Bacterial cytochrome c maturation system I

Bacterial cytochrome c maturation System I couples heme handling and ATP-dependent processing to covalent attachment of heme to exported c-type cytochrome apoproteins. The canonical histidine-CcmE route uses CcmG-supported redox preparation and CcmFH ligation, with lineage-dependent fused or separate CcmI-like accessories. The experimentally reconstructed G20 System I* route uses cysteine-linked CcmE and functions without CcmG/H; its CcmI enhances yield. Sec export, heme biosynthesis and lineage-specific upstream reductant supply are external dependencies. Archaeal and mitochondrial implementations are outside this bacterial module.

MODULE:bacterial_cytochrome_c_maturation_system_iCOMPLETEABSTRACTBiological Processmodules/bacterial_cytochrome_c_maturation_system_i.yaml
cytochrome c-heme linkageGO:0018063
GO:0018063
cytochrome c-heme linkage
GO:0018063 defines the process boundary as covalent linkage of heme to cytochrome c.
GO:0004408
holocytochrome-c synthase activity
GO:0004408 defines the terminal molecular function as conversion of apocytochrome c and heme to holocytochrome c.
PMID:10339610
Heme transfer to the heme chaperone CcmE during cytochrome c maturation requires the CcmC protein, which may function independently of the ABC-transporter CcmAB.
Direct experiments distinguish the CcmAB energy-coupling subcomplex from the CcmC-dependent heme-transfer step. Its proposal that CcmD stabilizes membrane-associated CcmE is disputed by PMID:18326572, which found CcmD dispensable for heme transfer to CcmE but required for holo-CcmE release.
PMID:18326572
Topology and function of CcmD in cytochrome c maturation.
In E. coli, CcmD is a component of the CcmABC complex that is not needed for heme transfer to CcmE but is absolutely required for release of holo-CcmE from CcmABCD.
PMID:17419738
Loss of ATP hydrolysis activity by CcmAB results in loss of c-type cytochrome synthesis and incomplete processing of CcmE.
Purified CcmAB ATPase and K40D perturbation distinguish ATP-dependent maturation/processing from retained CcmE heme attachment in E. coli.
PMID:19721088
Cytochrome c biogenesis: mechanisms for covalent modifications and trafficking of heme and for heme-iron redox control.
The System I synthesis distinguishes CcmABCD/CcmE heme handling, proposed CcmF-associated heme-iron reduction and CcmH-linked apocytochrome redox handling/ligation; it does not identify CcmH as a heme-iron reductase.
PMID:18753134
The cytochrome c maturation components CcmF, CcmH, and CcmI form a membrane-integral multisubunit heme ligation complex.
Tagged Rhodobacter F/H/I components associate in membrane-derived material; exact strain/construct limits are recorded and no universal obligate FHI stoichiometry is inferred.
PMID:20544959
Structural and functional characterization of CcmG from Pseudomonas aeruginosa, a key component of the bacterial cytochrome c maturation apparatus.
Structural analysis supports CcmG thiol-disulfide reductase activity and proposes a CcmH-apocytochrome mixed disulfide as a physiological substrate.
PMID:28634234
The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochrome c maturation.
Reconstituted biochemistry separates the efficiency contribution of CcmG from the stereospecific ligation role of CcmH.
PMID:8231805
Formation of several bacterial c-type cytochromes requires a novel membrane-anchored protein that faces the periplasm.
Bradyrhizobium CycH supports most tested cellular c-type cytochromes, with cytochrome c1 spared; accessory dependence is substrate-specific.
PMID:9712585
Prototype of a heme chaperone essential for cytochrome c maturation.
E. coli CcmE binds heme covalently through a histidine and delivers it to apocytochrome c, defining the heme-chaperone step.
PMID:16824107
ABC transporter-mediated release of a haem chaperone allows cytochrome c biogenesis.
Canonical E. coli holo-CcmE is trapped in a CcmC-associated complex without functional CcmAB; ATP-dependent release is supported but does not exclude additional heme-handling roles.
PMID:19629033
A conserved haem redox and trafficking pathway for cofactor attachment.
E. coli CcmF heme-b and in-vitro quinol:heme oxidoreductase data support a proposed heme-redox step; these do not establish the same required quinone site or electron donor in System I*.
PMID:11744735
A bacterial cytochrome c heme lyase. CcmF forms a complex with the heme chaperone CcmE and CcmH but not with apocytochrome c.
E. coli CcmF interacts with holo-CcmE and CcmH, supporting a CcmFH heme lyase complex.
PMID:9537397
The active-site cysteines of the periplasmic thioredoxin-like protein CcmG of Escherichia coli are important but not essential for cytochrome c maturation in vivo.
E. coli CcmG deletion and active-site-cysteine mutations have different outcomes: low maturation persists in the cysteine variants and exogenous thiols can improve these, whereas deletion is not rescued by those thiols.
PMID:40460019
Mechanisms and Control of Heme Transport and Incorporation into Cytochrome c.
Recent synthesis compares structures and mechanisms of three maturation systems; bacterial System I/II must be distinguished from mitochondrial System III.
PMID:21958041
Cytochrome c biogenesis System I.
System I* uses a cysteine-bearing CcmE and can omit the canonical CcmG/H requirement in characterized strains; not every cysteine-CcmE lineage lacks CcmH.
PMID:24631867
Cytochrome c biogenesis System I: an intricate process catalyzed by a maturase supercomplex?
Ccm components occur in distinct gene arrangements and CcmI is separate in Rhodobacter but fused to CcmH in E. coli.
PMID:40026579
Complexation of CcmB with CcmACD safeguards heme translocation for cytochrome c maturation.
The authors assign CcmB a heme-translocase role and complexation with CcmACD a routing role toward maturation.
PMID:40167305
Biochemical mapping reveals a conserved heme transport mechanism via CcmCD in System I bacterial cytochrome c biogenesis.
Mapped heme contacts span cytoplasmic acceptance and a proposed CcmC membrane channel leading to the WWD domain.
PMID:37626034
Architecture of the Heme-translocating CcmABCD/E complex required for Cytochrome c maturation.
E. coli CcmABCD forms a structurally resolved complex associated with CcmE; the structural transport model needs comparison with the two conflicting 2025 studies.
PMID:21956106
CcmI subunit of CcmFHI heme ligation complex functions as an apocytochrome c chaperone during c-type cytochrome maturation.
Rhodobacter CcmI binds apocytochrome c; full-length tagged construct donor and domain-specific MT1131 cloning are distinguished in the individual review.
PMID:20466730
c-Type cytochrome biogenesis can occur via a natural Ccm system lacking CcmH, CcmG, and the heme-binding histidine of CcmE.
The G20 cassette produces mature heterologous c-type cytochromes without CcmG/H and uses Cys127-linked CcmE. CcmI deletion retains product; further CcmD deletion removes detectable product. Full-text donor/deletion evidence and corrected detection limits are recorded in the source analysis.
PMID:24044352
Probing heme delivery processes in cytochrome c biogenesis System I.
CcmA/F/C mutagenesis separates ATP-dependent heme handling from downstream ligation; the experimental CcmC residue numbering differs from the current reference sequence by 18 residues.
file:genes/OLEA2/ccmE/ccmE-source-analysis/primary-evidence.md
G20 System I* primary evidence and identity
Records exact donor evidence, native sequence/CDS comparisons, CcmC numbering limits, sequential CcmI/CcmD truncation interpretation and the corrected detection sensitivity.
PMID:18786143
Compensatory thio-redox interactions between DsbA, CcdA and CcmG unveil the apocytochrome c holdase role of CcmG during cytochrome c maturation.
In Rhodobacter DsbA-null backgrounds, CcmG/CcdA redox requirements can be bypassed, while thiol-inactive CcmG improves maturation and binds apocytochrome in vitro; CcmH remains required under those tested conditions.
PMID:24397552
The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE.
Engineered E. coli CcmFGH-only expression produces covalently attached, correctly processed holocytochromes without CcmABCDE, supporting terminal synthase chemistry in the CcmFH apparatus. Engineered heme/expression conditions do not establish that native cells ordinarily dispense with upstream delivery.

The bacterial taxon is a scope boundary, not a universality assertion. Complete reviewed exemplar panels cover E. coli K-12, P. putida KT2440 and the G20 System I* cassette; RHOCB SB1003-reference proteins and SHEON MR1 CcmB provide selected experimentally informative roles, not complete-route panels. Rhodobacter assay strains/constructs and the G20 CcmC numbering discrepancy are documented in individual source analyses. Family labels alone do not define role: PTHR47870 SF1 contains both redox CcmH and accessory CcmI, PTHR30071 includes other heme-handling systems, and PTHR34128 includes both CcmE linkage chemistries. No ancestral node is invented for newly added exemplars. Conflicting CcmB and CcmCD conduit models remain explicit; structural/contact and conditional overproduction evidence do not settle a universal native conduit. System II and mitochondrial System III are separate implementations outside this boundary. CcmG redox bypasses in altered backgrounds and thiol-independent handling mean this canonical route is not an exhaustive list of all experimental rescue configurations. Engineered CcmFGH-only expression can bypass CcmABCDE under special heme/expression conditions (PMID:24397552); the canonical capacity route models ordinary upstream delivery, not all synthetic bypasses.

13Nodes
10Parts
1Variant Sets
2Variants
16Annotons
6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • bacterial_cytochrome_c_maturation_system_i-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ representative grounding skipped for abstract module.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

13 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (22 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
ccmc_heme_handling_subunit CcmC (Escherichia coli K-12)
UniProtKB:P0ABM1
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccmc_heme_handling_subunit CcmC (Pseudomonas putida KT2440)
UniProtKB:Q88EX7
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccme_heme_chaperone CcmE (Escherichia coli K-12)
UniProtKB:P69490
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccme_heme_chaperone CcmE (Pseudomonas putida KT2440)
UniProtKB:Q88EX9
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccma_atpase CcmA (Escherichia coli K-12)
UniProtKB:P33931
Family Representative 		ATP hydrolysis activity
GO:0016887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccma_atpase CcmA (Pseudomonas putida KT2440)
UniProtKB:Q88EX5
Family Representative 		ATP hydrolysis activity
GO:0016887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccmg_disulfide_reductase CcmG/DsbE (Escherichia coli K-12)
UniProtKB:P0AA86
Family Representative 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccmg_disulfide_reductase CcmG (Pseudomonas putida KT2440)
UniProtKB:Q88EY1
Family Representative 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccmg_disulfide_reductase helX (Rhodobacter capsulatus SB 1003)
UniProtKB:P36893
Family Representative 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccmfh_synthetase_activity PROTEIN_COMPLEX
Gene 		holocytochrome-c synthase activity
GO:0004408 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
istar_ccma_atpase ccmA (Oleidesulfovibrio alaskensis G20)
UniProtKB:Q311X1
Family Representative 		ATP hydrolysis activity
GO:0016887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
istar_ccmc_heme_handling_subunit ccmC (Oleidesulfovibrio alaskensis G20)
UniProtKB:Q311X3
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
istar_ccme_heme_chaperone ccmE (Oleidesulfovibrio alaskensis G20)
UniProtKB:Q311W9
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
istar_ccmf_ligation_component ccmF (Oleidesulfovibrio alaskensis G20)
UniProtKB:Q311X0
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ccmc_heme_handling_subunit CcmC/CcsA WWD-domain heme-handling family
PANTHER:PTHR30071:SF1
Family 		heme binding
GO:0020037 		Family Supported
Family review supports GO:0020037 for PANTHER:PTHR30071:SF1. Heme binding in the periplasmic WWD domain is demonstrated for E. coli CcmC and is the shared feature of the CcmC/CcsA members of SF1; it is not established for HemX (SF15).
ccme_heme_chaperone CcmE heme-chaperone family
PANTHER:PTHR34128:SF2
Family 		heme binding
GO:0020037 		Family Supported
Family review supports GO:0020037 FAMILY_WIDE. Root PTN002436954 asserts heme binding. Canonical histidine-bearing and System I* cysteine-bearing CcmE both support that function; ligand chemistry differs within SF2, as shown by G20 Q311W9.
ccma_atpase CcmA cytochrome-c-maturation ATPase family
PANTHER:PTHR43499:SF1
Family 		ATP hydrolysis activity
GO:0016887 		Family Supported
Family review supports GO:0016887 FAMILY_WIDE. ATP hydrolysis is the catalytic activity of the ABC nucleotide-binding fold shared by all members; it is directly demonstrated for purified E. coli CcmAB and is lost on Walker A mutation.
ccmg_disulfide_reductase CcmG/DsbE thioredoxin family
PANTHER:PTHR42852:SF6
Family 		protein-disulfide reductase activity
GO:0015035 		Family Supported
Family review supports GO:0015035 for PANTHER:PTHR42852:SF6. Reduction of protein disulfides (apocytochrome c and CcmH mixed disulfides) is demonstrated for system I CcmG of SF6; ResA in the same subfamily also reduces apocytochrome disulfides in system II. Other subfamilies act on other substrates.
istar_ccma_atpase System I* ccmA role
PANTHER:PTHR42939:SF1
Family 		ATP hydrolysis activity
GO:0016887 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR42939:SF1.
istar_ccmc_heme_handling_subunit System I* ccmC role
PANTHER:PTHR30071:SF1
Family 		heme binding
GO:0020037 		Family Supported
Family review supports GO:0020037 for PANTHER:PTHR30071:SF1. Heme binding in the periplasmic WWD domain is demonstrated for E. coli CcmC and is the shared feature of the CcmC/CcsA members of SF1; it is not established for HemX (SF15).
istar_ccme_heme_chaperone System I* ccmE role
PANTHER:PTHR34128:SF2
Family 		heme binding
GO:0020037 		Family Supported
Family review supports GO:0020037 FAMILY_WIDE. Root PTN002436954 asserts heme binding. Canonical histidine-bearing and System I* cysteine-bearing CcmE both support that function; ligand chemistry differs within SF2, as shown by G20 Q311W9.
istar_ccmf_ligation_component System I* ccmF role
PANTHER:PTHR43653:SF1
Family 		heme binding
GO:0020037 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0020037.

Gene-review completeness (29/29 grounded genes reviewed)

17 complete review(s) · 0 with deep research · 0 missing review · 29 reviewed but lacking deep research

Gene Review Complete Deep research
ccl1 Q00500 ✓ ✓ ✗
ccl2 Q00501 ✓ ✓ ✗
ccmA P33931 ✓ 14/17 ✗
ccmA Q311X1 ✓ ✓ ✗
ccmA Q88EX5 ✓ 4/8 ✗
ccmB P0ABL8 ✓ 13/15 ✗
ccmB Q311X2 ✓ 3/4 ✗
ccmB Q88EX6 ✓ 5/6 ✗
ccmB Q8EK41 ✓ 6/7 ✗
ccmC P0ABM1 ✓ 23/27 ✗
ccmC Q311X3 ✓ 5/6 ✗
ccmC Q88EX7 ✓ 5/6 ✗
ccmD F9XXF9 ✓ ✓ ✗
ccmD P0ABM5 ✓ 14/15 ✗
ccmD Q88EX8 ✓ ✓ ✗
ccmE P69490 ✓ 17/18 ✗
ccmE Q311W9 ✓ ✓ ✗
ccmE Q88EX9 ✓ ✓ ✗
ccmF P33927 ✓ ✓ ✗
ccmF Q311X0 ✓ ✓ ✗
ccmF Q88EY0 ✓ ✓ ✗
ccmG Q88EY1 ✓ ✓ ✗
ccmH A0A140FWM4 ✓ ✓ ✗
ccmH P0ABM9 ✓ 10/11 ✗
ccmI Q311X4 ✓ ✓ ✗
cycH A0A140FWM3 ✓ ✓ ✗
cycH D5ALI6 ✓ ✓ ✗
dsbE P0AA86 ✓ ✓ ✗
helX P36893 ✓ ✓ ✗

Details

Context
bacteriaNCBITaxon:2
Bacterial cytochrome c maturation system IBiological Processbacterial_cytochrome_c_maturation_system_i

Alternative intact bacterial System I architectures couple heme handling to covalent attachment. Route alternatives retain compatible CcmE chemistry and terminal machinery together.

cytochrome c-heme linkageGO:0018063
Context
bacteriaNCBITaxon:2
Variant set: Compatible System I architectures by CcmE linkage chemistry and terminal maturation machinery [Route] (One Or More)

Variants are complete compatible architectures. Selecting a heme-handling subunit from one and ligation machinery from the other does not establish a functioning hybrid.

Canonical CcmG-supported, CcmH-dependent System IBiological Processcanonical_ccmgh_supported_system_i

Canonical architecture with histidine-linked CcmE, CcmAB-coupled holo-CcmE processing and a CcmG-supported CcmFH ligation branch. This models the ordinary oxidizing periplasm; CcmG/CcdA bypasses in altered redox backgrounds and thiol-independent CcmG chaperoning mean that a required protein role is not a claim of universally indispensable reductase chemistry. ECOLI and KT2440 panels cover the whole route; the RHOCB and SHEON exemplars cover selected roles only.

cytochrome c-heme linkageGO:0018063
Context
bacteriaNCBITaxon:2
PMID:21958041
Cytochrome c biogenesis System I.
Comparative review distinguishes canonical histidine-CcmE machinery from System I* and discusses separate versus fused CcmH/I architectures.
PMID:24631867
Cytochrome c biogenesis System I: an intricate process catalyzed by a maturase supercomplex?
Comparative Rhodobacter-centered synthesis supports interacting heme-delivery and apocytochrome-handling branches; a single obligatory maturase supercomplex remains a hypothesis.
PMID:18786143
Compensatory thio-redox interactions between DsbA, CcdA and CcmG unveil the apocytochrome c holdase role of CcmG during cytochrome c maturation.
In Rhodobacter DsbA-null backgrounds, CcmG/CcdA redox requirements can be bypassed, while thiol-inactive CcmG improves maturation and binds apocytochrome in vitro; CcmH remains required under those tested conditions.

Connections

Part 1: heme trafficking and holo-CcmE formation
CcmABCDE heme trafficking and holo-CcmE formationBiological Processccmabcde_heme_trafficking

CcmC-dependent heme loading of CcmE and CcmAB-dependent ATP coupling for holo-CcmE processing/release are experimentally separable in E. coli. CcmD participates in the membrane assembly and release. Primary models disagree about the membrane-crossing conduit: CcmB-dependent heme loss in overproduction assays and CcmCD contact mapping are retained with their assay limits. Neither chronology alone nor the old exporter names settle native flux.

Connections

Part 1: heme transfer and covalent loading of CcmE
CcmCDE holo-CcmE-forming assemblyProtein Complexccmcde_holo_ccme_formation

CcmC-dependent heme loading of CcmE occurs within an assembly containing CcmD. CcmD is required for downstream release rather than for initial heme transfer; its presence is not a Boolean prerequisite for the loading reaction alone.

Annotons

CcmC heme-handling subunit
ccmc_heme_handling_subunit
Participant: Family: CcmC/CcsA WWD-domain heme-handling family
Family:
CcmC/CcsA WWD-domain heme-handling familyPANTHER:PTHR30071:SF1
Representative Members: CcmC (Escherichia coli K-12)UniProtKB:P0ABM1 CcmC (Pseudomonas putida KT2440)UniProtKB:Q88EX7

Function

heme bindingGO:0020037

Binds heme and supports loading of CcmE. The 2025 CcmCD contact-mapping model proposes a CcmC conduit, whereas the competing CcmB model assigns membrane crossing elsewhere; specific transmembrane transporter activity remains unresolved here.

PMID:10339610
Heme transfer to the heme chaperone CcmE during cytochrome c maturation requires the CcmC protein, which may function independently of the ABC-transporter CcmAB.
E. coli CcmC is required for heme loading of CcmE independently of CcmAB in the reported assays.
PMID:40167305
Biochemical mapping reveals a conserved heme transport mechanism via CcmCD in System I bacterial cytochrome c biogenesis.
Engineered cysteine/heme contacts support the authors' proposed CcmCD acceptance/channel model; contact mapping is not an isolated vectorial-flux measurement.
CcmD accessory subunit
ccmd_accessory_subunit
Participant: Family: CcmD cytochrome-c-maturation family
Family:
CcmD cytochrome-c-maturation familyPANTHER:PTHR37531:SF1
Representative Members: CcmD (Escherichia coli K-12)UniProtKB:P0ABM5 CcmD (Pseudomonas putida KT2440)UniProtKB:Q88EX8

Small membrane assembly component required for holo-CcmE release in the canonical E. coli experiments. Holo-CcmE can form without CcmD; newer engineered-cysteine contacts support a role in heme handling, without demonstrating autonomous catalysis.

PMID:18326572
Topology and function of CcmD in cytochrome c maturation.
CcmD deletion separates retained holo-CcmE formation from failed release in E. coli.
PMID:40167305
Biochemical mapping reveals a conserved heme transport mechanism via CcmCD in System I bacterial cytochrome c biogenesis.
Engineered CcmD cysteine contacts support heme contact in the assembly, distinct from an earlier negative wild-type binding assay.
CcmE heme chaperone
ccme_heme_chaperone
Participant: Family: CcmE heme-chaperone family
Family:
CcmE heme-chaperone familyPANTHER:PTHR34128:SF2
Representative Members: CcmE (Escherichia coli K-12)UniProtKB:P69490 CcmE (Pseudomonas putida KT2440)UniProtKB:Q88EX9

Function

heme bindingGO:0020037

Processes

cytochrome c-heme linkageGO:0018063

Transiently carries covalently bound heme from the CcmCDE assembly to the downstream ligation machinery.

PMID:9712585
Prototype of a heme chaperone essential for cytochrome c maturation.
E. coli CcmE covalently binds heme through histidine and participates in transfer to apocytochrome; KT2440 histidine chemistry is sequence/HAMAP-supported inference.

Connections

Part 2: ATP-dependent holo-CcmE processing
CcmAB energy-coupling subcomplexProtein Complexccmab_energy_coupling

Annotons

CcmA ATPase
ccma_atpase
Participant: Family: CcmA cytochrome-c-maturation ATPase family
Family:
CcmA cytochrome-c-maturation ATPase familyPANTHER:PTHR43499:SF1
Representative Members: CcmA (Escherichia coli K-12)UniProtKB:P33931 CcmA (Pseudomonas putida KT2440)UniProtKB:Q88EX5

Function

ATP hydrolysis activityGO:0016887

Hydrolyzes ATP to support processing and release of holo-CcmE; no substrate-specific transporter activity is asserted.

PMID:17419738
Loss of ATP hydrolysis activity by CcmAB results in loss of c-type cytochrome synthesis and incomplete processing of CcmE.
Purified CcmAB ATPase and the E. coli CcmA K40D perturbation support ATP hydrolysis and maturation-associated CcmE processing.
PMID:16824107
ABC transporter-mediated release of a haem chaperone allows cytochrome c biogenesis.
Without functional CcmAB, holo-CcmE remains associated with CcmC; ATP-dependent release is supported in the canonical E. coli system.
CcmB membrane subunit
ccmb_membrane_subunit
Participant: Family: CcmB cytochrome-c-maturation family
Family:
CcmB cytochrome-c-maturation familyPANTHER:PTHR30070:SF1
Representative Members: CcmB (Escherichia coli K-12)UniProtKB:P0ABL8 CcmB (Pseudomonas putida KT2440)UniProtKB:Q88EX6 ccmB (Shewanella oneidensis MR-1)UniProtKB:Q8EK41

Membrane partner of the ATPase in CcmABCD. SHEON overproduction experiments support conditional heme-translocation-associated activity, while CcmCD mapping supports a different native conduit model. The maturation role is retained without requiring a universal CcmB-specific transport molecular function.

PMID:37626034
Architecture of the Heme-translocating CcmABCD/E complex required for Cytochrome c maturation.
The E. coli structures support physical CcmABCD/E assembly; the accompanying transport model requires separate evaluation.
PMID:40026579
Complexation of CcmB with CcmACD safeguards heme translocation for cytochrome c maturation.
Shewanella MR1 deletion/complementation and overproduction assays support the proposed CcmB heme-translocation role, with conditional excess-free-CcmB phenotypes.
PMID:40167305
Biochemical mapping reveals a conserved heme transport mechanism via CcmCD in System I bacterial cytochrome c biogenesis.
The alternative CcmCD contact-mapping model explicitly disputes CcmB as the native conduit; retain this disagreement rather than selecting by publication date.
Part 2: reductive preparation of apocytochrome CXXCH motifs
CcmG/CcmH apocytochrome thiol-redox preparationBiological Processccmgh_redox_preparation

CcmG reduces apocytochrome disulfides and resolves CcmH-apocytochrome intermediates in studied systems, while also contributing substrate handling. CcmH helps orient the substrate for stereospecific ligation. Upstream reducing equivalents can arrive via DsbD or CcdA, depending on lineage; altered redox backgrounds can bypass part of this branch.

PMID:18786143
Compensatory thio-redox interactions between DsbA, CcdA and CcmG unveil the apocytochrome c holdase role of CcmG during cytochrome c maturation.
In Rhodobacter DsbA-null backgrounds, CcmG/CcdA redox requirements can be bypassed, while thiol-inactive CcmG improves maturation and binds apocytochrome in vitro; CcmH remains required under those tested conditions.

Annotons

CcmG thiol-disulfide oxidoreductase
ccmg_disulfide_reductase
Participant: Family: CcmG/DsbE thioredoxin family
Family:
CcmG/DsbE thioredoxin familyPANTHER:PTHR42852:SF6
Representative Members: CcmG/DsbE (Escherichia coli K-12)UniProtKB:P0AA86 CcmG (Pseudomonas putida KT2440)UniProtKB:Q88EY1 helX (Rhodobacter capsulatus SB 1003)UniProtKB:P36893

Function

protein-disulfide reductase activityGO:0015035

Supplies thiol-reducing activity by reducing apocytochrome disulfides and/or resolving CcmH-apocytochrome mixed-disulfide intermediates, depending on system architecture. A separate thiol-independent apocytochrome-binding role is demonstrated in Rhodobacter; this MF annoton does not assert that all chaperone effects are reductase chemistry.

PMID:9537397
The active-site cysteines of the periplasmic thioredoxin-like protein CcmG of Escherichia coli are important but not essential for cytochrome c maturation in vivo.
E. coli CcmG deletion prevents detectable maturation in the tested background, whereas active-site-cysteine variants retain low production and can benefit from exogenous thiols.
PMID:20544959
Structural and functional characterization of CcmG from Pseudomonas aeruginosa, a key component of the bacterial cytochrome c maturation apparatus.
Purified soluble P. aeruginosa CcmG supports reductase chemistry and a proposed CcmH-linked substrate; this is comparative support, not a KT2440 experiment.
PMID:28634234
The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochrome c maturation.
Soluble RHOCB-derived CcmG directly reduces relevant disulfide substrates; strain and truncation limits are documented in the helX review.
PMID:18786143
Compensatory thio-redox interactions between DsbA, CcdA and CcmG unveil the apocytochrome c holdase role of CcmG during cytochrome c maturation.
In Rhodobacter DsbA-null backgrounds, CcmG/CcdA redox requirements can be bypassed, while thiol-inactive CcmG improves maturation and binds apocytochrome in vitro; CcmH remains required under those tested conditions.
CcmH redox component
ccmh_redox_component
Participant: Family: CcmH cytochrome-c-maturation family
Family:
CcmH cytochrome-c-maturation familyPANTHER:PTHR47870:SF1
Representative Members: CcmH (Escherichia coli K-12)UniProtKB:P0ABM9 CcmH (Pseudomonas putida KT2440)UniProtKB:A0A140FWM4 ccl2 (Rhodobacter capsulatus SB 1003)UniProtKB:Q00501

A redox-active CcmH component forms mixed disulfides with apocytochrome and contributes to stereospecific heme ligation. CcmH architecture and curated role must be checked because its PANTHER SF1 also includes the distinct TPR accessory CcmI. A net standalone reductase activity is not generalized.

PMID:28634234
The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochrome c maturation.
Rhodobacter CcmH mixed-disulfide chemistry and stereospecific substrate handling are distinguished from CcmG thioreduction; soluble constructs and engineered strain backgrounds limit transfer.

Connections

Part 3: covalent heme ligation to reduced apocytochrome
CcmF/CcmH heme-ligation machineryBiological Processccmfh_heme_ligation

CcmF and redox-active CcmH contribute to stereospecific covalent heme attachment in canonical System I. A separate CcmI accessory associates in Rhodobacter; E. coli instead has a fused CcmH accessory domain. GO:0004408 is asserted for the collective assembly, not isolated F or H.

Part 1: holocytochrome-c synthase complex
CcmF/CcmH holocytochrome-c synthase complexProtein Complexccmfh_ligation_complex

Annotons

CcmF/CcmH holocytochrome-c synthase activity
ccmfh_synthetase_activity
Participant: Protein Complex: bacterial CcmF/CcmH heme-ligation complex
Protein Complex:
bacterial CcmF/CcmH heme-ligation complex
Active units:
CcmF catalytic subunit
Participant: Family: CcmF cytochrome-c-maturation family
Family:
CcmF cytochrome-c-maturation familyPANTHER:PTHR43653:SF1
Representative Members: CcmF (Escherichia coli K-12)UniProtKB:P33927 CcmF (Pseudomonas putida KT2440)UniProtKB:Q88EY0 ccl1 (Rhodobacter capsulatus SB 1003)UniProtKB:Q00500
Role: Binds heme and forms the membrane catalytic core of the ligation machinery.
CcmH ligation subunit
Participant: Family: CcmH cytochrome-c-maturation family
Family:
CcmH cytochrome-c-maturation familyPANTHER:PTHR47870:SF1
Representative Members: CcmH (Escherichia coli K-12)UniProtKB:P0ABM9 CcmH (Pseudomonas putida KT2440)UniProtKB:A0A140FWM4 ccl2 (Rhodobacter capsulatus SB 1003)UniProtKB:Q00501
Role: Couples apocytochrome redox state and orientation to stereospecific heme attachment.
Required Function:
holocytochrome-c synthase activityGO:0004408

Function

holocytochrome-c synthase activityGO:0004408
Substrates: apocytochrome c with a reduced CXXCH motif heme supplied by holo-CcmE
Products: holocytochrome c

Processes

cytochrome c-heme linkageGO:0018063

Represents the complex-level ligase function without assigning holocytochrome-c synthase activity to CcmF or CcmH alone.

PMID:11744735
A bacterial cytochrome c heme lyase. CcmF forms a complex with the heme chaperone CcmE and CcmH but not with apocytochrome c.
E. coli CcmF interactions with CcmE/H and essential residues support a collective heme-ligation function.
PMID:18753134
The cytochrome c maturation components CcmF, CcmH, and CcmI form a membrane-integral multisubunit heme ligation complex.
Rhodobacter membrane-integral F/H/I association supports the complex architecture in the tested strains and tagged constructs, not a universal fixed stoichiometry.
PMID:24397552
The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE.
Engineered E. coli CcmFGH-only expression produces covalently attached, correctly processed holocytochromes without CcmABCDE, supporting terminal synthase chemistry in the CcmFH apparatus. Engineered heme/expression conditions do not establish that native cells ordinarily dispense with upstream delivery.
Part 2: lineage-dependent maturation accessory (optional)
CcmI/CycH-family accessory factorBiological Processccmi_cych_accessory

Annotons

CycH-family maturation accessory
cych_accessory_component
Participant: Family: Separate CcmI/CycH substrate-handling accessories within the mixed CcmH/CcmI family
Family:
Separate CcmI/CycH substrate-handling accessories within the mixed CcmH/CcmI familyPANTHER:PTHR47870
Representative Members: CycH (Pseudomonas putida KT2440)UniProtKB:A0A140FWM3 cycH (Rhodobacter capsulatus SB 1003)UniProtKB:D5ALI6

Processes

cytochrome c biosynthetic processGO:1903607

Separate TPR-rich accessory, distinct from redox CcmH despite overlapping PANTHER membership. Rhodobacter CcmI binds apocytochrome substrates in vitro; dependence varies with substrate and strain background. Pseudomonas assignment is orthology-based. E. coli provides a related accessory domain fused to CcmH.

PMID:21956106
CcmI subunit of CcmFHI heme ligation complex functions as an apocytochrome c chaperone during c-type cytochrome maturation.
Rhodobacter CcmI binds apocytochrome c; full-length tagged construct donor and domain-specific MT1131 cloning are distinguished in the individual review.
PMID:8231805
Formation of several bacterial c-type cytochromes requires a novel membrane-anchored protein that faces the periplasm.
Bradyrhizobium CycH disruption affects most tested c-type cytochromes but spares cytochrome c1; it does not establish universal absolute requirement.
G20-like cysteine-CcmE System I*Biological Processg20_like_cysteine_ccme_system_i_star

Experimentally reconstructed G20 ccmEFABCDI machinery, now assigned to Oleidesulfovibrio alaskensis G20. It matures heterologous cytochromes in E. coli EC06 lacking endogenous ccm genes, without cassette-encoded CcmG/H. CcmI enhances yield but is dispensable in that test. This is a tested architecture, not a claim that all cysteine-CcmE lineages omit CcmH or that native cells need no other reductants.

PMID:20466730
c-Type cytochrome biogenesis can occur via a natural Ccm system lacking CcmH, CcmG, and the heme-binding histidine of CcmE.
The G20 cassette produces mature heterologous c-type cytochromes without CcmG/H and uses Cys127-linked CcmE. CcmI deletion retains product; further CcmD deletion removes detectable product. Full-text donor/deletion evidence and corrected detection limits are recorded in the source analysis.
PMID:24044352
Probing heme delivery processes in cytochrome c biogenesis System I.
CcmA/F/C mutagenesis separates ATP-dependent heme handling from downstream ligation; the experimental CcmC residue numbering differs from the current reference sequence by 18 residues.

Connections

Part 1: heme handling and energy coupling
System I* heme handling and ATP couplingBiological Processistar_heme_handling_energy

Functional roles in the reconstructed cassette, without asserting an isolated obligate five-subunit complex or the canonical exclusive post-loading ATP timing.

Annotons

System I* ccmA
istar_ccma_atpase
Participant: Family: System I* ccmA role
Family:
System I* ccmA rolePANTHER:PTHR42939:SF1
Representative Members: ccmA (Oleidesulfovibrio alaskensis G20)UniProtKB:Q311X1

Function

ATP hydrolysis activityGO:0016887

Processes

cytochrome c-heme linkageGO:0018063

ATPase-class energy-coupling component. K41D eliminates detectable mature cytochrome and leaves about35% holo-CcmE, favoring a role before or concomitant with covalent loading; purified timing/rate was not measured.

PMID:24044352
Probing heme delivery processes in cytochrome c biogenesis System I.
G20 CcmA Walker-A perturbation supports ATP-dependent maturation and differs from canonical accumulation of holo-CcmE.
System I* ccmB
istar_ccmb_membrane_subunit
Participant: Family: System I* ccmB role
Family:
System I* ccmB roleInterPro:IPR003544
Representative Members: ccmB (Oleidesulfovibrio alaskensis G20)UniProtKB:Q311X2

Processes

cytochrome c-heme linkageGO:0018063

Conserved membrane-subunit role inferred from CcmB architecture and the functional reconstructed operon; neither an individual G20 deletion phenotype nor a membrane-crossing molecular activity is claimed.

PMID:20466730
c-Type cytochrome biogenesis can occur via a natural Ccm system lacking CcmH, CcmG, and the heme-binding histidine of CcmE.
CcmB is encoded in the functional G20 cassette; its specific mechanical role is inferred, not individually assayed in this reconstruction.
System I* ccmC
istar_ccmc_heme_handling_subunit
Participant: Family: System I* ccmC role
Family:
System I* ccmC rolePANTHER:PTHR30071:SF1
Representative Members: ccmC (Oleidesulfovibrio alaskensis G20)UniProtKB:Q311X3

Function

heme bindingGO:0020037

Processes

cytochrome c-heme linkageGO:0018063

Heme-handling component upstream of CcmE. Histidine mutants abolish detectable holo-CcmE and cytochrome; paper H68/H192 versus reference H50/H174 numbering remains unresolved.

PMID:24044352
Probing heme delivery processes in cytochrome c biogenesis System I.
Experimental CcmC histidine substitutions disrupt heme loading; donor locus is established but exact assayed full-sequence equivalence is not.
System I* ccmD
istar_ccmd_accessory_subunit
Participant: Family: System I* ccmD role
Family:
System I* ccmD roleInterPro:IPR030888
Representative Members: ccmD (Oleidesulfovibrio alaskensis G20)UniProtKB:F9XXF9

Processes

cytochrome c-heme linkageGO:0018063

Alternate small CcmD family. Further truncation from active ccmEFABCD to ccmEFABC loses detectable mature product, supporting requirement in the tested reconstruction; no isolated catalytic activity is assigned.

PMID:20466730
c-Type cytochrome biogenesis can occur via a natural Ccm system lacking CcmH, CcmG, and the heme-binding histidine of CcmE.
Sequential cassette truncations distinguish optional CcmI from required CcmD under the reported heterologous conditions; source analysis records the 2011 detection-limit correction.
System I* ccmE
istar_ccme_heme_chaperone
Participant: Family: System I* ccmE role
Family:
System I* ccmE rolePANTHER:PTHR34128:SF2
Representative Members: ccmE (Oleidesulfovibrio alaskensis G20)UniProtKB:Q311W9

Function

heme bindingGO:0020037

Processes

cytochrome c-heme linkageGO:0018063

Chemically participates in heme delivery through a covalent Cys127 linkage. Same family as canonical CcmE does not imply interchangeable linkage chemistry or compatibility.

PMID:20466730
c-Type cytochrome biogenesis can occur via a natural Ccm system lacking CcmH, CcmG, and the heme-binding histidine of CcmE.
Heme-containing peptide analysis and Cys127 variants support cysteine-linked CcmE; canonical and G20 CcmE proteins are not functionally interchangeable.
Part 2: covalent heme attachment
System I* terminal heme attachmentBiological Processistar_heme_ligation

Annotons

System I* ccmF
istar_ccmf_ligation_component
Participant: Family: System I* ccmF role
Family:
System I* ccmF rolePANTHER:PTHR43653:SF1
Representative Members: ccmF (Oleidesulfovibrio alaskensis G20)UniProtKB:Q311X0

Function

heme bindingGO:0020037

Processes

cytochrome c-heme linkageGO:0018063

Heme-binding membrane component that contributes to collective holocytochrome-c synthase activity (GO:0004408) in the reconstructed system without CcmH. Isolated F sufficiency, exact electron donor and a universally required quinol reaction are not established.

PMID:24044352
Probing heme delivery processes in cytochrome c biogenesis System I.
CcmF conserved-histidine mutations block cytochrome formation while altered holo-CcmE accumulation distinguishes loading and ligation roles; P147A retains maturation.
Part 3: maturation efficiency accessory (optional)
System I* accessory efficiency factorBiological Processistar_ccmi_accessory

Annotons

System I* ccmI
istar_ccmi_accessory_component
Participant: Family: System I* ccmI role
Family:
System I* ccmI role
Representative Members: ccmI (Oleidesulfovibrio alaskensis G20)UniProtKB:Q311X4

Processes

cytochrome c-heme linkageGO:0018063

Membrane-anchored TPR accessory whose deletion retains about20% mature cytochrome yield in the tested reconstruction. The broad Cdc27-labeled PANTHER placement is not used as a specific functional family assignment; descriptor intent and the verified representative are retained.

PMID:20466730
c-Type cytochrome biogenesis can occur via a natural Ccm system lacking CcmH, CcmG, and the heme-binding histidine of CcmE.
CcmI deletion reduces but does not eliminate mature c550, so this role is optional under the tested conditions.