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Protein

Inositol 1,4,5-trisphosphate receptor type 1

Gene

ITPR1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Apoptosis, Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
Recommended name:
Inositol 1,4,5-trisphosphate receptor type 1
Alternative name(s):
IP3 receptor isoform 1
Short name:
IP3R 1
Short name:
InsP3R1
Type 1 inositol 1,4,5-trisphosphate receptor
Short name:
Type 1 InsP3 receptor
Gene namesi
Name:ITPR1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 22332233CytoplasmicSequence analysisAdd
BLAST
Transmembranei2234 – 225421HelicalSequence analysisAdd
BLAST
Topological domaini2255 – 226612LumenalSequence analysisAdd
BLAST
Transmembranei2267 – 228721HelicalSequence analysisAdd
BLAST
Topological domaini2288 – 231225CytoplasmicSequence analysisAdd
BLAST
Transmembranei2313 – 233321HelicalSequence analysisAdd
BLAST
Topological domaini2334 – 235623LumenalSequence analysisAdd
BLAST
Transmembranei2357 – 237721HelicalSequence analysisAdd
BLAST
Topological domaini2378 – 239922CytoplasmicSequence analysisAdd
BLAST
Transmembranei2400 – 242021HelicalSequence analysisAdd
BLAST
Topological domaini2421 – 2528108LumenalSequence analysisAdd
BLAST
Transmembranei2529 – 254921HelicalSequence analysisAdd
BLAST
Topological domaini2550 – 2709160CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • rough endoplasmic reticulum Source: CACAO
  • secretory granule Source: CACAO
  • transport vesicle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 27092709Inositol 1,4,5-trisphosphate receptor type 1PRO_0000153919Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei482 – 4821PhosphotyrosineSequence analysis
Cross-linki916 – 916Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki962 – 962Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1571 – 1571Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei1588 – 15881PhosphoserineBy similarity
Modified residuei1715 – 17151Phosphoserine; by PKASequence analysisBy similarity
Cross-linki1731 – 1731Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1844 – 1844Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1845 – 1845Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1846 – 1846Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1861 – 1861Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1884 – 1884Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki2078 – 2078Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki2217 – 2217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei2615 – 26151PhosphotyrosineSequence analysis

Post-translational modificationi

Phosphorylated by cAMP kinase (PKA). Phosphorylation prevents the ligand-induced opening of the calcium channels. Phosphorylation by PKA increases the interaction with inositol 1,4,5-trisphosphate and decreases the interaction with AHCYL1.By similarity
Phosphorylated on tyrosine residues.By similarity
Ubiquitination at multiple lysines targets ITPR1 for proteasomal degradation. Approximately 40% of the ITPR1-associated ubiquitin is monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'-linked (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9TU34.
PRIDEiQ9TU34.

Interactioni

Subunit structurei

omotetramer. Interacts with TRPC4. The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium-dependent manner which results in the inhibition the calcium channel activity. The strength of this interaction inversely correlates with calcium concentration. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with MRVI1 and CABP1 (via N-terminus). Interacts with TESPA1. Interacts (when not phosphorylated) with AHCYL1 (when phosphorylated); the interaction suppresses inositol 1,4,5-trisphosphate binding to ITPR1. Interacts with AHCYL2 (with lower affinity than with AHCYL1) (By similarity).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000047903.

Structurei

3D structure databases

ProteinModelPortaliQ9TU34.
SMRiQ9TU34. Positions 7-225, 236-602.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini112 – 16655MIR 1PROSITE-ProRule annotationAdd
BLAST
Domaini173 – 22351MIR 2PROSITE-ProRule annotationAdd
BLAST
Domaini231 – 28757MIR 3PROSITE-ProRule annotationAdd
BLAST
Domaini294 – 37380MIR 4PROSITE-ProRule annotationAdd
BLAST
Domaini379 – 43557MIR 5PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni265 – 2695Inositol 1,4,5-trisphosphate bindingBy similarity
Regioni508 – 5114Inositol 1,4,5-trisphosphate bindingBy similarity
Regioni567 – 5693Inositol 1,4,5-trisphosphate bindingBy similarity
Regioni2423 – 248866Interaction with ERP44By similarityAdd
BLAST

Domaini

The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.

Sequence similaritiesi

Belongs to the InsP3 receptor family.Curated
Contains 5 MIR domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3533. Eukaryota.
ENOG410XR97. LUCA.
HOGENOMiHOG000007660.
HOVERGENiHBG052158.
InParanoidiQ9TU34.
KOiK04958.

Family and domain databases

Gene3Di1.25.10.30. 2 hits.
InterProiIPR016024. ARM-type_fold.
IPR014821. Ins145_P3_rcpt.
IPR000493. InsP3_rcpt-bd.
IPR005821. Ion_trans_dom.
IPR016093. MIR_motif.
IPR013662. RIH_assoc-dom.
IPR000699. RIH_dom.
IPR015925. Ryanodine_recept-rel.
[Graphical view]
PANTHERiPTHR13715. PTHR13715. 1 hit.
PfamiPF08709. Ins145_P3_rec. 1 hit.
PF00520. Ion_trans. 1 hit.
PF02815. MIR. 1 hit.
PF08454. RIH_assoc. 1 hit.
PF01365. RYDR_ITPR. 2 hits.
[Graphical view]
PRINTSiPR00779. INSP3RECEPTR.
SMARTiSM00472. MIR. 4 hits.
[Graphical view]
SUPFAMiSSF100909. SSF100909. 2 hits.
SSF48371. SSF48371. 7 hits.
SSF82109. SSF82109. 2 hits.
PROSITEiPS50919. MIR. 5 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9TU34-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSDKMSSFLH IGDICSLYAE GSTNGFISTL GLVDDRCVVQ PETGDLNNPP
60 70 80 90 100
KKFRDCLFKL CPMNRYSAQK QFWKAAKPGA NSTTDAVLLN KLHHAADLEK
110 120 130 140 150
KQNETENRKL LGTVIQYGNV IQLLHLKSNK YLTVNKRLPA LLEKNAMRVT
160 170 180 190 200
LDEAGNEGSW FYIQPFYKLR SIGDSVVIGD KVVLNPVNAG QPLHASSHQL
210 220 230 240 250
VDNPGCNEVN SVNCNTSWKI VLFMKWSDNK DDILKGGDVV RLFHAEQEKF
260 270 280 290 300
LTCDEHRKKQ HVFLRTTGRQ SATSATSSKA LWEVEVVQHD PCRGGAGYWN
310 320 330 340 350
SLFRFKHLAT GHYLAAEVDP DFEEECLEFQ PSVDPDQDAS RSRLRNAQEK
360 370 380 390 400
MVYSLVSVPE GNDISSIFEL DPTTLRGGDS LVPRNSYVRL RHLCTNTWVH
410 420 430 440 450
STNIPIDKEE EKPVMLKIGT SPVKEDKEAF AIVPVSPAEV RDLDFANDAS
460 470 480 490 500
KVLGSIAGKL EKGTITQNER RSVTKLLEDL VYFVTGGTNS GQDVLEVVFS
510 520 530 540 550
KPNRERQKLM REQNILKQIF KLLQAPFTDC GDGPMLRLEE LGDQRHAPFR
560 570 580 590 600
HICRLCYRVL RHSQQDYRKN QEYIAKQFGF MQKQIGYDVL AEDTITALLH
610 620 630 640 650
NNRKLLEKHI TAAEIDTFVS LVRKNREPRF LDYLSDLCVS MNKSIPVTQE
660 670 680 690 700
LICKAVLNPT NADILIETKL VLSRFEFEGV STGENALEAG EDEEEVWVFW
710 720 730 740 750
RDSNKEVRSK SVRELAQDAK EGQKEDRDVL GYYRYQLNLF ARMCLDRQYL
760 770 780 790 800
AINEISGQLD VDLILRCMSD ENLPSDLRAS FCRLMLHMHV DRDPQEQVTP
810 820 830 840 850
VKYARLWSEI PSEIAIDDYD SSGTSKDEIK ERFAQTMEFV EEYLRDVVCQ
860 870 880 890 900
RFPFSDKEKN KLTFEVVNLA RNLIYFGFYN FSDLLRLTKI LLAILDCVHV
910 920 930 940 950
TTIFPISKMA KGEENKGSNV MRSIHGVGEL MTQVVLRGGG FLPMTPTATA
960 970 980 990 1000
PEGNVKQAEP EKEDIMVMDT KLKIIEILQF ILNVRLDYRI SCLLCIFKRE
1010 1020 1030 1040 1050
FDESNSQTSE TSSGNSSQEG PSNVPGALDF EHIEEQAEGI FGGSEETTPL
1060 1070 1080 1090 1100
DLDDHGGRTF LRVLLHLTMH DYPPLVSGAL QLLFRHFSQR QEVLQAFKQV
1110 1120 1130 1140 1150
QLLVTSQDVD NYKQIKQDLD QLRSIVEKSE LWVYKGQGPD EAMDGASGEN
1160 1170 1180 1190 1200
EHKKTEEGNN KSQQHESTSS YNYRVVKEIL IRLSKLCVQE SASVRKSRKQ
1210 1220 1230 1240 1250
QQRLLRNMGA HAVVLELLQI PYEKAEDTMM QEIMRLAHEF LQNFCAGNHP
1260 1270 1280 1290 1300
NQALLHKHIN LFLNPGILEA VTMQHIFMNN FQLCSEINER VVQHFVHCIE
1310 1320 1330 1340 1350
THGRNVQYIK FLQTIVKAEG KFIKKCQDMV MAELVNSGED VLVFYNDRAS
1360 1370 1380 1390 1400
FQTLIQMMRS ERDRMDENSP LMYHIHLVEL LAVCTEGKNV YTEIKCNSLL
1410 1420 1430 1440 1450
PLDDIVRVVT HEDCIPEVKI AYINFLNHCY VDPEVEMKEI YTSNHMWKLF
1460 1470 1480 1490 1500
ENFLVDICRA CNNTSDRKHA DSILEKYVTE IVMSIVTTFF SSPFSDQSTT
1510 1520 1530 1540 1550
LQTRQPVFVQ LLQGVFRVYH CNWLMPSQKA SVESCIRVLS DVAKSRAIAI
1560 1570 1580 1590 1600
PVDLDSQVNN LFLKSHNLVQ KTAMNWRLTA RNAARRDSVL PVSRDYRNII
1610 1620 1630 1640 1650
ERLQDIVSAL EDRLRPLVQA ELSVLVDVLH RPELLFPENT DARRKCESGG
1660 1670 1680 1690 1700
FICKLIKHTK QLLEENEEKL CIKVLQTLRE MMTKDRGYGE KGEALRQILV
1710 1720 1730 1740 1750
NRYYGNIRPS GRRESLTSFG NGPLSPGGPS KPGGGGGGSG SSPMSRGEMS
1760 1770 1780 1790 1800
LAEVQCHLDK EGASNLVIDL IMNASSDRVF HESILLAIAL LEGGNTTIQH
1810 1820 1830 1840 1850
SFFCRLTEDK KSEKFFKVFY DRMKVAQQEI KATVTVNTSD LGNKKKDDEV
1860 1870 1880 1890 1900
DRDAPSRKKA KEPATQITEE VRDQLLEASA ATRKAFTTFR READPDDHYQ
1910 1920 1930 1940 1950
SGEGAQAAAD KSKDDLEMSA VITIMQPILR FLQLLCENHN RDLQNFLRCQ
1960 1970 1980 1990 2000
NNKTNYNLVC ETLQFLDCIC GSTTGGLGLL GLYINEKNVA LINQTLESLT
2010 2020 2030 2040 2050
EYCQGPCHEN QNCIATHESN GIDIITALIL NDINPLGKKR MDLVLELKNN
2060 2070 2080 2090 2100
ASKLLLAIME SRHDSENAER ILYNMRPKEL VEVIKKAYMQ GEVEFEDGEN
2110 2120 2130 2140 2150
GEDGAASPRN VGHNIYILAH QLARHNKELQ TMLKPGGQVD GDETLDFYAQ
2160 2170 2180 2190 2200
PTGPNEIVRL DRTMEQIVFP VPSICEFLTK ESKLRIYYTT ERDEQGSKIN
2210 2220 2230 2240 2250
DFFLRSEDLF NEMNWQKKLR AQPVLYWCAR NMSFWSSISF NLAVLMNLLV
2260 2270 2280 2290 2300
AFFYPFKGVR GGTLEPHWSG LLWTAMLISL AIVIALPKPH GIRALIASTI
2310 2320 2330 2340 2350
LRLIFSVGLQ PTLFLLGAFN VCNKIIFLMS FVGNCGTFTR GYRAMVLDVE
2360 2370 2380 2390 2400
FLYHLLXLLI CAMGLFVHEF FYSLLLFDLV YREETLLNVI KSVTRNGRSI
2410 2420 2430 2440 2450
ILMAVLALIL VYLFSIVGYL FFKDDFILEV DRLPNETSLP EASESLASEF
2460 2470 2480 2490 2500
LYSDVCRVET GENCSSPAPK EELVPAEETE QDKEHTCETL LMCIVTVLSH
2510 2520 2530 2540 2550
GLRSGGGVGD VLRKPSKEEP LFAARVIYDL LFFFMVIIIV LNLIFGVIID
2560 2570 2580 2590 2600
TFADLRSEKQ KKEEILKTTC FICGLERDKF DNKTVTFEEH IKEEHNMWHY
2610 2620 2630 2640 2650
LCFIVLVKVK DSTEYTGPES YVAEMIKERN LDWFPRMRAM SLVSSDSEGE
2660 2670 2680 2690 2700
QNELRNLQEK LESTMKLVTN LSGLLSELKD QMTDQRKQKQ RMGLLGHPPH

INVNPQQPA
Length:2,709
Mass (Da):308,318
Last modified:May 1, 2000 - v1
Checksum:i87E9F69422AE9356
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF157625 mRNA. Translation: AAF00613.1.
PIRiA38318.
RefSeqiNP_777266.1. NM_174841.2.
UniGeneiBt.22305.

Genome annotation databases

GeneIDi317697.
KEGGibta:317697.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF157625 mRNA. Translation: AAF00613.1.
PIRiA38318.
RefSeqiNP_777266.1. NM_174841.2.
UniGeneiBt.22305.

3D structure databases

ProteinModelPortaliQ9TU34.
SMRiQ9TU34. Positions 7-225, 236-602.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000047903.

Proteomic databases

PaxDbiQ9TU34.
PRIDEiQ9TU34.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi317697.
KEGGibta:317697.

Organism-specific databases

CTDi3708.

Phylogenomic databases

eggNOGiKOG3533. Eukaryota.
ENOG410XR97. LUCA.
HOGENOMiHOG000007660.
HOVERGENiHBG052158.
InParanoidiQ9TU34.
KOiK04958.

Miscellaneous databases

NextBioi20807145.

Family and domain databases

Gene3Di1.25.10.30. 2 hits.
InterProiIPR016024. ARM-type_fold.
IPR014821. Ins145_P3_rcpt.
IPR000493. InsP3_rcpt-bd.
IPR005821. Ion_trans_dom.
IPR016093. MIR_motif.
IPR013662. RIH_assoc-dom.
IPR000699. RIH_dom.
IPR015925. Ryanodine_recept-rel.
[Graphical view]
PANTHERiPTHR13715. PTHR13715. 1 hit.
PfamiPF08709. Ins145_P3_rec. 1 hit.
PF00520. Ion_trans. 1 hit.
PF02815. MIR. 1 hit.
PF08454. RIH_assoc. 1 hit.
PF01365. RYDR_ITPR. 2 hits.
[Graphical view]
PRINTSiPR00779. INSP3RECEPTR.
SMARTiSM00472. MIR. 4 hits.
[Graphical view]
SUPFAMiSSF100909. SSF100909. 2 hits.
SSF48371. SSF48371. 7 hits.
SSF82109. SSF82109. 2 hits.
PROSITEiPS50919. MIR. 5 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Localization of three types of the inositol 1,4,5-trisphosphate receptor/Ca2+ channel in the secretory granules and coupling with the Ca2+ storage proteins chromogranins A and B."
    Yoo S.H., Oh Y.S., Kang M.K., Huh Y.H., So S.H., Park H.S., Park H.Y.
    J. Biol. Chem. 276:45806-45812(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
    Tissue: Adrenal medulla.
  2. "Smooth muscle and brain inositol 1,4,5-trisphosphate receptors are structurally and functionally similar."
    Marks A.R., Tempst P., Chadwick C.C., Riviere L., Fleischer S., Nadal-Ginard B.
    J. Biol. Chem. 265:20719-20722(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 75-87; 149-167; 429-440; 833-843; 936-955; 1000-1012; 1130-1135; 1547-1554; 2071-2078 AND 2207-2217.
  3. "Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta."
    Schlossmann J., Ammendola A., Ashman K., Zong X., Huber A., Neubauer G., Wang G.-X., Allescher H.-D., Korth M., Wilm M., Hofmann F., Ruth P.
    Nature 404:197-201(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MRVI1.
  4. "Molecular determinants of the interaction between the inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP kinase Ibeta."
    Ammendola A., Geiselhoeringer A., Hofmann F., Schlossmann J.
    J. Biol. Chem. 276:24153-24159(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MRVI1.
  5. Cited for: SUBUNIT.

Entry informationi

Entry nameiITPR1_BOVIN
AccessioniPrimary (citable) accession number: Q9TU34
Secondary accession number(s): Q7M2U0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 2, 2001
Last sequence update: May 1, 2000
Last modified: May 11, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.