PRKN_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PRKN_RAT
• UniProt AC: Q9JK66
• Protein Name: E3 ubiquitin-protein ligase parkin {ECO:0000305}
• Gene Name: Prkn {ECO:0000250|UniProtKB:O60260}
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 465
• Subcellular Localization: Nucleus. Endoplasmic reticulum. Cytoplasm, cytosol . Cell projection, dendrite. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Mitochondrion . Cell junction, synapse. Mainly localizes in the cytosol. Expressed in the endopl
• Protein Description: Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene..
• Protein Sequence: MIVFVRFNSSYGFPVEVDSDTSIFQLKEVVAKRQGVPADQLRVIFAGKELQNHLTVQNCDLEQQSIVHIVQRPQRKSHETNASGGDKPQSTPEGSIWEPRSLTRVDLSSHILPADSVGLAVILDTDSKSDSEAARGPEAKPTYHSFFVYCKGPCHKVQPGKLRVQCGTCRQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVALNLITNNSRSIPCIACTDVRNPVLVFQCNHRHVICLDCFHLYCVTRLNDRQFVHDAQLGYSLPCVAGCPNSLIKELHHFRILGEEQYNRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQKKVTCEGGNGLGCGFVFCRDCKEAYHEGECDSMFEASGATSQAYRVDQRAAEQARWEEASKETIKKTTKPCPRCNVPIEKNGGCMHMKCPQPQCKLEWCWNCGCEWNRACMGDHWFDV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
65	Phosphorylation	NCDLEQQSIVHIVQR CCCHHHHHHEEEEEC		-
77	Phosphorylation	VQRPQRKSHETNASG EECCCCCCCCCCCCC		25575281
80	Phosphorylation	PQRKSHETNASGGDK CCCCCCCCCCCCCCC		25575281
83	Phosphorylation	KSHETNASGGDKPQS CCCCCCCCCCCCCCC		25575281
108	Phosphorylation	SLTRVDLSSHILPAD CCCEEECCCCCCCCC		25575281
109	Phosphorylation	LTRVDLSSHILPADS CCEEECCCCCCCCCC		25575281
116	Phosphorylation	SHILPADSVGLAVIL CCCCCCCCCEEEEEE		25575281
175	Phosphorylation	TCRQATLTLAQGPSC CCCCEEEEECCCCCC		-
217	Phosphorylation	FKCGAHPTSDKDTSV EECCCCCCCCCCCHH		-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
65	S	Phosphorylation	Kinase	PINK1	Q9BXM7	PSP
65	S	Phosphorylation	Kinase	PINK1	B5DFG1	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Prkn	Q9JK66	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
65	S	Phosphorylation	Activation requires phosphorylation at Ser-65 by PINK1 and binding to PINK1 phosphorylated ubiquitin.	-
65	S	ubiquitylation	Activation requires phosphorylation at Ser-65 by PINK1 and binding to PINK1 phosphorylated ubiquitin.	-
175	T	Phosphorylation	Phosphorylation at Thr-175 by PINK1 and at Thr-217 is important for mitochondrial localization.	-
217	T	Phosphorylation	Phosphorylation at Thr-175 by PINK1 and at Thr-217 is important for mitochondrial localization.	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of PRKN_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SC6A3_RAT	Slc6a3	physical	17873367
PRKN_RAT	Park2	physical	23258539
PRKN_RAT	Park2	physical	23661642
UB2L3_HUMAN	UBE2L3	physical	23661642
BECN1_RAT	Becn1	physical	24879156
AFAD_RAT	Mllt4	physical	23393160
ARRB1_RAT	Arrb1	physical	21466165
UBC_HUMAN	UBC	physical	26260794
TRIB3_RAT	Trib3	physical	26224857

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.