| UniProt ID | GRK5_HUMAN | |
|---|---|---|
| UniProt AC | P34947 | |
| Protein Name | G protein-coupled receptor kinase 5 | |
| Gene Name | GRK5 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 590 | |
| Subcellular Localization |
Cytoplasm. Nucleus. Cell membrane Peripheral membrane protein. Predominantly localized at the plasma membrane targeted to the cell surface through the interaction with phospholipids. Nucleus localization is regulated in a GPCR and Ca(2+)/calmodulin |
|
| Protein Description | Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro).. | |
| Protein Sequence | MELENIVANTVLLKAREGGGGKRKGKSKKWKEILKFPHISQCEDLRRTIDRDYCSLCDKQPIGRLLFRQFCETRPGLECYIQFLDSVAEYEVTPDEKLGEKGKEIMTKYLTPKSPVFIAQVGQDLVSQTEEKLLQKPCKELFSACAQSVHEYLRGEPFHEYLDSMFFDRFLQWKWLERQPVTKNTFRQYRVLGKGGFGEVCACQVRATGKMYACKRLEKKRIKKRKGESMALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPGFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKIPEGDLIRGRVGTVGYMAPEVLNNQRYGLSPDYWGLGCLIYEMIEGQSPFRGRKEKVKREEVDRRVLETEEVYSHKFSEEAKSICKMLLTKDAKQRLGCQEEGAAEVKRHPFFRNMNFKRLEAGMLDPPFVPDPRAVYCKDVLDIEQFSTVKGVNLDHTDDDFYSKFSTGSVSIPWQNEMIETECFKELNVFGPNGTLPPDLNRNHPPEPPKKGLLQRLFKRQHQNNSKSSPSSKTSFNHHINSNHVSSNSTGSS | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
|
|
||
* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 10 | Phosphorylation | LENIVANTVLLKARE HHHHHHCEEEEHHHC | 11.64 | 24719451 | |
| 14 | Ubiquitination | VANTVLLKAREGGGG HHCEEEEHHHCCCCC | 41.03 | - | |
| 24 | Acetylation | EGGGGKRKGKSKKWK CCCCCCCCCCCHHHH | 74.34 | 7614495 | |
| 26 | Acetylation | GGGKRKGKSKKWKEI CCCCCCCCCHHHHHH | 63.24 | 7833967 | |
| 27 | Phosphorylation | GGKRKGKSKKWKEIL CCCCCCCCHHHHHHH | 48.40 | - | |
| 28 | Acetylation | GKRKGKSKKWKEILK CCCCCCCHHHHHHHC | 67.16 | 7833981 | |
| 29 | Acetylation | KRKGKSKKWKEILKF CCCCCCHHHHHHHCC | 71.27 | 7833995 | |
| 40 | Phosphorylation | ILKFPHISQCEDLRR HHCCCCHHHCHHHHH | 26.24 | - | |
| 107 | Phosphorylation | EKGKEIMTKYLTPKS HHHHHHHHHHCCCCC | 23.38 | 22210691 | |
| 109 | Phosphorylation | GKEIMTKYLTPKSPV HHHHHHHHCCCCCCE | 13.47 | 22210691 | |
| 111 | Phosphorylation | EIMTKYLTPKSPVFI HHHHHHCCCCCCEEE | 26.11 | 22210691 | |
| 113 | Ubiquitination | MTKYLTPKSPVFIAQ HHHHCCCCCCEEEEE | 63.26 | 29967540 | |
| 183 | Ubiquitination | LERQPVTKNTFRQYR HHCCCCCCCCCHHEE | 54.98 | - | |
| 194 | Ubiquitination | RQYRVLGKGGFGEVC HHEEECCCCCCCCCC | 52.26 | 29967540 | |
| 210 | Ubiquitination | CQVRATGKMYACKRL EEEEECCCEEEHHHH | 25.12 | - | |
| 226 | Acetylation | KKRIKKRKGESMALN HHHHHHHCCCCCCCC | 75.74 | 18584391 | |
| 235 | Ubiquitination | ESMALNEKQILEKVN CCCCCCHHHHHHHHH | 41.38 | 29967540 | |
| 408 | Phosphorylation | VLETEEVYSHKFSEE HHCCHHHHHHCCCHH | 14.34 | 18083107 | |
| 411 | Ubiquitination | TEEVYSHKFSEEAKS CHHHHHHCCCHHHHH | 44.65 | 29967540 | |
| 443 | Ubiquitination | EEGAAEVKRHPFFRN CCCCHHHHHCHHHHC | 36.17 | - | |
| 484 | Phosphorylation | VLDIEQFSTVKGVNL CCCHHHHCCCCCCCC | 31.80 | 29255136 | |
| 485 | Phosphorylation | LDIEQFSTVKGVNLD CCHHHHCCCCCCCCC | 27.76 | 29255136 | |
| 487 | Ubiquitination | IEQFSTVKGVNLDHT HHHHCCCCCCCCCCC | 58.17 | 29967540 | |
| 494 | Phosphorylation | KGVNLDHTDDDFYSK CCCCCCCCCCCHHHH | 40.57 | 28060719 | |
| 548 | Methylation | HPPEPPKKGLLQRLF CCCCCCCCHHHHHHH | 61.64 | - | |
| 548 | Trimethylation | HPPEPPKKGLLQRLF CCCCCCCCHHHHHHH | 61.64 | - | |
| 565 | Phosphorylation | QHQNNSKSSPSSKTS HHHCCCCCCCCCCHH | 47.50 | 30576142 | |
| 568 | Phosphorylation | NNSKSSPSSKTSFNH CCCCCCCCCCHHHCC | 46.55 | 30576142 | |
| 571 | Phosphorylation | KSSPSSKTSFNHHIN CCCCCCCHHHCCCCC | 40.26 | 23898821 | |
| 572 | Phosphorylation | SSPSSKTSFNHHINS CCCCCCHHHCCCCCC | 27.99 | 27251275 | |
| 579 | Phosphorylation | SFNHHINSNHVSSNS HHCCCCCCCCCCCCC | 27.92 | 23401153 | |
| 583 | Phosphorylation | HINSNHVSSNSTGSS CCCCCCCCCCCCCCC | 19.09 | 27251275 | |
| 584 | Phosphorylation | INSNHVSSNSTGSS- CCCCCCCCCCCCCC- | 33.44 | 27251275 | |
| 586 | Phosphorylation | SNHVSSNSTGSS--- CCCCCCCCCCCC--- | 35.77 | 30576142 | |
| 587 | Phosphorylation | NHVSSNSTGSS---- CCCCCCCCCCC---- | 45.38 | 30108239 | |
| 589 | Phosphorylation | VSSNSTGSS------ CCCCCCCCC------ | 32.72 | 30108239 | |
| 590 | Phosphorylation | SSNSTGSS------- CCCCCCCC------- | 45.65 | 30108239 |
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of GRK5_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of GRK5_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
loading...
| Phosphorylation | |
| Reference | PubMed |
| "Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484 AND THR-485, ANDMASS SPECTROMETRY. | |
| "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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484 AND THR-485, ANDMASS SPECTROMETRY. | |
