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Protein

KH domain-containing, RNA-binding, signal transduction-associated protein 3

Gene

Khdrbs3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds preferentially to the 5'-[AU]UAAA-3' motif in vitro (PubMed:19457263). Binds optimally to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides (By similarity). Binds poly(A). RNA-binding abilities are down-regulated by tyrosine kinase PTK6 (PubMed:15471878). Involved in splice site selection of vascular endothelial growth factor (By similarity). In vitro regulates CD44 alternative splicing by direct binding to purine-rich exonic enhancer (By similarity). Can regulate alternative splicing of neurexins NRXN1-3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners such as neuroligins and LRRTM family members. High concentrations in forebrain structures block splicing inclusion of NRXN1-3 AS4 exons while low concentrations favor their inclusion. Targeted, cell-type specific splicing regulation of NRXN1 at AS4 is involved in neuronal glutamatergic synapse function and plasticity and is linked to behavioral aspects (PubMed:22196734, PubMed:23637638, PubMed:24469635, PubMed:27174676). Regulates expression of KHDRBS2/SLIM-1 in defined neuron populations in the hippocampus by modifying its alternative splicing resulting in a transcript predicted to undergo nonsense-mediated decay (PubMed:25505328). Can bind FABP9 mRNA (PubMed:19916944). May play a role as a negative regulator of cell growth. Inhibits cell proliferation.By similarity7 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processmRNA processing, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-8849468 PTK6 Regulates Proteins Involved in RNA Processing

Names & Taxonomyi

Protein namesi
Recommended name:
KH domain-containing, RNA-binding, signal transduction-associated protein 3
Alternative name(s):
RNA-binding protein Etoile
Sam68-like mammalian protein 2
Short name:
SLM-2
Gene namesi
Name:Khdrbs3
Synonyms:Salp, Slm2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1313312 Khdrbs3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi129V → F: Abolishes splicing regulation. 1 Publication1
Mutagenesisi215 – 217AVG → GVV: Confers SIAH1-mediated degradation and strong SIAH1 binding. 1 Publication3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002325231 – 346KH domain-containing, RNA-binding, signal transduction-associated protein 3Add BLAST346

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki4Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

Phosphorylated on tyrosine residues by PTK6.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9R226
PaxDbiQ9R226
PeptideAtlasiQ9R226
PRIDEiQ9R226

PTM databases

iPTMnetiQ9R226
PhosphoSitePlusiQ9R226

Expressioni

Tissue specificityi

Highly expressed in testis and brain. In adult cerebellum expressed predominantly in internal granular layer interneurons and in hippocampus is exclusively expressed in CA neurons; expression is restricted to neuronal subpopulations largely non-overlapping with expression of KHDRBS2/SLM-1.4 Publications

Developmental stagei

In the developping cerebellum expression is decreasing in the first 3 postnatal weeks.1 Publication

Gene expression databases

BgeeiENSMUSG00000022332 Expressed in 259 organ(s), highest expression level in visual cortex
GenevisibleiQ9R226 MM

Interactioni

Subunit structurei

Self-associates to form homooligomers; dimerization increases RNA affinity (By similarity). Interacts with KHDRBS2/SLM-1 (By similarity). Interacts with KHDRBS1/SAM68; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity (PubMed:10077576). Interacts with the splicing regulatory proteins SFRS9, SAFB and YTHDC1. Interacts with HNRPL, RBMX, RBMY1A1, p85 subunit of PI3-kinase, SERPINB5 (By similarity).By similarityCurated1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9R226, 3 interactors
MINTiQ9R226
STRINGi10090.ENSMUSP00000022954

Structurei

3D structure databases

ProteinModelPortaliQ9R226
SMRiQ9R226
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 127KHAdd BLAST67

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 160Involved in homodimerizationBy similarityAdd BLAST160

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi250 – 261Pro-richAdd BLAST12
Compositional biasi266 – 316Tyr-richAdd BLAST51

Domaini

The proline-rich site binds the SH3 domain of the p85 subunit of PI3-kinase.By similarity

Sequence similaritiesi

Belongs to the KHDRBS family.Curated

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG1588 Eukaryota
COG5176 LUCA
GeneTreeiENSGT00550000074434
HOGENOMiHOG000230771
HOVERGENiHBG079164
InParanoidiQ9R226
KOiK14942
OMAiRTTKGVY
OrthoDBiEOG091G0EED
PhylomeDBiQ9R226
TreeFamiTF314878

Family and domain databases

Gene3Di3.30.1370.10, 1 hit
InterProiView protein in InterPro
IPR004087 KH_dom
IPR004088 KH_dom_type_1
IPR036612 KH_dom_type_1_sf
IPR032571 Qua1_dom
IPR032335 Sam68-YY
PfamiView protein in Pfam
PF00013 KH_1, 1 hit
PF16274 Qua1, 1 hit
PF16568 Sam68-YY, 1 hit
SMARTiView protein in SMART
SM00322 KH, 1 hit
SUPFAMiSSF54791 SSF54791, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q9R226-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEEKYLPELM AEKDSLDPSF THALRLVNRE IEKFQKGEGK EEEKYIDVVI
60 70 80 90 100
NKNMKLGQKV LIPVKQFPKF NFVGKLLGPR GNSLKRLQEE TLTKMSILGK
110 120 130 140 150
GSMRDKAKEE ELRKSGEAKY FHLNDDLHVL IEVFAPPAEA YARMGHALEE
160 170 180 190 200
IKKFLIPDYN DEIRQAQLQE LTYLNGGSEN ADVPVVRGKS TLRTRGVTTP
210 220 230 240 250
AITRGRGGVT ARPVAVGVPR GTPTPRGVLS TRGPVSRGRG LLTPRARGVP
260 270 280 290 300
PTGYRPPPPP PTQETYGEYD YDDGYGTAYD EQSYDSYDNS YSTPAQSAAD
310 320 330 340
YYDYGHGLSE DAYDSYGQEE WTNSRHKAPS ARTAKGVYRD QPYGRY
Length:346
Mass (Da):38,807
Last modified:May 1, 2000 - v1
Checksum:iF061C85FC698FF40
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8VHM1A0A2R8VHM1_MOUSE
KH domain-containing, RNA-binding, ...
Khdrbs3
126Annotation score:
A0A2R8VJR4A0A2R8VJR4_MOUSE
KH domain-containing, RNA-binding, ...
Khdrbs3
258Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti160N → Y in AAC31753 (PubMed:10332027).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079763 mRNA Translation: AAC31753.1
AF099092 mRNA Translation: AAC72396.1
BC031507 mRNA Translation: AAH31507.1
BC057577 mRNA Translation: AAH57577.1
CCDSiCCDS27513.1
RefSeqiNP_034288.2, NM_010158.2
UniGeneiMm.17964

Genome annotation databases

EnsembliENSMUST00000022954; ENSMUSP00000022954; ENSMUSG00000022332
ENSMUST00000229234; ENSMUSP00000154887; ENSMUSG00000022332
ENSMUST00000229683; ENSMUSP00000155136; ENSMUSG00000022332
GeneIDi13992
KEGGimmu:13992
UCSCiuc007wbf.1 mouse

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079763 mRNA Translation: AAC31753.1
AF099092 mRNA Translation: AAC72396.1
BC031507 mRNA Translation: AAH31507.1
BC057577 mRNA Translation: AAH57577.1
CCDSiCCDS27513.1
RefSeqiNP_034288.2, NM_010158.2
UniGeneiMm.17964

3D structure databases

ProteinModelPortaliQ9R226
SMRiQ9R226
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9R226, 3 interactors
MINTiQ9R226
STRINGi10090.ENSMUSP00000022954

PTM databases

iPTMnetiQ9R226
PhosphoSitePlusiQ9R226

Proteomic databases

MaxQBiQ9R226
PaxDbiQ9R226
PeptideAtlasiQ9R226
PRIDEiQ9R226

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022954; ENSMUSP00000022954; ENSMUSG00000022332
ENSMUST00000229234; ENSMUSP00000154887; ENSMUSG00000022332
ENSMUST00000229683; ENSMUSP00000155136; ENSMUSG00000022332
GeneIDi13992
KEGGimmu:13992
UCSCiuc007wbf.1 mouse

Organism-specific databases

CTDi10656
MGIiMGI:1313312 Khdrbs3

Phylogenomic databases

eggNOGiKOG1588 Eukaryota
COG5176 LUCA
GeneTreeiENSGT00550000074434
HOGENOMiHOG000230771
HOVERGENiHBG079164
InParanoidiQ9R226
KOiK14942
OMAiRTTKGVY
OrthoDBiEOG091G0EED
PhylomeDBiQ9R226
TreeFamiTF314878

Enzyme and pathway databases

ReactomeiR-MMU-8849468 PTK6 Regulates Proteins Involved in RNA Processing

Miscellaneous databases

PROiPR:Q9R226
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022332 Expressed in 259 organ(s), highest expression level in visual cortex
GenevisibleiQ9R226 MM

Family and domain databases

Gene3Di3.30.1370.10, 1 hit
InterProiView protein in InterPro
IPR004087 KH_dom
IPR004088 KH_dom_type_1
IPR036612 KH_dom_type_1_sf
IPR032571 Qua1_dom
IPR032335 Sam68-YY
PfamiView protein in Pfam
PF00013 KH_1, 1 hit
PF16274 Qua1, 1 hit
PF16568 Sam68-YY, 1 hit
SMARTiView protein in SMART
SM00322 KH, 1 hit
SUPFAMiSSF54791 SSF54791, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKHDR3_MOUSE
AccessioniPrimary (citable) accession number: Q9R226
Secondary accession number(s): O88624
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 122 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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