Lrrk2 leucine-rich repeat kinase 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Lrrk2provided by RGD
Official Full Name: leucine-rich repeat kinase 2provided by RGD
Primary source: RGD:1561168
See related: EnsemblRapid:ENSRNOG00000004048 AllianceGenome:RGD:1561168
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Predicted to enable several functions, including GTP binding activity; cytoskeletal protein binding activity; and protein serine/threonine kinase activity. Involved in several processes, including nervous system development; positive regulation of macromolecule metabolic process; and positive regulation of microglial cell activation. Located in several cellular components, including axon; dendrite; and perikaryon. Used to study neurodegenerative disease. Biomarker of diabetic neuropathy. Human ortholog(s) of this gene implicated in Crohn's disease; Parkinson's disease; Parkinson's disease 8; Parkinsonism; and cancer. Orthologous to human LRRK2 (leucine rich repeat kinase 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Lung (RPKM 204.9), Spleen (RPKM 172.7) and 8 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q35

Exon count:: 53

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (124706246..124867234)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (122826696..122987711)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (132857311..133018549)

Chromosome 7 - NC_086025.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Knocking out the LRRK2 gene increases sensitivity to wavelength information in rats.
Title: Knocking out the LRRK2 gene increases sensitivity to wavelength information in rats.
A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.
Title: A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.
The Relationship between Iron and LRRK2 in a 6-OHDA-Induced Parkinson's Disease Model.
Title: The Relationship between Iron and LRRK2 in a 6-OHDA-Induced Parkinson's Disease Model.
LRRK2 Ablation Attenuates Alphalpha-Synuclein-Induced Neuroinflammation Without Affecting Neurodegeneration or Neuropathology In Vivo.
Title: LRRK2 Ablation Attenuates Αlpha-Synuclein-Induced Neuroinflammation Without Affecting Neurodegeneration or Neuropathology In Vivo.
Inhibition of LRRK2 restores parkin-mediated mitophagy and attenuates intervertebral disc degeneration.
Title: Inhibition of LRRK2 restores parkin-mediated mitophagy and attenuates intervertebral disc degeneration.
VIP Induces Changes in the F-/G-Actin Ratio of Schlemm's Canal Endothelium via LRRK2 Transcriptional Regulation.
Title: VIP Induces Changes in the F-/G-Actin Ratio of Schlemm's Canal Endothelium via LRRK2 Transcriptional Regulation.
Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity.
Title: Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity.
Repeated exposure to inflammatory triggers may be needed for LRRK2 mutation carriers to develop active PD.
Title: Single Inflammatory Trigger Leads to Neuroinflammation in LRRK2 Rodent Model without Degeneration of Dopaminergic Neurons.
Our work defines a novel interaction between the LRRK2 protein and the vATPase a1 subunit and demonstrates a mode of action by which drugs may rescue lysosomal dysfunction. These results demonstrate the importance of LRRK2 in lysosomal biology, as well as the critical role of the lysosome in PD.
Title: LRRK2 interacts with the vacuolar-type H+-ATPase pump a1 subunit to regulate lysosomal function.
Our study demonstrates extensive alterations across the endocytic pathway associated with LRRK2 mutations in iPSC-derived dopaminergic neurons and BAC transgenic rats
Title: An integrated transcriptomics and proteomics analysis reveals functional endocytic dysregulation caused by mutations in LRRK2.

Submit: New GeneRIF Correction See all GeneRIFs (35)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D7Rat6 (e-PCR)
- UniSTS:119051

RH138644 (e-PCR)
- UniSTS:220731

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GTP binding	ISO Inferred from Sequence Orthology more info
enables GTP-dependent protein kinase activity	ISO Inferred from Sequence Orthology more info
enables GTPase activator activity	ISO Inferred from Sequence Orthology more info
enables GTPase activity	ISO Inferred from Sequence Orthology more info
enables JUN kinase kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables JUN kinase kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables MAP kinase kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables SNARE binding	ISO Inferred from Sequence Orthology more info
enables actin binding	ISO Inferred from Sequence Orthology more info
enables beta-catenin destruction complex binding	ISO Inferred from Sequence Orthology more info
enables clathrin binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables kinase activity	ISO Inferred from Sequence Orthology more info
enables kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables peroxidase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein kinase A binding	ISO Inferred from Sequence Orthology more info
enables protein kinase activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables signaling receptor complex adaptor activity	ISO Inferred from Sequence Orthology more info
enables small GTPase binding	ISO Inferred from Sequence Orthology more info
enables syntaxin-1 binding	ISO Inferred from Sequence Orthology more info
enables transmembrane transporter binding	ISO Inferred from Sequence Orthology more info
enables tubulin binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in GTP metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within Golgi organization	ISO Inferred from Sequence Orthology more info
involved_in Golgi organization	ISO Inferred from Sequence Orthology more info
involved_in JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in Rho protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in Wnt signalosome assembly	ISO Inferred from Sequence Orthology more info
involved_in calcium-mediated signaling	ISO Inferred from Sequence Orthology more info
involved_in cellular response to dopamine	ISO Inferred from Sequence Orthology more info
involved_in cellular response to manganese ion	ISO Inferred from Sequence Orthology more info
involved_in cellular response to organic cyclic compound	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in cellular response to reactive oxygen species	ISO Inferred from Sequence Orthology more info
involved_in cellular response to starvation	ISO Inferred from Sequence Orthology more info
involved_in determination of adult lifespan	ISO Inferred from Sequence Orthology more info
involved_in endocytosis	ISO Inferred from Sequence Orthology more info
involved_in endoplasmic reticulum organization	ISO Inferred from Sequence Orthology more info
involved_in excitatory postsynaptic potential	ISO Inferred from Sequence Orthology more info
involved_in excitatory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in exploration behavior	ISO Inferred from Sequence Orthology more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in intracellular distribution of mitochondria	ISO Inferred from Sequence Orthology more info
involved_in intracellular signal transduction	ISO Inferred from Sequence Orthology more info
involved_in intracellular signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in locomotory exploration behavior	ISO Inferred from Sequence Orthology more info
involved_in locomotory exploration behavior	ISS Inferred from Sequence or Structural Similarity more info
involved_in lysosome organization	ISO Inferred from Sequence Orthology more info
involved_in mitochondrion localization	ISO Inferred from Sequence Orthology more info
involved_in mitochondrion organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of Notch signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of autophagosome assembly	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of excitatory postsynaptic potential	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of macroautophagy	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of protein processing	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein targeting to mitochondrion	ISO Inferred from Sequence Orthology more info
involved_in neuromuscular junction development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuron differentiation	ISO Inferred from Sequence Orthology more info
involved_in neuron projection arborization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron projection morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in neuron projection morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in olfactory bulb development	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of dopamine receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of microglial cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of nitric-oxide synthase biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of programmed cell death	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein autoubiquitination	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic vesicle endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein import into nucleus	ISO Inferred from Sequence Orthology more info
involved_in protein localization	ISO Inferred from Sequence Orthology more info
involved_in protein localization	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to endoplasmic reticulum exit site	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of CAMKK-AMPK signaling cascade	ISO Inferred from Sequence Orthology more info
involved_in regulation of ER to Golgi vesicle-mediated transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in regulation of branching morphogenesis of a nerve	ISO Inferred from Sequence Orthology more info
involved_in regulation of canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in regulation of dendritic spine morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in regulation of dendritic spine morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of dopamine receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in regulation of dopamine receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in regulation of kidney size	ISO Inferred from Sequence Orthology more info
involved_in regulation of locomotion	ISO Inferred from Sequence Orthology more info
involved_in regulation of lysosomal lumen pH	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in regulation of mitochondrial depolarization	ISO Inferred from Sequence Orthology more info
involved_in regulation of neuroblast proliferation	ISO Inferred from Sequence Orthology more info
involved_in regulation of neuron maturation	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein kinase A signaling	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein kinase A signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of protein stability	ISO Inferred from Sequence Orthology more info
involved_in regulation of reactive oxygen species metabolic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of retrograde transport, endosome to Golgi	ISO Inferred from Sequence Orthology more info
involved_in regulation of synaptic transmission, glutamatergic	ISO Inferred from Sequence Orthology more info
involved_in regulation of synaptic transmission, glutamatergic	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of synaptic vesicle endocytosis	ISO Inferred from Sequence Orthology more info
involved_in regulation of synaptic vesicle exocytosis	ISO Inferred from Sequence Orthology more info
involved_in regulation of synaptic vesicle transport	ISO Inferred from Sequence Orthology more info
involved_in response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in spermatogenesis	IEP Inferred from Expression Pattern more info	PubMed
involved_in striatum development	IEP Inferred from Expression Pattern more info	PubMed
involved_in tangential migration from the subventricular zone to the olfactory bulb	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in Golgi-associated vesicle	ISO Inferred from Sequence Orthology more info
part_of Wnt signalosome	ISO Inferred from Sequence Orthology more info
located_in amphisome	ISO Inferred from Sequence Orthology more info
located_in autolysosome	ISO Inferred from Sequence Orthology more info
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in axon	ISO Inferred from Sequence Orthology more info
located_in caveola neck	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic side of mitochondrial outer membrane	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic vesicle	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dendrite cytoplasm	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum exit site	ISO Inferred from Sequence Orthology more info
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in endosome	ISS Inferred from Sequence or Structural Similarity more info
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in growth cone	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in lysosome	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane raft	ISO Inferred from Sequence Orthology more info
located_in microvillus	ISO Inferred from Sequence Orthology more info
located_in mitochondrial inner membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrial inner membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial matrix	ISO Inferred from Sequence Orthology more info
located_in mitochondrial matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrial outer membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrial outer membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in multivesicular body, internal vesicle	ISO Inferred from Sequence Orthology more info
located_in neuron projection	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in perikaryon	IDA Inferred from Direct Assay more info	PubMed
located_in perikaryon	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info
is_active_in presynaptic cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic cytosol	ISO Inferred from Sequence Orthology more info
part_of ribonucleoprotein complex	ISO Inferred from Sequence Orthology more info
located_in synapse	ISO Inferred from Sequence Orthology more info
located_in synaptic vesicle	ISO Inferred from Sequence Orthology more info
located_in trans-Golgi network	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: leucine-rich repeat serine/threonine-protein kinase 2

NP_001178718.2

EC 2.7.11.1

XP_038934829.1

EC 2.7.11.1

XP_038934830.1

EC 2.7.11.1

XP_038934831.1

EC 2.7.11.1

XP_063119437.1

EC 2.7.11.1

XP_063119438.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001191789.2 → NP_001178718.2 leucine-rich repeat serine/threonine-protein kinase 2

Status: VALIDATED

Source sequence(s)

JAXUCZ010000007

UniProtKB/TrEMBL

F1LNJ1

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086025.1 Reference GRCr8

Range

124706246..124867234

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063263367.1 → XP_063119437.1 leucine-rich repeat serine/threonine-protein kinase 2 isoform X1

Related

ENSRNOP00000005438.8, ENSRNOT00000005438.9
XM_063263368.1 → XP_063119438.1 leucine-rich repeat serine/threonine-protein kinase 2 isoform X2

UniProtKB/TrEMBL

A0A8I6GFN0

Related

ENSRNOP00000087057.1, ENSRNOT00000104823.2
XM_039078901.2 → XP_038934829.1 leucine-rich repeat serine/threonine-protein kinase 2 isoform X3

Conserved Domains (5) summary

PRK15370
Location:1010 → 1258

PRK15370; type III secretion system effector E3 ubiquitin transferase SlrP

cd09914
Location:1333 → 1506

RocCOR; Ras of complex proteins (Roc) C-terminal of Roc (COR) domain family

cd14068
Location:1883 → 2126

STKc_LRRK2; Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2

sd00033
Location:1012 → 1035

LRR_RI; leucine-rich repeat [structural motif]

pfam16095
Location:1526 → 1739

COR; C-terminal of Roc, COR, domain
XM_039078902.2 → XP_038934830.1 leucine-rich repeat serine/threonine-protein kinase 2 isoform X4

Conserved Domains (5) summary

PLN03150
Location:1240 → 1300

PLN03150; hypothetical protein; Provisional

PRK15370
Location:1010 → 1258

PRK15370; type III secretion system effector E3 ubiquitin transferase SlrP

cd09914
Location:1333 → 1506

RocCOR; Ras of complex proteins (Roc) C-terminal of Roc (COR) domain family

sd00033
Location:1012 → 1035

LRR_RI; leucine-rich repeat [structural motif]

pfam16095
Location:1526 → 1609

COR; C-terminal of Roc, COR, domain
XM_039078903.2 → XP_038934831.1 leucine-rich repeat serine/threonine-protein kinase 2 isoform X5

Conserved Domains (4) summary

PLN03150
Location:1240 → 1300

PLN03150; hypothetical protein; Provisional

PRK15370
Location:1010 → 1258

PRK15370; type III secretion system effector E3 ubiquitin transferase SlrP

cd09914
Location:1333 → 1506

RocCOR; Ras of complex proteins (Roc) C-terminal of Roc (COR) domain family

sd00033
Location:1012 → 1035

LRR_RI; leucine-rich repeat [structural motif]