SRSF1
entrez
6426
canonical
uniprot
Q07955
canonical
ensembl
ENSG00000136450
resolver
ensembl
ENSG00000266086
resolver
ensp
ENSP00000258962
resolver
ensp
ENSP00000462215
resolver
genesymbol
SRSF1
resolver
genesymbol_syn
ASF
resolver
genesymbol_syn
SF2
resolver
genesymbol_syn
SF2P33
resolver
genesymbol_syn
SFRS1
resolver
hgnc
HGNC:10780
resolver
uniprot
B2R6Z7
resolver
uniprot
D3DTZ3
resolver
uniprot
Q13809
resolver
uniprot
Q59FA2
resolver
uniprot_entry
Q59FA2_HUMAN
resolver
uniprot_entry
SRSF1_HUMAN
resolver
uniprot_sec
B2R6Z7
resolver
uniprot_sec
D3DTZ3
resolver
uniprot_sec
Q13809
resolver
amino_acid_sequence
MSGGGVIRGPAGNNDCRIYVGNLPPDIRTKDIEDVFYKYGAIRDIDLKNRRGGPPFAFVEFEDPRDAEDAVYGRDGYDYDGYRLRVEFPRSGRGTGRGGGGGGGGGAPRGRYGPPSRRSENRVVVSGLPPSGSWQDLKDHMREAGDVCYADVYRDGTGVVEFVRKEDMTYAVRKLDNTKFRSHEGETAYIRVKVDGPRSPSYGRSRSRSRSRSRSRSRSNSRSRSYSPRRSRGSPRYSPRHSRSRSRT
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities (NEDFBA) [MIM:620489]: An autosomal dominant disorder characterized by developmental delay, intellectual disability, speech delay, hypotonia, behavioral abnormalities, and non-specific dysmorphic facial features. Some patients have variable skeletal and cardiac anomalies. {ECO:0000269|PubMed:37071997}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway. {ECO:0000269|PubMed:37595559, ECO:0000269|PubMed:8139654}.
uniprot
proteins
mass_dalton
27745
uniprot
proteins
mutagenesis
MUTAGEN 58..59; /note="FV->SR: In FV1; loss of ability to activate splicing. Slight reduction in splice site switching activity and no effect on RNA-binding."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 93; /note="R->A: Predominantly localizes to cytoplasm and fails to modulate splicing of endogenous pre-mRNAs; when associated with Ala-97 and Ala-109."; /evidence="ECO:0000269|PubMed:20308322"; MUTAGEN 97; /note="R->A: Predominantly localizes to cytoplasm and fails to modulate splicing of endogenous pre-mRNAs; when associated with Ala-93 and Ala-109."; /evidence="ECO:0000269|PubMed:20308322"; MUTAGEN 109; /note="R->A: Predominantly localizes to cytoplasm and fails to modulate splicing of endogenous pre-mRNAs; when associated with Ala-93 and Ala-97."; /evidence="ECO:0000269|PubMed:20308322"; MUTAGEN 162..163; /note="FV->SR: In FV2; loss of ability to activate splicing. Great reduction in splice site switching activity and RNA-binding."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 162; /note="F->A: In AV; loss of ability to activate splicing. Great reduction in splice site switching activity and no effect on RNA-binding."; /evidence="ECO:0000269|PubMed:9420331"; MUTAGEN 162; /note="F->D: Reduced nucleocytoplasmic shuttling; when associated with D-190."; /evidence="ECO:0000269|PubMed:9420331"; MUTAGEN 180; /note="F->D: Reduced nucleocytoplasmic shuttling; when associated with D-162."; /evidence="ECO:0000269|PubMed:9420331"; MUTAGEN 182..248; /note="Missing: In MR-B; strongly inhibits splicing."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 182..199; /note="Missing: In MR-E; loss of ability to activate splicing."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 192..248; /note="Missing: In MR-A; loss of ability to activate splicing."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 192..199; /note="Missing: In MR-D; loss of ability to activate splicing."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 199..224; /note="Missing: In RS-A; loss of ability to activate splicing but retains splice site switching."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 215..248; /note="Missing: In RS-C; loss of ability to activate splicing but retains splice site switching."; /evidence="ECO:0000269|PubMed:8223481"; MUTAGEN 226..248; /note="Missing: In RS-B; retains both splice activation and splice site switching activity."; /evidence="ECO:0000269|PubMed:8223481
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by CLK1, CLK2, CLK3 and CLK4. Phosphorylated by SRPK1 at multiple serines in its RS domain via a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds to a docking groove in the large lobe of the kinase domain of SRPK1 and this induces certain structural changes in SRPK1 and/or RRM 2 domain of SRSF1, allowing RRM 2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM 2, which then docks at the docking groove of SRPK1. This also signals RRM 2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. {ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:18155240, ECO:0000269|PubMed:18687337, ECO:0000269|PubMed:19477182, ECO:0000269|PubMed:19886675}.; PTM: Asymmetrically dimethylated at arginines, probably by PRMT1, methylation promotes localization to nuclear speckles. {ECO:0000269|PubMed:20308322}.
uniprot
proteins
protein_family
Splicing factor SR family
uniprot
proteins
pubmed
10757789
uniprot
proteins
pubmed
11991638
uniprot
proteins
pubmed
12215544
uniprot
proteins
pubmed
12667464
uniprot
proteins
pubmed
14555757
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1577277
uniprot
proteins
pubmed
15798186
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
1741384
uniprot
proteins
pubmed
18155240
uniprot
proteins
pubmed
18216018
uniprot
proteins
pubmed
1830244
uniprot
proteins
pubmed
18342604
uniprot
proteins
pubmed
1855257
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18687337
uniprot
proteins
pubmed
19477182
uniprot
proteins
pubmed
19561594
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19886675
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20308322
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21296756
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23604122
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24449914
uniprot
proteins
pubmed
24644279
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
37071997
uniprot
proteins
pubmed
37595559
uniprot
proteins
pubmed
7512732
uniprot
proteins
pubmed
7543047
uniprot
proteins
pubmed
8139654
uniprot
proteins
pubmed
8223481
uniprot
proteins
pubmed
8261509
uniprot
proteins
pubmed
9237760
uniprot
proteins
pubmed
9420331
uniprot
proteins
pubmed
9671816
uniprot
proteins
pubmed
9885563
uniprot
proteins
sequence_length
248
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:37595559}. Cytoplasm {ECO:0000269|PubMed:12215544, ECO:0000269|PubMed:20308322, ECO:0000269|PubMed:24449914, ECO:0000269|PubMed:9420331}. Nucleus speckle {ECO:0000269|PubMed:12215544, ECO:0000269|PubMed:20308322, ECO:0000269|PubMed:24449914, ECO:0000269|PubMed:24644279, ECO:0000269|PubMed:9420331}. Note=In nuclear speckles. Shuttles between the nucleus and the cytoplasm (PubMed:12215544, PubMed:20308322, PubMed:24449914, PubMed:9420331). Nuclear import is mediated via interaction with TNPO3 (PubMed:24449914). {ECO:0000269|PubMed:12215544, ECO:0000269|PubMed:20308322, ECO:0000269|PubMed:24449914, ECO:0000269|PubMed:9420331}.
uniprot
proteins