Molecule Information

General Information of the Molecule (ID: Mol04098)

• Name: Cluster of differentiation 276 (CD276) ,Homo sapiens
• Synonyms: 4Ig-B7-H3; B7 homolog 3; Costimulatory molecule; CD_antigen=CD276
• Molecule Type: Protein
• Gene Name: CD276
• Gene ID: 80381
• Location: chr15:73683966-73714514[+]
• Sequence:
  MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPGFSL
  AQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSF
  TCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQD
  GQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQ
  RSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEG
  RDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY
  SKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
  DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIAL
  LVALAFVCWRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
• Function: May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling. .
• Uniprot ID: CD276_HUMAN
• Ensembl ID: ENSG00000103855
• HGNC ID: HGNC:19137

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

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

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

H-mMnO2

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Nucleic acid metabolism
• Sensitive Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Sensitive Drug: H-mMnO2
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.12E-50; Fold-change: 8.24E-01; Z-score: 2.07E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786O/R cells; Liver; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: CD276 and MTHFD2 were identified as a potential surface marker and a therapeutic target, respectively, for targeting sunitinib-resistant ccRCC and its CSC population. MTHFD2 knockdown remodeled the folate-nucleotide metabolism of tumor cells. Moreover, H-mMnO6was confirmed to be able of altering GABA metabolism by enhancing GABA catabolism in drug-resistant tumor cells.

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

Sunitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Nucleic acid metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.12E-50; Fold-change: 8.24E-01; Z-score: 2.07E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki1/R cells; Liver; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: CD276 and MTHFD2 were identified as a potential surface marker and a therapeutic target, respectively, for targeting sunitinib-resistant ccRCC and its CSC population. MTHFD2 knockdown remodeled the folate-nucleotide metabolism of tumor cells. Moreover, H-mMnO3was confirmed to be able of altering GABA metabolism by enhancing GABA catabolism in drug-resistant tumor cells.

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Nucleic acid metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.12E-50; Fold-change: 8.24E-01; Z-score: 2.07E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786O/R cells; Liver; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: CD276 and MTHFD2 were identified as a potential surface marker and a therapeutic target, respectively, for targeting sunitinib-resistant ccRCC and its CSC population. MTHFD2 knockdown remodeled the folate-nucleotide metabolism of tumor cells. Moreover, H-mMnO2was confirmed to be able of altering GABA metabolism by enhancing GABA catabolism in drug-resistant tumor cells.

References

• Ref 1: Engineered Biomimetic Nanovesicles Synergistically Remodel Folate-Nucleotide and gamma-Aminobutyric Acid Metabolism to Overcome Sunitinib-Resistant Renal Cell Carcinoma. ACS Nano. 2024 Oct 8;18(40):27487-27502.