Q9P2Y5 · UVRAG_HUMAN
- ProteinUV radiation resistance-associated gene protein
- GeneUVRAG
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids699 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (PtdIns3P) (PubMed:16799551, PubMed:18552835, PubMed:20643123, PubMed:24056303, PubMed:28306502).
During autophagy acts as a 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 (PubMed:16799551, PubMed:20643123, PubMed:24056303, PubMed:28306502).
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 (PubMed:16799551, PubMed:20643123, PubMed:24056303).
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 (PubMed:18552835, PubMed:28306502).
Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion (PubMed:24550300).
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 (PubMed:24550300).
During autophagy acts as a 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 (PubMed:16799551, PubMed:20643123, PubMed:24056303, PubMed:28306502).
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 (PubMed:16799551, PubMed:20643123, PubMed:24056303).
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 (PubMed:18552835, PubMed:28306502).
Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion (PubMed:24550300).
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 (PubMed:24550300).
Involved in maintaining chromosomal stability. Promotes DNA double-strand break (DSB) repair by association with DNA-dependent protein kinase complex DNA-PK and activating it in non-homologous end joining (NHEJ) (PubMed:22542840).
Required for centrosome stability and proper chromosome segregation (PubMed:22542840).
Required for centrosome stability and proper chromosome segregation (PubMed:22542840).
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameUV radiation resistance-associated gene protein
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9P2Y5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_059737 | 10 | in dbSNP:rs7118567 | |||
Sequence: P → H | ||||||
Mutagenesis | 498 | Abolishes phosphorylation by MTOR, decreases interaction with RUBCN, increases interaction with VPS16 and VPS39, promotes autophagosome maturation and endosome-lysosomal degradation of EGFR. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 718 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000065750 | 1-699 | UniProt | UV radiation resistance-associated gene protein | |||
Sequence: MSASASVGGPVPQPPPGPAAALPPGSAARALHVELPSQQRRLRHLRNIAARNIVNRNGHQLLDTYFTLHLCSTEKIYKEFYRSEVIKNSLNPTWRSLDFGIMPDRLDTSVSCFVVKIWGGKENIYQLLIEWKVCLDGLKYLGQQIHARNQNEIIFGLNDGYYGAPFEHKGYSNAQKTILLQVDQNCVRNSYDVFSLLRLHRAQCAIKQTQVTVQKIGKEIEEKLRLTSTSNELKKKSECLQLKILVLQNELERQKKALGREVALLHKQQIALQDKGSAFSAEHLKLQLQKESLNELRKECTAKRELFLKTNAQLTIRCRQLLSELSYIYPIDLNEHKDYFVCGVKLPNSEDFQAKDDGSIAVALGYTAHLVSMISFFLQVPLRYPIIHKGSRSTIKDNINDKLTEKEREFPLYPKGGEKLQFDYGVYLLNKNIAQLRYQHGLGTPDLRQTLPNLKNFMEHGLMVRCDRHHTSSAIPVPKRQSSIFGGADVGFSGGIPSPDKGHRKRASSENERLQYKTPPPSYNSALAQPVTTVPSMGETERKITSLSSSLDTSLDFSKENKKKGEDLVGSLNGGHANVHPSQEQGEALSGHRATVNGTLLPSEQAGSASVQLPGEFHPVSEAELCCTVEQAEEIIGLEATGFASGDQLEAFNCIPVDSAVAVECDEQVLGEFEEFSRRIYALNENVSSFRRPRRSSDK | |||||||
Modified residue (large scale data) | 482 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 483 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 493 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 493 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 498 | UniProt | Phosphoserine; by MTOR | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 498 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 508 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 508 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 509 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 516 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 518 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 518 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 522 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 525 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 549 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 550 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 550 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 553 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 554 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 571 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 571 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 582 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 689 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 689 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated at Ser-498 by MTOR under basal conditions; increases the interaction with RUBCN implicated in inhibitory effect of RUBCN on PI3KC3 and decreases interaction with RAB7,A and VPS16 and VPS39 (indicative for a class C Vps complex, possibly the HOPS complex) (PubMed:25533187).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in brain, lung, kidney and liver.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex II (PI3KC3-C2) in which the core composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 is associated with UVRAG; in the complex interacts directly with BECN1. PI3KC3-C2 can associate with further regulatory subunits such as RUBCN and probably SH3GLB1/Bif-1 (PubMed:16799551, PubMed:18843052, PubMed:19050071, PubMed:19270696, PubMed:20643123, PubMed:23878393, PubMed:24056303).
Interacts with SH3GLB1; UVRAG bridges the interaction to BECN1 indicative for an association with the PI3K complex PI3KC3-C2 (PubMed:17891140).
Interacts with RINT1. Associates with the NRZ complex under basal conditions and dissociates from it under autophagy conditions to associate with the PI3K complex; these complex associations seem to be mutually exclusive (PubMed:24056303).
Interacts with VPS16; VPS11; VPS18; VPS33 (VPS33A or VPS33B) and VPS39; indicative for an association with a class C Vps tethering complex (possibly the HOPS complex) (PubMed:18552835, PubMed:25533187).
Interacts with RAB7A; RAB7A competes with UVRAG for RUBCN binding (PubMed:20974968, PubMed:25533187).
Interacts with STX7, VTI1B, STX8 (PubMed:24550300).
Interacts with PRKDC, XRCC6 and XRCC5; indicative for an association with the DNA-dependent protein kinase complex DNA-PK. Interacts with CEP63 (PubMed:22542840).
Directly interacts with FEZ1 and SCOC; the interaction with SCOC is reduced by amino acid starvation, but the complex is stabilized in the presence of FEZ1 (PubMed:22354037).
Interacts with BECN1P1/BECN2 (PubMed:23954414).
Interacts with SLAMF1 (PubMed:22493499).
Interacts with RUBCNL/PACER; promoting targeting of UVRAG to autophagosome (PubMed:28306502).
Interacts with WNK1 (PubMed:27911840).
Interacts with SH3GLB1; UVRAG bridges the interaction to BECN1 indicative for an association with the PI3K complex PI3KC3-C2 (PubMed:17891140).
Interacts with RINT1. Associates with the NRZ complex under basal conditions and dissociates from it under autophagy conditions to associate with the PI3K complex; these complex associations seem to be mutually exclusive (PubMed:24056303).
Interacts with VPS16; VPS11; VPS18; VPS33 (VPS33A or VPS33B) and VPS39; indicative for an association with a class C Vps tethering complex (possibly the HOPS complex) (PubMed:18552835, PubMed:25533187).
Interacts with RAB7A; RAB7A competes with UVRAG for RUBCN binding (PubMed:20974968, PubMed:25533187).
Interacts with STX7, VTI1B, STX8 (PubMed:24550300).
Interacts with PRKDC, XRCC6 and XRCC5; indicative for an association with the DNA-dependent protein kinase complex DNA-PK. Interacts with CEP63 (PubMed:22542840).
Directly interacts with FEZ1 and SCOC; the interaction with SCOC is reduced by amino acid starvation, but the complex is stabilized in the presence of FEZ1 (PubMed:22354037).
Interacts with BECN1P1/BECN2 (PubMed:23954414).
Interacts with SLAMF1 (PubMed:22493499).
Interacts with RUBCNL/PACER; promoting targeting of UVRAG to autophagosome (PubMed:28306502).
Interacts with WNK1 (PubMed:27911840).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q9P2Y5 | 3a P0DTC3 | 6 | EBI-2952704, EBI-25475894 | |
BINARY | Q9P2Y5 | BAX Q07812 | 6 | EBI-2952704, EBI-516580 | |
BINARY | Q9P2Y5 | BECN1 Q14457 | 47 | EBI-2952704, EBI-949378 | |
BINARY | Q9P2Y5 | NEDD4 P46934 | 2 | EBI-2952704, EBI-726944 | |
BINARY | Q9P2Y5 | PIK3C3 Q8NEB9 | 25 | EBI-2952704, EBI-1056470 | |
BINARY | Q9P2Y5 | RINT1 Q6NUQ1 | 18 | EBI-2952704, EBI-726876 | |
BINARY | Q9P2Y5 | RUBCN Q92622 | 11 | EBI-2952704, EBI-2952709 | |
BINARY | Q9P2Y5 | SH3GLB1 Q9Y371 | 11 | EBI-2952704, EBI-2623095 | |
XENO | Q9P2Y5 | Slamf1 Q9QUM4 | 6 | EBI-2952704, EBI-7910086 | |
BINARY | Q9P2Y5 | VPS33A Q96AX1 | 4 | EBI-2952704, EBI-2527283 | |
BINARY | Q9P2Y5 | YAP1 P46937 | 2 | EBI-2952704, EBI-1044059 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, coiled coil, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-24 | Disordered | ||||
Sequence: MSASASVGGPVPQPPPGPAAALPP | ||||||
Domain | 23-149 | C2 | ||||
Sequence: PPGSAARALHVELPSQQRRLRHLRNIAARNIVNRNGHQLLDTYFTLHLCSTEKIYKEFYRSEVIKNSLNPTWRSLDFGIMPDRLDTSVSCFVVKIWGGKENIYQLLIEWKVCLDGLKYLGQQIHARN | ||||||
Region | 200-269 | Sufficient for interaction with STX7; VTI1B AND STX8 | ||||
Sequence: HRAQCAIKQTQVTVQKIGKEIEEKLRLTSTSNELKKKSECLQLKILVLQNELERQKKALGREVALLHKQQ | ||||||
Coiled coil | 224-305 | |||||
Sequence: LRLTSTSNELKKKSECLQLKILVLQNELERQKKALGREVALLHKQQIALQDKGSAFSAEHLKLQLQKESLNELRKECTAKRE | ||||||
Region | 270-442 | Sufficient for interaction with VPS16, required for interaction with CEP63 | ||||
Sequence: IALQDKGSAFSAEHLKLQLQKESLNELRKECTAKRELFLKTNAQLTIRCRQLLSELSYIYPIDLNEHKDYFVCGVKLPNSEDFQAKDDGSIAVALGYTAHLVSMISFFLQVPLRYPIIHKGSRSTIKDNINDKLTEKEREFPLYPKGGEKLQFDYGVYLLNKNIAQLRYQHGL | ||||||
Region | 443-699 | Required for interaction with PRKDC, XRCC6 and XRCC5 | ||||
Sequence: GTPDLRQTLPNLKNFMEHGLMVRCDRHHTSSAIPVPKRQSSIFGGADVGFSGGIPSPDKGHRKRASSENERLQYKTPPPSYNSALAQPVTTVPSMGETERKITSLSSSLDTSLDFSKENKKKGEDLVGSLNGGHANVHPSQEQGEALSGHRATVNGTLLPSEQAGSASVQLPGEFHPVSEAELCCTVEQAEEIIGLEATGFASGDQLEAFNCIPVDSAVAVECDEQVLGEFEEFSRRIYALNENVSSFRRPRRSSDK | ||||||
Region | 486-591 | Disordered | ||||
Sequence: GGADVGFSGGIPSPDKGHRKRASSENERLQYKTPPPSYNSALAQPVTTVPSMGETERKITSLSSSLDTSLDFSKENKKKGEDLVGSLNGGHANVHPSQEQGEALSG | ||||||
Compositional bias | 513-555 | Polar residues | ||||
Sequence: RLQYKTPPPSYNSALAQPVTTVPSMGETERKITSLSSSLDTSL | ||||||
Compositional bias | 576-591 | Polar residues | ||||
Sequence: HANVHPSQEQGEALSG |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9P2Y5-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length699
- Mass (Da)78,151
- Last updated2000-10-01 v1
- Checksum23C4413B10F641BA
Q9P2Y5-2
- Name2
- Differences from canonical
- 1-372: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056176 | 1-372 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 513-555 | Polar residues | ||||
Sequence: RLQYKTPPPSYNSALAQPVTTVPSMGETERKITSLSSSLDTSL | ||||||
Compositional bias | 576-591 | Polar residues | ||||
Sequence: HANVHPSQEQGEALSG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X99050 EMBL· GenBank· DDBJ | CAA67507.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
AB012958 EMBL· GenBank· DDBJ | BAA90829.1 EMBL· GenBank· DDBJ | mRNA | ||
AK095352 EMBL· GenBank· DDBJ | BAG53033.1 EMBL· GenBank· DDBJ | mRNA | ||
AK296871 EMBL· GenBank· DDBJ | BAG59434.1 EMBL· GenBank· DDBJ | mRNA | ||
AK316133 EMBL· GenBank· DDBJ | BAH14504.1 EMBL· GenBank· DDBJ | mRNA | ||
AP002340 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP003031 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP003168 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |