Dardarina

LRRK2
Egitura erabilgarria PDB Ortologoaren bilaketa: PDBe RCSB PDB ID kodeen zerrenda 2ZEJ, 3D6T
Identifikatzaileak
Aliasak	LRRK2 (HUGO), AURA17, DARDARIN, PARK8, RIPK7, ROCO2, leucine-rich repeat kinase 2, leucine rich repeat kinase 2
Kanpoko IDak	OMIM: 609007   MGI: 1913975   HomoloGene: 18982   GeneCards: LRRK2   OMA: LRRK2 - orthologs
EC Zenbakia	2.7.11.1
Genetikoki lotutako gaixotasunak
Parkinsonen gaixotasun, autosomal dominant Parkinson disease 8 , Parkinsonen gaixotasun, young-onset Parkinson disease , hereditary late onset Parkinson disease
Genearen kokapena (gizakia) Kromosoma: 12 (gizakia) Banda 12q12 Hasiera 40.196.744 bp Amaiera 40.369.285 bp
Genearen kokapena (sagua) Kromosoma: 15 (sagua) Banda 15|15 E3 Hasiera 91.557.378 bp Amaiera 91.700.323 bp
RNA adierazpen eredua Bgee gizakia sagua (ortholog) Adierazpen ohikoena buccal mucosa cell  Monozito lower lobe of lung  odol upper lobe of lung  upper lobe of left lung  eskumako birika  Orpazurda granulozito visceral pleura  Adierazpen ohikoena granulozito human kidney  Hurbileko hodixka bihurgunetsu ezkerreko birika  left lung lobe  right kidney  superior frontal gyrus  lumbar spinal ganglion  Bare eskumako birika  Erreferentziazko adierazpen datu gehiago BioGPS Erreferentziazko adierazpen datu gehiago
Gene ontologia Funtzio molekularra protein homodimerization activity  signaling receptor complex adaptor activity  clathrin binding  co-receptor binding  transferase activity  GTPase activator activity  protein kinase activity  protein kinase A binding  peroxidase inhibitor activity  SNARE binding  nucleotide binding  identical protein binding  GTPase activity  syntaxin-1 binding  protein serine/threonine kinase activity  tubulin binding  transmembrane transporter binding  microtubule binding  MAP kinase kinase activity  GTP binding  ATP binding  GTP-dependent protein kinase activity  beta-catenin destruction complex binding  proteina lotura  kinase activity  actin binding  magnesium ion binding  Zelularen osagaia cytoplasmic vesicle  endosoma  extracellular exosome  Wnt signalosome  soma  trans-Golgi sarea  mitochondrial membranes  sinapsi  zitoplasma  mitochondrial outer membrane  synaptic vesicle membrane  Soma  Erretikulu endoplasmatiko  zelula mintz  mikrobilo  mitochondrial matrix  dendrite cytoplasm  growth cone  cell projection  Dendrita  Lisosoma  neuron projection  Golgi-associated vesicle  mitokondrio  mitochondrial inner membrane  autolysosome  terminal bouton  intrazelular  mintza  lipido baltsa  Axoi  amphisome  multivesicular body, internal vesicle  synaptic vesicle  inklusio-gorputz  Zelulen arteko loturak  cytoplasmic side of mitochondrial outer membrane  zitosol  Golgi aparatu  postsynapse  extracellular space  zelula nukleo  intracellular membrane-bounded organelle  caveola neck  endoplasmic reticulum exit site  glutamatergic synapse  presynaptic cytosol  ribonucleoprotein complex  Prozesu biologikoa lysosome organization  response to oxidative stress  cellular response to dopamine  regulation of autophagy  positive regulation of autophagy  positive regulation of dopamine receptor signaling pathway  regulation of neuroblast proliferation  intracellular distribution of mitochondria  negative regulation of protein processing  negative regulation of protein processing involved in protein targeting to mitochondrion  protein localization to mitochondrion  positive regulation of canonical Wnt signaling pathway  autophagy  neuromuscular junction development  fosforilazio  positive regulation of protein binding  regulation of branching morphogenesis of a nerve  mitochondrion localization  positive regulation of protein autoubiquitination  regulation of synaptic vesicle transport  positive regulation of protein phosphorylation  regulation of kidney size  regulation of synaptic vesicle exocytosis  positive regulation of MAP kinase activity  peptidyl-threonine phosphorylation  MAPK cascade  Wnt signalosome assembly  protein phosphorylation  regulation of synaptic transmission, glutamatergic  excitatory postsynaptic potential  negative regulation of hydrogen peroxide-induced cell death  regulation of dopamine receptor signaling pathway  regulation of membrane potential  protein autophosphorylation  regulation of mitochondrial fission  regulation of neuron maturation  reactive oxygen species metabolic process  positive regulation of programmed cell death  regulation of neuron death  regulation of mitochondrial depolarization  cellular response to oxidative stress  negative regulation of late endosome to lysosome transport  komunikazio intrazelularraren transdukzio  regulation of lysosomal lumen pH  negative regulation of GTPase activity  locomotory exploration behavior  Golgi organization  canonical Wnt signaling pathway  neuron projection morphogenesis  positive regulation of protein ubiquitination  regulation of canonical Wnt signaling pathway  exploration behavior  cellular response to organic cyclic compound  tangential migration from the subventricular zone to the olfactory bulb  regulation of protein kinase A signaling  calcium-mediated signaling  negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation  negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  negative regulation of neuron death  negative regulation of protein targeting to mitochondrion  peptidyl-serine phosphorylation  determination of adult lifespan  negative regulation of excitatory postsynaptic potential  negative regulation of protein phosphorylation  neuron death  GTP metabolic process  negative regulation of autophagosome assembly  olfactory bulb development  cellular response to starvation  regulation of dendritic spine morphogenesis  Zelula bereizte  Endozitosi  negative regulation of protein binding  mitochondrion organization  cellular response to manganese ion  negative regulation of macroautophagy  regulation of locomotion  positive regulation of GTPase activity  regulation of retrograde transport, endosome to Golgi  regulation of CAMKK-AMPK signaling cascade  positive regulation of histone deacetylase activity  endoplasmic reticulum organization  Espermatogenesi  gene-erregulazio  negative regulation of neuron projection development  striatum development  regulation of protein stability  positive regulation of nitric-oxide synthase biosynthetic process  regulation of ER to Golgi vesicle-mediated transport  protein localization to endoplasmic reticulum exit site  neuron projection arborization  regulation of synaptic vesicle endocytosis  positive regulation of synaptic vesicle endocytosis  positive regulation of microglial cell activation  protein import into nucleus  Iturburuak: : Amigo / QuickGO
Ortologoak Espeziea Gizakia Sagua Entrez 120892 66725 Ensembl ENSG00000188906 ENSMUSG00000036273 UniProt Q5S007 Q5S006 RefSeq (RNAm) NM_198578 NM_025730 RefSeq (proteina) NP_940980 NP_080006 Kokapena (UCSC) Chr 12: 40.2 – 40.37 Mb Chr 15: 91.56 – 91.7 Mb PubMed bilaketa
Wikidata
Ikusi/Editatu giza genea Ikusi/Editatu saguaren genea

Dardarina, LRRK2 (ingelesez: Leucine-rich repeat kinase 2) edo PARK8 (Parkinsonen gaixotasunarekin duen lotura dela eta) LRRK2 geneak kodetzen duen giza entzima bat da. Leuzinan aberatsa den errepikapen kinasen familiakoa da. Gene honen aldaerak Parkinsonen gaixotasunarekin eta Crohn gaitzarekin lotzen dira. Mutazio honek Euskal Herrian du jatorria, eta hortik datorkio izena.

Funtzioa

LRRK2 geneak proteina bat kodetzen du, honako ezaugarriekin: armadillo errepikapen eskualde bat, ankirina errepikapen eskualde bat, leuzinan aberatsa den errepikapen domeinu bat, kinasa domeinu bat, RAS domeinu bat, GTPasa domeinu bat eta WD40 domeinu bat. Proteina zitoplasman ugaria da, baina mitokondrien kanpoko mintzarekin loturik agertu ohi da.

LRRK2ek parkinaren R2 RING zink-behatzaren C-terminusarekin elkarrekintza du, eta parkinak LRRK2ren COR domeinuarekin. LRRK2aren espresio mutanteak neuroblastomatan apoptosia eragiten du, baita saguen neurona kortikaletan ere.

Euskal Herriarekiko harremana

Javier Ruiz Martinez neurologoak parte hartzen zuen talde batek aurkitu zuen dardarina Donostiako ospitalean, 2004an. Euskal Herriko hainbat familiatan PARK8 genearen mutazio bat gertatzen ohi da, topatu zutenez. Mutazio horrek LRRK2 entzima eraldatzen du, eta hori lotuta dago Parkinsonen gaitzarekin. Eritasun hori genetikoki transmititzen zela frogatzeko lehen adibidetako bat izan zen. «Euskal mutazioa esaten diote fenomenoari, eta Azpeitia, Azkoitia, Aia eta Itziar [Gipuzkoa] inguruan gertatu zen, lehen aldiz». Ruizek Berriari eskainitako elkarrizketa batean esan zuen fenomenoa noiz gertatu zen kalkula daitekeela: «VIII. edo IX. mendean, uste dugunez».

Harrezkero, inguru horretan zabaldu da gaitza dakarren gene eraldatua. Ondoren, Atlantikoko kostaldean hedatu zen, eta baita Uruguaira heldu ere, euskaldunen batek eramanda. Familia bat Asturiasera (Espainia) bizitzera joan zen, eta han «gune txiki bat daukate». Duela bi urte, Japonian aurkitu dute mutazio bera, baina uste dute ez duela loturarik Euskal Herrikoarekin.

Edonola ere, dardarina ez zen izan LRRK2 entzimari izena jartzeko lehen aukera. «Motelina pentsatu zuten hasieran, jendea ahultzen duelako, baina bazegoen antzeko izena duen beste gauza bat». Azkenean, Jose Felix Marti Masso eta Adolfo Lopez de Muniain sendagileek dardarina jartzea erabaki zuten. Bada Dardarina izeneko tximeleta bat, Mexiko eta Costa Rica artean bizi dena, baina ez da erraz nahastuko euskarazko lehen proteinarekin.

Kanpo estekak

• Parkinsonaren euskal mutazioa sakon ikertu du Javier Ruiz medikuak

• Datuak: Q409961