D6WMX4 · PINK1_TRICA
- ProteinSerine/threonine-protein kinase Pink1, mitochondrial
- GenePink1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids570 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a serine/threonine-protein kinase (PubMed:24751536, PubMed:25474007, PubMed:26116755, PubMed:26784449, PubMed:28980524, PubMed:29475881, PubMed:29991771, PubMed:32484300).
Exhibits a substrate preference for proline at position P+1 and a general preference at several residues for basic residues such as arginine (PubMed:22645651).
Also exhibits moderate preferences for a phosphotyrosine at position P-3 and a tryptophan at P-5 (PubMed:22645651).
Critical to mitochondrial homeostasis it mediates several pathways that maintain mitochondrial health and function (By similarity).
Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as park and likely Drp1, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:24751536, PubMed:25474007, PubMed:26116755, PubMed:28980524, PubMed:29991771, PubMed:32484300).
Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (By similarity).
Appears to be particularly important in maintaining the physiology and function of cells with high energy demands that are undergoing stress or altered metabolic environment, including spermatids, muscle cells and neurons such as the dopaminergic (DA) neurons (By similarity).
Mediates the translocation and activation of park at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:25474007, PubMed:26116755).
At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains, the Pink1-phosphorylated polyubiquitin then recruits park from the cytosol to the OMM where park is fully activated by phosphorylation at 'Ser-80' by Pink1 (PubMed:24751536, PubMed:25474007, PubMed:26116755, PubMed:29475881, PubMed:29991771).
When cellular stress results in irreversible mitochondrial damage, functions with park to promote the clearance of dysfunctional and/or depolarized mitochondria by selective autophagy (mitophagy) (By similarity).
The Pink1-park pathway also promotes fission and/or inhibits fusion of damaged mitochondria, by phosphorylating and thus promoting the park-dependent degradation of proteins involved in mitochondrial fusion/fission such as Marf, Opa1 and fzo (By similarity).
This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity).
Also likely to promote mitochondrial fission independently of park and Atg7-mediated mitophagy, via the phosphorylation and activation of Drp1 (PubMed:32484300).
Regulates motility of damaged mitochondria by phosphorylating Miro which likely promotes its park-dependent degradation by the proteasome; in motor neurons, this inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria being eliminated in the soma (By similarity).
The Pink1-park pathway is also involved in mitochondrial regeneration processes such as promoting mitochondrial biogenesis, activating localized mitochondrial repair, promoting selective turnover of mitochondrial proteins and initiating the mitochondrial import of endogenous proteins (By similarity).
Involved in mitochondrial biogenesis by promoting the park-dependent ubiquitination of transcriptional repressor Paris which leads to its subsequent proteasomal degradation and allows activation of the transcription factor srl (By similarity).
Functions with park to promote localized mitochondrial repair by activating the translation of specific nuclear-encoded mitochondrial RNAs (nc-mtRNAs) on the mitochondrial surface, including several key electron transport chain component nc-mtRNAs (By similarity).
During oogenesis, phosphorylates and inactivates larp on the membrane of defective mitochondria, thus impairing local translation and mtDNA replication and consequently, reducing transmission of deleterious mtDNA mutations to the mature oocyte (By similarity).
Phosphorylates the mitochondrial acyl-CoA dehydrogenase Mcad, and appears to be important for maintaining fatty acid and amino acid metabolism via a mechanism that is independent of it's role in maintaining production of ATP (By similarity).
Exhibits a substrate preference for proline at position P+1 and a general preference at several residues for basic residues such as arginine (PubMed:22645651).
Also exhibits moderate preferences for a phosphotyrosine at position P-3 and a tryptophan at P-5 (PubMed:22645651).
Critical to mitochondrial homeostasis it mediates several pathways that maintain mitochondrial health and function (By similarity).
Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as park and likely Drp1, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:24751536, PubMed:25474007, PubMed:26116755, PubMed:28980524, PubMed:29991771, PubMed:32484300).
Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (By similarity).
Appears to be particularly important in maintaining the physiology and function of cells with high energy demands that are undergoing stress or altered metabolic environment, including spermatids, muscle cells and neurons such as the dopaminergic (DA) neurons (By similarity).
Mediates the translocation and activation of park at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:25474007, PubMed:26116755).
At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains, the Pink1-phosphorylated polyubiquitin then recruits park from the cytosol to the OMM where park is fully activated by phosphorylation at 'Ser-80' by Pink1 (PubMed:24751536, PubMed:25474007, PubMed:26116755, PubMed:29475881, PubMed:29991771).
When cellular stress results in irreversible mitochondrial damage, functions with park to promote the clearance of dysfunctional and/or depolarized mitochondria by selective autophagy (mitophagy) (By similarity).
The Pink1-park pathway also promotes fission and/or inhibits fusion of damaged mitochondria, by phosphorylating and thus promoting the park-dependent degradation of proteins involved in mitochondrial fusion/fission such as Marf, Opa1 and fzo (By similarity).
This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity).
Also likely to promote mitochondrial fission independently of park and Atg7-mediated mitophagy, via the phosphorylation and activation of Drp1 (PubMed:32484300).
Regulates motility of damaged mitochondria by phosphorylating Miro which likely promotes its park-dependent degradation by the proteasome; in motor neurons, this inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria being eliminated in the soma (By similarity).
The Pink1-park pathway is also involved in mitochondrial regeneration processes such as promoting mitochondrial biogenesis, activating localized mitochondrial repair, promoting selective turnover of mitochondrial proteins and initiating the mitochondrial import of endogenous proteins (By similarity).
Involved in mitochondrial biogenesis by promoting the park-dependent ubiquitination of transcriptional repressor Paris which leads to its subsequent proteasomal degradation and allows activation of the transcription factor srl (By similarity).
Functions with park to promote localized mitochondrial repair by activating the translation of specific nuclear-encoded mitochondrial RNAs (nc-mtRNAs) on the mitochondrial surface, including several key electron transport chain component nc-mtRNAs (By similarity).
During oogenesis, phosphorylates and inactivates larp on the membrane of defective mitochondria, thus impairing local translation and mtDNA replication and consequently, reducing transmission of deleterious mtDNA mutations to the mature oocyte (By similarity).
Phosphorylates the mitochondrial acyl-CoA dehydrogenase Mcad, and appears to be important for maintaining fatty acid and amino acid metabolism via a mechanism that is independent of it's role in maintaining production of ATP (By similarity).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Note: Binds 2 Mg2+ ions per subunit.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
287.5 μM | Drp1 | 30 | ||||
84.4 μM | ubiquitin | 30 | ||||
391 μM | ubiquitin | 7.5 | 30 | |||
36 μM | ubiquitinated rat Prkn | 7.5 | 30 |
kcat is 4.6 sec-1 for phosphorylation of Drp1 (at pH 7.5 and 30 degrees Celsius) (PubMed:32484300).
kcat is 20.9 sec-1 for phosphorylation of ubiquitin (at pH 7.5 and 30 degrees Celsius) (PubMed:32484300).
kcat is 18 min-1 for phosphorylation of ubiquitin (at pH 7.5 and 30 degrees Celsius) (PubMed:29475881).
kcat is 7.8 min-1 for phosphorylation of ubiquitinated rat Prkn (at pH 7.5 and 30 degrees Celsius) (PubMed:29475881).
kcat is 20.9 sec-1 for phosphorylation of ubiquitin (at pH 7.5 and 30 degrees Celsius) (PubMed:32484300).
kcat is 18 min-1 for phosphorylation of ubiquitin (at pH 7.5 and 30 degrees Celsius) (PubMed:29475881).
kcat is 7.8 min-1 for phosphorylation of ubiquitinated rat Prkn (at pH 7.5 and 30 degrees Celsius) (PubMed:29475881).
Features
Showing features for site, binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 44 | Important for interaction with substrates Prkn and ubiquitin | ||||
Sequence: P | ||||||
Site | 48 | Important for interaction with substrates Prkn and ubiquitin | ||||
Sequence: P | ||||||
Site | 68 | Important for interaction with substrates Prkn and ubiquitin | ||||
Sequence: Q | ||||||
Site | 72 | Important for interaction with substrates Prkn and ubiquitin | ||||
Sequence: I | ||||||
Binding site | 196 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 217 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 295 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 297 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 300 | ATP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 337 | Proton acceptor | ||||
Sequence: D | ||||||
Binding site | 341 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 342 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 359 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 359 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 359 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial outer membrane | |
Cellular Component | mitochondrion | |
Molecular Function | ATP binding | |
Molecular Function | metal ion binding | |
Molecular Function | protein serine/threonine kinase activity | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | autophagy of mitochondrion | |
Biological Process | peptidyl-serine phosphorylation | |
Biological Process | positive regulation of free ubiquitin chain polymerization | |
Biological Process | positive regulation of mitochondrial fission | |
Biological Process | positive regulation of protein ubiquitination | |
Biological Process | protein autophosphorylation | |
Biological Process | regulation of apoptotic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase Pink1, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Coleoptera > Polyphaga > Cucujiformia > Tenebrionidae > Tenebrionidae incertae sedis > Tribolium
Accessions
- Primary accessionD6WMX4
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion outer membrane ; Single-pass membrane protein
Mitochondrion inner membrane ; Single-pass membrane protein
Note: Localizes mostly in mitochondrion, and the smaller proteolytic processed fragment localizes in the cytosol as well (By similarity).
When mitochondria are damaged, defective and/or enriched with deleterious mtDNA mutations, Pink1 import is arrested which induces its accumulation on the outer mitochondrial membrane where it acquires kinase activity (By similarity).
When mitochondria are damaged, defective and/or enriched with deleterious mtDNA mutations, Pink1 import is arrested which induces its accumulation on the outer mitochondrial membrane where it acquires kinase activity (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 6-96 | Mitochondrial intermembrane | ||||
Sequence: VGSRLFKHGRSLIQQFCKRDLNTTIGDKINAVSQATAAPSSLPKTQIPKNFALRNVGVQLGLQARRILIDNVLNRVTNSLSAELRKKATRR | ||||||
Transmembrane | 97-120 | Helical | ||||
Sequence: ILFGDSAPFFALVGVSIASGTGIL | ||||||
Topological domain | 121-570 | Cytoplasmic | ||||
Sequence: TKEEELEGVCWEIREAISKIKWQYYDIDESRFESNPITLNDLSLGKPIAKGTNGVVYSAKVKDDETDDNKYPFALKMMFNYDIQSNSMEILKAMYRETVPARMYYSNHDLNNWEIELANRRKHLPPHPNIVAIFSVFTDLIQELEGSKDLYPAALPPRLHPEGEGRNMSLFLLMKRYDCNLQSFLSTAPSTRTSLLLLAQLLEGVAHMTAHGIAHRDLKSDNLLLDTSEPESPILVISDFGCCLADKTNGLSLPYTSYEMDKGGNTALMAPEIICQKPGTFSVLNYSKADLWAVGAIAYEIFNCHNPFYGPSRLKNFNYKEGDLPKLPDEVPTVIQALVANLLKRNPNKRLDPEVAANVCQLFLWAPSTWLKPGLKVPTSGEILQWLLSLTTKVLCEGKINNKSFGEKFTRNWRRTYPEYLLISSFLCRAKLANVRNALHWIQENLPELD |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 130 | Moderately reduces enzyme activity. | ||||
Sequence: C → G | ||||||
Mutagenesis | 168 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: I → N | ||||||
Mutagenesis | 176 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: V → N | ||||||
Mutagenesis | 194 | Almost complete loss of enzyme activity. | ||||
Sequence: A → D | ||||||
Mutagenesis | 194 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: A → N | ||||||
Mutagenesis | 196 | Almost complete loss of enzyme activity, but still undergoes autophosphorylation at Ser-205 and is able to bind rat Prkn. Abolishes phosphorylation of polyubiquitin chains at Ser-65; when associated with A-337 and A-359. | ||||
Sequence: K → A | ||||||
Mutagenesis | 205 | Strongly reduces enzyme activity. Abolishes phosphorylation of rat ubiquitin and strongly reduced phosphorylation of rat Prkn. | ||||
Sequence: S → A | ||||||
Mutagenesis | 205 | Phosphomimetic mutant which retains some residual ubiquitin phosphorylation activity; when associated with D-377, E-386 and E-530. | ||||
Sequence: S → D | ||||||
Mutagenesis | 205 | Strongly reduces enzyme activity. Abolishes phosphorylation of rat ubiquitin and strongly reduced phosphorylation of rat Prkn. | ||||
Sequence: S → N | ||||||
Mutagenesis | 207 | No effect on enzyme activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 209 | Drastically reduces phosphorylation of ubiquitin. | ||||
Sequence: E → R | ||||||
Mutagenesis | 210 | Drastically reduces phosphorylation of ubiquitin. | ||||
Sequence: I → N | ||||||
Mutagenesis | 212 | Slight reduction in phosphorylation of ubiquitin. | ||||
Sequence: K → A | ||||||
Mutagenesis | 216 | Reduced phosphorylation of ubiquitin. | ||||
Sequence: R → A | ||||||
Mutagenesis | 217 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: E → A | ||||||
Mutagenesis | 217 | Abolishes enzyme activity. | ||||
Sequence: E → K | ||||||
Mutagenesis | 222-242 | No effect on enzyme activity. | ||||
Sequence: Missing | ||||||
Mutagenesis | 231-242 | No effect on enzyme activity. | ||||
Sequence: Missing | ||||||
Mutagenesis | 240 | Reduced phosphorylation of ubiquitin. | ||||
Sequence: R → A | ||||||
Mutagenesis | 243-253 | Abolishes enzyme activity. | ||||
Sequence: Missing | ||||||
Mutagenesis | 247 | Strongly reduces enzyme activity. | ||||
Sequence: H → Q | ||||||
Mutagenesis | 251 | Reduced phosphorylation of ubiquitin. | ||||
Sequence: V → N | ||||||
Mutagenesis | 251 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: V → R | ||||||
Mutagenesis | 261-270 | Strongly reduces enzyme activity. Unable to phosphorylate ubiquitin and park, but retains its autophosphorylation activity. | ||||
Sequence: Missing | ||||||
Mutagenesis | 285 | Strongly reduces enzyme activity. | ||||
Sequence: G → D | ||||||
Mutagenesis | 294 | Decreases phosphorylation of ubiquitin. | ||||
Sequence: M → A or L | ||||||
Mutagenesis | 294 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: M → N | ||||||
Mutagenesis | 322 | Almost complete loss of enzyme activity. | ||||
Sequence: L → P | ||||||
Mutagenesis | 337 | Abolishes enzyme activity, loss of autophosphorylation and phosphorylation of ubiquitin. Abolishes phosphorylation of polyubiquitin chains at Ser-65; when associated with A-196 and A-359. | ||||
Sequence: D → A | ||||||
Mutagenesis | 337 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: D → H | ||||||
Mutagenesis | 337 | Abolishes enzyme activity. Able to undergo autophosphorylation and bind to rat Prkn. | ||||
Sequence: D → N | ||||||
Mutagenesis | 341 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: D → A | ||||||
Mutagenesis | 342 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: N → A | ||||||
Mutagenesis | 342 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: N → S | ||||||
Mutagenesis | 344 | No effect on phosphorylation of ubiquitin. | ||||
Sequence: L → N | ||||||
Mutagenesis | 344 | Almost complete loss of enzyme activity. | ||||
Sequence: L → P | ||||||
Mutagenesis | 344 | Abolishes phosphorylation of ubiquitin. | ||||
Sequence: L → R | ||||||
Mutagenesis | 359 | Abolishes enzyme activity. No effect on autophosphorylation activity. However, another report found that it significantly reduced autophosphorylation. Abolishes phosphorylation of polyubiquitin chains at Ser-65; when associated with A-196 and A-337. | ||||
Sequence: D → A | ||||||
Mutagenesis | 359 | Abolishes enzyme activity. | ||||
Sequence: D → N | ||||||
Mutagenesis | 361 | Almost complete loss of enzyme activity. | ||||
Sequence: G → A | ||||||
Mutagenesis | 362 | Slight reduction in phosphorylation of ubiquitin. | ||||
Sequence: C → A | ||||||
Mutagenesis | 363 | Abolishes enzyme activity. | ||||
Sequence: C → R | ||||||
Mutagenesis | 363 | No effect on phosphorylation of rat ubiquitin. | ||||
Sequence: C → S | ||||||
Mutagenesis | 368 | No effect on autophosphorylation levels; when associated with A-372. | ||||
Sequence: T → A | ||||||
Mutagenesis | 371 | Almost complete loss of enzyme activity. | ||||
Sequence: L → A | ||||||
Mutagenesis | 372 | No effect on autophosphorylation levels; when associated with A-368. | ||||
Sequence: S → A | ||||||
Mutagenesis | 375 | Almost complete loss of enzyme activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 376 | No effect on autophosphorylation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 377 | Phosphomimetic mutant which retains some residual ubiquitin phosphorylation activity; when associated with D-205, E-386 and E-530. | ||||
Sequence: S → D | ||||||
Mutagenesis | 381 | Reduced phosphorylation of ubiquitin. | ||||
Sequence: D → A | ||||||
Mutagenesis | 381 | Drastically reduces phosphorylation of ubiquitin. | ||||
Sequence: D → R | ||||||
Mutagenesis | 382 | Almost complete loss of enzyme activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 384 | Almost complete loss of enzyme activity. | ||||
Sequence: G → V | ||||||
Mutagenesis | 385 | Drastically reduces phosphorylation of ubiquitin. | ||||
Sequence: N → A | ||||||
Mutagenesis | 386 | Decreased autophosphorylation levels. | ||||
Sequence: T → A | ||||||
Mutagenesis | 386 | Phosphomimetic mutant which retains some residual ubiquitin phosphorylation activity; when associated with D-205, D-377 and E-530. | ||||
Sequence: T → E | ||||||
Mutagenesis | 391 | Almost complete loss of enzyme activity. | ||||
Sequence: P → R | ||||||
Mutagenesis | 392 | Abolishes enzyme activity. | ||||
Sequence: E → G | ||||||
Mutagenesis | 415 | Abolishes enzyme activity. | ||||
Sequence: G → E | ||||||
Mutagenesis | 420 | Slight reduction in phosphorylation of ubiquitin. | ||||
Sequence: E → A | ||||||
Mutagenesis | 426 | Slight reduction in phosphorylation of ubiquitin. | ||||
Sequence: N → A | ||||||
Mutagenesis | 429 | Drastically reduces phosphorylation of ubiquitin. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 462 | Almost complete loss of enzyme activity. | ||||
Sequence: L → P | ||||||
Mutagenesis | 530 | Phosphomimetic mutant which retains some residual ubiquitin phosphorylation activity; when associated with D-205, D-377 and E-386. | ||||
Sequence: T → E |
Chemistry
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-5 | Mitochondrion | ||||
Sequence: MSVRA | ||||||
Chain | PRO_0000454926 | 6-570 | Serine/threonine-protein kinase Pink1, mitochondrial | |||
Sequence: VGSRLFKHGRSLIQQFCKRDLNTTIGDKINAVSQATAAPSSLPKTQIPKNFALRNVGVQLGLQARRILIDNVLNRVTNSLSAELRKKATRRILFGDSAPFFALVGVSIASGTGILTKEEELEGVCWEIREAISKIKWQYYDIDESRFESNPITLNDLSLGKPIAKGTNGVVYSAKVKDDETDDNKYPFALKMMFNYDIQSNSMEILKAMYRETVPARMYYSNHDLNNWEIELANRRKHLPPHPNIVAIFSVFTDLIQELEGSKDLYPAALPPRLHPEGEGRNMSLFLLMKRYDCNLQSFLSTAPSTRTSLLLLAQLLEGVAHMTAHGIAHRDLKSDNLLLDTSEPESPILVISDFGCCLADKTNGLSLPYTSYEMDKGGNTALMAPEIICQKPGTFSVLNYSKADLWAVGAIAYEIFNCHNPFYGPSRLKNFNYKEGDLPKLPDEVPTVIQALVANLLKRNPNKRLDPEVAANVCQLFLWAPSTWLKPGLKVPTSGEILQWLLSLTTKVLCEGKINNKSFGEKFTRNWRRTYPEYLLISSFLCRAKLANVRNALHWIQENLPELD | ||||||
Modified residue | 205 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 377 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 386 | Phosphothreonine; by autocatalysis | ||||
Sequence: T | ||||||
Modified residue | 530 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Proteolytically cleaved. In healthy cells, the precursor is continuously imported into mitochondria where it is proteolytically cleaved into its short form by the mitochondrial rhomboid protease rho-7 (TcasGA2_TC013516). The short form is then released into the cytosol where it rapidly undergoes proteasome-dependent degradation. In unhealthy cells, when cellular stress conditions lead to the loss of mitochondrial membrane potential, mitochondrial import is impaired leading to the precursor accumulating on the outer mitochondrial membrane (OMM).
Autophosphorylated on Ser-205, which activates kinase activity and is required for substrate recognition (PubMed:22645651, PubMed:26784449, PubMed:28980524, PubMed:29475881, PubMed:29991771).
Loss of mitochondrial membrane potential results in the precursor accumulating on the outer mitochondrial membrane (OMM) where it is activated by autophosphorylation at Ser-205 (By similarity).
Autophosphorylation is sufficient and essential for selective recruitment of park to depolarized mitochondria, likely via Pink1-dependent phosphorylation of polyubiquitin chains (PubMed:24751536).
Also autophosphorylated at Ser-377, Thr-386 and possibly Thr-530 (PubMed:29991771).
Another report found evidence of autophosphorylation at Ser-154, Thr-186, Thr-218, Ser-267 and Thr-530, as well as a number of other minor sites, but determined that phosphorylation at these sites is not required for enzyme activity and may not occur in vivo (PubMed:29475881).
Loss of mitochondrial membrane potential results in the precursor accumulating on the outer mitochondrial membrane (OMM) where it is activated by autophosphorylation at Ser-205 (By similarity).
Autophosphorylation is sufficient and essential for selective recruitment of park to depolarized mitochondria, likely via Pink1-dependent phosphorylation of polyubiquitin chains (PubMed:24751536).
Also autophosphorylated at Ser-377, Thr-386 and possibly Thr-530 (PubMed:29991771).
Another report found evidence of autophosphorylation at Ser-154, Thr-186, Thr-218, Ser-267 and Thr-530, as well as a number of other minor sites, but determined that phosphorylation at these sites is not required for enzyme activity and may not occur in vivo (PubMed:29475881).
Keywords
- PTM
PTM databases
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 162-484 | Protein kinase | ||||
Sequence: LSLGKPIAKGTNGVVYSAKVKDDETDDNKYPFALKMMFNYDIQSNSMEILKAMYRETVPARMYYSNHDLNNWEIELANRRKHLPPHPNIVAIFSVFTDLIQELEGSKDLYPAALPPRLHPEGEGRNMSLFLLMKRYDCNLQSFLSTAPSTRTSLLLLAQLLEGVAHMTAHGIAHRDLKSDNLLLDTSEPESPILVISDFGCCLADKTNGLSLPYTSYEMDKGGNTALMAPEIICQKPGTFSVLNYSKADLWAVGAIAYEIFNCHNPFYGPSRLKNFNYKEGDLPKLPDEVPTVIQALVANLLKRNPNKRLDPEVAANVCQLFL |
Sequence similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length570
- Mass (Da)64,072
- Last updated2010-08-10 v1
- ChecksumE58A6C0EA9809A1E
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
KQ971343 EMBL· GenBank· DDBJ | EFA03268.1 EMBL· GenBank· DDBJ | Genomic DNA |