LAF4 (lymphoid nuclear protein related to AF4)

Identity

Other names	MLLT2-related protein, lymphoid nuclear protein 4
HGNC	AFF3
Location	2q11.2-2q12
Location_base_pair	Starts at 99530148 and ends at 100088477 bp from pter ( according to hg18-Mar_2006).

DNA/RNA

Description	at least 17 exons.
Transcription	in a telomere to centromere direction; 3857 bp mRNA; 3684 bp open reading frame.

Protein

Description	1227 amino acids; 133734 Da.
Expression	Preferentially expressed in lymphoid tissues, highest levels being found in the thymus. Lower expression in brain and lung.
Localisation	Nuclear
Function	Putative transcription activator that may function in lymphoid development and oncogenesis. Binds in vitro to double-stranded DNA
Homology	Belongs to the AF4/LAF4/FMR2/AF5q31 family.

Implicated in

Entity	t(2;11)(q11;q23) . --> MLL-LAF4
Note	MLL fusion partner at chromosome 2 in infant ALL
Disease	The three cases reported to date were all infant-ALL with proB phenotype
Prognosis	Prognosis is poor, although based on only three cases.
Cytogenetics	The three reported cases harboured different rearrangements involving chromosomes 2 and 11: t(2;11)(q11;q23), t(2;11)(p15;p14), and ins(11;2)(q23;q11.2q11.2).
Abnormal Protein	The MLL-LAF4 fusion protein includes the transactivation domain of LAF4 that is part of the AF4/LAF4/FMR2 homology domain.
	Coding sequence of LAF4 compared to AF4 and site of fusion. Schematic representation of MLL, LAF4, AF4, and the putative MLL-LAF4 fusion protein. Domains in MLL are shaded: MT, DNA methyltransferase homology region; TRX, Drosophila trithorax homology. The percentage of amino acid homology between corresponding regions of LAF4 and AF4 is indicated: NHD, N-terminal homology domain; ALF, AF4/LAF4/FMR2 homology domain; TAD, transactivation domain; NLS, nuclear localization sequence; CHD, C-terminal homology domain. Arrows indicate the fusion sites with MLL. The breakpoint in LAF4 corresponds to one of the known breakpoints in AF4.

External links

	Nomenclature
HGNC	AFF3   6473
Entrez_Gene	AFF3  3899  AF4/FMR2 family, member 3
	Cards
Atlas	LAF4ID315
GeneCards	AFF3
Ensembl	AFF3 [Search_View]   ENSG00000144218 [Gene_View]
Genatlas	AFF3
GeneLynx	AFF3
eGenome	AFF3
euGene	3899
	Genomic and cartography
GoldenPath	AFF3  -     chr2:99530148-100088477 -  2q11.2-q12   [Description]    (hg18-Mar_2006)
Ensembl	AFF3 - 2q11.2-q12 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	AFF3
	Gene and transcription
Genbank	AB209634 [ ENTREZ ]
Genbank	AK055117 [ ENTREZ ]
Genbank	AK091320 [ ENTREZ ]
Genbank	AK092327 [ ENTREZ ]
Genbank	AK290468 [ ENTREZ ]
RefSeq	NM_001025108 [ SRS ]    NM_001025108 [ ENTREZ ]
RefSeq	NM_002285 [ SRS ]    NM_002285 [ ENTREZ ]
RefSeq	AC_000045 [ SRS ]    AC_000045 [ ENTREZ ]
RefSeq	AC_000134 [ SRS ]    AC_000134 [ ENTREZ ]
RefSeq	NC_000002 [ SRS ]    NC_000002 [ ENTREZ ]
RefSeq	NT_022171 [ SRS ]    NT_022171 [ ENTREZ ]
RefSeq	NW_001838818 [ SRS ]    NW_001838818 [ ENTREZ ]
RefSeq	NW_928052 [ SRS ]    NW_928052 [ ENTREZ ]
AceView	AFF3 AceView - NCBI
Unigene	Hs.444414 [ SRS ]    Hs.444414 [ NCBI ]     HS444414 [ spliceNest ]
Fast-db	8910 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P51826 [ SRS]    P51826 [ EXPASY ]     P51826 [ INTERPRO ]     P51826 [ UNIPROT ]
Interpro	IPR007797 AF-4 [ SRS ]    IPR007797 AF-4 [ EBI ]
CluSTr	P51826
Pfam	PF05110 AF-4 [ SRS ]    PF05110 AF-4 [ Sanger ]    pfam05110 [ NCBI-CDD ]
Blocks	P51826
HPRD	03272
	Protein Interaction databases
DIP	P51826
IntAct	P51826
	Polymorphism : SNP, mutations, diseases
OMIM	601464    [ map ]
GENECLINICS	601464
SNP	AFF3 [dbSNP-NCBI]
SNP	NM_001025108 [SNP-NCI]
SNP	NM_002285 [SNP-NCI]
SNP	AFF3 [GeneSNPs - Utah]  AFF3] [HGBASE - SRS]
HAPMAP	AFF3 [HAPMAP]
COSMIC	AFF3 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	AFF3 [Translocation breakpoints In Cancer]
HGMD	AFF3
	General knowledge
Family Browser	AFF3 [UCSC Family Browser]
SOURCE	NM_001025108
SOURCE	NM_002285
SMD	Hs.444414
SAGE	Hs.444414
GO	DNA binding [Amigo]  DNA binding
GO	nucleus [Amigo]  nucleus
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	multicellular organismal development [Amigo]  multicellular organismal development
PubGene	AFF3
TreeFam	AFF3
CTD	3899 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	AFF3 Related clones (RZPD - Berlin)
	PubMed
PubMed	11 Pubmed reference(s) in Entrez

Bibliography

LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias.

Ma C, Staudt LM

Blood. 1996 ; 87 (2) : 734-745.

PMID 8555498

LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia.

von Bergh AR, Beverloo HB, Rombout P, van Wering ER, van Weel MH, Beverstock GC, Kluin PM, Slater RM, Schuuring E

Genes, chromosomes & cancer. 2002 ; 35 (1) : 92-96.

PMID 12203795

Occurrence of an MLL/LAF4 fusion gene caused by the insertion ins(11;2)(q23;q11.2q11.2) in an infant with acute lymphoblastic leukemia.

Bruch J, Wilda M, Teigler-Schlegel A, Harbott J, Borkhardt A, Metzler M

Genes, chromosomes & cancer. 2003 ; 37 (1) : 106-109.

PMID 12661012

Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).

Hiwatari M, Taki T, Taketani T, Taniwaki M, Sugita K, Okuya M, Eguchi M, Ida K, Hayashi Y

Oncogene. 2003 ; 22 (18) : 2851-2855.

PMID 12743608

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	08-2003	Anne RM von Bergh

Citation

This paper should be referenced as such :

von Bergh ARM . LAF4 (lymphoid nuclear protein related to AF4). Atlas Genet Cytogenet Oncol Haematol. August 2003 . URL : http://AtlasGeneticsOncology.org/Genes/LAF4ID315.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Tue Oct 14 21:21:04 2008