CHAF1A

UniProt ID: Q13111
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

CHAF1A (p150) is the large subunit of Chromatin Assembly Factor 1 (CAF-1), a heterotrimeric histone H3-H4 chaperone composed of CHAF1A, CHAF1B (p60) and RBBP4 (p48). CAF-1 performs the first step of nucleosome assembly, depositing newly synthesized histones H3 and H4 (the replicative variant H3.1) onto DNA during replication-coupled and repair-coupled chromatin assembly; histones H2A/H2B are subsequently added to complete the octamer. CHAF1A binds histones H3-H4 directly and couples assembly to the replication fork by binding the sliding clamp PCNA via its N-terminal region. It also contains a PxVxL motif that binds the chromo shadow domain of HP1 (CBX5), contributing to heterochromatin maintenance by delivering newly synthesized HP1 proteins to heterochromatic replication foci. CHAF1A homodimerizes, an activity required for chromatin assembly, and acts in the nucleus, concentrating at DNA replication foci during S phase.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005634 nucleus
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: CHAF1A is a nuclear protein; as the large subunit of CAF-1 it assembles chromatin in the nucleus and concentrates at DNA replication foci during S phase. Nucleus is correct but is a broad localization term.
Reason: Nuclear localization is well-supported by direct experimental data and by the phylogenetic inference, but is a general cellular component term rather than the core histone chaperone function. More specific localization (chromatin, nucleoplasm) is captured by other annotations.
Supporting Evidence:
PMID:9614144
During S phase, p150 and p60 are concentrated at sites of intranuclear DNA replication.
file:human/CHAF1A/CHAF1A-uniprot.txt
SUBCELLULAR LOCATION; Nucleus. Note=DNA replication foci.
GO:0005634 nucleus
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Nuclear localization assigned by UniProt subcellular location keyword mapping. Consistent with experimental data but a broad term.
Reason: Correct localization but general; duplicates the IBA nucleus annotation and is less specific than the chromatin/nucleoplasm annotations.
Supporting Evidence:
file:human/CHAF1A/CHAF1A-uniprot.txt
SUBCELLULAR LOCATION; Nucleus.
GO:0005515 protein binding
IPI
PMID:15805117
Proliferating cell nuclear antigen (PCNA) may function as a ... 		MARK AS OVER ANNOTATED
Summary: This IPI annotation (WITH PCNA, P12004) reflects the biologically important CHAF1A-PCNA interaction that couples chromatin assembly to the replication fork, but is captured only by the uninformative generic term protein binding.
Reason: The bare protein binding term conveys no specific molecular function. The underlying PCNA interaction is biologically meaningful and is represented more informatively by a proposed PCNA binding annotation; the generic term should not be retained as a core function.
Supporting Evidence:
PMID:15805117
PCNA may function as a double homotrimer complex in the mammalian cell.
GO:0005515 protein binding
IPI
PMID:16826239
The replication kinase Cdc7-Dbf4 promotes the interaction of... 		MARK AS OVER ANNOTATED
Summary: IPI annotation (WITH PCNA, P12004) from the study showing Cdc7-Dbf4 phosphorylation of p150 promotes PCNA binding. Biologically meaningful but captured only by the generic protein binding term.
Reason: Bare protein binding is uninformative. The specific p150-PCNA interaction is better represented by a dedicated PCNA binding annotation.
Supporting Evidence:
PMID:16826239
its targeting to sites of DNA synthesis involves a physical interaction between its largest subunit, p150, and the homotrimeric sliding clamp, proliferating cell nuclear antigen (PCNA).
GO:0005515 protein binding
IPI
PMID:17474147
Systematic identification of SH3 domain-mediated human prote... 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from a high-throughput SH3 domain peptide array screen (WITH NCK1, PIK3R1). No specific function conveyed.
Reason: Generic protein binding from a large-scale interaction screen does not represent a specific molecular function and these interactions are not part of the core histone chaperone activity.
Supporting Evidence:
PMID:17474147
Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.
GO:0005515 protein binding
IPI
PMID:19498464
The HP1alpha-CAF1-SetDB1-containing complex provides H3K9me1... 		MARK AS OVER ANNOTATED
Summary: IPI annotation (WITH CBX5/HP1alpha, P45973) from the HP1alpha-CAF1-SetDB1 study. Reflects the HP1 interaction but only via the generic protein binding term.
Reason: Bare protein binding is uninformative. The CHAF1A-HP1 (CBX5) interaction is captured more specifically by the chromo shadow domain binding annotation.
Supporting Evidence:
PMID:19498464
the histone H3K9 methyltransferase SetDB1 associates with the specific heterochromatin protein 1alpha (HP1alpha)-chromatin assembly factor 1 (CAF1) chaperone complex.
GO:0005515 protein binding
IPI
PMID:20562864
Human POGZ modulates dissociation of HP1alpha from mitotic c... 		MARK AS OVER ANNOTATED
Summary: IPI annotation (WITH CBX5, P45973) from the POGZ/HP1alpha study, which also mapped the V240/L242 PxVxL residues required for CBX5 binding. Captured only by generic protein binding.
Reason: Bare protein binding is uninformative. The CHAF1A-CBX5 interaction is represented specifically by the chromo shadow domain binding annotation.
Supporting Evidence:
PMID:20562864
Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation.
GO:0005515 protein binding
IPI
PMID:20936779
A human MAP kinase interactome. 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from a large-scale MAP kinase interactome screen (WITH YWHAE/14-3-3 epsilon). No specific function conveyed.
Reason: Generic protein binding from a high-throughput interactome map; not a specific molecular function and not part of the core activity.
Supporting Evidence:
PMID:20936779
A human MAP kinase interactome.
GO:0005515 protein binding
IPI
PMID:21570500
The p150 subunit of the histone chaperone Caf-1 interacts wi... 		MARK AS OVER ANNOTATED
Summary: IPI annotation (WITH GFI1, Q99684) showing p150 is part of the Gfi1 transcriptional repression complex; the same study confirms p150 binds histones H3 and H4 directly. The Gfi1 interaction itself is captured only by generic protein binding.
Reason: The bare protein binding term for the Gfi1 interaction is uninformative. The biologically core histone H3/H4 binding demonstrated in this paper is captured by a proposed histone binding annotation rather than this generic term.
Supporting Evidence:
PMID:21570500
Since p150 binds directly to histones H3 and H4, our findings suggest that p150 may link the DNA-bound Gfi1 repressor complex to histones enabling modifications required for transcriptional silencing.
GO:0005515 protein binding
IPI
PMID:23075851
DAXX envelops a histone H3.3-H4 dimer for H3.3-specific reco... 		MARK AS OVER ANNOTATED
Summary: IPI annotation (WITH histones H3-3B/H3C15) from a DAXX-H3.3 structural study. Although histone partners are involved, this is a DAXX-focused study and the annotation is captured only by generic protein binding.
Reason: Bare protein binding is uninformative. CHAF1A histone H3-H4 binding is better represented by a dedicated histone binding annotation supported by direct CAF-1 studies.
Supporting Evidence:
PMID:23075851
DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.
GO:0005515 protein binding
IPI
PMID:24981860
Human-chromatin-related protein interactions identify a deme... 		MARK AS OVER ANNOTATED
Summary: IPI annotation (WITH CBX5, P45973) from a chromatin-protein interaction study. Reflects the HP1 interaction but only via generic protein binding.
Reason: Bare protein binding is uninformative; the CHAF1A-CBX5 interaction is captured specifically by chromo shadow domain binding.
Supporting Evidence:
PMID:24981860
Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from a proteome-scale binary interactome map. No specific function conveyed.
Reason: Generic protein binding from a high-throughput interactome study; not a specific molecular function.
Supporting Evidence:
PMID:25416956
A proteome-scale map of the human interactome network.
GO:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz... 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from a quantitative interactome study (WITH PCNA, PIK3R1). No specific function conveyed by the generic term.
Reason: Generic protein binding from a high-throughput interactome map; the PCNA interaction is better captured by a dedicated PCNA binding annotation.
Supporting Evidence:
PMID:26496610
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
GO:0005515 protein binding
IPI
PMID:27705803
A High-Density Map for Navigating the Human Polycomb Complex... 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from a Polycomb complexome map (WITH CBX5). No specific function conveyed.
Reason: Generic protein binding from a high-throughput complexome study; not a specific molecular function.
Supporting Evidence:
PMID:27705803
A High-Density Map for Navigating the Human Polycomb Complexome.
GO:0005515 protein binding
IPI
PMID:31980649
Extensive rewiring of the EGFR network in colorectal cancer ... 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from an EGFR/KRAS network rewiring study (WITH YWHAE). No specific function conveyed.
Reason: Generic protein binding from a large-scale network study; not a specific molecular function and not part of the core activity.
Supporting Evidence:
PMID:31980649
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from a reference binary interactome map (multiple partners). No specific function conveyed.
Reason: Generic protein binding from a high-throughput binary interactome study; not a specific molecular function.
Supporting Evidence:
PMID:32296183
A reference map of the human binary protein interactome.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from a proteome-scale interactome study (WITH histone H3-3B). No specific function conveyed by the generic term.
Reason: Generic protein binding from a high-throughput interactome map; histone binding is better captured by a dedicated annotation.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		MARK AS OVER ANNOTATED
Summary: Bare protein binding from the OpenCell endogenous-tagging interactome (WITH YWHAE). No specific function conveyed.
Reason: Generic protein binding from a high-throughput cartography study; not a specific molecular function.
Supporting Evidence:
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
GO:0042802 identical protein binding
IPI
PMID:16826239
The replication kinase Cdc7-Dbf4 promotes the interaction of... 		ACCEPT
Summary: IPI annotation (WITH CHAF1A, Q13111) capturing the homodimerization of p150. CHAF1A is a homodimer, and dimerization is required for competence for chromatin assembly.
Reason: Identical protein binding accurately represents the well-documented p150 homodimerization, which is functionally important for chromatin assembly.
Supporting Evidence:
file:human/CHAF1A/CHAF1A-uniprot.txt
SUBUNIT; Homodimer. REGION 642..678; Necessary for homodimerization and competence for chromatin assembly.
GO:0006335 DNA replication-dependent chromatin assembly
IDA
PMID:14718166
Histone H3.1 and H3.3 complexes mediate nucleosome assembly ... 		ACCEPT
Summary: CAF-1 (with the replicative histone variant H3.1) mediates DNA-synthesis-dependent nucleosome assembly. This is the core biological process for CHAF1A.
Reason: Directly supported by experimental data distinguishing CAF-1/H3.1 (replication-coupled) from HIRA/H3.3 (replication-independent) assembly; represents the core function.
Supporting Evidence:
PMID:14718166
The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome assembly, respectively.
GO:0005654 nucleoplasm
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: Immunofluorescence (HPA) localizes CHAF1A to the nucleoplasm, consistent with its nuclear histone chaperone role.
Reason: Accurate subcellular localization but a general component term, not the core molecular function.
Supporting Evidence:
file:human/CHAF1A/CHAF1A-uniprot.txt
SUBCELLULAR LOCATION; Nucleus. Note=DNA replication foci.
GO:0000785 chromatin
IDA
PMID:9614144
Nucleosome assembly activity and intracellular localization ... 		ACCEPT
Summary: CHAF1A localizes to chromatin, concentrating at intranuclear DNA replication foci during S phase, consistent with deposition of histones onto replicating DNA.
Reason: Direct experimental localization to chromatin/replication sites is well-supported and biologically appropriate for a histone chaperone acting at the replication fork.
Supporting Evidence:
PMID:9614144
During S phase, p150 and p60 are concentrated at sites of intranuclear DNA replication.
GO:0006335 DNA replication-dependent chromatin assembly
IDA
PMID:9614144
Nucleosome assembly activity and intracellular localization ... 		ACCEPT
Summary: CAF-1 nucleosome assembly activity is cell-cycle regulated, and active CAF-1 (isolated as a 6.5S complex) deposits histones at S-phase replication foci. Core biological process for CHAF1A.
Reason: Directly supported experimental evidence for replication-coupled chromatin assembly; represents the core function.
Supporting Evidence:
PMID:9614144
Active CAF-1 can be isolated as a 6.5 S complex from G1, S, and G2 phase nuclei.
GO:0033186 CAF-1 complex
IPI
PMID:9614144
Nucleosome assembly activity and intracellular localization ... 		ACCEPT
Summary: CHAF1A (p150) is a constitutive subunit of the CAF-1 complex together with CHAF1B (p60) and RBBP4 (p48). Core complex membership.
Reason: Well-established as the large subunit of the heterotrimeric CAF-1 complex; directly supported.
Supporting Evidence:
PMID:9614144
Active CAF-1 can be isolated as a 6.5 S complex from G1, S, and G2 phase nuclei.
file:human/CHAF1A/CHAF1A-uniprot.txt
SUBUNIT; Part of the CAF-1 complex that contains RBBP4, CHAF1B and CHAF1A.
GO:0006335 DNA replication-dependent chromatin assembly
IDA
PMID:8858152
Nucleosome assembly by a complex of CAF-1 and acetylated his... 		ACCEPT
Summary: A complex of CAF-1 and acetylated histones H3/H4 carries out nucleosome assembly. Core biological process.
Reason: Direct experimental demonstration of CAF-1-mediated nucleosome assembly with newly synthesized acetylated histones; core function.
Supporting Evidence:
PMID:8858152
Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
GO:0032991 protein-containing complex
IDA
PMID:14718166
Histone H3.1 and H3.3 complexes mediate nucleosome assembly ... 		MARK AS OVER ANNOTATED
Summary: CHAF1A is part of a protein complex (the H3.1-CAF-1 histone chaperone complex). This is a very general complex term.
Reason: The generic protein-containing complex term is uninformative; the specific CAF-1 complex membership is captured by the GO:0033186 annotations.
Supporting Evidence:
PMID:14718166
Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis.
GO:0000785 chromatin
IDA
PMID:14718166
Histone H3.1 and H3.3 complexes mediate nucleosome assembly ... 		ACCEPT
Summary: CHAF1A/CAF-1 associates with chromatin in the context of H3.1 deposition onto replicating DNA.
Reason: Direct experimental localization to chromatin is appropriate for a histone chaperone depositing histones onto DNA.
Supporting Evidence:
PMID:14718166
The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA.
GO:0033186 CAF-1 complex
IDA
PMID:8858152
Nucleosome assembly by a complex of CAF-1 and acetylated his... 		ACCEPT
Summary: CHAF1A is part of the CAF-1 chromatin assembly complex (CAC) containing p150, p60 and p48. Core complex membership.
Reason: Directly supported membership in the heterotrimeric CAF-1 complex; core.
Supporting Evidence:
PMID:8858152
a chromatin assembly complex (CAC), which contains the three subunits of CAF-1 (p150, p60, p48).
GO:0070087 chromo shadow domain binding
IPI
PMID:15882967
The mammalian heterochromatin protein 1 binds diverse nuclea... 		ACCEPT
Summary: CHAF1A p150 carries a PxVxL motif that binds directly and with high affinity to the chromo shadow domain of HP1 (CBX5), mediating recruitment of HP1 to heterochromatic replication foci.
Reason: Specific, experimentally supported molecular function (PxVxL-chromo shadow domain binding) underlying CHAF1A's role in heterochromatin maintenance.
Supporting Evidence:
PMID:15882967
KAP-1, CAF-1 p150, and NIPBL carry a canonical amino acid motif, PxVxL, which binds directly to the CSD with high affinity.
GO:0003682 chromatin binding
TAS
PMID:7600578
The p150 and p60 subunits of chromatin assembly factor I: a ... 		ACCEPT
Summary: CHAF1A binds chromatin, consistent with its function depositing histones onto replicating DNA as the large subunit of CAF-1.
Reason: Supported molecular function; CHAF1A engages chromatin/DNA during nucleosome assembly.
Supporting Evidence:
PMID:7600578
The p150 and p60 subunits of chromatin assembly factor I; a molecular link between newly synthesized histones and DNA replication.
GO:0042393 histone binding
IC
PMID:21570500
The p150 subunit of the histone chaperone Caf-1 interacts wi... 		NEW
Summary: Proposed annotation not present in the current GOA for CHAF1A.
Reason: CHAF1A p150 binds directly to histones H3 and H4 (including the replicative variants H3.1, H3.2 and H3.1t), the core substrate-recognition activity of its histone chaperone function, yet there is no histone binding MF annotation; the histone interactions are currently captured only by generic protein binding.
Supporting Evidence:
PMID:21570500
p150 binds directly to histones H3 and H4.
file:human/CHAF1A/CHAF1A-uniprot.txt
Interacts with histones H3.1, H3.2 and H3.1t (PubMed:33857403).
GO:0140713 histone chaperone activity
IC
PMID:8858152
Nucleosome assembly by a complex of CAF-1 and acetylated his... 		NEW
Summary: Proposed annotation not present in the current GOA for CHAF1A.
Reason: As the large subunit of CAF-1, CHAF1A directly mediates histone chaperone activity (escorting and depositing H3-H4), which is its core molecular function but is not currently annotated as a molecular function term.
Supporting Evidence:
PMID:8858152
Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
PMID:14718166
The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA.
GO:0006334 nucleosome assembly
IC
file:human/CHAF1A/CHAF1A-uniprot.txt 		NEW
Summary: Proposed annotation not present in the current GOA for CHAF1A.
Reason: CHAF1A drives nucleosome assembly; this BP is asserted by UniProt GO refs (IDA, GO_Central) but is absent from the current GOA set and complements the more specific DNA replication-dependent chromatin assembly term.
Supporting Evidence:
file:human/CHAF1A/CHAF1A-uniprot.txt
GO:0006334; P:nucleosome assembly; IDA:GO_Central.

Core Functions

Histone H3-H4 chaperone that, as the large p150 subunit of the CAF-1 complex, deposits newly synthesized histones H3.1-H4 onto DNA to perform the first step of replication-coupled (and repair-coupled) nucleosome assembly.

Molecular Function:
histone chaperone activity
Directly Involved In:
DNA replication-dependent chromatin assembly
In Complex:
CAF-1 complex
Supporting Evidence:
  • PMID:7600578
    The p150 and p60 subunits of chromatin assembly factor I; a molecular link between newly synthesized histones and DNA replication.
  • PMID:8858152
    Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
  • PMID:14718166
    The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome assembly, respectively.

Couples chromatin assembly to the replication fork by directly binding the sliding clamp PCNA via its N-terminal region, targeting CAF-1 to sites of DNA synthesis.

Supporting Evidence:
  • PMID:16826239
    its targeting to sites of DNA synthesis involves a physical interaction between its largest subunit, p150, and the homotrimeric sliding clamp, proliferating cell nuclear antigen (PCNA).
  • file:human/CHAF1A/CHAF1A-uniprot.txt
    REGION 1..49; Binds to PCNA. SUBUNIT; Interacts with PCNA; the interaction is direct.

Contributes to heterochromatin maintenance by binding the chromo shadow domain of HP1 (CBX5) through its PxVxL motif, delivering newly synthesized HP1 proteins to heterochromatic replication foci.

Molecular Function:
chromo shadow domain binding
Supporting Evidence:
  • PMID:15882967
    KAP-1, CAF-1 p150, and NIPBL carry a canonical amino acid motif, PxVxL, which binds directly to the CSD with high affinity.

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
PMID:14718166
Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis.
PMID:15805117
Proliferating cell nuclear antigen (PCNA) may function as a double homotrimer complex in the mammalian cell.
PMID:15882967
The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain.
PMID:16826239
The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit of chromatin assembly factor 1 with proliferating cell nuclear antigen.
PMID:17474147
Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.
PMID:19498464
The HP1alpha-CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin.
PMID:20562864
Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation.
PMID:20936779
A human MAP kinase interactome.
PMID:21570500
The p150 subunit of the histone chaperone Caf-1 interacts with the transcriptional repressor Gfi1.
PMID:23075851
DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.
PMID:24981860
Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:26496610
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
PMID:27705803
A High-Density Map for Navigating the Human Polycomb Complexome.
PMID:31980649
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
PMID:32296183
A reference map of the human binary protein interactome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:7600578
The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication.
PMID:8858152
Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
PMID:9614144
Nucleosome assembly activity and intracellular localization of human CAF-1 changes during the cell division cycle.
PMID:33857403
DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network.
file:human/CHAF1A/CHAF1A-uniprot.txt
UniProtKB Q13111 CHAF1A record

Suggested Questions for Experts

Q: How is CHAF1A-mediated histone deposition coordinated with the upstream histone supply chaperones (ASF1A/ASF1B) and the downstream H2A/H2B deposition machinery during a single round of replication?

Q: To what extent is the heterochromatin-maintenance role of CHAF1A (via HP1/CBX5 delivery) separable from its bulk replication-coupled nucleosome assembly function?

Suggested Experiments

Experiment: Acute degron-mediated depletion of CHAF1A in synchronized cells followed by nascent-chromatin (NCC/iPOND) proteomics and MNase-seq to quantify the kinetics of replication-coupled H3.1-H4 deposition and nucleosome maturation genome-wide.

Experiment: Structure-guided separation-of-function mutants disrupting the PCNA-binding region (1-49), the PxVxL/HP1 motif (V240/L242), or the homodimerization region (642-678), assayed for in vitro nucleosome assembly and for heterochromatin re-establishment after replication.

📚 Additional Documentation

Notes

(CHAF1A-notes.md)

CHAF1A (Q13111) review notes

Identity

  • CHAF1A = Chromatin Assembly Factor 1 subunit A, the large p150 subunit of CAF-1 (also CAF-I p150, hp150). HGNC:1910, UniProt Q13111, 956 aa, chromosome 19.
  • CAF-1 is a heterotrimeric histone H3-H4 chaperone composed of CHAF1A (p150), CHAF1B (p60), and RBBP4 (p48) [PMID:7600578 "Chromatin assembly factor I (CAF-I) from human cell nuclei is a three-subunit protein complex that assembles histone octamers onto replicating DNA in a cell-free system"; PMID:8858152 "a chromatin assembly complex (CAC), which contains the three subunits of CAF-1 (p150, p60, p48)"].

Core function: replication-coupled nucleosome/chromatin assembly

  • CAF-1 performs the first step of nucleosome assembly, depositing newly synthesized histones H3 and H4 onto replicating DNA; H2A/H2B are added subsequently [UniProt FUNCTION; PMID:7600578 "p150 and p60 form complexes with newly synthesized histones H3 and acetylated H4 in human cell extracts, suggesting that such complexes are intermediates between histone synthesis and assembly onto replicating DNA"].
  • CAF-1 mediates DNA-synthesis-coupled nucleosome assembly specifically with the replicative histone variant H3.1 (vs HIRA which uses H3.3 for replication-independent deposition) [PMID:14718166 "The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome assembly, respectively"; "these complexes possess one molecule each of H3.1/H3.3 and H4"].
  • p150 directly interacts with p60 (CHAF1B) and this is required for assembly; deletion of the p60-binding domain abolishes chromatin assembly PMID:7600578.
  • CAF-1 activity is cell-cycle regulated; in S phase p150 and p60 concentrate at intranuclear DNA replication foci; active CAF-1 isolated as a 6.5S complex in G1/S/G2 [PMID:9614144 "During S phase, p150 and p60 are concentrated at sites of intranuclear DNA replication"; "Active CAF-1 can be isolated as a 6.5 S complex from G1, S, and G2 phase nuclei"].
  • p150 directly binds histones H3.1, H3.2 and H3.1t [UniProt SUBUNIT, PMID:33857403] and histones H3 and H4 PMID:21570500.

Coupling to replication fork: PCNA

  • CAF-1 is recruited to sites of DNA synthesis through direct interaction of p150 with PCNA, the sliding clamp [UniProt SUBUNIT "Interacts with PCNA; the interaction is direct"; PMID:16826239 "its targeting to sites of DNA synthesis involves a physical interaction between its largest subunit, p150, and the homotrimeric sliding clamp, proliferating cell nuclear antigen (PCNA)"]. PCNA-binding region is residues 1-49 (UniProt FT REGION 1..49 "Binds to PCNA").
  • The Cdc7-Dbf4 kinase phosphorylates p150 in S phase, shifting it toward a monomer that binds PCNA, coupling assembly to origin firing PMID:16826239.
  • PMID:15805117 (PCNA double-trimer) shows CAF-1 + Pol delta can be simultaneously accommodated on a PCNA double trimer; this is the IPI annotation source (WITH PCNA P12004) supporting bare protein binding.
  • The IPI on PMID:16826239 (identical protein binding, WITH Q13111) supports p150 homodimerization, consistent with UniProt "Homodimer" [PMID:11296234 dimerization, EMBO J].

Heterochromatin / HP1

  • p150 contains a PxVxL motif (residues 233-246) that directly binds the chromo shadow domain (CSD) of HP1 proteins (CBX5/HP1alpha) PMID:15882967. Mutation of V240/L242 abolishes CBX5 binding [UniProt MUTAGEN, PMID:20562864].
  • CAF-1 may bring newly synthesized CBX/HP1 proteins to heterochromatic DNA replication foci, contributing to heterochromatin maintenance [UniProt FUNCTION "It may play a role in heterochromatin maintenance in proliferating cells by bringing newly synthesized cbx proteins to heterochromatic DNA replication foci"].
  • HP1alpha-CAF1-SetDB1 complex monomethylates non-nucleosomal H3K9, proposed to provide H3K9me1 for Suv39-mediated K9me3 at pericentric heterochromatin during replication PMID:19498464. (Note: the related MBD1-SetDB1 paper PMID:15327775 was RETRACTED, PMID:30849389; UniProt CAUTION.)

Repair-coupled assembly

  • CAF-1 is the only characterized histone chaperone promoting nucleosome assembly coupled both to DNA replication and to nucleotide excision repair (DNA synthesis at repair sites) PMID:16826239. Supports DNA repair (GO:0006281) keyword/IEA.

Other interactions (context, not core MF)

  • Transcriptional repressor Gfi1: p150 is part of the Gfi1/LSD1/HDAC1 repression complex, may link DNA-bound repressor to histones PMID:21570500.
  • MBD1 [UniProt SUBUNIT, PMID:12697822].

Bare protein-binding (GO:0005515) IPI annotations

Many GOA protein binding IPI annotations derive from high-throughput interactome screens and large-scale studies, which do not convey a specific molecular function:
- PMID:17474147 (SH3 domain peptide array; WITH NCK1 P16333, PIK3R1 P27986)
- PMID:20936779 (MAP kinase interactome; WITH YWHAE P62258)
- PMID:23075851 (DAXX/H3.3 structure; WITH H3-3B P84243, H3C15 Q71DI3) — histone partners but from a DAXX-focused study
- PMID:24981860 (chromatin protein interactions; WITH CBX5 P45973)
- PMID:25416956, PMID:26496610, PMID:32296183, PMID:33961781 (proteome-scale interactome maps)
- PMID:27705803 (Polycomb complexome)
- PMID:31980649 (EGFR/KRAS network)
- PMID:35271311 (OpenCell endogenous tagging)
These are best treated as MARK_AS_OVER_ANNOTATED for the bare protein binding term. The specific, biologically meaningful binding activities (histone H3-H4 binding, HP1 chromo shadow domain binding, PCNA binding) are captured by dedicated annotations or should be added as more informative MF terms.

Specific MF/CC/BP terms supported

  • Histone binding (GO:0042393): directly binds H3.1/H3.2/H3.1t and H3/H4 [PMID:33857403; PMID:21570500].
  • H3-H4 histone complex chaperone activity (GO:0000510) / histone chaperone activity (GO:0140713): CAF-1 is the H3-H4 chaperone [PMID:7600578; PMID:14718166].
  • chromo shadow domain binding (GO:0070087): PxVxL-CSD binding to HP1 PMID:15882967.
  • chromatin binding (GO:0003682): TAS PMID:7600578.
  • CAF-1 complex (GO:0033186): part_of [PMID:9614144, PMID:8858152].
  • DNA replication-dependent chromatin assembly (GO:0006335): IDA [PMID:14718166, PMID:9614144, PMID:8858152].
  • nucleosome assembly (GO:0006334): supported, present in UniProt GO refs (IDA GO_Central).
  • nucleus (GO:0005634) / nucleoplasm (GO:0005654) / chromatin (GO:0000785): subcellular localization, DNA replication foci [PMID:9614144; UniProt SUBCELLULAR LOCATION].

Conclusion

Core function = histone H3-H4 chaperone (large p150 subunit of CAF-1) mediating replication-coupled (and repair-coupled) nucleosome/chromatin assembly, coupled to the replication fork via direct PCNA binding, and contributing to heterochromatin maintenance via HP1 (chromo shadow domain) binding.

Pn Notes

(CHAF1A-pn-notes.md)

CHAF1A PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q13111
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: CHAF1A (p150) is the large subunit of Chromatin Assembly Factor 1 (CAF-1), a heterotrimeric histone H3-H4 chaperone composed of CHAF1A, CHAF1B (p60) and RBBP4 (p48). CAF-1 performs the first step of nucleosome assembly, depositing newly synthesized histones H3 and H4 (the replicative variant H3.1) onto DNA during replication-coupled and repair-coupled chromatin assembly; histones H2A/H2B are subsequently added to complete the octamer. CHAF1A binds histones H3-H4 directly and couples assembly to the replication fork by binding the sliding clamp PCNA via its N-terminal region. It also contains a PxVxL motif that binds the chromo shadow domain of HP1 (CBX5), contributing to heterochromatin maintenance by delivering newly synthesized HP1 proteins to heterochromatic replication foci. CHAF1A homodimerizes, an activity required for chromatin assembly, and acts in the nucleus, concentrating at DNA replication foci during S phase.
  • Existing/core annotation action counts: ACCEPT: 10; KEEP_AS_NON_CORE: 3; MARK_AS_OVER_ANNOTATED: 17; NEW: 3

PN Consistency Summary

  • Consistency: Strong. Review, notes, PN annotation and node mapping all agree CHAF1A (p150) is the large subunit of the CAF-1 H3-H4 histone chaperone, depositing H3.1-H4 in replication-coupled nucleosome assembly. The review already carries GO:0140713 "histone chaperone activity" as a NEW (IC) annotation — exactly matching the PN projection. No contradictions.
  • PN story / NEW pressure: PN projects GO:0140713 (verified real; in CHAF1A/B reviews already) as new_to_goa — confirmed: GOA captures histone interactions only as bare protein binding / chromatin binding, with no MF histone-chaperone term. Already independently flagged ADD in the review (NEW GO:0140713, plus NEW GO:0042393 histone binding and GO:0006334 nucleosome assembly). PN and review converge; nothing over-reaches.
  • Evidence alignment: PN row carries no explicit reference list, but the projected MF rests on the same CAF-1 biology the review documents with PMID:8858152, PMID:14718166, PMID:7600578, PMID:21570500 (direct H3/H4 binding). Concordant; no divergence.
  • Verdict: CONSISTENT — PN GO:0140713 already captured by the review's NEW annotation. Recommended edits: none (review and PN aligned).

Full Consistency Review

  • UniProt: Q13111 · batch: proteostasis-batch-2026-06-07 · review status: COMPLETE
  • PN placement: Nuclear proteostasis|Chaperone|Histone chaperone ; PN-node mapping: Histone-chaperone group→GO:0140713 histone chaperone activity (new_to_goa). Chaperone class + NU branch = no_mapping.
  • Consistency: Strong. Review, notes, PN annotation and node mapping all agree CHAF1A (p150) is the large subunit of the CAF-1 H3-H4 histone chaperone, depositing H3.1-H4 in replication-coupled nucleosome assembly. The review already carries GO:0140713 "histone chaperone activity" as a NEW (IC) annotation — exactly matching the PN projection. No contradictions.
  • PN story / NEW pressure: PN projects GO:0140713 (verified real; in CHAF1A/B reviews already) as new_to_goa — confirmed: GOA captures histone interactions only as bare protein binding / chromatin binding, with no MF histone-chaperone term. Already independently flagged ADD in the review (NEW GO:0140713, plus NEW GO:0042393 histone binding and GO:0006334 nucleosome assembly). PN and review converge; nothing over-reaches.
  • Mapping strategy: Node mapping is correctly placed at the "Histone chaperone" group (narrower than generic "Nuclear proteostasis"/"Chaperone"), aligning to a precise MF (GO:0140713) rather than a broad process — appropriate, not TOMM20/HSPA8-style over-broad. No change needed.
  • Evidence alignment: PN row carries no explicit reference list, but the projected MF rests on the same CAF-1 biology the review documents with PMID:8858152, PMID:14718166, PMID:7600578, PMID:21570500 (direct H3/H4 binding). Concordant; no divergence.
  • Verdict: CONSISTENT — PN GO:0140713 already captured by the review's NEW annotation. Recommended edits: none (review and PN aligned).

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07
  • review_yaml: genes/human/CHAF1A/CHAF1A-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Nuclear proteostasis | Chaperone | Histone chaperone

  • UniProt: Q13111
  • In branches: NU
  • PN-node mapping records (path + ancestors):
    • [group] Nuclear proteostasis|Chaperone|Histone chaperone
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0140713 histone chaperone activity]
      rationale: This PN group collects nuclear histone-chaperone factors involved in histone handling, deposition, or exchange. The PN bucket is narrower than general nuclear proteostasis and aligns well with the GO molecular function histone chaperone activity.
    • [class] Nuclear proteostasis|Chaperone
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the nuclear chaperone class. The current member set includes histone chaperone and nuclear proteostasis context, but the class is not a single GO-equivalent activity; the histone-chaperone child mapping carries the defensible propagation.
    • [branch] Nuclear proteostasis
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (1)

  • GO:0140713 histone chaperone activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Nuclear proteostasis|Chaperone|Histone chaperone

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q13111
gene_symbol: CHAF1A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: CHAF1A (p150) is the large subunit of Chromatin Assembly Factor 1 (CAF-1),
  a heterotrimeric histone H3-H4 chaperone composed of CHAF1A, CHAF1B (p60) and RBBP4
  (p48). CAF-1 performs the first step of nucleosome assembly, depositing newly synthesized
  histones H3 and H4 (the replicative variant H3.1) onto DNA during replication-coupled
  and repair-coupled chromatin assembly; histones H2A/H2B are subsequently added to
  complete the octamer. CHAF1A binds histones H3-H4 directly and couples assembly to
  the replication fork by binding the sliding clamp PCNA via its N-terminal region.
  It also contains a PxVxL motif that binds the chromo shadow domain of HP1 (CBX5),
  contributing to heterochromatin maintenance by delivering newly synthesized HP1
  proteins to heterochromatic replication foci. CHAF1A homodimerizes, an activity
  required for chromatin assembly, and acts in the nucleus, concentrating at DNA
  replication foci during S phase.
alternative_products:
- name: '1'
  id: Q13111-1
- name: '2'
  id: Q13111-2
  sequence_note: VSP_004149, VSP_004150
- name: '3'
  id: Q13111-3
  sequence_note: VSP_004151
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: CHAF1A is a nuclear protein; as the large subunit of CAF-1 it assembles
      chromatin in the nucleus and concentrates at DNA replication foci during S phase.
      Nucleus is correct but is a broad localization term.
    action: KEEP_AS_NON_CORE
    reason: Nuclear localization is well-supported by direct experimental data and
      by the phylogenetic inference, but is a general cellular component term rather
      than the core histone chaperone function. More specific localization (chromatin,
      nucleoplasm) is captured by other annotations.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: During S phase, p150 and p60 are concentrated at sites of
        intranuclear DNA replication.
    - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
      supporting_text: SUBCELLULAR LOCATION; Nucleus. Note=DNA replication foci.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear localization assigned by UniProt subcellular location keyword
      mapping. Consistent with experimental data but a broad term.
    action: KEEP_AS_NON_CORE
    reason: Correct localization but general; duplicates the IBA nucleus annotation
      and is less specific than the chromatin/nucleoplasm annotations.
    supported_by:
    - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
      supporting_text: SUBCELLULAR LOCATION; Nucleus.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15805117
  qualifier: enables
  review:
    summary: This IPI annotation (WITH PCNA, P12004) reflects the biologically important
      CHAF1A-PCNA interaction that couples chromatin assembly to the replication
      fork, but is captured only by the uninformative generic term protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: The bare protein binding term conveys no specific molecular function.
      The underlying PCNA interaction is biologically meaningful and is represented
      more informatively by a proposed PCNA binding annotation; the generic term
      should not be retained as a core function.
    supported_by:
    - reference_id: PMID:15805117
      supporting_text: PCNA may function as a double homotrimer complex in the mammalian
        cell.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16826239
  qualifier: enables
  review:
    summary: IPI annotation (WITH PCNA, P12004) from the study showing Cdc7-Dbf4
      phosphorylation of p150 promotes PCNA binding. Biologically meaningful but
      captured only by the generic protein binding term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative. The specific p150-PCNA interaction
      is better represented by a dedicated PCNA binding annotation.
    supported_by:
    - reference_id: PMID:16826239
      supporting_text: its targeting to sites of DNA synthesis involves a physical
        interaction between its largest subunit, p150, and the homotrimeric sliding
        clamp, proliferating cell nuclear antigen (PCNA).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17474147
  qualifier: enables
  review:
    summary: Bare protein binding from a high-throughput SH3 domain peptide array
      screen (WITH NCK1, PIK3R1). No specific function conveyed.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a large-scale interaction screen does not
      represent a specific molecular function and these interactions are not part
      of the core histone chaperone activity.
    supported_by:
    - reference_id: PMID:17474147
      supporting_text: Systematic identification of SH3 domain-mediated human protein-protein
        interactions by peptide array target screening.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19498464
  qualifier: enables
  review:
    summary: IPI annotation (WITH CBX5/HP1alpha, P45973) from the HP1alpha-CAF1-SetDB1
      study. Reflects the HP1 interaction but only via the generic protein binding
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative. The CHAF1A-HP1 (CBX5) interaction
      is captured more specifically by the chromo shadow domain binding annotation.
    supported_by:
    - reference_id: PMID:19498464
      supporting_text: the histone H3K9 methyltransferase SetDB1 associates with the
        specific heterochromatin protein 1alpha (HP1alpha)-chromatin assembly factor
        1 (CAF1) chaperone complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20562864
  qualifier: enables
  review:
    summary: IPI annotation (WITH CBX5, P45973) from the POGZ/HP1alpha study, which
      also mapped the V240/L242 PxVxL residues required for CBX5 binding. Captured
      only by generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative. The CHAF1A-CBX5 interaction is
      represented specifically by the chromo shadow domain binding annotation.
    supported_by:
    - reference_id: PMID:20562864
      supporting_text: Human POGZ modulates dissociation of HP1alpha from mitotic
        chromosome arms through Aurora B activation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20936779
  qualifier: enables
  review:
    summary: Bare protein binding from a large-scale MAP kinase interactome screen
      (WITH YWHAE/14-3-3 epsilon). No specific function conveyed.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a high-throughput interactome map; not a
      specific molecular function and not part of the core activity.
    supported_by:
    - reference_id: PMID:20936779
      supporting_text: A human MAP kinase interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21570500
  qualifier: enables
  review:
    summary: IPI annotation (WITH GFI1, Q99684) showing p150 is part of the Gfi1
      transcriptional repression complex; the same study confirms p150 binds histones
      H3 and H4 directly. The Gfi1 interaction itself is captured only by generic
      protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: The bare protein binding term for the Gfi1 interaction is uninformative.
      The biologically core histone H3/H4 binding demonstrated in this paper is
      captured by a proposed histone binding annotation rather than this generic
      term.
    supported_by:
    - reference_id: PMID:21570500
      supporting_text: >-
        Since p150 binds directly to histones H3 and H4, our findings suggest that p150 may
        link the DNA-bound Gfi1 repressor complex to histones enabling modifications required
        for transcriptional silencing.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23075851
  qualifier: enables
  review:
    summary: IPI annotation (WITH histones H3-3B/H3C15) from a DAXX-H3.3 structural
      study. Although histone partners are involved, this is a DAXX-focused study
      and the annotation is captured only by generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative. CHAF1A histone H3-H4 binding is
      better represented by a dedicated histone binding annotation supported by
      direct CAF-1 studies.
    supported_by:
    - reference_id: PMID:23075851
      supporting_text: DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24981860
  qualifier: enables
  review:
    summary: IPI annotation (WITH CBX5, P45973) from a chromatin-protein interaction
      study. Reflects the HP1 interaction but only via generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative; the CHAF1A-CBX5 interaction is
      captured specifically by chromo shadow domain binding.
    supported_by:
    - reference_id: PMID:24981860
      supporting_text: Human-chromatin-related protein interactions identify a demethylase
        complex required for chromosome segregation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Bare protein binding from a proteome-scale binary interactome map. No
      specific function conveyed.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a high-throughput interactome study; not a
      specific molecular function.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Bare protein binding from a quantitative interactome study (WITH PCNA,
      PIK3R1). No specific function conveyed by the generic term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a high-throughput interactome map; the
      PCNA interaction is better captured by a dedicated PCNA binding annotation.
    supported_by:
    - reference_id: PMID:26496610
      supporting_text: A human interactome in three quantitative dimensions organized
        by stoichiometries and abundances.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27705803
  qualifier: enables
  review:
    summary: Bare protein binding from a Polycomb complexome map (WITH CBX5). No
      specific function conveyed.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a high-throughput complexome study; not a
      specific molecular function.
    supported_by:
    - reference_id: PMID:27705803
      supporting_text: A High-Density Map for Navigating the Human Polycomb Complexome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31980649
  qualifier: enables
  review:
    summary: Bare protein binding from an EGFR/KRAS network rewiring study (WITH
      YWHAE). No specific function conveyed.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a large-scale network study; not a specific
      molecular function and not part of the core activity.
    supported_by:
    - reference_id: PMID:31980649
      supporting_text: Extensive rewiring of the EGFR network in colorectal cancer
        cells expressing transforming levels of KRAS(G13D).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Bare protein binding from a reference binary interactome map (multiple
      partners). No specific function conveyed.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a high-throughput binary interactome study;
      not a specific molecular function.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Bare protein binding from a proteome-scale interactome study (WITH
      histone H3-3B). No specific function conveyed by the generic term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a high-throughput interactome map; histone
      binding is better captured by a dedicated annotation.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling
        of the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Bare protein binding from the OpenCell endogenous-tagging interactome
      (WITH YWHAE). No specific function conveyed.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a high-throughput cartography study; not a
      specific molecular function.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: 'OpenCell: Endogenous tagging for the cartography of human
        cellular organization.'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:16826239
  qualifier: enables
  review:
    summary: IPI annotation (WITH CHAF1A, Q13111) capturing the homodimerization of
      p150. CHAF1A is a homodimer, and dimerization is required for competence for
      chromatin assembly.
    action: ACCEPT
    reason: Identical protein binding accurately represents the well-documented
      p150 homodimerization, which is functionally important for chromatin assembly.
    supported_by:
    - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
      supporting_text: SUBUNIT; Homodimer. REGION 642..678; Necessary for homodimerization
        and competence for chromatin assembly.
- term:
    id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  evidence_type: IDA
  original_reference_id: PMID:14718166
  qualifier: involved_in
  review:
    summary: CAF-1 (with the replicative histone variant H3.1) mediates DNA-synthesis-dependent
      nucleosome assembly. This is the core biological process for CHAF1A.
    action: ACCEPT
    reason: Directly supported by experimental data distinguishing CAF-1/H3.1 (replication-coupled)
      from HIRA/H3.3 (replication-independent) assembly; represents the core function.
    supported_by:
    - reference_id: PMID:14718166
      supporting_text: The H3.1 and H3.3 complexes contain distinct histone chaperones,
        CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent
        and -independent nucleosome assembly, respectively.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence (HPA) localizes CHAF1A to the nucleoplasm, consistent
      with its nuclear histone chaperone role.
    action: KEEP_AS_NON_CORE
    reason: Accurate subcellular localization but a general component term, not the
      core molecular function.
    supported_by:
    - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
      supporting_text: SUBCELLULAR LOCATION; Nucleus. Note=DNA replication foci.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:9614144
  qualifier: located_in
  review:
    summary: CHAF1A localizes to chromatin, concentrating at intranuclear DNA replication
      foci during S phase, consistent with deposition of histones onto replicating
      DNA.
    action: ACCEPT
    reason: Direct experimental localization to chromatin/replication sites is well-supported
      and biologically appropriate for a histone chaperone acting at the replication
      fork.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: During S phase, p150 and p60 are concentrated at sites of
        intranuclear DNA replication.
- term:
    id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  evidence_type: IDA
  original_reference_id: PMID:9614144
  qualifier: involved_in
  review:
    summary: CAF-1 nucleosome assembly activity is cell-cycle regulated, and active
      CAF-1 (isolated as a 6.5S complex) deposits histones at S-phase replication
      foci. Core biological process for CHAF1A.
    action: ACCEPT
    reason: Directly supported experimental evidence for replication-coupled chromatin
      assembly; represents the core function.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: Active CAF-1 can be isolated as a 6.5 S complex from G1, S,
        and G2 phase nuclei.
- term:
    id: GO:0033186
    label: CAF-1 complex
  evidence_type: IPI
  original_reference_id: PMID:9614144
  qualifier: part_of
  review:
    summary: CHAF1A (p150) is a constitutive subunit of the CAF-1 complex together
      with CHAF1B (p60) and RBBP4 (p48). Core complex membership.
    action: ACCEPT
    reason: Well-established as the large subunit of the heterotrimeric CAF-1 complex;
      directly supported.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: Active CAF-1 can be isolated as a 6.5 S complex from G1, S,
        and G2 phase nuclei.
    - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
      supporting_text: SUBUNIT; Part of the CAF-1 complex that contains RBBP4, CHAF1B
        and CHAF1A.
- term:
    id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  evidence_type: IDA
  original_reference_id: PMID:8858152
  qualifier: involved_in
  review:
    summary: A complex of CAF-1 and acetylated histones H3/H4 carries out nucleosome
      assembly. Core biological process.
    action: ACCEPT
    reason: Direct experimental demonstration of CAF-1-mediated nucleosome assembly
      with newly synthesized acetylated histones; core function.
    supported_by:
    - reference_id: PMID:8858152
      supporting_text: Nucleosome assembly by a complex of CAF-1 and acetylated histones
        H3/H4.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:14718166
  qualifier: part_of
  review:
    summary: CHAF1A is part of a protein complex (the H3.1-CAF-1 histone chaperone
      complex). This is a very general complex term.
    action: MARK_AS_OVER_ANNOTATED
    reason: The generic protein-containing complex term is uninformative; the specific
      CAF-1 complex membership is captured by the GO:0033186 annotations.
    supported_by:
    - reference_id: PMID:14718166
      supporting_text: Histone H3.1 and H3.3 complexes mediate nucleosome assembly
        pathways dependent or independent of DNA synthesis.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:14718166
  qualifier: located_in
  review:
    summary: CHAF1A/CAF-1 associates with chromatin in the context of H3.1 deposition
      onto replicating DNA.
    action: ACCEPT
    reason: Direct experimental localization to chromatin is appropriate for a histone
      chaperone depositing histones onto DNA.
    supported_by:
    - reference_id: PMID:14718166
      supporting_text: The H3.1 and H3.3 complexes contain distinct histone chaperones,
        CAF-1 and HIRA.
- term:
    id: GO:0033186
    label: CAF-1 complex
  evidence_type: IDA
  original_reference_id: PMID:8858152
  qualifier: part_of
  review:
    summary: CHAF1A is part of the CAF-1 chromatin assembly complex (CAC) containing
      p150, p60 and p48. Core complex membership.
    action: ACCEPT
    reason: Directly supported membership in the heterotrimeric CAF-1 complex; core.
    supported_by:
    - reference_id: PMID:8858152
      supporting_text: a chromatin assembly complex (CAC), which contains the three
        subunits of CAF-1 (p150, p60, p48).
- term:
    id: GO:0070087
    label: chromo shadow domain binding
  evidence_type: IPI
  original_reference_id: PMID:15882967
  qualifier: enables
  review:
    summary: CHAF1A p150 carries a PxVxL motif that binds directly and with high
      affinity to the chromo shadow domain of HP1 (CBX5), mediating recruitment of
      HP1 to heterochromatic replication foci.
    action: ACCEPT
    reason: Specific, experimentally supported molecular function (PxVxL-chromo shadow
      domain binding) underlying CHAF1A's role in heterochromatin maintenance.
    supported_by:
    - reference_id: PMID:15882967
      supporting_text: KAP-1, CAF-1 p150, and NIPBL carry a canonical amino acid
        motif, PxVxL, which binds directly to the CSD with high affinity.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: TAS
  original_reference_id: PMID:7600578
  qualifier: enables
  review:
    summary: CHAF1A binds chromatin, consistent with its function depositing histones
      onto replicating DNA as the large subunit of CAF-1.
    action: ACCEPT
    reason: Supported molecular function; CHAF1A engages chromatin/DNA during nucleosome
      assembly.
    supported_by:
    - reference_id: PMID:7600578
      supporting_text: The p150 and p60 subunits of chromatin assembly factor I; a
        molecular link between newly synthesized histones and DNA replication.
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: IC
  original_reference_id: PMID:21570500
  qualifier: enables
  review:
    summary: Proposed annotation not present in the current GOA for CHAF1A.
    action: NEW
    reason: CHAF1A p150 binds directly to histones H3 and H4 (including the replicative 
      variants H3.1, H3.2 and H3.1t), the core substrate-recognition activity of its 
      histone chaperone function, yet there is no histone binding MF annotation; the 
      histone interactions are currently captured only by generic protein binding.
    supported_by:
    - reference_id: PMID:21570500
      supporting_text: p150 binds directly to histones H3 and H4.
    - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
      supporting_text: Interacts with histones H3.1, H3.2 and H3.1t (PubMed:33857403).
- term:
    id: GO:0140713
    label: histone chaperone activity
  evidence_type: IC
  original_reference_id: PMID:8858152
  qualifier: enables
  review:
    summary: Proposed annotation not present in the current GOA for CHAF1A.
    action: NEW
    reason: As the large subunit of CAF-1, CHAF1A directly mediates histone chaperone 
      activity (escorting and depositing H3-H4), which is its core molecular function 
      but is not currently annotated as a molecular function term.
    supported_by:
    - reference_id: PMID:8858152
      supporting_text: Nucleosome assembly by a complex of CAF-1 and acetylated histones
        H3/H4.
    - reference_id: PMID:14718166
      supporting_text: The H3.1 and H3.3 complexes contain distinct histone chaperones, 
        CAF-1 and HIRA.
- term:
    id: GO:0006334
    label: nucleosome assembly
  evidence_type: IC
  original_reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
  qualifier: involved_in
  review:
    summary: Proposed annotation not present in the current GOA for CHAF1A.
    action: NEW
    reason: CHAF1A drives nucleosome assembly; this BP is asserted by UniProt GO refs 
      (IDA, GO_Central) but is absent from the current GOA set and complements the more 
      specific DNA replication-dependent chromatin assembly term.
    supported_by:
    - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
      supporting_text: 'GO:0006334; P:nucleosome assembly; IDA:GO_Central.'
core_functions:
- description: Histone H3-H4 chaperone that, as the large p150 subunit of the CAF-1
    complex, deposits newly synthesized histones H3.1-H4 onto DNA to perform the
    first step of replication-coupled (and repair-coupled) nucleosome assembly.
  supported_by:
  - reference_id: PMID:7600578
    supporting_text: The p150 and p60 subunits of chromatin assembly factor I; a
      molecular link between newly synthesized histones and DNA replication.
  - reference_id: PMID:8858152
    supporting_text: Nucleosome assembly by a complex of CAF-1 and acetylated histones
      H3/H4.
  - reference_id: PMID:14718166
    supporting_text: The H3.1 and H3.3 complexes contain distinct histone chaperones,
      CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent
      and -independent nucleosome assembly, respectively.
  molecular_function:
    id: GO:0140713
    label: histone chaperone activity
  directly_involved_in:
  - id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  in_complex:
    id: GO:0033186
    label: CAF-1 complex
- description: Couples chromatin assembly to the replication fork by directly binding
    the sliding clamp PCNA via its N-terminal region, targeting CAF-1 to sites of
    DNA synthesis.
  supported_by:
  - reference_id: PMID:16826239
    supporting_text: its targeting to sites of DNA synthesis involves a physical
      interaction between its largest subunit, p150, and the homotrimeric sliding
      clamp, proliferating cell nuclear antigen (PCNA).
  - reference_id: file:human/CHAF1A/CHAF1A-uniprot.txt
    supporting_text: REGION 1..49; Binds to PCNA. SUBUNIT; Interacts with PCNA; the
      interaction is direct.
- description: Contributes to heterochromatin maintenance by binding the chromo shadow
    domain of HP1 (CBX5) through its PxVxL motif, delivering newly synthesized HP1
    proteins to heterochromatic replication foci.
  supported_by:
  - reference_id: PMID:15882967
    supporting_text: KAP-1, CAF-1 p150, and NIPBL carry a canonical amino acid motif,
      PxVxL, which binds directly to the CSD with high affinity.
  molecular_function:
    id: GO:0070087
    label: chromo shadow domain binding
proposed_new_terms: []
suggested_questions:
- question: How is CHAF1A-mediated histone deposition coordinated with the upstream
    histone supply chaperones (ASF1A/ASF1B) and the downstream H2A/H2B deposition
    machinery during a single round of replication?
- question: To what extent is the heterochromatin-maintenance role of CHAF1A (via
    HP1/CBX5 delivery) separable from its bulk replication-coupled nucleosome assembly
    function?
suggested_experiments:
- description: Acute degron-mediated depletion of CHAF1A in synchronized cells followed by nascent-chromatin (NCC/iPOND) proteomics and MNase-seq to quantify the kinetics of replication-coupled H3.1-H4 deposition and nucleosome maturation genome-wide.
- description: Structure-guided separation-of-function mutants disrupting the PCNA-binding region (1-49), the PxVxL/HP1 motif (V240/L242), or the homodimerization region (642-678), assayed for in vitro nucleosome assembly and for heterochromatin re-establishment after replication.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: PMID:14718166
  title: Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent
    or independent of DNA synthesis.
  findings: []
- id: PMID:15805117
  title: Proliferating cell nuclear antigen (PCNA) may function as a double homotrimer
    complex in the mammalian cell.
  findings: []
- id: PMID:15882967
  title: The mammalian heterochromatin protein 1 binds diverse nuclear proteins through
    a common motif that targets the chromoshadow domain.
  findings: []
- id: PMID:16826239
  title: The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit
    of chromatin assembly factor 1 with proliferating cell nuclear antigen.
  findings: []
- id: PMID:17474147
  title: Systematic identification of SH3 domain-mediated human protein-protein interactions
    by peptide array target screening.
  findings: []
- id: PMID:19498464
  title: The HP1alpha-CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated
    K9me3 in pericentric heterochromatin.
  findings: []
- id: PMID:20562864
  title: Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms
    through Aurora B activation.
  findings: []
- id: PMID:20936779
  title: A human MAP kinase interactome.
  findings: []
- id: PMID:21570500
  title: The p150 subunit of the histone chaperone Caf-1 interacts with the transcriptional
    repressor Gfi1.
  findings: []
- id: PMID:23075851
  title: DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.
  findings: []
- id: PMID:24981860
  title: Human-chromatin-related protein interactions identify a demethylase complex
    required for chromosome segregation.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries
    and abundances.
  findings: []
- id: PMID:27705803
  title: A High-Density Map for Navigating the Human Polycomb Complexome.
  findings: []
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing
    transforming levels of KRAS(G13D).
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:7600578
  title: 'The p150 and p60 subunits of chromatin assembly factor I: a molecular link
    between newly synthesized histones and DNA replication.'
  findings: []
- id: PMID:8858152
  title: Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
  findings: []
- id: PMID:9614144
  title: Nucleosome assembly activity and intracellular localization of human CAF-1
    changes during the cell division cycle.
  findings: []
- id: PMID:33857403
  title: DNAJC9 integrates heat shock molecular chaperones into the histone chaperone
    network.
  findings: []
- id: file:human/CHAF1A/CHAF1A-uniprot.txt
  title: UniProtKB Q13111 CHAF1A record
  findings: []