Atlas of Genetics and Cytogenetics in Oncology and Haematology


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HLF (hepatic leukemia factor)

Identity

HGNC HLF
Location 17q22

DNA/RNA

 
  DNA diagram
Transcription 3.9 kb

Protein

 
  Protein diagram
Description 295 amino acids, MW 43 kDa
Expression HLF is normally expressed in hepatocytes and liver-derived cell lines, and, to a lesser extent, in lung, kidney and neurons of the central nervous system; it is not expressed in hematopoietic tissues or cell lines
Localisation nuclear
Function the normal function of HLF is largely unknown; HLF is a member of the PAR (proline and acidic amino acid-rich region) subfamily of b/ZIP (basic region leucine zipper) transcription factors; PAR and b/ZIP proteins bind to the DNA as dimers; HLF acts as a transcriptionnal transactivator; there are evidences that HLF protein transactivates factor VIII and factor IX genes, by binding as a homodimer (HLF/HLF) or a heterodimer with one albumin D-element binding protein sub unit (HLF/DBP), to multiple sites in the promoter of these genes; in the mouse central nervous system ontogeny, HLF expression increases markedly with synaptogenesis, suggesting that HLF plays a role in the function of adult differentiated neurons
Homology other members of the b/ZIP PAR subfamily; in mammals: albumin D-element binding protein (DBP) and thyrotroph embryonic factor / vitellogenin gene binding protein (TEF/VBP); like HLF, they are transcription activators; the three proteins have an ability to form heterodimers with one another through the leucine-zipper domain; in other species : vitellogenin binding protein (VBP) in the chicken and Ces-2 gene in the nematode Caenorhabditis elegans

Implicated in

Entity t(17;19)(q22;p13) in acute lymphoblastic leukemia --> E2A - HLF fusion gene
Disease childhood pro-B cell acute lymphoblastic leukemia
Prognosis poor prognosis is likely
Abnormal Protein fusion encodes a protein which contains the AD1 and AD2 transactivation domains of E2A, linked to the bZIP DNA binding / protein dimerization region of HLF
Oncogenesis E2A-HLF alters the apoptotic pathway of pro-B lymphocytic cells, leading to the survival of defective cells that would normally be eliminated; it is to be noted that, in normal tissues, there is no evidence in favour of a role of native HLF in apoptosis regulation
  

External links

Nomenclature
HGNCHLF   4977
Entrez_GeneHLF  3131  hepatic leukemia factor
Cards
AtlasHLFID47
GeneCardsHLF
EnsemblHLF [Search_View]   ENSG00000108924 [Gene_View]
GenatlasHLF
GeneLynxHLF
eGenomeHLF
euGene3131
Genomic and cartography
GoldenPathHLF  -  17q22   chr17:50697320-50757425 +  17q22   [Description]    (hg18-Mar_2006)
EnsemblHLF - 17q22 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneHLF
Gene and transcription
GenbankAA021027 [ ENTREZ ]
GenbankAF035305 [ ENTREZ ]
GenbankAK074289 [ ENTREZ ]
GenbankAK290043 [ ENTREZ ]
GenbankAK315079 [ ENTREZ ]
RefSeqNM_002126 [ SRS ]    NM_002126 [ ENTREZ ]
RefSeqAC_000060 [ SRS ]    AC_000060 [ ENTREZ ]
RefSeqAC_000149 [ SRS ]    AC_000149 [ ENTREZ ]
RefSeqNC_000017 [ SRS ]    NC_000017 [ ENTREZ ]
RefSeqNT_010783 [ SRS ]    NT_010783 [ ENTREZ ]
RefSeqNW_001838448 [ SRS ]    NW_001838448 [ ENTREZ ]
RefSeqNW_926894 [ SRS ]    NW_926894 [ ENTREZ ]
AceViewHLF AceView - NCBI
UnigeneHs.196952 [ SRS ]    Hs.196952 [ NCBI ]     HS196952 [ spliceNest ]
Fast-db13074 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ16534 [ SRS]    Q16534 [ EXPASY ]     Q16534 [ INTERPRO ]     Q16534 [ UNIPROT ]
PrositePS50217 BZIP [ SRS ]    PS50217 BZIP [ Expasy ]
PrositePS00036 BZIP_BASIC [ SRS ]    PS00036 BZIP_BASIC [ Expasy ]
InterproIPR011700 bZIP_2 [ SRS ]    IPR011700 bZIP_2 [ EBI ]
InterproIPR004827 TF_bZIP [ SRS ]    IPR004827 TF_bZIP [ EBI ]
CluSTrQ16534
PfamPF07716 bZIP_2 [ SRS ]    PF07716 bZIP_2 [ Sanger ]    pfam07716 [ NCBI-CDD ]
SmartSM00338 BRLZ [EMBL]
BlocksQ16534
HPRD00797
Protein Interaction databases
DIPQ16534
IntActQ16534
Polymorphism : SNP, mutations, diseases
OMIM142385    [ map ]   
GENECLINICS142385
SNPHLF [dbSNP-NCBI]  
SNPNM_002126 [SNP-NCI]  
SNPHLF [GeneSNPs - Utah]  HLF] [HGBASE - SRS]
HAPMAPHLF [HAPMAP]  
COSMICHLF [Somatic mutation (COSMIC-CGP-Sanger)]  
TICdbHLF [Translocation breakpoints In Cancer]  
HGMDHLF
General knowledge
Family BrowserHLF [UCSC Family Browser]
SOURCENM_002126
SMDHs.196952
SAGEHs.196952
GOdouble-stranded DNA binding [Amigo]  double-stranded DNA binding
GOtranscription factor activity [Amigo]  transcription factor activity
GOnucleus [Amigo]  nucleus
GOtranscription [Amigo]  transcription
GOregulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GOtranscription from RNA polymerase II promoter [Amigo]  transcription from RNA polymerase II promoter
GOmulticellular organismal development [Amigo]  multicellular organismal development
GOsequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GOprotein dimerization activity [Amigo]  protein dimerization activity
GOrhythmic process [Amigo]  rhythmic process
PubGeneHLF
TreeFamHLF
CTD3131 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeHLF Related clones (RZPD - Berlin)
PubMed
PubMed24 Pubmed reference(s) in LocusLink

Bibliography

Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.
Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD, Look AT
Science (New York, N.Y.). 1992 ; 257 (5069) : 531-534.
PMID 1386162
 
The proto-oncogene HLF and the related basic leucine zipper protein TEF display highly similar DNA-binding and transcriptional regulatory properties.
Hunger SP, Li S, Fall MZ, Naumovski L, Cleary ML
Blood. 1996 ; 87 (11) : 4607-4617.
PMID 8639829
 
Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.
Hunger SP
Blood. 1996 ; 87 (4) : 1211-1224.
PMID 8608207
 
Cell transformation mediated by homodimeric E2A-HLF transcription factors.
Inukai T, Inaba T, Yoshihara T, Look AT
Molecular and cellular biology. 1997 ; 17 (3) : 1417-1424.
PMID 9032268
 
Regulation of the DBP promoter by PAR proteins and in leukemic cells bearing an E2A/HLF translocation.
Newcombe K, Glassco T, Mueller C
Biochemical and biophysical research communications. 1998 ; 245 (2) : 633-639.
PMID 9571207
 
Enhanced binding of HLF/DBP heterodimers represents one mechanism of PAR protein transactivation of the factor VIII and factor IX genes.
Begbie M, Mueller C, Lillicrap D
DNA and cell biology. 1999 ; 18 (2) : 165-173.
PMID 10073576
 
Expression patterns of the hepatic leukemia factor gene in the nervous system of developing and adult mice.
Hitzler JK, Soares HD, Drolet DW, Inaba T, O'Connel S, MG Rosenfeld, Morgan JI, Look AT
Brain research. 1999 ; 820 (1-2) : 1-11.
PMID 10023025
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-1999Franck Viguié

Citation

This paper should be referenced as such :
Viguié F . HLF (hepatic leukemia factor). Atlas Genet Cytogenet Oncol Haematol. September 1999 .
URL : http://AtlasGeneticsOncology.org/Genes/HLFID47.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Aug 11 21:14:20 2008


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