KHDR1_RAT
ID KHDR1_RAT Reviewed; 443 AA.
AC Q91V33;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=KH domain-containing, RNA-binding, signal transduction-associated protein 1;
DE AltName: Full=GAP-associated tyrosine phosphoprotein p62;
DE AltName: Full=Src-associated in mitosis 68 kDa protein;
DE Short=Sam68;
DE AltName: Full=p21 Ras GTPase-activating protein-associated p62;
DE AltName: Full=p68;
GN Name=Khdrbs1 {ECO:0000312|RGD:621459};
GN Synonyms=Sam68 {ECO:0000312|EMBL:AAH61987.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAL09361.1}
RP NUCLEOTIDE SEQUENCE [MRNA], HOMOOLIGOMERIZATION, AND INTERACTION WITH
RP KHDRB2.
RX PubMed=15345239; DOI=10.1016/j.mcn.2004.04.011;
RA Stoss O., Novoyatleva T., Gencheva M., Olbrich M., Benderska N., Stamm S.;
RT "p59(fyn)-mediated phosphorylation regulates the activity of the tissue-
RT specific splicing factor rSLM-1.";
RL Mol. Cell. Neurosci. 27:8-21(2004).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAK77001.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAK77001.1};
RA Wang J.-M., Tseng C.-N., Yao Y., Wang Z.-Z.;
RT "Characterization of Sam68 in skeletal muscle and brain of rat.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAH61987.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate {ECO:0000312|EMBL:AAH61987.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0000305}
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH PIK3R1.
RX PubMed=10437794; DOI=10.1016/s0014-5793(99)00887-x;
RA Sanchez-Margalet V., Najib S.;
RT "p68 Sam is a substrate of the insulin receptor and associates with the SH2
RT domains of p85 PI3K.";
RL FEBS Lett. 455:307-310(1999).
RN [5] {ECO:0000305}
RP INTERACTION WITH FNBP4; WBP4; FYN AND PLCG1, AND METHYLATION.
RX PubMed=10748127; DOI=10.1074/jbc.m909368199;
RA Bedford M.T., Frankel A., Yaffe M.B., Clarke S., Leder P., Richard S.;
RT "Arginine methylation inhibits the binding of proline-rich ligands to Src
RT homology 3, but not WW, domains.";
RL J. Biol. Chem. 275:16030-16036(2000).
CC -!- FUNCTION: Recruited and tyrosine phosphorylated by several receptor
CC systems, for example the T-cell, leptin and insulin receptors. Once
CC phosphorylated, functions as an adapter protein in signal transduction
CC cascades by binding to SH2 and SH3 domain-containing proteins. Role in
CC G2-M progression in the cell cycle. Represses CBP-dependent
CC transcriptional activation apparently by competing with other nuclear
CC factors for binding to CBP. Also acts as a putative regulator of mRNA
CC stability and/or translation rates and mediates mRNA nuclear export.
CC Positively regulates the association of constitutive transport element
CC (CTE)-containing mRNA with large polyribosomes and translation
CC initiation. May not be involved in the nucleocytoplasmic export of
CC unspliced (CTE)-containing RNA species. RNA-binding protein that plays
CC a role in the regulation of alternative splicing and influences mRNA
CC splice site selection and exon inclusion. Binds to RNA containing 5'-
CC [AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides.
CC Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-
CC dependent manner. In cooperation with HNRNPA1 modulates alternative
CC splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and
CC of SMN1. Can regulate alternative splicing of NRXN1 and NRXN3 in the
CC laminin G-like domain 6 containing the evolutionary conserved neurexin
CC alternative spliced segment 4 (AS4) involved in neurexin selective
CC targeting to postsynaptic partners. In a neuronal activity-dependent
CC manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of
CC NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is
CC antagonistic for regulation of NXRN3 alternative splicing at AS4 (By
CC similarity). {ECO:0000250|UniProtKB:Q07666,
CC ECO:0000250|UniProtKB:Q60749, ECO:0000269|PubMed:10437794}.
CC -!- SUBUNIT: Self-associates to form homooligomers when bound to RNA,
CC oligomerization appears to be limited when binding to proteins.
CC Interacts with KHDRBS3/SLIM-2 (By similarity). Interacts with
CC KHDRBS2/SLIM-1; heterooligomer formation of KHDRBS family proteins may
CC modulate RNA substrate specificity (PubMed:15345239). Interacts with
CC PIK3R1, PLCG1 (PubMed:10437794, PubMed:10748127). Interacts with RASA1,
CC GRB2, SRC, RBMY1A1, CBP, PRMT1, APC, HNRNPA1. Interacts with PTK6 (via
CC SH3 and SH2 domains). Forms a complex with ILF2, ILF3, YLPM1, RBMX,
CC NCOA5 and PPP1CA (By similarity). Binds WBP4/FBP21 (via WW domains),
CC FNBP4/FBP30 (via WW domains). Interacts (via Arg/Gly-rich-flanked Pro-
CC rich regions) with FYN (via the SH3 domain) (PubMed:10748127).
CC Interacts with the non-receptor tyrosine kinase SRMS; the interaction
CC leads to phosphorylation of KHDRBS1 (By similarity). Interacts with
CC ZBTB7A; negatively regulates KHDRBS1 splicing activity toward BCL2L1
CC (By similarity). {ECO:0000250|UniProtKB:Q07666,
CC ECO:0000250|UniProtKB:Q60749, ECO:0000269|PubMed:10437794,
CC ECO:0000269|PubMed:10748127, ECO:0000269|PubMed:15345239}.
CC -!- INTERACTION:
CC Q91V33; Q63787: Pik3r1; NbExp=2; IntAct=EBI-518436, EBI-518443;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q07666}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q07666}. Membrane
CC {ECO:0000250|UniProtKB:Q07666}. Note=Predominantly located in the
CC nucleus but also located partially in the cytoplasm.
CC {ECO:0000250|UniProtKB:Q07666}.
CC -!- DOMAIN: The KH domain is required for binding to RNA.
CC {ECO:0000269|PubMed:15345239}.
CC -!- DOMAIN: The Pro-rich domains are flanked by Arg/Gly-rich motifs which
CC can be asymmetric dimethylated on arginine residues to give the
CC DMA/Gly-rich regions. Selective methylation on these motifs can
CC modulate protein-protein interactions.
CC -!- PTM: Tyrosine phosphorylated by several non-receptor tyrosine kinases
CC including LCK, FYN and JAK3. Also tyrosine phosphorylated by the non-
CC receptor tyrosine kinase SRMS in an EGF-dependent manner.
CC Phosphorylation by PTK6 negatively regulates its RNA binding ability.
CC Phosphorylation by PTK6 at Tyr-440 dictates the nuclear localization of
CC KHDRBS1. {ECO:0000250|UniProtKB:Q07666}.
CC -!- PTM: Acetylated. Positively correlates with ability to bind RNA (By
CC similarity). {ECO:0000250|UniProtKB:Q07666}.
CC -!- PTM: Arginine methylation is required for nuclear localization,
CC Inhibits interaction with Src-like SH3 domains, but not interaction
CC with WW domains of WBP4/FBP21 AND FNBP4/FBP30.
CC {ECO:0000250|UniProtKB:Q07666}.
CC -!- SIMILARITY: Belongs to the KHDRBS family. {ECO:0000255}.
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DR EMBL; AF305619; AAL09361.1; -; mRNA.
DR EMBL; AF393783; AAK77001.1; -; mRNA.
DR EMBL; BC061987; AAH61987.1; -; mRNA.
DR RefSeq; NP_569089.1; NM_130405.1.
DR AlphaFoldDB; Q91V33; -.
DR SMR; Q91V33; -.
DR BioGRID; 250715; 4.
DR CORUM; Q91V33; -.
DR IntAct; Q91V33; 2.
DR STRING; 10116.ENSRNOP00000066894; -.
DR iPTMnet; Q91V33; -.
DR PhosphoSitePlus; Q91V33; -.
DR SwissPalm; Q91V33; -.
DR jPOST; Q91V33; -.
DR PaxDb; Q91V33; -.
DR PRIDE; Q91V33; -.
DR Ensembl; ENSRNOT00000075270; ENSRNOP00000066894; ENSRNOG00000046794.
DR GeneID; 117268; -.
DR KEGG; rno:117268; -.
DR CTD; 10657; -.
DR RGD; 621459; Khdrbs1.
DR eggNOG; KOG1588; Eukaryota.
DR GeneTree; ENSGT00940000155718; -.
DR HOGENOM; CLU_034976_0_0_1; -.
DR InParanoid; Q91V33; -.
DR OMA; TPYREHP; -.
DR OrthoDB; 1012406at2759; -.
DR PhylomeDB; Q91V33; -.
DR Reactome; R-RNO-8849468; PTK6 Regulates Proteins Involved in RNA Processing.
DR PRO; PR:Q91V33; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000046794; Expressed in thymus and 19 other tissues.
DR Genevisible; Q91V33; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0070618; C:Grb2-Sos complex; IDA:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0008143; F:poly(A) binding; ISO:RGD.
DR GO; GO:0008266; F:poly(U) RNA binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; IDA:RGD.
DR GO; GO:0035591; F:signaling adaptor activity; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0046833; P:positive regulation of RNA export from nucleus; ISS:UniProtKB.
DR GO; GO:0045948; P:positive regulation of translational initiation; ISS:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; ISO:RGD.
DR GO; GO:0046831; P:regulation of RNA export from nucleus; ISS:UniProtKB.
DR GO; GO:0009966; P:regulation of signal transduction; NAS:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
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.
DR PROSITE; PS50084; KH_TYPE_1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell cycle; Cytoplasm; Isopeptide bond; Membrane; Methylation;
KW mRNA processing; Nucleus; Phosphoprotein; Reference proteome; RNA-binding;
KW SH3-binding; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..443
FT /note="KH domain-containing, RNA-binding, signal
FT transduction-associated protein 1"
FT /id="PRO_0000050126"
FT DOMAIN 171..197
FT /note="KH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 1..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..260
FT /note="Involved in homodimerization"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT REGION 280..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 351..443
FT /note="Interaction with HNRNPA1"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT REGION 400..420
FT /note="Interaction with ZBTB7A"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT REGION 411..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 21
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q60749"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 45
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 52
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60749"
FT MOD_RES 84
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q60749"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60749"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 175
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 183
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 282
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 284
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 291
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q60749"
FT MOD_RES 304
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 310
FT /note="Omega-N-methylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 315
FT /note="Omega-N-methylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 320
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 320
FT /note="Omega-N-methylarginine; by PRMT1; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 325
FT /note="Omega-N-methylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 331
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60749"
FT MOD_RES 331
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 331
FT /note="Omega-N-methylarginine; by PRMT1; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 340
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 340
FT /note="Omega-N-methylarginine; by PRMT1; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 387
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 435
FT /note="Phosphotyrosine; by PTK6"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 440
FT /note="Phosphotyrosine; by PTK6"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT MOD_RES 443
FT /note="Phosphotyrosine; by PTK6"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT CROSSLNK 102
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT CROSSLNK 139
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT CROSSLNK 175
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
FT CROSSLNK 432
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q07666"
SQ SEQUENCE 443 AA; 48315 MW; C41A42831E7DCBC7 CRC64;
MQRRDDPAAR LTRSSGRSCS KDPSGAHPSV RLTPSRPSPL PHRSRGGGGG PRGGARASPA
TQPPPLLPPS NPGPDATVVG SAPTPLLPPS ATAAAKMEPE NKYLPELMAE KDSLDPSFTH
AMQLLSVEIE KIQKGESKKD DEENYLDLFS HKNMKLKERV LIPVKQYPKF NFVGKILGPQ
GNTIKRLQEE TGAKISVLGK GSMRDKAKEE ELRKGGDPKY AHLNMDLHVF IEVFGPPCEA
YALMAHAMEE VKKFLVPDMM DDICQEQFLE LSYLNGVPEP SRGRGVSVRG RGAAPPPPPV
PRGRGVGPPR GALVRGTPVR GSITRGATVT RGVPPPPTVR GAPTPRARTA GIQRIPLPPT
PAPETYEDYG YDDSYAEQSY EGYEGYYSQS QGESEYYDYG HGELQDSYEA YGQDDWNGTR
PSLKAPPARP VKGAYREHPY GRY
