ROCK1 (Rho associated coiled-coil containing protein kinase 1)

Gene

• Entrez ID: 6093
• Gene name: Rho associated coiled-coil containing protein kinase 1
• Gene symbol: ROCK1
• Synonyms: P160ROCK, ROCK-I
• Chromosome: 18
• Chromosome location: 18q11.1
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1057520015	G>A	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000945	hsa-miR-146a-5p	flow, Western blot, Northern blot, Luciferase reporter assay	18174313
MIRT000945	hsa-miR-146a-5p	Luciferase reporter assay, qRT-PCR, Western blot	26306811
MIRT000945	hsa-miR-146a-5p	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	27221467
MIRT004047	hsa-miR-584-5p	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	21119662
MIRT006776	hsa-miR-124-3p	Luciferase reporter assay	22085528
MIRT006776	hsa-miR-124-3p	Luciferase reporter assay, qRT-PCR, Western blot	25169484
MIRT006776	hsa-miR-124-3p	Luciferase reporter assay, Western blot, qRT-PCR	23936026
MIRT007070	hsa-miR-1280	Immunoblot, In situ hybridization, Luciferase reporter assay, qRT-PCR	23056431
MIRT007315	hsa-miR-148b-3p	Western blot	23238785
MIRT007315	hsa-miR-148b-3p	Luciferase reporter assay	23233531
MIRT007315	hsa-miR-148b-3p	Luciferase reporter assay, Western blot	26530325
MIRT053076	hsa-miR-335-5p	Luciferase reporter assay, qRT-PCR, Western blot	23975506
MIRT053076	hsa-miR-335-5p	Luciferase reporter assay, Western blot	27035227
MIRT053483	hsa-miR-148a-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	21994419
MIRT053483	hsa-miR-148a-3p	Luciferase reporter assay	23670799
MIRT054402	hsa-miR-135a-5p	Immunohistochemistry, Luciferase reporter assay, Western blot, qRT-PCR	24465504
MIRT054402	hsa-miR-135a-5p	Luciferase reporter assay, qRT-PCR, Western blot	25065599
MIRT438282	hsa-miR-145-5p	Luciferase reporter assay, Western blot	24573110
MIRT438654	hsa-miR-340-5p	Luciferase reporter assay, qRT-PCR, Western blot	23872151
MIRT441619	hsa-miR-4662a-5p	PAR-CLIP	22100165
MIRT441619	hsa-miR-4662a-5p	PAR-CLIP	23708386
MIRT441619	hsa-miR-4662a-5p	PAR-CLIP	22291592
MIRT441620	hsa-miR-4753-5p	PAR-CLIP	22100165
MIRT441620	hsa-miR-4753-5p	PAR-CLIP	23708386
MIRT441620	hsa-miR-4753-5p	PAR-CLIP	22291592
MIRT441621	hsa-miR-6507-5p	PAR-CLIP	22100165
MIRT441621	hsa-miR-6507-5p	PAR-CLIP	23708386
MIRT441621	hsa-miR-6507-5p	PAR-CLIP	22291592
MIRT441622	hsa-miR-6768-3p	PAR-CLIP	22100165
MIRT441622	hsa-miR-6768-3p	PAR-CLIP	23708386
MIRT441622	hsa-miR-6768-3p	PAR-CLIP	22291592
MIRT494982	hsa-miR-548aw	PAR-CLIP	23708386
MIRT494983	hsa-miR-5093	PAR-CLIP	23708386
MIRT494984	hsa-miR-1468-3p	PAR-CLIP	23708386
MIRT494985	hsa-miR-548x-5p	PAR-CLIP	23708386
MIRT494986	hsa-miR-548g-5p	PAR-CLIP	23708386
MIRT494987	hsa-miR-548f-5p	PAR-CLIP	23708386
MIRT494988	hsa-miR-548aj-5p	PAR-CLIP	23708386
MIRT494989	hsa-miR-3688-3p	PAR-CLIP	23708386
MIRT731498	hsa-miR-300	Luciferase reporter assay	27145462
MIRT731717	hsa-miR-506-3p	Luciferase reporter assay, qRT-PCR, Western blot	26474697
MIRT734188	hsa-miR-584-3p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	26715733
MIRT734471	hsa-miR-126-3p	Luciferase reporter assay, qRT-PCR, Western blot	27108693
MIRT735210	hsa-miR-144-5p	qRT-PCR, Western blot	26458302
MIRT735210	hsa-miR-144-5p	Luciferase reporter assay, qRT-PCR, Western blot	25912304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0000281	Process	Mitotic cytokinesis	IBA	21873635
GO:0001726	Component	Ruffle	ISS
GO:0003180	Process	Aortic valve morphogenesis	ISS
GO:0004672	Function	Protein kinase activity	TAS	8798490, 10436159
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	10652353, 11018042, 18694941, 19036714, 23093407
GO:0004674	Function	Protein serine/threonine kinase activity	NAS	27853422
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0005515	Function	Protein binding	IPI	10652353, 14660612, 17853893, 20230755, 21281639, 22085929, 23093407, 25416956, 25448675, 27853422, 28514442
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005814	Component	Centriole	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IBA	21873635
GO:0005856	Component	Cytoskeleton	ISS
GO:0005886	Component	Plasma membrane	ISS
GO:0006468	Process	Protein phosphorylation	IDA	23093407
GO:0006915	Process	Apoptotic process	IEA
GO:0006939	Process	Smooth muscle contraction	TAS	12778124
GO:0007159	Process	Leukocyte cell-cell adhesion	IDA	12082081
GO:0007165	Process	Signal transduction	TAS	10436159
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	IMP	25816133
GO:0007266	Process	Rho protein signal transduction	IBA	21873635
GO:0007266	Process	Rho protein signal transduction	IGI	27160703
GO:0010494	Component	Cytoplasmic stress granule	IBA	21873635
GO:0010494	Component	Cytoplasmic stress granule	ISS
GO:0010506	Process	Regulation of autophagy	TAS	27853422
GO:0010508	Process	Positive regulation of autophagy	IGI	27853422
GO:0010613	Process	Positive regulation of cardiac muscle hypertrophy	IMP	28679962
GO:0010628	Process	Positive regulation of gene expression	IMP	27853422, 28679962
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0010951	Process	Negative regulation of endopeptidase activity	IEA
GO:0016525	Process	Negative regulation of angiogenesis	IMP	19181962
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	18573880
GO:0018107	Process	Peptidyl-threonine phosphorylation	IBA	21873635
GO:0019828	Function	Aspartic-type endopeptidase inhibitor activity	IMP	24305806
GO:0022614	Process	Membrane to membrane docking	IDA	12082081
GO:0030027	Component	Lamellipodium	ISS
GO:0030036	Process	Actin cytoskeleton organization	TAS	10436159
GO:0030155	Process	Regulation of cell adhesion	TAS	12778124
GO:0030334	Process	Regulation of cell migration	IDA	23093407
GO:0030866	Process	Cortical actin cytoskeleton organization	IBA	21873635
GO:0030866	Process	Cortical actin cytoskeleton organization	IGI	25816133
GO:0030866	Process	Cortical actin cytoskeleton organization	IMP	25816133
GO:0031032	Process	Actomyosin structure organization	IBA	21873635
GO:0031175	Process	Neuron projection development	IGI	27160703
GO:0032059	Component	Bleb	IEA
GO:0032091	Process	Negative regulation of protein binding	IDA	18573880
GO:0032956	Process	Regulation of actin cytoskeleton organization	IDA	25911094
GO:0032956	Process	Regulation of actin cytoskeleton organization	ISS
GO:0032956	Process	Regulation of actin cytoskeleton organization	TAS	12778124
GO:0034774	Component	Secretory granule lumen	TAS
GO:0035509	Process	Negative regulation of myosin-light-chain-phosphatase activity	IGI	25816133
GO:0035509	Process	Negative regulation of myosin-light-chain-phosphatase activity	IMP	25816133
GO:0042326	Process	Negative regulation of phosphorylation	ISS
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043410	Process	Positive regulation of MAPK cascade	IMP	28679962
GO:0045616	Process	Regulation of keratinocyte differentiation	IMP	19997641
GO:0045664	Process	Regulation of neuron differentiation	IGI	27160703
GO:0046872	Function	Metal ion binding	IEA
GO:0048010	Process	Vascular endothelial growth factor receptor signaling pathway	TAS
GO:0048013	Process	Ephrin receptor signaling pathway	TAS
GO:0048156	Function	Tau protein binding	NAS	28386764
GO:0048598	Process	Embryonic morphogenesis	IBA	21873635
GO:0050321	Function	Tau-protein kinase activity	NAS	28386764
GO:0050900	Process	Leukocyte migration	IDA	12082081
GO:0050901	Process	Leukocyte tethering or rolling	IDA	12082081
GO:0051045	Process	Negative regulation of membrane protein ectodomain proteolysis	TAS	27853422
GO:0051451	Process	Myoblast migration	ISS
GO:0051492	Process	Regulation of stress fiber assembly	TAS	12778124
GO:0051893	Process	Regulation of focal adhesion assembly	TAS	12778124
GO:0051894	Process	Positive regulation of focal adhesion assembly	ISS
GO:0061157	Process	MRNA destabilization	ISS
GO:0070168	Process	Negative regulation of biomineral tissue development	ISS
GO:0070507	Process	Regulation of microtubule cytoskeleton organization	IDA	23093407
GO:0071559	Process	Response to transforming growth factor beta	ISS
GO:0072518	Function	Rho-dependent protein serine/threonine kinase activity	IBA	21873635
GO:0072518	Function	Rho-dependent protein serine/threonine kinase activity	IDA	18573880
GO:0072659	Process	Protein localization to plasma membrane	IGI	25816133
GO:0072659	Process	Protein localization to plasma membrane	IMP	25816133
GO:0090521	Process	Glomerular visceral epithelial cell migration	ISS
GO:0097746	Process	Blood vessel diameter maintenance	ISS
GO:0106003	Component	Amyloid-beta complex	IDA	27853422
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:0110061	Process	Regulation of angiotensin-activated signaling pathway	IMP	28679962
GO:0140058	Process	Neuron projection arborization	IGI	27160703
GO:1900223	Process	Positive regulation of amyloid-beta clearance	IGI	27853422
GO:1900242	Process	Regulation of synaptic vesicle endocytosis	IGI	27160703
GO:1901888	Process	Regulation of cell junction assembly	IBA	21873635
GO:1902003	Process	Regulation of amyloid-beta formation	TAS	27853422
GO:1902430	Process	Negative regulation of amyloid-beta formation	IMP	24305806, 27853422
GO:1902992	Process	Negative regulation of amyloid precursor protein catabolic process	IMP	24305806, 27853422
GO:1903140	Process	Regulation of establishment of endothelial barrier	IGI	25816133
GO:1903140	Process	Regulation of establishment of endothelial barrier	IMP	25816133
GO:1903347	Process	Negative regulation of bicellular tight junction assembly	IGI	25816133
GO:1905205	Process	Positive regulation of connective tissue replacement	IMP	28679962
GO:1990776	Process	Response to angiotensin	ISS
GO:2000114	Process	Regulation of establishment of cell polarity	TAS	20803696
GO:2000145	Process	Regulation of cell motility	TAS	12778124

Other IDs

• MIM: 601702
• HGNC: 10251
• e!Ensembl: ENSG00000067900

Protein

• UniProt ID: Q13464
• Protein name: Rho-associated protein kinase 1 (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-35) (Rho-associated, coiled-coil-containing protein kinase 1) (Rho-associated, coiled-coil-containing protein kinase I) (ROCK-I) (p160 ROCK-1) (p160ROCK)
• Protein function: Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579). 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, TPPP, PFN1 and PPP1R12A (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579, PubMed:23093407, PubMed:23355470). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing (PubMed:18694941). Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (PubMed:19036714). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation (PubMed:19181962). Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (PubMed:21072057). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation (PubMed:19997641). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity).
• PDB: 1S1C, 2ESM, 2ETK, 2ETR, 2V55, 3D9V, 3NCZ, 3NDM, 3O0Z, 3TV7, 3TWJ, 3V8S, 4L2W, 4W7P, 4YVC, 4YVE, 5BML, 5F5P, 5HVU, 5KKS, 5KKT, 5UZJ, 5WNE, 5WNF, 5WNG, 5WNH, 6E9W, 7JOU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	76 → 338	Protein kinase domain	Domain
  PF08912	Rho_Binding	948 → 1014	Rho Binding	Coiled-coil

• Sequence:

  MSTGDSFETRFEKMDNLLRDPKSEVNSDCLLDGLDALVYDLDFPALRKNKNIDNFLSRYK
  DTINKIRDLRMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAF
  FWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLVNLMSNYDVPEKWARFYTA
  EVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRCDTAVGTPDY
  ISPEVLKSQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSLTFP
  DDNDISKEAKNLICAFLTDREVRLGRNGVEEIKRHLFFKNDQWAWETLRDTVAPVVPDLS
  SDIDTSNFDDLEEDKGEEETFPIPKAFVGNQLPFVGFTYYSNRRYLSSANPNDNRTSSNA
  DKSLQESLQKTIYKLEEQLHNEMQLKDEMEQKCRTSNIKLDKIMKELDEEGNQRRNLEST
  VSQIEKEKMLLQHRINEYQRKAEQENEKRRNVENEVSTLKDQLEDLKKVSQNSQLANEKL
  SQLQKQLEEANDLLRTESDTAVRLRKSHTEMSKSISQLESLNRELQERNRILENSKSQTD
  KDYYQLQAILEAERRDRGHDSEMIGDLQARITSLQEEVKHLKHNLEKVEGERKEAQDMLN
  HSEKEKNNLEIDLNYKLKSLQQRLEQEVNEHKVTKARLTDKHQSIEEAKSVAMCEMEKKL
  KEEREAREKAENRVVQIEKQCSMLDVDLKQSQQKLEHLTGNKERMEDEVKNLTLQLEQES
  NKRLLLQNELKTQAFEADNLKGLEKQMKQEINTLLEAKRLLEFELAQLTKQYRGNEGQMR
  ELQDQLEAEQYFSTLYKTQVKELKEEIEEKNRENLKKIQELQNEKETLATQLDLAETKAE
  SEQLARGLLEEQYFELTQESKKAASRNRQEITDKDHTVSRLEEANSMLTKDIEILRRENE
  ELTEKMKKAEEEYKLEKEEEISNLKAAFEKNINTERTLKTQAVNKLAEIMNRKDFKIDRK
  KANTQDLRKKEKENRKLQLELNQEREKFNQMVVKHQKELNDMQAQLVEECAHRNELQMQL
  ASKESDIEQLRAKLLDLSDSTSVASFPSADETDGNLPESRIEGWLSVPNRGNIKRYGWKK
  QYVVVSSKKILFYNDEQDKEQSNPSMVLDIDKLFHVRPVTQGDVYRAETEEIPKIFQILY
  ANEGECRKDVEMEPVQQAEKTNFQNHKGHEFIPTLYHFPANCDACAKPLWHVFKPPPALE
  CRRCHVKCHRDHLDKKEDLICPCKVSYDVTSARDMLLLACSQDEQKKWVTHLVKKIPKNP
  PSGFVRASPRTLSTRSTANQSFRKVVKNTSGKTS

• Sequence length: 1354