PRKN_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PRKN_MOUSE
• UniProt AC: Q9WVS6
• Protein Name: E3 ubiquitin-protein ligase parkin {ECO:0000305}
• Gene Name: Prkn {ECO:0000250|UniProtKB:O60260}
• Organism: Mus musculus (Mouse).
• Sequence Length: 464
• 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 endopla
• 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: MIVFVRFNSSYGFPVEVDSDTSILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSIVHIVQRPRRRSHETNASGGDEPQSTSEGSIWESRSLTRVDLSSHTLPVDSVGLAVILDTDSKRDSEAARGPVKPTYNSFFIYCKGPCHKVQPGKLRVQCGTCKQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVALNLITSNRRSIPCIACTDVRSPVLVFQCNHRHVICLDCFHLYCVTRLNDRQFVHDAQLGYSLPCVAGCPNSLIKELHHFRILGEEQYTRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQRKVTCEGGNGLGCGFVFCRDCKEAYHEGDCDSLLEPSGATSQAYRVDKRAAEQARWEEASKETIKKTTKPCPRCNVPIEKNGGCMHMKCPQPQCKLEWCWNCGCEWNRACMGDHWFDV

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 CCCCHHHHHEEEECC		-
77	Phosphorylation	VQRPRRRSHETNASG ECCCCCCCCCCCCCC		19060867
80	Phosphorylation	PRRRSHETNASGGDE CCCCCCCCCCCCCCC		11122330
83	Phosphorylation	RSHETNASGGDEPQS CCCCCCCCCCCCCCC		29899451
90	Phosphorylation	SGGDEPQSTSEGSIW CCCCCCCCCCCCCCC		21183079
108	Phosphorylation	SLTRVDLSSHTLPVD CCEEEECCCCCCCCC		21183079
109	Phosphorylation	LTRVDLSSHTLPVDS CEEEECCCCCCCCCC		19060867
111	Phosphorylation	RVDLSSHTLPVDSVG EEECCCCCCCCCCEE		23984901
174	Phosphorylation	TCKQATLTLAQGPSC CCCCEEEEECCCCCC		-
216	Phosphorylation	FKCGAHPTSDKDTSV EECCCCCCCCCCCHH		-
312	Phosphorylation	ILGEEQYTRYQQYGA ECCHHHHHHHHHHCC		21454597

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	Q99MQ3	Uniprot
131	S	Phosphorylation	Kinase	P38A	P47811	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	Prkn	Q9WVS6	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.	-
174	T	Phosphorylation	Phosphorylation at Thr-174 by PINK1 and at Thr-216 is important for mitochondrial localization.	-
216	T	Phosphorylation	Phosphorylation at Thr-174 by PINK1 and at Thr-216 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_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
BCL2_MOUSE	Bcl2	physical	20889974
ABL1_MOUSE	Abl1	physical	20823226
AMRA1_MOUSE	Ambra1	physical	21753002
CSKP_MOUSE	Cask	physical	17553932
SH3G2_MOUSE	Sh3gl2	physical	20064468
SH3G1_MOUSE	Sh3gl1	physical	20064468
SH3G3_MOUSE	Sh3gl3	physical	20064468
SYUA_HUMAN	SNCA	genetic	19680561
ACTS_MOUSE	Acta1	physical	19909785
BAX_MOUSE	Bax	physical	22460798
HDAC6_MOUSE	Hdac6	physical	23258539
TADBP_HUMAN	TARDBP	physical	23258539
BECN1_MOUSE	Becn1	physical	24879156
ACTB_MOUSE	Actb	physical	24879156
BECN1_MOUSE	Becn1	physical	23737459
UCHL1_MOUSE	Uchl1	physical	25403879
MFN2_MOUSE	Mfn2	physical	24379352
HS71A_MOUSE	Hspa1a	physical	24379352
UB2L3_MOUSE	Ube2l3	physical	20064468
PTN5_MOUSE	Ptpn5	physical	25583483
BECN1_MOUSE	Becn1	physical	24386307
GRIK2_MOUSE	Grik2	physical	25316086
CAV1_MOUSE	Cav1	physical	26627850

Drug and Disease Associations

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