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Protein

Serine/arginine-rich splicing factor 1

Gene

Srsf1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity). Specifically regulates alternative splicing of cardiac isoforms of CAMK2D, LDB3/CYPHER and TNNT2/CTNT during heart remodeling at the juvenile to adult transition. The inappropriate accumulation of a neonatal and neuronal isoform of CAMKD2 in the adult heart results in aberrant calcium handling and defective excitation-contraction coupling in cardiomyocytes. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway.By similarity1 Publication

GO - Molecular functioni

  • mRNA binding Source: MGI
  • nucleotide binding Source: InterPro
  • poly(A) RNA binding Source: MGI
  • RNA binding Source: UniProtKB
  • RS domain binding Source: MGI

GO - Biological processi

  • alternative mRNA splicing, via spliceosome Source: MGI
  • cardiac muscle contraction Source: MGI
  • in utero embryonic development Source: MGI
  • liver regeneration Source: Ensembl
  • mRNA 5'-splice site recognition Source: UniProtKB
  • mRNA transport Source: UniProtKB-KW
  • oligodendrocyte differentiation Source: Ensembl
  • positive regulation of RNA splicing Source: Ensembl
  • RNA splicing Source: MGI
Complete GO annotation...

Keywords - Biological processi

mRNA processing, mRNA splicing, mRNA transport, Transport

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-109688. Cleavage of Growing Transcript in the Termination Region.
R-MMU-159236. Transport of Mature mRNA derived from an Intron-Containing Transcript.
R-MMU-72163. mRNA Splicing - Major Pathway.
R-MMU-72165. mRNA Splicing - Minor Pathway.
R-MMU-72187. mRNA 3'-end processing.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/arginine-rich splicing factor 1
Alternative name(s):
ASF/SF2
Pre-mRNA-splicing factor SRp30a
Splicing factor, arginine/serine-rich 1
Gene namesi
Name:Srsf1
Synonyms:Sfrs1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:98283. Srsf1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus speckle By similarity

  • Note: In nuclear speckles. Shuttles between the nucleus and the cytoplasm.By similarity

GO - Cellular componenti

  • catalytic step 2 spliceosome Source: MGI
  • cytoplasm Source: UniProtKB-SubCell
  • exon-exon junction complex Source: Ensembl
  • extracellular exosome Source: MGI
  • nuclear speck Source: MGI
  • nucleoplasm Source: UniProtKB
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Spliceosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000819122 – 248Serine/arginine-rich splicing factor 1Add BLAST247

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineSequence analysisBy similarity1
Modified residuei2PhosphoserineBy similarity1
Modified residuei38N6-acetyllysine; alternateBy similarity1
Cross-linki38Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei93Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei93Omega-N-methylarginine; alternateCombined sources1
Modified residuei97Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei97Omega-N-methylarginine; alternateCombined sources1
Modified residuei109Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei109Omega-N-methylarginine; alternateCombined sources1
Modified residuei111Omega-N-methylarginineBy similarity1
Modified residuei133PhosphoserineBy similarity1
Modified residuei179N6-acetyllysineBy similarity1
Modified residuei199PhosphoserineCombined sources1
Modified residuei201PhosphoserineCombined sources1
Modified residuei202PhosphotyrosineBy similarity1
Modified residuei205PhosphoserineBy similarity1
Modified residuei231PhosphoserineBy similarity1
Modified residuei234PhosphoserineBy similarity1
Modified residuei238PhosphoserineBy similarity1

Post-translational modificationi

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 (By similarity).By similarity
Asymmetrically dimethylated at arginines, probably by PRMT1, methylation promotes localization to nuclear speckles.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ6PDM2.
PaxDbiQ6PDM2.
PeptideAtlasiQ6PDM2.
PRIDEiQ6PDM2.
TopDownProteomicsiQ6PDM2-1. [Q6PDM2-1]

PTM databases

iPTMnetiQ6PDM2.
PhosphoSitePlusiQ6PDM2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000018379.
CleanExiMM_SFRS1.
ExpressionAtlasiQ6PDM2. baseline and differential.
GenevisibleiQ6PDM2. MM.

Interactioni

Subunit structurei

Consists of two polypeptides of p32 and p33. In vitro, self-associates and binds SRSF2, SNRNP70 and U2AF1 but not U2AF2. Binds SREK1/SFRS12. Interacts with SAFB/SAFB1. Interacts with PSIP1/LEDGF. Identified in the spliceosome C complex. Interacts with RSRC1 (via Arg/Ser-rich domain). Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus) (By similarity). Interacts with SRPK1 and a sliding docking interaction is essential for its sequential and processive phosphorylation by SRPK1. Interacts with NXF1 (By similarity). Interacts with CCNL1, CCNL2 and CDK11B (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Hexim1Q8R4094EBI-2550360,EBI-6261031
Polr2aP087752EBI-2550360,EBI-2549849
Tial1P703183EBI-2550360,EBI-299820
Traf5P701912EBI-2550360,EBI-523899

GO - Molecular functioni

  • RS domain binding Source: MGI

Protein-protein interaction databases

BioGridi225922. 75 interactors.
DIPiDIP-48723N.
IntActiQ6PDM2. 78 interactors.
MINTiMINT-1867664.
STRINGi10090.ENSMUSP00000120595.

Structurei

Secondary structure

1248
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi122 – 127Combined sources6
Helixi134 – 141Combined sources8
Helixi142 – 144Combined sources3
Beta strandi147 – 152Combined sources6
Beta strandi156 – 164Combined sources9
Helixi165 – 174Combined sources10
Beta strandi175 – 181Combined sources7
Beta strandi187 – 196Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X4CNMR-A113-207[»]
ProteinModelPortaliQ6PDM2.
SMRiQ6PDM2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ6PDM2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 91RRM 1PROSITE-ProRule annotationAdd BLAST76
Domaini121 – 195RRM 2PROSITE-ProRule annotationAdd BLAST75

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni198 – 247Interaction with SAFB1By similarityAdd BLAST50

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi94 – 113Gly-rich (hinge region)Add BLAST20
Compositional biasi198 – 247Arg/Ser-rich (RS domain)Add BLAST50

Domaini

The RRM 2 domain plays an important role in governing both the binding mode and the phosphorylation mechanism of the RS domain by SRPK1. RS domain and RRM 2 are uniquely positioned to initiate a highly directional (C-terminus to N-terminus) phosphorylation reaction in which the RS domain slides through an extended electronegative channel separating the docking groove of SRPK1 and the active site. RRM 2 binds toward the periphery of the active site and guides the directional phosphorylation mechanism. Both the RS domain and an RRM domain are required for nucleocytoplasmic shuttling (By similarity).By similarity

Sequence similaritiesi

Belongs to the splicing factor SR family.Curated
Contains 2 RRM (RNA recognition motif) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0105. Eukaryota.
COG0724. LUCA.
GeneTreeiENSGT00700000104103.
HOVERGENiHBG002295.
InParanoidiQ6PDM2.
KOiK12890.
PhylomeDBiQ6PDM2.
TreeFamiTF106261.

Family and domain databases

Gene3Di3.30.70.330. 2 hits.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00076. RRM_1. 2 hits.
[Graphical view]
SMARTiSM00360. RRM. 2 hits.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6PDM2-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSGGGVIRGP AGNNDCRIYV GNLPPDIRTK DIEDVFYKYG AIRDIDLKNR
60 70 80 90 100
RGGPPFAFVE FEDPRDAEDA VYGRDGYDYD GYRLRVEFPR SGRGTGRGGG
110 120 130 140 150
GGGGGGAPRG RYGPPSRRSE NRVVVSGLPP SGSWQDLKDH MREAGDVCYA
160 170 180 190 200
DVYRDGTGVV EFVRKEDMTY AVRKLDNTKF RSHEGETAYI RVKVDGPRSP
210 220 230 240
SYGRSRSRSR SRSRSRSRSN SRSRSYSPRR SRGSPRYSPR HSRSRSRT
Length:248
Mass (Da):27,745
Last modified:January 23, 2007 - v3
Checksum:iC28A0B2F112EA713
GO
Isoform 2 (identifier: Q6PDM2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     185-203: GETAYIRVKVDGPRSPSYG → VGYTLILFFGQNWIQFS
     204-248: Missing.

Note: May be due to intron retention.
Show »
Length:201
Mass (Da):22,320
Checksum:i16B6D495BD77613F
GO
Isoform 3 (identifier: Q6PDM2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     185-199: GETAYIRVKVDGPRS → TYLKRWIKNALD
     200-248: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:196
Mass (Da):21,807
Checksum:i6723D202662FF71D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti119S → A in BAC25546 (PubMed:16141072).Curated1
Sequence conflicti162 – 164FVR → CVP in BAC25546 (PubMed:16141072).Curated3
Sequence conflicti185G → W in BAC25546 (PubMed:16141072).Curated1
Sequence conflicti191 – 196RVKVDG → PRIVDR in BAC25546 (PubMed:16141072).Curated6
Sequence conflicti209 – 210SR → VC in BAC25546 (PubMed:16141072).Curated2
Sequence conflicti226 – 228YSP → DSR in BAC25546 (PubMed:16141072).Curated3

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013770185 – 203GETAY…SPSYG → VGYTLILFFGQNWIQFS in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_013771185 – 199GETAY…DGPRS → TYLKRWIKNALD in isoform 3. CuratedAdd BLAST15
Alternative sequenceiVSP_013772200 – 248Missing in isoform 3. CuratedAdd BLAST49
Alternative sequenceiVSP_013773204 – 248Missing in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK018176 mRNA. Translation: BAC25546.1.
AK078715 mRNA. Translation: BAC37367.1.
AK150535 mRNA. Translation: BAE29641.1.
AL593853 Genomic DNA. Translation: CAI24416.1.
CU406964 Genomic DNA. Translation: CAQ51705.1.
BC046773 mRNA. Translation: AAH46773.1.
BC058627 mRNA. Translation: AAH58627.1.
CCDSiCCDS36273.1. [Q6PDM2-1]
CCDS36274.1. [Q6PDM2-2]
PIRiS26404.
RefSeqiNP_001071635.1. NM_001078167.2. [Q6PDM2-2]
NP_775550.2. NM_173374.4. [Q6PDM2-1]
UniGeneiMm.391719.

Genome annotation databases

EnsembliENSMUST00000079866; ENSMUSP00000133517; ENSMUSG00000018379. [Q6PDM2-2]
ENSMUST00000139129; ENSMUSP00000120595; ENSMUSG00000018379. [Q6PDM2-1]
ENSMUST00000183352; ENSMUSP00000138980; ENSMUSG00000098301. [Q6PDM2-1]
ENSMUST00000193491; ENSMUSP00000141939; ENSMUSG00000098301. [Q6PDM2-2]
GeneIDi110809.
KEGGimmu:110809.
UCSCiuc007kvc.2. mouse. [Q6PDM2-1]
uc007kvd.2. mouse. [Q6PDM2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK018176 mRNA. Translation: BAC25546.1.
AK078715 mRNA. Translation: BAC37367.1.
AK150535 mRNA. Translation: BAE29641.1.
AL593853 Genomic DNA. Translation: CAI24416.1.
CU406964 Genomic DNA. Translation: CAQ51705.1.
BC046773 mRNA. Translation: AAH46773.1.
BC058627 mRNA. Translation: AAH58627.1.
CCDSiCCDS36273.1. [Q6PDM2-1]
CCDS36274.1. [Q6PDM2-2]
PIRiS26404.
RefSeqiNP_001071635.1. NM_001078167.2. [Q6PDM2-2]
NP_775550.2. NM_173374.4. [Q6PDM2-1]
UniGeneiMm.391719.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X4CNMR-A113-207[»]
ProteinModelPortaliQ6PDM2.
SMRiQ6PDM2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi225922. 75 interactors.
DIPiDIP-48723N.
IntActiQ6PDM2. 78 interactors.
MINTiMINT-1867664.
STRINGi10090.ENSMUSP00000120595.

PTM databases

iPTMnetiQ6PDM2.
PhosphoSitePlusiQ6PDM2.

Proteomic databases

EPDiQ6PDM2.
PaxDbiQ6PDM2.
PeptideAtlasiQ6PDM2.
PRIDEiQ6PDM2.
TopDownProteomicsiQ6PDM2-1. [Q6PDM2-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000079866; ENSMUSP00000133517; ENSMUSG00000018379. [Q6PDM2-2]
ENSMUST00000139129; ENSMUSP00000120595; ENSMUSG00000018379. [Q6PDM2-1]
ENSMUST00000183352; ENSMUSP00000138980; ENSMUSG00000098301. [Q6PDM2-1]
ENSMUST00000193491; ENSMUSP00000141939; ENSMUSG00000098301. [Q6PDM2-2]
GeneIDi110809.
KEGGimmu:110809.
UCSCiuc007kvc.2. mouse. [Q6PDM2-1]
uc007kvd.2. mouse. [Q6PDM2-2]

Organism-specific databases

CTDi6426.
MGIiMGI:98283. Srsf1.

Phylogenomic databases

eggNOGiKOG0105. Eukaryota.
COG0724. LUCA.
GeneTreeiENSGT00700000104103.
HOVERGENiHBG002295.
InParanoidiQ6PDM2.
KOiK12890.
PhylomeDBiQ6PDM2.
TreeFamiTF106261.

Enzyme and pathway databases

ReactomeiR-MMU-109688. Cleavage of Growing Transcript in the Termination Region.
R-MMU-159236. Transport of Mature mRNA derived from an Intron-Containing Transcript.
R-MMU-72163. mRNA Splicing - Major Pathway.
R-MMU-72165. mRNA Splicing - Minor Pathway.
R-MMU-72187. mRNA 3'-end processing.

Miscellaneous databases

ChiTaRSiSrsf1. mouse.
EvolutionaryTraceiQ6PDM2.
PROiQ6PDM2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000018379.
CleanExiMM_SFRS1.
ExpressionAtlasiQ6PDM2. baseline and differential.
GenevisibleiQ6PDM2. MM.

Family and domain databases

Gene3Di3.30.70.330. 2 hits.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00076. RRM_1. 2 hits.
[Graphical view]
SMARTiSM00360. RRM. 2 hits.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSRSF1_MOUSE
AccessioniPrimary (citable) accession number: Q6PDM2
Secondary accession number(s): B2KGJ5
, Q3UCH2, Q5SXC5, Q8BJV3, Q8C1H9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.