| Aspect | Key findings | Key citations | Source details |
|---|---|---|---|
| Identity | UniProt P03739 matches Enterobacteria phage T4 gene product 38 (gp38), annotated as a tail fiber assembly/receptor-recognizing protein. In the T4 literature, gp38 is specifically discussed in the context of long tail fiber (LTF) gp37 assembly, distinguishing it from unrelated “gene 38” proteins in other organisms. | (pqac-00000000, pqac-00000004) | Hyman 2018, *Biophysical Reviews*, https://doi.org/10.1007/s12551-017-0348-5; Haggård-Ljungquist 1992, *Journal of Bacteriology*, https://doi.org/10.1128/jb.174.5.1462-1477.1992 |
| Primary role in T4 | In bacteriophage T4, gp38 functions primarily as a specific assembly chaperone for gp37, the distal long tail fiber protein that contains the receptor-binding tip. gp38 is required, together with gp57A, for correct folding/trimerization of gp37. | (pqac-00000000, pqac-00000003, pqac-00000007, pqac-00000012) | Hyman 2018, *Biophysical Reviews*, https://doi.org/10.1007/s12551-017-0348-5; Bartual 2010, *Protein Expression and Purification*, https://doi.org/10.1016/j.pep.2009.11.005; Islam 2019, *PLOS Pathogens*, https://doi.org/10.1371/journal.ppat.1008193; Mourosi 2022, *IJMS*, https://doi.org/10.3390/ijms232012146 |
| Mechanism | Genetic and biochemical evidence supports a coiled-coil initiation model: gp38 acts at/near a short coiled-coil region in the gp37 C-terminus to align gp37 protomers and initiate trimer formation. A 21-bp duplication suppressor in gp37 and engineered heptad-repeat extensions (4–5 heptads) can bypass the need for functional gene 38, supporting this mechanism. | (pqac-00000005, pqac-00000009, pqac-00000010) | Hyman 2018, *Biophysical Reviews*, https://doi.org/10.1007/s12551-017-0348-5 |
| Localization | gp38 acts during intracellular morphogenesis/assembly of the distal long tail fiber rather than as the mature receptor-binding tip in T4. Reviews and experimental work state that gp38 is not detected in the assembled T4 long tail fiber or mature virion. | (pqac-00000000, pqac-00000008, pqac-00000009) | Hyman 2018, *Biophysical Reviews*, https://doi.org/10.1007/s12551-017-0348-5; Ivantsiv 2019, thesis/unknown journal |
| Virion incorporation distinction | T4 gp38 is generally absent from mature particles, but homologous gp38/Tfa proteins in some related phages can remain attached to the distal fiber and function as adhesins. This distinction is important: T4 gp38 is a non-structural chaperone, whereas T2 and S16 gp38 homologs can modulate receptor specificity as structural receptor-binding components. | (pqac-00000002, pqac-00000011, pqac-00000018, pqac-00000020) | Trojet/Ivantsiv-derived evidence 2019, thesis/unknown journal; Oliveira 2023, *Applied Microbiology and Biotechnology*, https://doi.org/10.1007/s00253-023-12547-8; Marti 2013, *Molecular Microbiology*, https://doi.org/10.1111/mmi.12134 |
| Direct interaction partner(s) | gp38 interacts functionally with gp37, especially its C-terminal region. In gp38-deficient mutants, gp37 accumulates as insoluble/monomeric species rather than properly assembled oligomers, indicating gp38 promotes gp37 oligomerization/trimerization. | (pqac-00000002, pqac-00000008) | Ivantsiv 2019, thesis/unknown journal |
| Assembly pathway context | T4 LTF assembly proceeds through gp34/gp37 trimerization, addition of gp36 to gp37, recruitment of gp35 hinge, and final joining of proximal and distal half-fibers. gp38 is specifically required for proper folding/functionality of gp37 within this pathway, whereas gp37 itself forms the distal receptor-binding module. | (pqac-00000012, pqac-00000024) | Mourosi 2022, *IJMS*, https://doi.org/10.3390/ijms232012146 |
| Receptor recognition context | In T4, receptor recognition is carried out by gp37 rather than gp38. The gp37 tip binds LPS and OmpC, and the T4 LTF tip contains three sets of alternating binding sites for LPS and/or OmpC. Thus gp38 supports formation of the receptor-binding apparatus but is not the principal mature receptor-binding protein in T4. | (pqac-00000003, pqac-00000007, pqac-00000019, pqac-00000022) | Bartual 2010, *Protein Expression and Purification*, https://doi.org/10.1016/j.pep.2009.11.005; Islam 2019, *PLOS Pathogens*, https://doi.org/10.1371/journal.ppat.1008193 |
| Family/domains | gp38 belongs to the widespread Tfa (tail fibre assembly) family, placed in Pfam Caudo_Tap17/Caudo_Tap. Tfa proteins are described as modular, with a variable N-terminal domain implicated in binding the fiber C-terminus and a more conserved C-terminal domain implicated in oligomerization/assembly. About ~4,000 related proteins were noted in phage/prophage genomes. | (pqac-00000001, pqac-00000006) | North 2019, *Nature Microbiology*, https://doi.org/10.1038/s41564-019-0477-7; Ivantsiv 2019, thesis/unknown journal |
| Functional interchangeability/evolution | T4 gp38 is evolutionarily related to λ Tfa and other tail fiber assembly proteins; λ tfa can complement T4 gene 38 mutants. Sequence comparisons show ~27% identity over the full Tfa length to gp38 and 29–30% identity over an 87-aa shared region. | (pqac-00000004) | Haggård-Ljungquist 1992, *Journal of Bacteriology*, https://doi.org/10.1128/jb.174.5.1462-1477.1992 |
| Quantitative data: co-expression requirement | Soluble, correctly folded T4 gp37 was obtained only when gp37 was co-expressed with both gp38 and gp57 in a two-vector system; expression with either chaperone alone did not yield good amounts of correctly folded trimeric gp37. Reported purified yield was ~4 mg/L. | (pqac-00000003, pqac-00000021) | Bartual 2010, *Protein Expression and Purification*, https://doi.org/10.1016/j.pep.2009.11.005 |
| Quantitative data: structural context | T4 long tail fibers are ~145 nm long overall; proximal and distal halves are ~70 nm and ~74–75 nm, respectively, connected at ~160°. Recombinant gp37 fibers measured ~63 nm by EM. gp37 is 1026 aa and 109 kDa; gp36 is 221 aa and 23 kDa. These numbers define the assembly context in which gp38 acts. | (pqac-00000017, pqac-00000019, pqac-00000021) | Mourosi 2022, *IJMS*, https://doi.org/10.3390/ijms232012146; Islam 2019, *PLOS Pathogens*, https://doi.org/10.1371/journal.ppat.1008193; Bartual 2010, *Protein Expression and Purification*, https://doi.org/10.1016/j.pep.2009.11.005 |
| Quantitative data: infection/recognition context | T4 infection efficiency has been described as approaching the theoretical value of 1, reflecting the effectiveness of the mature LTF receptor-binding apparatus whose formation depends on gp38-assisted gp37 folding. At least three of the six LTFs must recognize receptor to trigger the baseplate conformational change. | (pqac-00000019, pqac-00000021, pqac-00000022) | Islam 2019, *PLOS Pathogens*, https://doi.org/10.1371/journal.ppat.1008193; Bartual 2010, *Protein Expression and Purification*, https://doi.org/10.1016/j.pep.2009.11.005 |
| Evidence type | Evidence includes classical genetics (suppressor duplications bypassing gene 38), complementation/sequence homology, heterologous co-expression and EM/biochemistry, structural review synthesis, and family-level comparative/structural analysis. A schematic figure also places gp38 in the distal gp37 assembly pathway. | (pqac-00000003, pqac-00000004, pqac-00000005, pqac-00000024) | Bartual 2010, *Protein Expression and Purification*, https://doi.org/10.1016/j.pep.2009.11.005; Haggård-Ljungquist 1992, *Journal of Bacteriology*, https://doi.org/10.1128/jb.174.5.1462-1477.1992; Hyman 2018, *Biophysical Reviews*, https://doi.org/10.1007/s12551-017-0348-5; Mourosi 2022, *IJMS*, https://doi.org/10.3390/ijms232012146 |
| Recent relevance (2023–2024) | Recent work emphasizes that T4-like tail fiber assembly/adhesin modules are actionable targets for host-range engineering, diagnostics, and therapy. A 2023 S16-like myovirus study showed a T4-like distal tail fiber binds host LPS with nanomolar affinity and can be used for pathogen detection/control; 2024 bioanalysis/engineering reviews highlight gp38/Tfa-like modules as key determinants for engineering receptor specificity. | (pqac-00000011, pqac-00000018) | Oliveira 2023, *Applied Microbiology and Biotechnology*, https://doi.org/10.1007/s00253-023-12547-8; Parker 2024, *Annual Review of Analytical Chemistry*, https://doi.org/10.1146/annurev-anchem-071323-084224 |


*Table: This table summarizes the verified functional annotation of Enterobacteria phage T4 gp38 (gene 38; UniProt P03739), including its role as a gp37 assembly chaperone, mechanistic models, localization, family assignment, and quantitative structural context. It also highlights the important distinction between T4 gp38 and gp38 homologs in related phages that act as mature adhesins.*