KHDR2_MOUSE
ID KHDR2_MOUSE Reviewed; 349 AA.
AC Q9WU01; Q6NXZ3;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=KH domain-containing, RNA-binding, signal transduction-associated protein 2;
DE AltName: Full=Sam68-like mammalian protein 1;
DE Short=SLM-1;
DE Short=mSLM-1;
GN Name=Khdrbs2; Synonyms=Slm1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PHOSPHORYLATION,
RP INTERACTION WITH FYN; GRB2; PLCG1; RASA1; KHDRBS1, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=10077576; DOI=10.1073/pnas.96.6.2710;
RA Di Fruscio M., Chen T., Richard S.;
RT "Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1
RT is a Src substrate during mitosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2710-2715(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=CD-1; TISSUE=Brain, and Neural stem cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION BY PTK6, FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING, AND
RP TISSUE SPECIFICITY.
RX PubMed=15471878; DOI=10.1074/jbc.m409579200;
RA Haegebarth A., Heap D., Bie W., Derry J.J., Richard S., Tyner A.L.;
RT "The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-
RT binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2.";
RL J. Biol. Chem. 279:54398-54404(2004).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=22196734; DOI=10.1016/j.cell.2011.11.028;
RA Iijima T., Wu K., Witte H., Hanno-Iijima Y., Glatter T., Richard S.,
RA Scheiffele P.;
RT "SAM68 regulates neuronal activity-dependent alternative splicing of
RT neurexin-1.";
RL Cell 147:1601-1614(2011).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24469635; DOI=10.1083/jcb.201310136;
RA Iijima T., Iijima Y., Witte H., Scheiffele P.;
RT "Neuronal cell type-specific alternative splicing is regulated by the KH
RT domain protein SLM1.";
RL J. Cell Biol. 204:331-342(2014).
RN [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-230 AND ARG-240, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: RNA-binding protein that plays a role in the regulation of
CC alternative splicing and influences mRNA splice site selection and exon
CC inclusion (By similarity). Binds both poly(A) and poly(U) homopolymers.
CC Phosphorylation by PTK6 inhibits its RNA-binding ability. Induces an
CC increased concentration-dependent incorporation of exon in CD44 pre-
CC mRNA by direct binding to purine-rich exonic enhancer (By similarity).
CC Can regulate alternative splicing of neurexins NRXN1-3 in the laminin
CC G-like domain 6 containing the evolutionary conserved neurexin
CC alternative spliced segment 4 (AS4) involved in neurexin selective
CC targeting to postsynaptic partners. Regulates cell-type specific
CC alternative splicing of NRXN1 at AS4 and acts synergystically with
CC SAM68 in exon skipping. In contrast acts antagonistically with SAM68 in
CC NRXN3 exon skipping at AS4 (PubMed:22196734, PubMed:24469635). Its
CC phosphorylation by FYN inhibits its ability to regulate splice site
CC selection (By similarity). May function as an adapter protein for Src
CC kinases during mitosis (PubMed:10077576).
CC {ECO:0000250|UniProtKB:Q920F3, ECO:0000269|PubMed:10077576,
CC ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:22196734,
CC ECO:0000269|PubMed:24469635}.
CC -!- SUBUNIT: Self-associates to form homooligomers (By similarity).
CC Interacts with KHDRBS1/SAM68; heterooligomer formation of KHDRBS family
CC proteins may modulate RNA substrate specificity (PubMed:10077576).
CC Interacts with RBMX, SAFB, SFRS9 and YTHDC1 (By similarity). Interacts
CC with FYN and PLCG1 (via SH3 domain). Interacts (phosphorylated) with
CC FYN, GRB2, PLCG1 and RASA1 (via SH2 domain) (PubMed:10077576).
CC {ECO:0000250|UniProtKB:Q5VWX1, ECO:0000250|UniProtKB:Q920F3,
CC ECO:0000269|PubMed:10077576}.
CC -!- INTERACTION:
CC Q9WU01; P39688: Fyn; NbExp=2; IntAct=EBI-8339046, EBI-524514;
CC Q9WU01; P10686: Plcg1; Xeno; NbExp=2; IntAct=EBI-8339046, EBI-520788;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10077576,
CC ECO:0000269|PubMed:15471878}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9WU01-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WU01-2; Sequence=VSP_029065, VSP_029066;
CC -!- TISSUE SPECIFICITY: Expressed in heart, skin, brain, colon, spleen,
CC kidney, cervix and testis. In adult cerebellum expressed predominantly
CC in Purkinje cells and in the hippocampus is abundantly expressed in
CC glutamatergic dentate granule cells and in specific inhibitory Schaffer
CC collateral-associated and path-associated interneurons; expression is
CC restricted to neuronal subpopulations largely non-overlapping with
CC expression of KHDRBS3/SLM-2 (at protein level).
CC {ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:22196734}.
CC -!- DEVELOPMENTAL STAGE: In the developing cerebellum expression is
CC increasing in the first 3 postnatal weeks.
CC {ECO:0000269|PubMed:22196734}.
CC -!- PTM: Methylated. {ECO:0000250|UniProtKB:Q5VWX1}.
CC -!- PTM: Tyrosine phosphorylated by FYN, PTK6 and SRC. Tyrosine
CC phosphorylated by SRC during mitosis. {ECO:0000269|PubMed:10077576,
CC ECO:0000269|PubMed:15471878}.
CC -!- SIMILARITY: Belongs to the KHDRBS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH66814.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF098796; AAD20451.1; -; mRNA.
DR EMBL; BC066814; AAH66814.1; ALT_INIT; mRNA.
DR EMBL; BC132117; AAI32118.1; -; mRNA.
DR EMBL; BC132119; AAI32120.1; -; mRNA.
DR CCDS; CCDS14861.1; -. [Q9WU01-1]
DR RefSeq; NP_573498.1; NM_133235.3. [Q9WU01-1]
DR AlphaFoldDB; Q9WU01; -.
DR SMR; Q9WU01; -.
DR IntAct; Q9WU01; 6.
DR MINT; Q9WU01; -.
DR STRING; 10090.ENSMUSP00000027226; -.
DR iPTMnet; Q9WU01; -.
DR PhosphoSitePlus; Q9WU01; -.
DR MaxQB; Q9WU01; -.
DR PaxDb; Q9WU01; -.
DR PeptideAtlas; Q9WU01; -.
DR PRIDE; Q9WU01; -.
DR ProteomicsDB; 264747; -. [Q9WU01-1]
DR ProteomicsDB; 264748; -. [Q9WU01-2]
DR Antibodypedia; 17553; 145 antibodies from 20 providers.
DR DNASU; 170771; -.
DR Ensembl; ENSMUST00000027226; ENSMUSP00000027226; ENSMUSG00000026058. [Q9WU01-1]
DR Ensembl; ENSMUST00000188257; ENSMUSP00000140157; ENSMUSG00000026058. [Q9WU01-2]
DR GeneID; 170771; -.
DR KEGG; mmu:170771; -.
DR UCSC; uc007ano.1; mouse. [Q9WU01-2]
DR UCSC; uc007anp.1; mouse. [Q9WU01-1]
DR CTD; 202559; -.
DR MGI; MGI:2159649; Khdrbs2.
DR VEuPathDB; HostDB:ENSMUSG00000026058; -.
DR eggNOG; KOG1588; Eukaryota.
DR GeneTree; ENSGT00940000157134; -.
DR HOGENOM; CLU_034976_0_0_1; -.
DR InParanoid; Q9WU01; -.
DR OMA; HETYEEY; -.
DR OrthoDB; 1012406at2759; -.
DR PhylomeDB; Q9WU01; -.
DR TreeFam; TF314878; -.
DR Reactome; R-MMU-8849468; PTK6 Regulates Proteins Involved in RNA Processing.
DR BioGRID-ORCS; 170771; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Khdrbs2; mouse.
DR PRO; PR:Q9WU01; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9WU01; protein.
DR Bgee; ENSMUSG00000026058; Expressed in cortical plate and 121 other tissues.
DR ExpressionAtlas; Q9WU01; baseline and differential.
DR Genevisible; Q9WU01; MM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0008143; F:poly(A) binding; IDA:MGI.
DR GO; GO:0008266; F:poly(U) RNA binding; IDA:MGI.
DR GO; GO:0042169; F:SH2 domain binding; IDA:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IDA:MGI.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; IDA:UniProtKB.
DR Gene3D; 3.30.1370.10; -; 1.
DR InterPro; IPR045071; BBP-like.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR032571; Qua1_dom.
DR InterPro; IPR032335; Sam68-YY.
DR PANTHER; PTHR11208; PTHR11208; 1.
DR Pfam; PF00013; KH_1; 1.
DR Pfam; PF16274; Qua1; 1.
DR Pfam; PF16568; Sam68-YY; 1.
DR SMART; SM00322; KH; 1.
DR SUPFAM; SSF54791; SSF54791; 1.
DR PROSITE; PS50084; KH_TYPE_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Methylation; mRNA processing; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; SH3-binding;
KW Transcription; Transcription regulation.
FT CHAIN 1..349
FT /note="KH domain-containing, RNA-binding, signal
FT transduction-associated protein 2"
FT /id="PRO_0000308954"
FT DOMAIN 65..135
FT /note="KH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 181..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 321..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..220
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 230
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 240
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 113..192
FT /note="EEELRKSGEAKYAHLSDELHVLIEVFAPPGEAYSRMSHALEEIKKFLVPDYN
FT DEIRQEQLRELSYLNGSEESGRGRGIRG -> VLSFEVASSHVKQGSSIWSPVYNMWGW
FT RSLFSMRLAFWYHTVAQSEVTIFFHHPPASFSGHSSCVAFCSSLCRSLSYCYTF (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029065"
FT VAR_SEQ 193..349
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029066"
FT CONFLICT 44
FT /note="D -> N (in Ref. 2; AAH66814)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 349 AA; 38866 MW; 4B003DA8D94EFED8 CRC64;
MGEEKYLPEL MAEKDSLDPS FVHASRLLAE EIEKFQGSDG KKEDEEKKYL DVISNKNIKL
SERVLIPVKQ YPKFNFVGKL LGPRGNSLKR LQEETGAKMS ILGKGSMRDK TKEEELRKSG
EAKYAHLSDE LHVLIEVFAP PGEAYSRMSH ALEEIKKFLV PDYNDEIRQE QLRELSYLNG
SEESGRGRGI RGRGIRITPT APSRGRGGAV PPPPPPGRGV LTPRGTTVTR GALPVPPIAR
GVPTPRARGT AAVPGYRAPP PPAHDAYEEY GYDDGYGGEY DDQTYEAYDN SYVTPTQSVP
EYYDYGHGVN EDAYDSYAPE EWATTRSSLK APPPRSARGG YREHPYGRY
