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Protein

UV radiation resistance-associated gene protein

Gene

UVRAG

Organism
Homo sapiens (Human)
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) (PubMed:24056303). 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 (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). 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).Curated3 Publications
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).1 Publication

GO - Molecular functioni

GO - Biological processi

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

Keywords - Biological processi

DNA damage, DNA repair

Enzyme and pathway databases

BRENDAi2.7.1.137. 2681.
ReactomeiR-HSA-1632852. Macroautophagy.
SIGNORiQ9P2Y5.

Names & Taxonomyi

Protein namesi
Recommended name:
UV radiation resistance-associated gene protein
Alternative name(s):
p63
Gene namesi
Name:UVRAG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:12640. UVRAG.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • chromosome, centromeric region Source: UniProtKB-SubCell
  • cytoplasm Source: ProtInc
  • early endosome Source: UniProtKB
  • endoplasmic reticulum Source: CACAO
  • late endosome Source: UniProtKB
  • lysosome Source: UniProtKB
  • midbody Source: UniProtKB
  • phagocytic vesicle Source: Ensembl
  • protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Endoplasmic reticulum, Endosome, Lysosome

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving UVRAG has been observed in a patient with heterotaxy (left-right axis malformation). Inversion Inv(11)(q13.5;q25).

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi498S → A: Abolishes phosphorylation by MTOR, decreases interaction with RUBCN, increases interaction with VPS16 and VPS39, promotes autophagosome maturation and endosome-lysosomal degradation of EGFR. 1 Publication1

Organism-specific databases

DisGeNETi7405.
OpenTargetsiENSG00000198382.
PharmGKBiPA37264.

Polymorphism and mutation databases

BioMutaiUVRAG.
DMDMi20140879.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000657501 – 699UV radiation resistance-associated gene proteinAdd BLAST699

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei493Phosphoserine1 Publication1
Modified residuei498Phosphoserine; by MTORCombined sources1 Publication1
Modified residuei508Phosphoserine1 Publication1
Modified residuei518PhosphothreonineCombined sources1
Modified residuei522Phosphoserine1 Publication1
Modified residuei549Phosphoserine1 Publication1
Modified residuei550PhosphoserineCombined sources1 Publication1
Modified residuei571PhosphoserineCombined sources1
Modified residuei582Phosphoserine1 Publication1
Modified residuei689PhosphoserineCombined sources1

Post-translational modificationi

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).1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9P2Y5.
MaxQBiQ9P2Y5.
PaxDbiQ9P2Y5.
PeptideAtlasiQ9P2Y5.
PRIDEiQ9P2Y5.

PTM databases

iPTMnetiQ9P2Y5.
PhosphoSitePlusiQ9P2Y5.

Expressioni

Tissue specificityi

Highly expressed in brain, lung, kidney and liver.1 Publication

Gene expression databases

BgeeiENSG00000198382.
CleanExiHS_UVRAG.
ExpressionAtlasiQ9P2Y5. baseline and differential.
GenevisibleiQ9P2Y5. HS.

Organism-specific databases

HPAiHPA016932.

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 (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:25533187, PubMed:20974968). 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). Interracts with SLAMF1( PubMed:22493499).16 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BAXQ078126EBI-2952704,EBI-516580
BECN1Q1445729EBI-2952704,EBI-949378
PIK3C3Q8NEB916EBI-2952704,EBI-1056470
RINT1Q6NUQ117EBI-2952704,EBI-726876
RUBCNQ926227EBI-2952704,EBI-2952709
SH3GLB1Q9Y3716EBI-2952704,EBI-2623095
Slamf1Q9QUM46EBI-2952704,EBI-7910086From a different organism.
VPS33AQ96AX14EBI-2952704,EBI-2527283

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113248. 20 interactors.
DIPiDIP-48652N.
IntActiQ9P2Y5. 53 interactors.
MINTiMINT-4658044.
STRINGi9606.ENSP00000348455.

Structurei

3D structure databases

ProteinModelPortaliQ9P2Y5.
SMRiQ9P2Y5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 128C2Add BLAST85

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni200 – 269Sufficient for interaction with STX7; VTI1B AND STX81 PublicationAdd BLAST70
Regioni270 – 442Sufficient for interaction with VPS16, required for interaction with CEP632 PublicationsAdd BLAST173
Regioni443 – 699Required for interaction with PRKDC, XRCC6 and XRCC51 PublicationAdd BLAST257

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili224 – 305Sequence analysisAdd BLAST82

Sequence similaritiesi

Contains 1 C2 domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2896. Eukaryota.
ENOG410YZ0H. LUCA.
GeneTreeiENSGT00390000012877.
HOGENOMiHOG000147825.
HOVERGENiHBG059846.
InParanoidiQ9P2Y5.
OMAiLPGEFHP.
OrthoDBiEOG091G0HDH.
PhylomeDBiQ9P2Y5.
TreeFamiTF323546.

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]
SMARTiSM00239. C2. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9P2Y5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSASASVGGP VPQPPPGPAA ALPPGSAARA LHVELPSQQR RLRHLRNIAA
60 70 80 90 100
RNIVNRNGHQ LLDTYFTLHL CSTEKIYKEF YRSEVIKNSL NPTWRSLDFG
110 120 130 140 150
IMPDRLDTSV SCFVVKIWGG KENIYQLLIE WKVCLDGLKY LGQQIHARNQ
160 170 180 190 200
NEIIFGLNDG YYGAPFEHKG YSNAQKTILL QVDQNCVRNS YDVFSLLRLH
210 220 230 240 250
RAQCAIKQTQ VTVQKIGKEI EEKLRLTSTS NELKKKSECL QLKILVLQNE
260 270 280 290 300
LERQKKALGR EVALLHKQQI ALQDKGSAFS AEHLKLQLQK ESLNELRKEC
310 320 330 340 350
TAKRELFLKT NAQLTIRCRQ LLSELSYIYP IDLNEHKDYF VCGVKLPNSE
360 370 380 390 400
DFQAKDDGSI AVALGYTAHL VSMISFFLQV PLRYPIIHKG SRSTIKDNIN
410 420 430 440 450
DKLTEKEREF PLYPKGGEKL QFDYGVYLLN KNIAQLRYQH GLGTPDLRQT
460 470 480 490 500
LPNLKNFMEH GLMVRCDRHH TSSAIPVPKR QSSIFGGADV GFSGGIPSPD
510 520 530 540 550
KGHRKRASSE NERLQYKTPP PSYNSALAQP VTTVPSMGET ERKITSLSSS
560 570 580 590 600
LDTSLDFSKE NKKKGEDLVG SLNGGHANVH PSQEQGEALS GHRATVNGTL
610 620 630 640 650
LPSEQAGSAS VQLPGEFHPV SEAELCCTVE QAEEIIGLEA TGFASGDQLE
660 670 680 690
AFNCIPVDSA VAVECDEQVL GEFEEFSRRI YALNENVSSF RRPRRSSDK
Length:699
Mass (Da):78,151
Last modified:October 1, 2000 - v1
Checksum:i23C4413B10F641BA
GO
Isoform 2 (identifier: Q9P2Y5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-372: Missing.

Note: No experimental confirmation available.
Show »
Length:327
Mass (Da):35,988
Checksum:iA8CEAAF764965297
GO

Sequence cautioni

The sequence CAA67507 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05973710P → H.Corresponds to variant rs7118567dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561761 – 372Missing in isoform 2. 1 PublicationAdd BLAST372

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X99050 Genomic DNA. Translation: CAA67507.1. Sequence problems.
AB012958 mRNA. Translation: BAA90829.1.
AK095352 mRNA. Translation: BAG53033.1.
AK296871 mRNA. Translation: BAG59434.1.
AK316133 mRNA. Translation: BAH14504.1.
AP002340 Genomic DNA. No translation available.
AP003031 Genomic DNA. No translation available.
AP003168 Genomic DNA. No translation available.
CCDSiCCDS8241.1. [Q9P2Y5-1]
RefSeqiNP_003360.2. NM_003369.3. [Q9P2Y5-1]
UniGeneiHs.202470.

Genome annotation databases

EnsembliENST00000356136; ENSP00000348455; ENSG00000198382. [Q9P2Y5-1]
ENST00000531818; ENSP00000434082; ENSG00000198382. [Q9P2Y5-2]
ENST00000532130; ENSP00000436270; ENSG00000198382. [Q9P2Y5-2]
ENST00000533454; ENSP00000431256; ENSG00000198382. [Q9P2Y5-2]
GeneIDi7405.
KEGGihsa:7405.
UCSCiuc001oxc.4. human. [Q9P2Y5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X99050 Genomic DNA. Translation: CAA67507.1. Sequence problems.
AB012958 mRNA. Translation: BAA90829.1.
AK095352 mRNA. Translation: BAG53033.1.
AK296871 mRNA. Translation: BAG59434.1.
AK316133 mRNA. Translation: BAH14504.1.
AP002340 Genomic DNA. No translation available.
AP003031 Genomic DNA. No translation available.
AP003168 Genomic DNA. No translation available.
CCDSiCCDS8241.1. [Q9P2Y5-1]
RefSeqiNP_003360.2. NM_003369.3. [Q9P2Y5-1]
UniGeneiHs.202470.

3D structure databases

ProteinModelPortaliQ9P2Y5.
SMRiQ9P2Y5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113248. 20 interactors.
DIPiDIP-48652N.
IntActiQ9P2Y5. 53 interactors.
MINTiMINT-4658044.
STRINGi9606.ENSP00000348455.

PTM databases

iPTMnetiQ9P2Y5.
PhosphoSitePlusiQ9P2Y5.

Polymorphism and mutation databases

BioMutaiUVRAG.
DMDMi20140879.

Proteomic databases

EPDiQ9P2Y5.
MaxQBiQ9P2Y5.
PaxDbiQ9P2Y5.
PeptideAtlasiQ9P2Y5.
PRIDEiQ9P2Y5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356136; ENSP00000348455; ENSG00000198382. [Q9P2Y5-1]
ENST00000531818; ENSP00000434082; ENSG00000198382. [Q9P2Y5-2]
ENST00000532130; ENSP00000436270; ENSG00000198382. [Q9P2Y5-2]
ENST00000533454; ENSP00000431256; ENSG00000198382. [Q9P2Y5-2]
GeneIDi7405.
KEGGihsa:7405.
UCSCiuc001oxc.4. human. [Q9P2Y5-1]

Organism-specific databases

CTDi7405.
DisGeNETi7405.
GeneCardsiUVRAG.
HGNCiHGNC:12640. UVRAG.
HPAiHPA016932.
MIMi602493. gene.
neXtProtiNX_Q9P2Y5.
OpenTargetsiENSG00000198382.
PharmGKBiPA37264.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2896. Eukaryota.
ENOG410YZ0H. LUCA.
GeneTreeiENSGT00390000012877.
HOGENOMiHOG000147825.
HOVERGENiHBG059846.
InParanoidiQ9P2Y5.
OMAiLPGEFHP.
OrthoDBiEOG091G0HDH.
PhylomeDBiQ9P2Y5.
TreeFamiTF323546.

Enzyme and pathway databases

BRENDAi2.7.1.137. 2681.
ReactomeiR-HSA-1632852. Macroautophagy.
SIGNORiQ9P2Y5.

Miscellaneous databases

ChiTaRSiUVRAG. human.
GeneWikiiUVRAG.
GenomeRNAii7405.
PROiQ9P2Y5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198382.
CleanExiHS_UVRAG.
ExpressionAtlasiQ9P2Y5. baseline and differential.
GenevisibleiQ9P2Y5. HS.

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]
SMARTiSM00239. C2. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiUVRAG_HUMAN
AccessioniPrimary (citable) accession number: Q9P2Y5
Secondary accession number(s): B3KTC1, O00392
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.