The Holin Superfamily III is a superfamily of integral membrane transport proteins. It is one of the seven different holin superfamilies in total. In general, these proteins are thought to play a role in regulated cell death, although functionality varies between families and individual members.
Members of the holin superfamily III are derived from Proteobacteria, Synergistetes, Actinobacteria, Deinococcus and Archaea. This superfamily includes seven TC families:
Members of all families (with the exception of the Hol-X family; TC# 1.E.34) appear to have three transmembrane segments (TMSs). Members of the Hol-X family appear to have two putative TMSs. The missing TMS in family 34 proteins is the N-terminal TMS as revealed by multiple alignments. [1] These seven families have average sizes of 110, 96, 105, 112, 143, 159 and 108 amino acyl residues (aas), respectively. Notice that the only family with members predicted to have just two TMSs is the one containing the largest homologues; this is due to hydrophilic extensions. The average size of proteins in the entire superfamily is 114 aas with a standard deviation o 23 aas. [1]
Holins are a diverse group of small proteins produced by dsDNA bacteriophages in order to trigger and control the degradation of the host's cell wall at the end of the lytic cycle. Holins form pores in the host's cell membrane, allowing lysins to reach and degrade peptidoglycan, a component of bacterial cell walls. Holins have been shown to regulate the timing of lysis with great precision. Over 50 unrelated gene families encode holins, making them the most diverse group of proteins with common function. Together with lysins, holins are being studied for their potential use as antibacterial agents.
The Holin superfamily II is a superfamily of putative pore-forming proteins. It is one of the seven different holin superfamilies in total. In general, these proteins are thought to play a role in regulated cell death, although functionality varies between families and individual members. The Holin superfamily II includes the TC families:
The Lambda Holin S Family is a group of integral membrane transporter proteins belonging to the Holin Superfamily III. Members of this family generally consist of the characteristic three transmembrane segments (TMSs) and are of 110 amino acyl residues (aas) in length, on average. A representative list of members belonging to this family can be found in the Transporter Classification Database.
The LydA Holin Family, named after the lydA gene which codes for its prototype member, belongs to the Holin Superfamily III. Members of this family have 3 transmembrane segments (TMSs) and appear to possess between 90 and 120 amino acyl residues (aas). A representative list of proteins belonging to this family can be found in the Transporter Classification Database.
The PRD1 Phage P35 Holin Family is a member of Holin Superfamily III. The prototype for this family is the lipid-containing PRD1 enterobacterial phage holin protein P35 encoded by gene XXXV (orfT). It is a component of a typical holin-endolysin system which functions to lyse the host bacterial cell.
The putative actinobacterial holin-X (Hol-X) family was retrieved as a distant member of TC family 1.E.20, suggesting membership of the holin superfamily III. Most Hol-X proteins are less than 200 amino acyl residues (aas) in length and possess two transmembrane segments (TMSs). A representative list of proteins belonging to this family can be found in the Transporter Classification Database.
The Deinococcus/Thermus Holin (D/T-Hol) Family consists of a single protein with no close homologues ; however, its distant homology to members of the Holin superfamily III suggest an evolutionary relationship. The putative holin of Meiothermus silvanus is 108 amino acyl residues in length and possesses 3 transmembrane segments.
The Holin superfamily IV is a superfamily of integral membrane transport proteins. It is one of the seven different holin superfamilies in total.
The Holin superfamily V is a superfamily of integral membrane transport proteins. It is one of the seven different holin superfamilies in total. In general, these proteins are thought to play a role in regulated cell death, although functionality varies between families and individual members. The Holin superfamily V includes the TC families:
The Holin superfamily VII is a superfamily of integral membrane transport proteins. It is one of the seven different holin superfamilies in total. In general, these proteins are thought to play a role in regulated cell death, although functionality varies between families and individual members.
The Listeria Phage A118 Holin (Hol118) Family is a group of transporters belonging to the Holin Superfamily V. A representative list of proteins belonging to the Hol118 family can be found in the Transporter Classification Database.
The Lactococcus lactis Phage r1t Holin Family is a family of putative pore-forming proteins that typically range in size between about 65 and 95 amino acyl residues (aas) in length, although a few r1t holins have been found to be significantly larger. Phage r1t holins exhibit between 2 and 4 transmembrane segments (TMSs), with the 4 TMS proteins resulting from an intragenic duplication of a 2 TMS region. A representative list of the proteins belonging to the r1t holin family can be found in the Transporter Classification Database.
The 2 or 3 TMS Putative Holin Family consists of many proteobacterial proteins ranging in size from about 70 to 120 amino acyl residues (aas) in length that exhibit 2 or 3 predicted transmembrane segments (TMSs). Although annotated as holins, these proteins are not yet functionally characterized. A representative list of proteins belonging to the 2/3 Holin family can be found in the Transporter Classification Database.
The putative holin-like toxin (Hol-Tox) family consists of many small proteins, between 34 and 48 amino acyl residues (aas) with a single transmembrane segment (TMSs). Rajesh et al. first identified the gene and designated it tmp1, which coded for a 34 amino acyl peptide that acts as an antibacterial agent on gram-positive bacteria. This peptide exhibits a single transmembrane domain (TMD) that is believed to play a role in facilitating the antibacterial activity. A representative list of proteins belonging to the Hol-Tox family can be found in the Transporter Classification Database.
The Putative 3-4 TMS Transglycosylase-associated Holin Family is believed to be a group of holins that does not belong to one of the seven holin superfamilies. Homologues include thousands of diverse phage and bacterial proteins between 80 and 140 amino acyl residues (aas) in length that exhibit 3 to 4 transmembrane segments (TMSs). These proteins are holin-like in their size and topology and are designated 'Transglycosylase-associated', 'Putative holin', 'Phage-like transmembrane protein', 'YeaQ protein', etc. in the NCBI protein database. As of early 2016, they remain functionally uncharacterized. They derive from a wide range of bacterial and archaeal phyla including both Gram-negative and Gram-positive bacteria. These proteins are related to the RDD family in the conserved domain database. A representative list of proteins belonging to the T-A Hol family can be found in the Transporter Classification Database.
The Putative Treponema 4 TMS Holin (Tre4Hol) Family consists of several proteins from Treponema species. They range in size from 100 to 110 amino acyl residues (aas) in length and exhibit 4 transmembrane segments (TMSs). A fragment has been sequenced from Treponema phage Phi td1 (D2ECI8) and was designated a putative holin.
The Flp/Fap Pilin Putative Holin (FFPP-Hol) Family is a large diverse family with members from many bacterial phyla. Some members are annotated as Flp or Fap pilin subunits; others are identified as Holin BlyA family members. They range in size of 50 to 80 amino acyl residues (aas) with a single N-terminal transmembrane segment (TMS) although one member has 99 aas and 2 TMSs. Flp homologues are included in TCDB under TC# 3.A.7.13.1 (pXO1-63) and TC# 3.A.7.15.1 (Flp-1). As on March 2016, their precise functions appear to be unknown. A representative list of proteins belonging to the FFPP-Hol family can be found in the Transporter Classification Database.
The Putative 3 TMS Holin (3-Hol) Family is large, consisting of many members derived from proteobacteria and their phage, all of small size and usually with 3 transmembrane segments (TMSs). A representative list of the proteins belonging to this family can be found in the Transporter Classification Database. While many of the proteins belonging to this family are annotated in holins, they remain functionally uncharacterized.
The Putative Archaeal 2 TMS Holin (A2-Hol) Family consists of a few putative holins from Thaumarchaeota ranging in size from about 130 to 165 amino acyl residues (aas) and exhibiting 2 transmembrane segments (TMSs). A representative list of proteins belonging to the A2-Hol family can be found in the Transporter Classification Database. The archaeon, Candidatus Nitrosoarchaeum limnia, encodes adjacent genes designated Toxin Secretion/Lysis Holin. The "toxin" gene encodes a soluble protein of 325 aas stated as belonging to the "Glycosyltransferase GBT-type Superfamily". This protein brings up other glycosyltransferases in a NCBI BLAST search. The adjacent gene encodes a small protein of 132 aas and 2 TMSs that could be a holin, based on its size and topology. This protein has the UniProt accession number of S2E3C4. Paralogues are found in this same organism and other closely related species.
The Putative Bacterial Archaeal Holin(BAH) Family consists of several uncharacterized proteins. However, these proteins were retrieved when functionally characterized holins from the T-A Hol family were BLASTED against the NCBI database, and thus may be related to the T-A Hol family. Most BAH proteins are between 125 and 140 amino acyl residues (aas) in length and exhibit 4 transmembrane segments (TMSs), although at least one putative holin is almost 260 aas long. A representative list of proteins belonging to the BAH family can be found in the Transporter Classification Database.
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