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FLASH GENE

Symbol

AFF2

contributors: mct/npt/pgu - updated : 15-05-2018

HGNC name	AF4/FMR2 family, member 2
HGNC id	3776

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	FRAXE mental retardation, associated with fragile site
Location	Xq28      Physical location : 147.582.138 - 148.082.192
Synonym name	fragile X mental retardation gene associated with FRAXE
	mild or borderline mental retardation
	Ox19 protein
Synonym symbol(s)	OX19, FMR2, FMR2P, MRX2, FRAXE

DNA

TYPE	functioning gene
SPECIAL FEATURE	head to head, opposite orientation
text	head to head with FMR3
STRUCTURE	500.04 kb     21 Exon(s)

motif	repetitive sequence   triplet
text structure	a CCG repeat in 5'utr

MAPPING

cloned

Y

linked

status

provisional

Map

see FRAXE

regionally located

transcribed distally from the CGG repeat of FRAXE, head to head with FMR3, FRAXE in the interval

RNA

TRANSCRIPTS	type	messenger

text	several possibilities of alternative splicing for exons 2, 3, 5, 7 and 21 (PMID: 19136466)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002025 21 - 13746 NP_002016 145 1311 - 2013 23562910 NM_001169124 20 - 13641 NP_001162595 - 1276 - 2013 23562910 NM_001169123 21 - 13716 NP_001162594 - 1301 - 2013 23562910 NM_001169122 20 - 13641 NP_001162593 - 1276 - 2013 23562910 NM_001169125 20 - 13629 NP_001162596 - 1272 - 2013 23562910 NM_001170628 18 - 12280 NP_001164099 - 952 - 2013 23562910

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node         Nervous brain hindbrain cerebellum     Homo sapiens   brain diencephalon hypothalamus   highly Homo sapiens   brain diencephalon amygdala   highly Homo sapiens   brain limbic system hippocampus     Reproductive female system placenta     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	fetal brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal homology domain is a region of homology shared by the four AFF members
	an ALF domain
	a transactivation domain
	a NTD domain at the N terminus required for the transactivation
	and able to affect transcription
	a nuclear localization signal
	a C terminal CHD domain, modulating splicing, C-terminal homology domain, another region of homology among the AFF proteins, is involved in the intranuclear localization of FMR2 as well as in its ability to bind the G-quadruplex RNA-forming structure

HOMOLOGY

interspecies

homolog to drosophila Lili

intraspecies

homolog to MLLT2 (AF4), LAF4,highly

Homologene

FAMILY

AF4 family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
	intracellular,nucleus,nucleolus
text	localized in the nucleolus when splicing is blocked
	also localized in SC35-containing nuclear speckles, being implicated in splicing
	localizes to nuclear speckles, subnuclear structures considered as storage/modification sites of pre-mRNA splicing factors
	is localized to the nuclear speckles

basic FUNCTION	activator of transcription involved in non-specific X-linked mental retardation
	playing a role in early embryonic stages of the development of brain and other tissues
	may be a RNA-binding protein, which might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure
	multifunctional protein linking RNA metabolism and transcriptional control
	potential role for AFF2/FMR2 protein in synaptic plasticity
	modulates alternative splicing via the interaction with the G-quadruplex RNA-forming structure
	possible functional redundancy among the AFF family members in the regulation of splicing and transcription
	functional redundancy for AFF2/AFF3/AFF4 proteins during brain development
	regulates transcription, promotes alternative splicing with preference for G-quartet structure harbouring exons

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

text	brain development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	binding to SIAH proteins
	interacting with FMR1 (influences the alternative splicing pattern of the mRNA of FMR1, which contains a G-quartet nearby an acceptor site of the alternatively spliced exon 14)
	is an upstream regulator of FOS and JUN, and further link deregulation of the immediate early response genes to the pathology of intellectual disability (ID)- and FRAXE-associated ID in particular

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

FRAXE

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       microdeletions in FMR2 may be a significant cause of premature ovarian failure

Susceptibility

to Autism spectrum disorder (ASD)

Variant & Polymorphism other	rare AFF2 3prime UTR variants at conserved sites which alter gene expression are associated to ASD

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Aff2/Fmr2-null mice display a delay-dependent conditioned fear impairment and hippocampal increased long-term potentiation (LTP)