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Fragile X mental retardation 1 protein; protein FMR-1; FMRP (FMR1)
Function:
- RNA-binding protein that plays a role in intracellular RNA transport & in regulation of translation of target mRNAs
- associated with polysomes
- may play a role in the transport of mRNA from the nucleus to the cytoplasm
- binds strongly to poly(G), binds moderately to poly(U) but shows very little binding to poly(A) or poly(C)
- RNA-binding activity is inhibited by RANBP9
- phosphorylated on several Ser (putative)
- found in a RNP granule complex with IGF2BP1
- directly interacts with SMN & TDRD3
- interacts with the SMN core complex
- interacts with FXR1, FXR2, IGF2BP1, NUFIP1, NUFIP2, MCRS1 & RANBP9
- interacts with CYFIP1 & CYFIP2
Structure:
- homooligomer
- belongs to the FMR1 family
- contains 2 KH domains
Compartment: cytoplasm, nucleus, nucleolus
Alternative splicing: named isoforms=8; at least 12 different isoforms are produced
Expression:
- highest levels found in neurons, brain, testis, placenta & lymphocytes
- also expressed in epithelial tissues & at very low levels in glial cells
Pathology:
- defects in FMR1 are the cause of:
a) fragile X syndrome
b) fragile X tremor/ataxia syndrome (FXTAS)
- severe fragile X syndrome phenotype with Asn-304; involves sequestration of bound mRNAs in nontranslatable mRNP particles; in the absence of FMRP, these same mRNAs may be partially translated via alternate mRNPs, although perhaps abnormally localized or regulated, resulting in typical fragile X syndrome; Asn-304 mutation maps to a position within the 2nd KH domain of FMRP that is critical for stabilizing sequence-specific RNA-protein interactions; Asn-304 mutation abrogates the association of the 2nd FMRP KH domain with its target, kissing complex RNA
Related
FMR-1 gene
FMR1 gene activation
FMR1 gene allele 1 CGG repeats
FMR1 gene allele 2 CGG repeats
FMR1 gene CGG repeats
FMR1 gene methylation
FMR1 gene mutation
General
nuclear protein
RNA-binding protein
Properties
SIZE: entity length = 632 aa
MW = 71 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: KH domain
SITE: 222-251
FOR-BINDING-OF: ribonucleic acid
KH domain
SITE: 285-314
FOR-BINDING-OF: ribonucleic acid
RANBP9 interaction {419-632}
MOTIF: Ser phosphorylation site {S500}
binding site
SITE: 534-548
FOR-BINDING-OF: ribonucleic acid
Database Correlations
OMIM correlations
MORBIDMAP 309550
UniProt Q06787
PFAM correlations
Entrez Gene 2332
Kegg hsa:2332
References
- Ross CA, McInnis MG, Margolis RL, Li SH.
Genes with triplet repeats: candidate mediators of
neuropsychiatric disorders.
Trends Neurosci. 1993 Jul;16(7):254-60. Review.
PMID: 7689767
- Siomi H, Siomi MC, Nussbaum RL, Dreyfuss G.
The protein product of the fragile X gene, FMR1, has
characteristics of an RNA-binding protein.
Cell. 1993 Jul 30;74(2):291-8.
PMID: 7688265
- UniProt :accession Q06787
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=FMR1