Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

RYR1 (P21817) - Overview - Molecular Target Synopsis

Protein


RYR1, Ryanodine receptor 1
UniProt P21817

Also Known as RYR1_HUMAN, RYR1, RYDR

Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:11741831, PubMed:16163667). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335). Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis. Homotetramer. Can also form heterotetramers with RYR2 (By similarity). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335). Repeated very high-level exercise decreases interaction with PDE4D and protein phosphatase 1 (PP1) (PubMed:18268335). Interacts with CALM; CALM with bound calcium inhibits the RYR1 channel activity (PubMed:18650434). Interacts with S100A1 (PubMed:18650434). Interacts with FKBP1A; this stabilizes the closed conformation of the channel. Interacts with CACNA1S; interaction with CACNA1S is important for activation of the RYR1 channel. Interacts with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate RYR1 channel activity. Interacts with SELENON (By similarity). Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253).

Isoforms / Transcripts (Protein Coding)


Drugs


RYR1 is targeted by Approved Drug Dantrolene. (see details)
Dantrolene

Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project RYR1 has gain in 9 cell-lines, loss in 1 cell-lines and no signal in 995 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_8, NCI_ADR_RES, OVCAR_4

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: LXFL529, SJCRH30, OVKATE

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, SK-N-SH, NHLF

(see details)

3D Structures


At greater than 90% identity similarity to RYR1 there are:
22 structures (42 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RYR1 has been screened with 36 compounds (56 bioactivities), 1 compounds have bioactivities that show binding affinity of <= 500nM (3 bioactivities). (see details)