Temperate phage lysogenic-lytic decision, transcription antitermination, and prophage integration/excision

A coupled gene-regulatory and site-specific recombination module that governs the bistable decision between prophage latency (lysogeny) and productive lytic development in lambdoid temperate bacteriophages. Early transcription initiated at promoters PL and PR is extended past intrinsic and Rho-dependent terminators by the nut-site antitermination protein N, expressing the CII transcriptional activator, its FtsH-inhibiting stabilizer CIII, and the integrative/recombinational genes. High CII activity activates promoters PRE (driving synthesis of the CI immunity repressor), PI (driving synthesis of the tyrosine integrase Int), and PaQ (antisense inhibition of late antiterminator Q), establishing integrated proviral latency in which CI dimers cooperatively repress PL and PR while maintaining PRM. Conversely, low CII activity permits Cro accumulation at OR3/OL3 and Q-mediated antitermination of the late PR' transcript, committing the phage to lytic replication and virion morphogenesis. Host SOS DNA damage activates RecA* coprotease-stimulated autocleavage of CI, derepressing PL and PR so that Int and the directionality factor Xis catalyze excisive recombination (attL x attR) to release the prophage genome for lytic replication.

MODULE:phage_temperate_lysogeny_switchCOMPLETECONCRETEBiological Processmodules/phage_temperate_lysogeny_switch.yaml
latency-replication decisionGO:0098689 establishment of integrated proviral latencyGO:0075713 maintenance of viral latencyGO:0019044 provirus excisionGO:0032359
PMID:11711436
Octamerization of lambda CI repressor is needed for effective repression of P(RM) and efficient switching from lysogeny.
Establishes the long-range octameric operator-looping mechanism of CI at OR and OL that maintains lysogeny and enables efficient switching to lytic development upon induction.
PMID:25114241
Nucleoprotein architectures regulating the directionality of viral integration and excision.
Establishes the nucleoprotein architecture of Int-catalyzed integrative (attP x attB) and Xis-directed excisive (attL x attR) site-specific recombination in phage lambda.
GO:0098689
latency-replication decision
Defines the biological process governing the choice between viral latency and lytic replication.
GO:0075713
establishment of integrated proviral latency
Defines integration of the temperate phage genome into the host chromosome to establish a prophage.
GO:0032359
provirus excision
Defines site-specific excision of the integrated prophage genome upon induction.

Exemplar phage: Escherichia phage lambda (NCBITaxon:2681611). Generalizes across lambdoid and temperate tailed phages (including Salmonella phage P22, coliphages HK97, 434, and 21) that couple a CII/CI/Cro-like bistable transcriptional switch and N/Q-like antitermination to tyrosine or serine integrase/excisionase-mediated prophage integration and excision.

9Nodes
8Parts
0Variant Sets
0Variants
8Annotons
10Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:phage_temperate_lysogeny_switch deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

8 gene-function check(s) reflected in core functions · 0 conflict(s) · 8 evidence or coverage gap(s) (16 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
n_antiterminator_activity N (Escherichia phage lambda)
UniProtKB:P03045
Family Representative 		transcription antitermination factor activity, RNA binding
GO:0001072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ciii_inhibitor_activity cIII (Escherichia phage lambda)
UniProtKB:P03044
Family Representative 		endopeptidase inhibitor activity
GO:0004866 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cii_activator_activity cII (Escherichia phage lambda)
UniProtKB:P03042
Family Representative 		DNA binding
GO:0003677 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
int_integrase_activity int (Escherichia phage lambda)
UniProtKB:P03700
Family Representative 		integrase activity
GO:0008907 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ci_repressor_activity cI (Escherichia phage lambda)
UniProtKB:P03034
Family Representative 		core promoter sequence-specific DNA binding
GO:0001046 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cro_repressor_activity cro (Escherichia phage lambda)
UniProtKB:P03040
Family Representative 		core promoter sequence-specific DNA binding
GO:0001046 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
xis_excisionase_activity xis (Escherichia phage lambda)
UniProtKB:P03699
Family Representative 		DNA binding
GO:0003677 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
q_antiterminator_activity Q (Escherichia phage lambda)
UniProtKB:P03047
Family Representative 		DNA binding
GO:0003677 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
n_antiterminator_activity Phage lambda N antitermination protein family (InterPro:IPR020952 / Pfam:PF11438)
Family 		transcription antitermination factor activity, RNA binding
GO:0001072 		Family Id Missing
The family has no identifier linking it to a curated family review.
ciii_inhibitor_activity Phage lambda CIII protease inhibitor family (InterPro:IPR013056 / Pfam:PF02061)
Family 		endopeptidase inhibitor activity
GO:0004866 		Family Id Missing
The family has no identifier linking it to a curated family review.
cii_activator_activity Phage CII transcriptional activator family (InterPro:IPR007933 / Pfam:PF05269)
Family 		DNA binding
GO:0003677 		Family Id Missing
The family has no identifier linking it to a curated family review.
int_integrase_activity Prophage tyrosine integrase family
PANTHER:PTHR30629:SF2
Family 		integrase activity
GO:0008907 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR30629:SF2.
ci_repressor_activity LexA/CI-like S24 peptidase repressor family
PANTHER:PTHR33516:SF2
Family 		core promoter sequence-specific DNA binding
GO:0001046 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0001046.
cro_repressor_activity Cro transcriptional repressor family (InterPro:IPR000655 / Pfam:PF09048)
Family 		core promoter sequence-specific DNA binding
GO:0001046 		Family Id Missing
The family has no identifier linking it to a curated family review.
xis_excisionase_activity Phage excisionase family (InterPro:IPR012884 / Pfam:PF07825)
Family 		DNA binding
GO:0003677 		Family Id Missing
The family has no identifier linking it to a curated family review.
q_antiterminator_activity Phage Q late antiterminator family (InterPro:IPR003222 / Pfam:PF03589)
Family 		DNA binding
GO:0003677 		Family Id Missing
The family has no identifier linking it to a curated family review.

Feedback loops (advisory, prose-driven: a regulator counts as "feedback" when its own description says so)

✓ every negative regulator described as feedback has an upstream edge closing the loop.

  • cii_activation_step ⊣ q_late_antitermination_step [closed]
    cii_activation_step is regulated by early_antitermination_step, ciii_stabilization_step: feedback loop closed
  • ci_maintenance_step ⊣ cro_lytic_commitment_step [closed]
    ci_maintenance_step is regulated by cii_activation_step: feedback loop closed
  • cro_lytic_commitment_step ⊣ ci_maintenance_step [input]
    cro_lytic_commitment_step is a negative regulator with no upstream edge (not described as feedback)

Gene-review completeness (8/8 grounded genes reviewed)

8 complete review(s) · 0 with deep research · 0 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
cI P03034 ✓ ✓ ✗
cII P03042 ✓ ✓ ✗
cIII P03044 ✓ ✓ ✗
cro P03040 ✓ ✓ ✗
int P03700 ✓ ✓ ✗
N P03045 ✓ ✓ ✗
Q P03047 ✓ ✓ ✗
xis P03699 ✓ ✓ ✗

Details

Context
CaudoviricetesNCBITaxon:2731619 Escherichia phage lambdaNCBITaxon:2681611
Temperate phage lysogenic-lytic decision and prophage integration/excisionBiological Processphage_temperate_lysogeny_switch
latency-replication decisionGO:0098689 establishment of integrated proviral latencyGO:0075713 maintenance of viral latencyGO:0019044 provirus excisionGO:0032359
Context
CaudoviricetesNCBITaxon:2731619 Escherichia phage lambdaNCBITaxon:2681611

Connections

cii_activation_step -> ci_maintenance_step Positively Regulates
ci_maintenance_step -> xis_excision_step Negatively Regulates
Part 1: early transcription antitermination
N-mediated early transcription antitermination at nutL and nutRRegulatory Stepearly_antitermination_step

Annotons

Antitermination protein N
n_antiterminator_activity
Participant: Family: Phage lambda N antitermination protein family (InterPro:IPR020952 / Pfam:PF11438)
Family:
Phage lambda N antitermination protein family (InterPro:IPR020952 / Pfam:PF11438)
Representative Members: N (Escherichia phage lambda)UniProtKB:P03045

Function

transcription antitermination factor activity, RNA bindingGO:0001072

Processes

transcription antiterminationGO:0031564

Locations

host cell cytoplasmGO:0030430

Binds nascent nutL and nutR boxB RNA hairpins and remodels host RNA polymerase with NusA, NusB, NusE (S10), and NusG into a termination-resistant elongation complex to transcribe delayed-early genes including cIII, cII, int, and Q.

Part 2: host protease inhibition and CII stabilization
CIII-mediated competitive inhibition of host FtsH (HflB) proteaseRegulatory Stepciii_stabilization_step

Annotons

Protease inhibitor CIII
ciii_inhibitor_activity
Participant: Family: Phage lambda CIII protease inhibitor family (InterPro:IPR013056 / Pfam:PF02061)
Family:
Phage lambda CIII protease inhibitor family (InterPro:IPR013056 / Pfam:PF02061)
Representative Members: cIII (Escherichia phage lambda)UniProtKB:P03044

Function

endopeptidase inhibitor activityGO:0004866

Processes

latency-replication decisionGO:0098689 establishment of viral latencyGO:0019043

Locations

host cell plasma membraneGO:0020002

Acts as a competitive substrate/inhibitor of the host membrane-bound AAA+ metalloprotease FtsH (HflB), extending the half-life of CII under high multiplicity of infection or nutrient limitation.

Part 3: lysogenic promoter activation
CII-mediated transcriptional activation of PRE, PI, and PaQRegulatory Stepcii_activation_step

Annotons

Transcriptional activator CII
cii_activator_activity
Participant: Family: Phage CII transcriptional activator family (InterPro:IPR007933 / Pfam:PF05269)
Family:
Phage CII transcriptional activator family (InterPro:IPR007933 / Pfam:PF05269)
Representative Members: cII (Escherichia phage lambda)UniProtKB:P03042

Function

DNA bindingGO:0003677

Processes

latency-replication decisionGO:0098689 establishment of viral latencyGO:0019043

Locations

host cell cytoplasmGO:0030430

Homotetrameric transcription factor that recognizes direct-repeat TTGC(N6)TTGC motifs flanking the -35 region of promoters PRE, PI, and PaQ to coordinately drive CI repressor synthesis, Int synthesis, and antisense suppression of late regulator Q.

Part 4: site-specific prophage integration
Int-mediated site-specific integration at attP and attBReactionprophage_integration_step

Annotons

Prophage tyrosine integrase Int
int_integrase_activity
Participant: Family: Prophage tyrosine integrase family
Family:
Prophage tyrosine integrase familyPANTHER:PTHR30629:SF2
Representative Members: int (Escherichia phage lambda)UniProtKB:P03700

Function

integrase activityGO:0008907

Processes

establishment of integrated proviral latencyGO:0075713 DNA integrationGO:0015074

Locations

host cell cytoplasmGO:0030430

Heterobivalent tyrosine recombinase that assembles with host IHF on supercoiled attP to form the intasome, capturing host chromosomal attB and catalyzing strand exchange via a Holliday junction intermediate to generate attL and attR flanking the integrated prophage.

Part 5: maintenance of lysogenic immunity and SOS prophage induction
CI repressor maintenance of lysogeny and RecA*-stimulated autocleavageRegulatory Stepci_maintenance_step

Annotons

Repressor protein CI
ci_repressor_activity
Participant: Family: LexA/CI-like S24 peptidase repressor family
Family:
LexA/CI-like S24 peptidase repressor familyPANTHER:PTHR33516:SF2
Representative Members: cI (Escherichia phage lambda)UniProtKB:P03034

Function

core promoter sequence-specific DNA bindingGO:0001046

Processes

maintenance of viral latencyGO:0019044 release from viral latencyGO:0019046

Locations

host cell cytoplasmGO:0030430

Cooperatively binds operators OR1/OR2 and OL1/OL2 as a long-range octamer loop to repress lytic promoters PR and PL while auto-activating PRM; upon host DNA damage, RecA* nucleoprotein filaments stimulate intramolecular S24 serine peptidase cleavage of the CI hinge, abolishing cooperative operator binding and inducing the prophage.

Part 6: lytic commitment and PRM repression
Cro-mediated repression of PRM and commitment to lytic developmentRegulatory Stepcro_lytic_commitment_step

Annotons

Regulatory protein Cro
cro_repressor_activity
Participant: Family: Cro transcriptional repressor family (InterPro:IPR000655 / Pfam:PF09048)
Family:
Cro transcriptional repressor family (InterPro:IPR000655 / Pfam:PF09048)
Representative Members: cro (Escherichia phage lambda)UniProtKB:P03040

Function

core promoter sequence-specific DNA bindingGO:0001046

Processes

latency-replication decisionGO:0098689

Locations

host cell cytoplasmGO:0030430

Binds with highest affinity to OR3 (opposite to CI's preference for OR1), shutting off CI maintenance transcription from PRM and locking the bistable switch into the lytic state, before repressing PR and PL at higher concentrations.

Part 7: directionality control and prophage excision
Xis-directed excisive recombination of attL and attRReactionxis_excision_step

Annotons

Excisionase Xis
xis_excisionase_activity
Participant: Family: Phage excisionase family (InterPro:IPR012884 / Pfam:PF07825)
Family:
Phage excisionase family (InterPro:IPR012884 / Pfam:PF07825)
Representative Members: xis (Escherichia phage lambda)UniProtKB:P03699

Function

DNA bindingGO:0003677

Processes

provirus excisionGO:0032359

Locations

host cell cytoplasmGO:0030430

Architectural winged-helix DNA-bending protein that binds X1/X2 sites in attR alongside Int and host IHF/Fis to assemble the excisive intasome, promoting attL x attR recombination while inhibiting re-integration.

Part 8: late gene transcription antitermination
Q-mediated antitermination of late PR' transcription past tR'Regulatory Stepq_late_antitermination_step

Annotons

Antitermination protein Q
q_antiterminator_activity
Participant: Family: Phage Q late antiterminator family (InterPro:IPR003222 / Pfam:PF03589)
Family:
Phage Q late antiterminator family (InterPro:IPR003222 / Pfam:PF03589)
Representative Members: Q (Escherichia phage lambda)UniProtKB:P03047

Function

DNA bindingGO:0003677

Processes

transcription antiterminationGO:0031564

Locations

host cell cytoplasmGO:0030430

Binds the qut DNA element between the -35 and -10 boxes of PR' and engages sigma-70-paused RNA polymerase with NusA to form a nozzle around the RNA exit channel that prevents terminator hairpin formation at tR', licensing expression of the entire late lysis and morphogenesis operon.