ROCK2 Rho associated coiled-coil containing protein kinase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ROCK2provided by HGNC
Official Full Name: Rho associated coiled-coil containing protein kinase 2provided by HGNC
Primary source: HGNC:HGNC:10252
See related: Ensembl:ENSG00000134318 MIM:604002
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ROCK-II
Summary: The protein encoded by this gene is a serine/threonine kinase that regulates cytokinesis, smooth muscle contraction, the formation of actin stress fibers and focal adhesions, and the activation of the c-fos serum response element. This protein, which is an isozyme of ROCK1 is a target for the small GTPase Rho. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in fat (RPKM 15.2), colon (RPKM 13.4) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2p25.1

Exon count:: 37

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (11179759..11345437, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (11319894..11484711, complement)

Chromosome 2 - NC_000002.12 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

We describe the functional connection between ROCK2 and YAP in the regulation of OS cell migration and metastasis formation. These data provide support for the use of verteporfin as a possible therapeutic option to prevent OS cell dissemination.
Title: ROCK2 deprivation leads to the inhibition of tumor growth and metastatic potential in osteosarcoma cells through the modulation of YAP activity.
The results indicated that carvedilol dose-dependently inhibited Ang II-induced hepatic stellate cell (HSC) proliferation by impeding cell cycle progression, thus alleviating hepatic fibrosis. Furthermore, carvedilol could inhibit Ang II-induced HSC contraction by interfering with the AT1R-mediated RhoA/ROCK2 pathway.
Title: Carvedilol Inhibits Angiotensin II-Induced Proliferation and Contraction in Hepatic Stellate Cells through the RhoA/Rho-Kinase Pathway.
ROCK1 phosphorylated the myosin regulatory light chain (MRLC) and facilitated the generation of traction force, while ROCK2 phosphorylated cofilin and regulated the cytoskeletal remodeling by suppressing F-actin depolymerization.
Title: ROCK isoforms differentially modulate cancer cell motility by mechanosensing the substrate stiffness.
Functional models that more accurately represent the clinical setting are necessary to dissect the role of ROCK1 and -2 in melanoma. Additionally, our study indicates that ROCK activity in tumor-infiltrating lymphocytes may be involved in the pathogenesis of cancer, and thus merits further investigations.
Title: ROCK1 and ROCK2 Are Down-regulated in Aggressive and Advanced Skin Melanomas - A Clinicopathological Perspective.
ROCK2 negatively regulates Parkin-mediated mitophagy.
Title: ROCK inhibitors upregulate the neuroprotective Parkin-mediated mitophagy pathway.
RhoBTB1 associates with ROCK1 and ROCK2 and its association with ROCK1 is via its Rho domain.
Title: RhoBTB1 interacts with ROCKs and inhibits invasion.
Results show that rhoC GTP-binding protein (RhoC)/Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) may have a major effect on VM in hepatocellular carcinoma (HCC) via ERK/MMPs signaling and might be a potential therapeutic target for the treatment of HCC.
Title: RhoC/ROCK2 promotes vasculogenic mimicry formation primarily through ERK/MMPs in hepatocellular carcinoma.
the inhibition of RhoC and ROCK2 sensitizes tumor cells to irradiation. Based on transcriptomic analysis, we find that the gene network supporting DNA repair is enriched in RhoC overexpressing cells and this is also true for ROCK2hi cells, which have an enrichment of genes supporting DNA repair, cell survival and cell division.
Title: RhoC regulates radioresistance via crosstalk of ROCK2 with the DNA repair machinery in cervical cancer.
Study identified ROCK2 as an essential kinase controlling the invasive behaviour of colorectal carcinoma (CRC) models such as cysts and organoids. The siRNA screens revealed that ROCK2 inhibition triggers the initial leader/follower polarization of the CRC cell cohorts and induces collective invasion.
Title: ROCK2 inhibition triggers the collective invasion of colorectal adenocarcinomas.
Rock inhibition-mediated alteration of senescent cell morphology may be associated with the decreased actin stress fibers formation. Since it is known that secretory activity is accompanied by the changes of cell morphology, these morphological alterations observed by the inhibition of Rho/Rho kinase pathway may also lead to important secretory functions of senescent cells.
Title: The connection between the cardiac glycoside-induced senescent cell morphology and Rho/Rho kinase pathway.

Submit: New GeneRIF Correction See all GeneRIFs (159)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Filamin-A-dependent activation of the RhoA-ROCK-LIMK-cofilin pathway is a major event in HIV-1 gp120-induced receptor clustering	PubMed
matrix	gag	HIV-1 p17-mediated activation of the Rho/ROCK-signaling pathway is required for p17-mediated monocyte adhesion and migration	PubMed
	gag	HIV-1 p17-induced activation of PTEN is regulated by RhoA-associated kinase (ROCK)	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-152111 (e-PCR)
- UniSTS:184367

Rock2 (e-PCR), detects polymorphism
- UniSTS:516658

D17S1239 (e-PCR)
- UniSTS:149852

SHGC-33406 (e-PCR)
- UniSTS:78175

RH75524 (e-PCR)
- UniSTS:89456

WI-11377 (e-PCR)
- UniSTS:46218

D2S168 (e-PCR)
- UniSTS:32432

ROCK2_815 (e-PCR)
- UniSTS:277687

D2S1805 (e-PCR)
- UniSTS:25273

Homology

Homologs of the ROCK2 gene: The ROCK2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, and frog.
Orthologs from Annotation Pipeline: 313 organisms have orthologs with human gene ROCK2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
GTP-Rho binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
RNA binding	HDA more info	PubMed
Rho-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Rho-dependent protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
Rho-dependent protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
protein serine/threonine kinase activity	NAS Non-traceable Author Statement more info	PubMed
structural molecule activity	NAS Non-traceable Author Statement more info	PubMed
tau protein binding	NAS Non-traceable Author Statement more info	PubMed
tau-protein kinase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
Rho protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
actomyosin structure organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
aortic valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
cellular response to acetylcholine	ISS Inferred from Sequence or Structural Similarity more info
cellular response to testosterone stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
centrosome duplication	IMP Inferred from Mutant Phenotype more info	PubMed
cortical actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cortical actin cytoskeleton organization	IGI Inferred from Genetic Interaction more info	PubMed
cortical actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
embryonic morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ephrin receptor signaling pathway	TAS Traceable Author Statement more info
mRNA destabilization	ISS Inferred from Sequence or Structural Similarity more info
mitotic cytokinesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of bicellular tight junction assembly	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of biomineral tissue development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of myosin-light-chain-phosphatase activity	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of myosin-light-chain-phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of nitric oxide biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of nitric oxide biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of protein localization to lysosome	IMP Inferred from Mutant Phenotype more info	PubMed
peptidyl-serine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
peptidyl-serine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
peptidyl-threonine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptidyl-threonine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of amyloid precursor protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
positive regulation of amyloid-beta formation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of amyloid-beta formation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
positive regulation of cardiac muscle hypertrophy	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of centrosome duplication	IEA Inferred from Electronic Annotation more info
positive regulation of connective tissue growth factor production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of connective tissue replacement	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of fibroblast growth factor production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein localization to early endosome	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of stress fiber assembly	IMP Inferred from Mutant Phenotype more info	PubMed
protein localization to plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of actin cytoskeleton organization	TAS Traceable Author Statement more info	PubMed
regulation of angiotensin-activated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
regulation of blood vessel diameter	ISS Inferred from Sequence or Structural Similarity more info
regulation of cell adhesion	TAS Traceable Author Statement more info	PubMed
regulation of cell junction assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of cell motility	TAS Traceable Author Statement more info	PubMed
regulation of cellular response to hypoxia	ISS Inferred from Sequence or Structural Similarity more info
regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
regulation of establishment of cell polarity	TAS Traceable Author Statement more info	PubMed
regulation of establishment of endothelial barrier	IGI Inferred from Genetic Interaction more info	PubMed
regulation of establishment of endothelial barrier	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of focal adhesion assembly	TAS Traceable Author Statement more info	PubMed
regulation of keratinocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of neurological system process	ISS Inferred from Sequence or Structural Similarity more info
regulation of protein metabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
regulation of stress fiber assembly	TAS Traceable Author Statement more info	PubMed
response to angiotensin	ISS Inferred from Sequence or Structural Similarity more info
response to ischemia	ISS Inferred from Sequence or Structural Similarity more info
response to transforming growth factor beta	ISS Inferred from Sequence or Structural Similarity more info
rhythmic process	IEA Inferred from Electronic Annotation more info
smooth muscle contraction	TAS Traceable Author Statement more info	PubMed
vascular endothelial growth factor receptor signaling pathway	TAS Traceable Author Statement more info
viral RNA genome replication	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
centrosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
centrosome	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasmic ribonucleoprotein granule	IDA Inferred from Direct Assay more info	PubMed
cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info
plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: rho-associated protein kinase 2

Names: p164 ROCK-2; rho-associated, coiled-coil-containing protein kinase II

NP_001308572.1

EC 2.7.11.1

NP_004841.2

EC 2.7.11.1

XP_005246247.1

EC 2.7.11.1

XP_011508719.1

EC 2.7.11.1

XP_016860867.1

EC 2.7.11.1

XP_016860868.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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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.

Genomic

NG_029769.1 RefSeqGene

Range

4950..169827

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001321643.2 → NP_001308572.1 rho-associated protein kinase 2 isoform 2

Status: REVIEWED

Source sequence(s)

AB014519, AC018463, AC099344, AL049383, BC111801

UniProtKB/Swiss-Prot

O75116

UniProtKB/TrEMBL

Q14DU5

Related

ENSP00000385509.1, ENST00000401753.5

Conserved Domains (7) summary

cd11638
Location:419 → 485

HR1_ROCK2; Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Rho-associated coiled-coil containing protein kinase 2

smart00220
Location:6 → 268

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1196
Location:350 → 1015

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

cd00029
Location:1175 → 1221

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

cd01242
Location:1065 → 1171

PH_ROCK; Rho-associated coiled-coil containing protein kinase pleckstrin homology (PH) domain

cd05596
Location:1 → 330

STKc_ROCK; Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase

pfam08912
Location:893 → 960

Rho_Binding; Rho Binding
NM_004850.5 → NP_004841.2 rho-associated protein kinase 2 isoform 1

See identical proteins and their annotated locations for NP_004841.2

Status: REVIEWED

Source sequence(s)

AB014519, AC018463, AC099344, AL049383, BC111801

Consensus CDS

CCDS42654.1

UniProtKB/Swiss-Prot

O75116

UniProtKB/TrEMBL

Q14DU5

Related

ENSP00000317985.6, ENST00000315872.11

Conserved Domains (5) summary

cd11638
Location:505 → 571

HR1_ROCK2; Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Rho-associated coiled-coil containing protein kinase 2

cd00029
Location:1261 → 1307

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

cd01242
Location:1151 → 1257

PH_ROCK; Rho-associated coiled-coil containing protein kinase pleckstrin homology (PH) domain

cd05621
Location:39 → 417

STKc_ROCK2; Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2

cl25732
Location:436 → 1101

SMC_N; RecF/RecN/SMC N terminal domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p13 Primary Assembly

Range

11179759..11345437 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005246190.3 → XP_005246247.1 rho-associated protein kinase 2 isoform X1

Conserved Domains (7) summary

pfam05483
Location:412 → 1080

SCP-1; Synaptonemal complex protein 1 (SCP-1)

cd11638
Location:505 → 571

HR1_ROCK2; Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Rho-associated coiled-coil containing protein kinase 2

smart00220
Location:92 → 354

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd00029
Location:1261 → 1307

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

cd01242
Location:1151 → 1257

PH_ROCK; Rho-associated coiled-coil containing protein kinase pleckstrin homology (PH) domain

cd05621
Location:39 → 417

STKc_ROCK2; Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2

pfam08912
Location:979 → 1046

Rho_Binding; Rho Binding
XM_017005379.2 → XP_016860868.1 rho-associated protein kinase 2 isoform X3

Conserved Domains (7) summary

cd11638
Location:419 → 485

HR1_ROCK2; Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Rho-associated coiled-coil containing protein kinase 2

smart00220
Location:6 → 268

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1196
Location:350 → 1015

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

cd00029
Location:1175 → 1221

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

cd01242
Location:1065 → 1171

PH_ROCK; Rho-associated coiled-coil containing protein kinase pleckstrin homology (PH) domain

cd05596
Location:1 → 330

STKc_ROCK; Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase

pfam08912
Location:893 → 960

Rho_Binding; Rho Binding
XM_011510417.2 → XP_011508719.1 rho-associated protein kinase 2 isoform X3

Conserved Domains (7) summary

cd11638
Location:419 → 485

HR1_ROCK2; Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Rho-associated coiled-coil containing protein kinase 2

smart00220
Location:6 → 268

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1196
Location:350 → 1015

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

cd00029
Location:1175 → 1221

C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...

cd01242
Location:1065 → 1171

PH_ROCK; Rho-associated coiled-coil containing protein kinase pleckstrin homology (PH) domain

cd05596
Location:1 → 330

STKc_ROCK; Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase

pfam08912
Location:893 → 960

Rho_Binding; Rho Binding
XM_017005378.2 → XP_016860867.1 rho-associated protein kinase 2 isoform X2