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Protein

KH domain-containing, RNA-binding, signal transduction-associated protein 1

Gene

Khdrbs1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. May not be involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species. RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner. In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1. Can regulate alternative splicing of NRXN1 and NRXN3 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. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • poly(A) binding Source: Ensembl
  • poly(A) RNA binding Source: Ensembl
  • poly(U) RNA binding Source: Ensembl
  • protein complex binding Source: RGD
  • RNA binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB
  • SH3 domain binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, mRNA processing, Transcription, Transcription regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
KH domain-containing, RNA-binding, signal transduction-associated protein 1
Alternative name(s):
GAP-associated tyrosine phosphoprotein p62
Src-associated in mitosis 68 kDa protein
Short name:
Sam68
p21 Ras GTPase-activating protein-associated p62
p68
Gene namesi
Name:Khdrbs1Imported
Synonyms:Sam68Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi621459. Khdrbs1.

Subcellular locationi

  • Nucleus By similarity
  • Membrane By similarity

GO - Cellular componenti

  • cytoplasm Source: RGD
  • Grb2-Sos complex Source: RGD
  • membrane Source: UniProtKB
  • nucleoplasm Source: Ensembl
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000501261 – 443KH domain-containing, RNA-binding, signal transduction-associated protein 1Add BLAST443

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei18PhosphoserineBy similarity1
Modified residuei20PhosphoserineBy similarity1
Modified residuei21N6-acetyllysineBy similarity1
Modified residuei29PhosphoserineBy similarity1
Modified residuei33PhosphothreonineBy similarity1
Modified residuei45Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei45Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei52Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei52Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei58PhosphoserineBy similarity1
Modified residuei84Phosphothreonine; by MAPK1By similarity1
Cross-linki102Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei113PhosphoserineBy similarity1
Modified residuei150PhosphoserineBy similarity1
Modified residuei175N6-acetyllysineBy similarity1
Modified residuei183PhosphothreonineBy similarity1
Modified residuei282Omega-N-methylarginineBy similarity1
Modified residuei284Omega-N-methylarginineBy similarity1
Modified residuei291Omega-N-methylarginine; alternateBy similarity1
Modified residuei291Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei304Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei304Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei310Omega-N-methylarginine; alternateBy similarity1
Modified residuei310Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei315Omega-N-methylarginine; alternateBy similarity1
Modified residuei315Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei320Dimethylated arginine; alternateBy similarity1
Modified residuei320Omega-N-methylarginine; alternateBy similarity1
Modified residuei320Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei325Omega-N-methylarginine; alternateBy similarity1
Modified residuei325Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei331Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei331Dimethylated arginine; alternateBy similarity1
Modified residuei331Omega-N-methylarginine; alternateBy similarity1
Modified residuei331Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei340Dimethylated arginine; alternateBy similarity1
Modified residuei340Omega-N-methylarginine; alternateBy similarity1
Modified residuei340Omega-N-methylated arginine; by PRMT1; alternateBy similarity1
Modified residuei346Omega-N-methylated arginine; by PRMT1By similarity1
Modified residuei390PhosphoserineBy similarity1
Modified residuei435Phosphotyrosine; by PTK6By similarity1
Modified residuei440Phosphotyrosine; by PTK6By similarity1
Modified residuei443Phosphotyrosine; by PTK6By similarity1

Post-translational modificationi

Tyrosine phosphorylated by several non-receptor tyrosine kinases, LCK, FYN and JAK3. Phosphorylation by PTK6 negatively regulates its RNA binding ability. Phosphorylation by PTK6 at Tyr-440 dictates the nulear localization of KHDRBS1 (By similarity).By similarity
Acetylated. Positively correlates with ability to bind RNA (By similarity).By similarity
Arginine methylation is required for nuclear localization, Inhibits interaction with Src-like SH3 domains, but not interaction with WW domains of WBP4/FBP21 AND FNBP4/FBP30.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ91V33.
PRIDEiQ91V33.

PTM databases

iPTMnetiQ91V33.
PhosphoSitePlusiQ91V33.
SwissPalmiQ91V33.

Expressioni

Gene expression databases

BgeeiENSRNOG00000046794.
GenevisibleiQ91V33. RN.

Interactioni

Subunit structurei

Self-associates to form homooligomers when bound to RNA, oligomerization appears to be limited when binding to proteins. Interacts with KHDRBS3/SLIM-2 (By similarity). Interacts with KHDRBS2/SLIM-1; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity (PubMed:15345239). Interacts with PIK3R1, PLCG1 (PubMed:10437794, PubMed:10748127). Interacts with RASA1, GRB2, SRC, RBMY1A1, CBP, PRMT1, APC, HNRNPA1. Interacts with PTK6 (via SH3 and SH2 domains). Forms a complex with ILF2, ILF3, YLPM1, RBMX, NCOA5 and PPP1CA (By similarity). Binds WBP4/FBP21 (via WW domains), FNBP4/FBP30 (via WW domains). Interacts (via Arg/Gly-rich-flanked Pro-rich regions) with FYN (via the SH3 domain) (PubMed:10748127).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Pik3r1Q637872EBI-518436,EBI-518443

GO - Molecular functioni

  • protein complex binding Source: RGD
  • SH3/SH2 adaptor activity Source: UniProtKB
  • SH3 domain binding Source: RGD

Protein-protein interaction databases

BioGridi250715. 3 interactors.
IntActiQ91V33. 1 interactor.
STRINGi10116.ENSRNOP00000066894.

Structurei

3D structure databases

ProteinModelPortaliQ91V33.
SMRiQ91V33.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini171 – 197KHPROSITE-ProRule annotationAdd BLAST27

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni100 – 260Involved in homodimerizationBy similarityAdd BLAST161
Regioni351 – 443Interaction with HNRNPA1By similarityAdd BLAST93

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi34 – 41Pro-richSequence analysis8
Compositional biasi44 – 55Arg/Gly-richSequence analysisAdd BLAST12
Compositional biasi59 – 89Pro-richSequence analysisAdd BLAST31
Compositional biasi282 – 292Arg/Gly-richSequence analysisAdd BLAST11
Compositional biasi295 – 301Pro-richSequence analysis7
Compositional biasi302 – 332Arg/Gly-richSequence analysisAdd BLAST31
Compositional biasi334 – 363Pro-richSequence analysisAdd BLAST30

Domaini

The KH domain is required for binding to RNA.1 Publication
The Pro-rich domains are flanked by Arg/Gly-rich motifs which can be asymmetric dimethylated on arginine residues to give the DMA/Gly-rich regions. Selective methylation on these motifs can modulate protein-protein interactions.

Sequence similaritiesi

Belongs to the KHDRBS family.Sequence analysis
Contains 1 KH domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG1588. Eukaryota.
COG5176. LUCA.
GeneTreeiENSGT00550000074434.
HOGENOMiHOG000230771.
HOVERGENiHBG079164.
InParanoidiQ91V33.
KOiK13198.
OMAiFLFPDMM.
OrthoDBiEOG091G0EED.
PhylomeDBiQ91V33.

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.
PROSITEiPS50084. KH_TYPE_1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q91V33-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRRDDPAAR LTRSSGRSCS KDPSGAHPSV RLTPSRPSPL PHRSRGGGGG
60 70 80 90 100
PRGGARASPA TQPPPLLPPS NPGPDATVVG SAPTPLLPPS ATAAAKMEPE
110 120 130 140 150
NKYLPELMAE KDSLDPSFTH AMQLLSVEIE KIQKGESKKD DEENYLDLFS
160 170 180 190 200
HKNMKLKERV LIPVKQYPKF NFVGKILGPQ GNTIKRLQEE TGAKISVLGK
210 220 230 240 250
GSMRDKAKEE ELRKGGDPKY AHLNMDLHVF IEVFGPPCEA YALMAHAMEE
260 270 280 290 300
VKKFLVPDMM DDICQEQFLE LSYLNGVPEP SRGRGVSVRG RGAAPPPPPV
310 320 330 340 350
PRGRGVGPPR GALVRGTPVR GSITRGATVT RGVPPPPTVR GAPTPRARTA
360 370 380 390 400
GIQRIPLPPT PAPETYEDYG YDDSYAEQSY EGYEGYYSQS QGESEYYDYG
410 420 430 440
HGELQDSYEA YGQDDWNGTR PSLKAPPARP VKGAYREHPY GRY
Length:443
Mass (Da):48,315
Last modified:December 1, 2001 - v1
Checksum:iC41A42831E7DCBC7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF305619 mRNA. Translation: AAL09361.1.
AF393783 mRNA. Translation: AAK77001.1.
BC061987 mRNA. Translation: AAH61987.1.
RefSeqiNP_569089.1. NM_130405.1.
UniGeneiRn.92906.

Genome annotation databases

EnsembliENSRNOT00000075270; ENSRNOP00000066894; ENSRNOG00000046794.
GeneIDi117268.
KEGGirno:117268.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF305619 mRNA. Translation: AAL09361.1.
AF393783 mRNA. Translation: AAK77001.1.
BC061987 mRNA. Translation: AAH61987.1.
RefSeqiNP_569089.1. NM_130405.1.
UniGeneiRn.92906.

3D structure databases

ProteinModelPortaliQ91V33.
SMRiQ91V33.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250715. 3 interactors.
IntActiQ91V33. 1 interactor.
STRINGi10116.ENSRNOP00000066894.

PTM databases

iPTMnetiQ91V33.
PhosphoSitePlusiQ91V33.
SwissPalmiQ91V33.

Proteomic databases

PaxDbiQ91V33.
PRIDEiQ91V33.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000075270; ENSRNOP00000066894; ENSRNOG00000046794.
GeneIDi117268.
KEGGirno:117268.

Organism-specific databases

CTDi10657.
RGDi621459. Khdrbs1.

Phylogenomic databases

eggNOGiKOG1588. Eukaryota.
COG5176. LUCA.
GeneTreeiENSGT00550000074434.
HOGENOMiHOG000230771.
HOVERGENiHBG079164.
InParanoidiQ91V33.
KOiK13198.
OMAiFLFPDMM.
OrthoDBiEOG091G0EED.
PhylomeDBiQ91V33.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ91V33.

Gene expression databases

BgeeiENSRNOG00000046794.
GenevisibleiQ91V33. RN.

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.
PROSITEiPS50084. KH_TYPE_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKHDR1_RAT
AccessioniPrimary (citable) accession number: Q91V33
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 119 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. 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.