Human Gene SRSF1 (uc002ivi.3)
  Description: Homo sapiens serine/arginine-rich splicing factor 1 (SRSF1), transcript variant 1, mRNA.
RefSeq Summary (NM_006924): This gene encodes a member of the arginine/serine-rich splicing factor protein family. The encoded protein can either activate or repress splicing, depending on its phosphorylation state and its interaction partners. Multiple transcript variants have been found for this gene. There is a pseudogene of this gene on chromosome 13. [provided by RefSeq, Jun 2014].
Transcript (Including UTRs)
   Position: hg19 chr17:56,078,280-56,084,707 Size: 6,428 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg19 chr17:56,082,767-56,084,498 Size: 1,732 Coding Exon Count: 4 

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Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:56,078,280-56,084,707)mRNA (may differ from genome)Protein (248 aa)
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-  Comments and Description Text from UniProtKB
  ID: SRSF1_HUMAN
DESCRIPTION: RecName: Full=Serine/arginine-rich splicing factor 1; AltName: Full=Alternative-splicing factor 1; Short=ASF-1; AltName: Full=Splicing factor, arginine/serine-rich 1; AltName: Full=pre-mRNA-splicing factor SF2, P33 subunit;
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.
SUBUNIT: 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. Interacts with SRPK1. 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). Interacts with SRPK1 and a sliding docking interaction is essential for its sequential and processive phosphorylation by SRPK1.
INTERACTION: Q86X95:CIR1; NbExp=3; IntAct=EBI-398920, EBI-627102; P23511:NFYA; NbExp=5; IntAct=EBI-398920, EBI-389739; Q9UBU9:NXF1; NbExp=5; IntAct=EBI-398920, EBI-398874; Q96SB4:SRPK1; NbExp=2; IntAct=EBI-398920, EBI-539478; O70551:Srpk1 (xeno); NbExp=5; IntAct=EBI-398920, EBI-593343; O54781:Srpk2 (xeno); NbExp=3; IntAct=EBI-398920, EBI-593325;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus speckle. Note=In nuclear speckles. Shuttles between the nucleus and the cytoplasm.
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.
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.
PTM: Arg-97 is dimethylated, probably to asymmetric dimethylarginine.
SIMILARITY: Belongs to the splicing factor SR family.
SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: SRSF1
Diseases sorted by gene-association score: afibrinogenemia (2), congenital myasthenic syndrome (1), spinocerebellar ataxia 31 (1), growth hormone deficiency, isolated, type ii (1), korean hemorrhagic fever (1), breast adenoma (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 104.37 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 2087.18 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -79.10209-0.378 Picture PostScript Text
3' UTR -1224.154487-0.273 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR012677 - Nucleotide-bd_a/b_plait
IPR000504 - RRM_dom

Pfam Domains:
PF00076 - RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain)

SCOP Domains:
54928 - RNA-binding domain, RBD

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1X4A - NMR MuPIT 2O3D - NMR MuPIT 3BEG - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q07955
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
   Gene DetailsGene Details 
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  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003676 nucleic acid binding
GO:0003723 RNA binding
GO:0003729 mRNA binding
GO:0005515 protein binding
GO:0043422 protein kinase B binding
GO:0044547 DNA topoisomerase binding
GO:0050733 RS domain binding

Biological Process:
GO:0000380 alternative mRNA splicing, via spliceosome
GO:0000395 mRNA 5'-splice site recognition
GO:0000398 mRNA splicing, via spliceosome
GO:0001701 in utero embryonic development
GO:0006376 mRNA splice site selection
GO:0006397 mRNA processing
GO:0006405 RNA export from nucleus
GO:0006406 mRNA export from nucleus
GO:0008380 RNA splicing
GO:0031124 mRNA 3'-end processing
GO:0033120 positive regulation of RNA splicing
GO:0048709 oligodendrocyte differentiation
GO:0051028 mRNA transport
GO:0060048 cardiac muscle contraction
GO:0097421 liver regeneration

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005681 spliceosomal complex
GO:0005737 cytoplasm
GO:0016607 nuclear speck
GO:0071013 catalytic step 2 spliceosome
GO:0035145 exon-exon junction complex


-  Descriptions from all associated GenBank mRNAs
  MF436148 - Homo sapiens serine and arginine rich splicing factor 1 transcript variant 4 (SRSF1) mRNA, 3' UTR; alternatively spliced.
MF436149 - Homo sapiens serine and arginine rich splicing factor 1 transcript variant 5 (SRSF1) mRNA, partial cds and 3' UTR; alternatively spliced.
JD560739 - Sequence 541763 from Patent EP1572962.
JD560740 - Sequence 541764 from Patent EP1572962.
JD441830 - Sequence 422854 from Patent EP1572962.
AK225711 - Homo sapiens mRNA for Splice isoform ASF-2 of Q07955 variant, clone: TMS07306.
AB062124 - Homo sapiens mRNA, complete cds, similar to splicing factor SF2p33.
AB209558 - Homo sapiens mRNA for splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) variant protein.
BC010264 - Homo sapiens splicing factor, arginine/serine-rich 1, mRNA (cDNA clone MGC:5228 IMAGE:2900101), complete cds.
BC033785 - Homo sapiens splicing factor, arginine/serine-rich 1, mRNA (cDNA clone MGC:45185 IMAGE:5166554), complete cds.
JD138706 - Sequence 119730 from Patent EP1572962.
M72709 - Human alternative splicing factor mRNA, complete cds.
JD488932 - Sequence 469956 from Patent EP1572962.
JD374741 - Sequence 355765 from Patent EP1572962.
JD318655 - Sequence 299679 from Patent EP1572962.
JD450541 - Sequence 431565 from Patent EP1572962.
JD236328 - Sequence 217352 from Patent EP1572962.
AK298527 - Homo sapiens cDNA FLJ53078 complete cds, highly similar to Splicing factor, arginine/serine-rich 1.
JD241198 - Sequence 222222 from Patent EP1572962.
JD264808 - Sequence 245832 from Patent EP1572962.
JD467833 - Sequence 448857 from Patent EP1572962.
JD428780 - Sequence 409804 from Patent EP1572962.
JD058528 - Sequence 39552 from Patent EP1572962.
M69040 - Human SF2p33 mRNA, complete cds.
AK289933 - Homo sapiens cDNA FLJ77645 complete cds, highly similar to Homo sapiens splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) (SFRS1), mRNA.
JD281235 - Sequence 262259 from Patent EP1572962.
JD348418 - Sequence 329442 from Patent EP1572962.
JD278657 - Sequence 259681 from Patent EP1572962.
DQ571955 - Homo sapiens piRNA piR-40067, complete sequence.
AK312781 - Homo sapiens cDNA, FLJ93198, Homo sapiens splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) (SFRS1), mRNA.
KJ892127 - Synthetic construct Homo sapiens clone ccsbBroadEn_01521 SRSF1 gene, encodes complete protein.
CU679661 - Synthetic construct Homo sapiens gateway clone IMAGE:100018607 5' read SFRS1 mRNA.
AB384975 - Synthetic construct DNA, clone: pF1KB4679, Homo sapiens SFRS1 gene for splicing factor, arginine/serine-rich 1, complete cds, without stop codon, in Flexi system.
JD230819 - Sequence 211843 from Patent EP1572962.
JD140556 - Sequence 121580 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03040 - Spliceosome

Reactome (by CSHL, EBI, and GO)

Protein Q07955 (Reactome details) participates in the following event(s):

R-HSA-72107 Formation of the Spliceosomal E complex
R-HSA-75080 Formation of AT-AC A complex
R-HSA-75096 Docking of the TAP:EJC Complex with the NPC
R-HSA-72143 Lariat Formation and 5'-Splice Site Cleavage
R-HSA-72139 Formation of the active Spliceosomal C (B*) complex
R-HSA-72124 Formation of the Spliceosomal A Complex
R-HSA-72127 Formation of the Spliceosomal B Complex
R-HSA-72130 Formation of an intermediate Spliceosomal C (Bact) complex
R-HSA-8849157 TREX complex binds spliced, capped mRNA:CBC:EJC cotranscriptionally
R-HSA-72185 mRNA polyadenylation
R-HSA-72180 Cleavage of mRNA at the 3'-end
R-HSA-75081 Formation of AT-AC B Complex
R-HSA-75082 ATAC spliceosome mediated Lariat formation,5' splice site cleavage
R-HSA-75079 Formation of AT-AC C complex
R-HSA-75083 ATAC spliceosome mediated 3' splice site cleavage, exon ligation
R-HSA-156661 Formation of Exon Junction Complex
R-HSA-159101 NXF1:NXT1 (TAP:p15) binds capped mRNA:CBC:EJC:TREX (minus DDX39B)
R-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-72165 mRNA Splicing - Minor Pathway
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187 mRNA 3'-end processing
R-HSA-109688 Cleavage of Growing Transcript in the Termination Region
R-HSA-72172 mRNA Splicing
R-HSA-72202 Transport of Mature Transcript to Cytoplasm
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73856 RNA Polymerase II Transcription Termination
R-HSA-8953854 Metabolism of RNA
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: ASF, B2R6Z7, D3DTZ3, NM_006924, NP_008855, OK/SW-cl.3, Q07955, Q13809, SF2, SF2P33, SFRS1, SRSF1_HUMAN
UCSC ID: uc002ivi.3
RefSeq Accession: NM_006924
Protein: Q07955 (aka SRSF1_HUMAN)
CCDS: CCDS11600.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_006924.4
exon count: 4CDS single in 3' UTR: no RNA size: 5468
ORF size: 747CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1694.00frame shift in genome: no % Coverage: 99.54
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 4004# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.