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Protein

UV radiation resistance associated protein

Gene

Uvrag

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Versatile protein that is involved in regulation of differenent 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). 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 (By similarity).By similarityCurated
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). Required for centrosome stability and proper chromosome segregation (By similarity).By similarity

GO - Molecular functioni

  • SH3 domain binding Source: MGI
  • SNARE binding Source: MGI

GO - Biological processi

  • autophagy Source: MGI
  • centrosome organization Source: UniProtKB
  • chromosome segregation Source: UniProtKB
  • DNA repair Source: UniProtKB
  • double-strand break repair via classical nonhomologous end joining Source: MGI
  • maintenance of Golgi location Source: MGI
  • positive regulation of autophagy Source: InterPro
  • receptor catabolic process Source: MGI
  • regulation of cytokinesis Source: MGI
  • regulation of protein serine/threonine kinase activity Source: MGI
  • retrograde vesicle-mediated transport, Golgi to ER Source: MGI
  • SNARE complex assembly Source: MGI
  • spindle organization Source: UniProtKB
  • viral entry into host cell Source: MGI
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.

Names & Taxonomyi

Protein namesi
Recommended name:
UV radiation resistance associated protein
Gene namesi
Name:Uvrag
Synonyms:Uvrag1
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1925860. Uvrag.

Subcellular locationi

  • Late endosome By similarity
  • Lysosome By similarity
  • Early endosome By similarity
  • Endoplasmic reticulum By similarity
  • Midbody By similarity
  • Chromosomecentromere By similarity

  • Note: Colocalizes with RAB9-positive compartments involved in retrograde transport from late endosomes to trans-Golgi network. Colocalization with early endosomes is only partial (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Endoplasmic reticulum, Endosome, Lysosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 698698UV radiation resistance associated proteinPRO_0000433403Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei492 – 4921PhosphoserineBy similarity
Modified residuei497 – 4971Phosphoserine; by MTORBy similarity
Modified residuei507 – 5071PhosphoserineBy similarity
Modified residuei517 – 5171PhosphothreonineBy similarity
Modified residuei521 – 5211PhosphoserineBy similarity
Modified residuei548 – 5481PhosphoserineBy similarity
Modified residuei549 – 5491PhosphoserineBy similarity
Modified residuei570 – 5701PhosphoserineBy similarity
Modified residuei688 – 6881PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated at Ser-497 by MTOR under basal conditions; increases the interaction with RUBCN implicated in inhibitory effect of RUBCN on PI3KC3 and decreases interaction with RAB7A, and VPS16 and VPS39 (indicative for a class C Vps complex, possibly the HOPS complex) (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8K245.
PaxDbiQ8K245.
PRIDEiQ8K245.

PTM databases

iPTMnetiQ8K245.
PhosphoSiteiQ8K245.

Expressioni

Gene expression databases

BgeeiENSMUSG00000035354.

Interactioni

Subunit structurei

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. Interacts with SH3GLB1; UVRAG bridges the interaction to BECN1 indicative for an association with the PI3K complex PI3KC3-C2. 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. 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). Interacts with RAB7A; RAB7A competes with UVRAG for RUBCN binding. Interacts with STX7, VTI1B, STX8. Interacts with PRKDC, XRCC6 and XRCC5; indicative for an association with the DNA-dependent protein kinase complex DNA-PK. Interacts with CEP63. 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. Interacts with BECN1P1/BECN2 (By similarity). Interacts with SLAMF1 (PubMed:22493499).By similarity1 Publication

GO - Molecular functioni

  • SH3 domain binding Source: MGI
  • SNARE binding Source: MGI

Protein-protein interaction databases

IntActiQ8K245. 5 interactions.
STRINGi10090.ENSMUSP00000045297.

Structurei

3D structure databases

ProteinModelPortaliQ8K245.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 12885C2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni199 – 26870Sufficient for interaction with STX7; VTI1B AND STX8By similarityAdd
BLAST
Regioni269 – 441173Sufficient for interaction with VPS16, required for interaction with CEP63By similarityAdd
BLAST
Regioni442 – 698257Required for interaction with PRKDC, XRCC6 and XRCC5By similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili200 – 304105Sequence analysisAdd
BLAST

Sequence similaritiesi

Contains 1 C2 domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2896. Eukaryota.
ENOG410YZ0H. LUCA.
GeneTreeiENSGT00390000012877.
HOGENOMiHOG000147825.
HOVERGENiHBG059846.
OMAiLPGEFHP.
OrthoDBiEOG091G0HDH.
PhylomeDBiQ8K245.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR018791. UV_resistance/autophagy_Atg14.
[Graphical view]
PfamiPF10186. Atg14. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.

Sequencei

Sequence statusi: Complete.

Q8K245-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSCASLGGP VPLPPPGPSA ALTSGAPARA LHVELPSQQR RLRHLRNIAA
60 70 80 90 100
RNIVNRNGHQ LLDTYFTLHL CDNEKIFKEF YRSEVIKNSL NPTWRSLDFG
110 120 130 140 150
IMPDRLDTSV SCFVVKIWGG KEEAFQLLIE WKVYLDGLKY LGQQIHARNQ
160 170 180 190 200
NEIIFGLNDG YYGAPCEHKG HPNAQKNLLQ VDQNCVRNSY DVFSLLRLHR
210 220 230 240 250
AQCAIKQTQV TVQRLGKEIE EKLRLTSTSN ELKKESECLR LKILVLRNEL
260 270 280 290 300
ERQKKALGRE VAFLHKQQMA LQDKGSAFST EHGKLQLQKD SLSELRKECT
310 320 330 340 350
AKRELFLKTN AQLTIRCRQL LSELSYIYPI DLNENKDYFV CGVKLPNSED
360 370 380 390 400
FQAKDDGSIA VALGYTAHLV SMISFFLQVP LRYPIIHKGS RSTIKDNIND
410 420 430 440 450
KLTEKEREFP LYPKGGEKLQ FDYGVYLLNK NIAQLRYQHG LGTPDLRQTL
460 470 480 490 500
PNLKNFMEHG LMVRCDRHHI SNAIPVPKRQ SSTFGGADGG FSAGIPSPDK
510 520 530 540 550
VHRKRASSEN ERLQYKTPPP SYNSALTQPG VAMPTSGDSE RKVAPLSSSL
560 570 580 590 600
DTSLDFSKEN KKAGVDLGSS VSGDHGNSDS GQEQGEALPG HLAAVNGTAL
610 620 630 640 650
PSEQAGPAGT LLPGSCHPAP SAELCCAVEQ AEEIIGLEAT GFTSGDQLEA
660 670 680 690
LSCIPVDSAV AVECDEQVLG EFEEFSRRIY ALSENVSSFR RPRRSSDK
Length:698
Mass (Da):77,525
Last modified:June 24, 2015 - v2
Checksum:i245A411198286F33
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti335 – 3351N → H in AAH34176 (PubMed:15489334).Curated
Sequence conflicti355 – 3551D → E in AAH34176 (PubMed:15489334).Curated
Sequence conflicti497 – 4971S → T in BAC37120 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK030814 mRNA. Translation: BAC27144.1.
AK078085 mRNA. Translation: BAC37120.1.
AK154903 mRNA. Translation: BAE32914.1.
AC093351 Genomic DNA. No translation available.
AC115850 Genomic DNA. No translation available.
BC034176 mRNA. Translation: AAH34176.1.
CCDSiCCDS21476.1.
RefSeqiNP_848750.3. NM_178635.3.
UniGeneiMm.323072.

Genome annotation databases

EnsembliENSMUST00000037968; ENSMUSP00000045297; ENSMUSG00000035354.
GeneIDi78610.
KEGGimmu:78610.
UCSCiuc009ikz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK030814 mRNA. Translation: BAC27144.1.
AK078085 mRNA. Translation: BAC37120.1.
AK154903 mRNA. Translation: BAE32914.1.
AC093351 Genomic DNA. No translation available.
AC115850 Genomic DNA. No translation available.
BC034176 mRNA. Translation: AAH34176.1.
CCDSiCCDS21476.1.
RefSeqiNP_848750.3. NM_178635.3.
UniGeneiMm.323072.

3D structure databases

ProteinModelPortaliQ8K245.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8K245. 5 interactions.
STRINGi10090.ENSMUSP00000045297.

PTM databases

iPTMnetiQ8K245.
PhosphoSiteiQ8K245.

Proteomic databases

MaxQBiQ8K245.
PaxDbiQ8K245.
PRIDEiQ8K245.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000037968; ENSMUSP00000045297; ENSMUSG00000035354.
GeneIDi78610.
KEGGimmu:78610.
UCSCiuc009ikz.2. mouse.

Organism-specific databases

CTDi7405.
MGIiMGI:1925860. Uvrag.

Phylogenomic databases

eggNOGiKOG2896. Eukaryota.
ENOG410YZ0H. LUCA.
GeneTreeiENSGT00390000012877.
HOGENOMiHOG000147825.
HOVERGENiHBG059846.
OMAiLPGEFHP.
OrthoDBiEOG091G0HDH.
PhylomeDBiQ8K245.

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.

Miscellaneous databases

ChiTaRSiUvrag. mouse.
PROiQ8K245.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035354.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR018791. UV_resistance/autophagy_Atg14.
[Graphical view]
PfamiPF10186. Atg14. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiUVRAG_MOUSE
AccessioniPrimary (citable) accession number: Q8K245
Secondary accession number(s): Q8BVI8, Q8C0K8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 24, 2015
Last sequence update: June 24, 2015
Last modified: September 7, 2016
This is version 81 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.