Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q6PDM2 (SRSF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/arginine-rich splicing factor 1
Alternative name(s):
ASF/SF2
Pre-mRNA-splicing factor SRp30a
Splicing factor, arginine/serine-rich 1
Gene names
Name:Srsf1
Synonyms:Sfrs1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length248 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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 ofCAMKD2 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. Ref.6

Subunit structure

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.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Nucleus speckle By similarity. Note: Shuttles between the nucleus and the cytoplasm By similarity.

Domain

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.

Post-translational modification

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. Ref.5

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

Sequence similarities

Belongs to the splicing factor SR family.

Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
   Biological processmRNA processing
mRNA splicing
mRNA transport
Transport
   Cellular componentCytoplasm
Nucleus
Spliceosome
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandRNA-binding
   PTMAcetylation
Methylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Inferred from direct assay PubMed 15798186. Source: MGI

cardiac muscle contraction

Inferred from genetic interaction Ref.6. Source: MGI

in utero embryonic development

Inferred from mutant phenotype Ref.6. Source: MGI

mRNA 5'-splice site recognition

Inferred from sequence or structural similarity. Source: UniProtKB

mRNA transport

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcatalytic step 2 spliceosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

exon-exon junction complex

Inferred from electronic annotation. Source: Ensembl

nuclear speck

Inferred from direct assay PubMed 20729808PubMed 21191184. Source: MGI

nucleoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 15615787. Source: MGI

   Molecular_functionRNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

RS domain binding

Inferred from physical interaction PubMed 15798186. Source: MGI

mRNA binding

Inferred from sequence orthology PubMed 21984414. Source: MGI

nucleotide binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 20477871PubMed 21822258PubMed 23042150PubMed 23663783. Source: IntAct

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6PDM2-1)

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.
Isoform 2 (identifier: Q6PDM2-2)

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.
Isoform 3 (identifier: Q6PDM2-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 248247Serine/arginine-rich splicing factor 1
PRO_0000081912

Regions

Domain16 – 9176RRM 1
Domain121 – 19575RRM 2
Region198 – 24750Interacts with SAFB1 By similarity
Compositional bias94 – 11320Gly-rich (hinge region)
Compositional bias198 – 24750Arg/Ser-rich (RS domain)

Amino acid modifications

Modified residue21N-acetylserine Potential
Modified residue21Phosphoserine By similarity
Modified residue381N6-acetyllysine By similarity
Modified residue931Asymmetric dimethylarginine By similarity
Modified residue971Asymmetric dimethylarginine By similarity
Modified residue1091Asymmetric dimethylarginine By similarity
Modified residue1791N6-acetyllysine By similarity
Modified residue1991Phosphoserine Ref.7
Modified residue2011Phosphoserine Ref.7
Modified residue2051Phosphoserine By similarity
Modified residue2311Phosphoserine By similarity
Modified residue2341Phosphoserine By similarity
Modified residue2381Phosphoserine By similarity

Natural variations

Alternative sequence185 – 20319GETAY…SPSYG → VGYTLILFFGQNWIQFS in isoform 2.
VSP_013770
Alternative sequence185 – 19915GETAY…DGPRS → TYLKRWIKNALD in isoform 3.
VSP_013771
Alternative sequence200 – 24849Missing in isoform 3.
VSP_013772
Alternative sequence204 – 24845Missing in isoform 2.
VSP_013773

Experimental info

Sequence conflict1191S → A in BAC25546. Ref.1
Sequence conflict162 – 1643FVR → CVP in BAC25546. Ref.1
Sequence conflict1851G → W in BAC25546. Ref.1
Sequence conflict191 – 1966RVKVDG → PRIVDR in BAC25546. Ref.1
Sequence conflict209 – 2102SR → VC in BAC25546. Ref.1
Sequence conflict226 – 2283YSP → DSR in BAC25546. Ref.1

Secondary structure

.............. 248
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: C28A0B2F112EA713

FASTA24827,745
        10         20         30         40         50         60 
MSGGGVIRGP AGNNDCRIYV GNLPPDIRTK DIEDVFYKYG AIRDIDLKNR RGGPPFAFVE 

        70         80         90        100        110        120 
FEDPRDAEDA VYGRDGYDYD GYRLRVEFPR SGRGTGRGGG GGGGGGAPRG RYGPPSRRSE 

       130        140        150        160        170        180 
NRVVVSGLPP SGSWQDLKDH MREAGDVCYA DVYRDGTGVV EFVRKEDMTY AVRKLDNTKF 

       190        200        210        220        230        240 
RSHEGETAYI RVKVDGPRSP SYGRSRSRSR SRSRSRSRSN SRSRSYSPRR SRGSPRYSPR 


HSRSRSRT 

« Hide

Isoform 2 [UniParc].

Checksum: 16B6D495BD77613F
Show »

FASTA20122,320
Isoform 3 [UniParc].

Checksum: 6723D202662FF71D
Show »

FASTA19621,807

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J.
Tissue: Bone marrow macrophage, Eye and Medulla oblongata.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6.
Tissue: Embryonic brain.
[4]Lubec G., Yang J.W., Zigmond M.
Submitted (JUL-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 18-28.
Tissue: Brain.
[5]"Characterization and comparison of four serine- and arginine-rich (SR) protein kinases."
Nayler O., Stamm S., Ullrich A.
Biochem. J. 326:693-700(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CLK1; CLK2; CLK3 AND CLK4.
[6]"ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle."
Xu X., Yang D., Ding J.-H., Wang W., Chu P.-H., Dalton N.D., Wang H.-Y., Bermingham J.R. Jr., Ye Z., Liu F., Rosenfeld M.G., Manley J.L., Ross J. Jr., Chen J., Xiao R.-P., Cheng H., Fu X.-D.
Cell 120:59-72(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199 AND SER-201, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[8]"Solution structure of RRM domain in splicing factor 2."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 113-207.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS36273.1. [Q6PDM2-1]
CCDS36274.1. [Q6PDM2-2]
PIRS26404.
RefSeqNP_001071635.1. NM_001078167.2. [Q6PDM2-2]
NP_775550.2. NM_173374.4. [Q6PDM2-1]
XP_006543028.1. XM_006542965.1. [Q6PDM2-1]
UniGeneMm.391719.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X4CNMR-A113-207[»]
ProteinModelPortalQ6PDM2.
SMRQ6PDM2. Positions 6-102, 116-197.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid225922. 8 interactions.
DIPDIP-48723N.
IntActQ6PDM2. 10 interactions.
MINTMINT-1867664.

PTM databases

PhosphoSiteQ6PDM2.

Proteomic databases

MaxQBQ6PDM2.
PaxDbQ6PDM2.
PRIDEQ6PDM2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000079866; ENSMUSP00000133517; ENSMUSG00000018379. [Q6PDM2-2]
ENSMUST00000139129; ENSMUSP00000120595; ENSMUSG00000018379. [Q6PDM2-1]
GeneID102641923.
110809.
KEGGmmu:102641923.
mmu:110809.
UCSCuc007kvc.1. mouse. [Q6PDM2-1]
uc007kvd.1. mouse. [Q6PDM2-2]

Organism-specific databases

CTD6426.
MGIMGI:98283. Srsf1.

Phylogenomic databases

eggNOGCOG0724.
GeneTreeENSGT00700000104103.
HOVERGENHBG002295.
InParanoidB2KGJ5.
KOK12890.
OrthoDBEOG76X620.
PhylomeDBQ6PDM2.
TreeFamTF106261.

Gene expression databases

ArrayExpressQ6PDM2.
BgeeQ6PDM2.
CleanExMM_SFRS1.
GenevestigatorQ6PDM2.

Family and domain databases

Gene3D3.30.70.330. 2 hits.
InterProIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamPF00076. RRM_1. 2 hits.
[Graphical view]
SMARTSM00360. RRM. 2 hits.
[Graphical view]
PROSITEPS50102. RRM. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ6PDM2.
NextBio364697.
PROQ6PDM2.
SOURCESearch...

Entry information

Entry nameSRSF1_MOUSE
AccessionPrimary (citable) accession number: Q6PDM2
Secondary accession number(s): B2KGJ5 expand/collapse secondary AC list , Q3UCH2, Q5SXC5, Q8BJV3, Q8C1H9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot