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649  structures 83  species 0  interactions 83  sequences 9  architectures

Family: CoV_S2 (PF01601)

Summary: Coronavirus spike glycoprotein S2

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Coronavirus spike glycoprotein S2 Provide feedback

The coronavirus spike glycoprotein forms the characteristic 'corona' after which the group is named. The Spike glycoprotein is translated as a large polypeptide that is subsequently cleaved to S1 PF01600 and S2 [1] [2]. The S2 subunit normally contains multiple key components, including one or more fusion peptides (FP), a second proteolytic site (S2') and two conserved heptad repeats (HRs), driving membrane penetration and virus-cell fusion. The HRs can trimerize into a coiled-coil structure built of three HR1-HR2 helical hairpins presenting as a canonical six-helix bundle and drag the virus envelope and the host cell bilayer into close proximity, preparing for fusion to occur [3].

Literature references

  1. Binns MM, Boursnell ME, Cavanagh D, Pappin DJ, Brown TD; , J Gen Virol 1985;66:719-726.: Cloning and sequencing of the gene encoding the spike protein of the coronavirus IBV. PUBMED:2984314 EPMC:2984314

  2. Shang J, Wan Y, Liu C, Yount B, Gully K, Yang Y, Auerbach A, Peng G, Baric R, Li F;, PLoS Pathog. 2020;16:e1008392.: Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry. PUBMED:32150576 EPMC:32150576

  3. Lu G, Wang Q, Gao GF;, Trends Microbiol. 2015;23:468-478.: Bat-to-human: spike features determining 'host jump' of coronaviruses SARS-CoV, MERS-CoV, and beyond. PUBMED:26206723 EPMC:26206723


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002552

The type I glycoprotein S of Coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. The spike glycoprotein is translated as a large polypeptide that is subsequently cleaved to S1 ( INTERPRO ) and S2 [ PUBMED:2984314 ]. The cleavage of S can occur at two distinct sites: S2 or S2' [ PUBMED:19321428 ]. The spike is present in two very different forms: pre-fusion (the form on mature virions) and post-fusion (the form after membrane fusion has been completed). The spike is cleaved sequentially by host proteases at two sites: first at the S1/S2 boundary (i.e. S1/S2 site) and second within S2 (i.e. S2' site). After the cleavages, S1 dissociates from S2, allowing S2 to transition to the post-fusion structure [ PUBMED:32150576 ]. Both chimeric S proteins appeared to cause cell fusion when expressed individually, suggesting that they were biologically fully active [ PUBMED:10627571 ]. The spike is a type I membrane glycoprotein that possesses a conserved transmembrane anchor and an unusual cysteine-rich (cys) domain that bridges the putative junction of the anchor and the cytoplasmic tail [ PUBMED:10725213 ].

SARS-CoV S is largely uncleaved after biosynthesis. It can be later processed by endosomal cathepsin L, trypsin, thermolysin, and elastase, which are shown to induce syncytia formation and virus entry. Other proteases that are of potential biological relevance in potentiating SARS-CoV S include TMPRSS2, TMPRSS11a, and HAT which are localized on the cell surface and are highly expressed in the human airway [ PUBMED:26206723 ]. The furin-like S2' cleavage site at KR/SF with P1 and P2 basic residues and a P2' hydrophobic Phe downstream of the IFP is identical between the 2019-nCoV and SARS-CoV. One or more furin-like enzymes would cleave the S2' site at KR/SF [ PUBMED:25445340 , PUBMED:32057769 ].

The S2 subunit normally contains multiple key components, including one or more fusion peptides (FP), a second proteolytic site (S2') and two conserved heptad repeats (HRs), driving membrane penetration and virus-cell fusion. The HRs can trimerize into a coiled-coil structure built of three HR1-HR2 helical hairpins presenting as a canonical six-helix bundle and drag the virus envelope and the host cell bilayer into close proximity, preparing for fusion to occur [ PUBMED:26206723 ]. The fusion core is composed of HR1 and HR2 and at least three membranotropic regions that are denoted as the fusion peptide (FP), internal fusion peptide (IFP), and pretransmembrane domain (PTM). The HR regions are further flanked by the three membranotropic components. Both FP and IFP are located upstream of HR1, while PTM is distally downstream of HR2 and directly precedes the transmembrane domain of SARS-CoV S. All of these three components are able to partition into the phospholipid bilayer to disturb membrane integrity. [ PUBMED:26206723 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Fusion_gly (CL0595), which has the following description:

This superfamily includes several families of viral glycoproteins that mediate fusion with target membranes.

The clan contains the following 4 members:

Baculo_F CoV_S2 Fusion_gly Spike_torovirin

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(43)
Full
(83)
Representative proteomes UniProt
(7941)
RP15
(84)
RP35
(84)
RP55
(84)
RP75
(84)
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PP/heatmap 1 View           

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

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  Seed
(43)
Full
(83)
Representative proteomes UniProt
(7941)
RP15
(84)
RP35
(84)
RP55
(84)
RP75
(84)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(43)
Full
(83)
Representative proteomes UniProt
(7941)
RP15
(84)
RP35
(84)
RP55
(84)
RP75
(84)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: Corona_S2;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A , Chuguransky S
Number in seed: 43
Number in full: 83
Average length of the domain: 538.30 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 41.41 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 40.0 40.0
Trusted cut-off 297.9 273.1
Noise cut-off 39.8 39.5
Model length: 521
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CoV_S2 domain has been found. There are 649 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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