Molecule Information

General Information of the Molecule (ID: Mol04153)

• Name: Rho associated coiled-coil containing protein kinase 2 (ROCK2) ,Homo sapiens
• Synonyms: Rho kinase 2; Rho-associated, coiled-coil-containing protein kinase 2; Rho-associated, coiled-coil-containing protein kinase II; p164 ROCK-2
• Molecule Type: Protein
• Gene Name: ROCK2
• Gene ID: 9475
• Location: chr2:11179759-11348330[-]
• Sequence:
  MSRPPPTGKMPGAPETAPGDGAGASRQRKLEALIRDPRSPINVESLLDGLNSLVLDLDFP
  ALRKNKNIDNFLNRYEKIVKKIRGLQMKAEDYDVVKVIGRGAFGEVQLVRHKASQKVYAM
  KLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLVNL
  MSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKHGHLKLADFGTCMKMD
  ETGMVHCDTAVGTPDYISPEVLKSQGGDGFYGRECDWWSVGVFLYEMLVGDTPFYADSLV
  GTYSKIMDHKNSLCFPEDAEISKHAKNLICAFLTDREVRLGRNGVEEIRQHPFFKNDQWH
  WDNIRETAAPVVPELSSDIDSSNFDDIEDDKGDVETFPIPKAFVGNQLPFIGFTYYRENL
  LLSDSPSCRETDSIQSRKNEESQEIQKKLYTLEEHLSNEMQAKEELEQKCKSVNTRLEKT
  AKELEEEITLRKSVESALRQLEREKALLQHKNAEYQRKADHEADKKRNLENDVNSLKDQL
  EDLKKRNQNSQISTEKVNQLQRQLDETNALLRTESDTAARLRKTQAESSKQIQQLESNNR
  DLQDKNCLLETAKLKLEKEFINLQSALESERRDRTHGSEIINDLQGRICGLEEDLKNGKI
  LLAKVELEKRQLQERFTDLEKEKSNMEIDMTYQLKVIQQSLEQEEAEHKATKARLADKNK
  IYESIEEAKSEAMKEMEKKLLEERTLKQKVENLLLEAEKRCSLLDCDLKQSQQKINELLK
  QKDVLNEDVRNLTLKIEQETQKRCLTQNDLKMQTQQVNTLKMSEKQLKQENNHLMEMKMN
  LEKQNAELRKERQDADGQMKELQDQLEAEQYFSTLYKTQVRELKEECEEKTKLGKELQQK
  KQELQDERDSLAAQLEITLTKADSEQLARSIAEEQYSDLEKEKIMKELEIKEMMARHKQE
  LTEKDATIASLEETNRTLTSDVANLANEKEELNNKLKDVQEQLSRLKDEEISAAAIKAQF
  EKQLLTERTLKTQAVNKLAEIMNRKEPVKRGNDTDVRRKEKENRKLHMELKSEREKLTQQ
  MIKYQKELNEMQAQIAEESQIRIELQMTLDSKDSDIEQLRSQLQALHIGLDSSSIGSGPG
  DAEADDGFPESRLEGWLSLPVRNNTKKFGWVKKYVIVSSKKILFYDSEQDKEQSNPYMVL
  DIDKLFHVRPVTQTDVYRADAKEIPRIFQILYANEGESKKEQEFPVEPVGEKSNYICHKG
  HEFIPTLYHFPTNCEACMKPLWHMFKPPPALECRRCHIKCHKDHMDKKEEIIAPCKVYYD
  ISTAKNLLLLANSTEEQQKWVSRLVKKIPKKPPAPDPFARSSPRTSMKIQQNQSIRRPSR
  QLAPNKPS
• 3D-structure: PDB ID: 6ED6; Classification: Transferase/transferase inhibitor; Method: X-ray diffraction; Resolution: 2.86 Å
• 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 ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1- p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. .
• Uniprot ID: ROCK2_HUMAN
• Ensembl ID: ENSG00000134318
• HGNC ID: HGNC:10252

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK signaling pathway; Activation; hsa04010
• Cell Pathway Regulation: PI3K-Akt signaling pathway; Activation; hsa04151
• In Vitro Model: HL-60/ADM cells; Blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: In this study, we found that there was a pronounced upregulation of ROCK2 in AML cells. Suppressing ROCK2 significantly boosts the effectiveness of drugs in both AML cell lines and primary AML specimens while causing a substantial decrease in the activation of MAPK and PI3K/AKT pathways.

Investigative Drug(s) 1 drug(s) in total

Peg-Loxenatide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Type 2 diabetes mellitus [ICD-11: 5A11.0] [2]

• Sensitive Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Sensitive Drug: Peg-Loxenatide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hepatic cells; Liver; Homo sapiens (Human); N.A.
• In Vivo Model: Sprague-Dawley rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Immunohistochemistry; ELISA assay; RNA immunoprecipitation assay; RT-qPCR; Western blot assay
• Experiment for Drug Resistance: Fasting blood glucose level testing; Oral glucose tolerance testing; Biochemical assay; Reactive oxygen species assay
• Mechanism Description: PEG-Loxe mitigated inflammatory response and oxidative stress. High-PEG-Loxe reduced RhoA and Rho-associated coiled-coil kinase 2 (ROCK2) in liver tissues of type 2 diabetes mellitus rats, while both doses of PEG-Loxe decreased steroid receptor RNA activator (SRA). SRA overexpression reversed the protective functions of high-PEG-Loxe. SRA cooperated with cellular nucleic acid binding protein (CNBP) to enhance ROCK2 mRNA stability.High-PEG-Loxe relieves insulin resistance and lipid metabolism disorder in type 2 diabetes mellitus through SRA/CNBP/ROCK2 axis. This research provides a molecular mechanism of PEG-Loxe for treating type 2 diabetes mellitus.

References

• Ref 1: ROCK2 increases drug resistance in acute myeloid leukemia via metabolic reprogramming and MAPK/PI3K/AKT signaling. Int Immunopharmacol. 2024 Oct 25;140:112897.
• Ref 2: Polyethylene glycol loxenatide modulates lipid metabolism and insulin resistance through lncRNA steroid receptor RNA activator/cellular nucleic acid binding protein/Rho-associated coiled-coil kinase 2 axis in type 2 diabetes mellitus. J Diabetes Investig. 2025 Apr;16(4):715-727.