MLLT7 ( myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7)

Identity

Other names	AFX1 (ALL1 fused gene from chromosome X, 1)
	MLLT7 (myeloid/lymphoid leukemia translocated to, 7)
	AFX
	FOXO4
Hugo	FOXO4
Location	Xq13

DNA/RNA

Transcription

7,5kb consisting of 3 exons. RNA App. 3.5 kb mRNA; coding sequence. Placental secondary transcript: App. 2.8kb Expression pattern: Heavily expressed in skeletal muscle, placenta and ovary

Protein

Description	504 amino acids; NH2 -- similarity region with AF6q21 and FHKR -- forkhead motif -- COOH
Expression	wide
Localisation	nuclear
Function	Transcription factor binding to the motive TTGTTTAC. Target genes: Akt, AFX is able to induce Rb-independent, p27kip1-mediated G1-arrest. Phosphorylation of AFX by protein kinase B inhibits its transcriptional activity.
Homology	daf-16 (C.elegans) and other forkhead-transcription factors (i.e. FKHR, FKHRL1, FKHRP1, FKHRL1P1) and AF6q21, involved in the t(6;11)(q21;q23). In the fusion protein AFX/MLL, AFX fuses to MLL in the same aminoacid as FHKR fuses to PAX3 in the PAX3/FKHR-fusion protein of alveolar rabdomyosarcoma.

Implicated in

Entity	t(X;11)(q13q23)/acute leukaemias --> MLL - AFX
Disease	ANLL, T-ALL
Prognosis	very poor
Hybrid/Mutated Gene	5' MLL-3' AFX as well as the reciprocal 5' AFX-3' MLL on DNA and mRNA level
Abnormal Protein	comprises about 1400 amino acids from N-term MLL and 354 amino acids from AFX C-term; the reciprocal may be expressed

Breakpoints

External links

	Nomenclature
Hugo	MLLT7
GDB	FOXO4
Entrez_Gene	FOXO4  4303  forkhead box O4
	Cards
Atlas	AFX1ID57
GeneCards	FOXO4
Ensembl	FOXO4 [Search_View]   ENSG00000184481 [Gene_View]
Genatlas	FOXO4
GeneLynx	FOXO4
eGenome	FOXO4
euGene	4303
	Genomic and cartography
GoldenPath	FOXO4  -  Xq13   chrX:70232751-70240109 +  Xq13.1    (hg18-Mar_2006)
Ensembl	FOXO4 - Xq13.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	FOXO4
	Gene and transcription
Genbank	AF384029 [ ENTREZ ]
Genbank	BC026735 [ ENTREZ ]
Genbank	BC106761 [ ENTREZ ]
Genbank	BP349083 [ ENTREZ ]
Genbank	CR595958 [ ENTREZ ]
RefSeq	NM_005938 [ SRS ]    NM_005938 [ ENTREZ ]
RefSeq	AC_000066 [ SRS ]    AC_000066 [ ENTREZ ]
RefSeq	NC_000023 [ SRS ]    NC_000023 [ ENTREZ ]
RefSeq	NT_011669 [ SRS ]    NT_011669 [ ENTREZ ]
RefSeq	NW_927711 [ SRS ]    NW_927711 [ ENTREZ ]
AceView	FOXO4 AceView - NCBI
Unigene	Hs.584654 [ SRS ]    Hs.584654 [ NCBI ]     HS584654 [ spliceNest ]
Fast-db	10205 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P98177 [ SRS]    P98177 [ EXPASY ]     P98177 [ INTERPRO ]
Prosite	PS00657 FORK_HEAD_1 [ SRS ]    PS00657 FORK_HEAD_1 [ Expasy ]
Prosite	PS00658 FORK_HEAD_2 [ SRS ]    PS00658 FORK_HEAD_2 [ Expasy ]
Prosite	PS50039 FORK_HEAD_3 [ SRS ]    PS50039 FORK_HEAD_3 [ Expasy ]
Interpro	IPR001766 TF_Fork_head [ SRS ]    IPR001766 TF_Fork_head [ EBI ]
Interpro	IPR011991 Wing_hlx_DNA_bd [ SRS ]    IPR011991 Wing_hlx_DNA_bd [ EBI ]
CluSTr	P98177
Pfam	PF00250 Fork_head [ SRS ]    PF00250 Fork_head [ Sanger ]    pfam00250 [ NCBI-CDD ]
Smart	SM00339 FH [EMBL]
Prodom	PD000425 TF_Fork_head[INRA-Toulouse]
Prodom	P98177 FOXO4_HUMAN [ Domain structure ]   P98177 FOXO4_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P98177
PDB	1E17 [ SRS ]    1E17 [ PdbSum ],   1E17 [ IMB ]   1E17 [ RSDB ]
HPRD	02070
	Protein Interaction databases
DIP	P98177
IntAct	P98177
	Polymorphism : SNP, mutations, diseases
OMIM	300033    [ map ]
GENECLINICS	300033
SNP	FOXO4 [dbSNP-NCBI]
SNP	NM_005938 [SNP-NCI]
SNP	FOXO4 [GeneSNPs - Utah]  FOXO4] [HGBASE - SRS]
HAPMAP	FOXO4 [HAPMAP]
HGMD	MLLT7
	General knowledge
Family Browser	FOXO4 [UCSC Family Browser]
SOURCE	NM_005938
SMD	Hs.584654
SAGE	Hs.584654
GO	G1 phase of mitotic cell cycle [Amigo]  G1 phase of mitotic cell cycle
GO	transcription factor activity [Amigo]  transcription factor activity
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	transcription from RNA polymerase II promoter [Amigo]  transcription from RNA polymerase II promoter
GO	cell cycle [Amigo]  cell cycle
GO	cell cycle arrest [Amigo]  cell cycle arrest
GO	multicellular organismal development [Amigo]  multicellular organismal development
GO	skeletal muscle development [Amigo]  skeletal muscle development
GO	transcription factor binding [Amigo]  transcription factor binding
GO	negative regulation of cell proliferation [Amigo]  negative regulation of cell proliferation
GO	insulin receptor signaling pathway [Amigo]  insulin receptor signaling pathway
GO	negative regulation of angiogenesis [Amigo]  negative regulation of angiogenesis
GO	enzyme binding [Amigo]  enzyme binding
GO	cell differentiation [Amigo]  cell differentiation
GO	sequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GO	negative regulation of smooth muscle cell differentiation [Amigo]  negative regulation of smooth muscle cell differentiation
BIOCARTA	AKT Signaling Pathway    [Genes]
BIOCARTA	Ras Signaling Pathway    [Genes]
PubGene	FOXO4
TreeFam	MLLT7
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	FOXO4 Related clones (RZPD - Berlin)
	PubMed
PubMed	35 Pubmed reference(s) in LocusLink

Bibliography

Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.

Parry P, Wei Y, Evans G

Genes, chromosomes & cancer. 1994 ; 11 (2) : 79-84.

PMID 7529552

Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23).

Borkhardt A, Repp R, Haas OA, Leis T, Harbott J, Kreuder J, Hammermann J, Henn T, Lampert F

Oncogene. 1997 ; 14 (2) : 195-202.

PMID 9010221

AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism.

Peters U, Haberhausen G, Kostrzewa M, Nolte D, Mˆºller U

Human genetics. 1997 ; 100 (5-6) : 569-572.

PMID 9341872

Direct control of the Forkhead transcription factor AFX by protein kinase B.

Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM

Nature. 1999 ; 398 (6728) : 630-634.

PMID 10217147

AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.

Medema RH, Kops GJ, Bos JL, Burgering BM

Nature. 2000 ; 404 (6779) : 782-787.

PMID 10783894

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

Search in all EBI   NCBI

Contributor(s)

Written	04-1998	Olivier Bernard

Citation

This paper should be referenced as such :

Bernard O . MLLT7 ( myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7). Atlas Genet Cytogenet Oncol Haematol. April 1998 . URL : http://AtlasGeneticsOncology.org/Genes/AFX1ID57.html

Bojesen SE . MLLT7 ( myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7). Atlas Genet Cytogenet Oncol Haematol. . URL : http://AtlasGeneticsOncology.org/Genes/AFX1ID57.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon May 12 18:01:19 2008