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Protein

Pre-B-cell leukemia transcription factor 1

Gene

Pbx1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Biological processi

  • adrenal gland development Source: MGI
  • anterior/posterior pattern specification Source: MGI
  • branching involved in ureteric bud morphogenesis Source: MGI
  • embryonic hemopoiesis Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • embryonic organ development Source: MGI
  • embryonic skeletal system development Source: MGI
  • negative regulation of neuron differentiation Source: MGI
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • organ morphogenesis Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of G2/M transition of mitotic cell cycle Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • proximal/distal pattern formation Source: MGI
  • regulation of cell proliferation Source: MGI
  • regulation of ossification Source: MGI
  • sex differentiation Source: UniProtKB-KW
  • spleen development Source: MGI
  • steroid biosynthetic process Source: UniProtKB-KW
  • thymus development Source: MGI
  • urogenital system development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Differentiation, Sexual differentiation, Steroidogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:97495. Pbx1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei126 – 1261PhosphoserineBy similarity
Modified residuei321 – 3211PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP41778.
PRIDEiP41778.

PTM databases

PhosphoSiteiP41778.

Expressioni

Tissue specificityi

Widely distributed in steroidogenic and non-steroidogenic cells.

Gene expression databases

BgeeiP41778.
CleanExiMM_PBX1.
ExpressionAtlasiP41778. baseline and differential.
GenevisibleiP41778. MM.

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.
STRINGi10090.ENSMUSP00000135516.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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. AlignAdd to basket

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

        10         20         30         40         50
MDEQPRLMHS HAGVGMAGHP GLSQHLQDGA GGTEGEGGRK QDIGDILQQI
60 70 80 90 100
MTITDQSLDE AQARKHALNC HRMKPALFNV LCEIKEKTVL SIRGAQEEEP
110 120 130 140 150
TDPQLMRLDN MLLAEGVAGP EKGGGSAAAA AAAAASGGAG SDNSVEHSDY
160 170 180 190 200
RAKLSQIRQI YHTELEKYEQ ACNEFTTHVM NLLREQSRTR PISPKEIERM
210 220 230 240 250
VSIIHRKFSS IQMQLKQSTC EAVMILRSRF LDARRKRRNF NKQATEILNE
260 270 280 290 300
YFYSHLSNPY PSEEAKEELA KKCGITVSQV SNWFGNKRIR YKKNIGKFQE
310 320 330 340 350
EANIYAAKTA VTATNVSAHG SQANSPSTPN SAGSSSSFNM SNSGDLFMSV
360 370 380 390 400
QSLNGDSYQG AQVGANVQSQ VDTLRHVISQ TGGYSDGLAA SQMYSPQGIS
410 420 430
ANGGWQDATT PSSVTSPTEG PGSVHSDTSN
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:
EMBLi
GenBanki
DDBJi
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]
ENSMUST00000188912; ENSMUSP00000140606; 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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi202037. 23 interactions.
DIPiDIP-6107N.
IntActiP41778. 1 interaction.
MINTiMINT-96519.
STRINGi10090.ENSMUSP00000135516.

PTM databases

PhosphoSiteiP41778.

Proteomic databases

PaxDbiP41778.
PRIDEiP41778.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000072863; ENSMUSP00000072640; ENSMUSG00000052534. [P41778-2]
ENSMUST00000176540; ENSMUSP00000135516; ENSMUSG00000052534. [P41778-1]
ENSMUST00000176790; ENSMUSP00000134925; ENSMUSG00000052534. [P41778-2]
ENSMUST00000188912; ENSMUSP00000140606; ENSMUSG00000052534. [P41778-2]
GeneIDi18514.
KEGGimmu:18514.
UCSCiuc007dle.1. mouse. [P41778-1]

Organism-specific databases

CTDi5087.
MGIiMGI:97495. Pbx1.

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiPbx1. mouse.
EvolutionaryTraceiP41778.
NextBioi294252.
PROiP41778.
SOURCEiSearch...

Gene expression databases

BgeeiP41778.
CleanExiMM_PBX1.
ExpressionAtlasiP41778. baseline and differential.
GenevisibleiP41778. MM.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 156 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.