ITPR1_MOUSE
ID ITPR1_MOUSE Reviewed; 2749 AA.
AC P11881; P20943; Q99LG5;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Inositol 1,4,5-trisphosphate receptor type 1;
DE AltName: Full=IP3 receptor isoform 1;
DE Short=IP3R 1;
DE Short=InsP3R1;
DE AltName: Full=Inositol 1,4,5-trisphosphate-binding protein P400;
DE AltName: Full=Protein PCD-6;
DE AltName: Full=Purkinje cell protein 1;
DE AltName: Full=Type 1 inositol 1,4,5-trisphosphate receptor;
DE Short=Type 1 InsP3 receptor;
GN Name=Itpr1; Synonyms=Insp3r, Pcd6, Pcp1;
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 [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Purkinje cell;
RX PubMed=2554142; DOI=10.1038/342032a0;
RA Furuichi T., Yoshikawa S., Miyawaki A., Wada K., Maeda N., Mikoshiba K.;
RT "Primary structure and functional expression of the inositol 1,4,5-
RT trisphosphate-binding protein P400.";
RL Nature 342:32-38(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Cerebellum;
RX PubMed=2762133; DOI=10.1093/nar/17.13.5385;
RA Furuichi T., Yoshikawa S., Mikoshiba K.;
RT "Nucleotide sequence of cDNA encoding P400 protein in the mouse
RT cerebellum.";
RL Nucleic Acids Res. 17:5385-5386(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 318-332 AND 1692-1731, AND ALTERNATIVE
RP SPLICING.
RC STRAIN=ICR;
RX PubMed=1648733; DOI=10.1073/pnas.88.14.6244;
RA Nakagawa T., Okano H., Furuichi T., Aruga J., Mikoshiba K.;
RT "The subtypes of the mouse inositol 1,4,5-trisphosphate receptor are
RT expressed in a tissue-specific and developmentally specific manner.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:6244-6248(1991).
RN [5]
RP PROTEIN SEQUENCE OF 862-871, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2098-2749.
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2250-2749.
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=3199205; DOI=10.1523/jneurosci.08-12-04780.1988;
RA Nordquist D.T., Kozak C.A., Orr H.T.;
RT "cDNA cloning and characterization of three genes uniquely expressed in
RT cerebellum by Purkinje neurons.";
RL J. Neurosci. 8:4780-4789(1988).
RN [8]
RP INTERACTION WITH AHCYL1.
RX PubMed=12525476; DOI=10.1074/jbc.m210119200;
RA Ando H., Mizutani A., Matsu-ura T., Mikoshiba K.;
RT "IRBIT, a novel inositol 1,4,5-trisphosphate (IP3) receptor-binding
RT protein, is released from the IP3 receptor upon IP3 binding to the
RT receptor.";
RL J. Biol. Chem. 278:10602-10612(2003).
RN [9]
RP INTERACTION WITH ERP44, AND MUTAGENESIS OF CYS-2496; CYS-2504 AND CYS-2527.
RX PubMed=15652484; DOI=10.1016/j.cell.2004.11.048;
RA Higo T., Hattori M., Nakamura T., Natsume T., Michikawa T., Mikoshiba K.;
RT "Subtype-specific and ER lumenal environment-dependent regulation of
RT inositol 1,4,5-trisphosphate receptor type 1 by ERp44.";
RL Cell 120:85-98(2005).
RN [10]
RP INTERACTION WITH AHCYL1.
RX PubMed=16527252; DOI=10.1016/j.bbrc.2006.02.119;
RA Devogelaere B., Nadif Kasri N., Derua R., Waelkens E., Callewaert G.,
RA Missiaen L., Parys J.B., De Smedt H.;
RT "Binding of IRBIT to the IP3 receptor: determinants and functional
RT effects.";
RL Biochem. Biophys. Res. Commun. 343:49-56(2006).
RN [11]
RP INTERACTION WITH IRAG1, AND SUBCELLULAR LOCATION.
RX PubMed=16990611; DOI=10.1182/blood-2005-10-026294;
RA Antl M., von Bruehl M.-L., Eiglsperger C., Werner M., Konrad I., Kocher T.,
RA Wilm M., Hofmann F., Massberg S., Schlossmann J.;
RT "IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and
RT thrombus formation.";
RL Blood 109:552-559(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1588, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200;
RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.;
RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and
RT MS/MS/MS.";
RL Mol. Cell. Proteomics 6:669-676(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1588, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [14]
RP FUNCTION.
RX PubMed=19752026; DOI=10.1083/jcb.200904060;
RA Li G., Mongillo M., Chin K.T., Harding H., Ron D., Marks A.R., Tabas I.;
RT "Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate
RT receptor activity in endoplasmic reticulum stress-induced apoptosis.";
RL J. Cell Biol. 186:783-792(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1588, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF TYR-167; LYS-168 AND LEU-169.
RX PubMed=20813840; DOI=10.1074/jbc.m110.140129;
RA Yamazaki H., Chan J., Ikura M., Michikawa T., Mikoshiba K.;
RT "Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates
RT functional coupling between ligand binding and channel opening.";
RL J. Biol. Chem. 285:36081-36091(2010).
RN [17]
RP INTERACTION WITH TESPA1.
RX PubMed=23650607; DOI=10.1016/j.fob.2012.08.005;
RA Matsuzaki H., Fujimoto T., Ota T., Ogawa M., Tsunoda T., Doi K.,
RA Hamabashiri M., Tanaka M., Shirasawa S.;
RT "Tespa1 is a novel inositol 1,4,5-trisphosphate receptor binding protein in
RT T and B lymphocytes.";
RL FEBS Open Bio 2:255-259(2012).
RN [18]
RP INTERACTION WITH AHCYL1, MUTAGENESIS OF SER-1588 AND SER-1755,
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=23542070; DOI=10.1053/j.gastro.2013.03.047;
RA Park S., Shcheynikov N., Hong J.H., Zheng C., Suh S.H., Kawaai K., Ando H.,
RA Mizutani A., Abe T., Kiyonari H., Seki G., Yule D., Mikoshiba K.,
RA Muallem S.;
RT "Irbit mediates synergy between ca(2+) and cAMP signaling pathways during
RT epithelial transport in mice.";
RL Gastroenterology 145:232-241(2013).
RN [19]
RP INTERACTION WITH BOK.
RX PubMed=23884412; DOI=10.1074/jbc.m113.496570;
RA Schulman J.J., Wright F.A., Kaufmann T., Wojcikiewicz R.J.;
RT "The Bcl-2 protein family member Bok binds to the coupling domain of
RT inositol 1,4,5-trisphosphate receptors and protects them from proteolytic
RT cleavage.";
RL J. Biol. Chem. 288:25340-25349(2013).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=24374158; DOI=10.1016/j.ydbio.2013.12.025;
RA Kim B., Zhang X., Kan R., Cohen R., Mukai C., Travis A.J., Coonrod S.A.;
RT "The role of MATER in endoplasmic reticulum distribution and calcium
RT homeostasis in mouse oocytes.";
RL Dev. Biol. 386:331-339(2014).
RN [21]
RP PALMITOYLATION AT CYS-56 AND CYS-849, AND MUTAGENESIS OF CYS-56; CYS-849
RP AND CYS-2215.
RX PubMed=25368151; DOI=10.1073/pnas.1417176111;
RA Fredericks G.J., Hoffmann F.W., Rose A.H., Osterheld H.J., Hess F.M.,
RA Mercier F., Hoffmann P.R.;
RT "Stable expression and function of the inositol 1,4,5-triphosphate receptor
RT requires palmitoylation by a DHHC6/selenoprotein K complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:16478-16483(2014).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 224-604 IN COMPLEX WITH INOSITOL
RP 1,4,5-TRISPHOSPHATE, AND MUTAGENESIS OF THR-267 AND TYR-567.
RX PubMed=12442173; DOI=10.1038/nature01268;
RA Bosanac I., Alattia J.R., Mal T.K., Chan J., Talarico S., Tong F.K.,
RA Tong K.I., Yoshikawa F., Furuichi T., Iwai M., Michikawa T., Mikoshiba K.,
RA Ikura M.;
RT "Structure of the inositol 1,4,5-trisphosphate receptor binding core in
RT complex with its ligand.";
RL Nature 420:696-700(2002).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 2-223.
RX PubMed=15664189; DOI=10.1016/j.molcel.2004.11.047;
RA Bosanac I., Yamazaki H., Matsu-Ura T., Michikawa T., Mikoshiba K.,
RA Ikura M.;
RT "Crystal structure of the ligand binding suppressor domain of type 1
RT inositol 1,4,5-trisphosphate receptor.";
RL Mol. Cell 17:193-203(2005).
CC -!- FUNCTION: Intracellular channel that mediates calcium release from the
CC endoplasmic reticulum following stimulation by inositol 1,4,5-
CC trisphosphate. Involved in the regulation of epithelial secretion of
CC electrolytes and fluid through the interaction with AHCYL1
CC (PubMed:23542070). Plays a role in ER stress-induced apoptosis.
CC Cytoplasmic calcium released from the ER triggers apoptosis by the
CC activation of CaM kinase II, eventually leading to the activation of
CC downstream apoptosis pathways. {ECO:0000269|PubMed:19752026,
CC ECO:0000269|PubMed:20813840, ECO:0000269|PubMed:23542070,
CC ECO:0000269|PubMed:2554142}.
CC -!- SUBUNIT: Homotetramer. Interacts with TRPC4. The PPXXF motif binds
CC HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and
CC SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium-
CC dependent manner which results in the inhibition the calcium channel
CC activity. The strength of this interaction inversely correlates with
CC calcium concentration. Part of cGMP kinase signaling complex at least
CC composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban,
CC PRKG1 and ITPR1. Interacts with IRAG1 (PubMed:16990611). Interacts with
CC CABP1 (via N-terminus) (By similarity). Interacts with TESPA1.
CC Interacts (when not phosphorylated) with AHCYL1 (when phosphorylated);
CC the interaction suppresses inositol 1,4,5-trisphosphate binding to
CC ITPR1 and is increased in the presence of BCL2L10 (PubMed:23542070).
CC Interacts with AHCYL2 (with lower affinity than with AHCYL1) (By
CC similarity). Interacts with BCL2L10; the interaction is increased in
CC the presence of AHCLY1 (By similarity). Interacts with BOK (via BH4
CC domain); protects ITPR1 from proteolysis by CASP3 during apoptosis
CC (PubMed:23884412). {ECO:0000250|UniProtKB:P29994,
CC ECO:0000250|UniProtKB:Q14643, ECO:0000250|UniProtKB:Q9TU34,
CC ECO:0000269|PubMed:12442173, ECO:0000269|PubMed:12525476,
CC ECO:0000269|PubMed:15652484, ECO:0000269|PubMed:16527252,
CC ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:23542070,
CC ECO:0000269|PubMed:23650607, ECO:0000269|PubMed:23884412}.
CC -!- INTERACTION:
CC P11881; Q8VDN2: Atp1a1; NbExp=3; IntAct=EBI-541478, EBI-444536;
CC P11881; Q6PIE5: Atp1a2; NbExp=3; IntAct=EBI-541478, EBI-6665421;
CC P11881; Q9D1Q6: Erp44; NbExp=5; IntAct=EBI-541478, EBI-541567;
CC P11881; O35157: Slc8a1; NbExp=4; IntAct=EBI-541478, EBI-8351080;
CC P11881; P10415: BCL2; Xeno; NbExp=3; IntAct=EBI-541478, EBI-77694;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:25368151}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250|UniProtKB:Q9TU34}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q14643}. Note=Endoplasmic reticulum and
CC secretory granules. {ECO:0000250|UniProtKB:Q9TU34,
CC ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:24374158}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=There is a combination of two alternatively spliced domains
CC at site SI and site SII (A, B and C). Experimental confirmation may
CC be lacking for some isoforms.;
CC Name=1; Synonyms=SISIIABC;
CC IsoId=P11881-1; Sequence=Displayed;
CC Name=2; Synonyms=SI-SIIABC;
CC IsoId=P11881-2; Sequence=VSP_002691;
CC Name=3; Synonyms=SISIIAC;
CC IsoId=P11881-3; Sequence=VSP_002693;
CC Name=4; Synonyms=SI-SIIAC;
CC IsoId=P11881-4; Sequence=VSP_002691, VSP_002693;
CC Name=5; Synonyms=SISIIA;
CC IsoId=P11881-5; Sequence=VSP_002693, VSP_002694;
CC Name=6; Synonyms=SI-SIIA;
CC IsoId=P11881-6; Sequence=VSP_002691, VSP_002693, VSP_002694;
CC Name=7; Synonyms=SISII;
CC IsoId=P11881-7; Sequence=VSP_002692, VSP_002693, VSP_002694;
CC Name=8; Synonyms=SI-SII;
CC IsoId=P11881-8; Sequence=VSP_002691, VSP_002692, VSP_002693,
CC VSP_002694;
CC -!- DOMAIN: The receptor contains a calcium channel in its C-terminal
CC extremity. Its large N-terminal cytoplasmic region has the ligand-
CC binding site in the N-terminus and modulatory sites in the middle
CC portion immediately upstream of the channel region.
CC -!- PTM: Phosphorylated by cAMP kinase (PKA). Phosphorylation prevents the
CC ligand-induced opening of the calcium channels. Phosphorylation by PKA
CC increases the interaction with inositol 1,4,5-trisphosphate and
CC decreases the interaction with AHCYL1. {ECO:0000305|PubMed:23542070}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q14643}.
CC -!- PTM: Ubiquitination at multiple lysines targets ITPR1 for proteasomal
CC degradation. Approximately 40% of the ITPR1-associated ubiquitin is
CC monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'-
CC linked (By similarity). {ECO:0000250|UniProtKB:P29994}.
CC -!- PTM: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of
CC ITPR1 stability and function (PubMed:25368151).
CC {ECO:0000269|PubMed:25368151}.
CC -!- MISCELLANEOUS: Calcium appears to inhibit ligand binding to the
CC receptor, most probably by interacting with a distinct calcium-binding
CC protein which then inhibits the receptor.
CC -!- SIMILARITY: Belongs to the InsP3 receptor family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA88319.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH03271.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X15373; CAA33433.1; -; mRNA.
DR EMBL; AC120411; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC153986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC156506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M75986; AAA39316.1; -; Genomic_DNA.
DR EMBL; M75987; AAA39317.1; -; Genomic_DNA.
DR EMBL; BC003271; AAH03271.1; ALT_INIT; mRNA.
DR EMBL; M21530; AAA88319.1; ALT_INIT; mRNA.
DR CCDS; CCDS51869.1; -. [P11881-1]
DR PIR; S04844; ACMSIT.
DR RefSeq; NP_034715.3; NM_010585.5. [P11881-1]
DR RefSeq; XP_006505693.1; XM_006505630.1. [P11881-2]
DR RefSeq; XP_006505699.1; XM_006505636.1. [P11881-7]
DR RefSeq; XP_006505700.1; XM_006505637.1. [P11881-8]
DR RefSeq; XP_017176897.1; XM_017321408.1. [P11881-3]
DR RefSeq; XP_017176899.1; XM_017321410.1. [P11881-4]
DR PDB; 1N4K; X-ray; 2.20 A; A=224-604.
DR PDB; 1XZZ; X-ray; 1.80 A; A=2-223.
DR PDB; 5GUG; X-ray; 7.40 A; A/B=1-2217.
DR PDB; 5X9Z; X-ray; 7.31 A; A/B=1-2217.
DR PDB; 5XA0; X-ray; 5.81 A; A/B=1-1581.
DR PDB; 5XA1; X-ray; 6.20 A; A/B=1-1581.
DR PDBsum; 1N4K; -.
DR PDBsum; 1XZZ; -.
DR PDBsum; 5GUG; -.
DR PDBsum; 5X9Z; -.
DR PDBsum; 5XA0; -.
DR PDBsum; 5XA1; -.
DR SASBDB; P11881; -.
DR SMR; P11881; -.
DR BioGRID; 200847; 40.
DR CORUM; P11881; -.
DR DIP; DIP-32243N; -.
DR IntAct; P11881; 21.
DR MINT; P11881; -.
DR STRING; 10090.ENSMUSP00000032192; -.
DR GlyConnect; 2438; 14 N-Linked glycans (1 site). [P11881-3]
DR iPTMnet; P11881; -.
DR PhosphoSitePlus; P11881; -.
DR SwissPalm; P11881; -.
DR EPD; P11881; -.
DR jPOST; P11881; -.
DR MaxQB; P11881; -.
DR PaxDb; P11881; -.
DR PeptideAtlas; P11881; -.
DR PRIDE; P11881; -.
DR ProteomicsDB; 269006; -. [P11881-1]
DR ProteomicsDB; 269007; -. [P11881-2]
DR ProteomicsDB; 269008; -. [P11881-3]
DR ProteomicsDB; 269009; -. [P11881-4]
DR ProteomicsDB; 269010; -. [P11881-5]
DR ProteomicsDB; 269011; -. [P11881-6]
DR ProteomicsDB; 269012; -. [P11881-7]
DR ProteomicsDB; 269013; -. [P11881-8]
DR ABCD; P11881; 1 sequenced antibody.
DR Antibodypedia; 5503; 421 antibodies from 41 providers.
DR DNASU; 16438; -.
DR Ensembl; ENSMUST00000032192; ENSMUSP00000032192; ENSMUSG00000030102. [P11881-1]
DR Ensembl; ENSMUST00000203615; ENSMUSP00000144880; ENSMUSG00000030102. [P11881-3]
DR GeneID; 16438; -.
DR KEGG; mmu:16438; -.
DR UCSC; uc033itt.1; mouse. [P11881-1]
DR CTD; 3708; -.
DR MGI; MGI:96623; Itpr1.
DR VEuPathDB; HostDB:ENSMUSG00000030102; -.
DR eggNOG; KOG3533; Eukaryota.
DR GeneTree; ENSGT00940000155071; -.
DR HOGENOM; CLU_000206_1_0_1; -.
DR InParanoid; P11881; -.
DR OMA; GLIDKTW; -.
DR OrthoDB; 94996at2759; -.
DR PhylomeDB; P11881; -.
DR TreeFam; TF312815; -.
DR Reactome; R-MMU-114508; Effects of PIP2 hydrolysis.
DR Reactome; R-MMU-139853; Elevation of cytosolic Ca2+ levels.
DR Reactome; R-MMU-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-MMU-418457; cGMP effects.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR BioGRID-ORCS; 16438; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Itpr1; mouse.
DR EvolutionaryTrace; P11881; -.
DR PRO; PR:P11881; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P11881; protein.
DR Bgee; ENSMUSG00000030102; Expressed in cerebellar vermis and 266 other tissues.
DR ExpressionAtlas; P11881; baseline and differential.
DR Genevisible; P11881; MM.
DR GO; GO:0005955; C:calcineurin complex; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; IDA:MGI.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0031088; C:platelet dense granule membrane; ISO:MGI.
DR GO; GO:0031094; C:platelet dense tubular network; ISO:MGI.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0098793; C:presynapse; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IPI:MGI.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IMP:SynGO.
DR GO; GO:0030667; C:secretory granule membrane; ISO:MGI.
DR GO; GO:0030868; C:smooth endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0045202; C:synapse; IPI:MGI.
DR GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019855; F:calcium channel inhibitor activity; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0015278; F:calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IBA:GO_Central.
DR GO; GO:0098695; F:inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels; IMP:SynGO.
DR GO; GO:0005220; F:inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; IDA:MGI.
DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; ISO:MGI.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IGI:MGI.
DR GO; GO:0042045; P:epithelial fluid transport; IDA:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; ISO:MGI.
DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL.
DR GO; GO:0050882; P:voluntary musculoskeletal movement; IMP:MGI.
DR InterPro; IPR014821; Ins145_P3_rcpt.
DR InterPro; IPR000493; InsP3_rcpt.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR036300; MIR_dom_sf.
DR InterPro; IPR016093; MIR_motif.
DR InterPro; IPR013662; RIH_assoc-dom.
DR InterPro; IPR000699; RIH_dom.
DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf.
DR Pfam; PF08709; Ins145_P3_rec; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF02815; MIR; 1.
DR Pfam; PF08454; RIH_assoc; 1.
DR Pfam; PF01365; RYDR_ITPR; 2.
DR PRINTS; PR00779; INSP3RECEPTR.
DR SMART; SM00472; MIR; 4.
DR SUPFAM; SSF100909; SSF100909; 2.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50919; MIR; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Calcium; Calcium channel;
KW Calcium transport; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Endoplasmic reticulum; Ion channel;
KW Ion transport; Isopeptide bond; Ligand-gated ion channel; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..2749
FT /note="Inositol 1,4,5-trisphosphate receptor type 1"
FT /id="PRO_0000153921"
FT TOPO_DOM 1..2273
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2274..2294
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2295..2305
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2306..2326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2327..2352
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2353..2373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2374..2396
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2397..2417
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2418..2439
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2440..2460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2461..2569
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2570..2590
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2591..2749
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 112..166
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 173..223
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 231..287
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 294..373
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 379..435
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT REGION 1005..1026
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1136..1167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1695..1730
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1751..1788
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1881..1906
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1932..1952
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2463..2528
FT /note="Interaction with ERP44"
FT /evidence="ECO:0000269|PubMed:15652484"
FT REGION 2721..2749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1006..1023
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1145..1163
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1705..1719
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 265..269
FT /ligand="1D-myo-inositol 1,4,5-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:203600"
FT BINDING 508..511
FT /ligand="1D-myo-inositol 1,4,5-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:203600"
FT BINDING 567..569
FT /ligand="1D-myo-inositol 1,4,5-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:203600"
FT MOD_RES 482
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 1588
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17208939,
FT ECO:0007744|PubMed:18630941, ECO:0007744|PubMed:21183079"
FT MOD_RES 1755
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q14643, ECO:0000255"
FT MOD_RES 2655
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255"
FT LIPID 56
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:25368151"
FT LIPID 849
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:25368151"
FT CROSSLNK 916
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 962
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 1571
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 1771
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 1884
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 1885
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 1886
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 1901
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 1924
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 2118
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT CROSSLNK 2257
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P29994"
FT VAR_SEQ 318..332
FT /note="Missing (in isoform 2, isoform 4, isoform 6 and
FT isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_002691"
FT VAR_SEQ 1692..1714
FT /note="Missing (in isoform 7 and isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_002692"
FT VAR_SEQ 1715
FT /note="Missing (in isoform 3, isoform 4, isoform 5, isoform
FT 6, isoform 7 and isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_002693"
FT VAR_SEQ 1716..1731
FT /note="Missing (in isoform 5, isoform 6, isoform 7 and
FT isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_002694"
FT MUTAGEN 56
FT /note="C->A: Strongly reduced palmitoylation; when
FT associated with A-849 and A-2215."
FT /evidence="ECO:0000269|PubMed:25368151"
FT MUTAGEN 167
FT /note="Y->A: Nearly abolishes calcium flux."
FT /evidence="ECO:0000269|PubMed:20813840"
FT MUTAGEN 168
FT /note="K->A: Reduces calcium flux by about 50%."
FT /evidence="ECO:0000269|PubMed:20813840"
FT MUTAGEN 169
FT /note="L->A: Reduces calcium flux by about 50%."
FT /evidence="ECO:0000269|PubMed:20813840"
FT MUTAGEN 267
FT /note="T->A: Abolishes inositol 1,4,5-triphosphate
FT binding."
FT /evidence="ECO:0000269|PubMed:12442173"
FT MUTAGEN 567
FT /note="Y->A,F: Abolishes inositol 1,4,5-triphosphate
FT binding."
FT /evidence="ECO:0000269|PubMed:12442173"
FT MUTAGEN 849
FT /note="C->A: Strongly reduced palmitoylation; when
FT associated with A-56 and A-2215."
FT /evidence="ECO:0000269|PubMed:25368151"
FT MUTAGEN 1588
FT /note="S->A: Increases interaction with AHCYL1; when
FT associated with A-1755."
FT /evidence="ECO:0000269|PubMed:23542070"
FT MUTAGEN 1588
FT /note="S->E: Decreases interaction with AHCYL1; when
FT associated with A-1755."
FT /evidence="ECO:0000269|PubMed:23542070"
FT MUTAGEN 1755
FT /note="S->A: Increases interaction with AHCYL1; when
FT associated with A-1588."
FT /evidence="ECO:0000269|PubMed:23542070"
FT MUTAGEN 1755
FT /note="S->E: Decreases interaction with AHCYL1; when
FT associated with A-1588."
FT /evidence="ECO:0000269|PubMed:23542070"
FT MUTAGEN 2215
FT /note="C->A: Strongly reduced palmitoylation; when
FT associated with A-56 and A-849."
FT /evidence="ECO:0000269|PubMed:25368151"
FT MUTAGEN 2496
FT /note="C->S: No effect on channel activity. Significant
FT decrease of interaction with ERP44. Complete loss of
FT channel inhibition by ERP44."
FT /evidence="ECO:0000269|PubMed:15652484"
FT MUTAGEN 2504
FT /note="C->S: No effect on channel activity. Significant
FT decrease of interaction with ERP44. Complete loss of
FT channel inhibition by ERP44."
FT /evidence="ECO:0000269|PubMed:15652484"
FT MUTAGEN 2527
FT /note="C->S: Complete loss of channel activity. Significant
FT decrease of interaction with ERP44."
FT /evidence="ECO:0000269|PubMed:15652484"
FT CONFLICT 1264
FT /note="N -> K (in Ref. 1; CAA33433)"
FT /evidence="ECO:0000305"
FT CONFLICT 2675
FT /note="P -> L (in Ref. 1; CAA33433)"
FT /evidence="ECO:0000305"
FT STRAND 14..23
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 25..30
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:1XZZ"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:1XZZ"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:1XZZ"
FT HELIX 67..74
FT /evidence="ECO:0007829|PDB:1XZZ"
FT HELIX 86..109
FT /evidence="ECO:0007829|PDB:1XZZ"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:1XZZ"
FT TURN 126..129
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 130..139
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 146..154
FT /evidence="ECO:0007829|PDB:1XZZ"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 181..189
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:1XZZ"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:1N4K"
FT TURN 245..248
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 249..255
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 257..265
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 303..307
FT /evidence="ECO:0007829|PDB:1N4K"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 353..359
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 388..392
FT /evidence="ECO:0007829|PDB:1N4K"
FT TURN 393..396
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 397..406
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 409..412
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 415..423
FT /evidence="ECO:0007829|PDB:1N4K"
FT STRAND 430..434
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 437..461
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 467..484
FT /evidence="ECO:0007829|PDB:1N4K"
FT TURN 485..487
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 495..499
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 504..512
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 515..524
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 525..527
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 547..564
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 568..585
FT /evidence="ECO:0007829|PDB:1N4K"
FT HELIX 589..599
FT /evidence="ECO:0007829|PDB:1N4K"
SQ SEQUENCE 2749 AA; 313167 MW; FC4CF3ABB85EB82B CRC64;
MSDKMSSFLH IGDICSLYAE GSTNGFISTL GLVDDRCVVQ PEAGDLNNPP KKFRDCLFKL
CPMNRYSAQK QFWKAAKPGA NSTTDAVLLN KLHHAADLEK KQNETENRKL LGTVIQYGNV
IQLLHLKSNK YLTVNKRLPA LLEKNAMRVT LDEAGNEGSW FYIQPFYKLR SIGDSVVIGD
KVVLNPVNAG QPLHASSHQL VDNPGCNEVN SVNCNTSWKI VLFMKWSDNK DDILKGGDVV
RLFHAEQEKF LTCDEHRKKQ HVFLRTTGRQ SATSATSSKA LWEVEVVQHD PCRGGAGYWN
SLFRFKHLAT GHYLAAEVDP DFEEECLEFQ PSVDPDQDAS RSRLRNAQEK MVYSLVSVPE
GNDISSIFEL DPTTLRGGDS LVPRNSYVRL RHLCTNTWVH STNIPIDKEE EKPVMLKIGT
SPLKEDKEAF AIVPVSPAEV RDLDFANDAS KVLGSIAGKL EKGTITQNER RSVTKLLEDL
VYFVTGGTNS GQDVLEVVFS KPNRERQKLM REQNILKQIF KLLQAPFTDC GDGPMLRLEE
LGDQRHAPFR HICRLCYRVL RHSQQDYRKN QEYIAKQFGF MQKQIGYDVL AEDTITALLH
NNRKLLEKHI TAAEIDTFVS LVRKNREPRF LDYLSDLCVS MNKSIPVTQE LICKAVLNPT
NADILIETKL VLSRFEFEGV STGENALEAG EDEEEVWLFW RDSNKEIRSK SVRELAQDAK
EGQKEDRDIL SYYRYQLNLF ARMCLDRQYL AINEISGQLD VDLILRCMSD ENLPYDLRAS
FCRLMLHMHV DRDPQEQVTP VKYARLWSEI PSEIAIDDYD SSGTSKDEIK ERFAQTMEFV
EEYLRDVVCQ RFPFSDKEKN KLTFEVVNLA RNLIYFGFYN FSDLLRLTKI LLAILDCVHV
TTIFPISKMT KGEENKGSNV MRSIHGVGEL MTQVVLRGGG FLPMTPMAAA PEGNVKQAEP
EKEDIMVMDT KLKIIEILQF ILNVRLDYRI SCLLCIFKRE FDESNSQSSE TSSGNSSQEG
PSNVPGALDF EHIEEQAEGI FGGSEENTPL DLDDHGGRTF LRVLLHLTMH DYPPLVSGAL
QLLFRHFSQR QEVLQAFKQV QLLVTSQDVD NYKQIKQDLD QLRSIVEKSE LWVYKGQGPD
EPMDGASGEN EHKKTEEGTS KPLKHESTSS YNYRVVKEIL IRLSKLCVQE SASVRKSRKQ
QQRLLRNMGA HAVVLELLQI PYEKAEDTKM QEIMRLAHEF LQNFCAGNQQ NQALLHKHIN
LFLNPGILEA VTMQHIFMNN FQLCSEINER VVQHFVHCIE THGRNVQYIK FLQTIVKAEG
KFIKKCQDMV MAELVNSGED VLVFYNDRAS FQTLIQMMRS ERDRMDENSP LMYHIHLVEL
LAVCTEGKNV YTEIKCNSLL PLDDIVRVVT HEDCIPEVKI AYINFLNHCY VDTEVEMKEI
YTSNHMWKLF ENFLVDICRA CNNTSDRKHA DSILEKYVTE IVMSIVTTFF SSPFSDQSTT
LQTRQPVFVQ LLQGVFRVYH CNWLMPSQKA SVESCIRVLS DVAKSRAIAI PVDLDSQVNN
LFLKSHNIVQ KTALNWRLSA RNAARRDSVL AASRDYRNII ERLQDIVSAL EDRLRPLVQA
ELSVLVDVLH RPELLFPENT DARRKCESGG FICKLIKHTK QLLEENEEKL CIKVLQTLRE
MMTKDRGYGE KQISIDESEN AELPQAPEAE NSTEQELEPS PPLRQLEDHK RGEALRQILV
NRYYGNIRPS GRRESLTSFG NGPLSPGGPS KPGGGGGGPG SSSTSRGEMS LAEVQCHLDK
EGASNLVIDL IMNASSDRVF HESILLAIAL LEGGNTTIQH SFFCRLTEDK KSEKFFKVFY
DRMKVAQQEI KATVTVNTSD LGNKKKDDEV DRDAPSRKKA KEPTTQITEE VRDQLLEASA
ATRKAFTTFR READPDDHYQ SGEGTQATTD KAKDDLEMSA VITIMQPILR FLQLLCENHN
RDLQNFLRCQ NNKTNYNLVC ETLQFLDCIC GSTTGGLGLL GLYINEKNVA LINQTLESLT
EYCQGPCHEN QNCIATHESN GIDIITALIL NDINPLGKKR MDLVLELKNN ASKLLLAIME
SRHDSENAER ILYNMRPKEL VEVIKKAYMQ GEVEFEDGEN GEDGAASPRN VGHNIYILAH
QLARHNKELQ TMLKPGGQVD GDEALEFYAK HTAQIEIVRL DRTMEQIVFP VPSICEFLTK
ESKLRIYYTT ERDEQGSKIN DFFLRSEDLF NEMNWQKKLR AQPVLYWCAR NMSFWSSISF
NLAVLMNLLV AFFYPFKGVR GGTLEPHWSG LLWTAMLISL AIVIALPKPH GIRALIASTI
LRLIFSVGLQ PTLFLLGAFN VCNKIIFLMS FVGNCGTFTR GYRAMVLDVE FLYHLLYLLI
CAMGLFVHEF FYSLLLFDLV YREETLLNVI KSVTRNGRSI ILTAVLALIL VYLFSIVGYL
FFKDDFILEV DRLPNETAVP ETGESLANDF LYSDVCRVET GENCTSPAPK EELLPAEETE
QDKEHTCETL LMCIVTVLSH GLRSGGGVGD VLRKPSKEEP LFAARVIYDL LFFFMVIIIV
LNLIFGVIID TFADLRSEKQ KKEEILKTTC FICGLERDKF DNKTVTFEEH IKEEHNMWHY
LCFIVLVKVK DSTEYTGPES YVAEMIRERN LDWFPRMRAM SLVSSDSEGE QNELRNLQEK
LESTMKLVTN LSGQLSELKD QMTEQRKQKQ RIGLLGHPPH MNVNPQQPA
