Affinage

PACS1

Phosphofurin acidic cluster sorting protein 1 · UniProt Q6VY07

Length
963 aa
Mass
104.9 kDa
Annotated
2026-06-10
51 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PACS-1 is a multifunctional cytosolic sorting adaptor that controls the trans-Golgi network (TGN) localization of membrane cargo bearing phosphorylated acidic-cluster motifs (PMID:9695949). Its furin-binding region (FBR) recognizes acidic clusters that have been phosphorylated by CK2 on cargo such as furin, the mannose-6-phosphate receptor, VAMP4, nephrocystin, the olfactory CNG channel, SorLA/SORLA, and HCMV glycoprotein B, and it connects these cargo to the clathrin adaptor complexes AP-1 and AP-3 to drive endosome-to-TGN retrieval and ciliary or secretory-granule targeting (PMID:9695949, PMID:11331585, PMID:14608369, PMID:16308564, PMID:19710307, PMID:30458990). PACS-1 acts as a node in CK2-based phosphorylation cascades, coordinating opposing sorting events by both binding CK2 and being phosphorylated by it (e.g. at Ser278 to control CI-MPR retrieval) (PMID:16977309). Through these trafficking functions PACS-1 is exploited by pathogens — HIV-1 Nef engages a cargo subsite on PACS-1 through its acidic cluster to reroute MHC-I (PMID:10707087, PMID:22496420) — and modulates neuronal SORLA/APP sorting to limit amyloidogenic processing (PMID:17855360, PMID:24001769). Beyond the secretory pathway, PACS-1 shuttles between nucleus and cytoplasm via importin-α5 and CRM1 (PMID:34822171), accumulates in the nucleus at G1-S where it stabilizes HDAC2/HDAC3 to maintain histone acetylation and genomic integrity (PMID:31988453, PMID:33028635), is required upstream of BAX/BAK oligomerization for intrinsic apoptosis (PMID:28060382), and forms a complex with WDR37 needed for ER Ca²⁺ homeostasis and lymphocyte quiescence (PMID:33630350, PMID:41279321). The de novo p.R203W substitution in the FBR causes PACS1 syndrome: it disrupts an intramolecular regulatory interaction within the FBR (PMID:41858172), aberrantly enhancing HDAC6 deacetylase activity to reduce α-tubulin/cortactin acetylation and fragment the Golgi (PMID:37848409), and promoting a BICD2/dynein loss-of-function that disperses the Golgi and impairs cargo motility, with HDAC6 inhibition or Lis1 rescuing the defects (PMID:41888583).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 High

    Established the founding function of PACS-1: how cargo such as furin returns to the TGN was unknown, and PACS-1 was identified as the adaptor that reads phosphorylated acidic clusters and links cargo to clathrin sorting machinery.

    Evidence In vitro binding, in vivo localization, antisense knockdown, and cell-free TGN retrieval assays for furin and M6PR

    PMID:9695949

    Open questions at the time
    • Did not define which clathrin adaptor subunit PACS-1 contacts
    • Did not resolve the cargo-recognition domain structurally
  2. 2001 High

    Resolved how PACS-1 couples cargo to coats by mapping its association with AP-1 and AP-3 (but not AP-2) and showing a ternary furin–PACS-1–AP-1 complex, establishing the adaptor-bridging logic.

    Evidence Co-IP and dominant-negative mutagenesis of the AP-1-binding motif with cargo mislocalization readouts

    PMID:11331585

    Open questions at the time
    • Did not establish stoichiometry or the structural basis of AP-1 engagement
  3. 2006 High

    Showed PACS-1 is not a passive adaptor but a CK2-organized phosphorylation hub, both delivering CK2 to phosphorylate GGA3 and being phosphorylated at Ser278 to coordinate opposing CI-MPR sorting steps.

    Evidence In vitro kinase assays, reciprocal Co-IP, and Ser278 mutagenesis with localization readouts

    PMID:16977309

    Open questions at the time
    • Did not generalize the cascade to other cargo
    • Did not define CK2-binding interface on PACS-1
  4. 2009 High

    Extended PACS-1 cargo-sorting beyond the TGN to ciliary and regulated-secretory targeting, establishing it as a general CK2-phosphorylation-dependent adaptor for acidic-cluster cargo.

    Evidence Co-IP, dominant-negative PACS-1, CK2 inhibition, and electrophysiology for CNG channel ciliary trafficking; later siRNA/secretion assays for POMC granule packaging

    PMID:19710307 PMID:30458990

    Open questions at the time
    • Did not establish whether ciliary and granule targeting use the same adaptor partners as TGN retrieval
  5. 2012 High

    Mapped the molecular basis of pathogen hijacking by defining a bipartite Nef site engaging a cargo subsite on PACS-1/PACS-2 on Rab5/Rab7 endosomes, refining where and how Nef downregulates MHC-I.

    Evidence Bimolecular fluorescence complementation, interaction-site mutagenesis, and MHC-I downregulation assays in PBMCs

    PMID:10707087 PMID:22496420

    Open questions at the time
    • A negative siRNA study in HeLa cells (idx 8) indicates the requirement for PACS-1 in Nef/MHC-I is cell-type dependent and not fully reconciled
  6. 2013 High

    Connected PACS-1 trafficking to disease-relevant biology by showing it sorts SORLA/APP to the TGN in neurons, controlling amyloidogenic processing and Aβ degradation.

    Evidence siRNA knockdown, transgenic mice with a PACS1-binding-defective SORLA, APP/Aβ ELISA and CI-MPR/cathepsin B blots

    PMID:17855360 PMID:24001769

    Open questions at the time
    • Did not establish a causal role in human Alzheimer's disease
  7. 2017 Medium

    Revealed unexpected nuclear and apoptotic functions for PACS-1: it stabilizes HDAC2/HDAC3 to maintain chromatin acetylation and genomic integrity, and is required upstream of BAX/BAK oligomerization for intrinsic apoptosis.

    Evidence Subcellular fractionation, Co-IP with HDAC2/3, siRNA, histone-acetylation and DNA-damage assays; separate BAX/BAK oligomerization native gels with multiple apoptotic stimuli

    PMID:28060382 PMID:31988453 PMID:33028635

    Open questions at the time
    • Single-lab findings without reciprocal structural validation
    • Mechanism linking cytosolic sorting role to nuclear HDAC stabilization unresolved
    • How PACS-1 acts upstream of BAX/BAK is undefined
  8. 2021 High

    Identified the PACS-1–WDR37 complex as a regulator of ER Ca²⁺ handling and lymphocyte quiescence, and defined the nucleocytoplasmic transport machinery (importin-α5, CRM1) governing PACS-1 shuttling.

    Evidence Pacs1-/- knockout mouse with Ca²⁺ imaging and forward genetics; NLS/NES mutagenesis and Co-IP with PTBP1

    PMID:33630350 PMID:34822171

    Open questions at the time
    • Did not establish the molecular link between PACS-1/WDR37 and IP3 receptor expression
    • Functional role of the PACS-1/PTBP1 complex undefined
  9. 2023 High

    Defined the mechanism of PACS1 syndrome: the de novo R203W substitution aberrantly enhances HDAC6 deacetylase activity, reducing α-tubulin/cortactin acetylation and fragmenting the Golgi, with HDAC6 inhibition or ASOs rescuing neuronal structure.

    Evidence Co-IP from patient cells and mice, HDAC6 activity assays, acetylation blots, synapse electrophysiology, and ASO therapy in mice and patient NPCs

    PMID:23159249 PMID:37848409

    Open questions at the time
    • Did not resolve how R203W structurally enables aberrant HDAC6 binding
  10. 2026 High

    Provided the structural and motor-pathway mechanism for the R203W gain-of-function: an intramolecular FBR regulatory interaction is disrupted by R203W, and the mutant couples HDAC6 to BICD2/dynein causing dynein loss-of-function and Golgi dispersal.

    Evidence NMR solution structure of the FBR with HDAC6 binding assays; cryo-EM of the Pacs1–Wdr37 complex; Co-IP with DHC1/BICD2, cargo motility assays, HDAC6 inhibition and Lis1 rescue

    PMID:41279321 PMID:41858172 PMID:41888583

    Open questions at the time
    • Cryo-EM/phospholipid-binding inference from synaptotagmin homology is from a preprint
    • How the FBR intramolecular state is normally regulated in cells is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PACS-1's diverse functions — cytosolic cargo sorting, nuclear HDAC stabilization, apoptosis, and ER/store-operated Ca²⁺ regulation — are coordinated by one protein, and which are physiologically dominant, remains unresolved.
  • No unified model linking cytosolic and nuclear pools
  • Relative contribution of trafficking vs HDAC vs dynein defects to PACS1 syndrome unsettled
  • Structure of full-length PACS-1 with bound cargo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005794 Golgi apparatus 3 GO:0005829 cytosol 2 GO:0005768 endosome 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 3 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
AP-1AP-3BICD2GGA3HDAC2HDAC3HDAC6WDR37
Complex memberships
PACS-1–GGA3–CK2 trimeric complexPACS-1–WDR37 complexfurin–PACS-1–AP-1 ternary complex

Evidence

Reading pass · 27 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; PACS-1 connects furin to the clathrin-sorting machinery (AP-1) and functions as a coat-like protein mediating endosome-to-TGN retrieval. Antisense knockdown showed that TGN localization of furin and mannose-6-phosphate receptor, but not TGN46, depends strictly on PACS-1. In vitro binding assays, in vivo localization studies, antisense knockdown, cell-free TGN retrieval assays Cell High 9695949
2000 HIV-1 Nef binds PACS-1 via its acidic cluster (EEEE) motif; this interaction is required for Nef-induced downregulation of cell-surface MHC-I and its relocalization to the TGN. A chimeric protein bearing Nef as cytoplasmic domain localizes to the TGN after internalization in an acidic-cluster- and PACS-1-dependent manner. Co-immunoprecipitation, dominant-negative PACS-1 expression, chimeric protein localization assays, 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 mediates AP-1 binding; mutation of this motif creates a dominant-negative that mislocalizes furin and mannose-6-phosphate receptor from the TGN and inhibits Nef-mediated MHC-I downregulation. Co-immunoprecipitation, dominant-negative mutagenesis, subcellular localization assays The EMBO journal High 11331585
2002 Nef and PACS-1 cooperate to usurp the ARF6 endocytic pathway in a PI3K-dependent manner to downregulate cell-surface MHC-I to the TGN. Three Nef motifs act hierarchically: acidic cluster 62EEEE65 controls PACS-1-dependent TGN sorting, 72PXXP75 controls ARF6 activation, and M20 sequesters internalized MHC-I to the TGN. Dominant-negative expression, ARF6 activation assays, PI3K inhibition, mutagenesis of Nef motifs, subcellular localization Cell High 12526811
2003 PACS-1 interacts with the acidic cluster in the cytoplasmic domain of HCMV glycoprotein B (gB) and is required for normal TGN localization of gB. Inhibition of PACS-1 function in infected cells decreases HCMV titer; overexpression of functional PACS-1 increases titer. Co-immunoprecipitation, dominant-negative PACS-1 expression, viral titer assays, subcellular localization Journal of virology High 14512558
2003 PACS-1 mediates phosphorylation-dependent recruitment to VAMP4: CK2 phosphorylation of Ser30 on VAMP4 promotes PACS-1 binding and enhances AP-1 association with VAMP4. Dominant-negative PACS-1 causes mislocalization of VAMP4 in the regulated secretory pathway. Co-immunoprecipitation, mutagenesis of phosphorylation site, dominant-negative PACS-1, subcellular localization in AtT20 cells EMBO reports High 14608369
2005 CK2-mediated phosphorylation of three critical serine residues within an acidic cluster of nephrocystin promotes PACS-1 binding; this interaction is required for colocalization of nephrocystin with PACS-1 at the base of cilia. CK2 inhibition abolishes the interaction and causes loss of correct nephrocystin targeting. Co-immunoprecipitation, CK2 inhibition, mutagenesis of nephrocystin phosphorylation sites, immunofluorescence colocalization The EMBO journal High 16308564
2006 PACS-1 forms a trimeric complex with GGA3 and CK2 to control CI-MPR sorting. CK2 bound to PACS-1 phosphorylates GGA3, releasing it from CI-MPR, and also phosphorylates PACS-1 Ser278, promoting PACS-1 binding to CI-MPR for retrieval to the TGN. PACS-1 thus links GGA3 to CK2 in a phosphorylation cascade coordinating opposing sorting steps. Co-immunoprecipitation, in vitro kinase assays, mutagenesis of PACS-1 Ser278, GGA3 phosphorylation assays, subcellular localization The EMBO journal High 16977309
2007 PACS-1 knockdown (siRNA) has no effect on Nef-induced HLA-A2 downregulation or on localization of other acidic-cluster-containing proteins in HeLa cells, in contrast to AP-1 and clathrin knockdown which do inhibit Nef activity. Immuno-EM shows Nef reroutes MHC-I to endosomes rather than the TGN. siRNA knockdown of PACS-1, AP-1, clathrin; flow cytometry; immuno-electron microscopy Molecular biology of the cell Medium 17581864
2007 SorLA TGN localization and its activity in retaining APP requires functional interaction with PACS-1 and GGA adaptors. Aberrant targeting of sorLA to the recycling compartment or plasma membrane causes faulty APP trafficking and increased amyloidogenic processing. Co-immunoprecipitation, dominant-negative adaptor expression, subcellular localization assays, APP processing readout The Journal of biological chemistry Medium 17855360
2009 PACS-1 mediates CK2 phosphorylation-dependent ciliary trafficking of the olfactory CNG channel. CNGB1b contains PACS-1 binding sites phosphorylated by CK2; PACS-1 interacts with the CNG channel complex, and adenoviral expression of dominant-negative PACS-1 or CK2 inhibition causes CNG channel loss from cilia and olfactory dysfunction. Co-immunoprecipitation, dominant-negative PACS-1 adenoviral expression, CK2 inhibition, electrophysiology (olfactory function), immunofluorescence The Journal of neuroscience High 19710307
2012 A bipartite site on Nef (EEEE65 acidic cluster + W113 in core domain) interacts with a cargo subsite on PACS-1 and PACS-2. This interaction occurs on Rab5- and Rab7-positive endosomes (demonstrated by bimolecular fluorescence complementation). Disruption of the Nef–PACS interaction prevents Nef-induced MHC-I downregulation in PBMCs. Bimolecular fluorescence complementation, mutagenesis of Nef and PACS interaction sites, Co-immunoprecipitation, MHC-I downregulation assay in PBMCs Molecular biology of the cell High 22496420
2012 The PACS1 p.Arg203Trp de novo missense mutation causes PACS-1 to form cytoplasmic aggregates with increased protein stability in vitro. Mutant PACS1 shows impaired binding to a TRPV4 isoform but not the full-length protein. Expression of mutant PACS1 mRNA in zebrafish disrupts cranial (SOX10-positive) neural-crest cell specification and migration, causing craniofacial defects in a dominant-negative fashion. In vitro protein expression/aggregation assays, co-immunoprecipitation with TRPV4 isoforms, zebrafish mRNA injection with SOX10 reporter imaging American journal of human genetics High 23159249
2013 PACS1 interaction with SORLA is required for SORLA/APP complex sorting to the TGN in neurons. PACS1 knockdown or a PACS1-binding-defective SORLA mutant in transgenic mice increases APP processing and Aβ production. PACS1 loss also impairs CI-MPR and cathepsin B expression, affecting Aβ degradation independently of SORLA. siRNA knockdown in neuronal cell lines, transgenic mice with PACS1-binding-defective SORLA mutant, APP processing/Aβ ELISA, CI-MPR and cathepsin B Western blot Molecular and cellular biology High 24001769
2017 PACS-1 protein accumulates in the nucleus during cell cycle progression and interacts with HDAC2 and HDAC3 to regulate chromatin dynamics by maintaining histone acetylation status. PACS-1 knockdown leads to proteasome-mediated degradation of HDAC2/HDAC3, elevated H3K9 and H4K16 acetylation, and increased replication stress-induced DNA damage and genomic instability. Subcellular fractionation/nuclear accumulation during cell cycle, Co-immunoprecipitation of PACS-1 with HDAC2/HDAC3, siRNA knockdown, histone acetylation Western blot, DNA damage assays Oncogene Medium 31988453
2017 Par3 facilitates BACE1 retrograde endosome-to-TGN trafficking through aPKC-mediated phosphorylation of BACE1 Ser498, which promotes BACE1 interaction with PACS-1; disruption of this phosphorylation in AD brains correlates with reduced retrograde transport. Co-immunoprecipitation, site-directed mutagenesis of BACE1 Ser498, subcellular localization assays, human AD brain phosphorylation analysis Neurobiology of aging Medium 28946017
2017 PCAF and ADA3 transcriptionally regulate PACS1 expression. Cells with decreased PACS1 expression fail to undergo mitochondrial apoptosis (cytochrome c release) in response to granzyme B, staurosporine, UV, and etoposide due to perturbed BAX and BAK oligomerization, placing PACS1 as a required component for intrinsic apoptosis upstream of BAX/BAK oligomerization. siRNA knockdown of PACS1, cytochrome c release assay, BAX/BAK oligomerization native gel assay, cell death assays with multiple stimuli Cell death and differentiation Medium 28060382
2019 PACS1 shuttles between nucleus and cytoplasm, associates with HIV-1 Rev and CRM1, and contributes to nuclear export of unspliced viral RNA. Overexpression of PACS1 increases nuclear export of unspliced viral RNA and p24 in HIV-1-infected CD4+ T cells; siRNA depletion reduces this activity. Nuclear/cytoplasmic fractionation, Co-immunoprecipitation with Rev and CRM1, siRNA knockdown and overexpression, viral RNA export assays, p24 ELISA Virology Medium 31759187
2018 PACS-1 and AP-1 are required for targeting of POMC (pro-ACTH) to dense core secretory granules (DCSGs). Knockdown of PACS-1 or AP-1 causes POMC to be secreted into the extracellular milieu rather than packaged into DCSGs. siRNA knockdown, subcellular fractionation, secretion assay Biochemical and biophysical research communications Medium 30458990
2020 PACS-1 nuclear localization occurs at G1-S phase of the cell cycle (detected by immunofluorescence post-serum starvation release). Loss of PACS-1 via siRNA increases nuclear γH2AX and Lys382-p53 acetylation, indicating DNA damage response; PACS-1 re-expression reverses these effects. siRNA knockdown, serum starvation/release cell cycle synchronization, immunofluorescence for γH2AX and p53 acetylation, flow cytometry The Journal of biological chemistry Medium 33028635
2021 Pacs1 and Wdr37 form a complex required for normal ER Ca2+ handling in lymphocytes. Pacs1 deletion causes peripheral lymphopenia linked to blunted Ca2+ release from ER after antigen receptor stimulation, diminished IP3 receptor expression, and increased ER and oxidative stress. Mature Pacs1-/- B cells lose quiescence spontaneously, and Pacs1-Wdr37 disruption suppresses lymphoproliferative disease in mouse models. Knockout mouse (Pacs1-/-), Ca2+ imaging, forward genetic screening, IP3 receptor expression analysis, lymphocyte proliferation assays The EMBO journal High 33630350
2021 PACS-1 nuclear-cytoplasmic trafficking is mediated by importin alpha 5 (nuclear import) and exportin 1/CRM1 (nuclear export), defined by an NLS (residues 311–318) and NES3 (residues 366–375). PACS-1 forms a complex with the RNA-binding protein PTBP1 in both nucleus and cytosol; mutation of the NLS or NES3 alters localization of this PACS-1/PTBP1 complex. Mutagenesis of NLS and NES, importin/exportin interaction assays, Co-immunoprecipitation with PTBP1, subcellular localization FEBS letters Medium 34822171
2023 PACS1 p.R203W mutation increases PACS1 interaction with HDAC6, aberrantly potentiating its deacetylase activity, reducing acetylation of α-tubulin and cortactin, causing Golgi ribbon fragmentation and overpopulation of dendrites. Dendrites show varicosities, diminished spine density, and fewer functional synapses. PACS1- or HDAC6-targeting antisense oligonucleotides, or HDAC6 inhibitors, restore neuronal structure and synaptic transmission in PACS1 syndrome mice and patient NPCs. Co-immunoprecipitation (patient cells and mouse), HDAC6 activity assay, α-tubulin/cortactin acetylation Western blot, Golgi morphology imaging, spine density/synapse electrophysiology, ASO treatment in mice and patient iPSC-derived NPCs Nature communications High 37848409
2024 PACS-1 interacts with TRPC3 calcium channel and ESyt1 ER-plasma membrane tethering protein, promotes TRPC3–ESyt1 interactions, and regulates their plasma membrane localization. PACS-1 is required for proper store-operated calcium entry (SOCE) response, and ESyt1 regulates ACTH secretion through a mechanism dependent on PACS-1. Co-immunoprecipitation, plasma membrane localization assays, SOCE calcium imaging, ACTH secretion assay with knockdown ACS omega Medium 39157130
2025 Cryo-EM structure of the Pacs1–Wdr37 complex shows Pacs1 binds Wdr37 through a conserved interface within its furin-binding region (FBR). This interaction stabilizes Wdr37 and is critical for expression of both proteins. The pathogenic R203W mutation lies on a solvent-exposed surface of the FBR and does not disrupt complex formation. Structural homology of the FBR to synaptotagmin C2 domains reveals Pacs1 can bind negatively charged phospholipids through a positively charged cleft. Cryo-electron microscopy structure determination, biochemical stability assays, phospholipid binding assays, expression analysis of R203W mutant bioRxivpreprint High 41279321
2026 PACS1 interacts with cytoplasmic dynein-1 heavy chain (DHC1) and is required for furin localization at the TGN. PACS1R203W induces a dynein loss-of-function phenotype: PACS1R203W-HDAC6 recruits adaptor BICD2, forming a complex that disperses the Golgi. Cargo motility assays show PACS1R203W reduces dynein initiation frequency and velocity; these defects are rescued by HDAC6 inhibition or Lis1 expression. Co-immunoprecipitation of PACS1 with DHC1 and BICD2, cargo motility assays, HDAC6 inhibition, Lis1 overexpression rescue, Golgi morphology imaging Communications biology High 41888583
2026 NMR solution structure of the PACS-1 FBR (residues 101–273) reveals that the PACS-1/HDAC6 interaction is regulated by an intramolecular mechanism: the central unstructured region folds back across the FBR and engages a positively charged extended loop. The R203W substitution, located in this loop, disrupts this regulatory intramolecular interaction and in vitro promotes aberrant protein-protein interactions. NMR structure determination of chimeric FBR, in vitro binding assays with HDAC6, NMR-based interaction mapping, R203W 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 331 9695949
2000 HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes. Nature cell biology 252 10707087
2002 HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway. Cell 249 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 105 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 58 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 25 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 17 37848409
2024 iPSC-derived models of PACS1 syndrome reveal transcriptional and functional deficits in neuron activity. Nature communications 15 38280846
2019 PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA. Virology 15 31759187
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 14 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

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