Details for: GRK1

Gene ID: 6011

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GRK1

Ensembl ID: ENSG00000185974

Description: G protein-coupled receptor kinase 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • retinal rod cell CL0000604
    CSI 5.33
    rCSI 9.4%
    PRS 99.84
  • retinal cone cell CL0000573
    CSI 3.95
    rCSI 6.36%
    PRS 99.76

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GRK1](/details-gene/6011), or G protein-coupled receptor kinase 1, is a protein-coding gene located on chromosome 13q34. It encodes the enzyme rhodopsin kinase, which plays a pivotal role in the visual phototransduction cascade. The primary function of [GRK1](/details-gene/6011) is to phosphorylate light-activated rhodopsin, a critical step for terminating the G protein-mediated signaling pathway and allowing photoreceptor cells to reset and adapt to changing light conditions. Its expression is highly specific to the retina, with data from the **Overall** context showing it as a defining marker for [retinal rod cells](/details-cell/CL0000604) and [retinal cone cells](/details-cell/CL0000573). Clinically, mutations in this gene are associated with the Oguchi form of congenital stationary night blindness ([180381](https://omim.org/entry/180381)), a disorder characterized by impaired night vision ([Link](https://doi.org/10.1038/ng0297-175)). ## Cellular Roles and Expression Landscape The expression profile of [GRK1](/details-gene/6011) demonstrates exceptional tissue and cell-type specificity, establishing it as a key component of the retinal photoreceptor machinery. **Overall**, its significance is almost exclusively confined to two cell types: [retinal rod cells](/details-cell/CL0000604) (CSI: 5.33) and [retinal cone cells](/details-cell/CL0000573) (CSI: 3.95). This highly restricted expression pattern underscores its specialized role in vision, with its highest significance observed in rod cells, which are responsible for scotopic (low-light) vision. While both photoreceptor types depend on [GRK1](/details-gene/6011), differences in its expression relative to other kinases like GRK7 can contribute to the distinct signaling kinetics of rods and cones ([Link](https://doi.org/10.1523/jneurosci.21-23-09175.2001)). The gene's localization has been confirmed within the mammalian pineal gland as well, though its primary functional and clinical relevance remains centered on the retina ([Link](https://doi.org/10.1017/s0952523800011366)). The absence of significant expression in other cell types suggests that its function is tightly regulated and dedicated almost entirely to the process of visual perception. ## Pathways and Molecular Function The molecular function of [GRK1](/details-gene/6011) is directly aligned with its specific expression in photoreceptor cells. As a protein kinase ([GO:0004672](https://www.ebi.ac.uk/QuickGO/term/GO:0004672)), its principal substrate is rhodopsin, giving it a specific '[Rhodopsin kinase activity](/details-go/GO:0050254)'. This activity is central to the '[G protein-coupled opsin signaling pathway](/details-go/GO:0016056)' and essential for the '[regulation of signal transduction](/details-go/GO:0009966)'. Functionally, [GRK1](/details-gene/6011) operates within the '[photoreceptor disc membrane](/details-go/GO:0097381)', where it phosphorylates activated opsin to facilitate the binding of arrestin. This process is a key step in the Reactome pathway '[Inactivation, recovery and regulation of the phototransduction cascade](/details-pathway/R-HSA-2514859)', which is fundamental to the broader biological process of '[Visual perception](/details-go/GO:0007601)'. The kinase activity of [GRK1](/details-gene/6011) itself can be regulated, for instance through phosphorylation by cAMP-dependent protein kinase, which attenuates its enzymatic function ([Link](https://doi.org/10.1074/jbc.m505117200)). ## Research Directions Given the highly specialized role of [GRK1](/details-gene/6011) in visual phototransduction, research can focus on understanding the subtler aspects of its regulation and its contribution to visual performance outside of severe monogenic diseases. **Proposed Hypotheses:** 1. Genetic variants within the regulatory regions of the [GRK1](/details-gene/6011) gene, which result in subtle variations in its expression level in photoreceptors, may contribute to inter-individual differences in visual performance metrics such as the speed of dark adaptation or sensitivity to glare. 2. Beyond its known regulation by cAMP-dependent protein kinase, the activity of [GRK1](/details-gene/6011) may be dynamically modulated by a network of other kinases and phosphatases in response to ambient light levels, serving as a rheostat to fine-tune photoreceptor sensitivity and recovery over circadian or adaptational timescales. **Experimental Approach:** To test the second hypothesis regarding dynamic regulation, a phosphoproteomic approach could be employed. Retinas could be isolated from an animal model (e.g., mice) exposed to distinct lighting paradigms (e.g., prolonged complete darkness vs. continuous bright light exposure). [GRK1](/details-gene/6011) would be immunoprecipitated from retinal lysates, and interacting proteins and post-translational modifications would be identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Novel, light-dependent phosphorylation sites could then be validated and their functional significance assessed by generating phosphomimetic or non-phosphorylatable mutants of [GRK1](/details-gene/6011] and testing their kinase activity on rhodopsin in *in vitro* reconstitution assays. **Therapeutic Potential:** The therapeutic potential of [GRK1](/details-gene/6011) is primarily in the context of gene replacement therapy for recessive retinal diseases like Oguchi disease, which are caused by loss-of-function mutations ([Link](https://doi.org/10.1016/j.ophtha.2006.05.069)). In these cases, the therapeutic strategy is **activation** or supplementation of function. Given the gene's highly specific expression in photoreceptors, it represents an excellent candidate for AAV (adeno-associated virus)-mediated gene therapy. AAV vectors engineered to express a functional copy of [GRK1](/details-gene/6011) under the control of a photoreceptor-specific promoter could be delivered to the subretinal space, with the goal of restoring normal protein function and rescuing the visual deficit. This targeted approach would minimize the risk of off-target effects in other tissues.

Genular Protein ID: 4033699989

Symbol: GRK1_HUMAN

Name: Rhodopsin kinase GRK1

UniProtKB Accession Codes:

Q15835 Q53X14

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugCentral 1 EC 2 EMBL 11 Ensembl 2 EvolutionaryTrace 1 GO 11 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 1 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 6 SABIO-RK 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9147475

Title: Molecular cloning and localization of rhodopsin kinase in the mammalian pineal.

PubMed ID: 9147475

DOI: 10.1017/s0952523800011366

PubMed ID: 8812493

Title: Characterization and chromosomal localization of the gene for human rhodopsin kinase.

PubMed ID: 8812493

DOI: 10.1006/geno.1996.0399

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057823

Title: The DNA sequence and analysis of human chromosome 13.

PubMed ID: 15057823

DOI: 10.1038/nature02379

PubMed ID: 11717351

Title: Species-specific differences in expression of G-protein-coupled receptor kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications for cone cell phototransduction.

PubMed ID: 11717351

DOI: 10.1523/jneurosci.21-23-09175.2001

PubMed ID: 15946941

Title: Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities.

PubMed ID: 15946941

DOI: 10.1074/jbc.m505117200

PubMed ID: 25979333

Title: Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions.

PubMed ID: 25979333

DOI: 10.1074/jbc.m114.627059

PubMed ID: 9268593

Title: Evaluation of the rhodopsin kinase gene in patients with retinitis pigmentosa.

PubMed ID: 9268593

DOI: 10.1006/exer.1997.9998

PubMed ID: 9020843

Title: Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness.

PubMed ID: 9020843

DOI: 10.1038/ng0297-175

PubMed ID: 17070587

Title: A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses.

PubMed ID: 17070587

DOI: 10.1016/j.ophtha.2006.05.069

Sequence Information:

  • Length: 563
  • Mass: 63526
  • Checksum: 1244DCB97D40F53D
  • Sequence:
    • MDFGSLETVV ANSAFIAARG SFDGSSSQPS RDKKYLAKLK LPPLSKCESL RDSLSLEFES 
VCLEQPIGKK LFQQFLQSAE KHLPALELWK DIEDYDTADN DLQPQKAQTI LAQYLDPQAK 
LFCSFLDEGI VAKFKEGPVE IQDGLFQPLL QATLAHLGQA PFQEYLGSLY FLRFLQWKWL 
EAQPMGEDWF LDFRVLGKGG FGEVSACQMK ATGKLYACKK LNKKRLKKRK GYQGAMVEKK 
ILMKVHSRFI VSLAYAFETK ADLCLVMTIM NGGDIRYHIY NVNEENPGFP EPRALFYTAQ 
IICGLEHLHQ RRIVYRDLKP ENVLLDNDGN VRISDLGLAV ELLDGQSKTK GYAGTPGFMA 
PELLQGEEYD FSVDYFALGV TLYEMIAARG PFRARGEKVE NKELKHRIIS EPVKYPDKFS 
QASKDFCEAL LEKDPEKRLG FRDETCDKLR AHPLFKDLNW RQLEAGMLMP PFIPDSKTVY 
AKDIQDVGAF STVKGVAFDK TDTEFFQEFA TGNCPIPWQE EMIETGIFGE LNVWRSDGQM 
PDDMKGISGG SSSSSKSGMC LVS