Molecule Information

General Information of the Molecule (ID: Mol00191)

• Name: UV radiation resistance-associated gene protein (UVRAG) ,Homo sapiens
• Synonyms: p63
• Molecule Type: Protein
• Gene Name: UVRAG
• Gene ID: 7405
• Location: chr11:75815210-76144232[+]
• Sequence:
  MSASASVGGPVPQPPPGPAAALPPGSAARALHVELPSQQRRLRHLRNIAARNIVNRNGHQ
  LLDTYFTLHLCSTEKIYKEFYRSEVIKNSLNPTWRSLDFGIMPDRLDTSVSCFVVKIWGG
  KENIYQLLIEWKVCLDGLKYLGQQIHARNQNEIIFGLNDGYYGAPFEHKGYSNAQKTILL
  QVDQNCVRNSYDVFSLLRLHRAQCAIKQTQVTVQKIGKEIEEKLRLTSTSNELKKKSECL
  QLKILVLQNELERQKKALGREVALLHKQQIALQDKGSAFSAEHLKLQLQKESLNELRKEC
  TAKRELFLKTNAQLTIRCRQLLSELSYIYPIDLNEHKDYFVCGVKLPNSEDFQAKDDGSI
  AVALGYTAHLVSMISFFLQVPLRYPIIHKGSRSTIKDNINDKLTEKEREFPLYPKGGEKL
  QFDYGVYLLNKNIAQLRYQHGLGTPDLRQTLPNLKNFMEHGLMVRCDRHHTSSAIPVPKR
  QSSIFGGADVGFSGGIPSPDKGHRKRASSENERLQYKTPPPSYNSALAQPVTTVPSMGET
  ERKITSLSSSLDTSLDFSKENKKKGEDLVGSLNGGHANVHPSQEQGEALSGHRATVNGTL
  LPSEQAGSASVQLPGEFHPVSEAELCCTVEQAEEIIGLEATGFASGDQLEAFNCIPVDSA
  VAVECDEQVLGEFEEFSRRIYALNENVSSFRRPRRSSDK
• Function: Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P). During autophagy acts as regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in maturation of autophagosomes and endocytosis. Activates lipid kinase activity of PIK3C3. Involved in the regulation of degradative endocytic trafficking and cytokinesis, and in regulation of ATG9A transport from the Golgi to the autophagosome; the functions seems to implicate its association with PI3KC3-C2. Involved in maturation of autophagosomes and degradative endocytic trafficking independently of BECN1 but depending on its association with a class C Vps complex (possibly the HOPS complex); the association is also proposed to promote autophagosome recruitment and activation of Rab7 and endosome-endosome fusion events. Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion. In case of negative-strand RNA virus infection is required for efficient virus entry, promotes endocytic transport of virions and is implicated in a VAMP8-specific fusogenic SNARE complex assembly.
• Uniprot ID: UVRAG_HUMAN
• Ensembl ID: ENSG00000198382
• HGNC ID: HGNC:12640

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

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

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

Vemurafenib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Melanoma [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Sensitive Drug: Vemurafenib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375-R cells; Skin; Homo sapiens (Human); CVCL_6234
• In Vitro Model: G-361 cells; Skin; Homo sapiens (Human); CVCL_1220
• In Vitro Model: G361/R cells; Skin; Homo sapiens (Human); CVCL_IW13
• In Vitro Model: MeWo cells; Skin; Homo sapiens (Human); CVCL_0445
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR216b enhances the efficacy of vemurafenib by targeting Beclin-1, UVRAG and ATG5 in melanoma. miR216b suppresses autophagy in both BRAFi-sensitive and -resistant melanoma cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Melanoma [ICD-11: 2C30]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Skin
• The Specified Disease: Melanoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.69E-01; Fold-change: -3.54E-01; Z-score: -4.74E-01

References

• Ref 1: miR-216b enhances the efficacy of vemurafenib by targeting Beclin-1, UVRAG and ATG5 in melanoma. Cell Signal. 2018 Jan;42:30-43. doi: 10.1016/j.cellsig.2017.09.024. Epub 2017 Oct 2.