Reviewed,
UniProtKB/Swiss-Prot Q14643 (ITPR1_HUMAN)
Last modified
June 16, 2009.
Version 104.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
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Names and origin
| Protein names | Recommended name: Inositol 1,4,5-trisphosphate receptor type 1 Alternative name(s): Type 1 inositol 1,4,5-trisphosphate receptor Type 1 InsP3 receptor IP3 receptor isoform 1 InsP3R1 Short name=IP3R | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 2758 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. |
| Subunit structure | Homotetramer. 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 AHCYL1 By similarity. Interacts with MRVI1. |
| Subcellular location | Endoplasmic reticulum membrane; Multi-pass membrane protein. |
| Tissue specificity | Widely expressed. |
| Domain | 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. |
| Post-translational modification | Phosphorylated by cAMP kinase. Phosphorylation prevents the ligand-induced opening of the calcium channels By similarity. Phosphorylated on tyrosine residues. Ref.2 Ref.7 Ref.10 Ref.11 |
| Involvement in disease | Defects in ITPR1 are the cause of spinocerebellar ataxia type 15 (SCA15) (SCA15) [MIM:606658]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA15 is an autosomal dominant cerebellar ataxia (ADCA). It is very slow progressing form with a wide range of onset, ranging from childhood to adult. Most patients remain ambulatory. Ref.9 |
| 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. |
| Sequence similarities | Belongs to the InsP3 receptor family. Contains 5 MIR domains. |
Ontologies
Alternative products
| This entry describes 8 isoforms produced by alternative splicing. [Align] [Select] Note: There is a combination of three alternatively spliced domains at site SI, SIII and site SII (A and C). Experimental confirmation may be lacking for some isoforms. | ||||||
| Isoform 1 (identifier: Q14643-1) Also known as: SISIIISIIAC; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q14643-2) Also known as: SI-SIIISIIAC; The sequence of this isoform differs from the canonical sequence as follows: 322-336: Missing. | ||||||
| Isoform 3 (identifier: Q14643-3) Also known as: SISIII-SII; The sequence of this isoform differs from the canonical sequence as follows: 919-927: Missing. 1702-1725: Missing. 1726-1740: Missing. | ||||||
| Isoform 4 (identifier: Q14643-4) Also known as: SI-SIII-SII; The sequence of this isoform differs from the canonical sequence as follows: 322-336: Missing. 919-927: Missing. 1702-1725: Missing. 1726-1740: Missing. | ||||||
| Isoform 5 (identifier: Q14643-5) Also known as: SI-SIII-SIIAC; The sequence of this isoform differs from the canonical sequence as follows: 322-336: Missing. 919-927: Missing. | ||||||
| Isoform 6 (identifier: Q14643-6) Also known as: SISIIISIIA; The sequence of this isoform differs from the canonical sequence as follows: 1726-1740: Missing. | ||||||
| Isoform 7 (identifier: Q14643-7) Also known as: SI-SIII-SIIA; The sequence of this isoform differs from the canonical sequence as follows: 322-336: Missing. 1726-1740: Missing. | ||||||
| Isoform 8 (identifier: Q14643-8) Also known as: SI-SIII-SIIA; The sequence of this isoform differs from the canonical sequence as follows: 322-336: Missing. 919-927: Missing. 1726-1740: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2758 | 2758 | Inositol 1,4,5-trisphosphate receptor type 1 | PRO_0000153920 | |||||
Regions | |||||||||
| Topological domain | 1 – 2282 | 2282 | Cytoplasmic Potential | ||||||
| Transmembrane | 2283 – 2303 | 21 | Potential | ||||||
| Topological domain | 2304 – 2314 | 11 | Lumenal Potential | ||||||
| Transmembrane | 2315 – 2335 | 21 | Potential | ||||||
| Topological domain | 2336 – 2361 | 26 | Cytoplasmic Potential | ||||||
| Transmembrane | 2362 – 2382 | 21 | Potential | ||||||
| Topological domain | 2383 – 2405 | 23 | Lumenal Potential | ||||||
| Transmembrane | 2406 – 2426 | 21 | Potential | ||||||
| Topological domain | 2427 – 2448 | 22 | Cytoplasmic Potential | ||||||
| Transmembrane | 2449 – 2469 | 21 | Potential | ||||||
| Topological domain | 2470 – 2577 | 108 | Lumenal Potential | ||||||
| Transmembrane | 2578 – 2598 | 21 | Potential | ||||||
| Topological domain | 2599 – 2758 | 160 | Cytoplasmic Potential | ||||||
| Domain | 112 – 166 | 55 | MIR 1 | ||||||
| Domain | 173 – 223 | 51 | MIR 2 | ||||||
| Domain | 231 – 287 | 57 | MIR 3 | ||||||
| Domain | 294 – 373 | 80 | MIR 4 | ||||||
| Domain | 379 – 435 | 57 | MIR 5 | ||||||
| Region | 2472 – 2537 | 66 | Interaction with ERP44 By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 482 | 1 | Phosphotyrosine Potential | ||||||
| Modified residue | 704 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 1598 | 1 | Phosphoserine Ref.7 Ref.11 | ||||||
| Modified residue | 1764 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 2664 | 1 | Phosphotyrosine Potential | ||||||
| Glycosylation | 2512 | 1 | N-linked (GlcNAc...) | ||||||
Natural variations | |||||||||
| Alternative sequence | 322 – 336 | 15 | Missing in isoform 2, isoform 4, isoform 5, isoform 7 and isoform 8. | VSP_002687 | |||||
| Alternative sequence | 919 – 927 | 9 | Missing in isoform 3, isoform 4, isoform 5 and isoform 8. | VSP_002688 | |||||
| Alternative sequence | 1702 – 1725 | 24 | Missing in isoform 3 and isoform 4. | VSP_002689 | |||||
| Alternative sequence | 1726 – 1740 | 15 | Missing in isoform 3, isoform 4, isoform 6, isoform 7 and isoform 8. | VSP_002690 | |||||
| Natural variant | 769 | 1 | M → V: dbSNP rs35789999. | VAR_037005 | |||||
| Natural variant | 1430 | 1 | I → V: dbSNP rs3749383. | VAR_037006 | |||||
Experimental info | |||||||||
| Sequence conflict | 1557 – 1581 | 25 | AIAIP…SIVQK → HCHSRGPGQPSQQPLSQVPQ HCAE Ref.5 | ||||||
| Sequence conflict | 1722 | 1 | S → A in U23850. Ref.4 | ||||||
| Sequence conflict | 2302 | 1 | F → L in AAB04947. Ref.2 | ||||||
| Sequence conflict | 2305 | 1 | F → L in AAB04947. Ref.2 | ||||||
| Sequence conflict | 2448 | 1 | S → A in U23850. Ref.4 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human inositol 1,4,5-trisphosphate type-1 receptor, InsP3R1: structure, function, regulation of expression and chromosomal localization." Yamada N., Makino Y., Clark R.A., Pearson D.W., Mattei M.-G., Guenet J.-L., Ohama E., Fujino I., Miyawaki A., Furuichi T., Mikoshiba K. Biochem. J. 302:781-790(1994) [PubMed: 7945203] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). Tissue: Myeloid and Uterus. |
| [2] | "The human type 1 inositol 1,4,5-trisphosphate receptor from T lymphocytes. Structure, localization, and tyrosine phosphorylation." Harnick D.J., Jayaraman T., Ma Y., Mulieri P., Go L.O., Marks A.R. J. Biol. Chem. 270:2833-2840(1995) [PubMed: 7852357] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PHOSPHORYLATION. Tissue: T-cell. |
| [3] | Marks A. Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 431; 1012-1017; 1460; 1823; 2324; 2330; 2334; 2337; 2346; 2358; 2361; 2372; 2396; 2418; 2426; 2434 AND 2741. |
| [4] | "Molecular cloning of a cDNA for the human inositol 1,4,5-trisphosphate receptor type 1, and the identification of a third alternatively spliced variant." Nucifora F.C. Jr., Li S.-H., Danoff S., Ullrich A., Ross C.A. Brain Res. Mol. Brain Res. 32:291-296(1995) [PubMed: 7500840] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING. Tissue: Brain. |
| [5] | "Induction of inositol 1,4,5 trisphosphate receptor genes by ionizing radiation." Yan J., Khanna K.K., Lavin M.F. Int. J. Radiat. Biol. 69:539-546(1996) [PubMed: 8648241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1548-1723 (ISOFORMS 3 AND 4). |
| [6] | "Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44." Higo T., Hattori M., Nakamura T., Natsume T., Michikawa T., Mikoshiba K. Cell 120:85-98(2005) [PubMed: 15652484] [Abstract] Cited for: INTERACTION WITH ERP44. |
| [7] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598, MASS SPECTROMETRY. Tissue: Epithelium. |
| [8] | "IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation." Antl M., von Bruehl M.-L., Eiglsperger C., Werner M., Konrad I., Kocher T., Wilm M., Hofmann F., Massberg S., Schlossmann J. Blood 109:552-559(2007) [PubMed: 16990611] [Abstract] Cited for: INTERACTION WITH MRVI1. |
| [9] | "Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans." van de Leemput J., Chandran J., Knight M.A., Holtzclaw L.A., Scholz S., Cookson M.R., Houlden H., Gwinn-Hardy K., Fung H.-C., Lin X., Hernandez D., Simon-Sanchez J., Wood N.W., Giunti P., Rafferty I., Hardy J., Storey E., Gardner R.J.M. Singleton A.B.PLoS Genet. 3:1076-1082(2007) [PubMed: 17590087] [Abstract] Cited for: INVOLVEMENT IN SCA15. |
| [10] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704, MASS SPECTROMETRY. |
| [11] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598 AND SER-1764, MASS SPECTROMETRY. |
| [12] | "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-2512, MASS SPECTROMETRY. Tissue: Liver. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| D26070 mRNA. Translation: BAA05065.1. L38019 mRNA. Translation: AAB04947.2. U23850 mRNA. No translation available. S82269 mRNA. Translation: AAD14386.1. | |
| IPI | IPI00218658. IPI00218659. IPI00218660. IPI00218661. IPI00218662. IPI00218663. IPI00218664. IPI00333753. |
| PIR | A55713. S54974. |
| RefSeq | NP_001093422.1. NP_002213.4. |
| UniGene | Hs.567295 Hs.712541 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1N4K based on UniProtKB P11881. |
| SMR | Q14643. Positions 7-225, 236-602. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q14643. 2 interactions. |
PTM databases | |
| PhosphoSite | Q14643. |
Proteomic databases | |
| PRIDE | Q14643. |
Genome annotation databases | |
| Ensembl | ENSG00000150995. Homo sapiens. [Contig view] |
| GeneID | 3708. |
| KEGG | hsa:3708. |
Organism-specific databases | |
| GeneCards | GC03P004486. |
| H-InvDB | HIX0024342. |
| HGNC | HGNC:6180. ITPR1. |
| HPA | HPA014765. HPA016487. |
| MIM | 147265. gene. 606658. phenotype. |
| Orphanet | 98769. Ataxia, spinocerebellar, type 15. 98770. Ataxia, spinocerebellar, type 16. |
| PharmGKB | PA29978. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q14643. |
| HOVERGEN | Q14643. |
Enzyme and pathway databases | |
| Reactome | REACT_11061. Signalling by NGF. REACT_604. Hemostasis. |
Gene expression databases | |
| ArrayExpress | Q14643. |
| Bgee | Q14643. |
| CleanEx | HS_ITPR1. |
| GermOnline | ENSG00000150995. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR000699. Ca-rel_channel. IPR014821. Ins145_P3_rcpt. IPR000493. InsP3_rcpt_bd. IPR005821. Ion_trans. IPR003608. MIR. IPR016093. MIR_motif. IPR013662. RIH_assoc. IPR015925. Ryanodine_recept-rel. [Graphical view] |
| PANTHER | PTHR13715. Ryanodine_recept-rel. 1 hit. |
| Pfam | PF08709. 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] |
| PRINTS | PR00779. INSP3RECEPTR. |
| SMART | SM00472. MIR. 4 hits. [Graphical view] |
| PROSITE | PS50919. MIR. 5 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 14533. |
| SOURCE | Search... |
Entry information
| Entry name | ITPR1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q14643 Secondary accession number(s): Q14660, Q99897 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


