Molecule Information

General Information of the Molecule (ID: Mol00712)

• Name: DNA repair protein XRCC4 (XRCC4) ,Homo sapiens
• Synonyms: hXRCC4; X-ray repair cross-complementing protein 4; XRCC4/C
• Molecule Type: Protein
• Gene Name: XRCC4
• Gene ID: 7518
• Location: chr5:83077498-83353787[+]
• Sequence:
  MERKISRIHLVSEPSITHFLQVSWEKTLESGFVITLTDGHSAWTGTVSESEISQEADDMA
  MEKGKYVGELRKALLSGAGPADVYTFNFSKESCYFFFEKNLKDVSFRLGSFNLEKVENPA
  EVIRELICYCLDTIAENQAKNEHLQKENERLLRDWNDVQGRFEKCVSAKEALETDLYKRF
  ILVLNEKKTKIRSLHNKLLNAAQEREKDIKQEGETAICSEMTADRDPVYDESTDEESENQ
  TDLSGLASAAVSKDDSIISSLDVTDIAPSRKRRQRMQRNLGTEPKMAPQENQLQEKENSR
  PDSSLPETSKKEHISAENMSLETLRNSSPEDLFDEI
• Function: [DNA repair protein XRCC4]: DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination. Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired. The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other. The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors. Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed. XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity. Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends. Promotes displacement of PNKP from processed strand break termini.
• Uniprot ID: XRCC4_HUMAN
• Ensembl ID: ENSG00000152422
• HGNC ID: HGNC:12831

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

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioblastoma [1]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• In Vitro Model: A172 cells; Brain; Homo sapiens (Human); CVCL_0131
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: T98G cells; Brain; Homo sapiens (Human); CVCL_0556
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Inhibiting miR-151a leads to increased XRCC4 levels, resulting in activated DNA repair and subsequent resistance to TMZ.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.31E-104; Fold-change: 4.16E-01; Z-score: 1.53E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.98E-07; Fold-change: 4.95E-01; Z-score: 1.32E+01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.69E-04; Fold-change: 6.00E-01; Z-score: 1.47E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.81E-17; Fold-change: 1.27E+00; Z-score: 7.65E+00

References

• Ref 1: Exosomal transfer of miR-151a enhances chemosensitivity to temozolomide in drug-resistant glioblastoma. Cancer Lett. 2018 Nov 1;436:10-21. doi: 10.1016/j.canlet.2018.08.004. Epub 2018 Aug 10.