Affinage

SRCAP

Chromatin remodeling protein SRCAP · UniProt Q6ZRS2

Length
3230 aa
Mass
343.6 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRCAP is the catalytic ATPase subunit of a conserved multisubunit chromatin-remodeling complex that uses ATP hydrolysis to replace canonical H2A-H2B dimers with H2A.Z-H2B dimers in nucleosomes, the mammalian counterpart of the yeast SWR1 complex (PMID:14645854, PMID:16634648). Catalysis proceeds through an ordered reaction pathway in which motor-domain engagement at superhelical location 2 distorts and partially unwraps entry DNA (stabilized by ATP binding rather than hydrolysis), generating a hexasome intermediate that is stabilized during unwrapping, followed by eviction of H2A-H2B through the ZNHIT1 subunit and guided insertion of H2A.Z-H2B (PMID:26116819, PMID:30309918, PMID:38331872, PMID:39226902). H2A.Z recognition is achieved by dedicated chaperone modules of the catalytic subunit and the YL1/Swc2 subunit, which engage the H2A.Z αC helix and acidic patch to confer dimer specificity (PMID:24507717, PMID:26974124). The complex is targeted to gene promoters by combinatorial cues: preferential binding and ATP-promoted one-dimensional sliding toward long nucleosome-free regions sensed through Swc2 and a linker-length-reading Swc3 helix (PMID:24034247, PMID:35876491, PMID:39357520), and multivalent reading of acetylated histones, with NuA4-deposited H4/H2A acetylation stimulating exchange and the Yaf9 YEATS domain recognizing H3K27ac (PMID:20332092, PMID:29145630). Through promoter H2A.Z deposition SRCAP activates transcription and is recruited as a coactivator by CBP/CREB, steroid receptors, and YAP/TAZ (PMID:10347196, PMID:17617668, PMID:14500758, PMID:38280479). Beyond transcription, SRCAP is recruited to DNA double-strand breaks where it complexes with CtIP to promote end resection and homologous recombination in an ATPase-dependent manner (PMID:25176633), and associates with the mitotic apparatus to support mitosis and cytokinesis (PMID:34474679). SRCAP-dependent H2A.Z deposition governs developmental and stem-cell programs including muscle differentiation downstream of p38 MAPK via ZNHIT1, intestinal stem-cell self-renewal through REST/Prdm16, hematopoietic lineage commitment, and neuronal gene regulation via Satb2 (PMID:20473270, PMID:29138493, PMID:32449550, PMID:38733588). Truncating mutations clustered in the SRCAP C-terminal AT-hook region cause Floating-Harbor syndrome (PMID:22265015).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 High

    Established the core enzymatic identity of the complex by showing the yeast ortholog Swr1 is a Snf2-family ATPase that catalyzes ATP-dependent H2A-to-H2A.Z exchange, defining a new class of remodeler activity.

    Evidence In vitro histone exchange on nucleosome arrays plus genetic deletion and ChIP in yeast

    PMID:14645854

    Open questions at the time
    • Did not establish the human enzyme
    • Mechanism of dimer eviction/insertion unresolved
    • Targeting determinants unknown
  2. 2006 High

    Transferred the catalytic model to humans by demonstrating that purified native SRCAP complex performs ATP-dependent H2A.Z-H2B exchange on reconstituted nucleosomes.

    Evidence Immunoaffinity purification of native human SRCAP complex with in vitro exchange assay

    PMID:16634648

    Open questions at the time
    • Subunit roles not dissected
    • Promoter targeting in cells not addressed
  3. 1999 Medium

    First placed SRCAP in transcriptional control by identifying it as a CBP-interacting coactivator, linking the remodeler to coactivator function before its histone-exchange role was known.

    Evidence Yeast two-hybrid, co-IP, and reporter assays; E1A disruption of the interaction

    PMID:10347196

    Open questions at the time
    • Connection between CBP coactivation and histone exchange unresolved
    • No chromatin readout
  4. 2005 High

    Defined complex membership and cross-species function by identifying YL1 as a shared SRCAP/TIP60 subunit and showing human SRCAP rescues Drosophila domino in an ATPase-dependent manner while recruiting CBP and potentiating Notch.

    Evidence Mass spectrometry of native complexes; genetic complementation, polytene staining, and Notch reporter assays

    PMID:15647280 PMID:16024792

    Open questions at the time
    • Distinct functions of SRCAP vs TIP60 complexes not resolved
    • ATPase requirement for Notch not mechanistically dissected
  5. 2007 High

    Connected SRCAP to in vivo promoter biology and to DNA repair, showing it deposits H2A.Z at promoters to drive transcription and is recruited to DSBs to promote CtIP-dependent resection.

    Evidence ChIP-on-chip and ChIP with siRNA knockdown; laser micro-irradiation, co-IP, and ATPase-dead mutant analysis; yeast HO-break ChIP with genetic epistasis

    PMID:17617668 PMID:17762868 PMID:25176633

    Open questions at the time
    • Whether H2A.Z deposition itself drives repair vs a separable activity unclear
    • Recruitment determinants to DSBs incompletely defined
  6. 2010 High

    Linked SRCAP activity to signaling and chromatin marks, showing p38 MAPK-regulated ZNHIT1 directs H2A.Z deposition during muscle differentiation and that NuA4 acetylation of H4/H2A stimulates exchange.

    Evidence ChIP, siRNA, and p38 inhibition in myoblasts; in vitro exchange on NuA4-acetylated chromatin with histone-tail mutants

    PMID:20332092 PMID:20473270

    Open questions at the time
    • How acetylation is mechanistically read by the complex not yet structural
    • Locus-specific signaling integration incomplete
  7. 2013 High

    Explained promoter selectivity by showing the complex preferentially binds long nucleosome-free DNA adjoining nucleosomes, with NFR recognition dominant over acetylation cues.

    Evidence Competitive dinucleosome binding assays with mutant complexes and acetylated substrates

    PMID:24034247

    Open questions at the time
    • Structural basis of NFR sensing not yet resolved
    • Dynamics of targeting in vivo not addressed
  8. 2014 High

    Provided the structural basis for H2A.Z specificity by solving the Swr1-Z domain that recognizes the H2A.Z αC helix and chaperones the H2A.Z-H2B dimer to a tetrasome.

    Evidence 1.78 Å crystal structure with LxxLF motif mutagenesis and chaperone assay

    PMID:24507717

    Open questions at the time
    • Coordination with full-complex catalysis not shown
    • Eviction step not addressed
  9. 2015 High

    Defined substrate activation rules, showing the enzyme reads the H2A α2 helix and engages nucleosomal DNA at SHL2, requiring both nucleosome and H2A.Z-H2B substrates for activation.

    Evidence In vitro exchange with H2A mutant nucleosomes, DNA crosslinking, and hydroxyl-radical footprinting

    PMID:26116819

    Open questions at the time
    • How dual-substrate sensing is structurally coupled not yet resolved
  10. 2016 High

    Completed the dimer-recognition model with the YL1/Swc2 H2A.Z-binding domain structure, defining residues conferring H2A.Z selectivity essential for deposition in vivo.

    Evidence 1.9 Å crystal structure of YL1-Z/H2A.Z-H2B with mutagenesis and in vivo/in vitro validation

    PMID:26974124

    Open questions at the time
    • Handoff between YL1-Z and Swr1-Z chaperone surfaces not resolved
  11. 2018 High

    Revealed the catalytic mechanics by cryo-EM, showing motor engagement at SHL2 distorts and unwraps nucleosomal DNA in a manner stabilized by ATP binding but not hydrolysis, and defined H3K27ac reading by Yaf9 YEATS.

    Evidence 3.6 Å cryo-EM with single-molecule FRET and nucleotide-state mutants; Yaf9 YEATS-H3K27ac structure with in vivo H2A.Z ChIP

    PMID:29145630 PMID:30309918

    Open questions at the time
    • Full eviction-insertion trajectory not yet captured
    • Integration of reader domains with motor not structurally linked
  12. 2022 High

    Defined the search mechanism, showing ATP-binding-promoted one-dimensional sliding biases the complex toward NFR-length DNA and halts at roadblocks.

    Evidence Single-particle tracking on stretched DNA with ATPase mutants and dCas9 roadblocks

    PMID:35876491

    Open questions at the time
    • How sliding couples to productive engagement in chromatin not resolved
  13. 2024 High

    Resolved the human enzyme architecture and reaction pathway, defining the ARP and motor modules, ZNHIT1-mediated H2A-H2B extraction, Swc5-stabilized hexasome intermediate, Swc3 linker sensing, and structural distinctions from TIP60.

    Evidence Cryo-EM of human and yeast complexes in multiple nucleotide/intermediate states with crosslink trapping, mutagenesis, and ChIP-seq/CUT&Tag validation

    PMID:38331872 PMID:39131301 PMID:39226902 PMID:39357520

    Open questions at the time
    • Complete cycle of all reaction intermediates not yet unified
    • TIP60 vs SRCAP functional divergence based partly on preprint
  14. 2024 Medium

    Extended the physiological reach of SRCAP-dependent H2A.Z deposition to stem-cell, developmental, oncogenic, and disease contexts, and tied human disease to specific domain loss.

    Evidence Conditional mouse models, organoid assays, ChIP/CUT&Tag, AAV rescue, and exome sequencing across intestinal, hematopoietic, neuronal, epidermal, and YAP/TAZ cancer settings; Floating-Harbor mutation mapping

    PMID:20432434 PMID:22265015 PMID:22479200 PMID:29138493 PMID:31449550 PMID:37863054 PMID:38280479 PMID:38733588 PMID:40812470

    Open questions at the time
    • Whether locus-specific effects reflect direct H2A.Z deposition vs indirect transcription cascades not fully separated
    • Floating-Harbor domain-loss mechanism not functionally validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How signaling pathways (p38, ERK, mTOR) and partner coactivators direct SRCAP to specific loci genome-wide, and how its chromatin-remodeling versus mitotic/repair functions are mechanistically partitioned, remain unresolved.
  • No unified model linking promoter targeting cues to locus choice
  • Mitotic apparatus association lacks structural mechanism
  • Relationship between H2A.Z deposition and DSB repair function unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0140110 transcription regulator activity 4 GO:0140657 ATP-dependent activity 4 GO:0003677 DNA binding 3 GO:0042393 histone binding 3
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-73894 DNA Repair 2 R-HSA-1640170 Cell Cycle 1
Partners
ANDROGEN RECEPTORCBPCTIPRESTTAZYAPYL1ZNHIT1
Complex memberships
SRCAP complexSWR1 complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Swr1 (yeast ortholog of SRCAP), a Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit chromatin remodeling complex (SWR1) that catalyzes ATP-dependent replacement of canonical histone H2A with histone H2A.Z in nucleosome arrays. Swr1 is required for deposition of H2A.Z at specific chromosome locations in vivo. In vitro histone exchange assay with nucleosome arrays; genetic deletion; chromatin immunoprecipitation Science High 14645854
2006 The human SRCAP complex, purified by conventional and immunoaffinity chromatography, supports ATP-dependent exchange of H2B/H2A.Z-containing histone dimers into mononucleosomes reconstituted with recombinant histones, establishing SRCAP as the catalytic core of the human SWR1-type histone exchange complex. Immunoaffinity purification of native SRCAP complex; in vitro ATP-dependent histone exchange assay with reconstituted mononucleosomes Biochemistry High 16634648
1999 SRCAP (SNF2-related CBP activator protein) physically interacts with CBP and enhances CBP-mediated transcriptional activation; the adenoviral protein E1A disrupts the SRCAP-CBP interaction, providing a potential mechanism for E1A-mediated transcriptional repression. Yeast two-hybrid screen; co-immunoprecipitation; transient transfection transcription assays The Journal of Biological Chemistry Medium 10347196
2001 SRCAP functions as a coactivator for CREB-mediated transcription; SRCAP binds CBP at amino acids 280–460 and enhances PKA-activated transcription of the PEPCK promoter through this interaction. A dominant-negative SRCAP peptide corresponding to the CBP-binding domain inhibits CREB-mediated transcription. The N-terminal ATPase domain is dispensable for CREB coactivation. Transient transfection reporter assays; dominant-negative peptide expression; structure-function mutagenesis; in vivo CBP binding mapping The Journal of Biological Chemistry Medium 11522779
2005 YL1 protein is a shared subunit of both the TRRAP/TIP60 histone acetyltransferase complex and a novel mammalian complex containing the SNF2-related helicase SRCAP that resembles the yeast SWR1 complex. Affinity purification of TRRAP/TIP60 complex from HeLa cells followed by mass spectrometry; identification of YL1 as shared subunit The Journal of Biological Chemistry Medium 15647280
2007 Human SRCAP (the SWR1 ortholog) is recruited to DNA double-strand breaks (DSBs) and is required for CtIP-dependent DNA-end resection; SRCAP forms a complex with CtIP and promotes CtIP accumulation at DSBs through a mechanism requiring its ATPase activity. Loss of SRCAP impairs RPA and RAD51 recruitment and homologous recombination. siRNA knockdown; laser micro-irradiation and immunofluorescence; co-immunoprecipitation; ATPase-dead mutant analysis; RPA/RAD51 foci assays Current Biology Medium 25176633
2007 SRCAP is recruited to gene promoters in vivo and is required for H2A.Z and acetylated H2A.Z deposition at those promoters; siRNA knockdown of SRCAP reduces H2A.Z incorporation and decreases transcription of target genes (SP-1, G3BP, FAD synthetase). ChIP-on-chip; ChIP; siRNA knockdown; qRT-PCR The Journal of Biological Chemistry Medium 17617668
2007 In yeast, Swr1 is recruited to DSBs in a manner dependent on H2A phosphorylation (γH2AX), but H2A.Z levels do not increase at DSBs; instead Swr1 is required for error-free end-joining at DSBs, while INO80 (not SWR1) removes γH2AX and core histones near the break. ChIP at HO-induced DSBs; genetic deletion of SWR1 subunits; end-resection and checkpoint activation assays The EMBO Journal High 17762868
2008 The N-terminal region of the Swr1 ATPase subunit contains an H2A.Z-H2B-specific binding site (distinct from the Swc2 subunit binding site), and directs assembly of multiple SWR1 subunits (Bdf1, Swc7, Arp4, Act1, Yaf9, Swc4). Arp4 is required for basic H2A.Z histone replacement activity in vitro; Bdf1 and Swc7 are auxiliary subunits dispensable for this activity. Affinity purification of mutant SWR1 complexes; in vitro histone exchange assay; subunit depletion (arp4-td degron); biochemical fractionation The Journal of Biological Chemistry High 19088068
2010 The SRCAP subunit ZNHIT1 (p18Hamlet), a substrate of p38 MAPK, is recruited to the myogenin promoter at the onset of muscle differentiation in a p38 MAPK-dependent manner and is required for H2A.Z accumulation at that genomic region and for muscle gene transcriptional activation. Downregulation of multiple SRCAP complex subunits impairs muscle gene expression. ChIP; siRNA knockdown of SRCAP subunits; p38 MAPK inhibition; qRT-PCR; differentiation assays in myoblasts The EMBO Journal Medium 20473270
2010 NuA4-dependent acetylation of nucleosomal histones H4 and H2A directly stimulates SWR1-catalyzed H2A.Z incorporation; acetylation of either H4 or H2A N-terminal tails independently stimulates SWR1 activity in vitro, and Bdf1 is important for NuA4-dependent stimulation of SWR1. In vitro histone exchange assay with native chromatin pre-acetylated by NuA4; histone tail mutants; genetic analysis in yeast; Bdf1 depletion experiments The Journal of Biological Chemistry High 20332092
2013 SWR1 preferentially binds long nucleosome-free DNA and the adjoining nucleosome core particle, enabling discrimination of gene promoters over gene bodies. The Swc2/YL1 subunit and the Swr1 ATPase domain are primarily responsible for substrate binding. NuA4 acetylation enhances SWR1 binding, but recognition of nucleosome-free DNA is dominant over acetylation signals. Competitive binding assay with dinucleosome substrates; mutant SWR1 complex analysis; in vitro binding with acetylated nucleosomes Cell High 24034247
2014 The N-terminal region (residues 599-627) of the Swr1 catalytic subunit, termed the Swr1-Z domain, adopts a 310 helix and irregular chain structure that specifically recognizes the αC helix of H2A.Z via a conserved LxxLF motif, and can deliver the H2A.Z-H2B dimer to a DNA-(H3-H4)2 tetrasome by a histone chaperone mechanism. Crystal structure at 1.78 Å resolution; mutagenesis of LxxLF motif; in vitro nucleosome assembly/chaperone assay Molecular Cell High 24507717
2015 SWR1 primarily recognizes key residues within the α2 helix of the histone-fold of nucleosomal H2A for activation of histone exchange, and interacts preferentially with nucleosomal DNA at superhelix location 2 on the face distal to its linker-binding site; binding of both the canonical nucleosome and H2A.Z-H2B dimer substrates is required for SWR1 activation. In vitro histone exchange assay with H2A mutant nucleosomes; DNA crosslinking; hydroxyl radical footprinting eLife High 26116819
2016 The YL1 (Swc2) subunit of SRCAP/SWR1 contains an H2A.Z-binding domain (YL1-Z) that adopts a novel whip-like structure wrapping over the H2A.Z-H2B dimer. Preferential recognition is conferred by three residues in loop 2, the hyperacidic patch, and the extended αC helix of H2A.Z. This domain is essential for H2A.Z deposition in vivo and SRCAP-catalyzed histone exchange in vitro. Crystal structure at 1.9 Å resolution of dYL1-Z/H2A.Z-H2B; mutagenesis of recognition residues; in vivo H2A.Z deposition assay; in vitro histone exchange assay Nature Structural & Molecular Biology High 26974124
2018 Cryo-EM structure of the yeast SWR1 complex bound to a nucleosome at 3.6 Å reveals that Swr1 motor domain interactions with DNA at superhelical location 2 distort the DNA causing a bulge with one base pair translocation coupled to conformational changes of the histone core. Nucleosome binding also causes partial DNA unwrapping from the histone core, which is stabilized by ATP binding but does not require hydrolysis. Cryo-electron microscopy at 3.6 Å; single-molecule FRET to monitor DNA unwrapping dynamics; ATP binding/hydrolysis mutant analysis Science High 30309918
2018 Yaf9, a subunit of both NuA4 and SWR1 complexes, recognizes H3K27ac through its YEATS domain; mutation of the aromatic cage residues that accommodate the K27ac side chain abolishes H3K27ac interaction in vitro and leads to loss of SWR1-dependent H2A.Z incorporation in vivo. Crystal structure of Yaf9 YEATS domain/H3K27ac peptide; mutational analysis; in vivo H2A.Z ChIP Nucleic Acids Research High 29145630
2005 Human SRCAP functionally complements recessive Drosophila domino (DOM) mutant phenotypes in an ATPase-domain-dependent manner. SRCAP and DOM co-localize on polytene chromosomes at sites of active transcription; SRCAP recruits Drosophila CBP to ectopic chromosomal sites. DOM is a Notch pathway activator, and wild-type SRCAP (but not an ATPase mutant) can substitute for DOM in Notch-dependent wing development; SRCAP potentiates Notch-dependent gene activation in HeLa cells. Genetic complementation in Drosophila; polytene chromosome immunostaining; ectopic chromosomal targeting; ATPase domain mutagenesis; Notch reporter assay in HeLa cells Molecular and Cellular Biology High 16024792
2012 SRCAP-mediated H2A.Z insertion is required for the establishment of nucleosome-depleted regions at gene promoters following 5-aza-2'-deoxycytidine-induced DNA demethylation, and this is required for complete gene reactivation of silenced genes. SRCAP-mediated H2A.Z deposition is not required for maintaining the active status of constitutively expressed genes. ChIP; NOMe-seq; genome-wide expression profiling; siRNA knockdown of SRCAP PLoS Genetics Medium 22479200
2012 Mutations in SRCAP causing Floating-Harbor syndrome are truncating mutations tightly clustered in a small 111-codon region of the final exon (exon 34), predicted to abolish three C-terminal AT-hook DNA-binding motifs while leaving the CBP-binding and ATPase domains intact. Whole-exome sequencing; Sanger sequencing; de novo mutation verification in parent-offspring trios American Journal of Human Genetics Medium 22265015
2022 SWR1 undergoes ATP-binding-promoted one-dimensional diffusion (sliding) on DNA with a median diffusion coefficient of 0.024 μm²/s (helical sliding regime); ATP promotes diffusion through nucleotide binding rather than hydrolysis. The Swc2 subunit plays an important role in diffusive behavior. SWR1 slides until encountering protein roadblocks (dCas9 or nucleosomes) and shows kinetic preference for NDR-length DNA over shorter gene-body linker DNA. Single-particle tracking on DNA stretched with optical tweezers; dual-color single-molecule imaging; ATPase mutant analysis; dCas9 roadblock assay eLife High 35876491
2024 Cryo-EM structures of human SRCAP complex bound to an H2A-containing nucleosome at near-atomic resolution reveal that SRCAP integrates a 6-subunit ARP module and an ATPase-containing motor module; the ARP module encircles half the nucleosome and may restrain net DNA translocation. ATPase-driven movement destabilizes H2A-H2B by unwrapping entry DNA and pulls H2A-H2B out through the ZNHIT1 subunit. The motor module adopts distinct binding modes in apo, ADP-bound, and ADP-BeFx-bound states. Cryo-EM at near-atomic resolution; structure-guided ChIP-seq to validate ZNHIT1 requirement for H2A.Z occupancy Cell Discovery High 38331872
2024 Cryo-EM structures of native human SRCAP complex resolve six conformational states interpreted as stepwise nucleosome engagement intermediates. The ATPase-associated ARP module and ATPase motor adopt distinct architectures from TIP60 (the other H2A.Z regulator), structurally disfavoring nucleosome engagement for TIP60 despite shared subunit composition, suggesting SRCAP and TIP60 have mechanistically distinct biochemical functions. Cryo-EM of native purified complexes; comparative structural analysis bioRxivpreprint Medium 39131301
2024 Cryo-EM structure of an SWR1-bound hexasome intermediate (after H2A/H2B eviction, before Htz1/H2B insertion) reveals that the Swc5 subunit stabilizes DNA unwrapping from the hexasome histone core. Engineering a crosslink between the Htz1/H2B dimer and its chaperone Chz1 blocks exchange but permits insertion of the chaperone-dimer complex into the hexasome, trapping a subsequent intermediate. Cryo-EM; engineered disulfide crosslink between Htz1 and Chz1; in vitro histone exchange assay with crosslinked substrates Molecular Cell High 39226902
2024 Cryo-EM reveals the structural basis of SWR1 interaction with free DNA (open conformation of Swr1 ATPase enabling DNA-to-nucleosome sliding); Swc2 and Swc3 subunits mediate oriented nucleosome engagement; an extended α-helix in Swc3 senses nucleosome linker length and is essential for SWR1 promoter-specific recruitment and activity. The N-SWR1 subcomplex forms a flexible extended structure enabling multivalent recognition of acetylated histone tails by reader domains. Cryo-EM of SWR1-DNA and SWR1-nucleosome complexes; Swc3 helix mutagenesis; in vitro exchange assays; ChIP-seq Cell High 39357520
2021 SRCAP protein associates with components of the mitotic apparatus (centrosomes, spindle, midbody) in HeLa cells; it interacts with cytokinesis regulators and promotes their recruitment to the midbody. SRCAP depletion perturbs both mitosis and cytokinesis. The Drosophila SRCAP ortholog DOM-A similarly localizes to centrosomes and midbody, and its depletion also impairs mitosis and cytokinesis, indicating evolutionary conservation of this non-chromatin function. Immunofluorescence; co-immunoprecipitation with cytokinesis regulators; siRNA knockdown of SRCAP; live-cell imaging; analogous experiments with DOM-A in Drosophila cells BMC Biology Medium 34474679
2000 Hepatitis C virus NS5A protein interacts with the C-terminal region of SRCAP (verified by yeast two-hybrid, mammalian two-hybrid, in vitro pull-down, and co-immunoprecipitation in HepG2 cells); NS5A-SRCAP interaction enhances down-regulation of p21 promoter activity by NS5A. Yeast two-hybrid; mammalian two-hybrid; in vitro pull-down; co-immunoprecipitation; transient transfection reporter assay The Journal of Biological Chemistry Medium 10702287
2001 Adenovirus DNA binding protein (DBP) co-immunoprecipitates with SRCAP in infected cells, interacts directly in vitro, and inhibits SRCAP-mediated transcriptional activation in a dose-dependent manner. Co-immunoprecipitation from infected cell lysates; in vitro translation pull-down; transient transfection transcription reporter assay Journal of Virology Medium 11581372
2003 SRCAP functions as a coactivator for steroid receptor-mediated transcription (glucocorticoid and androgen receptors), showing synergistic activation with GRIP-1 and CARM-1 coactivators, and functionally interacting with these coactivators in vivo. Transient transfection reporter assays; co-transfection synergy assays with GRIP-1 and CARM-1; cell-based interaction assays Molecular Endocrinology Medium 14500758
2010 SRCAP is associated with androgen receptor (AR) in the nucleus of prostate cancer cells; SRCAP occupies the PSA enhancer in vivo, and SRCAP knockdown reduces H2A.Z binding at the PSA promoter and decreases PSA expression and androgen-dependent cell proliferation. Co-immunoprecipitation (SRCAP-AR); ChIP at PSA promoter; shRNA knockdown; cell proliferation assay Journal of Cellular Physiology Medium 20432434
2017 Pcid2 interacts with ZNHIT1 (a SRCAP complex subunit) in multipotent progenitors to block SRCAP activity, preventing H2A.Z deposition and transcription factor PU.1 access to lymphoid fate regulator gene loci; Znhit1 deletion abrogates H2A/H2A.Z exchange in multipotent progenitors, establishing SRCAP as a regulator of lymphoid lineage commitment. Co-immunoprecipitation (Pcid2-ZNHIT1); ChIP for H2A.Z and PU.1; conditional gene deletion; flow cytometry of hematopoietic progenitors Nature Communications Medium 29138493
2020 SRCAP is required for self-renewal of Lgr5+ intestinal stem cells; mechanistically, SRCAP recruits the transcriptional regulator REST to the Prdm16 promoter to induce Prdm16 expression, which in turn activates PPARδ signaling to sustain ISC stemness. REST or Prdm16 deficiency similarly abrogates ISC self-renewal. Conditional Srcap deletion; organoid self-renewal assays; ChIP (SRCAP and REST at Prdm16 promoter); siRNA knockdown of pathway components; in vivo intestinal regeneration assays The EMBO Journal Medium 32449550
2023 SRCAP mutations confer a selective advantage to hematopoietic stem cells upon treatment with anthracycline chemotherapy (doxorubicin) and bone marrow transplantation; Srcap mutations lead to lymphoid-biased expansion driven by loss of SRCAP-regulated H2A.Z deposition and increased DNA repair capacity. Conditional Srcap murine model; bone marrow transplantation; doxorubicin treatment; H2A.Z ChIP-seq; DNA repair assays; hematopoietic lineage analysis Cell Stem Cell Medium 37863054
2024 Srcap haploinsufficiency in mice causes ASD-like behaviors; Srcap regulates expression of Satb2 via H2A.Z deposition at the Satb2 promoter. AAV-mediated restoration of Satb2 in neonatal Srcap+/- mice ameliorates neurodevelopmental and ASD-like abnormalities. Srcap+/- mouse behavioral testing; RNA-seq; H2A.Z ChIP at Satb2 promoter; AAV-Satb2 rescue experiment Cell Reports Medium 38733588
2025 In epidermal progenitors, SRCAP (but not EP400) is the essential H2A.Z-depositing chromatin remodeler; loss of SRCAP causes DNA damage and nuclear morphology defects. H2A.Z chromatin occupancy is regulated downstream of extracellular signal-regulated kinase and mTOR signaling pathways. siRNA knockdown of SRCAP vs. EP400; H2A.Z ChIP; DNA damage assays (γH2AX); nuclear morphology imaging; kinase inhibitor screen The Journal of Investigative Dermatology Medium 40812470
2024 SRCAP complex components physically interact with YAP/TAZ transcriptional coactivators (validated by endogenous and exogenous co-immunoprecipitation and immunofluorescence); SRCAP complex facilitates H2A.Z deposition at YAP/TAZ target promoters, and depletion of SRCAP complex decreases H2A.Z occupancy and oncogenic transcription of YAP/TAZ target genes. BioID proximity labeling; co-immunoprecipitation; CUT&Tag for H2A.Z; siRNA depletion of SRCAP; tumor xenograft assay Cancer Letters Medium 38280479

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science (New York, N.Y.) 1032 14645854
2007 Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks. The EMBO journal 253 17762868
2009 Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. Nature reviews. Molecular cell biology 245 19424290
2006 Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry 214 16634648
2004 Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4. Proceedings of the National Academy of Sciences of the United States of America 209 15353583
2005 The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes. The Journal of biological chemistry 184 15647280
2006 Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptation in response to DNA damage. Genes & development 157 16951256
2013 Nucleosome-free region dominates histone acetylation in targeting SWR1 to promoters for H2A.Z replacement. Cell 155 24034247
2007 The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. The Journal of biological chemistry 146 17617668
2012 Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome. American journal of human genetics 142 22265015
2010 NuA4-dependent acetylation of nucleosomal histones H4 and H2A directly stimulates incorporation of H2A.Z by the SWR1 complex. The Journal of biological chemistry 141 20332092
2018 Structure and dynamics of the yeast SWR1-nucleosome complex. Science (New York, N.Y.) 140 30309918
2014 SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. Molecular cell 140 25066231
2009 The beauty of being a variant: H2A.Z and the SWR1 complex in plants. Molecular plant 112 19825639
2008 N terminus of Swr1 binds to histone H2AZ and provides a platform for subunit assembly in the chromatin remodeling complex. The Journal of biological chemistry 92 19088068
2009 NuA4 and SWR1-C: two chromatin-modifying complexes with overlapping functions and components. Biochemistry and cell biology = Biochimie et biologie cellulaire 91 19898529
2010 The SWR1 histone replacement complex causes genetic instability and genome-wide transcription misregulation in the absence of H2A.Z. PloS one 87 20711347
2016 Structural basis of H2A.Z recognition by SRCAP chromatin-remodeling subunit YL1. Nature structural & molecular biology 82 26974124
1999 Identification of a novel SNF2/SWI2 protein family member, SRCAP, which interacts with CREB-binding protein. The Journal of biological chemistry 73 10347196
2020 A plant-specific SWR1 chromatin-remodeling complex couples histone H2A.Z deposition with nucleosome sliding. The EMBO journal 72 32115743
2014 The catalytic subunit of the SWR1 remodeler is a histone chaperone for the H2A.Z-H2B dimer. Molecular cell 72 24507717
2000 Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP. The Journal of biological chemistry 72 10702287
2010 Essential role of p18Hamlet/SRCAP-mediated histone H2A.Z chromatin incorporation in muscle differentiation. The EMBO journal 71 20473270
2013 The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP. Orphanet journal of rare diseases 66 23621943
2019 INO80 and SWR1 complexes: the non-identical twins of chromatin remodelling. Current opinion in structural biology 60 31838293
2014 The human SRCAP chromatin remodeling complex promotes DNA-end resection. Current biology : CB 57 25176633
2006 Isw1 functions in parallel with the NuA4 and Swr1 complexes in stress-induced gene repression. Molecular and cellular biology 56 16880522
2021 Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature. American journal of human genetics 55 33909990
2005 Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Molecular and cellular biology 53 16024792
2015 H2A histone-fold and DNA elements in nucleosome activate SWR1-mediated H2A.Z replacement in budding yeast. eLife 52 26116819
2018 Yaf9 subunit of the NuA4 and SWR1 complexes targets histone H3K27ac through its YEATS domain. Nucleic acids research 45 29145630
2012 Gene reactivation by 5-aza-2'-deoxycytidine-induced demethylation requires SRCAP-mediated H2A.Z insertion to establish nucleosome depleted regions. PLoS genetics 45 22479200
2010 The chromatin remodeling factor SRCAP modulates expression of prostate specific antigen and cellular proliferation in prostate cancer cells. Journal of cellular physiology 41 20432434
2019 SWR1 Chromatin Remodeling Complex: A Key Transcriptional Regulator in Plants. Cells 40 31842357
2001 Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP. The Journal of biological chemistry 39 11522779
2014 Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome. BMC medical genetics 34 25433523
2011 Hepatitis C virus NS3 protein can activate the Notch-signaling pathway through binding to a transcription factor, SRCAP. PloS one 34 21673954
2003 SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1. Molecular endocrinology (Baltimore, Md.) 34 14500758
2019 Roles of the INO80 and SWR1 Chromatin Remodeling Complexes in Plants. International journal of molecular sciences 33 31533258
2017 Suppression of SRCAP chromatin remodelling complex and restriction of lymphoid lineage commitment by Pcid2. Nature communications 32 29138493
2016 Regulation of MicroRNA-Mediated Developmental Changes by the SWR1 Chromatin Remodeling Complex. Plant physiology 32 27208270
2016 When chromatin organisation floats astray: the Srcap gene and Floating-Harbor syndrome. Journal of medical genetics 29 27208210
2006 Purification and assay of the human INO80 and SRCAP chromatin remodeling complexes. Methods (San Diego, Calif.) 28 17101442
2020 Variation on a theme: Evolutionary strategies for H2A.Z exchange by SWR1-type remodelers. Current opinion in cell biology 27 33217681
2018 Merge and separation of NuA4 and SWR1 complexes control cell fate plasticity in Candida albicans. Cell discovery 27 30109121
2011 Podbat: a novel genomic tool reveals Swr1-independent H2A.Z incorporation at gene coding sequences through epigenetic meta-analysis. PLoS computational biology 26 21901086
2020 Drosophila SWR1 and NuA4 complexes are defined by DOMINO isoforms. eLife 25 32432549
2017 Functional characterization and architecture of recombinant yeast SWR1 histone exchange complex. Nucleic acids research 25 28499038
2023 SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation. Cell stem cell 24 37863054
2012 Not all floating-harbor syndrome cases are due to mutations in exon 34 of SRCAP. Human mutation 24 22965468
2024 Structural insights into histone exchange by human SRCAP complex. Cell discovery 23 38331872
2022 ATP binding facilitates target search of SWR1 chromatin remodeler by promoting one-dimensional diffusion on DNA. eLife 23 35876491
2012 Floating-Harbor syndrome and polycystic kidneys associated with SRCAP mutation. American journal of medical genetics. Part A 22 23165645
2003 Molecular cloning and characterization of an SRCAP chromatin remodeling homologue in Toxoplasma gondii. Parasitology research 22 12743798
2020 HBI1 acts downstream of ERECTA and SWR1 in regulating inflorescence architecture through the activation of the brassinosteroid and auxin signaling pathways. The New phytologist 20 32746499
2016 Splice variants of the SWR1-type nucleosome remodeling factor Domino have distinct functions during Drosophila melanogaster oogenesis. Development (Cambridge, England) 20 27578180
2021 The ATPase SRCAP is associated with the mitotic apparatus, uncovering novel molecular aspects of Floating-Harbor syndrome. BMC biology 19 34474679
2018 The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects. Nature communications 18 30206225
2024 SRCAP complex promotes lung cancer progression by reprograming the oncogenic transcription of Hippo-YAP/TAZ signaling pathway. Cancer letters 17 38280479
2008 Improved tools for efficient mapping of fission yeast genes: identification of microtubule nucleation modifier mod22-1 as an allele of chromatin- remodelling factor gene swr1. Yeast (Chichester, England) 17 19160458
2024 Molecular basis of global promoter sensing and nucleosome capture by the SWR1 chromatin remodeler. Cell 16 39357520
2023 Inherited mutations affecting the SRCAP complex are central in moderate-penetrance predisposition to uterine leiomyomas. American journal of human genetics 16 36773604
2020 The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells. The EMBO journal 16 32449550
2022 A neurodevelopmental disorder caused by a novel de novo SVA insertion in exon 13 of the SRCAP gene. European journal of human genetics : EJHG 15 35768521
2020 SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion. Frontiers in cell and developmental biology 14 33195270
2015 Overlapping Functions between SWR1 Deletion and H3K56 Acetylation in Candida albicans. Eukaryotic cell 14 25862154
2012 Biochemical assay for histone H2A.Z replacement by the yeast SWR1 chromatin remodeling complex. Methods in enzymology 13 22910211
2022 LINC00665 sponges miR-641 to promote the progression of breast cancer by targeting the SNF2-related CREBBP activator protein (SRCAP). Bioengineered 12 35152838
2013 Long-term follow-up study for a patient with Floating-Harbor syndrome due to a hotspot SRCAP mutation. American journal of medical genetics. Part A 12 24375913
2020 Cancer-related SRCAP and TPR mutations in colon cancers. Pathology, research and practice 11 33307343
2025 H3K4me3 binding ALFIN-LIKE proteins recruit SWR1 for gene-body deposition of H2A.Z. Genome biology 10 40399998
2014 16p11.2 de novo microdeletion encompassing SRCAP gene in a patient with speech impairment, global developmental delay and behavioural problems. European journal of medical genetics 10 25451714
2012 Physical and functional interactions between Drosophila homologue of Swc6/p18Hamlet subunit of the SWR1/SRCAP chromatin-remodeling complex with the DNA repair/transcription factor TFIIH. The Journal of biological chemistry 10 22865882
2024 Stabilization of the hexasome intermediate during histone exchange by yeast SWR1 complex. Molecular cell 9 39226902
2001 Adenovirus DNA binding protein interacts with the SNF2-related CBP activator protein (SrCap) and inhibits SrCap-mediated transcription. Journal of virology 9 11581372
2024 Srcap haploinsufficiency induced autistic-like behaviors in mice through disruption of Satb2 expression. Cell reports 8 38733588
2020 Swc4 positively regulates telomere length independently of its roles in NuA4 and SWR1 complexes. Nucleic acids research 8 33270890
2017 Ultra-rare mutations in SRCAP segregate in Caribbean Hispanic families with Alzheimer disease. Neurology. Genetics 8 28852706
2022 Facile Fabrication of 3D-Printed Porous Ti6Al4V Scaffolds with a Sr-CaP Coating for Bone Regeneration. ACS omega 7 35309469
2019 Identification of SWI2/SNF2-Related 1 Chromatin Remodeling Complex (SWR1-C) Subunits in Pineapple and the Role of Pineapple SWR1 COMPLEX 6 (AcSWC6) in Biotic and Abiotic Stress Response. Biomolecules 7 31412667
2018 Floating-Harbor Syndrome: Presentation of the First Romanian Patient with a SRCAP Mutation and Review of the Literature. Balkan journal of medical genetics : BJMG 7 30425916
2014 Maintenance of heterochromatin boundary and nucleosome composition at promoters by the Asf1 histone chaperone and SWR1-C chromatin remodeler in Saccharomyces cerevisiae. Genetics 7 24578349
2023 Missense variant in SRCAP with distinct DNA methylation signature associated with non-FLHS SRCAP-related neurodevelopmental disorder. American journal of medical genetics. Part A 6 37340855
2022 SWR1 chromatin remodeling complex prevents mitotic slippage during spindle position checkpoint arrest. Molecular biology of the cell 6 36542480
2005 Identification of proteins interacting with Toxoplasma SRCAP by yeast two-hybrid screening. Parasitology research 6 15729590
2022 The SWC4 subunit of the SWR1 chromatin remodeling complex is involved in varying virulence of Metarhizium brunneum isolates offering role of epigenetic regulation of pathogenicity. Virulence 5 35891589
2019 Actin and Nuclear Envelope Components Influence Ectopic Recombination in the Absence of Swr1. Genetics 5 31533921
2024 Structures of H2A.Z-associated human chromatin remodelers SRCAP and TIP60 reveal divergent mechanisms of chromatin engagement. bioRxiv : the preprint server for biology 4 39131301
2024 SRCAP is involved in porcine reproductive and respiratory syndrome virus activated Notch signaling pathway. Journal of virology 4 39530666
2018 The first Korean case with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing. Korean journal of pediatrics 4 30304910
2003 Adenovirus DNA binding protein inhibits SrCap-activated CBP and CREB-mediated transcription. Virology 4 12954226
2023 Chromatin Remodeling Complex SWR1 Regulates Root Development by Affecting the Accumulation of Reactive Oxygen Species (ROS). Plants (Basel, Switzerland) 3 36840288
2025 Bromodomain proteins IBD1 and IBD2 link histone acetylation to SWR1- and INO80-mediated H2A.Z regulation in Tetrahymena. Epigenetics & chromatin 2 40764940
2025 De novo SRCAP variants cause developmental and epileptic encephalopathy and the phenotypic spectrum. Epilepsia 2 41144712
2020 Generation of an iPSC line (UMGWi001-B) from a patient with Floating-Harbor Syndrome (FLHS) carrying a heterozygous SRCAP mutation (p.Arg2444). Stem cell research 2 33099107
2025 Identifying a novel SRCAP variant in floating-harbor syndrome and prenatal genetic diagnosis in this Chinese family: A case report. World journal of clinical cases 1 40671738
2025 Skin Epidermal Progenitor Maintenance by the SRCAP-H2A.Z Axis Downstream to Extracellular Signal-Regulated Kinase and mTOR Signaling. The Journal of investigative dermatology 1 40812470
2024 Combined exome and whole transcriptome sequencing identifies a de novo intronic SRCAP variant causing DEHMBA syndrome with severe sleep disorder. Journal of human genetics 1 38448605
2024 The Clonal Hematopoiesis-associated Gene Srcap Plays an Essential Role in Hematopoiesis. bioRxiv : the preprint server for biology 1 39229096
2020 [Identification of a novel frameshift variant in the SRCAP gene of a child with Floating-Harbor syndrome]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 32924116

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