Reviewed, UniProtKB/Swiss-Prot P40424 (PBX1_HUMAN)

Names and origin

Protein names

Recommended name:
    Pre-B-cell leukemia transcription factor 1
Alternative name(s):
    Homeobox protein PBX1
    Homeobox protein PRL

Gene names

Name:	PBX1
Synonyms:	PRL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	430 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds the sequence 5'-ATCAATCAA-3'. Acts as a transcriptional activator of PF4 in complex with MEIS1. Converted into a potent transcriptional activator by the (1;19) translocation. May have a role in steroidogenesis and, subsequently, sexual development and differentiation. Ref.10
Subunit structure	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. Ref.10 Ref.9
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in all tissues except in cells of the B and T lineage.
Involvement in disease	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. E2A-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family.
Sequence similarities	Belongs to the TALE/PBX homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Differentiation Sexual differentiation Steroidogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Repressor
Technical term	3D-structure
Gene Ontology (GO)
Biological process	C21-steroid hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW sex determination Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular function	protein binding Ref.11 Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HOXB1	P14653	1	EBI-301611,EBI-301331

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform PBX1a (identifier: P40424-1)

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.

Isoform PBX1b (identifier: P40424-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 430

430

Pre-B-cell leukemia transcription factor 1

PRO_0000049235

Regions

DNA binding

233 – 295

63

Homeobox; TALE-type

Compositional bias

127 – 135

9

Poly-Ala

Sites

Site

88 – 89

2

Breakpoint for translocation to form CAA67062A-PBX1 oncogene

Natural variations

Alternative sequence

334 – 347

14

SSSSF…SGDLF → GYPSPCYQPDRRIQ in isoform PBX1b.

VSP_002271

Alternative sequence

348 – 430

83

Missing in isoform PBX1b.

VSP_002272

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

430

Helix Strand Turn

Details...

Helix

242 – 253

12

Turn

254 – 257

4

Helix

263 – 273

11

Helix

277 – 293

17

Helix

295 – 298

4

Helix

299 – 304

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform PBX1a [UniParc]. Last modified February 1, 1995. Version 1. Checksum: AD3FFACBC5A9E715	FASTA	430	46,626
	10 20 30 40 50 60 MDEQPRLMHS HAGVGMAGHP GLSQHLQDGA GGTEGEGGRK QDIGDILQQI MTITDQSLDE 70 80 90 100 110 120 AQARKHALNC HRMKPALFNV LCEIKEKTVL SIRGAQEEEP TDPQLMRLDN MLLAEGVAGP 130 140 150 160 170 180 EKGGGSAAAA AAAAASGGAG SDNSVEHSDY RAKLSQIRQI YHTELEKYEQ ACNEFTTHVM 190 200 210 220 230 240 NLLREQSRTR PISPKEIERM VSIIHRKFSS IQMQLKQSTC EAVMILRSRF LDARRKRRNF 250 260 270 280 290 300 NKQATEILNE YFYSHLSNPY PSEEAKEELA KKCGITVSQV SNWFGNKRIR YKKNIGKFQE 310 320 330 340 350 360 EANIYAAKTA VTATNVSAHG SQANSPSTPN SAGSSSSFNM SNSGDLFMSV QSLNGDSYQG 370 380 390 400 410 420 AQVGANVQSQ VDTLRHVISQ TGGYSDGLAA SQMYSPQGIS ANGGWQDATT PSSVTSPTEG 430 PGSVHSDTSN
	Isoform PBX1b. Checksum: C4A2BDDD4A410C20	FASTA	347	38,427
	10 20 30 40 50 60 MDEQPRLMHS HAGVGMAGHP GLSQHLQDGA GGTEGEGGRK QDIGDILQQI MTITDQSLDE 70 80 90 100 110 120 AQARKHALNC HRMKPALFNV LCEIKEKTVL SIRGAQEEEP TDPQLMRLDN MLLAEGVAGP 130 140 150 160 170 180 EKGGGSAAAA AAAAASGGAG SDNSVEHSDY RAKLSQIRQI YHTELEKYEQ ACNEFTTHVM 190 200 210 220 230 240 NLLREQSRTR PISPKEIERM VSIIHRKFSS IQMQLKQSTC EAVMILRSRF LDARRKRRNF 250 260 270 280 290 300 NKQATEILNE YFYSHLSNPY PSEEAKEELA KKCGITVSQV SNWFGNKRIR YKKNIGKFQE 310 320 330 340 EANIYAAKTA VTATNVSAHG SQANSPSTPN SAGGYPSPCY QPDRRIQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1." Monica K., Galili N., Nourse J., Saltman D., Cleary M.L. Mol. Cell. Biol. 11:6149-6157(1991) [PubMed: 1682799] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians." Thameem F., Wolford J.K., Bogardus C., Prochazka M. Biochim. Biophys. Acta 1518:215-220(2001) [PubMed: 11267683] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM PBX1A).
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PBX1A). Tissue: Brain.
[5]	"A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL." Kamps M.P., Murre C., Sun X.-H., Baltimore D. Cell 60:547-555(1990) [PubMed: 1967983] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 89-430, CHROMOSOMAL TRANSLOCATION WITH TCF3.
[6]	"The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias." Hunger S.P., Galili N., Carroll A.J., Crist W.M., Link M.P., Cleary M.L. Blood 77:687-693(1991) [PubMed: 1671560] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH TCF3.
[7]	"Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia." van Dijk M.A., Voorhoeve P.M., Murre C. Proc. Natl. Acad. Sci. U.S.A. 90:6061-6065(1993) [PubMed: 8327485] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation." Lu Q., Wright D.D., Kamps M.P. Mol. Cell. Biol. 14:3938-3948(1994) [PubMed: 7910944] [Abstract] Cited for: CHARACTERIZATION.
[9]	"Functional cloning and characterization of a novel nonhomeodomain protein that inhibits the binding of PBX1-HOX complexes to DNA." Abramovich C., Shen W.-F., Pineault N., Imren S., Montpetit B., Largman C., Humphries R.K. J. Biol. Chem. 275:26172-26177(2000) [PubMed: 10825160] [Abstract] Cited for: INTERACTION WITH PBXIP1.
[10]	"Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene." Okada Y., Nagai R., Sato T., Matsuura E., Minami T., Morita I., Doi T. Blood 101:4748-4756(2003) [PubMed: 12609849] [Abstract] Cited for: FUNCTION, INTERACTION WITH MEIS1.
[11]	"Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation." Piper D.E., Batchelor A.H., Chang C.-P., Cleary M.L., Wolberger C. Cell 96:587-597(1999) [PubMed: 10052460] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 233-319 IN COMPLEX WITH HOXB1.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

M86546 mRNA. Translation: AAA60031.1.
AF313404 , AF313396, AF313397, AF313398, AF313399, AF313400, AF313401, AF313402, AF313403 Genomic DNA. Translation: AAG30941.1.
AL359255, AL357568, AL390119 Genomic DNA. Translation: CAI14854.1.
AL390119, AL359255, AL357568 Genomic DNA. Translation: CAH73499.1.
AL357568, AL390119, AL359255 Genomic DNA. Translation: CAI14908.1.
BC101578 mRNA. Translation: AAI01579.1.
M31522 mRNA. Translation: AAA36764.1. Different initiation.

IPI

IPI00028415.
IPI00215683.

PIR

B34734.

RefSeq

NP_002576.1.

UniGene

Hs.654412

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B72	X-ray	2.35	B	233-319	[»]
1PUF	X-ray	1.90	B	233-305	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P40424. 1 interaction.

Proteomic databases

PRIDE

P40424.

Genome annotation databases

Ensembl

ENSG00000185630. Homo sapiens. [Contig view]

GeneID

5087.

KEGG

hsa:5087.

Organism-specific databases

GeneCards

GC01P162795.

H-InvDB

HIX0001277.

HGNC

HGNC:8632. PBX1.

HPA

CAB018768.
HPA003505.
HPA003881.

MIM

176310. gene.

Orphanet

513. Leukemia, lymphoblastic, acute.

PharmGKB

PA32970.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P40424.

HOVERGEN

P40424.

OMA

P40424. STPNSAX.

Gene expression databases

ArrayExpress

P40424.

Bgee

P40424.

CleanEx

HS_PBX1.
HS_PRL.

GermOnline

ENSG00000185630. Homo sapiens.

Family and domain databases

InterPro

IPR001356. Homeobox.
IPR017970. Homeobox_CS.
IPR012287. Homeodomain-rel.
IPR005542. PBX.
[Graphical view]

Gene3D

G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.

Pfam

PF00046. Homeobox. 1 hit.
PF03792. PBC. 1 hit.
[Graphical view]

ProDom

PD000010. Homeobox. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00389. HOX. 1 hit.
[Graphical view]

PROSITE

PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

19618.

SOURCE

Search...

Entry information

Entry name

PBX1_HUMAN

Accession

Primary (citable) accession number: P40424
Secondary accession number(s): Q5T488

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	June 16, 2009
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)