Human LRRK2 (phospho S935) peptide

Specifications

Form

Lyophilized

General info

Function

Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed : 17114044, PubMed : 20949042, PubMed : 21850687, PubMed : 22012985, PubMed : 23395371, PubMed : 24687852, PubMed : 25201882, PubMed : 26014385, PubMed : 26824392, PubMed : 27830463, PubMed : 28720718, PubMed : 29125462, PubMed : 29127255, PubMed : 29212815, PubMed : 30398148, PubMed : 30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed : 26824392, PubMed : 28720718, PubMed : 29125462, PubMed : 29127255, PubMed : 29212815, PubMed : 30398148, PubMed : 30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed : 23395371, PubMed : 26824392, PubMed : 28720718, PubMed : 29125462, PubMed : 29127255, PubMed : 29212815, PubMed : 30398148, PubMed : 30635421, PubMed : 38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed : 26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed : 26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed : 29125462, PubMed : 30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed : 23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed : 17114044). Plays a role in synaptic vesicle trafficking (PubMed : 24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed : 25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed : 22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed : 22012985). Phosphorylates PRDX3 (PubMed : 21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed : 28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed : 27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed : 26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed : 18230735, PubMed : 26824392, PubMed : 28720718, PubMed : 29125462, PubMed : 29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed : 30209220, PubMed : 38227290).

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Post-translational modifications

Autophosphorylated at Ser-1292; autophosphorylation is stimulated by RAB29 (PubMed:28202711, PubMed:28720718, PubMed:29127255, PubMed:29212815, PubMed:30635421, PubMed:38127736). Phosphorylation of Ser-910 and either Ser-935 or Ser-1444 facilitates interaction with YWHAG (PubMed:28202711). Phosphorylation of Ser-910 and/or Ser-935 facilitates interaction with SFN (PubMed:28202711).. Ubiquitinated by TRIM1; undergoes 'Lys-48'-linked polyubiquitination leading to proteasomal degradation.

Subcellular localisation

Endosome