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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: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Biological processi

mRNA processing, Transcription, Transcription regulation

Keywords - Ligandi

RNA-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1313312. Khdrbs3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi129 – 1291V → F: Abolishes splicing regulation. 1 Publication
Mutagenesisi215 – 2173AVG → GVV: Confers SIAH1-mediated degradation and strong SIAH1 binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 346346KH domain-containing, RNA-binding, signal transduction-associated protein 3PRO_0000232523Add
BLAST

Post-translational modificationi

Phosphorylated on tyrosine residues by PTK6.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9R226.
PaxDbiQ9R226.
PeptideAtlasiQ9R226.
PRIDEiQ9R226.

PTM databases

iPTMnetiQ9R226.
PhosphoSiteiQ9R226.

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.
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

Protein-protein interaction databases

IntActiQ9R226. 2 interactions.
MINTiMINT-4130938.
STRINGi10090.ENSMUSP00000022954.

Structurei

3D structure databases

ProteinModelPortaliQ9R226.
SMRiQ9R226. Positions 2-183.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini61 – 12767KHAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 160160Involved in homodimerizationBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi250 – 26112Pro-richAdd
BLAST
Compositional biasi266 – 31651Tyr-richAdd
BLAST

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
Contains 1 KH domain.Curated

Keywords - Domaini

SH3-binding

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.1370.10. 1 hit.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR032571. Qua1_dom.
IPR032335. Sam68-YY.
[Graphical view]
PfamiPF00013. KH_1. 1 hit.
PF16274. Qua1. 1 hit.
PF16568. Sam68-YY. 1 hit.
[Graphical view]
SMARTiSM00322. KH. 1 hit.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti160 – 1601N → Y in AAC31753 (PubMed:10332027).Curated

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.
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. Positions 2-183.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9R226. 2 interactions.
MINTiMINT-4130938.
STRINGi10090.ENSMUSP00000022954.

PTM databases

iPTMnetiQ9R226.
PhosphoSiteiQ9R226.

Proteomic databases

MaxQBiQ9R226.
PaxDbiQ9R226.
PeptideAtlasiQ9R226.
PRIDEiQ9R226.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022954; ENSMUSP00000022954; 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.
OMAiDDYYEYG.
OrthoDBiEOG091G0EED.
PhylomeDBiQ9R226.
TreeFamiTF314878.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ9R226.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022332.
GenevisibleiQ9R226. MM.

Family and domain databases

Gene3Di3.30.1370.10. 1 hit.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR032571. Qua1_dom.
IPR032335. Sam68-YY.
[Graphical view]
PfamiPF00013. KH_1. 1 hit.
PF16274. Qua1. 1 hit.
PF16568. Sam68-YY. 1 hit.
[Graphical view]
SMARTiSM00322. KH. 1 hit.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKHDR3_MOUSE
AccessioniPrimary (citable) accession number: Q9R226
Secondary accession number(s): O88624
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: May 1, 2000
Last modified: September 7, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.