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Protein

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

Gene

Khdrbs1

Organism
Mus musculus (Mouse)
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). In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (By similarity). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner. 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 (PubMed:12478298, PubMed:22196734, PubMed:24469635).By similarity6 Publications

GO - Molecular functioni

  • identical protein binding Source: MGI
  • poly(A) binding Source: MGI
  • poly(U) RNA binding Source: MGI
  • protein complex binding Source: Ensembl
  • protein domain specific binding Source: MGI
  • RNA binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processCell cycle, mRNA 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 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:893579. Khdrbs1.

Subcellular locationi

  • Nucleus 1 Publication
  • Membrane 1 Publication

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • Grb2-Sos complex Source: Ensembl
  • membrane Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: MGI

Keywords - Cellular componenti

Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi58S → A: Abolishes phosphorylation, abolishes CD44 splicing regulation; when associated with A-71 and A-84. 1 Publication1
Mutagenesisi71T → A: Abolishes phosphorylation, abolishes CD44 splicing regulation; when associated with A-58 and A-84. 1 Publication1
Mutagenesisi84T → A: Abolishes phosphorylation, abolishes CD44 splicing regulation; when associated with A-58 and A-71. 1 Publication1
Mutagenesisi229V → F: Abolishes splicing regulation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000501251 – 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-acetyllysineCombined sources1
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 residuei58Phosphoserine; by MAPK11 Publication1
Modified residuei71Phosphothreonine; by MAPK11 Publication1
Modified residuei84Phosphothreonine; by MAPK11 Publication1
Cross-linki96Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki102Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei113Phosphoserine1 Publication1
Cross-linki139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei150PhosphoserineBy similarity1
Modified residuei175N6-acetyllysine; alternateBy similarity1
Cross-linki175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei183PhosphothreonineBy similarity1
Modified residuei282Omega-N-methylarginineCombined sources1
Modified residuei284Omega-N-methylarginineCombined sources1
Modified residuei291Omega-N-methylarginine; alternateCombined sources1
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; alternateCombined sources1
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
Cross-linki432Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
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. Phosphorylation by MAPK1 at Ser-58, Thr-71 and Thr-84 regulates CD44 alternative splicing by promoting CD44 exon v5 inclusion.2 Publications
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).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ60749.
MaxQBiQ60749.
PaxDbiQ60749.
PeptideAtlasiQ60749.
PRIDEiQ60749.

PTM databases

iPTMnetiQ60749.
PhosphoSitePlusiQ60749.
SwissPalmiQ60749.

Expressioni

Tissue specificityi

In adult cerebellum expressed in most neuronal cell populations, specifically in cerebellar granule cells of the internal granular layer, ROR(alpha)-positive Purkinje cells, internal granular layer and molecuar layer interneurons (at protein level).1 Publication

Developmental stagei

In the developping cerebellum expression is high at birth and declines over the first 3 weeks. At P7 highly expressed in granule cell precursor cells in the external granular layer and mature granule cells of the internal granule layer.1 Publication

Gene expression databases

BgeeiENSMUSG00000028790.
GenevisibleiQ60749. MM.

Interactioni

Subunit structurei

Self-associates to form homooligomers when bound to RNA, oligomerization appears to be limited when binding to proteins (PubMed:9315629). Interacts with KHDRBS3/SLIM-2 and KHDRBS2/SLIM-1; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity (PubMed:10077576, PubMed:24469635). Interacts with RASA1, FYN, GRB2, PLCG1, SRC, RBMY1A1, CBP, PRMT1 (PubMed:7799925, PubMed:7512695, PubMed:10077576, PubMed:10823932, PubMed:12496368, PubMed:12529443). Interacts with PTK6 (via SH3 and SH2 domains). Forms a complex with ILF2, ILF3, YLPM1, RBMX, NCOA5 and PPP1CA. 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). Interacts with APC, HNRNPA1 (By similarity).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203068. 15 interactors.
DIPiDIP-2861N.
IntActiQ60749. 17 interactors.
MINTiMINT-1613905.
STRINGi10090.ENSMUSP00000066516.

Structurei

3D structure databases

ProteinModelPortaliQ60749.
SMRiQ60749.
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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the KHDRBS family.Sequence analysis

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG1588. Eukaryota.
COG5176. LUCA.
GeneTreeiENSGT00550000074434.
HOVERGENiHBG079164.
InParanoidiQ60749.
KOiK13198.
OMAiFLFPDMM.
OrthoDBiEOG091G0EED.
PhylomeDBiQ60749.
TreeFamiTF314878.

Family and domain databases

Gene3Di3.30.1370.10. 1 hit.
InterProiView protein in InterPro
IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
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.
PROSITEiView protein in PROSITE
PS50084. KH_TYPE_1. 1 hit.

Sequencei

Sequence statusi: Complete.

Q60749-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRRDDPASR LTRSSGRSCS KDPSGAHPSV RLTPSRPSPL PHRPRGGGGG
60 70 80 90 100
PRGGARASPA TQPPPLLPPS TPGPDATVVG SAPTPLLPPS ATAAVKMEPE
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 YDDTYAEQSY EGYEGYYSQS QGESEYYDYG
410 420 430 440
HGELQDSYEA YGQDDWNGTR PSLKAPPARP VKGAYREHPY GRY
Length:443
Mass (Da):48,371
Last modified:April 12, 2005 - v2
Checksum:iD33DE960BEA9E5AA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti104L → P in AAA64997 (PubMed:7799925).Curated1
Sequence conflicti147D → N AA sequence (PubMed:7512695).Curated1
Sequence conflicti174G → R in AAA86693 (PubMed:7541765).Curated1
Sequence conflicti197V → VS in AAA86693 (PubMed:7541765).Curated1
Sequence conflicti225 – 230MDLHVF → LGENGL AA sequence (PubMed:7512695).Curated6
Sequence conflicti327A → S in AAA86693 (PubMed:7541765).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U17961 mRNA. Translation: AAA86693.1.
U17046 mRNA. Translation: AAA64997.1.
AK050520 mRNA. Translation: BAC34303.1.
AK152084 mRNA. Translation: BAE30934.1.
AL669834 Genomic DNA. Translation: CAM13766.1.
CU210913 Genomic DNA. Translation: CAQ51789.1.
BC002051 mRNA. Translation: AAH02051.1.
CCDSiCCDS18703.1.
PIRiI49140.
S43974.
RefSeqiNP_035447.3. NM_011317.4.
UniGeneiMm.489797.
Mm.8256.

Genome annotation databases

EnsembliENSMUST00000066257; ENSMUSP00000066516; ENSMUSG00000028790.
ENSMUST00000129342; ENSMUSP00000115402; ENSMUSG00000028790.
GeneIDi20218.
KEGGimmu:20218.
UCSCiuc008uyd.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiKHDR1_MOUSE
AccessioniPrimary (citable) accession number: Q60749
Secondary accession number(s): A2ACH3
, B2KG38, Q3U8T3, Q60735, Q7M4N5, Q99M33
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 12, 2005
Last modified: August 30, 2017
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, 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