Q6PDM2 (SRSF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Srsf1
Synonyms:	Sfrs1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	248 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 of CAMKD2 in the adult heart results in aberrant calcium handling and defective excitation-contraction coupling in cardiomyocytes. 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 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
Sequence similarities	Belongs to the splicing factor SR family. Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus Spliceosome
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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
Cellular_component	catalytic step 2 spliceosome Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from direct assay PubMed 20729808PubMed 21191184. Source: MGI
Molecular_function	RNA binding Inferred from sequence or structural similarity. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 248

247

Serine/arginine-rich splicing factor 1

PRO_0000081912

Regions

Domain

16 – 91

76

RRM 1

Domain

121 – 195

75

RRM 2

Region

198 – 247

50

Interacts with SAFB1 By similarity

Compositional bias

94 – 113

20

Gly-rich (hinge region)

Compositional bias

198 – 247

50

Arg/Ser-rich (RS domain)

Amino acid modifications

Modified residue

2

1

N-acetylserine Potential

Modified residue

2

1

Phosphoserine By similarity

Modified residue

38

1

N6-acetyllysine By similarity

Modified residue

93

1

Omega-N-methylated arginine By similarity

Modified residue

97

1

Omega-N-methylated arginine By similarity

Modified residue

109

1

Omega-N-methylated arginine By similarity

Modified residue

179

1

N6-acetyllysine By similarity

Modified residue

199

1

Phosphoserine Ref.8

Modified residue

201

1

Phosphoserine Ref.8

Modified residue

205

1

Phosphoserine By similarity

Modified residue

231

1

Phosphoserine Ref.7

Modified residue

234

1

Phosphoserine By similarity

Modified residue

238

1

Phosphoserine Ref.7

Natural variations

Alternative sequence

185 – 203

19

GETAY…SPSYG → VGYTLILFFGQNWIQFS in isoform 2.

VSP_013770

Alternative sequence

185 – 199

15

GETAY…DGPRS → TYLKRWIKNALD in isoform 3.

VSP_013771

Alternative sequence

200 – 248

49

Missing in isoform 3.

VSP_013772

Alternative sequence

204 – 248

45

Missing in isoform 2.

VSP_013773

Experimental info

Sequence conflict

119

1

S → A in BAC25546. Ref.1

Sequence conflict

162 – 164

3

FVR → CVP in BAC25546. Ref.1

Sequence conflict

185

1

G → W in BAC25546. Ref.1

Sequence conflict

191 – 196

6

RVKVDG → PRIVDR in BAC25546. Ref.1

Sequence conflict

209 – 210

2

SR → VC in BAC25546. Ref.1

Sequence conflict

226 – 228

3

YSP → DSR in BAC25546. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

248

Helix Strand Turn

Details...

Beta strand

122 – 127

6

Helix

134 – 141

8

Helix

142 – 144

3

Beta strand

147 – 152

6

Beta strand

156 – 164

9

Helix

165 – 174

10

Beta strand

175 – 181

7

Beta strand

187 – 196

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: C28A0B2F112EA713	FASTA	248	27,745
	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
	Isoform 2 [UniParc]. Checksum: 16B6D495BD77613F	FASTA	201	22,320
	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 RSHEVGYTLI LFFGQNWIQF S
	Isoform 3 [UniParc]. Checksum: 6723D202662FF71D	FASTA	196	21,807
	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 RSHETYLKRW IKNALD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231 AND SER-238, MASS SPECTROMETRY. Tissue: Liver.
[8]	"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, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[9]	"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.

IPI

IPI00420807.
IPI00457656.
IPI00515505.

PIR

S26404.

RefSeq

NP_001071635.1. NM_001078167.2.
NP_775550.2. NM_173374.4.

UniGene

Mm.391719.
Mm.478968.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X4C	NMR	-	A	113-207	[»]

ProteinModelPortal

Q6PDM2.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48723N.

IntAct

Q6PDM2. 1 interaction.

PTM databases

PhosphoSite

Q6PDM2.

Proteomic databases

PaxDb

Q6PDM2.

PRIDE

Q6PDM2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000079866; ENSMUSP00000133517; ENSMUSG00000018379.
ENSMUST00000139129; ENSMUSP00000120595; ENSMUSG00000018379.

GeneID

110809.

KEGG

mmu:110809.

UCSC

uc007kvc.1. mouse.
uc007kvd.1. mouse.

Organism-specific databases

CTD

6426.

MGI

MGI:98283. Srsf1.

Phylogenomic databases

eggNOG

COG0724.

GeneTree

ENSGT00700000104103.

HOVERGEN

HBG002295.

InParanoid

B2KGJ5.

KO

K12890.

Gene expression databases

ArrayExpress

Q6PDM2.

Bgee

Q6PDM2.

CleanEx

MM_SFRS1.

Genevestigator

Q6PDM2.

GermOnline

ENSMUSG00000018379. Mus musculus.

Family and domain databases

Gene3D

3.30.70.330. 2 hits.

InterPro

IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]

Pfam

PF00076. RRM_1. 2 hits.
[Graphical view]

SMART

SM00360. RRM. 2 hits.
[Graphical view]

PROSITE

PS50102. RRM. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q6PDM2.

NextBio

364697.

SOURCE

Search...

Entry information

Entry name

SRSF1_MOUSE

Accession

Primary (citable) accession number: Q6PDM2
Secondary accession number(s): B2KGJ5 , Q3UCH2, Q5SXC5, Q8BJV3, Q8C1H9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program