ID   QKI_RAT                 Reviewed;         341 AA.
AC   Q91XU1;
DT   13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   13-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 113.
DE   RecName: Full=KH domain-containing RNA-binding protein QKI {ECO:0000250|UniProtKB:Q9QYS9};
DE   AltName: Full=Protein quaking {ECO:0000312|RGD:1584886};
DE            Short=RqkI {ECO:0000312|RGD:1584886};
GN   Name=Qki {ECO:0000312|RGD:1584886};
GN   Synonyms=Qk {ECO:0000312|RGD:1584886};
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]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 98-302.
RC   TISSUE=Brain;
RA   Leng S., Tsutsumi M., Takase S., Abe S., Yamamoto Y., Fukunaga T.,
RA   Saijoh K.;
RT   "Differentially expressed genes.";
RL   Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=11178867; DOI=10.1006/mcne.2000.0941;
RA   Wu H.Y., Dawson M.R.L., Reynolds R., Hardy R.J.;
RT   "Expression of QKI proteins and MAP1B identifies actively myelinating
RT   oligodendrocytes in adult rat brain.";
RL   Mol. Cell. Neurosci. 17:292-302(2001).
CC   -!- FUNCTION: RNA reader protein, which recognizes and binds specific RNAs,
CC       thereby regulating RNA metabolic processes, such as pre-mRNA splicing,
CC       circular RNA (circRNA) formation, mRNA export, mRNA stability and/or
CC       translation. Involved in various cellular processes, such as mRNA
CC       storage into stress granules, apoptosis, lipid deposition, interferon
CC       response, glial cell fate and development. Binds to the 5'-NACUAAY-
CC       N(1,20)-UAAY-3' RNA core sequence. Acts as a mRNA modification reader
CC       that specifically recognizes and binds mRNA transcripts modified by
CC       internal N(7)-methylguanine (m7G). Promotes the formation of circular
CC       RNAs (circRNAs) during the epithelial to mesenchymal transition and in
CC       cardiomyocytes: acts by binding to sites flanking circRNA-forming
CC       exons. CircRNAs are produced by back-splicing circularization of pre-
CC       mRNAs. Plays a central role in myelinization via 3 distinct mechanisms
CC       (By similarity). First, acts by protecting and promoting stability of
CC       target mRNAs such as MBP, SIRT2 and CDKN1B, which promotes
CC       oligodendrocyte differentiation. Second, participates in mRNA transport
CC       by regulating the nuclear export of MBP mRNA. Finally, indirectly
CC       regulates mRNA splicing of MAG pre-mRNA during oligodendrocyte
CC       differentiation by acting as a negative regulator of MAG exon 12
CC       alternative splicing: acts by binding to HNRNPA1 mRNA splicing factor,
CC       preventing its translation. Involved in microglia differentiation and
CC       remyelination by regulating microexon alternative splicing of the Rho
CC       GTPase pathway (By similarity). Involved in macrophage differentiation:
CC       promotes monocyte differentiation by regulating pre-mRNA splicing in
CC       naive peripheral blood monocytes (By similarity). Acts as an important
CC       regulator of muscle development: required for the contractile function
CC       of cardiomyocytes by regulating alternative splicing of cardiomyocyte
CC       transcripts. Acts as a negative regulator of thermogenesis by
CC       decreasing stability, nuclear export and translation of mRNAs encoding
CC       PPARGC1A and UCP1. Also required for visceral endoderm function and
CC       blood vessel development (By similarity). May also play a role in
CC       smooth muscle development (By similarity). In addition to its RNA-
CC       binding activity, also acts as a nuclear transcription coactivator for
CC       SREBF2/SREBP2 (By similarity). {ECO:0000250|UniProtKB:Q96PU8,
CC       ECO:0000250|UniProtKB:Q9QYS9}.
CC   -!- SUBUNIT: Homodimer; does not require RNA to homodimerize (By
CC       similarity). Able to heterodimerize with BICC1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q96PU8, ECO:0000250|UniProtKB:Q9QYS9}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96PU8}. Cytoplasm
CC       {ECO:0000269|PubMed:11178867}.
CC   -!- TISSUE SPECIFICITY: Present in myelinating oligodendrocytes (at protein
CC       level). {ECO:0000269|PubMed:11178867}.
CC   -!- DOMAIN: The KH domain and the Qua2 region are involved in RNA binding.
CC       {ECO:0000250|UniProtKB:Q96PU8}.
CC   -!- PTM: Methylated by PRMT1. {ECO:0000250|UniProtKB:Q9QYS9}.
CC   -!- PTM: Tyrosine phosphorylated at its C-terminus, probably by FYN.
CC       Phosphorylation leads to decreased mRNA-binding affinity, affecting
CC       transport and/or stabilization of MBP mRNA (By similarity).
CC       {ECO:0000250|UniProtKB:Q9QYS9}.
CC   -!- PTM: Ubiquitinated by RNF6 in macrophages, leading to its degradation.
CC       {ECO:0000250|UniProtKB:Q9QYS9}.
CC   -!- SIMILARITY: Belongs to the quaking family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AABR03000138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AB054997; BAB62175.1; -; mRNA.
DR   AlphaFoldDB; Q91XU1; -.
DR   SMR; Q91XU1; -.
DR   STRING; 10116.ENSRNOP00000070460; -.
DR   iPTMnet; Q91XU1; -.
DR   PhosphoSitePlus; Q91XU1; -.
DR   jPOST; Q91XU1; -.
DR   PaxDb; 10116-ENSRNOP00000034413; -.
DR   ABCD; Q91XU1; 4 sequenced antibodies.
DR   AGR; RGD:1584886; -.
DR   RGD; 1584886; Qki.
DR   eggNOG; KOG1588; Eukaryota.
DR   InParanoid; Q91XU1; -.
DR   PhylomeDB; Q91XU1; -.
DR   PRO; PR:Q91XU1; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0045202; C:synapse; ISO:RGD.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0160089; F:internal N(7)-methylguanine-containing RNA reader activity; ISO:RGD.
DR   GO; GO:0035198; F:miRNA binding; ISS:UniProtKB.
DR   GO; GO:0003730; F:mRNA 3'-UTR binding; ISO:RGD.
DR   GO; GO:0003729; F:mRNA binding; ISO:RGD.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR   GO; GO:0008366; P:axon ensheathment; ISO:RGD.
DR   GO; GO:0008298; P:intracellular mRNA localization; ISO:RGD.
DR   GO; GO:0042759; P:long-chain fatty acid biosynthetic process; ISO:RGD.
DR   GO; GO:0014004; P:microglia differentiation; ISS:UniProtKB.
DR   GO; GO:0006397; P:mRNA processing; IMP:RGD.
DR   GO; GO:0048255; P:mRNA stabilization; IMP:RGD.
DR   GO; GO:0051028; P:mRNA transport; ISO:RGD.
DR   GO; GO:0042552; P:myelination; ISO:RGD.
DR   GO; GO:1990764; P:myofibroblast contraction; ISO:RGD.
DR   GO; GO:1905869; P:negative regulation of 3'-UTR-mediated mRNA stabilization; ISS:UniProtKB.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; ISO:RGD.
DR   GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:RGD.
DR   GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:UniProtKB.
DR   GO; GO:0045650; P:negative regulation of macrophage differentiation; ISS:UniProtKB.
DR   GO; GO:2000626; P:negative regulation of miRNA catabolic process; ISS:UniProtKB.
DR   GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR   GO; GO:1905870; P:positive regulation of 3'-UTR-mediated mRNA stabilization; ISO:RGD.
DR   GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISO:RGD.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR   GO; GO:0031643; P:positive regulation of myelination; ISO:RGD.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
DR   GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IMP:RGD.
DR   GO; GO:0048710; P:regulation of astrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR   GO; GO:0045649; P:regulation of macrophage differentiation; ISO:RGD.
DR   GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; ISS:UniProtKB.
DR   GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR   GO; GO:0007286; P:spermatid development; ISO:RGD.
DR   GO; GO:0035886; P:vascular associated smooth muscle cell differentiation; ISS:UniProtKB.
DR   GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR   CDD; cd22465; KH-I_Hqk; 1.
DR   Gene3D; 1.20.5.4010; -; 1.
DR   Gene3D; 3.30.1370.10; K Homology domain, type 1; 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; IPR032367; Quaking_NLS.
DR   InterPro; IPR032377; STAR_dimer.
DR   PANTHER; PTHR11208:SF125; PROTEIN QUAKING; 1.
DR   PANTHER; PTHR11208; RNA-BINDING PROTEIN RELATED; 1.
DR   Pfam; PF00013; KH_1; 1.
DR   Pfam; PF16551; Quaking_NLS; 1.
DR   Pfam; PF16544; STAR_dimer; 1.
DR   SMART; SM00322; KH; 1.
DR   SUPFAM; SSF54791; Eukaryotic type KH-domain (KH-domain type I); 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Developmental protein; Differentiation; DNA-binding;
KW   Methylation; mRNA processing; mRNA splicing; mRNA transport; Nucleus;
KW   Phosphoprotein; Reference proteome; RNA-binding; SH3-binding;
KW   Translation regulation; Transport; Ubl conjugation.
FT   CHAIN           1..341
FT                   /note="KH domain-containing RNA-binding protein QKI"
FT                   /id="PRO_0000239376"
FT   DOMAIN          87..153
FT                   /note="KH"
FT   REGION          11..82
FT                   /note="Qua1 domain; involved in homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:Q17339"
FT   REGION          182..213
FT                   /note="Qua2 domain; involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   MOTIF           276..279
FT                   /note="SH3-binding"
FT   MOTIF           324..330
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QYS9"
FT   SITE            97
FT                   /note="Involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   SITE            120
FT                   /note="Involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   SITE            124
FT                   /note="Involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   SITE            130
FT                   /note="Involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   SITE            190
FT                   /note="Involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   SITE            193
FT                   /note="Involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   MOD_RES         188
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   MOD_RES         227
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   MOD_RES         242
FT                   /note="Asymmetric dimethylarginine; by CARM1; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   MOD_RES         242
FT                   /note="Omega-N-methylarginine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PU8"
FT   MOD_RES         256
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QYS9"
SQ   SEQUENCE   341 AA;  37643 MW;  41B066F1711771C4 CRC64;
     MVGEMETKEN PNPTPDYLMQ LMNDKKLMSS LPNFCGIFNH LERLLDEEIS RVRKDMYNDT
     LNGSTEKRSA ELPDAVGPIV QLQEKLYVPV KEYPDFNFVG RILGPRGLTA KQLEAETGCK
     IMVRGKGSMR DKKKEEQNRG KPNWEHLNED LHVLITVEDA QNRAEIKLKR AVEEVKKLLV
     PAAEGEDSLK KMQLMELAIL NGTYRDANIK SPALAFSLAA TAQAAPRIIT GPAPVLPPAA
     LRTPTPAGPT IMPLIRQIQT AVMPNGTPHP TAAIVPPGPE AGLIYTPYEY PYTLAPATSI
     LEYPIEPSGV LGAVATKVRR HDMRVHPYQR IVTADRAATG N
//