC8","intActId":"EBI-1752118"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"O00470","geneName":"MEIS1","intActId":"EBI-1210694"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"O14770","geneName":"MEIS2","intActId":"EBI-2804934"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"O14770-4","geneName":"MEIS2","intActId":"EBI-8025850"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q13526","geneName":"PIN1","intActId":"EBI-714158"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"P55347","geneName":"PKNOX1","intActId":"EBI-1373569"},"numberOfExperiments":12,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424","intActId":"EBI-301611"},"interactantTwo":{"uniProtKBAccession":"Q96KN3","geneName":"PKNOX2","intActId":"EBI-2692890"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P40424-2","intActId":"EBI-6390251"},"interactantTwo":{"uniProtKBAccession":"P31314","geneName":"TLX1","intActId":"EBI-2820655"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28270404"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"PBX1a"},"isoformIds":["P40424-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"PBX1b"},"isoformIds":["P40424-2"],"sequenceIds":["VSP_002271","VSP_002272"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P40424-3"],"sequenceIds":["VSP_044499"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28270404"}],"value":"Expressed in the kidney. Expressed in the endothelial cells of the glomeruli and interstitium (at protein level) (PubMed:28270404). Expressed in all tissues except in cells of the B and T lineage. Expressed strongly in kidney and brain (PubMed:28270404)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P41778"}],"value":"The homeobox is required for PBX1 nuclear localization and for transcriptional activation of NFIL3"}],"commentType":"DOMAIN"},{"commentType":"DISEASE","disease":{"diseaseId":"Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay","diseaseAccession":"DI-05075","acronym":"CAKUTHED","description":"An autosomal dominant disorder characterized by variable congenital anomalies of the kidney and urinary tract, sometimes resulting in renal dysfunction or failure, dysmorphic facial features, and abnormalities of the outer ear. Most patients have hearing loss, and some may have global developmental delay.","diseaseCrossReference":{"database":"MIM","id":"617641"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28270404"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28566479"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1671560"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1967983"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8327485"}],"value":"A chromosomal aberration involving PBX1 is a cause of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with TCF3. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. TCF3-PBX1 binds the DNA sequence 5'-ATCAATCAA-3'"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the TALE/PBX homeobox family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAA36764.1","note":"Extended N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/2/PBX1","ftp":false}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":430,"modifier":"EXACT"}},"description":"Pre-B-cell leukemia transcription factor 1","featureId":"PRO_0000049235"},{"type":"Domain","location":{"start":{"value":38,"modifier":"EXACT"},"end":{"value":232,"modifier":"EXACT"}},"description":"PBC","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01322"}]},{"type":"DNA binding","location":{"start":{"value":233,"modifier":"EXACT"},"end":{"value":295,"modifier":"EXACT"}},"description":"Homeobox; 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