Browse ROCK1

Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole Golgi apparatus membrane; Peripheral membrane protein. Cell projection, bleb. Cytoplasm, cytoskeleton Cell membrane Cell projection, lamellipodium Cell projection, ruffle Note=Associated with the mother centriole and an intercentriolar linker. Colocalizes with ITGB1BP1 and ITGB1 at the cell membrane predominantly in lamellipodia and membrane ruffles, but also in retraction fibers. Localizes at the cell membrane in an ITGB1BP1-dependent manner (By similarity). A small proportion is associated with Golgi membranes.
Domain PF00069 Protein kinase domain
PF08912 Rho Binding
Function

Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization.

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001885 endothelial cell development
GO:0001952 regulation of cell-matrix adhesion
GO:0001954 positive regulation of cell-matrix adhesion
GO:0002064 epithelial cell development
GO:0003012 muscle system process
GO:0003158 endothelium development
GO:0003382 epithelial cell morphogenesis
GO:0003383 apical constriction
GO:0006470 protein dephosphorylation
GO:0006921 cellular component disassembly involved in execution phase of apoptosis
GO:0006936 muscle contraction
GO:0006939 smooth muscle contraction
GO:0007009 plasma membrane organization
GO:0007015 actin filament organization
GO:0007043 cell-cell junction assembly
GO:0007044 cell-substrate junction assembly
GO:0007045 cell-substrate adherens junction assembly
GO:0007159 leukocyte cell-cell adhesion
GO:0007160 cell-matrix adhesion
GO:0007163 establishment or maintenance of cell polarity
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007265 Ras protein signal transduction
GO:0007266 Rho protein signal transduction
GO:0008544 epidermis development
GO:0009913 epidermal cell differentiation
GO:0010810 regulation of cell-substrate adhesion
GO:0010811 positive regulation of cell-substrate adhesion
GO:0010921 regulation of phosphatase activity
GO:0010923 negative regulation of phosphatase activity
GO:0014812 muscle cell migration
GO:0016311 dephosphorylation
GO:0016525 negative regulation of angiogenesis
GO:0022406 membrane docking
GO:0022614 membrane to membrane docking
GO:0030010 establishment of cell polarity
GO:0030031 cell projection assembly
GO:0030038 contractile actin filament bundle assembly
GO:0030048 actin filament-based movement
GO:0030216 keratinocyte differentiation
GO:0030856 regulation of epithelial cell differentiation
GO:0030865 cortical cytoskeleton organization
GO:0030866 cortical actin cytoskeleton organization
GO:0031032 actomyosin structure organization
GO:0031589 cell-substrate adhesion
GO:0032060 bleb assembly
GO:0032091 negative regulation of protein binding
GO:0032231 regulation of actin filament bundle assembly
GO:0032515 negative regulation of phosphoprotein phosphatase activity
GO:0032878 regulation of establishment or maintenance of cell polarity
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0034329 cell junction assembly
GO:0034330 cell junction organization
GO:0034332 adherens junction organization
GO:0034333 adherens junction assembly
GO:0035303 regulation of dephosphorylation
GO:0035304 regulation of protein dephosphorylation
GO:0035305 negative regulation of dephosphorylation
GO:0035308 negative regulation of protein dephosphorylation
GO:0035507 regulation of myosin-light-chain-phosphatase activity
GO:0035509 negative regulation of myosin-light-chain-phosphatase activity
GO:0043149 stress fiber assembly
GO:0043297 apical junction assembly
GO:0043393 regulation of protein binding
GO:0043523 regulation of neuron apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0043588 skin development
GO:0043666 regulation of phosphoprotein phosphatase activity
GO:0044089 positive regulation of cellular component biogenesis
GO:0045123 cellular extravasation
GO:0045216 cell-cell junction organization
GO:0045446 endothelial cell differentiation
GO:0045601 regulation of endothelial cell differentiation
GO:0045604 regulation of epidermal cell differentiation
GO:0045616 regulation of keratinocyte differentiation
GO:0045682 regulation of epidermis development
GO:0045765 regulation of angiogenesis
GO:0045785 positive regulation of cell adhesion
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048013 ephrin receptor signaling pathway
GO:0048041 focal adhesion assembly
GO:0048514 blood vessel morphogenesis
GO:0050900 leukocyte migration
GO:0050901 leukocyte tethering or rolling
GO:0051017 actin filament bundle assembly
GO:0051098 regulation of binding
GO:0051100 negative regulation of binding
GO:0051346 negative regulation of hydrolase activity
GO:0051402 neuron apoptotic process
GO:0051451 myoblast migration
GO:0051492 regulation of stress fiber assembly
GO:0051493 regulation of cytoskeleton organization
GO:0051893 regulation of focal adhesion assembly
GO:0051894 positive regulation of focal adhesion assembly
GO:0061028 establishment of endothelial barrier
GO:0061572 actin filament bundle organization
GO:0061756 leukocyte adhesion to vascular endothelial cell
GO:0070252 actin-mediated cell contraction
GO:0070830 bicellular tight junction assembly
GO:0070997 neuron death
GO:0072657 protein localization to membrane
GO:0072659 protein localization to plasma membrane
GO:0090002 establishment of protein localization to plasma membrane
GO:0090109 regulation of cell-substrate junction assembly
GO:0090150 establishment of protein localization to membrane
GO:0097194 execution phase of apoptosis
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901342 regulation of vasculature development
GO:1901343 negative regulation of vasculature development
GO:1901550 regulation of endothelial cell development
GO:1901888 regulation of cell junction assembly
GO:1901889 negative regulation of cell junction assembly
GO:1901890 positive regulation of cell junction assembly
GO:1903140 regulation of establishment of endothelial barrier
GO:1903347 negative regulation of bicellular tight junction assembly
GO:1903391 regulation of adherens junction organization
GO:1903393 positive regulation of adherens junction organization
GO:1990778 protein localization to cell periphery
GO:2000114 regulation of establishment of cell polarity
GO:2000181 negative regulation of blood vessel morphogenesis
GO:2000810 regulation of bicellular tight junction assembly
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0017016 Ras GTPase binding
GO:0017048 Rho GTPase binding
GO:0017049 GTP-Rho binding
GO:0031267 small GTPase binding
GO:0051020 GTPase binding
Cellular Component GO:0001726 ruffle
GO:0005813 centrosome
GO:0005814 centriole
GO:0030027 lamellipodium
GO:0031252 cell leading edge
GO:0032059 bleb
GO:0044450 microtubule organizing center part
> KEGG and Reactome Pathway
 
KEGG hsa04022 cGMP-PKG signaling pathway
hsa04024 cAMP signaling pathway
hsa04062 Chemokine signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04270 Vascular smooth muscle contraction
hsa04350 TGF-beta signaling pathway
hsa04360 Axon guidance
hsa04510 Focal adhesion
hsa04530 Tight junction
hsa04611 Platelet activation
hsa04670 Leukocyte transendothelial migration
hsa04810 Regulation of actin cytoskeleton
hsa04921 Oxytocin signaling pathway
Reactome R-HSA-109581: Apoptosis
R-HSA-111465: Apoptotic cleavage of cellular proteins
R-HSA-75153: Apoptotic execution phase
R-HSA-422475: Axon guidance
R-HSA-1266738: Developmental Biology
R-HSA-2682334: EPH-Ephrin signaling
R-HSA-3928663: EPHA-mediated growth cone collapse
R-HSA-3928662: EPHB-mediated forward signaling
R-HSA-416482: G alpha (12/13) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6798695: Neutrophil degranulation
R-HSA-5357801: Programmed Cell Death
R-HSA-195258: RHO GTPase Effectors
R-HSA-5627117: RHO GTPases Activate ROCKs
R-HSA-400685: Sema4D in semaphorin signaling
R-HSA-416572: Sema4D induced cell migration and growth-cone collapse
R-HSA-373755: Semaphorin interactions
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-194315: Signaling by Rho GTPases
R-HSA-194138: Signaling by VEGF
R-HSA-4420097: VEGFA-VEGFR2 Pathway
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ROCK1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between ROCK1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27513300Chronic myeloid leukemiaInhibit immunityIn vitro treatment of CML mDCs with the Rho-associated protein kinase (ROCK) inhibitor Y-27632 partially restored both cell surface CD1d expression and CD1d-mediated antigen presentation, whereas it had no effect on HD mDCs. Our data support the conclusion that BCR-ABL-dependent ROCK, but not TK, is involved in CD1d downregulation.
24963846melanomaInhibit immunityRounded-amoeboid cancer cells use actomyosin contractility driven by Rho-ROCK and JAK-STAT3 to migrate efficiently.
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of ROCK1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 4 Resistant to T-cell proliferation
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of ROCK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.2210.516
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0930.956
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.4560.736
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.170.683
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.2140.93
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1140.971
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1560.712
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3190.865
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0430.984
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.7070.497
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.4330.344
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0420.507
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ROCK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.12.78.40.12
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 014014.3-14.31
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.1011.10.0286
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ROCK1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ROCK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ROCK1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ROCK1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ROCK1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ROCK1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolROCK1
NameRho-associated, coiled-coil containing protein kinase 1
Aliases p160ROCK; ROCK-I; p160 ROCK-1; renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing pro ......
Chromosomal Location18q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ROCK1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ROCK1.
ID Name Drug Type Targets #Targets
DB04707HydroxyfasudilSmall MoleculePKIA, PRKACA, ROCK13
DB07876(S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINESmall MoleculePKIA, PRKACA, ROCK13
DB08162FasudilSmall MoleculePKIA, PRKACA, ROCK1, ROCK24
DB08756(R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL) CYCLOHEXANECARBOXAMIDESmall MoleculePKIA, PRKACA, ROCK1, ROCK24
DB13165RipasudilSmall MoleculeROCK1, ROCK22
DB13931NetarsudilSmall MoleculeROCK1, ROCK22