Reactome | UniProt:P59594 S

chain	signal peptide:1-13 chain:14-1255 chain:14-667 chain:668-1255 chain:798-1255
checksum	1C49ACA2CFD38FC0
comment	FUNCTION May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.FUNCTION Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.FUNCTION Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.FUNCTION Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.SUBUNIT Homotrimer; each monomer consists of a S1 and a S2 subunit. The resulting peplomers protrude from the virus surface as spikes (By similarity). Binds to human and palm civet ACE2 and human CLEC4M/DC-SIGNR. Interacts with the accessory proteins 3a and 7a.INTERACTION Accumulates in the endoplasmic reticulum-Golgi intermediate compartment, where it participates in virus particle assembly. Colocalizes with S in the host endoplasmic reticulum-Golgi intermediate compartment (PubMed:20861307). Some S oligomers are transported to the host plasma membrane, where they may mediate cell-cell fusion.DOMAIN The KxHxx motif seems to function as an ER retrieval and binds COPI in vitro.DOMAIN Fusion peptide 1 (FP1) and fusion peptide 2 (FP2) function cooperatively and have a membrane-ordering effect on lipid headgroups and shallow hydrophobic regions of target bilayers. They are considered as two domains of an extended, bipartite FP. The membrane-ordering activity is calcium-dependent and also dependent on correct folding, which is maintained by an internal disulfide bond in FP2.PTM The cytoplasmic Cys-rich domain is palmitoylated. Spike glycoprotein is digested by cathepsin CTSL within endosomes.PTM Specific enzymatic cleavages in vivo yield mature proteins. The precursor is processed into S1 and S2 by host cell furin or another cellular protease to yield the mature S1 and S2 proteins. Additionally, a second cleavage leads to the release of a fusion peptide after viral attachment to host cell receptor.PTM The cytoplasmic Cys-rich domain is palmitoylated. Spike glycoprotein is digested within host endosomes.MISCELLANEOUS Tor2 is the prototype of the virus isolated during the severe SARS outbreak in 2002-2003. GD03 has been isolated from the second mild SARS outbreak in winter 2003-2004. SZ3 has been isolated from palm civet, the presumed animal reservoir. The spike proteins from those three isolates display a strong affinity for palm civet ACE2 receptor, whereas only the Tor2 spike protein efficiently binds human ACE2. This may explain the high pathogenicity of Tor2 virus, whose spike is highly adapted to the human host. Therefore, the lack of severity of disease during the 2003-2004 outbreak could be due to the incomplete adaptation of GD03 virus to bind human ACE2. Mutation Asn-479 and Thr-487 in palm civet coronavirus seems necessary and sufficient for the virus to acquire the ability to efficiently infect humans.SIMILARITY Belongs to the betacoronaviruses spike protein family.
created	[InstanceEdit:9678121] Orlic-Milacic, Marija, 2020-03-13
crossReference	[DatabaseIdentifier:12197776] PDB:6CS0 [DatabaseIdentifier:12156968] PDB:6ACG [DatabaseIdentifier:12197786] PDB:2RUO [DatabaseIdentifier:12156960] PDB:6ACK [DatabaseIdentifier:12197795] PDB:8KDT [DatabaseIdentifier:12157045] PDB:3SCJ [DatabaseIdentifier:12197789] PDB:2RUM [DatabaseIdentifier:12197787] PDB:2RUN [DatabaseIdentifier:12197782] PDB:8KEK [DatabaseIdentifier:12197784] PDB:2BEQ [DatabaseIdentifier:12157044] PDB:3SCI [DatabaseIdentifier:12197790] PDB:1WYY [DatabaseIdentifier:12156962] PDB:6ACJ [DatabaseIdentifier:12197792] PDB:8TC5 [DatabaseIdentifier:12197785] PDB:1WNC [DatabaseIdentifier:12197793] PDB:6ACD [DatabaseIdentifier:12157037] PDB:3SCK [DatabaseIdentifier:12197783] PDB:7Y3N [DatabaseIdentifier:12197788] PDB:5WRG [DatabaseIdentifier:12157038] PDB:3SCL [DatabaseIdentifier:12197791] PDB:6ACC [DatabaseIdentifier:12197794] PDB:8KDS [DatabaseIdentifier:12197780] PDB:2FXP [DatabaseIdentifier:12197745] PDB:8H14 [DatabaseIdentifier:12197763] PDB:8KDM [DatabaseIdentifier:12197754] PDB:7ZH1 [DatabaseIdentifier:12197734] PDB:6NB6 [DatabaseIdentifier:12197747] PDB:8H11 [DatabaseIdentifier:12197762] PDB:7JN5 [DatabaseIdentifier:12197781] PDB:5XJK [DatabaseIdentifier:12197778] PDB:8WCG [DatabaseIdentifier:12156939] PDB:8SPI [DatabaseIdentifier:12197757] PDB:5X4S [DatabaseIdentifier:12197749] PDB:8H15 [DatabaseIdentifier:12197728] PDB:6M3W [DatabaseIdentifier:12197731] PDB:5XLR [DatabaseIdentifier:12197773] PDB:2DD8 [DatabaseIdentifier:12156944] PDB:3D0I [DatabaseIdentifier:12197771] PDB:7AKJ [DatabaseIdentifier:12197753] PDB:8H10 [DatabaseIdentifier:12197752] PDB:2GHV [DatabaseIdentifier:12197744] PDB:5X5B [DatabaseIdentifier:12197755] PDB:7ZH2 [DatabaseIdentifier:12197746] PDB:7ZH5 [DatabaseIdentifier:12197741] PDB:8H0Y [DatabaseIdentifier:12197759] PDB:1ZV7 [DatabaseIdentifier:12197758] PDB:1ZV8 [DatabaseIdentifier:12197738] PDB:8H0X [DatabaseIdentifier:12197767] PDB:6CRX [DatabaseIdentifier:12180794] PDB:3BGF [DatabaseIdentifier:12197769] PDB:6CRZ [DatabaseIdentifier:12197760] PDB:7WR9 [DatabaseIdentifier:12197751] PDB:2GHW [DatabaseIdentifier:12197739] PDB:8JAG [DatabaseIdentifier:12197748] PDB:8H12 [DatabaseIdentifier:12197743] PDB:8H13 [DatabaseIdentifier:12197770] PDB:7WSG [DatabaseIdentifier:12197750] PDB:8H16 [DatabaseIdentifier:12197777] PDB:7SG4 [DatabaseIdentifier:12197733] PDB:6NB7 [DatabaseIdentifier:12156942] PDB:3D0H [DatabaseIdentifier:12197766] PDB:7WSF [DatabaseIdentifier:12197730] PDB:8VPF [DatabaseIdentifier:12157107] PDB:6VW1 [DatabaseIdentifier:12197775] PDB:8XZB [DatabaseIdentifier:12197756] PDB:7RKS [DatabaseIdentifier:12197735] PDB:7FC6 [DatabaseIdentifier:12197742] PDB:5ZVM [DatabaseIdentifier:12197779] PDB:7X7V [DatabaseIdentifier:12156938] PDB:8SPH [DatabaseIdentifier:12197729] PDB:7X2J [DatabaseIdentifier:12197772] PDB:8WOZ [DatabaseIdentifier:12157174] PDB:6CS2 [DatabaseIdentifier:12197768] PDB:6CRW [DatabaseIdentifier:12197737] PDB:1ZVB [DatabaseIdentifier:12197774] PDB:6CS1 [DatabaseIdentifier:12197764] PDB:6CRV [DatabaseIdentifier:12197732] PDB:2BEZ [DatabaseIdentifier:12197765] PDB:6WAQ [DatabaseIdentifier:12197761] PDB:5X58 [DatabaseIdentifier:12197740] PDB:1ZVA [DatabaseIdentifier:12197736] PDB:8H0Z [DatabaseIdentifier:12156940] PDB:3D0G [DatabaseIdentifier:12157180] PDB:2AJF
databaseName	UniProt
dbId	9678122
description	recommendedName: fullName evidence="2"Spike glycoprotein shortName evidence="2"S glycoprotein alternativeName: fullName evidence="2"E2 alternativeName: fullName evidence="2"Peplomer protein component recommendedName: fullName evidence="2"Spike protein S1 /component component recommendedName: fullName evidence="2"Spike protein S2 /component component recommendedName: fullName evidence="2"Spike protein S2' /component
displayName	UniProt:P59594 S
geneName	S 2
identifier	P59594
isSequenceChanged	false
keyword	3D-structure Coiled coil Disulfide bond Fusion of virus membrane with host endosomal membrane Fusion of virus membrane with host membrane Glycoprotein Host cell membrane Host membrane Host-virus interaction Inhibition of host innate immune response by virus Inhibition of host tetherin by virus Lipoprotein Membrane Palmitate Reference proteome Signal Transmembrane Transmembrane helix Viral attachment to host cell Viral envelope protein Viral immunoevasion Viral penetration into host cytoplasm Virion Virulence Virus entry into host cell
modified	[InstanceEdit:9909836] Weiser, Joel, 2024-05-14
moleculeType	Protein
name	S
physicalEntity	[EntityWithAccessionedSequence:R-COV-9686724] complex N-glycan-PALM-Spike S2 Fragment [virion membrane] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9686706] complex N-glycan-PALM-Spike S1 Fragment [virion membrane] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9686693] complex N-glycan-PALM-Spike S1 Fragment [endocytic vesicle membrane] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9686730] complex N-glycan-PALM-Spike S2 Fragment [endocytic vesicle membrane] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9685469] complex N-glycan-PALM-Spike [virion membrane] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9683617] complex N-glycan-PALM-Spike [endoplasmic reticulum-Golgi intermediate compartment] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9683657] trimmed N-glycan-PALM-Spike [endoplasmic reticulum-Golgi intermediate compartment] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9683638] trimmed N-glycan-PALM-Spike [endoplasmic reticulum lumen] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9683608] trimmed N-glycan Spike [endoplasmic reticulum lumen] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9683716] trimmed unfolded N-glycan Spike [endoplasmic reticulum lumen] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9683594] N-glycan Spike [endoplasmic reticulum lumen] - Human SARS coronavirus [EntityWithAccessionedSequence:R-COV-9682868] nascent Spike [endoplasmic reticulum lumen] - Human SARS coronavirus
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12714365] UCSC:P59594 S
schemaClass	ReferenceGeneProduct
secondaryIdentifier	SPIKE_SARS Q6QU82 Q7T696 Q7TA19 Q7TFA2 Q7TFB1 Q80BV6
sequenceLength	1255
species	[Species:9678119] Human SARS coronavirus
stId	uniprot:P59594
url	http://purl.uniprot.org/uniprot/P59594

(referenceEntity)	[EntityWithAccessionedSequence:R-COV-9686724] complex N-glycan-PALM-Spike S2 Fragment [virion membrane] [EntityWithAccessionedSequence:R-COV-9686706] complex N-glycan-PALM-Spike S1 Fragment [virion membrane] [EntityWithAccessionedSequence:R-COV-9686693] complex N-glycan-PALM-Spike S1 Fragment [endocytic vesicle membrane] [EntityWithAccessionedSequence:R-COV-9686730] complex N-glycan-PALM-Spike S2 Fragment [endocytic vesicle membrane] [EntityWithAccessionedSequence:R-COV-9685469] complex N-glycan-PALM-Spike [virion membrane] [EntityWithAccessionedSequence:R-COV-9683617] complex N-glycan-PALM-Spike [endoplasmic reticulum-Golgi intermediate compartment] [EntityWithAccessionedSequence:R-COV-9683657] trimmed N-glycan-PALM-Spike [endoplasmic reticulum-Golgi intermediate compartment] [EntityWithAccessionedSequence:R-COV-9683638] trimmed N-glycan-PALM-Spike [endoplasmic reticulum lumen] [EntityWithAccessionedSequence:R-COV-9683608] trimmed N-glycan Spike [endoplasmic reticulum lumen] [EntityWithAccessionedSequence:R-COV-9683716] trimmed unfolded N-glycan Spike [endoplasmic reticulum lumen] [EntityWithAccessionedSequence:R-COV-9683594] N-glycan Spike [endoplasmic reticulum lumen] [EntityWithAccessionedSequence:R-COV-9682868] nascent Spike [endoplasmic reticulum lumen]
(referenceSequence)	[ModifiedResidue:9683666] palmitoylated-L-cysteine at unknown position [ModifiedResidue:9683762] N-glycosylated residue at 109 [ModifiedResidue:9683632] N-glycosylated residue at 118 [ModifiedResidue:9683605] N-glycosylated residue at 589 [ModifiedResidue:9683733] N-glycosylated residue at 783 [ModifiedResidue:9683771] N-glycosylated residue at 1155 [ModifiedResidue:9683743] N-glycosylated residue at 1176 [ModifiedResidue:9683711] N-glycosylated residue at 269 [ModifiedResidue:9683710] N-glycosylated residue at 119 [ModifiedResidue:9683741] N-glycosylated residue at 318 [ModifiedResidue:9683619] N-glycosylated residue at 330 [ModifiedResidue:9683589] N-glycosylated residue at 1056 [ModifiedResidue:9683595] N-glycosylated residue at 1140 [ModifiedResidue:9683722] N-glycosylated residue at 227 [ModifiedResidue:9683695] N-glycosylated residue at 1080 [ModifiedResidue:9683727] N-glycosylated residue at 158 [ModifiedResidue:9683629] N-glycosylated residue at 357 [ModifiedResidue:9683693] N-glycosylated residue at 699
(interactor)	[UndirectedInteraction:11197459] UniProt:P59635 <-> UniProt:P59594 (IntAct) [UndirectedInteraction:11204799] UniProt:P07711 <-> UniProt:P59594 (IntAct) [UndirectedInteraction:11253817] UniProt:Q9BYF1 <-> UniProt:P59594 (IntAct) [UndirectedInteraction:11289821] UniProt:P59637 <-> UniProt:P59594 (IntAct) [UndirectedInteraction:11297711] UniProt:P59594 <-> UniProt:P59594 (IntAct) [UndirectedInteraction:11297711] UniProt:P59594 <-> UniProt:P59594 (IntAct) [UndirectedInteraction:11297715] UniProt:P59594 <-> UniProt:Q56NL1 (IntAct) [UndirectedInteraction:11297717] UniProt:P59594 <-> UniProt:O00303 (IntAct) [UndirectedInteraction:11297719] UniProt:P59594 <-> UniProt:Q5EGZ1 (IntAct) [UndirectedInteraction:11297721] UniProt:P59594 <-> UniProt:P84198 (IntAct) [UndirectedInteraction:11297723] UniProt:P59594 <-> UniProt:P59596 (IntAct) [UndirectedInteraction:11297727] UniProt:P59594 <-> UniProt:Q1LZX8 (IntAct)

UniProt:P59594 S Show undefined attributes

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