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HLF (hepatic leukemia factor)

Identity

HGNC (Hugo) HLF
LocusID (NCBI) 3131
Location 17q22
Location_base_pair Starts at 53342321 and ends at 53402426 bp from pter ( according to hg19-Feb_2009)  [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]  chr17:53342321-53402426 [Contig_View]  HLF [Vega]
AceView (NCBI)HLF
Genatlas (Paris)HLF
euGene (Indiana)3131
SOURCE (Stanford)NM_002126
Genomic and cartography
GoldenPath (UCSC)HLF  -  17q22   chr17:53342321-53402426 +  17q22   [Description]    (hg19-Feb_2009)
EnsemblHLF - 17q22 [CytoView]
Mapping of homologs : NCBIHLF [Mapview]
OMIM142385   
Gene and transcription
Genbank (Entrez)AA021027 AF035305 AK074289 AK290043 AK295726
RefSeq transcript (SRS)NM_002126
RefSeq transcript (Entrez)NM_002126
RefSeq genomic (SRS)AC_000149 NC_000017 NT_010783 NW_001838448
RefSeq genomic (Entrez)AC_000149 NC_000017 NT_010783 NW_001838448
Consensus coding sequences : CCDS (NCBI)HLF
Cluster EST : UnigeneHs.196952 [ SRS ] Hs.196952 [ NCBI ]
Alternative Splicing : Fast-db (Paris)13074
Alternative Splicing GalleryENSG00000108924
Gene ExpressionHLF [ NCBI-GEO ]   HLF [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ16534 (SRS) Q16534 (Uniprot)
With graphics : InterProQ16534
Splice isoforms : SwissVarQ16534(Swissvar)
Domaine pattern : Prosite (SRS)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domaine pattern : Prosite (Expaxy)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domains : Interpro (SRS)bZIP    bZIP_2   
Domains : Interpro (EBI)bZIP    bZIP_2   
Related proteins : CluSTrQ16534
Domain families : Pfam (SRS)bZIP_2 (PF07716)   
Domain families : Pfam (Sanger)bZIP_2 (PF07716)   
Domain families : Pfam (NCBI)pfam07716   
Domain families : Smart (EMBL)BRLZ (SM00338)  
Blocks (Seattle)Q16534
Human Protein AtlasENSG00000108924
HPRD00797
IPIIPI00002850   IPI01011539   IPI00910584   
Protein Interaction databases
DIP (DOE-UCLA)Q16534
IntAct (EBI)Q16534
FunCoupENSG00000108924
REACTOMEHLF
BioGRIDHLF
InParanoidQ16534
Interologous Interaction database Q16534
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)HLF
SNP (GeneSNP Utah)HLF
SNP : HGBaseHLF
Genetic variants : HAPMAPHLF
Cancer Gene: CensusHLF 
Somatic Mutations in Cancer : COSMICHLF 
CONAN: Copy Number AnalysisHLF 
Translocation Breakpoints in Cancer : TICdbHLF 
Mutations and Diseases : HGMDHLF
OMIM142385   
GENETests142385   
Disease Genetic AssociationHLF
Huge Navigator HLF [HugePedia]  HLF [HugeCancerGEM]
Genomic VariantsHLF
snp3D : Map Gene to Disease3131
General knowledge
Homologs : HomoloGeneHLF
Homology/Alignments : Family Browser (UCSC)HLF
Phylogenetic Trees/Animal Genes : TreeFamHLF
Chemical/Protein Interactions : CTD3131
Chemical/Pharm GKB GenePA29311
Clinical trialHLF
Cancer Resource (Charite)ENSG00000108924
Ontology : AmiGODNA binding  double-stranded DNA binding  sequence-specific DNA binding transcription factor activity  nucleus  transcription from RNA polymerase II promoter  multicellular organismal development  sequence-specific DNA binding  protein dimerization activity  rhythmic process  
Ontology : EGO-EBIDNA binding  double-stranded DNA binding  sequence-specific DNA binding transcription factor activity  nucleus  transcription from RNA polymerase II promoter  multicellular organismal development  sequence-specific DNA binding  protein dimerization activity  rhythmic process  
Other databases
Probes
Probes : ImagenesHLF Related clones (RZPD - Berlin)
Litterature
PubMed28 Pubmed reference(s) in Entrez
PubGeneHLF
iHOPHLF

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

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37532/1/09-1999-HLFID47.pdf   [ Bibliographic record ]

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Apr 28 15:05:51 CEST 2012

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