Affinage

PACS1

Phosphofurin acidic cluster sorting protein 1 · UniProt Q6VY07

Length
963 aa
Mass
104.9 kDa
Annotated
2026-04-29
51 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PACS1 is a cytosolic sorting adaptor that governs endosome-to-TGN retrieval and regulated secretory trafficking by recognizing CK2-phosphorylated acidic cluster motifs on diverse cargo proteins—including furin, CI-MPR, VAMP4, BACE1, SorLA, nephrocystin, CNGB1b, and viral proteins—and bridging them to clathrin adaptor complexes AP-1 and AP-3 through its furin-binding region (FBR) (PMID:9695949, PMID:11331585, PMID:16977309, PMID:14608369). Beyond membrane trafficking, PACS1 shuttles between nucleus and cytoplasm via importin-α5/CRM1, stabilizes nuclear HDAC2/HDAC3 to maintain histone deacetylation and genomic integrity, forms a stability complex with WDR37 that controls ER calcium handling and lymphocyte homeostasis, and promotes BAX/BAK oligomerization in intrinsic apoptosis (PMID:34822171, PMID:31988453, PMID:33630350, PMID:28060382). Structurally, the FBR adopts a synaptotagmin-C2-like fold that binds phospholipids and is auto-inhibited by an intramolecular contact from a central unstructured region; the recurrent R203W de novo mutation disrupts this auto-inhibition, hyperactivating HDAC6 and impairing dynein-dependent retrograde transport, which fragments the Golgi and causes the synaptic and craniofacial defects of PACS1 neurodevelopmental syndrome (PMID:41858172, PMID:37848409, PMID:41888583, PMID:23159249).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    The discovery that furin's TGN localization depends on a cytosolic adaptor recognizing its phosphorylated acidic cluster established PACS-1 as a new class of CK2-regulated sorting protein linking cargo to clathrin machinery.

    Evidence Cell-free TGN retrieval assay, in vitro binding, antisense knockdown in A7 melanoma cells

    PMID:9695949

    Open questions at the time
    • No structural information on the cargo-recognition domain
    • Identity of clathrin adaptor partner not yet defined
    • Generality to non-furin cargo unknown
  2. 2001 High

    Identification of AP-1 and AP-3 (but not AP-2) as PACS-1 effector adaptors, and demonstration that dominant-negative PACS-1 mislocalizes furin, CI-MPR, and blocks Nef-mediated MHC-I downregulation, established the ternary cargo–PACS-1–adaptor sorting paradigm.

    Evidence Co-immunoprecipitation, dominant-negative PACS-1 expression, subcellular fractionation in multiple cell lines

    PMID:10707087 PMID:11331585

    Open questions at the time
    • How CK2 phosphorylation of PACS-1 itself regulates adaptor binding was unknown
    • Whether PACS-1 requirement for Nef-MHC-I pathway is cell-type-dependent
  3. 2003 High

    Extension of the PACS-1 cargo repertoire to VAMP4 and HCMV glycoprotein B demonstrated that CK2-phosphorylated acidic clusters are a general sorting signal decoded by PACS-1 in both endogenous secretory and viral trafficking pathways.

    Evidence Co-IP, CK2 kinase assays, dominant-negative PACS-1, virus titer assays

    PMID:14512558 PMID:14608369

    Open questions at the time
    • Structural basis for acidic-cluster selectivity unresolved
    • Role in neuronal cargo not yet tested
  4. 2006 High

    Discovery that PACS-1 scaffolds a CK2–GGA3 phosphorylation cascade controlling CI-MPR endosome-to-TGN retrieval revealed PACS-1 as both a kinase scaffold and a regulated cargo receptor whose own Ser278 phosphorylation gates cargo binding.

    Evidence In vitro kinase assays, phospho-specific antibodies, dominant-negative constructs, immunofluorescence

    PMID:16977309

    Open questions at the time
    • Whether the CK2–PACS-1 complex regulates additional substrates beyond GGA3 is unexplored
    • In vivo validation of the cascade lacking
  5. 2007 High

    Linking PACS-1 to SorLA/APP trafficking in neurons showed that loss of PACS-1-mediated TGN retrieval increases amyloidogenic APP processing, connecting the sorting adaptor to Alzheimer's disease-relevant biology.

    Evidence Co-IP, siRNA, dominant-negative PACS-1, Aβ ELISA in neuronal cells; later confirmed in PACS1-binding-defective SorLA knock-in mice

    PMID:17855360 PMID:24001769

    Open questions at the time
    • Whether PACS1 loss affects Aβ clearance pathways independently of SorLA
    • Human genetic association of PACS1 with AD risk not established
  6. 2009 High

    Demonstration that PACS-1 directs CNG channel subunit CNGB1b to olfactory cilia via CK2-dependent acidic cluster recognition extended the paradigm from Golgi/TGN sorting to ciliary targeting, with functional consequences for sensory neuron physiology.

    Evidence Co-IP, CK2 inhibition, dominant-negative adenoviral PACS-1, electrophysiology in olfactory neurons

    PMID:19710307

    Open questions at the time
    • Whether PACS-1 accompanies cargo to the cilium or hands off to IFT machinery unknown
  7. 2012 High

    Identification of the recurrent R203W de novo mutation as the cause of PACS1 neurodevelopmental syndrome, with demonstration that mutant protein forms cytoplasmic aggregates and disrupts cranial neural crest specification in zebrafish, established PACS1 as a disease gene and implicated FBR integrity in brain development.

    Evidence Human exome sequencing, in vitro aggregation assay, zebrafish mRNA injection, SOX10 in situ hybridization

    PMID:23159249

    Open questions at the time
    • Molecular mechanism by which R203W causes aggregation unresolved
    • Whether gain-of-function or dominant-negative effect uncertain at this stage
  8. 2017 High

    Discovery that PACS1 knockdown blocks BAX/BAK oligomerization and cytochrome c release revealed an unexpected role in the intrinsic apoptotic pathway, broadening PACS1 function beyond membrane trafficking.

    Evidence siRNA knockdown, cytochrome c release assay, BAX/BAK oligomerization, multiple death stimuli panel

    PMID:28060382

    Open questions at the time
    • Direct physical mechanism linking PACS1 to BAX/BAK oligomerization not identified
    • Whether this reflects a trafficking-dependent or trafficking-independent function unclear
  9. 2020 Medium

    Finding that nuclear PACS-1 stabilizes HDAC2/HDAC3 to maintain histone deacetylation and protect against replication-stress-induced DNA damage revealed a chromatin-regulatory function separate from its TGN sorting role.

    Evidence Co-IP with HDAC2/HDAC3, siRNA, histone acetylation western blots, comet assay

    PMID:31988453

    Open questions at the time
    • Whether PACS-1 directly shields HDACs from proteasomal targeting or acts indirectly is unclear
    • Independent replication needed
    • Relationship to cell-cycle-dependent nuclear accumulation not fully defined
  10. 2021 High

    Forward genetic identification of Pacs1–Wdr37 as a complex essential for ER calcium handling, IP3R expression, and lymphocyte survival established PACS1 in ER-related signaling and immune homeostasis.

    Evidence Mouse Pacs1 knockout, calcium imaging, IP3R western blot, in vivo lymphoproliferation models

    PMID:33630350

    Open questions at the time
    • How the Pacs1–Wdr37 complex controls IP3R expression (transcriptional vs. post-translational) unknown
    • Whether the ER calcium defect contributes to PACS1 syndrome neuronal phenotypes untested
  11. 2023 High

    Demonstration that PACS1 is an HDAC6 effector and that R203W hyperactivates HDAC6 deacetylase activity, causing tubulin/cortactin deacetylation, Golgi fragmentation, and synaptic deficits rescued by ASOs, provided the first actionable disease mechanism for PACS1 syndrome.

    Evidence HDAC6 activity assay, acetylation blots, confocal Golgi/dendrite imaging, electrophysiology, ASO rescue in mouse model and patient NPCs

    PMID:37848409

    Open questions at the time
    • Whether HDAC6 hyperactivation explains all PACS1 syndrome phenotypes or only neuronal ones
    • Long-term ASO efficacy and safety in vivo unknown
  12. 2025 High

    Cryo-EM structure of the Pacs1–Wdr37 complex revealed FBR structural homology to synaptotagmin C2 domains and a phospholipid-binding cleft, redefining the FBR as both a protein- and lipid-recognition module; the R203W residue is surface-exposed but does not disrupt complex formation.

    Evidence Cryo-EM structure, targeted proteolysis, phospholipid binding assays (preprint)

    PMID:41279321

    Open questions at the time
    • Functional role of phospholipid binding in cargo sorting or membrane association not tested in cells
    • How R203W surface exposure relates to HDAC6 gain-of-interaction requires integration with NMR data
  13. 2026 High

    NMR structure of the FBR revealed that an intramolecular autoinhibitory contact normally restrains HDAC6 binding, and R203W disrupts this contact, while functional studies showed R203W also impairs dynein-driven retrograde transport through an aberrant PACS1–HDAC6–BICD2 complex, unifying the Golgi fragmentation and cargo mislocalization phenotypes.

    Evidence NMR solution structure, in vitro binding with HDAC6, co-IP of dynein/BICD2 complex, cargo motility assays, HDAC6i/Lis1 rescue

    PMID:41858172 PMID:41888583

    Open questions at the time
    • Whether the autoinhibitory mechanism also gates interactions with other partners (AP-1, WDR37) not addressed
    • Full-length PACS1 structure still unavailable
    • Therapeutic targeting of the R203W-specific HDAC6 interface not yet achieved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how PACS1 coordinates its multiple functions (trafficking, nuclear HDAC regulation, apoptosis, ER calcium) through a single FBR scaffold, whether phospholipid binding by the C2-like domain regulates membrane recruitment in vivo, and whether R203W-driven HDAC6 hyperactivation accounts for all clinical features of PACS1 syndrome.
  • Full-length PACS1 structure lacking
  • No systematic substrate/cargo interactome
  • ER calcium and apoptotic roles not integrated with trafficking paradigm

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0005794 Golgi apparatus 4 GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 4 R-HSA-112316 Neuronal System 3 R-HSA-5357801 Programmed Cell Death 1
Partners
AP1M1BICD2CSNK2A1FURINGGA3HDAC6SORL1WDR37
Complex memberships
PACS1-AP-1 ternary sorting complexPACS1-CK2-GGA3 scaffold complexPACS1-WDR37 complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PACS-1 directs TGN localization of furin by binding to the protease's phosphorylated cytosolic acidic cluster domain, acting as a coat protein that connects furin to clathrin-sorting machinery; cell-free assays showed TGN localization is directed by a PACS-1-mediated retrieval step from endosomes. In vitro binding assays, cell-free TGN localization assays, antisense studies, co-immunoprecipitation Cell High 9695949
2000 HIV-1 Nef binds PACS-1 via its acidic cluster (EEEE motif) to redirect internalized MHC-I from the cell surface to the TGN; Nef acts as a connector between MHC-I cytoplasmic tail and the PACS-1-dependent sorting pathway. Co-immunoprecipitation, chimeric protein localization, dominant-negative PACS-1 expression, confocal microscopy Nature cell biology High 10707087
2001 PACS-1 associates with adaptor complexes AP-1 and AP-3 (but not AP-2), forming a ternary complex with furin and AP-1; a short sequence in PACS-1 is essential for AP-1 binding, and dominant-negative PACS-1 (which binds cargo but not adaptors) mislocalizes furin, mannose-6-phosphate receptor, and blocks Nef-mediated MHC-I downregulation. Co-immunoprecipitation, dominant-negative mutant expression, subcellular fractionation, immunofluorescence The EMBO journal High 11331585
2002 Nef and PACS-1 combine to usurp the ARF6 endocytic pathway in a PI3K-dependent manner to downregulate cell-surface MHC-I to the TGN; three hierarchical Nef motifs (acidic cluster EEEE65, SH3-binding PXXP, and M20) control PACS-1-dependent TGN sorting, ARF6 activation, and MHC-I sequestration, respectively. Dominant-negative constructs, RNA interference, epistasis analysis, immunofluorescence, co-immunoprecipitation Cell High 12526811
2003 PACS-1 interacts with the cytoplasmic acidic cluster domain of HCMV glycoprotein B (gB) and is required for normal TGN localization of gB; inhibition of PACS-1 decreases HCMV titer while overexpression increases titer. Co-immunoprecipitation, dominant-negative PACS-1 expression, virus titer assays, immunofluorescence Journal of virology High 14512558
2003 PACS-1 mediates phosphorylation-dependent recruitment to VAMP4 by binding the phosphorylated acidic cluster (Ser30) of VAMP4, thereby enhancing AP-1 association with VAMP4 cargo; dominant-negative PACS-1 causes mislocalization of VAMP4 in the regulated secretory pathway. Co-immunoprecipitation, dominant-negative PACS-1 expression, immunofluorescence, casein kinase 2 phosphorylation assays EMBO reports High 14608369
2005 PACS-1 interacts with nephrocystin in a CK2-phosphorylation-dependent manner; CK2 phosphorylation of three critical serines in nephrocystin's acidic cluster mediates PACS-1 binding and is essential for nephrocystin localization to the base of cilia; CK2 inhibition disrupts this interaction and abrogates correct nephrocystin targeting. Co-immunoprecipitation, kinase inhibition assays, immunofluorescence, dominant-negative studies The EMBO journal High 16308564
2006 PACS-1 forms a multimeric complex with GGA3 and CK2 that controls CI-MPR sorting; PACS-1-bound CK2 phosphorylates GGA3 (releasing it from CI-MPR/endosomes) and phosphorylates PACS-1 Ser278 (promoting PACS-1 binding to CI-MPR for retrieval to TGN), constituting a CK2-controlled phosphorylation cascade. Co-immunoprecipitation, in vitro kinase assays, dominant-negative constructs, phospho-specific antibodies, immunofluorescence The EMBO journal High 16977309
2007 PACS-1 is required for SorLA localization to TGN compartments; SorLA interaction with PACS-1 (and GGA) controls intracellular routing of SorLA/APP complexes, and aberrant SorLA targeting caused by loss of PACS-1 function results in increased amyloidogenic APP processing. Co-immunoprecipitation, dominant-negative PACS-1, siRNA knockdown, immunofluorescence, ELISA for Aβ The Journal of biological chemistry High 17855360
2007 Knockdown of PACS-1 by siRNA does not inhibit Nef-mediated downregulation of HLA-A2 in HeLa cells, and does not affect localization of other acidic-cluster-motif proteins; instead, AP-1 and clathrin are required, and Nef reroutes MHC-I to endosomes rather than TGN. siRNA knockdown, immunoelectron microscopy, flow cytometry, immunofluorescence Molecular biology of the cell Medium 17581864
2009 PACS-1 is expressed in olfactory sensory neurons and interacts with the CNG channel subunit CNGB1b; CK2 phosphorylates two acidic cluster sites on CNGB1b to enable PACS-1 binding; CK2 inhibition or dominant-negative PACS-1 expression causes loss of CNG channel from cilia and olfactory dysfunction. Co-immunoprecipitation, adenoviral dominant-negative expression, CK2 inhibition, electrophysiology, immunofluorescence The Journal of neuroscience High 19710307
2012 HIV-1 Nef interacts with PACS-1 and PACS-2 through a bipartite site on Nef (EEEE65 acidic cluster and W113 in core domain) engaging a previously unidentified cargo subsite on PACS proteins; this interaction occurs on Rab5/Rab7-positive endosomes and is required for Nef-mediated MHC-I downregulation in PBMCs. Bimolecular fluorescence complementation, site-directed mutagenesis, co-immunoprecipitation, flow cytometry, immunofluorescence Molecular biology of the cell High 22496420
2012 Recurrent de novo PACS1 mutation (p.Arg203Trp) causes PACS1 protein to form cytoplasmic aggregates with increased protein stability, shows impaired binding to an isoform-specific TRPV4 variant, and expression of mutant PACS1 mRNA in zebrafish induces craniofacial defects by disrupting SOX10-positive cranial neural crest cell specification and migration. In vitro aggregation assay, co-immunoprecipitation (binding to TRPV4), zebrafish mRNA injection, in situ hybridization (SOX10 marker) American journal of human genetics High 23159249
2013 PACS1 interaction with SORLA is required for SORLA/APP complex sorting to the TGN in neurons; disruption of SORLA-PACS1 interaction (by PACS1 knockdown or PACS1-binding-defective SORLA knock-in mice) increases APP processing in the brain; PACS1 loss also impairs CI-MPR and cathepsin B expression, reducing Aβ degradation. siRNA knockdown in neuronal lines, transgenic knock-in mice with PACS1-binding-defective SORLA, ELISA for Aβ, immunofluorescence Molecular and cellular biology High 24001769
2017 PACS1 regulates intrinsic (mitochondrial) apoptosis: PACS1 knockdown renders cells refractory to mitochondrial pathway death stimuli (granzyme B, staurosporine, UV, etoposide) but not TRAIL; protected cells fail to release cytochrome c due to perturbed BAX and BAK oligomerization; PCAF and ADA3 transcriptionally regulate PACS1 expression. siRNA knockdown, cytochrome c release assay, BAX/BAK oligomerization assay, cell death assays, ChIP Cell death and differentiation High 28060382
2017 Par3 promotes BACE1 retrograde trafficking from endosomes to TGN through aPKC-mediated phosphorylation of BACE1 Ser498, which promotes BACE1 interaction with PACS-1 and facilitates endosome-to-TGN retrieval; decreased Ser498 phosphorylation is found in AD brains. Co-immunoprecipitation, site-directed mutagenesis, dominant-negative aPKC, immunofluorescence, human AD brain phospho-western blot Neurobiology of aging High 28946017
2018 PACS-1 and AP-1 are required for targeting POMC/ACTH to dense core secretory granules (DCSGs); knockdown of PACS-1 or AP-1 causes POMC to be secreted constitutively rather than sorted to DCSGs. siRNA knockdown, ELISA for secreted ACTH, immunofluorescence Biochemical and biophysical research communications Medium 30458990
2019 PACS1 shuttles between nucleus and cytoplasm, associates with HIV-1 Rev protein and its cofactor CRM1, and promotes nuclear export of unspliced viral RNA; overexpression increases nuclear export and p24 expression, while siRNA depletion reduces viral RNA export via the Rev-CRM1 pathway. Co-immunoprecipitation, siRNA knockdown, overexpression, nuclear fractionation, RT-PCR for viral RNA Virology Medium 31759187
2020 PACS-1 accumulates in the nucleus during cell cycle progression and interacts with HDAC2 and HDAC3; PACS-1 knockdown causes proteasome-mediated degradation of HDAC2/HDAC3, elevated H3K9 and H4K16 acetylation, and increased replication stress-induced DNA damage and genomic instability. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, histone acetylation western blots, comet assay Oncogene Medium 31988453
2021 Pacs1 forms a complex with Wdr37 that is required for normal ER calcium handling in lymphocytes; deletion of Pacs1 causes peripheral lymphopenia, blunted Ca2+ release from ER after antigen receptor stimulation, diminished inositol triphosphate receptor expression, and increased ER/oxidative stress; disruption of Pacs1-Wdr37 also suppresses lymphoproliferative disease. Forward genetic screen in mice, Pacs1 knockout, calcium imaging, IP3R expression western blot, in vivo lymphoproliferation models The EMBO journal High 33630350
2021 PACS-1 nuclear trafficking is mediated by interaction with importin alpha 5 (nuclear entry) and exportin 1/CRM1 (nuclear exit); a nuclear localization signal (NLS, residues 311-318) and nuclear export signal (NES3, residues 366-375) were identified; PACS-1 also forms a complex with RNA-binding protein PTBP1 in both nucleus and cytoplasm. Site-directed mutagenesis of NLS/NES, co-immunoprecipitation with importin alpha 5 and exportin 1, immunofluorescence of NLS/NES mutants FEBS letters Medium 34822171
2023 PACS1 is an HDAC6 effector; the R203W substitution increases the PACS1/HDAC6 interaction, aberrantly potentiating deacetylase activity; this reduces acetylation of α-tubulin and cortactin, causing Golgi ribbon fragmentation and overpopulation of dendrites, increased dendritic arborization, varicosities, reduced spine density, and fewer functional synapses in hippocampal neurons and patient-derived NPCs; treatment with PACS1- or HDAC6-targeting antisense oligonucleotides restores neuronal structure and synaptic transmission. Co-immunoprecipitation, HDAC6 activity assay, acetylation western blots, confocal microscopy of Golgi/dendrites, electrophysiology, ASO treatment in PACS1 syndrome mice Nature communications High 37848409
2024 PACS-1 interacts with TRPC3 calcium transporter and ESyt1 ER-plasma membrane tethering protein; PACS-1 promotes TRPC3-ESyt1 interactions and regulates their plasma membrane localization; PACS-1 is required for proper store-operated calcium entry (SOCE) response and for ESyt1-mediated regulation of ACTH secretion in corticotropic cells. Co-immunoprecipitation, siRNA knockdown, calcium imaging (SOCE assay), immunofluorescence, ACTH secretion ELISA ACS omega Medium 39157130
2025 Cryo-EM structure of the Pacs1-Wdr37 complex shows Pacs1 binds Wdr37 through its furin-binding region (FBR); this interaction stabilizes Wdr37 and is critical for expression of both proteins; the FBR has structural homology to synaptotagmin C2 domains and can bind negatively charged phospholipids through a unique positively charged cleft; the R203W pathogenic mutation lies on a solvent-exposed surface of the FBR and does not disrupt complex formation but remains dependent on Wdr37 for stability. Cryo-electron microscopy structure determination, targeted proteolysis, phospholipid binding assays bioRxivpreprint High 41279321
2026 Cytoplasmic dynein-1 heavy chain (DHC1) is a PACS1 interactor essential for maintaining furin localization at the TGN; PACS1R203W induces a dynein loss-of-function phenotype by recruiting BICD2 adaptor and forming a PACS1R203W-HDAC6-BICD2 complex that disperses the Golgi and impairs dynein-driven cargo motility (reduced initiation frequency and velocity); HDAC6 inhibition or Lis1 overexpression rescues dynein function. Co-immunoprecipitation, cargo motility assays, HDAC6 inhibition rescue, dominant-negative Lis1, immunofluorescence of Golgi/furin Communications biology High 41888583
2026 NMR solution structure of PACS-1 furin-binding region (FBR, residues 101-273) shows that the PACS-1/HDAC6 interaction is regulated by an intramolecular mechanism in which the central unstructured region of PACS-1 folds back across the FBR to engage a positively charged loop; the R203W substitution disrupts this intramolecular regulatory contact in vitro, promoting aberrant protein-protein interactions. NMR solution structure determination, in vitro binding assays with HDAC6, mutagenesis The FEBS journal High 41858172

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell 330 9695949
2000 HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes. Nature cell biology 251 10707087
2002 HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway. Cell 247 12526811
2001 PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic. The EMBO journal 164 11331585
2007 SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1. The Journal of biological chemistry 154 17855360
2012 Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome. American journal of human genetics 104 23159249
2007 HIV-1 Nef-induced down-regulation of MHC class I requires AP-1 and clathrin but not PACS-1 and is impeded by AP-2. Molecular biology of the cell 87 17581864
2006 A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking. The EMBO journal 78 16977309
2005 Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia. The EMBO journal 75 16308564
2003 Role of PACS-1 in trafficking of human cytomegalovirus glycoprotein B and virus production. Journal of virology 59 14512558
2012 An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I. Molecular biology of the cell 57 22496420
2003 AP-1 recruitment to VAMP4 is modulated by phosphorylation-dependent binding of PACS-1. EMBO reports 55 14608369
2017 Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization. Cell death and differentiation 54 28060382
2016 Clinical delineation of the PACS1-related syndrome--Report on 19 patients. American journal of medical genetics. Part A 49 26842493
2013 SORLA-dependent and -independent functions for PACS1 in control of amyloidogenic processes. Molecular and cellular biology 30 24001769
2009 PACS-1 mediates phosphorylation-dependent ciliary trafficking of the cyclic-nucleotide-gated channel in olfactory sensory neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 19710307
2020 Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer. The Journal of biological chemistry 28 33028635
2021 Calcium flux control by Pacs1-Wdr37 promotes lymphocyte quiescence and lymphoproliferative diseases. The EMBO journal 26 33630350
2017 Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1. Neurobiology of aging 24 28946017
2020 The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability. Oncogene 23 31988453
2021 Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review. Genes 20 34068396
2017 A novel missense mutation affecting the same amino acid as the recurrent PACS1 mutation in Schuurs-Hoeijmakers syndrome. Clinical genetics 20 28975623
2021 miR-485-5p alleviates Alzheimer's disease progression by targeting PACS1. Translational neuroscience 19 34594577
2023 Neural deficits in a mouse model of PACS1 syndrome are corrected with PACS1- or HDAC6-targeting therapy. Nature communications 16 37848409
2019 PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA. Virology 15 31759187
2024 iPSC-derived models of PACS1 syndrome reveal transcriptional and functional deficits in neuron activity. Nature communications 14 38280846
2022 Molecular Basis of the Schuurs-Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches. International journal of molecular sciences 14 36077045
2021 PACS1-Neurodevelopmental disorder: clinical features and trial readiness. Orphanet journal of rare diseases 14 34517877
2020 Renpenning Syndrome in a Turkish Patient: de novo Variant c.607C>T in PACS1 and Hypogammaglobulinemia Phenotype. Molecular syndromology 13 32903913
2018 Ocular manifestations of PACS1 mutation. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 12 29550517
2020 Coloboma may be a shared feature in a spectrum of disorders caused by mutations in the WDR37-PACS1-PACS2 axis. American journal of medical genetics. Part A 11 33369122
2021 PACS-1 contains distinct motifs for nuclear-cytoplasmic transport and interacts with the RNA-binding protein PTBP1 in the nucleus and cytosol. FEBS letters 8 34822171
2018 PACS-1 and adaptor protein-1 mediate ACTH trafficking to the regulated secretory pathway. Biochemical and biophysical research communications 5 30458990
2024 PACS-1 variant protein is aberrantly localized in Caenorhabditis elegans model of PACS1/PACS2 syndromes. Genetics 4 39031646
2023 Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability? American journal of medical genetics. Part A 4 37141437
2025 Expanding the Clinical Spectrum Associated with the Recurrent Arg203Trp Variant in PACS1: An Italian Cohort Study. Genes 2 40004556
2024 PACS-1 Interacts with TRPC3 and ESyt1 to Mediate Protein Trafficking while Promoting SOCE and Cooperatively Regulating Hormone Secretion. ACS omega 2 39157130
2022 A Novel PACS1 Variant Associated With Schuurs-Hoeijmakers Syndrome Phenotype in an Indigenous Descendant in Brazil: A Case Report. Cureus 2 36415352
2022 First Report of Mexican Patients with PACS1-Related Neurodevelopmental Disorder and Review of the PACS1-, PACS2-, and WDR37-Related Ophthalmological Manifestations. Molecular syndromology 2 37064331
2025 AI-Based Facial Phenotyping Supports a Shared Molecular Axis in PACS1-, PACS2-, and WDR37-Related Syndromes. International journal of molecular sciences 1 40869285
2024 PACS2, PACS1, and VACTERL: A Clinical Overlap. Molecular syndromology 1 39911171
2023 RNA-targeted therapy corrects neuronal deficits in PACS1 syndrome mice. Research square 1 36747781
2023 A case report of retinal dystrophy in patients with PACS1 syndrome. Ophthalmic genetics 1 37218682
2021 WITHDRAWN: Schuurs-Hoeijmakers syndrome: Severe expression of the recurrent PACS1 c.607C>T mutation. Brain & development 1 33994196
2026 The R203W substitution drives PACS-1 syndrome by disrupting intramolecular regulation. The FEBS journal 0 41858172
2026 DNA methylation signature and clinical delineation of PACS1-related disorder in 24 unreported individuals. European journal of human genetics : EJHG 0 41882293
2026 PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2. Communications biology 0 41888583
2025 The Structural Basis for Pacs1-Wdr37 Complex Assembly and Stability. bioRxiv : the preprint server for biology 0 41279321
2025 PACS1 syndrome variant alters proteomic landscape of developing cortical organoids. bioRxiv : the preprint server for biology 0 41497635
2024 PACS-1 variant protein is aberrantly localized in C. elegans model of PACS1/PACS2 syndromes. bioRxiv : the preprint server for biology 0 38712144
2023 Genetic characterization of Schuurs-Hoeijmakers syndrome in a moroccan individual with heterozygote PACS1 mutation. Molecular biology reports 0 37747683