P70335

SS
Gene name
Rock1
Protein name
Rho-associated protein kinase 1
Names
EC 2.7.11.1 , Rho-associated, coiled-coil-containing protein kinase 1 , Rho-associated, coiled-coil-containing protein kinase I , ROCK-I , p160 ROCK-1 , p160ROCK
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:19877
EC number
2.7.11.1: Protein-serine/threonine kinases
Protein Class

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 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.

Autoinhibitory domains (AIDs)

941-1018 (RBD domain) SS

Target domain

91-376 (Catalytic kinase domain)

Relief mechanism

Partner binding

Assay

1118-1317 (PH domain) SS

Target domain

91-376 (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

References

Autoinhibited structure

Activated structure

1 structures for P70335

Entry ID Method Resolution Chain Position Source
AF-P70335-F1 Predicted AlphaFoldDB

35 variants for P70335

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3408051430 138 Q>R No EVA
rs3389481934 260 D>E No EVA
rs3389454141 261 W>* No EVA
rs3389480893 263 S>L No EVA
rs3389435579 267 F>S No EVA
rs3407579271 432 I>V No EVA
rs3408272351 433 Y>F No EVA
rs3389495181 436 E>D No EVA
rs3408131668 436 E>V No EVA
rs3413075915 448 E>Q No EVA
rs3389490650 511 N>Y No EVA
rs1134843356 518 T>S No EVA
rs1133583225 522 Q>L No EVA
rs3389487196 561 A>P No EVA
rs3389445659 593 E>* No EVA
rs3389454142 593 E>D No EVA
rs3389466419 601 K>N No EVA
rs3389495190 616 D>N No EVA
rs3389478330 704 S>T No EVA
rs3389398563 719 K>R No EVA
rs3389488412 734 V>SDG* No EVA
rs3389466398 741 C>* No EVA
rs3508154309 794 A>V No EVA
rs3389481900 811 I>M No EVA
rs3389487160 835 N>D No EVA
rs3389487619 867 I>S No EVA
rs3389495216 870 K>Q No EVA
rs3389398600 886 E>D No EVA
rs3389453992 890 T>S No EVA
rs3389435537 895 A>T No EVA
rs3389488410 1119 S>L No EVA
rs3406361878 1155 D>Y No EVA
rs3408271640 1211 E>V No EVA
rs3389488492 1320 P>T No EVA
rs3389466354 1345 V>E No EVA

No associated diseases with P70335

9 regional properties for P70335

Type Name Position InterPro Accession
domain Protein kinase domain 76 - 338 IPR000719
domain AGC-kinase, C-terminal 341 - 409 IPR000961
domain Pleckstrin homology domain 1118 - 1319 IPR001849
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 1228 - 1283 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 (PubMed:16741948)
  • Colocalizes with ITGB1BP1 and ITGB1 at the cell membrane predominantly in lamellipodia and membrane ruffles, but also in retraction fibers (PubMed:16741948)
  • Localizes at the cell membrane in an ITGB1BP1-dependent manner (PubMed:16741948)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

11 GO annotations of cellular component

Name Definition
amyloid-beta complex Protein complex involved in modulation of signaling and synaptic function in the brain, predominantly in the cerebral cortex and hippocampus. Forms dimers and multimers of amyloid beta peptide 40 and peptide 42 (proteolytic cleavage products of amyloid beta A4 protein, also known as amyloid beta precursor protein). Mostly found in the extracellular space with a proportion occurring as membrane-bound species. Influences synaptic plasticity through various receptors, mediates dendritic spine loss leading to decreased synapse density, inhibits long-term potentiation (LTP) and enhances long-term depression (LTD). Soluble multimeric form is the main pathogenic species linked to Alzheimer's disease.
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.
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.
Schaffer collateral - CA1 synapse A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell.

7 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.
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
protein serine/threonine kinase activity Catalysis of the reactions
Rho-dependent protein serine/threonine kinase activity Rho GTPase-dependent catalysis of the reaction
small GTPase binding Binding to a small monomeric GTPase.

47 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.
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.
blood vessel diameter maintenance Any process that modulates the diameter of blood vessels.
canonical NF-kappaB signal transduction 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.
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.
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.
motor neuron apoptotic process Any apoptotic process in a motor neuron, an efferent neuron that passes from the central nervous system or a ganglion toward or to a muscle and conducts an impulse that causes movement.
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-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 motor neuron apoptotic process Any process that stops, prevents or reduces the frequency, rate or extent of motor neuron apoptotic process.
negative regulation of phosphorylation Any process that stops, prevents or decreases the rate of addition of phosphate groups to a molecule.
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.
podocyte 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.
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 dephosphorylation Any process that activates or increases the frequency, rate or extent of removal of phosphate groups from a molecule.
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 synapse maturation Any process that modulates the extent of synapse maturation, the process that organizes a synapse so that it attains its fully functional state.
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
Q5VT25 CDC42BPA Serine/threonine-protein kinase MRCK alpha Homo sapiens (Human) EV
Q9Y5S2 CDC42BPB Serine/threonine-protein kinase MRCK beta Homo sapiens (Human) SS
Q13464 ROCK1 Rho-associated protein kinase 1 Homo sapiens (Human) 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
P70336 Rock2 Rho-associated protein kinase 2 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
Q63644 Rock1 Rho-associated protein kinase 1 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 ASENRSSSNV
430 440 450 460 470 480
DKSLQESLQK TIYKLEEQLH NEMQLKDEME QKCRTSNLKL DKIMKELDEE GNQRRNLESA
490 500 510 520 530 540
VSQIEKEKML LQHRINEYQR KVEQENEKRR NIENEVSTLK DQLEDLRKAS QTSQLANEKL
550 560 570 580 590 600
TQLQKQLEEA NDLLRTESDT AVRLRKSHTE MSKSISQLES LNRELQERNR ILENSKSQAD
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 NKERMEDEVK NLALQLEQES
790 800 810 820 830 840
NKRLLLQNEL 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 LEETNSVLTK DIEMLRKENE
970 980 990 1000 1010 1020
ELNERMRTAE EEYKLKKEEE INNLKAAFEK NISTERTLKT QAVNKLAEIM NRKDFKIDRK
1030 1040 1050 1060 1070 1080
KANTQDLRKK EKENRKLQLE LNQEREKFNQ MVVKHQKELN DMQAQLVEEC THRNELQMQL
1090 1100 1110 1120 1130 1140
ASKESDIEQL RAKLLDLSDS TSVASFPSAD ETDGNLPESR IEGWLSVPNR GNIKRYGWKK
1150 1160 1170 1180 1190 1200
QYVVVSSKKI LFYNDEQDKE QSSPSMVLDI DKLFHVRPVT QGDVYRAETE EIPKIFQILY
1210 1220 1230 1240 1250 1260
ANEGECRKDI EVEPVQQGEK TNFQNHKGHE FIPTLYHFPA NCEACAKPLW HVFKPPPALE
1270 1280 1290 1300 1310 1320
CRRCHVKCHR DHLDKKEDLI SPCKVSYDVT SARDMLLLAC SQDEQKKWVT HLVKKIPKNP
1330 1340 1350
PSGFVRASPR TLSTRSTANQ SFRKVVKNTS GKTS