UniProtKB - P0DTC3 (AP3A_SARS2)
ORF3a protein
3a
Functioni
Plays a role in viral egress via lysosomal trafficking (PubMed:33157038, PubMed:33422265).
Forms homotetrameric ion channels (viroporin) localized at endosomes and lysosomes, that may induce deacidification of lysosomes, allowing safe egress of virions via lysosomal trafficking (PubMed:33157038, PubMed:33422265,PubMed:34158638).
Also blocks autolysosomes formation by binding and sequestering the host component VPS39 for homotypic fusion and protein sorting (HOPS) on late endosomes. This prevents fusion of autophagosomes with lysosomes, disrupting autophagy and facilitating virus egress (PubMed:33422265).
3 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 133 | Involved in polymerizationBy similarity | 1 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- ion channel activity Source: InterPro
GO - Biological processi
- inorganic cation transmembrane transport Source: ComplexPortal
- pore formation by virus in membrane of host cell Source: InterPro
Keywordsi
Molecular function | Ion channel, Viral ion channel |
Biological process | Ion transport, Transport |
Enzyme and pathway databases
Reactomei | R-HSA-9694322, Virion Assembly and Release R-HSA-9694614, Attachment and Entry R-HSA-9694635, Translation of Structural Proteins R-HSA-9694719, Maturation of protein 3a |
Protein family/group databases
TCDBi | 1.A.57.1.5, the human sars coronavirus viroporin (sars-vp) |
Names & Taxonomyi
Protein namesi | Recommended name: ORF3a proteinShort name: ORF3a Alternative name(s): Accessory protein 3a Protein 3a Protein U274 Protein X1 |
Gene namesi | ORF Names:3a |
Organismi | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2) |
Taxonomic identifieri | 2697049 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Pisuviricota › Pisoniviricetes › Nidovirales › Cornidovirineae › Coronaviridae › Orthocoronavirinae › Betacoronavirus › Sarbecovirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Subcellular locationi
- Virion By similarity
- Host cell membrane By similarity2 Publications; Multi-pass membrane protein By similarity1 Publication
- Secreted By similarity
- Host cytoplasm By similarity1 Publication
- Host endosome 2 Publications
- Host lysosome 1 Publication Note: The cell surface expressed protein can undergo endocytosis. The protein is secreted in association with membranous structures.By similarity
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 42 | Extracellular1 PublicationAdd BLAST | 42 | |
Transmembranei | 43 – 61 | Helical1 PublicationAdd BLAST | 19 | |
Topological domaini | 62 – 67 | Cytoplasmic1 Publication | 6 | |
Transmembranei | 68 – 93 | Helical1 PublicationAdd BLAST | 26 | |
Topological domaini | 94 – 101 | Extracellular1 Publication | 8 | |
Transmembranei | 102 – 126 | Helical1 PublicationAdd BLAST | 25 | |
Topological domaini | 127 – 275 | Cytoplasmic1 PublicationAdd BLAST | 149 |
Keywords - Cellular componenti
Host cell membrane, Host cytoplasm, Host endosome, Host lysosome, Host membrane, Membrane, Secreted, VirionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 41 | Missing : Partial loss of Ca(2+) and NMDG(+) permeability. Increased localization at host plasma membrane. 1 PublicationAdd BLAST | 41 | |
Mutagenesisi | 57 – 58 | QS → EL: Partial loss of Ca(2+) and NMDG(+) permeability. 1 Publication | 2 | |
Mutagenesisi | 57 | Q → H: No effect on ion permeability. 1 Publication | 1 | |
Mutagenesisi | 116 | Q → L: Partial loss of Ca(2+) and NMDG(+) permeability. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000449650 | 1 – 275 | ORF3a proteinAdd BLAST | 275 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 32 | O-linked (GalNAc...) threonine; by hostBy similarity | 1 | |
Glycosylationi | 34 | O-linked (GalNAc...) threonine; by hostSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
GlycoproteinPTM databases
GlyGeni | P0DTC3, 2 sites |
Interactioni
Subunit structurei
Homodimer (PubMed:34158638), a subset forms homotetramer of two homodimers linked non covalently (PubMed:34158638, PubMed:34158638).
Interacts with M, S and E proteins.
Also interacts with the accessory protein 7a (By similarity).
Interacts with host VPS39, sequestering it on late endosomes (PubMed:33422265).
By similarity2 PublicationsBinary interactionsi
P0DTC3
With | #Exp. | IntAct |
---|---|---|
itself | 2 | EBI-25475894,EBI-25475894 |
UVRAG [Q9P2Y5] from Homo sapiens. | 6 | EBI-25475894,EBI-2952704 |
VPS39 [Q96JC1] from Homo sapiens. | 15 | EBI-25475894,EBI-1050197 |
VPS41 [P49754] from Homo sapiens. | 4 | EBI-25475894,EBI-2130459 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 4383868, 1111 interactors |
ComplexPortali | CPX-6098, SARS-CoV-2 3a complex |
IntActi | P0DTC3, 442 interactors |
Structurei
Secondary structure
3D structure databases
SMRi | P0DTC3 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 33 – 141 | CoV 3a-like viroporin TMPROSITE-ProRule annotationAdd BLAST | 109 | |
Domaini | 145 – 237 | CoV 3a-like viroporin CDPROSITE-ProRule annotationAdd BLAST | 93 |
Domaini
Keywords - Domaini
Transmembrane, Transmembrane helixFamily and domain databases
CDDi | cd21648, SARS-CoV-like_ORF3a, 1 hit |
DisProti | DP03003 |
InterProi | View protein in InterPro IPR024407, Protein_3a_bCoV |
Pfami | View protein in Pfam PF11289, bCoV_viroporin, 1 hit |
PROSITEi | View protein in PROSITE PS51967, COV_VIROPORIN_3A_CD, 1 hit PS51966, COV_VIROPORIN_3A_TM, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MDLFMRIFTI GTVTLKQGEI KDATPSDFVR ATATIPIQAS LPFGWLIVGV
60 70 80 90 100
ALLAVFQSAS KIITLKKRWQ LALSKGVHFV CNLLLLFVTV YSHLLLVAAG
110 120 130 140 150
LEAPFLYLYA LVYFLQSINF VRIIMRLWLC WKCRSKNPLL YDANYFLCWH
160 170 180 190 200
TNCYDYCIPY NSVTSSIVIT SGDGTTSPIS EHDYQIGGYT EKWESGVKDC
210 220 230 240 250
VVLHSYFTSD YYQLYSTQLS TDTGVEHVTF FIYNKIVDEP EEHVQIHTID
260 270
GSSGVVNPVM EPIYDEPTTT TSVPL
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 26 | S → L in strain: Delta/B.1.617.2 and Kappa/B.1.617.1. Curated | 1 | |
Natural varianti | 42 | P → L in strain: Iota/B.1.526. Curated | 1 | |
Natural varianti | 57 | Q → H in strain: Beta/B.1.351, Epsilon/B.1.429, Iota/B.1.526 and Mu/B.1621. Curated | 1 | |
Natural varianti | 171 | S → L in strain: Beta/B.1.351. Curated | 1 | |
Natural varianti | 223 | T → I in strain: Omicron/BA.2. | 1 | |
Natural varianti | 253 | S → P in strain: Gamma/P.1. Curated | 1 | |
Natural varianti | 257 | Missing in strain: Mu/B.1.621. Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | MN908947 Genomic RNA Translation: QHD43417.1 |
RefSeqi | YP_009724391.1, NC_045512.2 |
Genome annotation databases
GeneIDi | 43740569 |
KEGGi | vg:43740569 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | MN908947 Genomic RNA Translation: QHD43417.1 |
RefSeqi | YP_009724391.1, NC_045512.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6XDC | electron microscopy | 2.90 | A/B | 1-275 | [»] | |
7KJR | electron microscopy | 2.08 | A/B | 1-275 | [»] | |
SMRi | P0DTC3 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4383868, 1111 interactors |
ComplexPortali | CPX-6098, SARS-CoV-2 3a complex |
IntActi | P0DTC3, 442 interactors |
Protein family/group databases
TCDBi | 1.A.57.1.5, the human sars coronavirus viroporin (sars-vp) |
PTM databases
GlyGeni | P0DTC3, 2 sites |
Protocols and materials databases
DNASUi | 43740569 |
Genome annotation databases
GeneIDi | 43740569 |
KEGGi | vg:43740569 |
Enzyme and pathway databases
Reactomei | R-HSA-9694322, Virion Assembly and Release R-HSA-9694614, Attachment and Entry R-HSA-9694635, Translation of Structural Proteins R-HSA-9694719, Maturation of protein 3a |
Miscellaneous databases
PROi | PR:P0DTC3 |
Family and domain databases
CDDi | cd21648, SARS-CoV-like_ORF3a, 1 hit |
DisProti | DP03003 |
InterProi | View protein in InterPro IPR024407, Protein_3a_bCoV |
Pfami | View protein in Pfam PF11289, bCoV_viroporin, 1 hit |
PROSITEi | View protein in PROSITE PS51967, COV_VIROPORIN_3A_CD, 1 hit PS51966, COV_VIROPORIN_3A_TM, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | AP3A_SARS2 | |
Accessioni | P0DTC3Primary (citable) accession number: P0DTC3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 22, 2020 |
Last sequence update: | April 22, 2020 | |
Last modified: | May 25, 2022 | |
This is version 11 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references