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MPP notes (dja) :

MPP OUTSIDE REQUEST FORM Review Date 8/3/11 Requestor(s): Brad Gibson/Liza Pon

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MPP notes (dja) :

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  1. MPP OUTSIDE REQUEST FORM Review Date 8/3/11 Requestor(s): Brad Gibson/Liza Pon Institution: Buck Institute, Novato, CA/Columbia University Request Title: mouse and human mitochondrial protein PINK1

  2. MPP notes (dja): Function and Medical Relevance: Serine/threonine protein kinase, “Protects against mitochondrial dysfunction during cellular stress, potentially by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). It is necessary for PARK2 recruitement to dysfunctional mitochondria to initiate their degradation.” (Uniprot) Physical Characteristics: Transit or Signal Peptides – transit peptide (1-77, Uniprot and TargetP; 1-28 DomainView). Functional Domains – protein kinase (156-511 Uniprot, 262-508 pfam), ATP-binding region (162-170), ATP-binding site (186), proton-accepting active site (362). C3HC4-type RING finger binding domain inferred. TMs – predicted single pass (94-110 Uniprot; 274-293 HMMTop). PTMs - Predicted to autophosphorylate. Quaternary Structure – no information. Isoforms – this is canonical, isoform 2 is missing 1-307 and 308-320 are altered. Similar Structures:271-386 is 43% identical to 3e7oB (human MAP Kinase), 335-453 is 43% identical to 2wntA (human ribosomal protein S6 kinase). Interactors: Substrates are ATP and unknown protein(s) , products are ADP and phosphorylated protein(s), cofactors are Mg2+ and possibly Ca2+ (calcium-dependent protein kinase activity has been cited). Binds PARK7, PARK2, HTRA2, CDC37, HSP90AA1, ubiquitin, ubiquitin protein ligase/Parkin, Hsp75 mitochondrial precursor. Status:MPP – full-length was selected in MPP10 (Collaborator Workgroup #3) and is in cloning. NESG (ID HR6725) – large number of constructs generated that have not expressed, 145-516 expressed insoluble. Other SG – none. Other: Human and mouse are 82% identical. Suggestions 1) Try in cell-free: -full-length - Nd77 (minus transit pep, uniprot and TargetP prediction) - Nd28 (minus transit pep, DomainView prediction) - C-term domain (e.g. 308-, corresponding to isoform 2) 2) Add mouse version?

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