Human Gene ROCK1 (ENST00000399799.3) from GENCODE V44
  Description: Homo sapiens Rho associated coiled-coil containing protein kinase 1 (ROCK1), mRNA. (from RefSeq NM_005406)
RefSeq Summary (NM_005406): This gene encodes a protein serine/threonine kinase that is activated when bound to the GTP-bound form of Rho. The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor. This protein, a downstream effector of Rho, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. A pseudogene, related to this gene, is also located on chromosome 18. [provided by RefSeq, Aug 2015].
Gencode Transcript: ENST00000399799.3
Gencode Gene: ENSG00000067900.9
Transcript (Including UTRs)
   Position: hg38 chr18:20,946,906-21,111,813 Size: 164,908 Total Exon Count: 33 Strand: -
Coding Region
   Position: hg38 chr18:20,951,384-21,110,910 Size: 159,527 Coding Exon Count: 33 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr18:20,946,906-21,111,813)mRNA (may differ from genome)Protein (1354 aa)
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-  Comments and Description Text from UniProtKB
  ID: ROCK1_HUMAN
DESCRIPTION: RecName: Full=Rho-associated protein kinase 1; EC=2.7.11.1; AltName: Full=Renal carcinoma antigen NY-REN-35; AltName: Full=Rho-associated, coiled-coil-containing protein kinase 1; AltName: Full=Rho-associated, coiled-coil-containing protein kinase I; Short=ROCK-I; AltName: Full=p160 ROCK-1; Short=p160ROCK;
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.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium.
ENZYME REGULATION: Activated by RHOA binding. Inhibited by Y- 27632.
SUBUNIT: Homodimer. Interacts with RHOB, RHOC, MYLC2B snd PTEN (By similarity). Interacts with RHOA (activated by GTP), CHORDC1, DAPK3, GEM, JIP3, RHOE, PPP1R12A, PFN1, LIMK1, LIMK2 and TSG101. Interacts with FHOD1 in a Src-dependent manner.
SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton, centrosome, centriole (By similarity). Golgi apparatus membrane; Peripheral membrane protein. Cell projection, bleb. Note=Associated with the mother centriole and an intercentriolar linker (By similarity). A small proportion is associated with Golgi membranes.
TISSUE SPECIFICITY: Detected in blood platelets.
DOMAIN: The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated.
PTM: Autophosphorylated on serine and threonine residues. Phosphorylated upon DNA damage, probably by ATM or ATR.
PTM: Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing.
SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
SIMILARITY: Contains 1 PH domain.
SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 REM (Hr1) repeat.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: ROCK1
Diseases sorted by gene-association score: sry-negative 46,xx testicular disorder of sex development (19), pediatric osteosarcoma (10), corticobasal degeneration (7), adhesions of uterus (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 29.36 RPKM in Artery - Tibial
Total median expression: 457.92 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -420.50903-0.466 Picture PostScript Text
3' UTR -1121.904478-0.251 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000961 - AGC-kinase_C
IPR011072 - HR1_rho-bd
IPR011009 - Kinase-like_dom
IPR011993 - PH_like_dom
IPR017892 - Pkinase_C
IPR001849 - Pleckstrin_homology
IPR002219 - Prot_Kinase_C-like_PE/DAG-bd
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR020684 - Rho-assoc_coiled-coil_kin
IPR015008 - Rho-bd
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF02185 - Hr1 repeat
PF00169 - PH domain
PF00069 - Protein kinase domain
PF00433 - Protein kinase C terminal domain
PF08912 - Rho Binding

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1S1C - X-ray MuPIT 2ESM - X-ray MuPIT 2ETK - X-ray MuPIT 2ETR - X-ray MuPIT 2V55 - X-ray MuPIT 3D9V - X-ray MuPIT 3NCZ - X-ray MuPIT 3NDM - X-ray MuPIT 3O0Z - X-ray MuPIT 3TV7 - X-ray MuPIT 3TWJ - X-ray MuPIT 3V8S - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q13464
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0017048 Rho GTPase binding
GO:0017049 GTP-Rho binding
GO:0046872 metal ion binding

Biological Process:
GO:0003383 apical constriction
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006939 smooth muscle contraction
GO:0007159 leukocyte cell-cell adhesion
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007266 Rho protein signal transduction
GO:0010506 regulation of autophagy
GO:0010508 positive regulation of autophagy
GO:0010628 positive regulation of gene expression
GO:0016310 phosphorylation
GO:0016525 negative regulation of angiogenesis
GO:0022614 membrane to membrane docking
GO:0030036 actin cytoskeleton organization
GO:0030155 regulation of cell adhesion
GO:0030866 cortical actin cytoskeleton organization
GO:0031175 neuron projection development
GO:0032060 bleb assembly
GO:0032091 negative regulation of protein binding
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0035509 negative regulation of myosin-light-chain-phosphatase activity
GO:0035556 intracellular signal transduction
GO:0043312 neutrophil degranulation
GO:0043524 negative regulation of neuron apoptotic process
GO:0045616 regulation of keratinocyte differentiation
GO:0045664 regulation of neuron differentiation
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048013 ephrin receptor signaling pathway
GO:0050900 leukocyte migration
GO:0050901 leukocyte tethering or rolling
GO:0051045 negative regulation of membrane protein ectodomain proteolysis
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:0072659 protein localization to plasma membrane
GO:1900223 positive regulation of beta-amyloid clearance
GO:1900242 regulation of synaptic vesicle endocytosis
GO:1902003 regulation of beta-amyloid formation
GO:1902430 negative regulation of beta-amyloid formation
GO:1902992 negative regulation of amyloid precursor protein catabolic process
GO:1903140 regulation of establishment of endothelial barrier
GO:1903347 negative regulation of bicellular tight junction assembly
GO:2000114 regulation of establishment of cell polarity
GO:2000145 regulation of cell motility

Cellular Component:
GO:0000139 Golgi membrane
GO:0001726 ruffle
GO:0005576 extracellular region
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005814 centriole
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0010494 cytoplasmic stress granule
GO:0016020 membrane
GO:0030027 lamellipodium
GO:0032059 bleb
GO:0034774 secretory granule lumen
GO:0042995 cell projection


-  Descriptions from all associated GenBank mRNAs
  JA482218 - Sequence 201 from Patent WO2011072091.
JE980510 - Sequence 201 from Patent EP2862929.
U43195 - Human Rho-associated, coiled-coil containing protein kinase p160ROCK mRNA, complete cds.
BC113114 - Homo sapiens Rho-associated, coiled-coil containing protein kinase 1, mRNA (cDNA clone MGC:131603 IMAGE:7961989), complete cds.
AB208965 - Homo sapiens mRNA for Rho-associated, coiled-coil containing protein kinase 1 variant protein.
AK307388 - Homo sapiens cDNA, FLJ97336.
AK057038 - Homo sapiens cDNA FLJ32476 fis, clone SKNMC2000649, highly similar to Human Rho-associated, coiled-coil containing protein kinase p160ROCK mRNA.
AL832995 - Homo sapiens mRNA; cDNA DKFZp666M193 (from clone DKFZp666M193).
JD296880 - Sequence 277904 from Patent EP1572962.
JD078209 - Sequence 59233 from Patent EP1572962.
DQ786321 - Homo sapiens clone HLS_IMAGE_824758 mRNA sequence.
JD023053 - Sequence 4077 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04062 - Chemokine signaling pathway
hsa04270 - Vascular smooth muscle contraction
hsa04310 - Wnt signaling pathway
hsa04350 - TGF-beta signaling pathway
hsa04360 - Axon guidance
hsa04510 - Focal adhesion
hsa04670 - Leukocyte transendothelial migration
hsa04810 - Regulation of actin cytoskeleton
hsa05130 - Pathogenic Escherichia coli infection
hsa05131 - Shigellosis

BioCarta from NCI Cancer Genome Anatomy Project
h_integrinPathway - Integrin Signaling Pathway
h_ecmPathway - Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia
h_malPathway - Role of MAL in Rho-Mediated Activation of SRF
h_myosinPathway - PKC-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase
h_Par1Pathway - Thrombin signaling and protease-activated receptors
h_rhoPathway - Rho cell motility signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q13464 (Reactome details) participates in the following event(s):

R-HSA-201611 Caspase-mediated cleavage of Rock-1
R-HSA-419049 ROCK activation by RHO
R-HSA-3928576 RHOA:GTP binds ROCK, activating it
R-HSA-3928647 RHOA:GTP:Mg2+ binds ROCK1,ROCK2
R-NUL-421733 ROCK1 phosphorylates LIMK2 (rat)
R-HSA-6798748 Exocytosis of secretory granule lumen proteins
R-HSA-5228992 ROCK1,ROCK2 are activated
R-HSA-419083 Myosin phosphatase inactivation by ROCK
R-HSA-419087 LIM kinase phosphorylation by ROCK
R-HSA-419197 Myosin regulatory light chain phosphorylation by ROCK
R-HSA-3928577 ROCK phosphorylates LIMK1,2
R-HSA-3928616 Activated ROCK phosphorylates MRLCs
R-HSA-5218826 Active ROCK1,ROCK2 phosphorylates p-5Y-PTK2 on S732
R-HSA-111465 Apoptotic cleavage of cellular proteins
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse
R-HSA-5627117 RHO GTPases Activate ROCKs
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-75153 Apoptotic execution phase
R-HSA-6798695 Neutrophil degranulation
R-HSA-388396 GPCR downstream signalling
R-HSA-400685 Sema4D in semaphorin signaling
R-HSA-195258 RHO GTPase Effectors
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-194138 Signaling by VEGF
R-HSA-109581 Apoptosis
R-HSA-168249 Innate Immune System
R-HSA-3928663 EPHA-mediated growth cone collapse
R-HSA-372790 Signaling by GPCR
R-HSA-373755 Semaphorin interactions
R-HSA-194315 Signaling by Rho GTPases
R-HSA-422475 Axon guidance
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-5357801 Programmed Cell Death
R-HSA-168256 Immune System
R-HSA-162582 Signal Transduction
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B0YJ91, ENST00000399799.1, ENST00000399799.2, NM_005406, Q13464, Q2KHM4, Q59GZ4, ROCK1_HUMAN, uc002kte.1, uc002kte.2, uc002kte.3, uc002kte.4, uc002kte.5
UCSC ID: ENST00000399799.3
RefSeq Accession: NM_005406
Protein: Q13464 (aka ROCK1_HUMAN or ROC1_HUMAN)
CCDS: CCDS11870.2

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.