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HLF (hepatic leukemia factor)

Identity

HGNC (Hugo) HLF
Location 17q22
Location_base_pair Starts at 50697320 and ends at 50757425 bp from pter ( according to hg18-Mar_2006)  [Mapping]

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
HGNC (Hugo)HLF   4977
Entrez_Gene (NCBI)HLF  3131  hepatic leukemia factor
Cards
AtlasHLFID47
GeneCards (Weizmann)HLF
Ensembl (Hinxton)ENSG00000108924 [Gene_View]  HLF [Vega]
AceView (NCBI)HLF
Genatlas (Paris)HLF
euGene (Indiana)3131
SOURCE (Stanford)NM_002126
Genomic and cartography
GoldenPath (UCSC)HLF  -  17q22   chr17:50697320-50757425 +  17q22   [Description]    (hg18-Mar_2006)
EnsemblHLF - 17q22 [CytoView]
Mapping of homologs : NCBIHLF [Mapview]
OMIM142385   
Gene and transcription
Gene : Genbank (Entrez)AA021027 AF035305 AK074289 AK290043 AK295726
Reference sequence (RefSeq transcript) :SRSNM_002126
Reference transcript : EntrezNM_002126
RefSeq genomic : SRSAC_000060 AC_000149 NC_000017 NT_010783 NW_001838448 NW_926894
RefSeq genomic : EntrezAC_000060 AC_000149 NC_000017 NT_010783 NW_001838448 NW_926894
Consensus coding sequences : CCDS NCBIHLF
Cluster EST : UnigeneHs.196952 [ SRS ] Hs.196952 [ NCBI ]
Alternative Splicing : Fast-db (Paris)13074
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ16534 (SRS) Q16534 (Expasy) Q16534 (Uniprot)
With graphics : InterProQ16534
Splice isoforms : VarSplice FASTAQ16534(VarSplice FASTA)
Domaine pattern : Prosite (SRS)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domain pattern : Prosite (Expaxy)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domains : Interpro (SRS)bZIP_2    TF_bZIP   
Domains : Interpro (EBI)bZIP_2    TF_bZIP   
Related proteins : CluSTrQ16534
Domain families : Pfam SRSbZIP_2 (PF07716)   
Domain families : Pfam SangerbZIP_2 (PF07716)   
Domain families : Pfam NCBIpfam07716   
Domain families : Smart EMBLBRLZ (SM00338)
Blocks (Seattle)Q16534
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD00797
Protein Interaction databases
DIP (DOE-UCLA)Q16534
IntAct (EBI)Q16534
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIHLF
SNP : GeneSNP UtahHLF
SNP : HGBaseHLF
Genetic variants : HAPMAPHLF
Somatic Mutations in Cancer : COSMICHLF 
Translocation Breakpoints in Cancer : TICdbHLF 
Mutations and Diseases : HGMDHLF
Hereditary diseases : OMIM142385   
Hereditary diseases : GENETests142385   
Diseases : Genetic AssociationHLF
General knowledge
Homologs : HomoloGeneHLF
Homology/Alignments : Family Browser UCSCHLF
Phylogenetic Trees/Animal Genes : TreeFamHLF
Chemical/Protein Interactions : CTD3131
Keywords Ontology : AmiGOdouble-stranded DNA binding  transcription factor activity  nucleus  transcription  regulation of transcription, DNA-dependent  transcription from RNA polymerase II promoter  multicellular organismal development  sequence-specific DNA binding  protein dimerization activity  rhythmic process  
Keywords Ontology : EGO-EBIdouble-stranded DNA binding  transcription factor activity  nucleus  transcription  regulation of transcription, DNA-dependent  transcription from RNA polymerase II promoter  multicellular organismal development  sequence-specific DNA binding  protein dimerization activity  rhythmic process  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesHLF Related clones (RZPD - Berlin)
Literature
PubMed23 Pubmed reference(s) in Entrez
PubGeneHLF

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

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indexed on : Sat Jun 27 16:40:01 CEST 2009

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