ID ITPR1_RAT Reviewed; 2750 AA. AC P29994; Q62869; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2001, sequence version 2. DT 27-MAR-2024, entry version 209. DE RecName: Full=Inositol 1,4,5-trisphosphate receptor type 1; DE AltName: Full=IP3 receptor isoform 1; DE Short=IP-3-R; DE Short=IP3R 1; DE Short=InsP3R1; DE AltName: Full=Type 1 inositol 1,4,5-trisphosphate receptor; DE Short=Type 1 InsP3 receptor; GN Name=Itpr1; Synonyms=Insp3r; 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 [MRNA] (ISOFORMS 3 AND 4), TISSUE SPECIFICITY, AND RP VARIANT PHE-1372 DEL. RX PubMed=2165071; DOI=10.1016/s0021-9258(19)38397-8; RA Mignery G.A., Newton C.L., Archer B.T. III, Suedhof T.C.; RT "Structure and expression of the rat inositol 1,4,5-trisphosphate RT receptor."; RL J. Biol. Chem. 265:12679-12685(1990). RN [2] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 7), AND TISSUE RP SPECIFICITY. RC TISSUE=Brain; RX PubMed=1849282; DOI=10.1073/pnas.88.7.2951; RA Danoff S.K., Ferris C.D., Donath C., Fischer G.A., Munemitsu S., RA Ullrich A., Snyder S.H., Ross C.A.; RT "Inositol 1,4,5-trisphosphate receptors: distinct neuronal and nonneuronal RT forms derived by alternative splicing differ in phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 88:2951-2955(1991). RN [3] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4; 7 AND 8). RC STRAIN=Sprague-Dawley; RX PubMed=9073177; DOI=10.1016/s0169-328x(96)00282-3; RA Smutzer G., Zimmerman J.E., Hahn C.-G., Ruscheinsky D.D., Rodriguez A., RA Han L.-Y., Arnold S.E.; RT "Inositol 1,4,5-trisphosphate receptor expression in mammalian olfactory RT tissue."; RL Brain Res. Mol. Brain Res. 44:347-354(1997). RN [4] RP CHARACTERIZATION. RX PubMed=10506212; DOI=10.1074/jbc.274.41.29483; RA Galvan D.L., Borrego-Diaz E., Perez P.J., Mignery G.A.; RT "Subunit oligomerization, and topology of the inositol 1,4, 5-trisphosphate RT receptor."; RL J. Biol. Chem. 274:29483-29492(1999). RN [5] RP INTERACTION WITH TRPC4. RX PubMed=11163362; DOI=10.1016/s0014-5793(00)02362-0; RA Mery L., Magnino F., Schmidt K., Krause K.-H., Dufour J.-F.; RT "Alternative splice variants of hTrp4 differentially interact with the C- RT terminal portion of the inositol 1,4,5-trisphosphate receptors."; RL FEBS Lett. 487:377-383(2001). RN [6] RP INTERACTION WITH CABP1. RX PubMed=12032348; DOI=10.1073/pnas.102006299; RA Yang J., McBride S., Mak D.-O.D., Vardi N., Palczewski K., Haeseleer F., RA Foskett J.K.; RT "Identification of a family of calcium sensors as protein ligands of RT inositol trisphosphate receptor Ca(2+) release channels."; RL Proc. Natl. Acad. Sci. U.S.A. 99:7711-7716(2002). RN [7] RP UBIQUITINATION AT LYS-916; LYS-962; LYS-1572; LYS-1772; LYS-1885; LYS-1886; RP LYS-1887; LYS-1902; LYS-1925; LYS-2119 AND LYS-2258. RX PubMed=18955483; DOI=10.1074/jbc.m807288200; RA Sliter D.A., Kubota K., Kirkpatrick D.S., Alzayady K.J., Gygi S.P., RA Wojcikiewicz R.J.; RT "Mass spectrometric analysis of type 1 inositol 1,4,5-trisphosphate RT receptor ubiquitination."; RL J. Biol. Chem. 283:35319-35328(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1589 AND SER-1756, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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 Plays a role CC in ER stress-induced apoptosis. Cytoplasmic calcium released from the CC ER triggers apoptosis by the activation of CaM kinase II, eventually CC leading to the activation of downstream apoptosis pathways. CC {ECO:0000250|UniProtKB:P11881}. CC -!- SUBUNIT: Homotetramer. Interacts with TRPC4 (PubMed:11163362). The CC PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, CC ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox CC state- and calcium-dependent manner which results in the inhibition the CC calcium channel activity. The strength of this interaction inversely CC correlates with calcium concentration. Part of cGMP kinase signaling CC complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, CC PLN/phospholamban, PRKG1 and ITPR1. Interacts with IRAG1 (By CC similarity). Interacts with CABP1 (via N-terminus) (PubMed:12032348). CC Interacts with TESPA1. Interacts (when not phosphorylated) with AHCYL1 CC (when phosphorylated); the interaction suppresses inositol 1,4,5- CC trisphosphate binding to ITPR1 and is increased in the presence of CC BCL2L10. Interacts with AHCYL2 (with lower affinity than with AHCYL1) CC (By similarity). Interacts with BCL2L10; the interaction is increased CC in the presence of AHCLY1 (By similarity). Interacts with BOK (via BH4. CC domain); protects ITPR1 from proteolysis by CASP3 during apoptosis (By CC similarity). {ECO:0000250|UniProtKB:P11881, CC ECO:0000250|UniProtKB:Q14643, ECO:0000250|UniProtKB:Q9TU34, CC ECO:0000269|PubMed:11163362, ECO:0000269|PubMed:12032348}. CC -!- INTERACTION: CC P29994; P54256-1: Hap1; NbExp=2; IntAct=EBI-8614640, EBI-994549; CC P29994; P54256-2: Hap1; NbExp=4; IntAct=EBI-8614640, EBI-994554; CC P29994; P51111: Htt; NbExp=4; IntAct=EBI-8614640, EBI-9674649; CC P29994; P42858: HTT; Xeno; NbExp=2; IntAct=EBI-8614640, EBI-466029; CC P29994-1; P29994-1: Itpr1; NbExp=2; IntAct=EBI-15683709, EBI-15683709; CC P29994-1; Q3U182: Crtc2; Xeno; NbExp=2; IntAct=EBI-15683709, EBI-8018890; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9TU34}; 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 (By similarity). {ECO:0000250|UniProtKB:Q9TU34}. 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=P29994-1; Sequence=Displayed; CC Name=2; Synonyms=SI-SIIABC; CC IsoId=P29994-2; Sequence=VSP_002695; CC Name=3; Synonyms=SISIIAC; CC IsoId=P29994-3; Sequence=VSP_002697; CC Name=4; Synonyms=SI-SIIAC; CC IsoId=P29994-4; Sequence=VSP_002695, VSP_002697; CC Name=5; Synonyms=SISIIA; CC IsoId=P29994-5; Sequence=VSP_002697, VSP_002698; CC Name=6; Synonyms=SI-SIIA; CC IsoId=P29994-6; Sequence=VSP_002695, VSP_002697, VSP_002698; CC Name=7; Synonyms=SISII; CC IsoId=P29994-7; Sequence=VSP_002696, VSP_002697, VSP_002698; CC Name=8; Synonyms=SI-SII; CC IsoId=P29994-8; Sequence=VSP_002695, VSP_002696, VSP_002697, CC VSP_002698; CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in the brain. CC {ECO:0000269|PubMed:2165071}. CC -!- TISSUE SPECIFICITY: [Isoform 7]: Expressed in the fetal brain and CC peripheral tissues. {ECO:0000269|PubMed:1849282}. 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:0000250|UniProtKB:P11881}. 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. {ECO:0000269|PubMed:18955483}. CC -!- PTM: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of CC ITPR1 stability and function. {ECO:0000250|UniProtKB:P11881}. 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 --------------------------------------------------------------------------- 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; J05510; AAA41358.1; -; mRNA. DR EMBL; J05510; AAA41357.1; -; mRNA. DR EMBL; M64699; AAA41447.1; -; mRNA. DR EMBL; M64698; AAA41448.1; -; mRNA. DR EMBL; U38653; AAC53099.1; -; mRNA. DR EMBL; U38812; AAC53100.1; -; mRNA. DR EMBL; U38665; AAB51330.1; -; mRNA. DR PIR; A36579; A36579. DR PIR; B36579; B36579. DR RefSeq; NP_001257526.1; NM_001270597.1. DR PDB; 3JAV; EM; 4.70 A; A/B/C/D=1-2750. DR PDB; 3T8S; X-ray; 3.77 A; A/B=7-602. DR PDB; 3UJ0; X-ray; 3.60 A; A/B=1-604. DR PDB; 3UJ4; X-ray; 3.00 A; A/B=1-604. DR PDB; 6MU1; EM; 4.10 A; A/B/C/D=1-2739. DR PDB; 6MU2; EM; 3.90 A; A/B/C/D=1-2750. DR PDB; 7LHE; EM; 3.30 A; A/B/C/D=6-2739. DR PDB; 7LHF; EM; 2.96 A; A/B/C/D=6-2741. DR PDB; 8EAQ; EM; 3.26 A; A/B/C/D=1-2750. DR PDB; 8EAR; EM; 3.50 A; A/B/C/D=1-2750. DR PDBsum; 3JAV; -. DR PDBsum; 3T8S; -. DR PDBsum; 3UJ0; -. DR PDBsum; 3UJ4; -. DR PDBsum; 6MU1; -. DR PDBsum; 6MU2; -. DR PDBsum; 7LHE; -. DR PDBsum; 7LHF; -. DR PDBsum; 8EAQ; -. DR PDBsum; 8EAR; -. DR EMDB; EMD-23337; -. DR EMDB; EMD-23338; -. DR EMDB; EMD-27982; -. DR EMDB; EMD-27983; -. DR EMDB; EMD-6369; -. DR EMDB; EMD-9243; -. DR EMDB; EMD-9244; -. DR EMDB; EMD-9247; -. DR EMDB; EMD-9248; -. DR SMR; P29994; -. DR BioGRID; 247302; 15. DR CORUM; P29994; -. DR DIP; DIP-29715N; -. DR IntAct; P29994; 9. DR MINT; P29994; -. DR STRING; 10116.ENSRNOP00000043615; -. DR BindingDB; P29994; -. DR ChEMBL; CHEMBL2804; -. DR GlyGen; P29994; 1 site, 1 N-linked glycan (1 site). DR iPTMnet; P29994; -. DR PhosphoSitePlus; P29994; -. DR SwissPalm; P29994; -. DR jPOST; P29994; -. DR PaxDb; 10116-ENSRNOP00000063885; -. DR ABCD; P29994; 1 sequenced antibody. DR GeneID; 25262; -. DR KEGG; rno:25262; -. DR AGR; RGD:2933; -. DR CTD; 3708; -. DR RGD; 2933; Itpr1. DR eggNOG; KOG3533; Eukaryota. DR InParanoid; P29994; -. DR OrthoDB; 5480299at2759; -. DR PhylomeDB; P29994; -. DR Reactome; R-RNO-114508; Effects of PIP2 hydrolysis. DR Reactome; R-RNO-139853; Elevation of cytosolic Ca2+ levels. DR Reactome; R-RNO-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion. DR Reactome; R-RNO-418457; cGMP effects. DR Reactome; R-RNO-5578775; Ion homeostasis. DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR PRO; PR:P29994; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005955; C:calcineurin complex; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:RGD. DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO. DR GO; GO:0016020; C:membrane; IDA:SynGO. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005635; C:nuclear envelope; IDA:RGD. DR GO; GO:0005637; C:nuclear inner membrane; ISO:RGD. DR GO; GO:0005730; C:nucleolus; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0031088; C:platelet dense granule membrane; ISO:RGD. DR GO; GO:0031094; C:platelet dense tubular network; ISO:RGD. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0014069; C:postsynaptic density; ISO:RGD. DR GO; GO:0098793; C:presynapse; IDA:SynGO. DR GO; GO:0032991; C:protein-containing complex; IDA:RGD. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:RGD. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD. DR GO; GO:0030667; C:secretory granule membrane; IBA:GO_Central. DR GO; GO:0030868; C:smooth endoplasmic reticulum membrane; IDA:SynGO. DR GO; GO:0045202; C:synapse; ISO:RGD. DR GO; GO:0097060; C:synaptic membrane; IDA:RGD. DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0019855; F:calcium channel inhibitor activity; ISO:RGD. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. 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; ISO:RGD. DR GO; GO:0005220; F:inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; IDA:RGD. DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD. DR GO; GO:0019903; F:protein phosphatase binding; IDA:RGD. DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD. DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:RGD. DR GO; GO:0006816; P:calcium ion transport; ISO:RGD. DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD. DR GO; GO:0000902; P:cell morphogenesis; ISO:RGD. DR GO; GO:0071320; P:cellular response to cAMP; IDA:RGD. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD. DR GO; GO:0016358; P:dendrite development; IEP:RGD. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISO:RGD. DR GO; GO:0042045; P:epithelial fluid transport; ISO:RGD. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB. DR GO; GO:0099105; P:ion channel modulating, G protein-coupled receptor signaling pathway; ISO:RGD. DR GO; GO:1990806; P:ligand-gated ion channel signaling pathway; ISO:RGD. DR GO; GO:0097421; P:liver regeneration; IMP:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD. DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; ISO:RGD. DR GO; GO:0007207; P:phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway; ISO:RGD. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISO:RGD. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:0051928; P:positive regulation of calcium ion transport; IDA:RGD. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD. DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IMP:RGD. DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:RGD. DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD. DR GO; GO:0009791; P:post-embryonic development; ISO:RGD. DR GO; GO:0099566; P:regulation of postsynaptic cytosolic calcium ion concentration; ISO:RGD. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; ISO:RGD. DR GO; GO:0050882; P:voluntary musculoskeletal movement; ISO:RGD. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 2.80.10.50; -; 2. DR Gene3D; 1.25.10.30; IP3 receptor type 1 binding core, RIH domain; 1. DR InterPro; IPR016024; ARM-type_fold. 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; IPR015925; Ryanodine_IP3_receptor. DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf. DR PANTHER; PTHR45816:SF2; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; 1. DR PANTHER; PTHR45816; MIR DOMAIN-CONTAINING PROTEIN; 1. 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; SSF48371; ARM repeat; 1. DR SUPFAM; SSF100909; IP3 receptor type 1 binding core, domain 2; 2. DR SUPFAM; SSF82109; MIR domain; 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; Endoplasmic reticulum; KW Ion channel; Ion transport; Isopeptide bond; Ligand-gated ion channel; KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport; KW Ubl conjugation. FT CHAIN 1..2750 FT /note="Inositol 1,4,5-trisphosphate receptor type 1" FT /id="PRO_0000153922" FT TOPO_DOM 1..2274 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2275..2295 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2296..2306 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2307..2327 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2328..2353 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2354..2374 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2375..2397 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2398..2418 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2419..2440 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2441..2461 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2462..2569 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2570..2590 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2591..2750 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 1705..1731 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1752..1790 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1882..1907 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1933..1953 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2464..2529 FT /note="Interaction with ERP44" FT REGION 2723..2750 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 BINDING 265..269 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000250" FT BINDING 508..511 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000250" FT BINDING 567..569 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000250" FT MOD_RES 482 FT /note="Phosphotyrosine" FT /evidence="ECO:0000255" FT MOD_RES 1589 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 1756 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 2656 FT /note="Phosphotyrosine" FT /evidence="ECO:0000255" FT LIPID 56 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P11881" FT LIPID 849 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P11881" FT CROSSLNK 916 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 962 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 1572 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 1772 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 1885 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 1886 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 1887 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 1902 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 1925 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 2119 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT CROSSLNK 2258 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18955483" FT VAR_SEQ 322..336 FT /note="Missing (in isoform 2, isoform 4, isoform 6 and FT isoform 8)" FT /evidence="ECO:0000303|PubMed:2165071" FT /id="VSP_002695" FT VAR_SEQ 1693..1715 FT /note="Missing (in isoform 7 and isoform 8)" FT /evidence="ECO:0000305" FT /id="VSP_002696" FT VAR_SEQ 1716 FT /note="Missing (in isoform 3, isoform 4, isoform 5, isoform FT 6, isoform 7 and isoform 8)" FT /evidence="ECO:0000303|PubMed:2165071" FT /id="VSP_002697" FT VAR_SEQ 1717..1732 FT /note="Missing (in isoform 5, isoform 6, isoform 7 and FT isoform 8)" FT /evidence="ECO:0000305" FT /id="VSP_002698" FT VARIANT 1372 FT /note="Missing (in all but PI17 clones)" FT /evidence="ECO:0000269|PubMed:2165071" FT CONFLICT 1764 FT /note="P -> R (in Ref. 2; AAA41447/AAA41448)" FT /evidence="ECO:0000305" FT STRAND 14..23 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 25..30 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 41..43 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 53..56 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 57..61 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 67..74 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 87..108 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 109..112 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 120..125 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 126..129 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 130..139 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 147..154 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 157..159 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 161..167 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 181..189 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 193..199 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 201..203 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 207..213 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 217..224 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 239..244 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 245..248 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 249..256 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 259..265 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 271..273 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 281..286 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 290..292 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 302..307 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 308..310 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 313..318 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 353..359 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 364..366 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 368..374 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 387..392 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 393..395 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 398..406 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 408..412 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 415..423 FT /evidence="ECO:0007829|PDB:3UJ4" FT STRAND 430..434 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 437..462 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 467..483 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 504..512 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 515..522 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 537..543 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 552..562 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 563..566 FT /evidence="ECO:0007829|PDB:3UJ4" FT HELIX 568..575 FT /evidence="ECO:0007829|PDB:3UJ4" FT TURN 576..584 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 585..589 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 591..598 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 603..608 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 612..620 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 621..624 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 629..638 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 641..643 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 646..656 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 659..661 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 663..665 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 703..706 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 713..717 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 720..722 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 725..727 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 728..741 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 744..747 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 750..753 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 754..757 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 762..767 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 776..785 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 786..788 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 792..794 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 807..809 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 823..825 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 827..829 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 831..850 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 857..859 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 860..875 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 881..891 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 892..894 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 965..1003 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1027..1040 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1059..1068 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1069..1072 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1075..1086 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1089..1100 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1113..1123 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1125..1127 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1173..1188 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1195..1198 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1199..1203 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1204..1206 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1207..1211 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1212..1218 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1226..1228 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1231..1244 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1245..1247 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1249..1255 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1256..1258 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1261..1264 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1270..1276 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1281..1283 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1289..1291 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1292..1294 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1296..1299 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1306..1310 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1312..1315 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1316..1321 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1327..1336 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1347..1358 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1363..1365 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1371..1373 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1374..1377 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1380..1383 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1384..1386 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1387..1389 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1395..1399 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1404..1411 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1417..1431 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1441..1461 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1600..1612 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1615..1629 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1635..1638 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1642..1647 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1648..1650 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1652..1660 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1663..1667 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1670..1683 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1685..1688 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1728..1744 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1792..1802 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1804..1811 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1812..1814 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1818..1832 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1837..1846 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1853..1868 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1869..1873 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1961..1965 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1966..1976 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1978..1980 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1982..1986 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 1987..1989 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 1993..1995 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 1999..2011 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2013..2016 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 2017..2019 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 2022..2024 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 2027..2029 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2030..2042 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 2049..2052 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2053..2056 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2057..2060 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2063..2066 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2068..2071 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2079..2081 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2082..2099 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2106..2113 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2119..2131 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2151..2163 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 2164..2166 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2170..2173 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2183..2191 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2193..2199 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2205..2211 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 2214..2217 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2221..2230 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2235..2237 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2240..2260 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2265..2271 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2273..2293 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2306..2326 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2333..2347 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2350..2374 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2383..2388 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2390..2407 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2408..2410 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2413..2421 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2425..2435 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2438..2461 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2464..2466 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2531..2533 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2534..2541 FT /evidence="ECO:0007829|PDB:7LHE" FT TURN 2550..2552 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2563..2608 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2618..2620 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2628..2634 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2638..2650 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2653..2655 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2658..2668 FT /evidence="ECO:0007829|PDB:7LHE" FT STRAND 2681..2683 FT /evidence="ECO:0007829|PDB:7LHE" FT HELIX 2688..2735 FT /evidence="ECO:0007829|PDB:7LHE" SQ SEQUENCE 2750 AA; 313264 MW; 174BB77CBF6F21AC 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 EGQKEDRDVL SYYRYQLNLF ARMCLDRQYL AINEISGQLD VDLILRCMSD ENLPYDLRAS FCRLMLHMHV DRDPQEQVTP VKYARLWSEI PSEIAIDDYD SSGASKDEIK 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 LFMYHIHLVE LLAVCTEGKN VYTEIKCNSL LPLDDIVRVV THEDCIPEVK IAYINFLNHC YVDTEVEMKE IYTSNHMWKL FENFLVDICR ACNNTSDRKH ADSVLEKYVT EIVMSIVTTF FSSPFSDQST TLQTRQPVFV QLLQGVFRVY HCNWLMPSQK ASVESCIRVL SDVAKSRAIA IPVDLDSQVN NLFLKSHNIV QKTAMNWRLS ARNAARRDSV LAASRDYRNI IERLQDIVSA LEDRLRPLVQ AELSVLVDVL HRPELLFPEN TDARRKCESG GFICKLIKHT KQLLEENEEK LCIKVLQTLR EMMTKDRGYG EKQISIDELE NAELPQPPEA ENSTEQELEP SPPLRQLEDH KRGEALRQIL VNRYYGNIRP SGRRESLTSF GNGPLSPGGP SKPGGGGGGP GSGSTSRGEM SLAEVQCHLD KEGASNLVID LIMNASSDRV FHESILLAIA LLEGGNTTIQ HSFFCRLTED KKSEKFFKVF YDRMKVAQQE IKATVTVNTS DLGNKKKDDE VDRDAPSRKK AKEPTTQITE EVRDQLLEAS AATRKAFTTF RREADPDDHY QSGEGTQATT DKAKDDLEMS AVITIMQPIL RFLQLLCENH NRDLQNFLRC QNNKTNYNLV CETLQFLDCI CGSTTGGLGL LGLYINEKNV ALINQTLESL TEYCQGPCHE NQNCIATHES NGIDIITALI LNDINPLGKK RMDLVLELKN NASKLLLAIM ESRHDSENAE RILYNMRPKE LVEVIKKAYM QGEVEFEDGE NGEDGAASPR NVGHNIYILA HQLARHNKEL QTMLKPGGQV DGDEALEFYA KHTAQIEIVR LDRTMEQIVF PVPSICEFLT KESKLRIYYT TERDEQGSKI NDFFLRSEDL FNEMNWQKKL RAQPVLYWCA RNMSFWSSIS FNLAVLMNLL VAFFYPFKGV RGGTLEPHWS GLLWTAMLIS LAIVIALPKP HGIRALIAST ILRLIFSVGL QPTLFLLGAF NVCNKIIFLM SFVGNCGTFT RGYRAMVLDV EFLYHLLYLL ICAMGLFVHE FFYSLLLFDL VYREETLLNV IKSVTRNGRP IILTAALALI LVYLFSIVGY LFFKDDFILE VDRLPNETAG PETGESLAND FLYSDVCRVE TGENCTSPAP KEELLPVEET EQDKEHTCET LLMCIVTVLS HGLRSGGGVG DVLRKPSKEE PLFAARVIYD LLFFFMVIII VLNLIFGVII DTFADLRSEK QKKEEILKTT CFICGLERDK FDNKTVTFEE HIKEEHNMWH YLCFIVLVKV KDSTEYTGPE SYVAEMIRER NLDWFPRMRA MSLVSSDSEG EQNELRNLQE KLESTMKLVT NLSGQLSELK DQMTEQRKQK QRIGLLGHPP HMNVNPQQPA //