IBTK_MOUSE
ID IBTK_MOUSE Reviewed; 1352 AA.
AC Q6ZPR6; B9EHE9; Q3V3X0; Q8BVL7;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Inhibitor of Bruton tyrosine kinase;
DE Short=IBtk;
GN Name=Ibtk; Synonyms=Kiaa1417;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-742 AND 1097-1352 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 85-1352 (ISOFORM 2).
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1046, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1005; SER-1046; SER-1111;
RP SER-1113 AND SER-1116, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Acts as an inhibitor of BTK tyrosine kinase activity, thereby
CC playing a role in B-cell development. Down-regulates BTK kinase
CC activity, leading to interference with BTK-mediated calcium
CC mobilization and NF-kappa-B-driven transcription (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with the PH domain of BTK. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Note=Translocates to the
CC plasma membrane upon IgM stimulation. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZPR6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZPR6-2; Sequence=VSP_023605;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC36779.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; CH466522; EDL26483.1; -; Genomic_DNA.
DR EMBL; BC137798; AAI37799.1; -; mRNA.
DR EMBL; AK030895; BAE20460.1; -; mRNA.
DR EMBL; AK077387; BAC36779.1; ALT_FRAME; mRNA.
DR EMBL; AK129353; BAC98163.1; -; mRNA.
DR CCDS; CCDS40712.1; -. [Q6ZPR6-1]
DR RefSeq; NP_001074751.1; NM_001081282.2. [Q6ZPR6-1]
DR AlphaFoldDB; Q6ZPR6; -.
DR SMR; Q6ZPR6; -.
DR BioGRID; 224442; 6.
DR STRING; 10090.ENSMUSP00000041145; -.
DR iPTMnet; Q6ZPR6; -.
DR PhosphoSitePlus; Q6ZPR6; -.
DR EPD; Q6ZPR6; -.
DR jPOST; Q6ZPR6; -.
DR MaxQB; Q6ZPR6; -.
DR PaxDb; Q6ZPR6; -.
DR PeptideAtlas; Q6ZPR6; -.
DR PRIDE; Q6ZPR6; -.
DR ProteomicsDB; 267207; -. [Q6ZPR6-1]
DR ProteomicsDB; 267208; -. [Q6ZPR6-2]
DR Antibodypedia; 18465; 133 antibodies from 24 providers.
DR DNASU; 108837; -.
DR Ensembl; ENSMUST00000039213; ENSMUSP00000041145; ENSMUSG00000035941. [Q6ZPR6-1]
DR GeneID; 108837; -.
DR KEGG; mmu:108837; -.
DR UCSC; uc009qww.2; mouse. [Q6ZPR6-1]
DR CTD; 25998; -.
DR MGI; MGI:1918677; Ibtk.
DR VEuPathDB; HostDB:ENSMUSG00000035941; -.
DR eggNOG; KOG0783; Eukaryota.
DR GeneTree; ENSGT00940000156277; -.
DR HOGENOM; CLU_005713_0_0_1; -.
DR InParanoid; Q6ZPR6; -.
DR OMA; FACGINT; -.
DR OrthoDB; 94875at2759; -.
DR PhylomeDB; Q6ZPR6; -.
DR TreeFam; TF323747; -.
DR BioGRID-ORCS; 108837; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Ibtk; mouse.
DR PRO; PR:Q6ZPR6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q6ZPR6; protein.
DR Bgee; ENSMUSG00000035941; Expressed in animal zygote and 257 other tissues.
DR ExpressionAtlas; Q6ZPR6; baseline and differential.
DR Genevisible; Q6ZPR6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0030292; F:protein tyrosine kinase inhibitor activity; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:MGI.
DR Gene3D; 1.25.40.20; -; 2.
DR Gene3D; 2.130.10.30; -; 1.
DR Gene3D; 3.30.710.10; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00651; BTB; 2.
DR Pfam; PF00415; RCC1; 3.
DR SMART; SM00248; ANK; 2.
DR SMART; SM00225; BTB; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF54695; SSF54695; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
DR PROSITE; PS50097; BTB; 2.
DR PROSITE; PS50012; RCC1_3; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1352
FT /note="Inhibitor of Bruton tyrosine kinase"
FT /id="PRO_0000280277"
FT REPEAT 51..80
FT /note="ANK 1"
FT REPEAT 85..114
FT /note="ANK 2"
FT REPEAT 141..194
FT /note="RCC1 1"
FT REPEAT 195..246
FT /note="RCC1 2"
FT REPEAT 248..301
FT /note="RCC1 3"
FT DOMAIN 565..645
FT /note="BTB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 769..837
FT /note="BTB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REGION 692..716
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 976..1002
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1032..1094
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 695..715
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2D0"
FT MOD_RES 1005
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1031
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2D0"
FT MOD_RES 1034
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2D0"
FT MOD_RES 1040
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2D0"
FT MOD_RES 1046
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1055
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2D0"
FT MOD_RES 1084
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2D0"
FT MOD_RES 1111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 137..237
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_023605"
FT CONFLICT 282
FT /note="K -> E (in Ref. 3; BAE20460)"
FT /evidence="ECO:0000305"
FT CONFLICT 1189
FT /note="A -> V (in Ref. 4; BAC98163)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1352 AA; 149569 MW; 5FA4BC368281D734 CRC64;
MDAATPDCTS KCRSLKHALD VLSVVTKGSE SQIKSFLARY CYNAATVKDA FGRNAGHLAS
SCGKKGVLDW LIEKGVDLLV KDKESGWTAL HRSVFYGHID CVWSLLKHGV SLYMQDKEGL
SPLDLLMKDR PTHVVFKDTD PTEVYTWGDN TNFTLGHGSQ NSKHHPELLD LFSRSGVYVK
QVVLCKFHSV FLSQKGQVYT CGHGRGGRLG HGDEQTCLVP RLVEGLSGHN CSQVAAAKDH
TVVLTDDGCV YTFGLNMFHQ LGIIPPPASC NVPRQIQAKY LKGRTIIGVA AGRFHTVLWT
REAVYTLGLN GGQLGHLLDP NGEKCVTTPR QVSALHHKDI AVSLVAASDG ATVCVTTRGD
IYLLADYQCK KMATKQLNLK KVLVSGGCME YKVDPEHLTE NGGQKICVLA MDGAGRVFCW
RSISSSLKQC RWAYPRQVSI SDIALNRNEI LFVTQDGEGF KGKWFEDKRK NSEKKADILP
NLHHSSSDVS CVPDTNSVYE RIRLEKLPFA HRAVSVSTDP SGCNFAILQS DPKTSLYEIP
VVSSSSFFEE FGKLLRETDE MDSFHDVTFQ VGNRHFPAHK YILAVRSDFF QKLFLSDGSS
LELTDVYQKD EDAAGCHLFV VEKVHPDLFE YLLQFMYTDT CDLLTHGFKP RMIVKRKAED
CEGSPDSHLH TVNCHVDDKQ KSAFEVYRSN QAHTLSERQK SKPKSSKKGK GVGDDDPVRM
LQSVAKKFGL SNLSSRLEGV RLENEKINVI AKKTGNKLKL SQKKCSFLYD VTMKSVDGKE
FSCHKCVLCA RLEYFHSMLS RSWIEASSCA ALEMPIQSEI LKVILDYLYT DEAVVIKESQ
NVDFVCSVLV VADQLLITRL KEICEVALTE NLTLKNAAML LEFAALYNAG QLKLSCLQFI
GLNMAALLEA RSLDVLSEDV LKDLSIFYRK MIPAMERRVI TPYQDGPDIS SMQVEDGEVF
FKEEINMEPN YSETMFKKAK TRAKKKPRKR SDSSGGYTLS DVIQSPPSAG LLKSAKTNSV
ESLPELLTSD SEGSYAGVAS PRDLQSPDFT AGFHSDKVEG KAKPYVNGIP PPCTREDVKP
WEKSPTTKSA PQFIPSNRVD TAASSSWLAG SCSPVSPPVV DLRTIMETEE NRQKYGAAPK
SNLGKIISHG IKLSQKQRKM IALTTKENNS GTNSMEAILT APSKSPKPAN AWAPLHSPLS
RSFRDFLLEE KKPVPGYGSG DHVKKVCFKG TENSPALNVA RCSTHGTPGL ESNHVSDFPL
LDSPNPWQSS SLAASPAVAP VTFASIVEEE RQQEAALIRS REKPLALIQV EEHAIQDLLV
FYEAFGNPEE FVVVERAPQG PLAVPMWNKH GC
