Molecule Information

General Information of the Molecule (ID: Mol00972)

• Name: GDH/6PGL endoplasmic bifunctional protein (H6PD) ,Mus musculus
• Synonyms: Glucose 1-dehydrogenase; Glucose-6-phosphate dehydrogenase; 6PGL
• Molecule Type: Protein
• Gene Name: H6pd
• Gene ID: 100198
• Location: chr 4: 150063932-150093480[-]
• Sequence:
  MLLAAMCLALLGCLQAQELKGHVSIILLGATGDLAKKYLWQGLFQLYLDEAGKGHSFSFH
  GAALTAPQQGQKLMDKVLESLSCPKDLVPSRCDELKGQFLQLSQYRQLKTVEDYQTLNKD
  IETQVQQDGLWEAGRIFYFSVPPFAYADIARNINSSCRPHPGAWLRVVFEKPFGHDHLSA
  QQLASELGSFFQEEEMYRVDHYLGKQAVAQILPFRDQNRKALDGLWNRHHVERVEIILKE
  TIDAEGRASFYEEYGVIRDTLQNHLTEILTLVAMELPLNISSSAAVLQHKLWAFQALRGL
  QKSSAILGQYQAYSGQVRRELQKPDGFQSLTPTFAGVLVHIDNLRWEGVPFILMSGKALD
  ERVGYVRIVFKNRAYCTQSERHWVPEQSRCLPQQIIFYIGHGELGHPAILVSRNLFKPSL
  PTQKWKEVQDQPGLRLFGRPLSDYYAYRPVREQDAYSTLLSHIFHCRKESFITTENLLAS
  WVFWTPLLDSLAFEVPRPYPGGAENGQLLDFEFSGGQLTFSQQQLEVLIPDLGSVPKPSD
  FQVLGARYRQSPLITAWPEELISKLASDIEAAAVQAVRHFGKFHLALSGGSSPIALFQQL
  ATGHYSFPWAHTHLWLVDERCVPLSDPDSNFQGLQAHLLQHVRVPYYNIHPMPVHLHQRL
  CAEEDQGAQTYASEISALVANSSFDLVLLGMGTDGHTASLFPQSPTGLDGDQLVVLTESP
  FRPHQRMSLSLPLINRAKKVAVLVMGRTKREITTLVSRVGHEPKKWPISGVVPLSGQLVW
  YMDYEAFLG
• Function: Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power and metabolic intermediates for biosynthetic processes. Has a hexose-6-phosphate dehydrogenase activity, with broad substrate specificity compared to glucose-6-phosphate 1-dehydrogenase/G6PD, and catalyzes the first step of the pentose phosphate pathway. In addition, acts as a 6-phosphogluconolactonase and catalyzes the second step of the pentose phosphate pathway. May have a dehydrogenase activity for alternative substrates including glucosamine 6-phosphate and glucose 6-sulfate. The main function of this enzyme is to provide reducing equivalents such as NADPH to maintain the adequate levels of reductive cofactors in the oxidizing environment of the endoplasmic reticulum. By producing NADPH that is needed by reductases of the lumen of the endoplasmic reticulum like corticosteroid 11-beta-dehydrogenase isozyme 1/HSD11B1, indirectly regulates their activity.
• Uniprot ID: G6PE_MOUSE
• Ensembl ID: ENSMUSG00000028980

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Mus
Species: Mus musculus

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

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

Cetuximab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Colorectal cancer [1]

• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Cetuximab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Pentose phosphate signaling pathway; Activation; hsa00030
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: GEO cells; Colon; Homo sapiens (Human); CVCL_0271
• In Vivo Model: Xenografts mouse model; Mus musculus
• Experiment for Molecule Alteration: 2D DIGE assay
• Mechanism Description: LDHB and PDHA1 were downregulated in GEO-CR tumor xenografts, similarly to the corresponding deregulations observed in the derived cell lines. Upregulation of G6PDH and transketolase (TkT) was also actually maintained in tumor xenografts. Indeed, PPP2CA expression in xenografted samples was similarly evaluated, demonstrating that protein downregulation in vivo was even more pronounced than that measured in GEO-CR cells.

References

• Ref 1: Increased anaerobic metabolism is a distinctive signature in a colorectal cancer cellular model of resistance to antiepidermal growth factor receptor antibody. Proteomics. 2013 Mar;13(5):866-77. doi: 10.1002/pmic.201200303. Epub 2013 Jan 24.