Protein:GRK4 |
Protein Summary |
 Gene summary |
| Gene name: GRK4 | ASpdb.0 ID: 2868 | Gene | Gene symbol | GRK4 | Gene ID | 2868 |
| Gene name | G protein-coupled receptor kinase 4 |
| Synonyms | GPRK2L|GPRK4|GRK4a|IT11 |
| Cytomap | 4p16.3 |
| Type of gene | protein-coding |
| Description | G protein-coupled receptor kinase 4G protein-coupled receptor kinase 2-like |
| Modification date | 20240411 |
| UniProtAcc | P32298 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | GRK4 | GO:0005829 | cytosol | - |
| Gene | GRK4 | GO:0005886 | plasma membrane | - |
| Gene | GRK4 | GO:0031623 | receptor internalization | 20074556 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P32298-1 | P32298-1_4yhj_B.pdb | 4YHJ | X-ray | 2.6 | B | 25 | 527 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P32298 | GRK4 | P32298-1 | P32298-2 | 578 | 546 | 18 | 49 | Deletion | none | none | 17 | 17 |
| P32298 | GRK4 | P32298-1 | P32298-3 | 578 | 500 | 18 | 49 | Deletion | none | none | 17 | 17 |
| P32298 | GRK4 | P32298-1 | P32298-3 | 578 | 500 | 516 | 561 | Deletion | none | none | 483 | 483 |
| P32298 | GRK4 | P32298-1 | P32298-4 | 578 | 532 | 516 | 561 | Deletion | none | none | 515 | 515 |
| Multiple sequence alignment of our canonical and alternatively spliced GRK4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of GRK4 |
| UniProt-id | ENSG | ENST | ENSP |
| P32298-1 | ENSG00000125388.20 | ENST00000398052.9 | ENSP00000381129.4 |
| P32298-2 | ENSG00000125388.20 | ENST00000345167.10 | ENSP00000264764.8 |
| P32298-3 | ENSG00000125388.20 | ENST00000398051.8 | ENSP00000381128.4 |
| P32298-4 | ENSG00000125388.20 | ENST00000504933.1 | ENSP00000427445.1 |
| UniProt-id | NM ID | NP ID |
| P32298-1 | NM_182982.2 | NP_892027.2 |
| P32298-2 | NM_001004056.1 | NP_001004056.1 |
| P32298-3 | NM_005307.2 | NP_005298.2 |
| P32298-4 | NM_001004057.1 | NP_001004057.1 |
| Amino acid sequences of our canonical and alternatively spliced GRK4 |
| accession_id | Protein sequence |
| P32298-1 | MELENIVANSLLLKARQGGYGKKSGRSKKWKEILTLPPVSQCSELRHSIEKDYSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEY EVADDEDRSDCGLSILDRFFNDKLAAPLPEIPPDVVTECRLGLKEENPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWKWLERQ PVTKNTFRHYRVLGKGGFGEVCACQVRATGKMYACKKLQKKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGG DLKFHIYNLGNPGFDEQRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLATEIPEGQRVRGRVGTVGYMAPEVVNN EKYTFSPDWWGLGCLIYEMIQGHSPFKKYKEKVKWEEVDQRIKNDTEEYSEKFSEDAKSICRMLLTKNPSKRLGCRGEGAAGVKQHPVFK DINFRRLEANMLEPPFCPDPHAVYCKDVLDIEQFSVVKGIYLDTADEDFYARFATGCVSIPWQNEMIESGCFKDINKSESEEALPLDLDK |
| P32298-2 | MELENIVANSLLLKARQEKDYSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEYEVADDEDRSDCGLSILDRFFNDKLAAPLPEIP PDVVTECRLGLKEENPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWKWLERQPVTKNTFRHYRVLGKGGFGEVCACQVRATGKM YACKKLQKKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNPGFDEQRAVFYAAELCCGLED LQRERIVYRDLKPENILLDDRGHIRISDLGLATEIPEGQRVRGRVGTVGYMAPEVVNNEKYTFSPDWWGLGCLIYEMIQGHSPFKKYKEK VKWEEVDQRIKNDTEEYSEKFSEDAKSICRMLLTKNPSKRLGCRGEGAAGVKQHPVFKDINFRRLEANMLEPPFCPDPHAVYCKDVLDIE QFSVVKGIYLDTADEDFYARFATGCVSIPWQNEMIESGCFKDINKSESEEALPLDLDKNIHTPVSRPNRGFFYRLFRRGGCLTMVPSEKE |
| P32298-3 | MELENIVANSLLLKARQEKDYSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEYEVADDEDRSDCGLSILDRFFNDKLAAPLPEIP PDVVTECRLGLKEENPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWKWLERQPVTKNTFRHYRVLGKGGFGEVCACQVRATGKM YACKKLQKKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNPGFDEQRAVFYAAELCCGLED LQRERIVYRDLKPENILLDDRGHIRISDLGLATEIPEGQRVRGRVGTVGYMAPEVVNNEKYTFSPDWWGLGCLIYEMIQGHSPFKKYKEK VKWEEVDQRIKNDTEEYSEKFSEDAKSICRMLLTKNPSKRLGCRGEGAAGVKQHPVFKDINFRRLEANMLEPPFCPDPHAVYCKDVLDIE |
| P32298-4 | MELENIVANSLLLKARQGGYGKKSGRSKKWKEILTLPPVSQCSELRHSIEKDYSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEY EVADDEDRSDCGLSILDRFFNDKLAAPLPEIPPDVVTECRLGLKEENPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWKWLERQ PVTKNTFRHYRVLGKGGFGEVCACQVRATGKMYACKKLQKKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGG DLKFHIYNLGNPGFDEQRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLATEIPEGQRVRGRVGTVGYMAPEVVNN EKYTFSPDWWGLGCLIYEMIQGHSPFKKYKEKVKWEEVDQRIKNDTEEYSEKFSEDAKSICRMLLTKNPSKRLGCRGEGAAGVKQHPVFK |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| GRK4 (go to UniProt):P32298 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P32298 | Region | 1 | 154 | Note=N-terminal | Type=Deletion;Start=18;End=49 |
| P32298 | Region | 1 | 154 | Note=N-terminal | Type=Deletion;Start=18;End=49 |
Gene Isoform Structures and Expression Levels for GRK4 |
| Gene structures of our canonical and alternative spliced genes of GRK4 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P32298-1 |
| 3D view using mol* of P32298-2 |
| 3D view using mol* of P32298-3 |
| 3D view using mol* of P32298-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P32298-1 |
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| pLDDT distribution across the protein length of P32298-2 |
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| pLDDT distribution across the protein length of P32298-3 |
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| pLDDT distribution across the protein length of P32298-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P32298-1 |
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| Ramachandran plot of P32298-3 |
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| Ramachandran plot of P32298-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P32298-1 | 1.063 | 246 | 1.024 | 715.498 | 0.442 | 0.793 | 1.05 | 0.763 | 1.2 | 0.636 | 0.974 | 16,193,194,195,196,197,198,199,201,214,216,218,226 ,231,235,248,264,265,266,267,268,270,271,273,274,2 77,278,312,314,315,316,317,319,329,330,332,333,350 ,351,352,378,384,387,388,389,390,473,474,475,476,4 80,481,482 |
| P32298-2 | 1.034 | 228 | 1.025 | 670.908 | 0.548 | 0.748 | 0.964 | 0.699 | 1.117 | 0.626 | 0.858 | 159,161,162,163,164,165,166,167,169,171,182,184,18 6,194,199,200,203,207,216,232,233,234,235,236,237, 238,239,241,242,245,246,280,282,284,285,287,290,29 7,298,299,300,301,302,317,357,436,437,438,439,440, 441,442,443,444,448,449,450 |
| P32298-3 | 1.016 | 288 | 1.029 | 745.682 | 0.535 | 0.723 | 0.891 | 0.659 | 1.056 | 0.624 | 0.839 | 159,160,161,162,163,164,165,166,167,169,171,182,18 4,186,191,196,199,200,203,207,216,232,233,234,235, 236,237,238,239,241,242,245,246,278,280,282,284,28 5,287,290,297,298,299,300,301,302,357,436,437,438, 439,440,441,442,443,444,445,446,449,450,452 |
| P32298-4 | 1.054 | 216 | 1.033 | 592.704 | 0.472 | 0.779 | 1.004 | 0.765 | 1.148 | 0.667 | 0.911 | 12,16,193,194,195,196,197,198,199,201,214,216,218, 231,232,235,239,248,264,265,266,267,268,270,271,27 3,274,277,278,310,312,314,316,317,319,329,330,331, 332,333,349,389,473,474,475,476,480,481,482 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P32298-1_P32298-1_4yhj_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P32298-1_4yhj_B_P32298-2.pdb |
| 3D view using mol* of P32298-1_4yhj_B_P32298-3.pdb |
| 3D view using mol* of P32298-1_4yhj_B_P32298-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P32298-1_P32298-2.pdb |
| 3D view using mol* of P32298-1_P32298-3.pdb |
| 3D view using mol* of P32298-1_P32298-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P32298-1_vs_P32298-2.png |
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| ./stats/secondary_structure/figure/P32298-1_vs_P32298-3.png |
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| ./stats/secondary_structure/figure/P32298-1_vs_P32298-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P32298-1_vs_P32298-2.png |
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| ./stats/relative_asa/P32298-1_vs_P32298-3.png |
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| ./stats/relative_asa/P32298-1_vs_P32298-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to GRK4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to GRK4 |
| Previous studies relating to the alternative splicing of GRK4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| GRK4 | 8626439 | Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants. | A novel human G protein-coupled receptor kinase was recently identified by positional cloning in the search for the Huntington's disease locus (Ambrose, C., James, M., Barnes, G., Lin, C., Bates, G., Altherr, M., Duyao, M., Groot, N., Church, D., Wasmuth, J. J., Lehrach, H., Housman, D., Buckler, A., Gusella, J. F., and MacDonald, M. E. (1993) Hum. Mol. Genet. 1, 697-703). Comparison of the deduced amino acid sequence of GRK4 with those of the closely related GRK5 and GRK6 suggested the apparent loss of 32 codons in the amino-terminal domain and 46 codons in the carboxyl-terminal domain of GRK4. These two regions undergo alternative splicing in the GRK4 mRNA, resulting from the presence or absence of exons filling one or both of these apparent gaps. Each inserted sequence maintains the open reading frame, and the deduced amino acid sequences are similar to corresponding regions of GRK5 and GRK6. Thus, the GRK4 mRNA and the GRK4 protein can exist as four distinct variant forms. The human GRK4 gene is composed of 16 exons extending over 75 kilobase pairs of DNA. The two alternatively spliced exons correspond to exons II and XV. The genomic organization of the GRK4 gene is completely distinct from that of the human GRK2 gene, highlighting the evolutionary distance since the divergence of these two genes. Human GRK4 mRNA is expressed highly only in testis, and both alternative exons are abundant in testis mRNA. The four GRK4 proteins have been expressed, and all incorporate [3H]palmitate. GRK4 is capable of augmenting the desensitization of the rat luteinizing hormone/chorionic gonadotropin receptor upon coexpression in HEK293 cells and of phosphorylating the agonist-occupied, purified beta2-adrenergic receptor, indicating that GRK4 is a functional protein kinase. | D006816 | Huntington Disease |
Clinically important variants in GRK4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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