Descriptions

Rho kinases (ROCKs) are serine/threonine kinases that are involved in many aspects of cell motility, from smooth-muscle contraction to cell migration and neurite outgrowth. ROCK2, one of ROCK isoforms, contains an N-terminal kinase domain, Rho-binding domain (RBD), and PH domain. RBD and PH domains interact with the catalytic kinase domain for autoinhibition. Rho binding to RBD relieves the autoinhibition. Since ROCK1 also contains the domains, ROCK1 may employ a similar autoinhibiton mechanism.

Autoinhibitory domains (AIDs)

Target domain

76-338 (Catalytic kinase domain)

Relief mechanism

Partner binding

Assay

Target domain

76-338 (Catalytic kinase domain)

Relief mechanism

Partner binding

Assay

Accessory elements

215-239 (Activation loop from InterPro)

Target domain

76-338 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

1 structures for Q63644

Entry ID Method Resolution Chain Position Source
AF-Q63644-F1 Predicted AlphaFoldDB

No variants for Q63644

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q63644

1 associated diseases with Q63644

Without disease ID

9 regional properties for Q63644

Type Name Position InterPro Accession
domain Protein kinase domain 76 - 338 IPR000719
domain AGC-kinase, C-terminal 341 - 409 IPR000961
domain Pleckstrin homology domain 1133 - 1334 IPR001849
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 1243 - 1298 IPR002219
active_site Serine/threonine-protein kinase, active site 194 - 206 IPR008271
domain HR1 rho-binding domain 479 - 556 IPR011072
domain ROCK, Rho binding domain 948 - 1015 IPR015008
binding_site Protein kinase, ATP binding site 82 - 105 IPR017441
domain Rho-associated protein kinase 1, HR1 489 - 554 IPR037310

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • 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
  • A small proportion is associated with Golgi membranes (By similarity)
  • Associated with the mother centriole and an intercentriolar linker (By similarity)
  • Colocalizes with ITGB1BP1 and ITGB1 at the cell membrane predominantly in lamellipodia and membrane ruffles, but also in retraction fibers (By similarity)
  • Localizes at the cell membrane in an ITGB1BP1-dependent manner (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
bleb A cell extension caused by localized decoupling of the cytoskeleton from the plasma membrane and characterized by rapid formation, rounded shape, and scarcity of organelles within the protrusion. Blebs are formed during apoptosis and other cellular processes, including cell locomotion, cell division, and as a result of physical or chemical stresses. [GOC:mtg_apoptosis, PMID:12083798, PMID:16624291, Wikipedia:Bleb_(cell_biology)]
centriole A cellular organelle, found close to the nucleus in many eukaryotic cells, consisting of a small cylinder with microtubular walls, 300-500 nm long and 150-250 nm in diameter. It contains nine short, parallel, peripheral microtubular fibrils, each fibril consisting of one complete microtubule fused to two incomplete microtubules. Cells usually have two centrioles, lying at right angles to each other. At division, each pair of centrioles generates another pair and the twin pairs form the pole of the mitotic spindle.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic stress granule A dense aggregation in the cytosol composed of proteins and RNAs that appear when the cell is under stress.
cytoskeleton A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles.
Golgi membrane The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
lamellipodium A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
ruffle Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork.

8 GO annotations of molecular function

Name Definition
aspartic-type endopeptidase inhibitor activity Binds to and stops, prevents or reduces the activity of aspartic-type endopeptidases, enzymes that catalyze the hydrolysis of nonterminal peptide bonds in a polypeptide chain; the optimum reaction pH is below 5 due to an aspartic residue involved in the catalytic process.
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
metal ion binding Binding to a metal ion.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
Rho-dependent protein serine/threonine kinase activity Rho GTPase-dependent catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein.
small GTPase binding Binding to a small monomeric GTPase.

53 GO annotations of biological process

Name Definition
actin cytoskeleton organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
actomyosin structure organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures containing both actin and myosin or paramyosin. The myosin may be organized into filaments.
apical constriction The actin-mediated process that results in the contraction of the apical end of a polarized columnar epithelial cell.
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
bleb assembly The assembly of a bleb, a cell extension caused by localized decoupling of the cytoskeleton from the plasma membrane and characterized by rapid formation, rounded shape, and scarcity of organelles within the protrusion. Plasma membrane blebbing occurs during apoptosis and other cellular processes, including cell locomotion, cell division, and as a result of physical or chemical stresses. [GOC:mah, GOC:mtg_apoptosis, PMID:12083798, PMID:16624291, Wikipedia:Bleb_(cell_biology)]
blood vessel diameter maintenance Any process that modulates the diameter of blood vessels.
cortical actin cytoskeleton organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of actin-based cytoskeletal structures in the cell cortex, i.e. just beneath the plasma membrane.
cytoskeleton organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures.
embryonic morphogenesis The process in which anatomical structures are generated and organized during the embryonic phase. The embryonic phase begins with zygote formation. The end of the embryonic phase is organism-specific. For example, it would be at birth for mammals, larval hatching for insects and seed dormancy in plants.
epithelial to mesenchymal transition A transition where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell.
glomerular visceral epithelial cell migration The orderly movement of a podocyte from one site to another, often during the development of a multicellular organism or multicellular structure. A podocyte is a specialized kidney epithelial cell.
I-kappaB kinase/NF-kappaB signaling The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription.
leukocyte cell-cell adhesion The attachment of a leukocyte to another cell via adhesion molecules.
leukocyte migration The movement of a leukocyte within or between different tissues and organs of the body.
leukocyte tethering or rolling Transient adhesive interactions between leukocytes and endothelial cells lining blood vessels. Carbohydrates on circulating leukocytes bind selectins on the vessel wall causing the leukocytes to slow down and roll along the inner surface of the vessel wall. During this rolling motion, transitory bonds are formed and broken between selectins and their ligands. Typically the first step in cellular extravasation (the movement of leukocytes out of the circulatory system, towards the site of tissue damage or infection).
membrane to membrane docking The initial attachment of a membrane to a target membrane, mediated by proteins protruding from the two membranes. Docking requires only that the membranes come close enough for the proteins to interact and adhere.
mitotic cytokinesis A cell cycle process that results in the division of the cytoplasm of a cell after mitosis, resulting in the separation of the original cell into two daughter cells.
mRNA destabilization Any process that decreases the stability of an mRNA molecule, making it more vulnerable to degradative processes. Messenger RNA is the intermediate molecule between DNA and protein. It includes UTR and coding sequences. It does not contain introns.
myoblast migration The orderly movement of a myoblast from one site to another, often during the development of a multicellular organism. A myoblast is a cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into skeletal muscle fibers.
negative regulation of amyloid precursor protein catabolic process Any process that stops, prevents or reduces the frequency, rate or extent of amyloid precursor protein catabolic process.
negative regulation of amyloid-beta formation Any process that stops, prevents or reduces the frequency, rate or extent of amyloid-beta formation.
negative regulation of angiogenesis Any process that stops, prevents, or reduces the frequency, rate or extent of angiogenesis.
negative regulation of bicellular tight junction assembly Any process that stops, prevents or reduces the frequency, rate or extent of tight junction assembly.
negative regulation of myosin-light-chain-phosphatase activity Any process that stops, prevents, or reduces the frequency, rate or extent of myosin-light-chain-phosphatase activity.
negative regulation of neuron apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
negative regulation of phosphorylation Any process that stops, prevents or decreases the rate of addition of phosphate groups to a molecule.
negative regulation of protein binding Any process that stops, prevents, or reduces the frequency, rate or extent of protein binding.
neuron projection arborization The process in which the anatomical structures of a neuron projection are generated and organized into branches. A neuron projection is any process extending from a neural cell, such as axons or dendrites.
neuron projection development The process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
peptidyl-serine phosphorylation The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
peptidyl-threonine phosphorylation The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
positive regulation of amyloid-beta clearance Any process that activates or increases the frequency, rate or extent of amyloid-beta clearance.
positive regulation of autophagy Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm.
positive regulation of cardiac muscle hypertrophy Any process that increases the rate, frequency or extent of the enlargement or overgrowth of all or part of the heart due to an increase in size (not length) of individual cardiac muscle fibers, without cell division.
positive regulation of connective tissue replacement Any process that activates or increases the frequency, rate or extent of connective tissue replacement.
positive regulation of focal adhesion assembly Any process that activates or increases the frequency, rate or extent of focal adhesion assembly, the establishment and maturation of focal adhesions.
positive regulation of gene expression Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of MAPK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade.
protein localization to plasma membrane A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane.
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of actin cytoskeleton organization Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
regulation of actin filament-based process Any process that modulates the frequency, rate or extent of any cellular process that depends upon or alters the actin cytoskeleton.
regulation of angiotensin-activated signaling pathway Any process that modulates the frequency, rate or extent of the angiotensin-activated signaling pathway.
regulation of cell junction assembly Any process that modulates the frequency, rate or extent of cell junction assembly.
regulation of cell migration Any process that modulates the frequency, rate or extent of cell migration.
regulation of establishment of endothelial barrier Any process that modulates the frequency, rate or extent of establishment of endothelial barrier.
regulation of keratinocyte differentiation Any process that modulates the frequency, rate or extent of keratinocyte differentiation.
regulation of microtubule cytoskeleton organization Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising microtubules and their associated proteins.
regulation of neuron differentiation Any process that modulates the frequency, rate or extent of neuron differentiation.
regulation of synaptic vesicle endocytosis Any process that modulates the frequency, rate or extent of synaptic vesicle endocytosis.
response to angiotensin Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an angiotensin stimulus. Angiotensin is any of three physiologically active peptides (angiotensin II, III, or IV) processed from angiotensinogen.
response to transforming growth factor beta Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus.
Rho protein signal transduction The series of molecular signals within the cell that are mediated by a member of the Rho family of proteins switching to a GTP-bound active state.

15 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q28021 ROCK2 Rho-associated protein kinase 2 Bos taurus (Bovine) SS
Q9W1B0 gek Serine/threonine-protein kinase Genghis Khan Drosophila melanogaster (Fruit fly) SS
O75116 ROCK2 Rho-associated protein kinase 2 Homo sapiens (Human) SS
Q9Y5S2 CDC42BPB Serine/threonine-protein kinase MRCK beta Homo sapiens (Human) SS
Q5VT25 CDC42BPA Serine/threonine-protein kinase MRCK alpha Homo sapiens (Human) EV
Q13464 ROCK1 Rho-associated protein kinase 1 Homo sapiens (Human) SS
P70336 Rock2 Rho-associated protein kinase 2 Mus musculus (Mouse) SS
Q80UW5 Cdc42bpg Serine/threonine-protein kinase MRCK gamma Mus musculus (Mouse) PR
Q7TT50 Cdc42bpb Serine/threonine-protein kinase MRCK beta Mus musculus (Mouse) SS
Q3UU96 Cdc42bpa Serine/threonine-protein kinase MRCK alpha Mus musculus (Mouse) SS
P70335 Rock1 Rho-associated protein kinase 1 Mus musculus (Mouse) SS
M3TYT0 ROCK2 Rho-associated protein kinase 2 Sus scrofa (Pig) SS
O54874 Cdc42bpa Serine/threonine-protein kinase MRCK alpha Rattus norvegicus (Rat) SS
Q62868 Rock2 Rho-associated protein kinase 2 Rattus norvegicus (Rat) EV
Q7TT49 Cdc42bpb Serine/threonine-protein kinase MRCK beta Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MSTGDSFETR FEKIDNLLRD PKSEVNSDCL LDGLDALVYD LDFPALRKNK NIDNFLSRYK
70 80 90 100 110 120
DTINKIRDLR MKAEDYEVVK VIGRGAFGEV QLVRHKSTRK VYAMKLLSKF EMIKRSDSAF
130 140 150 160 170 180
FWEERDIMAF ANSPWVVQLF YAFQDDRYLY MVMEYMPGGD LVNLMSNYDV PEKWARFYTA
190 200 210 220 230 240
EVVLALDAIH SMGFIHRDVK PDNMLLDKSG HLKLADFGTC MKMNKEGMVR CDTAVGTPDY
250 260 270 280 290 300
ISPEVLKSQG GDGYYGRECD WWSVGVFLYE MLVGDTPFYA DSLVGTYSKI MNHKNSLTFP
310 320 330 340 350 360
DDNDISKEAK NLICAFLTDR EVRLGRNGVE EIKRHLFFKN DQWAWETLRD TVAPVVPDLS
370 380 390 400 410 420
SDIDTSNFDD LEEDKGDEET FPIPKAFVGN QLPFVGFTYY SNRRYLPSAN PSENRSSSNV
430 440 450 460 470 480
DKNVQESLQK TIYKLEEQLH NEMQLKDEME QKCRTSNIKL DKIMKELDEE GNQRRNLESA
490 500 510 520 530 540
VSQIEKEKML LQHRINEYQR KVEQENEKRR NVENEVSTLK DQLEDLRKAS QSSQLANEKL
550 560 570 580 590 600
TQLQKQLEEA NDLLRTESDT AVRLRKSHTE MSKSVSQLES LNRELQERNR MLENSKSQAD
610 620 630 640 650 660
KDYYQLQAVL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKHNLERVEG ERKEAQDMLN
670 680 690 700 710 720
HSEKEKNNLE IDLNYKLKSI QQRLEQEVNE HKVTKARLTD KHQSIEEAKS VAMCEMEKKL
730 740 750 760 770 780
KEEREAREKA ENRVVETEKQ CSMLDVDLKQ SQQKLEHLTE NKERLEDAVK SLTLQLEQES
790 800 810 820 830 840
NKRILLQSEL KTQAFEADNL KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR
850 860 870 880 890 900
ELQDQLEAEQ YFSTLYKTQV KELKEEIEEK NRENLRKIQE LQSEKETLST QLDLAETKAE
910 920 930 940 950 960
SEQLARGILE EQYFELTQES KKAASRNRQE ITDKDHTVSR LEEANNALTK DIELLRKENE
970 980 990 1000 1010 1020
ELNERMRTAE EEYKLKKEEE ISNLKAAFEK NISTERTLKT QAVNKLAEIM NRKDFKIDRK
1030 1040 1050 1060 1070 1080
KANTQDLRKK EKENRKLQLE LNQEREKFNQ MVVKHQKELN DMQAQLVEEC THRNELQMQL
1090 1100 1110 1120 1130 1140
ASKESDIEQL RAKLLDLSDS TSVASFPSAD ETDGNLPVGS ACIPYLFIFY SSSSRIEGWL
1150 1160 1170 1180 1190 1200
SVPNRGNIKR YGWKKQYVVV SSKKMLFYND EQDKEQSSPS MVLDIDKLFH VRPVTQGDVY
1210 1220 1230 1240 1250 1260
RAETEEIPKI FQILYANEGE CRKDIEVEPV QQGEKTNFQN HKGHEFIPTL YHFPANCEAC
1270 1280 1290 1300 1310 1320
AKPLWHVFKP PPALECRRCH VKSHRDHLDK KEDLIPPCKV SYDVTSARDM LLLACPQDEQ
1330 1340 1350 1360
KKWVTHLVKK IPKKAPSGFV RASPRTLSTR STANQSFRKV VKNTSGKTS