Tchem Leucine-rich repeat serine/threonine-protein kinase 2

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Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. 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. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.

This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8. [provided by RefSeq, Jul 2008]

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Property Summary

Ligand Count	465
NCBI Gene PubMed Count	767
PubMed Score	1241.37

PubTator Score	1294.44

Knowledge Summary

Patent (36,126)

TINX Plot

Disease (8)

Disease	Target Count	Z-score	Confidence
Carcinoma, Renal Cell	124	0.0	0.0
Endometriosis	540	0.0	0.0
Nerve Degeneration	121	0.0	0.0
PARKINSON DISEASE 8, AUTOSOMAL DOMINANT	1	0.0	0.0
Parkinson Disease	64	0.0	0.0
Parkinsonian Disorders	56	0.0	0.0

Disease	Target Count
Autosomal dominant late onset Parkinson disease	7
Depressive Symptoms	28
PARKINSON DISEASE 19, JUVENILE-ONSET	10
PARKINSON DISEASE 8 (disorder)	1
Renal Cell Carcinoma	214
Schizophrenia	1160
Young onset Parkinson disease	10

Disease	Target Count	P-value
lung carcinoma	2843	2.2e-42
non-small cell lung cancer	2890	1.1e-25
tuberculosis	2010	2.0e-07
ovarian cancer	8520	3.8e-07
atypical teratoid / rhabdoid tumor	5112	3.6e-05
medulloblastoma, large-cell	6241	6.1e-05
acute quadriplegic myopathy	1158	1.1e-04
lung adenocarcinoma	2716	1.2e-04
Astrocytoma, Pilocytic	3081	1.7e-04
osteosarcoma	7950	5.0e-04
ulcerative colitis	1819	5.3e-04
intraductal papillary-mucinous adenoma (IPMA)	2955	6.9e-04
Pick disease	1894	1.2e-03
group 3 medulloblastoma	4104	1.2e-03
diabetes mellitus	1728	4.6e-03
intraductal papillary-mucinous carcinoma (IPMC)	2989	6.2e-03
mucosa-associated lymphoid tissue lymphoma	484	6.4e-03
invasive ductal carcinoma	2951	7.6e-03

Disease	Target Count	Confidence
Carcinoma	11493	1.5
Kidney cancer	2613	0.9
Large intestine cancer	126	0.9
Melanoma	711	0.5
Skin cancer	469	0.5

Disease	Target Count	Z-score	Confidence
Parkinson's disease	392	7.964	4.0
Crohn's disease	321	3.232	1.6

Disease	Target Count	Z-score	Confidence
Neurodegenerative disease	414	0.0	4.0

Disease	Target Count	Z-score	Confidence
Movement disease	11	5.147	2.6
Dementia	175	4.109	2.1
Leprosy	73	3.654	1.8
Multiple system atrophy	29	3.614	1.8
REM sleep behavior disorder	14	3.461	1.7
Alzheimer's disease	658	3.195	1.6
Toxic encephalopathy	141	3.138	1.6

Disease	Target Count
Common variable immunodeficiency	101
PARKINSON DISEASE, LATE-ONSET	20
autosomal dominant Parkinson disease 8	1

Differential Expression (18)

Disease	log2 FC	p
ovarian cancer	-1.600	3.8e-07
acute quadriplegic myopathy	2.021	1.1e-04
Astrocytoma, Pilocytic	1.700	1.7e-04
atypical teratoid / rhabdoid tumor	-2.200	3.6e-05
diabetes mellitus	-1.200	4.6e-03
group 3 medulloblastoma	-2.300	1.2e-03
intraductal papillary-mucinous adenoma (...	-1.800	6.9e-04
intraductal papillary-mucinous carcinoma...	-1.700	6.2e-03
invasive ductal carcinoma	-1.100	7.6e-03
lung adenocarcinoma	-1.300	1.2e-04
lung carcinoma	-5.300	2.2e-42
medulloblastoma, large-cell	-3.200	6.1e-05
mucosa-associated lymphoid tissue lympho...	2.146	6.4e-03
non-small cell lung cancer	-4.006	1.1e-25
osteosarcoma	-3.506	5.0e-04
Pick disease	-1.300	1.2e-03
tuberculosis	3.200	2.0e-07
ulcerative colitis	1.700	5.3e-04

Nerve - Tibial 18,007

Lung 18,057

Vagina 17,834

Uterus 17,618

Artery - Aorta 17,896

Artery - Coronary 17,949

Ovary 17,971

Artery - Tibial 17,631

Whole Blood 17,439

Spleen 17,614

Esophagus - Gastroesophageal Junction 18,000

Esophagus - Muscularis 18,017

Colon - Sigmoid 18,089

Thyroid 18,024

Small Intestine - Terminal Ileum 17,954

Adipose - Subcutaneous 18,110

Cells - EBV-transformed lymphocytes 18,186

Adipose - Visceral (Omentum) 17,937

Brain - Frontal Cortex (BA9) 18,069

Esophagus - Mucosa 18,076

Breast - Mammary Tissue 18,103

Brain - Cortex 18,039

Brain - Spinal cord (cervical c-1) 17,973

Cells - Transformed fibroblasts 17,577

Minor Salivary Gland 18,005

Prostate 18,213

Brain - Hypothalamus 18,169

Stomach 17,879

Brain - Nucleus accumbens (basal ganglia... 18,024

Brain - Anterior cingulate cortex (BA24) 17,989

Heart - Atrial Appendage 17,896

Brain - Substantia nigra 17,981

Skin - Not Sun Exposed (Suprapubic) 18,081

Skin - Sun Exposed (Lower leg) 17,968

Brain - Caudate (basal ganglia) 18,001

Kidney - Cortex 17,329

Adrenal Gland 18,071

Pituitary 18,147

Brain - Amygdala 18,006

Muscle - Skeletal 17,778

Brain - Cerebellum 17,983

Brain - Cerebellar Hemisphere 18,015

Brain - Putamen (basal ganglia) 17,863

Brain - Hippocampus 18,011

Liver 18,071

Colon - Transverse 17,825

Testis 18,518

Pancreas 18,123

Heart - Left Ventricle 18,006

Monocytes 7,422

B Cells 9,086

Adult Liver 9,113

Adult Frontal Cortex 9,048

Adult Ovary 10,192

Adult Adrenal 8,475

Adult Kidney 6,723

Platelets 6,131

Adult Lung 6,663

NK Cells 8,475

CD4 Cells 7,773

Adult Colon 7,915

Fetal Brain 7,866

CD8 Cells 9,840

Adult Retina 10,115

Fetal Gut 8,640

Adrenal gland

Brain

Colon

Frontal lobe

Gall bladder

Kidney

Liver

Lung

B-lymphocyte

Monocyte

Natural killer cell

Ovary

Pancreas

Prostate gland

Retina

Testis

Urinary bladder

BTO:0004410

BTO:0005453

adipose tissue 15,837

adrenal gland 15,963

appendix 16,247

bone marrow 14,571

breast 16,063

cerebral cortex 16,630

cervix, uterine 15,871

colon 15,959

duodenum 15,975

endometrium 16,349

epididymis 15,863

esophagus 15,898

fallopian tube 16,245

gallbladder 16,333

heart muscle 14,972

kidney 15,917

liver 14,587

lung 16,312

lymph node 15,833

ovary 15,408

pancreas 14,070

parathyroid gland 14,769

placenta 15,937

prostate 16,460

rectum 15,705

salivary gland 14,981

seminal vesicle 15,918

skeletal muscle 14,011

skin 16,206

small intestine 16,154

smooth muscle 15,857

spleen 15,972

stomach 16,099

testis 17,936

thyroid gland 15,959

tonsil 15,400

urinary bladder 15,814

Liver and Pancreas 16,750

Digestive Tract 17,369

Urinary Tract 16,678

Endocrine System 18,159

Blood and immune system 16,909

Respiratory system 16,393

Female tissues 17,400

Male tissues 17,142

Skin and soft tissues 17,230

Nervous System 16,725

Cardiovascular System 15,192

Brain 7,346

Liver 5,008

Testis 3,897

See source...

Neuron 779

Ganglion 334

Brain 1,516

SH-SY5Y cell 74

Spinal cord 549

Substantia nigra cell line 8

See source...

Synonym

Accession	Q5S007 A6NJU2 Q6ZS50 Q8NCX9
Symbols	PARK8 RIPK7 ROCO2 AURA17 DARDARIN

Gene

LRRK2

Ortholog (13)

Species	Source	Disease
Macaque 12,761	Inparanoid OMA EggNOG
Chimp 14,140	OMA EggNOG
Rat 15,117	Inparanoid OMA EggNOG
Mouse 16,570	Inparanoid OMA EggNOG
Horse 14,252	Inparanoid OMA EggNOG
Dog 15,073	Inparanoid OMA EggNOG
Pig 10,168	Inparanoid OMA EggNOG
Cow 15,320	Inparanoid OMA EggNOG
Chicken 7,827	OMA EggNOG
Opossum 12,230	Inparanoid OMA EggNOG
Xenopus 10,468	Inparanoid OMA EggNOG
Anole lizard 10,588	Inparanoid OMA EggNOG
Zebrafish 9,726	Inparanoid OMA

UniProt Keyword (35)

Complete proteome 20,231

Polymorphism 12,194

Reference proteome 20,231

Repeat 4,916

Cell projection 826

Cytoplasm 4,952

Disease mutation 2,804

Phosphoprotein 8,216

Membrane 7,361

WD repeat 277

See all...

GO Function (24)

identical protein binding 1,084

protein homodimerization activity 801

ATP binding 1,477

actin binding 272

clathrin binding 45

ion channel binding 118

GTPase activator activity 281

protein serine-threonine kinase activity 360

GTP binding 372

GTPase activity 286

See all...

GO Component (40)

nucleus 5,097

cytoplasm 4,094

cytosol 4,834

plasma membrane 4,414

cytoplasmic vesicle 217

Golgi apparatus 904

endoplasmic reticulum 938

extracellular space 1,380

intracellular membrane-bounded organelle 593

mitochondrial inner membrane 432

See all...

GO Process (83)

regulation of canonical Wnt signaling pa... 21

intracellular signal transduction 376

response to oxidative stress 101

endocytosis 128

calcium-mediated signaling 49

neuron death 11

Golgi organization 79

protein autophosphorylation 168

protein phosphorylation 334

positive regulation of protein binding 67

See all...

Compartment GO Term (115)

Amphisome 6

Autolysosome 23

Autophagosome 114

Axon 294

Axon part 97

Axon terminus 93

Bounding membrane of organelle 1,956

Caveola 63

Caveola neck 2

Cell 16,178

Cell body 251

Cell junction 960

Cell part 16,177

Cell periphery 5,382

Cell projection 1,541

See all...

OMIM Phenotype (1)

Phenotype: {Parkinson disease 8} 1

MGI Phenotype (14)

endocrine-exocrine gland phenotype 2,293

integument phenotype 1,874

homeostasis-metabolism phenotype 4,747

cellular phenotype 3,637

nervous system phenotype 3,447

hematopoietic system phenotype 3,383

cardiovascular system phenotype 2,660

mortality-aging 5,018

respiratory system phenotype 1,390

renal-urinary system phenotype 1,269

See all...

GWAS Trait (5)

Inflammatory bowel disease 235

Crohn's disease 215

Daytime sleep phenotypes 48

Parkinson's disease 90

Pediatric autoimmune diseases 43

HCA RNA Cell Line (44)

A549 15,174

AF22 16,160

ASC TERT1 14,842

BEWO 16,726

BJ 15,448

BJ hTERT+ 15,353

BJ hTERT+ SV40 Large T+ 15,609

BJ hTERT+ SV40 Large T+ RasG12V 15,493

CACO-2 15,436

CAPAN-2 16,102

See all...

Pathway (9)

Parkinson's disease 142

Signal Transduction 2,657

PTK6 promotes HIF1A stabilization 5

Signaling by Non-Receptor Tyrosine Kinas... 53

Signaling by PTK6 53

Wnt Signaling Pathway and Pluripotency 101

MAPK Signaling Pathway 245

Parkinsons Disease Pathway 39

Allograft Rejection 168

Protein-protein Interaction (1)

PTK6

PDB (4)

...
More...

Drug (1)

sunitinib
pIC50 7.55

Ligand (464)

CHEMBL3641807
pKi 7.54

CHEMBL2170016
pIC50 7.54

CHEMBL3122120
pIC50 7.54

CHEMBL3651763
pKi 7.54

CHEMBL3651802
pKi 7.54

CHEMBL2347823
pIC50 7.55

CHEMBL2347805
pIC50 7.55

CHEMBL3641893
pKi 7.55

CHEMBL3797298
pKi 7.55

CHEMBL3641836
pKi 7.55

CHEMBL2326726
pIC50 7.55

CHEMBL3393354
pIC50 7.55

CHEMBL3393343
pIC50 7.55

CHEMBL3641832
pKi 7.56

CHEMBL3651732
pKi 7.57

CHEMBL2333126
pIC50 7.57

CHEMBL2178127
pIC50 7.57

CHEMBL2347811
pIC50 7.57

CHEMBL2178137
pIC50 7.57

CHEMBL3694809
pKi 7.57

See all 464 ligands...

Gene RIF (829)

AA Sequence

MASGSCQGCEEDEETLKKLIVRLNNVQEGKQIETLVQILEDLLVFTYSERASKLFQGKNIHVPLLIVLDS      1 - 70
YMRVASVQQVGWSLLCKLIEVCPGTMQSLMGPQDVGNDWEVLGVHQLILKMLTVHNASVNLSVIGLKTLD     71 - 140
LLLTSGKITLLILDEESDIFMLIFDAMHSFPANDEVQKLGCKALHVLFERVSEEQLTEFVENKDYMILLS    141 - 210
ALTNFKDEEEIVLHVLHCLHSLAIPCNNVEVLMSGNVRCYNIVVEAMKAFPMSERIQEVSCCLLHRLTLG    211 - 280
NFFNILVLNEVHEFVVKAVQQYPENAALQISALSCLALLTETIFLNQDLEEKNENQENDDEGEEDKLFWL    281 - 350
EACYKALTWHRKNKHVQEAACWALNNLLMYQNSLHEKIGDEDGHFPAHREVMLSMLMHSSSKEVFQASAN    351 - 420
ALSTLLEQNVNFRKILLSKGIHLNVLELMQKHIHSPEVAESGCKMLNHLFEGSNTSLDIMAAVVPKILTV    421 - 490
MKRHETSLPVQLEALRAILHFIVPGMPEESREDTEFHHKLNMVKKQCFKNDIHKLVLAALNRFIGNPGIQ    491 - 560
KCGLKVISSIVHFPDALEMLSLEGAMDSVLHTLQMYPDDQEIQCLGLSLIGYLITKKNVFIGTGHLLAKI    561 - 630
LVSSLYRFKDVAEIQTKGFQTILAILKLSASFSKLLVHHSFDLVIFHQMSSNIMEQKDQQFLNLCCKCFA    631 - 700
KVAMDDYLKNVMLERACDQNNSIMVECLLLLGADANQAKEGSSLICQVCEKESSPKLVELLLNSGSREQD    701 - 770
VRKALTISIGKGDSQIISLLLRRLALDVANNSICLGGFCIGKVEPSWLGPLFPDKTSNLRKQTNIASTLA    771 - 840
RMVIRYQMKSAVEEGTASGSDGNFSEDVLSKFDEWTFIPDSSMDSVFAQSDDLDSEGSEGSFLVKKKSNS    841 - 910
ISVGEFYRDAVLQRCSPNLQRHSNSLGPIFDHEDLLKRKRKILSSDDSLRSSKLQSHMRHSDSISSLASE    911 - 980
REYITSLDLSANELRDIDALSQKCCISVHLEHLEKLELHQNALTSFPQQLCETLKSLTHLDLHSNKFTSF    981 - 1050
PSYLLKMSCIANLDVSRNDIGPSVVLDPTVKCPTLKQFNLSYNQLSFVPENLTDVVEKLEQLILEGNKIS   1051 - 1120
GICSPLRLKELKILNLSKNHISSLSENFLEACPKVESFSARMNFLAAMPFLPPSMTILKLSQNKFSCIPE   1121 - 1190
AILNLPHLRSLDMSSNDIQYLPGPAHWKSLNLRELLFSHNQISILDLSEKAYLWSRVEKLHLSHNKLKEI   1191 - 1260
PPEIGCLENLTSLDVSYNLELRSFPNEMGKLSKIWDLPLDELHLNFDFKHIGCKAKDIIRFLQQRLKKAV   1261 - 1330
PYNRMKLMIVGNTGSGKTTLLQQLMKTKKSDLGMQSATVGIDVKDWPIQIRDKRKRDLVLNVWDFAGREE   1331 - 1400
FYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKPWLFNIKARASSSPVILVGTHLDVSDEKQRKACMSKIT   1401 - 1470
KELLNKRGFPAIRDYHFVNATEESDALAKLRKTIINESLNFKIRDQLVVGQLIPDCYVELEKIILSERKN   1471 - 1540
VPIEFPVIDRKRLLQLVRENQLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKIMAQI   1541 - 1610
LTVKVEGCPKHPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVI   1611 - 1680
ELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYMLSGRERALRPNRMYWRQGIYLNWSPEAYCLV   1681 - 1750
GSEVLDNHPESFLKITVPSCRKGCILLGQVVDHIDSLMEEWFPGLLEIDICGEGETLLKKWALYSFNDGE   1751 - 1820
EHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEQAPEFLLGDGSF   1821 - 1890
GSVYRAAYEGEEVAVKIFNKHTSLRLLRQELVVLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQ   1891 - 1960
QDKASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIK   1961 - 2030
TSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPVKEYG   2031 - 2100
CAPWPMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNVIVECMVATHHNSRNASIWLG   2101 - 2170
CGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKESWIVSGTQSGTLLVINTEDGKKRHTLEK   2171 - 2240
MTDSVTCLYCNSFSKQSKQKNFLLVGTADGKLAIFEDKTVKLKGAAPLKILNIGNVSTPLMCLSESTNST   2241 - 2310
ERNVMWGGCGTKIFSFSNDFTIQKLIETRTSQLFSYAAFSDSNIITVVVDTALYIAKQNSPVVEVWDKKT   2311 - 2380
EKLCGLIDCVHFLREVMVKENKESKHKMSYSGRVKTLCLQKNTALWIGTGGGHILLLDLSTRRLIRVIYN   2381 - 2450
FCNSVRVMMTAQLGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHIEVRKELAEK   2451 - 2520
MRRTSVE                                                                  2521 - 2527
//

Text Mined References (771)

Summary
Details

	PMID	Year	Title

Tchem Leucine-rich repeat serine/threonine-protein kinase 2 Add to cart View Collections Empty Collection

Property Summary

Knowledge Summary

Patent (36,126)

TINX Plot

Disease (8)

Expression

Differential Expression (18)

Synonym

Gene

Ortholog (13)

UniProt Keyword (35)

GO Function (24)

GO Component (40)

GO Process (83)

Compartment GO Term (115)

OMIM Phenotype (1)

MGI Phenotype (14)

GWAS Trait (5)

HCA RNA Cell Line (44)

Pathway (9)

Protein-protein Interaction (1)

PDB (4)

Drug (1)

Ligand (464)

Gene RIF (829)

AA Sequence

Text Mined References (771)

Tchem Leucine-rich repeat serine/threonine-protein kinase 2

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