P51114 · FXR1_HUMAN
- ProteinRNA-binding protein FXR1
- GeneFXR1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids621 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:17382880, PubMed:34731628).
Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (By similarity).
Required to activate translation of stored mRNAs during late spermatogenesis: acts by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules that recruit translation initiation factor EIF4G3 to activate translation of stored mRNAs in late spermatids (By similarity).
Promotes translation of MYC transcripts by recruiting the eIF4F complex to the translation start site (PubMed:34731628).
Acts as a negative regulator of inflammation in response to IL19 by promoting destabilization of pro-inflammatory transcripts (PubMed:30067974).
Also acts as an inhibitor of inflammation by binding to TNF mRNA, decreasing TNF protein production (By similarity).
Acts as a negative regulator of AMPA receptor GRIA2/GluA2 synthesis during long-lasting synaptic potentiation of hippocampal neurons by binding to GRIA2/GluA2 mRNA, thereby inhibiting its translation (By similarity).
Regulates proliferation of adult neural stem cells by binding to CDKN1A mRNA and promoting its expression (By similarity).
Acts as a regulator of sleep and synaptic homeostasis by regulating translation of transcripts in neurons (By similarity).
Required for embryonic and postnatal development of muscle tissue by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules (PubMed:30770808).
Involved in the nuclear pore complex localization to the nuclear envelope by preventing cytoplasmic aggregation of nucleoporins: acts by preventing ectopic phase separation of nucleoporins in the cytoplasm via a microtubule-dependent mechanism (PubMed:32706158).
Plays a role in the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with PKP3 (PubMed:25225333).
May also do the same for PKP2, PKP3 and DSP via its interaction with PKP1 (PubMed:25225333).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRNA-binding protein FXR1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP51114
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Localizes to stress granules following phosphorylation at Ser-420 by PAK1 (PubMed:20417602).
Adjacent to Z-lines in muscles (By similarity).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Congenital myopathy 9A (CMYP9A)
- Note
- DescriptionAn autosomal recessive muscular disorder characterized by severe hypotonia apparent at birth, poor feeding, ulnar deviation of the hands, laterally deviated feet, fractures of the long bones, respiratory insufficiency due to muscle weakness, and death in infancy.
- See alsoMIM:618822
Congenital myopathy 9B, proximal, with minicore lesions (CMYP9B)
- Note
- DescriptionAn autosomal recessive, slowly progressive muscular disorder characterized by primarily proximal muscle weakness, neonatal hypotonia leading to delayed motor development, mildly delayed walking in childhood, and difficulty running or climbing. Cardiac function is unaffected, but most patients have obstructive sleep apnea. Muscle biopsy shows type 1 fiber predominance with disorganized Z-lines and minicores that disrupt the myofibrillar striation pattern.
- See alsoMIM:618823
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_036050 | 233 | in a breast cancer sample; somatic mutation | |||
Sequence: A → T | ||||||
Mutagenesis | 304 | Abolished binding to PAK1. | ||||
Sequence: I → N | ||||||
Mutagenesis | 345-346 | Does not affect binding to PAK1. | ||||
Sequence: GN → DA | ||||||
Mutagenesis | 348-352 | Abolished binding to PAK1. | ||||
Sequence: QVLLE → KVLLA | ||||||
Mutagenesis | 352-353 | Reduced binding to PAK1. | ||||
Sequence: EY → AA | ||||||
Mutagenesis | 420 | Abolished phosphorylation by PAK1, leading to impaired activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 420 | Mimics phosphorylation state; leading to increased activity. | ||||
Sequence: S → D | ||||||
Natural variant | VAR_016077 | 429 | in dbSNP:rs1051080 | |||
Sequence: D → N | ||||||
Natural variant | VAR_014890 | 614 | in dbSNP:rs11499 | |||
Sequence: A → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 509 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000050106 | 2-621 | UniProt | RNA-binding protein FXR1 | |||
Sequence: AELTVEVRGSNGAFYKGFIKDVHEDSLTVVFENNWQPERQVPFNEVRLPPPPDIKKEISEGDEVEVYSRANDQEPCGWWLAKVRMMKGEFYVIEYAACDATYNEIVTFERLRPVNQNKTVKKNTFFKCTVDVPEDLREACANENAHKDFKKAVGACRIFYHPETTQLMILSASEATVKRVNILSDMHLRSIRTKLMLMSRNEEATKHLECTKQLAAAFHEEFVVREDLMGLAIGTHGSNIQQARKVPGVTAIELDEDTGTFRIYGESADAVKKARGFLEFVEDFIQVPRNLVGKVIGKNGKVIQEIVDKSGVVRVRIEGDNENKLPREDGMVPFVFVGTKESIGNVQVLLEYHIAYLKEVEQLRMERLQIDEQLRQIGSRSYSGRGRGRRGPNYTSGYGTNSELSNPSETESERKDELSDWSLAGEDDRDSRHQRDSRRRPGGRGRSVSGGRGRGGPRGGKSSISSVLKDPDSNPYSLLDNTESDQTADTDASESHHSTNRRRRSRRRRTDEDAVLMDGMTESDTASVNENGLVTVADYISRAESQSRQRNLPRETLAKNKKEMAKDVIEEHGPSEKAINGPTSASGDDISKLQRTPGEEKINTLKEENTQEAAVLNGVS | |||||||
Cross-link | 56 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue | 68 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 401 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 401 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 403 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 403 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 406 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 406 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 409 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 409 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 411 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 413 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 420 | UniProt | Phosphoserine; by PAK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 420 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 423 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 423 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 432 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 432 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 447 | UniProt | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue | 447 | UniProt | Omega-N-methylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue | 453 | UniProt | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue | 453 | UniProt | Omega-N-methylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue | 455 | UniProt | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue | 455 | UniProt | Omega-N-methylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue (large scale data) | 464 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 477 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 483 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 483 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 485 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 485 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 491 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 496 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 524 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 524 | UniProt | In isoform P51114-2; Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 528 | UniProt | In isoform P51114-2; Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 585 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 587 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 587 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 597 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 611 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 611 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Phosphorylated by MAPK1/ERK2, promoting subsequent phosphorylation by GSK3B (By similarity).
Phosphorylated by GSK3B, promoting ubiquitination and degradation by the proteasome (By similarity).
Ubiquitinated and degraded in a GSK3B-dependent manner in during both scaling and sleep deprivation (By similarity).
Ubiquitinated via 'Lys-63'-linked ubiquitin, leading to its degradation: interaction with CEP63 inhibits 'Lys-63'-linked ubiquitination (PubMed:35989368).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
In brain, present at high level in neurons and especially in the Purkinje cells at the interface between the granular layer and the molecular layer (at protein level) (PubMed:9259278).
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with FRX2 (PubMed:7489725).
Interacts with TDRD3 (PubMed:18664458).
Interacts with HABP4 (PubMed:21771594).
Interacts with CYFIP2 but not with CYFIP1 (By similarity).
Interacts with EIF4G3; promoting translation of target mRNAs (By similarity).
Interacts with ELAVL1 (PubMed:30067974).
Interacts with CEP63; inhibiting 'Lys-63'-linked ubiquitination (PubMed:35989368).
Interacts with PKP3; the interaction facilitates the binding of PKP3 to PKP2 mRNA (PubMed:25225333).
Interacts with PKP1; the interaction may facilitate the binding of PKP1 to PKP2, PKP3 and DSP mRNA (PubMed:25225333).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 4-50 | Agenet-like 1 | ||||
Sequence: LTVEVRGSNGAFYKGFIKDVHEDSLTVVFENNWQPERQVPFNEVRLP | ||||||
Domain | 63-115 | Agenet-like 2 | ||||
Sequence: DEVEVYSRANDQEPCGWWLAKVRMMKGEFYVIEYAACDATYNEIVTFERLRPV | ||||||
Domain | 222-251 | KH 1 | ||||
Sequence: EFVVREDLMGLAIGTHGSNIQQARKVPGVT | ||||||
Domain | 285-314 | KH 2 | ||||
Sequence: FIQVPRNLVGKVIGKNGKVIQEIVDKSGVV | ||||||
Region | 381-530 | Disordered | ||||
Sequence: RSYSGRGRGRRGPNYTSGYGTNSELSNPSETESERKDELSDWSLAGEDDRDSRHQRDSRRRPGGRGRSVSGGRGRGGPRGGKSSISSVLKDPDSNPYSLLDNTESDQTADTDASESHHSTNRRRRSRRRRTDEDAVLMDGMTESDTASVN | ||||||
Compositional bias | 409-444 | Basic and acidic residues | ||||
Sequence: SETESERKDELSDWSLAGEDDRDSRHQRDSRRRPGG | ||||||
Region | 442-457 | RNA-binding RGG-box | ||||
Sequence: PGGRGRSVSGGRGRGG | ||||||
Compositional bias | 467-489 | Polar residues | ||||
Sequence: SVLKDPDSNPYSLLDNTESDQTA | ||||||
Region | 545-621 | Disordered | ||||
Sequence: ESQSRQRNLPRETLAKNKKEMAKDVIEEHGPSEKAINGPTSASGDDISKLQRTPGEEKINTLKEENTQEAAVLNGVS | ||||||
Compositional bias | 555-575 | Basic and acidic residues | ||||
Sequence: RETLAKNKKEMAKDVIEEHGP | ||||||
Compositional bias | 594-608 | Basic and acidic residues | ||||
Sequence: LQRTPGEEKINTLKE |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing. Alternative splicing appears to be tissue-specific.
P51114-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsLong
- Length621
- Mass (Da)69,721
- Last updated2008-05-20 v3
- Checksum0474A9B593C7C228
P51114-2
- Name2
- Synonymsb, Short
P51114-3
- Name3
- Differences from canonical
- 1-85: Missing
Computationally mapped potential isoform sequences
There are 13 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9IZ22 | C9IZ22_HUMAN | FXR1 | 94 | ||
C9J5B4 | C9J5B4_HUMAN | FXR1 | 75 | ||
E7EU85 | E7EU85_HUMAN | FXR1 | 454 | ||
C9JY20 | C9JY20_HUMAN | FXR1 | 123 | ||
C9JYQ6 | C9JYQ6_HUMAN | FXR1 | 19 | ||
C9JZE0 | C9JZE0_HUMAN | FXR1 | 119 | ||
B4DXZ6 | B4DXZ6_HUMAN | FXR1 | 608 | ||
C9JAJ4 | C9JAJ4_HUMAN | FXR1 | 151 | ||
H7C4S4 | H7C4S4_HUMAN | FXR1 | 246 | ||
E9PFF5 | E9PFF5_HUMAN | FXR1 | 490 | ||
A0A8V8TNP6 | A0A8V8TNP6_HUMAN | FXR1 | 568 | ||
A0A8V8TM97 | A0A8V8TM97_HUMAN | FXR1 | 54 | ||
A0A8V8TMQ1 | A0A8V8TMQ1_HUMAN | FXR1 | 650 |
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_019709 | 1-85 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 3-4 | in Ref. 1; AAC50155 | ||||
Sequence: EL → DV | ||||||
Sequence conflict | 27 | in Ref. 3; BAF85322 | ||||
Sequence: S → P | ||||||
Compositional bias | 409-444 | Basic and acidic residues | ||||
Sequence: SETESERKDELSDWSLAGEDDRDSRHQRDSRRRPGG | ||||||
Compositional bias | 467-489 | Polar residues | ||||
Sequence: SVLKDPDSNPYSLLDNTESDQTA | ||||||
Alternative sequence | VSP_019710 | 535-539 | in isoform 2 | |||
Sequence: VTVAD → GKRCD | ||||||
Alternative sequence | VSP_019711 | 540-621 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 555-575 | Basic and acidic residues | ||||
Sequence: RETLAKNKKEMAKDVIEEHGP | ||||||
Compositional bias | 594-608 | Basic and acidic residues | ||||
Sequence: LQRTPGEEKINTLKE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U25165 EMBL· GenBank· DDBJ | AAC50155.1 EMBL· GenBank· DDBJ | mRNA | ||
AY341428 EMBL· GenBank· DDBJ | AAQ20045.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292633 EMBL· GenBank· DDBJ | BAF85322.1 EMBL· GenBank· DDBJ | mRNA | ||
BC028983 EMBL· GenBank· DDBJ | AAH28983.1 EMBL· GenBank· DDBJ | mRNA |