KHDR3_MOUSE
ID KHDR3_MOUSE Reviewed; 346 AA.
AC Q9R226; O88624;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=KH domain-containing, RNA-binding, signal transduction-associated protein 3;
DE AltName: Full=RNA-binding protein Etoile;
DE AltName: Full=Sam68-like mammalian protein 2;
DE Short=SLM-2;
GN Name=Khdrbs3; Synonyms=Salp, Slm2;
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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10332027; DOI=10.1093/hmg/8.6.959;
RA Venables J.P., Vernet C., Chew S.L., Elliott D.J., Cowmeadow R.B., Wu J.,
RA Cooke H.J., Artzt K., Eperon I.C.;
RT "T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-
RT binding protein implicated in spermatogenesis.";
RL Hum. Mol. Genet. 8:959-969(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH KHDRBS1.
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 [3]
RP FUNCTION.
RX PubMed=19916944; DOI=10.1134/s0006297909110145;
RA Zhang L.Y., Zeng M., Chen P., Sun H.Q., Tao D.C., Liu Y.Q., Lin L.,
RA Yang Y., Zhang S.Z., Ma Y.X.;
RT "Identification of messenger RNA substrates for mouse T-STAR.";
RL Biochemistry (Mosc.) 74:1270-1277(2009).
RN [4]
RP MUTAGENESIS OF 215-ALA--GLY-217.
RX PubMed=15163637; DOI=10.1093/hmg/ddh165;
RA Venables J.P., Dalgliesh C., Paronetto M.P., Skitt L., Thornton J.K.,
RA Saunders P.T., Sette C., Jones K.T., Elliott D.J.;
RT "SIAH1 targets the alternative splicing factor T-STAR for degradation by
RT the proteasome.";
RL Hum. Mol. Genet. 13:1525-1534(2004).
RN [5]
RP PHOSPHORYLATION BY PTK6, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP 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 [6]
RP RNA-BINDING.
RX PubMed=19457263; DOI=10.1186/1471-2199-10-47;
RA Galarneau A., Richard S.;
RT "The STAR RNA binding proteins GLD-1, QKI, SAM68 and SLM-2 bind bipartite
RT RNA motifs.";
RL BMC Mol. Biol. 10:47-47(2009).
RN [7]
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 [8]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF VAL-129.
RX PubMed=23637638; DOI=10.1371/journal.pgen.1003474;
RA Ehrmann I., Dalgliesh C., Liu Y., Danilenko M., Crosier M., Overman L.,
RA Arthur H.M., Lindsay S., Clowry G.J., Venables J.P., Fort P., Elliott D.J.;
RT "The tissue-specific RNA binding protein T-STAR controls regional splicing
RT patterns of neurexin pre-mRNAs in the brain.";
RL PLoS Genet. 9:E1003474-E1003474(2013).
RN [9]
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 [10]
RP FUNCTION.
RX PubMed=25505328; DOI=10.1523/jneurosci.3395-14.2014;
RA Traunmueller L., Bornmann C., Scheiffele P.;
RT "Alternative splicing coupled nonsense-mediated decay generates neuronal
RT cell type-specific expression of SLM proteins.";
RL J. Neurosci. 34:16755-16761(2014).
RN [11]
RP FUNCTION.
RX PubMed=27174676; DOI=10.1126/science.aaf2397;
RA Traunmueller L., Gomez A.M., Nguyen T.M., Scheiffele P.;
RT "Control of neuronal synapse specification by a highly dedicated
RT alternative splicing program.";
RL Science 352:982-986(2016).
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. Binds preferentially to the 5'-[AU]UAAA-3' motif in vitro
CC (PubMed:19457263). Binds optimally to RNA containing 5'-[AU]UAA-3' as a
CC bipartite motif spaced by more than 15 nucleotides (By similarity).
CC Binds poly(A). RNA-binding abilities are down-regulated by tyrosine
CC kinase PTK6 (PubMed:15471878). Involved in splice site selection of
CC vascular endothelial growth factor (By similarity). In vitro regulates
CC CD44 alternative splicing by direct binding to purine-rich exonic
CC enhancer (By similarity). Can regulate alternative splicing of
CC neurexins NRXN1-3 in the laminin G-like domain 6 containing the
CC evolutionary conserved neurexin alternative spliced segment 4 (AS4)
CC involved in neurexin selective targeting to postsynaptic partners such
CC as neuroligins and LRRTM family members. High concentrations in
CC forebrain structures block splicing inclusion of NRXN1-3 AS4 exons
CC while low concentrations favor their inclusion. Targeted, cell-type
CC specific splicing regulation of NRXN1 at AS4 is involved in neuronal
CC glutamatergic synapse function and plasticity and is linked to
CC behavioral aspects (PubMed:22196734, PubMed:23637638, PubMed:24469635,
CC PubMed:27174676). Regulates expression of KHDRBS2/SLIM-1 in defined
CC neuron populations in the hippocampus by modifying its alternative
CC splicing resulting in a transcript predicted to undergo nonsense-
CC mediated decay (PubMed:25505328). Can bind FABP9 mRNA
CC (PubMed:19916944). May play a role as a negative regulator of cell
CC growth. Inhibits cell proliferation. {ECO:0000250|UniProtKB:O75525,
CC ECO:0000250|UniProtKB:Q9JLP1, ECO:0000269|PubMed:15471878,
CC ECO:0000269|PubMed:19457263, ECO:0000269|PubMed:19916944,
CC ECO:0000269|PubMed:22196734, ECO:0000269|PubMed:23637638,
CC ECO:0000269|PubMed:24469635, ECO:0000269|PubMed:27174676}.
CC -!- SUBUNIT: Self-associates to form homooligomers; dimerization increases
CC RNA affinity (By similarity). Interacts with KHDRBS2/SLM-1 (By
CC similarity). Interacts with KHDRBS1/SAM68; heterooligomer formation of
CC KHDRBS family proteins may modulate RNA substrate specificity
CC (PubMed:10077576). Interacts with the splicing regulatory proteins
CC SFRS9, SAFB and YTHDC1. Interacts with HNRPL, RBMX, RBMY1A1, p85
CC subunit of PI3-kinase, SERPINB5 (By similarity).
CC {ECO:0000250|UniProtKB:O75525, ECO:0000250|UniProtKB:Q9JLP1,
CC ECO:0000269|PubMed:10077576, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10332027,
CC ECO:0000269|PubMed:15471878}. Note=Localized in a compartment adjacent
CC to the nucleolus, but distinct from the peri-nucleolar one.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and brain. In adult
CC cerebellum expressed predominantly in internal granular layer
CC interneurons and in hippocampus is exclusively expressed in CA neurons;
CC expression is restricted to neuronal subpopulations largely non-
CC overlapping with expression of KHDRBS2/SLM-1.
CC {ECO:0000269|PubMed:10332027, ECO:0000269|PubMed:15471878,
CC ECO:0000269|PubMed:23637638, ECO:0000269|PubMed:24469635}.
CC -!- DEVELOPMENTAL STAGE: In the developing cerebellum expression is
CC decreasing in the first 3 postnatal weeks.
CC {ECO:0000269|PubMed:22196734}.
CC -!- DOMAIN: The proline-rich site binds the SH3 domain of the p85 subunit
CC of PI3-kinase. {ECO:0000250|UniProtKB:O75525}.
CC -!- PTM: Phosphorylated on tyrosine residues by PTK6.
CC {ECO:0000269|PubMed:15471878}.
CC -!- SIMILARITY: Belongs to the KHDRBS family. {ECO:0000305}.
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DR EMBL; AF079763; AAC31753.1; -; mRNA.
DR EMBL; AF099092; AAC72396.1; -; mRNA.
DR EMBL; BC031507; AAH31507.1; -; mRNA.
DR EMBL; BC057577; AAH57577.1; -; mRNA.
DR CCDS; CCDS27513.1; -.
DR RefSeq; NP_034288.2; NM_010158.2.
DR AlphaFoldDB; Q9R226; -.
DR SMR; Q9R226; -.
DR BioGRID; 199525; 1.
DR IntAct; Q9R226; 3.
DR MINT; Q9R226; -.
DR STRING; 10090.ENSMUSP00000022954; -.
DR iPTMnet; Q9R226; -.
DR PhosphoSitePlus; Q9R226; -.
DR MaxQB; Q9R226; -.
DR PaxDb; Q9R226; -.
DR PeptideAtlas; Q9R226; -.
DR PRIDE; Q9R226; -.
DR ProteomicsDB; 269214; -.
DR Antibodypedia; 612; 201 antibodies from 28 providers.
DR DNASU; 13992; -.
DR Ensembl; ENSMUST00000022954; ENSMUSP00000022954; ENSMUSG00000022332.
DR Ensembl; ENSMUST00000229234; ENSMUSP00000154887; ENSMUSG00000022332.
DR Ensembl; ENSMUST00000229683; ENSMUSP00000155136; ENSMUSG00000022332.
DR GeneID; 13992; -.
DR KEGG; mmu:13992; -.
DR UCSC; uc007wbf.1; mouse.
DR CTD; 10656; -.
DR MGI; MGI:1313312; Khdrbs3.
DR VEuPathDB; HostDB:ENSMUSG00000022332; -.
DR eggNOG; KOG1588; Eukaryota.
DR GeneTree; ENSGT00940000157280; -.
DR HOGENOM; CLU_034976_0_0_1; -.
DR InParanoid; Q9R226; -.
DR OMA; PPIVQET; -.
DR OrthoDB; 1012406at2759; -.
DR PhylomeDB; Q9R226; -.
DR TreeFam; TF314878; -.
DR Reactome; R-MMU-8849468; PTK6 Regulates Proteins Involved in RNA Processing.
DR BioGRID-ORCS; 13992; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Khdrbs3; mouse.
DR PRO; PR:Q9R226; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9R226; protein.
DR Bgee; ENSMUSG00000022332; Expressed in interventricular septum and 243 other tissues.
DR ExpressionAtlas; Q9R226; baseline and differential.
DR Genevisible; Q9R226; MM.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0003727; F:single-stranded RNA binding; ISO:MGI.
DR GO; GO:0006397; P:mRNA processing; ISO:MGI.
DR GO; GO:0033120; P:positive regulation of RNA splicing; ISO:MGI.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISO:MGI.
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.
PE 1: Evidence at protein level;
KW Isopeptide bond; mRNA processing; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; SH3-binding; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..346
FT /note="KH domain-containing, RNA-binding, signal
FT transduction-associated protein 3"
FT /id="PRO_0000232523"
FT DOMAIN 61..127
FT /note="KH"
FT REGION 1..160
FT /note="Involved in homodimerization"
FT /evidence="ECO:0000250|UniProtKB:O75525"
FT REGION 212..266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..264
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 4
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75525"
FT MUTAGEN 129
FT /note="V->F: Abolishes splicing regulation."
FT /evidence="ECO:0000269|PubMed:23637638"
FT MUTAGEN 215..217
FT /note="AVG->GVV: Confers SIAH1-mediated degradation and
FT strong SIAH1 binding."
FT /evidence="ECO:0000269|PubMed:15163637"
FT CONFLICT 160
FT /note="N -> Y (in Ref. 1; AAC31753)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 38807 MW; F061C85FC698FF40 CRC64;
MEEKYLPELM AEKDSLDPSF THALRLVNRE IEKFQKGEGK EEEKYIDVVI NKNMKLGQKV
LIPVKQFPKF NFVGKLLGPR GNSLKRLQEE TLTKMSILGK GSMRDKAKEE ELRKSGEAKY
FHLNDDLHVL IEVFAPPAEA YARMGHALEE IKKFLIPDYN DEIRQAQLQE LTYLNGGSEN
ADVPVVRGKS TLRTRGVTTP AITRGRGGVT ARPVAVGVPR GTPTPRGVLS TRGPVSRGRG
LLTPRARGVP PTGYRPPPPP PTQETYGEYD YDDGYGTAYD EQSYDSYDNS YSTPAQSAAD
YYDYGHGLSE DAYDSYGQEE WTNSRHKAPS ARTAKGVYRD QPYGRY
