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P41778

- PBX1_MOUSE

UniProt

P41778 - PBX1_MOUSE

Protein

Pre-B-cell leukemia transcription factor 1

Gene

Pbx1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 149 (01 Oct 2014)
      Sequence version 2 (21 Feb 2002)
      Previous versions | rss
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    Functioni

    Plays a role in the cAMP-dependent regulation of CYP17 gene expression via its cAMP-regulatory sequence (CRS1) 5'-ATCAATCAA-3'. Acts as a transcriptional activator of PF4 in complex with MEIS1. May have a role in steroidogenesis and, subsequently, sexual development and differentiation. Isoform PBX1b 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. Probably in complex with MEIS2, is involved in transcriptional regulation by KLF4. Acts as a transcriptional activator of NKX2-5 and a transcriptional repressor of CDKN2B. Together with NKX2-5, it is required for spleen development through a mechanism that involves CDKN2B repression.1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi233 – 29563Homeobox; TALE-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. protein binding Source: MGI
    3. protein heterodimerization activity Source: MGI
    4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    6. sequence-specific DNA binding Source: MGI

    GO - Biological processi

    1. adrenal gland development Source: MGI
    2. anterior/posterior pattern specification Source: MGI
    3. branching involved in ureteric bud morphogenesis Source: MGI
    4. embryonic hemopoiesis Source: MGI
    5. embryonic limb morphogenesis Source: MGI
    6. embryonic organ development Source: MGI
    7. embryonic skeletal system development Source: MGI
    8. negative regulation of neuron differentiation Source: MGI
    9. negative regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
    10. organ morphogenesis Source: MGI
    11. positive regulation of cell proliferation Source: MGI
    12. positive regulation of G2/M transition of mitotic cell cycle Source: MGI
    13. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
    14. proximal/distal pattern formation Source: MGI
    15. regulation of cell proliferation Source: MGI
    16. regulation of ossification Source: MGI
    17. sex differentiation Source: UniProtKB-KW
    18. spleen development Source: MGI
    19. steroid biosynthetic process Source: UniProtKB-KW
    20. thymus development Source: MGI
    21. urogenital system development Source: MGI

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Differentiation, Sexual differentiation, Steroidogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_216222. Transcriptional regulation of pluripotent stem cells.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pre-B-cell leukemia transcription factor 1
    Alternative name(s):
    Homeobox protein PBX1
    Gene namesi
    Name:Pbx1
    Synonyms:Pbx-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 1

    Organism-specific databases

    MGIiMGI:97495. Pbx1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. nucleus Source: MGI
    3. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 430430Pre-B-cell leukemia transcription factor 1PRO_0000049236Add
    BLAST

    Proteomic databases

    MaxQBiP41778.
    PaxDbiP41778.
    PRIDEiP41778.

    PTM databases

    PhosphoSiteiP41778.

    Expressioni

    Tissue specificityi

    Widely distributed in steroidogenic and non-steroidogenic cells.

    Gene expression databases

    ArrayExpressiP41778.
    BgeeiP41778.
    CleanExiMM_PBX1.
    GenevestigatoriP41778.

    Interactioni

    Subunit structurei

    Forms a heterodimer with MEIS1 which binds DNA including a cAMP-responsive sequence in CYP17. Also forms heterotrimers with MEIS1 and a number of HOX proteins including HOXA9, HOXD4, HOXD9 and HOXD10. Interacts with PBXIP1 and TLX1. Isoform PBX1a interacts with MEIS2 isoform Meis2D, SP1, SP3 and KLF4. Isoform PBX1b is part of a PDX1:PBX1b:MEIS2b complex; PBX1b recruits Meis2B to the complex.7 Publications

    Protein-protein interaction databases

    BioGridi202037. 23 interactions.
    DIPiDIP-6107N.
    IntActiP41778. 1 interaction.
    MINTiMINT-96519.

    Structurei

    Secondary structure

    1
    430
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi236 – 2405
    Turni241 – 2433
    Helixi244 – 25411
    Turni255 – 2573
    Helixi263 – 27311
    Helixi277 – 28711
    Turni288 – 2903
    Helixi295 – 30713

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DU6NMR-A241-294[»]
    1LFUNMR-P233-313[»]
    ProteinModelPortaliP41778.
    SMRiP41778. Positions 233-305.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP41778.

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi127 – 1359Poly-Ala

    Sequence similaritiesi

    Belongs to the TALE/PBX homeobox family.Curated
    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG248144.
    GeneTreeiENSGT00390000016426.
    HOGENOMiHOG000266972.
    HOVERGENiHBG000122.
    InParanoidiP41778.
    KOiK09355.
    OMAiNIQSQVD.
    OrthoDBiEOG75XGM1.
    PhylomeDBiP41778.
    TreeFamiTF314340.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    IPR005542. PBX.
    [Graphical view]
    PfamiPF00046. Homeobox. 1 hit.
    PF03792. PBC. 1 hit.
    [Graphical view]
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform PBX1a (identifier: P41778-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDEQPRLMHS HAGVGMAGHP GLSQHLQDGA GGTEGEGGRK QDIGDILQQI    50
    MTITDQSLDE AQARKHALNC HRMKPALFNV LCEIKEKTVL SIRGAQEEEP 100
    TDPQLMRLDN MLLAEGVAGP EKGGGSAAAA AAAAASGGAG SDNSVEHSDY 150
    RAKLSQIRQI YHTELEKYEQ ACNEFTTHVM NLLREQSRTR PISPKEIERM 200
    VSIIHRKFSS IQMQLKQSTC EAVMILRSRF LDARRKRRNF NKQATEILNE 250
    YFYSHLSNPY PSEEAKEELA KKCGITVSQV SNWFGNKRIR YKKNIGKFQE 300
    EANIYAAKTA VTATNVSAHG SQANSPSTPN SAGSSSSFNM SNSGDLFMSV 350
    QSLNGDSYQG AQVGANVQSQ VDTLRHVISQ TGGYSDGLAA SQMYSPQGIS 400
    ANGGWQDATT PSSVTSPTEG PGSVHSDTSN 430
    Length:430
    Mass (Da):46,626
    Last modified:February 21, 2002 - v2
    Checksum:iAD3FFACBC5A9E715
    GO
    Isoform PBX1b (identifier: P41778-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         334-347: SSSSFNMSNSGDLF → GYPSPCYQPDRRIQ
         348-430: Missing.

    Show »
    Length:347
    Mass (Da):38,427
    Checksum:iC4A2BDDD4A410C20
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei334 – 34714SSSSF…SGDLF → GYPSPCYQPDRRIQ in isoform PBX1b. 1 PublicationVSP_002273Add
    BLAST
    Alternative sequencei348 – 43083Missing in isoform PBX1b. 1 PublicationVSP_002274Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27453 mRNA. Translation: AAA21832.1.
    AF020196 mRNA. Translation: AAB71191.1.
    BC058390 mRNA. Translation: AAH58390.1.
    CCDSiCCDS15461.1. [P41778-1]
    CCDS15462.1. [P41778-2]
    PIRiA54863.
    RefSeqiNP_001278437.1. NM_001291508.1. [P41778-2]
    NP_032809.1. NM_008783.3. [P41778-2]
    NP_899198.1. NM_183355.3. [P41778-1]
    UniGeneiMm.43358.
    Mm.440114.

    Genome annotation databases

    EnsembliENSMUST00000072863; ENSMUSP00000072640; ENSMUSG00000052534. [P41778-2]
    ENSMUST00000176540; ENSMUSP00000135516; ENSMUSG00000052534. [P41778-1]
    ENSMUST00000176790; ENSMUSP00000134925; ENSMUSG00000052534. [P41778-2]
    GeneIDi18514.
    KEGGimmu:18514.
    UCSCiuc007dle.1. mouse. [P41778-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27453 mRNA. Translation: AAA21832.1 .
    AF020196 mRNA. Translation: AAB71191.1 .
    BC058390 mRNA. Translation: AAH58390.1 .
    CCDSi CCDS15461.1. [P41778-1 ]
    CCDS15462.1. [P41778-2 ]
    PIRi A54863.
    RefSeqi NP_001278437.1. NM_001291508.1. [P41778-2 ]
    NP_032809.1. NM_008783.3. [P41778-2 ]
    NP_899198.1. NM_183355.3. [P41778-1 ]
    UniGenei Mm.43358.
    Mm.440114.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1DU6 NMR - A 241-294 [» ]
    1LFU NMR - P 233-313 [» ]
    ProteinModelPortali P41778.
    SMRi P41778. Positions 233-305.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202037. 23 interactions.
    DIPi DIP-6107N.
    IntActi P41778. 1 interaction.
    MINTi MINT-96519.

    Chemistry

    BindingDBi P41778.

    PTM databases

    PhosphoSitei P41778.

    Proteomic databases

    MaxQBi P41778.
    PaxDbi P41778.
    PRIDEi P41778.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000072863 ; ENSMUSP00000072640 ; ENSMUSG00000052534 . [P41778-2 ]
    ENSMUST00000176540 ; ENSMUSP00000135516 ; ENSMUSG00000052534 . [P41778-1 ]
    ENSMUST00000176790 ; ENSMUSP00000134925 ; ENSMUSG00000052534 . [P41778-2 ]
    GeneIDi 18514.
    KEGGi mmu:18514.
    UCSCi uc007dle.1. mouse. [P41778-1 ]

    Organism-specific databases

    CTDi 5087.
    MGIi MGI:97495. Pbx1.

    Phylogenomic databases

    eggNOGi NOG248144.
    GeneTreei ENSGT00390000016426.
    HOGENOMi HOG000266972.
    HOVERGENi HBG000122.
    InParanoidi P41778.
    KOi K09355.
    OMAi NIQSQVD.
    OrthoDBi EOG75XGM1.
    PhylomeDBi P41778.
    TreeFami TF314340.

    Enzyme and pathway databases

    Reactomei REACT_216222. Transcriptional regulation of pluripotent stem cells.

    Miscellaneous databases

    ChiTaRSi PBX1. mouse.
    EvolutionaryTracei P41778.
    NextBioi 294252.
    PROi P41778.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P41778.
    Bgeei P41778.
    CleanExi MM_PBX1.
    Genevestigatori P41778.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    IPR005542. PBX.
    [Graphical view ]
    Pfami PF00046. Homeobox. 1 hit.
    PF03792. PBC. 1 hit.
    [Graphical view ]
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A cAMP-regulatory sequence (CRS1) of CYP17 is a cellular target for the homeodomain protein Pbx1."
      Kagawa N., Ogo A., Takahashi Y., Iwamatsu A., Waterman M.R.
      J. Biol. Chem. 269:18716-18719(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PBX1B), PARTIAL PROTEIN SEQUENCE.
      Tissue: Adrenal gland.
    2. Liu Y., MacDonald R.J.
      Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PBX1A).
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PBX1A).
      Strain: C57BL/6.
      Tissue: Brain.
    4. "Meis proteins are major in vivo DNA binding partners for wild-type but not chimeric Pbx proteins."
      Chang C.-P., Jacobs Y., Nakamura T., Jenkins N.A., Copeland N.G., Cleary M.L.
      Mol. Cell. Biol. 17:5679-5687(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MEIS1.
    5. "Members of the Meis1 and Pbx homeodomain protein families cooperatively bind a cAMP-responsive sequence (CRS1) from bovine CYP17."
      Bischof L.J., Kagawa N., Moskow J.J., Takahashi Y., Iwamatsu A., Buchberg A.M., Waterman M.R.
      J. Biol. Chem. 273:7941-7948(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MEIS1.
    6. "An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2)."
      Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S., Buchberg A.M., Wright C.V., MacDonald R.J.
      Mol. Cell. Biol. 18:5109-5120(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH PDX1 AND MEIS2.
    7. "HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells."
      Shen W.-F., Rozenfeld S., Kwong A., Koemueves L.G., Lawrence H.J., Largman C.
      Mol. Cell. Biol. 19:3051-3061(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HOXA9 AND MEIS1.
    8. "PBX and MEIS as non-DNA-binding partners in trimeric complexes with HOX proteins."
      Shanmugam K., Green N.C., Rambaldi I., Saragovi H.U., Featherstone M.S.
      Mol. Cell. Biol. 19:7577-7588(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HOXD4; HOXD9; HOXD10 AND MEIS1.
    9. "DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex."
      Liu Y., MacDonald R.J., Swift G.H.
      J. Biol. Chem. 276:17985-17993(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MEIS2, IDENTIFICATION IN A COMPLEX WITH PDX1 AND MEIS2.
    10. Cited for: FUNCTION.
    11. "Conformational changes in the PBX homeodomain and C-terminal extension upon binding DNA and HOX-derived YPWM peptides(,)."
      Sprules T., Green N., Featherstone M., Gehring K.
      Biochemistry 39:9943-9950(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 241-294.
    12. "Lock and key binding of the HOX YPWM peptide to the PBX homeodomain."
      Sprules T., Green N., Featherstone M., Gehring K.
      J. Biol. Chem. 278:1053-1058(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 233-313 IN COMPLEX WITH DNA.

    Entry informationi

    Entry nameiPBX1_MOUSE
    AccessioniPrimary (citable) accession number: P41778
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: February 21, 2002
    Last modified: October 1, 2014
    This is version 149 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3