The following text describes a protein:
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. Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation. Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43. Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (By similarity). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (By similarity). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain. 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 (By similarity). Regulates neuronal process morphology in the intact central nervous system (CNS) (By similarity). 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. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (By similarity). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (By similarity). Phosphorylates PRDX3 (By similarity). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis. Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (By similarity). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (By similarity). In addition, has GTPase activity via its Roc domain which regulates LRKK2 kinase activity (By similarity). 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.
Subcellular Localization:
Cytoplasmic vesicle. Perikaryon. Cell projection, axon. Cell projection, dendrite. Golgi apparatus membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane. Endosome. Lysosome. Mitochondrion outer membrane; Peripheral membrane protein. Cytoplasm, cytoskeleton. Cytoplasmic vesicle, phagosome. Note=Colocalized with RAB29 along tubular structures emerging from Golgi apparatus (By similarity). Localizes to endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). Detected on phagosomes and stressed lysosomes but not detected on autophagosomes induced by starvation. Recruitment to stressed lysosomes is dependent on the ATG8 conjugation system composed of ATG5, ATG12 and ATG16L1 and leads to lysosomal stress-induced activation of LRRK2.
Domain:
The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins (By similarity). It also mediates homodimerization and regulates kinase activity (By similarity); The COR domain mediates homodimerization; it also mediates homotetramerization via interaction with the protein kinase domain; The Roc domain mediates homodimerization and regulates kinase activity.
Sequence:
MASGACQGCEEEEEEEALKKLIVRLNNVQEGKQIETLLQLLEDMLVFTYSDRASKLFEDKNFHVPLLIVLDSYMRVASVQQAGWSLLCKLIEVCPGTLQSLIGPQDIGNDWEVLGIHRLILKMLTVHHANVNLSIVGLKALDLLLDSGKLTLLILDEECDIFLLIFDAMHRYSANDEVQKLGCKALHVLFERVSEEQLTEFVENKDYTILLSTFGSFRRDKEIVYHVLCCLHSLAVTCSNVEVLMSGNVRCYNLVVEAMKAFPTNENIQEVSCSLFQKLTLGNFFNILVLNEVHVFVVKAVRQYPENAALQISALSCLALLTETIFLNQDLEERSETQEQSEEEDSEKLFWLEPCYKALVRHRKDKHVQEAACWALNNLLMYQNSLHEKIGDEDGQFPAHREVMLSMLMHSSSKDVFQAAAHALSTLLEQNVNFRKILLAKGVYLNVLELMQKHAHAPEVAESGCKMLSHLFEGSNPSLDTMAAVVPKILTVMKAHGTSLSVQLEALRAILHFVVPGLLEESREDSQCRPNVLRKQCFRTDIHKLVLVALNRFIGNPGIQKCGLKVISSLAHLPDATETLSLQGAVDSVLHTLQMYPDDQEIQCLGLHLMGCLMTKKNFCIGTGHLLAKILASTLQRFKDVAEVQTTGLQTTLSILELSVSFSKLLVHYSFDVVIFHQMSSSVVEQKDEQFLNLCCKCFAKVAVDDELKNTMLERACDQNNSIMVECLLLLGADANQVKGATSLIYQVCEKESSPKLVELLLNGGCREQDVRKALTVSIQKGDSQVISLLLRKLALDLANNSICLGGFGIGKIDPSWLGPLFPDKSSNLRKQTNTGSVLARKVLRYQMRNTLQEGVASGSDGKFSEDALAKFGEWTFIPDSSMDSVFGQSDDLDSEGSESSFLVKRKSNSISVGEVYRDLALQRCSPNAQRHSNSLGPVFDHEDLLRRKRKILSSDESLRSSRLPSHMRQSDSSSSLASEREHITSLDLSANELKDIDALSQKCCLSSHLEHLTKLELHQNSLTSFPQQLCETLKCLIHLDLHSNKFTSFPSFVLKMPRITNLDASRNDIGPTVVLDPAMKCPSLKQLNLSYNQLSSIPENLAQVVEKLEQLLLEGNKISGICSPLSLKELKILNLSKNHIPSLPGDFLEACSKVESFSARMNFLAAMPALPSSITSLKLSQNSFTCIPEAIFSLPHLRSLDMSHNNIECLPGPAHWKSLNLRELIFSKNQISTLDFSENPHVWSRVEKLHLSHNKLKEIPPEIGCLENLTSLDVSYNLELRSFPNEMGKLSKIWDLPLDGLHLNFDFKHVGCKAKDIIRFLQQRLKKAVPYNRMKLMIVGNTGSGKTTLLQQLMKMKKPELGMQGATVGIDVRDWSIQIRGKRRKDLVLNVWDFAGREEFYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKPWLFNIKARASSSPVILVGTHLDVSDEKQRKACISKITKELLNKRGFPTIRDYHFVNATEESDALAKLRKTIINESLNFKIRDQPVVGQLIPDCYVELEKIILSERKAVPTEFPVINRKHLLQLVNEHQLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKVMAQILTVKVDGCLKHPKGIISRRDVEKFLSKKKRFPKNYMMQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPFMLSGRERALRPNRMYWRQGIYLNWSPEAYCLVGSEVLDNRPESFLKITVPSCRKGCILLGRVVDHIDSLMEEWFPGLLEIDICGEGETLLKKWALYSFNDGEEHQKILLDELMKKAEEGDLLINPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEEAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELVVLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLHDIWTTGSRIMEGLRFPNEFDELAIQGKLPDPVKEYGCAPWPMVEKLITKCLKENPQERPTSAQVFDILNSAELICLMRHILIPKNIIVECMVATNLNSKSATLWLGCGNTEKGQLSLFDLNTERYSYEEVADSRILCLALVHLAAEKESWVVCGTQSGALLVINVEEETKRHTLEKMTDSVTCLHCNSLAKQSKQSNFLLVGTADGNLMIFEDKAVKCKGAAPLKTLHIGDVSTPLMCLSESLNSSERHITWGGCGTKVFSFSNDFTIQKLIETKTNQLFSYAAFSDSNIIALAVDTALYIAKKNSPVVEVWDKKTEKLCELIDCVHFLKEVMVKLNKESKHQLSYSGRVKALCLQKNTALWIGTGGGHILLLDLSTRRVIRTIHNFCDSVRAMATAQLGSLKNVMLVLGYKRKSTEGIQEQKEIQSCLSIWDLNLPHEVQNLEKHIEVRTELADKMRKTSVE