Molecule Information

General Information of the Molecule (ID: Mol04403)

• Name: Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: CAMK2D
• Gene ID: 817
• Sequence:
  MASTTTCTRFTDEYQLFEELGKGAFSVVRRCMKIPTGQEYAAKIINTKKLSARDHQKLER
  EARICRLLKHPNIVRLHDSISEEGFHYLVFDLVTGGELFEDIVAREYYSEADASHCIQQ
  I LESVNHCHLNGIVHRDLKPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTP
  GY LSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDEDQHRLYQQIKAGAYDFPSPE
  WDT VTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASMMHRQETVDCLKKFNA
  RRKL KGAILTTMLATRNFSAAKSLLKKPDGVKESTESSNTTIEDEDVKARKQEIIKVTE
  QLIEA INNGDFEAYTKICDPGLTAFEPEALGNLVEGMDFHRFYFENALSKSNKPIHTII
  LNPHVH LVGDDAACIAYIRLTQYMDGSGMPKTMQSEETRVWHRRDGKWQNVHFHRSGSP
  TVPIKPP CIPNGKENFSGGTSLWQNI
• Function: Calcium/calmodulin-dependent protein kinase involved in theregulation of Ca homeostatis and excitation-contraction coupling in heart by targeting ion channels, transporters and accessoryproteins involved in Ca influx into the myocyte, Ca releasefrom the sarcoplasmic reticulum , SR Ca uptake and Na andK channel transport. Targets also transcription factors andsignaling molecules to regulate heart function. In its activated form,is involved in the pathogenesis of dilated cardiomyopathy and heartfailure. Contributes to cardiac decompensation and heart failure byregulating SR Ca release via direct phosphorylation of RYR2 Cachannel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2repressor HDAC4, promoting its nuclear export and binding to 14-3-3protein, and expression of MEF2 and genes involved in the hypertrophicprogram . Is essential for left ventricular remodelingresponses to myocardial infarction. In pathological myocardialremodeling acts downstream of the beta adrenergic receptor signalingcascade to regulate key proteins involved in ECC. Regulates Cainflux to myocytes by binding and phosphorylating the L-type Cachannel subunit beta-2 CACNB2. In addition to Ca channels, cantarget and regulate the cardiac sarcolemmal Na channel Nav1.5/SCN5Aand the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis inheart failure. Phosphorylates phospholamban , an endogenousinhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SRCa uptake that may be important in frequency-dependent accelerationof relaxation and maintenance of contractile function duringacidosis . May participate in the modulation ofskeletal muscle function in response to exercise, by regulating SRCa transport through phosphorylation of PLN/PLB and triadin, aryanodine receptor-coupling factor. In response to interferon-gamma stimulation, catalyzes phosphorylation of STAT1,stimulating the JAK-STAT signaling pathway .{ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701,ECO:0000269|PubMed:17179159}.
• Uniprot ID: KCC2D_HUMAN
• Ensembl ID: ENSG0000014534920
• HGNC ID: HGNC:1462

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

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Cloperastine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Sensitive Drug: Cloperastine
• Molecule Alteration: Phosphorylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Oxytocin signaling pathway; Activation; hsa04921
• In Vitro Model: DU145CR cells; prostate; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: MS analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor-signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. We identified the OXT-signaling pathway as a potential target for CBZ-resistant CRPC using single-cell transcriptomic analysis of CTCs. CLO may potentially overcome CBZ resistance in CRPC by inhibiting the OXT-signaling pathway.

References

• Ref 1: G-protein signaling of oxytocin receptor as a potential target for cabazitaxel-resistant prostate cancer. PNAS Nexus. 2024 Jan 4;3(1):pgae002.