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 Phi11 Holin Family constitutes the Holin Superfamily I.
The Phage 21 S Family is a member of the Holin Superfamily II.
The T7 Holin family is a member of the Holin Superfamily II. Members of this family are predominantly found in Caudovirales and Proteobacteria. They typically have only 1 transmembrane segment (TMS) and vary from 60 to 130 amino acyl residues in length. A representative list of proteins belonging to this family can be found in the Transporter Classification Database.
The HP1 Holin Family is a member of the Holin Superfamily II. Proteins in this family are typically found to contain two transmembrane segments (TMSs) and range between 70 and 80 amino acyl residues (aas) in length. A representative list of proteins belonging to the HP1 holin family can be found in the Transporter Classification Database.
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 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 Pseudomonas aeruginosa Hol Holin Family is a group of transporters belonging to the Holin Superfamily III.
The Bacillus subtilis φ29 Holin Family is a group of transporters belonging to the Holin Superfamily IV. A representative list of members belonging to the φ29 holin family can be found in the Transporter Classification Database.
The Holin Hol44 (Hol44) Family is a group of transporters belonging to the Holin Superfamily V. A representative list of proteins belonging to the Hol44 family from caudovirales and firmicutes can be found in the Transporter Classification Database.
The holin LLH family is a group of transporters belonging to the Holin superfamily VI. The Holin LLH family is found in Firmicutes and phage of Firmicutes as well as other bacteria. Members are fairly large, between 100 and 160 amino acyl residues in length, and have an N-terminal transmembrane segment (TMS). Some proteins, such as putative holin of Fusobacterium varium, may exhibit 2 TMSs. A representative list of proteins belonging to the Holin LLH family can be found in the Transporter Classification Database.
The T4 Holin Family is a group of putative pore-forming proteins that does not belong to one of the seven holin superfamilies. T-even phage such as T4 use a holin-endolysin system for host cell lysis. Although the endolysin of phage T4 encoded by the e gene was identified in 1961, the holin was not characterized until 2001. A representative list of proteins belonging to the T4 holin 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 Neisserial Phage-associated Holin (NP-Holin) Family is a family of small proteins, between 47 - 53 amino acyl residues in length, that exhibit a single N-terminal transmembrane segment (TMS). Although annotated as phage proteins or holins, NP-Holin proteins are not yet functionally characterized, thus more research is needed to confirm holin activity. A representative list of proteins belonging to the NP-Holin family can be found in the Transporter Classification Database.
The Bacterophase Dp-1 Holin Family is a family of proteins present in several Gram-positive bacteria and their phage. The genes coding for the lytic system of the pneumococcal phage, Dp-1, has been cloned and characterized. The holin of phage Dp-1 is 74 amino acyl residues (aas) long with two putative transmembrane segments (TMSs). The lytic enzyme of Dp-1 (Pal), an N-acetyl-muramoyl-L-alanine amidase, shows a modular organization similar to that described for the lytic enzymes of Streptococcus pneumoniae and its bacteriophage in which change in the order of the functional domains changes the enzyme specificity. A representative list of proteins belonging to the Dp-1 family can be found in the Transporter Classification Database.
The SPP1 Holin Family consists of proteins of between 90 and 160 amino acyl residues (aas) in length that exhibit two transmembrane segments (TMSs). SPP1 is a double-stranded DNA phage that infects the Gram-positive bacteria. Although annotated as holins, members of the SPP1 family are not yet functionally characterized. A representative list of proteins belonging to the SPP1 Holin family can be found in Transporter Classification Database.
The Actinobacterial 1 TMS Holin Family consists of proteins found in actinobacteria, their conjugative plasmids and their phage. They are usually between 90 and 140 amino acyl residues (aas) in length and exhibit 1 or sometimes even 2 transmembrane segments despite the families name. Although some are annotated as phage proteins or holins, members of the A-1 family are not yet functionally characterized. A representative list of proteins belonging to the A-1 Holin family can be found in the Transporter Classification Database (TCDB).
The Phage T1 Holin Family is represented in enterobacterial phages T1, RTP and F20, Klebsiella phage KP36, and Escherichia phage ADB-2. All of these possess a putative holin that share a high level of identity. Additionally, Gp9 of E. coli phage phiE49 is similar in sequence. These proteins are short, 55 to 71 amino acyl residues (aas) in length, and exhibit a single transmembrane segment (TMS). A representative list of proteins belonging to the T1 Holin family can be found in the Transporter Classification Database.
The CaulobacterPhage Holin (CauHol) Family consists of several putative holins of 157 to 159 amino acyl residues (aas) in length that exhibit 2 transmembrane segments (TMSs). They derive from phage specific for Caulobacter species. These proteins are not functionally characterized. A representative list of proteins belonging to the CauHol family can be found in the Transporter Classification Database.
The Firmicute PhageφU53 Holin Family consists of putative holins that range in size from 117 to 124 amino acyl residues (aas) in length and exhibit 3 transmembrane segments (TMSs) found in Firmicute phage. While annotated as holins, it appears as though many members of the φU53 holin family are not yet functionally characterized. A representative list of homologues can be found in the Transporter Classification Database.
