Affinage

HIP1

Huntingtin-interacting protein 1 · UniProt O00291

Length
1037 aa
Mass
116.2 kDa
Annotated
2026-06-10
84 papers in source corpus 24 papers cited in narrative 22 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

HIP1 is a multi-domain endocytic adaptor that links clathrin-coated vesicle assembly to actin dynamics, receptor trafficking, and—in the context of huntingtin biology—apoptotic and transcriptional regulation (PMID:11517213, PMID:11532990, PMID:11577110, PMID:12839988). It co-purifies with brain clathrin-coated vesicles and directly binds the clathrin heavy chain terminal domain and the AP-2 adaptor complex through discrete modular clathrin-box and AP2-binding motifs, while membrane anchoring through its ENTH domain, which binds 3-phosphate phosphoinositides, allows HIP1 and AP-2 to recruit clathrin to the bilayer and nucleate lattice biogenesis (PMID:11517213, PMID:11532990, PMID:11577110, PMID:14732715). Its central helical/coiled-coil domain binds clathrin light chain through residues Leu-451/Leu-452/Arg-453 and stimulates clathrin assembly; light-chain binding drives a compact coiled-coil conformation that suppresses the intrasterically regulated F-actin binding of the C-terminal I/LWEQ (THATCH) module, coupling coat assembly to actin regulation (PMID:11889126, PMID:15533940, PMID:15533941, PMID:18790740, PMID:15581353). Live-cell imaging places HIP1 at early clathrin-coated pits during pit maturation, and HIP1-null mice show defective endocytic complex assembly and impaired clathrin-mediated internalization of GluR1 AMPA receptors; HIP1 associates with NMDA receptors and is required for NMDA-induced AMPA receptor internalization, long-term depression, and excitotoxicity, while also stabilizing endocytosed receptor tyrosine kinases (PMID:19626275, PMID:12839988, PMID:17329427, PMID:14732715). Through its discovery as a polyglutamine-sensitive huntingtin partner, HIP1 connects to a death pathway: free HIP1 heterodimerizes with Hippi to recruit procaspase-8 and initiate extrinsic apoptosis, and acts as a nuclear transporter for Hippi, which binds promoters of caspase-1/-8/-10 and REST/NRSF to activate their transcription (PMID:9140394, PMID:11788820, PMID:19934260, PMID:21832040). In disease, HIP1 functions as a constitutively active oncogenic fusion partner of ALK in NSCLC and promotes RTK-driven invasion through integrin turnover and RAC1 activation (PMID:24496003, PMID:24518094, PMID:24790222, PMID:30049830).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 High

    Established HIP1's founding biological context by showing it is a huntingtin-interacting protein whose binding is inversely sensitive to polyglutamine length, tying it to both the neuronal cytoskeleton and Huntington's disease.

    Evidence Yeast two-hybrid, co-localization, and biochemical interaction assays in brain

    PMID:9140394

    Open questions at the time
    • Did not define HIP1's intrinsic molecular function
    • Mechanism by which polyQ expansion releases HIP1 not resolved
  2. 2001 High

    Defined HIP1 as a clathrin-coated vesicle adaptor by mapping direct binding to clathrin heavy chain and AP-2 and showing dominant-negative fragments block clathrin-mediated endocytosis, and reconstituted ENTH-anchored, AP-2-dependent clathrin recruitment to lipid bilayers.

    Evidence CCV purification, direct binding/deletion mapping, dominant-negative endocytosis block, liposome recruitment and clathrin assembly assays in vitro

    PMID:11517213 PMID:11532990 PMID:11577110

    Open questions at the time
    • Cargo specificity in cells not yet established
    • Role of actin-binding module not addressed
  3. 2002 High

    Resolved how HIP1 stimulates coat assembly versus binds actin, showing the central helical domain binds clathrin light chain to drive assembly while HIP1 (unlike paralogue HIP12) does not sediment with F-actin in vitro.

    Evidence In vitro binding, clathrin assembly assays, F-actin co-sedimentation, deletion/mutation mapping

    PMID:11889126

    Open questions at the time
    • Apparent lack of HIP1 actin binding later refined by intrasteric regulation findings
    • In vivo relevance of assembly stimulation untested here
  4. 2002 High

    Connected HIP1 to apoptosis by demonstrating that huntingtin-released HIP1 heterodimerizes with Hippi through pseudo-death-effector domains and recruits procaspase-8, defining a death-receptor-independent extrinsic apoptotic trigger.

    Evidence Reciprocal Co-IP, yeast two-hybrid, caspase-8 recruitment and apoptosis assays

    PMID:11788820

    Open questions at the time
    • Structural basis of the pseudo-DED interaction undefined at this stage
    • In vivo contribution to HD neuronal death not quantified
  5. 2003 High

    Provided in vivo proof that HIP1 is required for clathrin-mediated receptor trafficking, with knockout mice showing neurological deficits and a dose-dependent defect in GluR1 AMPA receptor internalization.

    Evidence Targeted gene knockout, neuronal internalization assays, liposome endocytic-complex assembly assay

    PMID:12839988

    Open questions at the time
    • Whether trafficking defect alone causes the neurological phenotype unresolved
    • Other cargo beyond AMPA receptors not surveyed
  6. 2004 High

    Defined the molecular interface and regulatory logic of clathrin assembly stimulation, identifying the CLC regulatory sequence and HIP1 residues L451/L452/R453 as required for assembly and CCV targeting, and showing CLC overexpression perturbs actin distribution.

    Evidence CLC and HIP1 mutagenesis, in vitro clathrin assembly assay, subcellular localization, in vivo actin distribution analysis

    PMID:15533940 PMID:15533941

    Open questions at the time
    • How CLC binding mechanistically couples to actin not yet established
    • Separation of assembly from dimerization functions only partially mapped
  7. 2004 Medium

    Extended HIP1's roles beyond coat assembly, showing ENTH-domain binding to PI(3,4)P2/PI(3,5)P2 and a function in stabilizing endocytosed receptor tyrosine kinases, while ENTH deletion triggers apoptosis.

    Evidence Lipid-binding assays with ENTH mutants, receptor half-life measurements, apoptosis assays

    PMID:14732715

    Open questions at the time
    • Single lab with two methods
    • Mechanism linking ENTH deletion to apoptosis unclear
  8. 2004 Medium

    Characterized the actin-binding module as intrasterically autoinhibited, explaining why full-length HIP1 actin binding is conditional and showing the I/LWEQ module stabilizes filaments and harbors a dimerization motif.

    Evidence F-actin co-sedimentation, affinity measurements, truncation/mutagenesis of the I/LWEQ module

    PMID:15581353

    Open questions at the time
    • Physiological trigger relieving autoinhibition not identified here
    • Single lab in vitro analysis
  9. 2006 Medium

    Provided structural insight into the coiled-coil dimerization domain, revealing a partially splayed-open dimer and a candidate CLC-interaction surface.

    Evidence X-ray crystallography of residues 482-586 at 2.8 Å

    PMID:17257618

    Open questions at the time
    • Proposed S3 CLC-binding surface not functionally validated in the study
    • Static structure does not capture conformational regulation
  10. 2007 Medium

    Structurally ruled out a canonical death-effector-domain fold for the Hippi-interaction module and proposed a basic surface as the binding site.

    Evidence X-ray crystallography of subfragment 371-481 at 2.8 Å with structural comparison

    PMID:18155047

    Open questions at the time
    • Hippi-binding surface assignment is structural inference without mutagenesis
    • Does not explain pseudo-DED functional behavior
  11. 2007 High

    Demonstrated HIP1's requirement for NMDA-receptor-dependent synaptic plasticity and neuroprotection, showing physical association with NMDARs, impaired NMDA-induced AMPA internalization and LTD, and partial protection from excitotoxicity in knockout neurons.

    Evidence GST pull-down, Co-IP, internalization assays in KO neurons, LTD electrophysiology, excitotoxicity assays

    PMID:17329427

    Open questions at the time
    • Direct versus indirect NMDAR association not fully distinguished
    • Link to Akt/huntingtin phosphorylation mechanistically open
  12. 2008 High

    Unified coat assembly and actin regulation by showing clathrin light chain binding induces a compact coiled-coil conformation that suppresses THATCH-domain actin binding, establishing CLC as a negative regulator of HIP1-actin interactions.

    Evidence Calorimetry, analytical ultracentrifugation, CD, actin co-sedimentation

    PMID:18790740

    Open questions at the time
    • In vivo timing of this conformational switch during endocytosis not measured
    • Whether HIP1 heterodimerizes with HIP1R in vivo remains unsettled
  13. 2009 Medium

    Placed HIP1 temporally and spatially in coated-pit maturation by live imaging, showing early recruitment, loss after vesicle closure, clathrin-dependent membrane localization, and dominant-negative inhibition of transferrin uptake.

    Evidence Live-cell imaging, pHluorin-transferrin assay, shRNA clathrin knockdown, dominant-negative fragment expression

    PMID:19626275

    Open questions at the time
    • Single lab
    • Quantitative kinetics relative to other coat proteins limited
  14. 2009 Medium

    Defined a nuclear, transcriptional arm of HIP1/Hippi signaling, showing HIP1 acts as nuclear transporter for Hippi, which binds caspase-1/-8/-10 promoters to upregulate them.

    Evidence Luciferase reporters, ChIP, R393E mutagenesis, HIP1 NLS deletion and knockdown

    PMID:19934260

    Open questions at the time
    • Single lab
    • Physiological stimulus driving nuclear translocation not defined
  15. 2011 Medium

    Connected the nuclear HIP1/Hippi function to Huntington's disease pathology, showing reduced mutant-huntingtin binding increases nuclear HIP1/Hippi, REST promoter occupancy and REST upregulation, repressing BDNF and proenkephalin.

    Evidence ChIP, luciferase reporter, HIP1 overexpression/knockdown, NLS mutation, polyQ HD model

    PMID:21832040

    Open questions at the time
    • Single lab
    • Endogenous quantitative contribution to HD transcriptional dysregulation untested
  16. 2014 Medium

    Identified HIP1 as an oncogenic driver, both as a constitutively active ALK fusion partner in NSCLC and as a c-Met effector promoting β1-integrin turnover and mesenchymal invasion.

    Evidence RNA-seq/RT-PCR/sequencing and crizotinib PDX study; siRNA screen, integrin trafficking and invasion assays

    PMID:24496003 PMID:24518094 PMID:24790222

    Open questions at the time
    • How the endocytic adaptor function relates to fusion oncogenicity unclear
    • Generality across tumor types not established
  17. 2018 Medium

    Broadened HIP1's signaling and physiological roles, showing it is required for PDGFR/RTK-driven RAC1 activation and invasion in arthritis, and that its degenerative phenotype involves choline metabolism (Gdpd3) and is not brain-autonomous.

    Evidence siRNA knockdown, RAC1 activation/invasion assays, KO arthritis model; conditional KO, tissue-specific rescue, metabolomics, double-KO epistasis

    PMID:30049830 PMID:30224518

    Open questions at the time
    • Mechanistic link between endocytic adaptor activity and choline metabolism unresolved
    • Tissue of origin of degenerative phenotype not pinpointed
  18. 2022 Medium

    Implicated HIP1 in prostate cancer signaling as a stabilized partner of UGT2B28 priming AR/EGFR-ERK1/2-driven proliferation and EMT.

    Evidence Co-IP, siRNA knockdown, ERK1/2/AR/EGFR signaling and proliferation assays

    PMID:36343786

    Open questions at the time
    • Single lab with limited mechanistic depth on HIP1 specifically
    • Direct versus indirect role of HIP1 in receptor signaling unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HIP1's conformational regulation, lipid/actin/clathrin coupling, and nuclear apoptotic/transcriptional functions are integrated and switched in living cells, and how its endocytic activity mechanistically underlies its oncogenic and metabolic roles, remains unresolved.
  • No unified model linking membrane and nuclear functions
  • Physiological triggers for HIP1 release from huntingtin and nuclear translocation undefined
  • Connection between endocytic adaptor mechanism and cancer/metabolic phenotypes unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0008289 lipid binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005634 nucleus 2 GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ALKAP2CLTACLTCGRIN1HIPPIHTTUGT2B28
Complex memberships
HIP1/Hippi heterodimerclathrin coat

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 HIP1 (human homologue of S. cerevisiae Sla2p) directly interacts with huntingtin in the brain; this interaction is inversely correlated with polyglutamine length in huntingtin, and HIP1 co-localizes with membrane-associated huntingtin, providing a molecular link between huntingtin and the neuronal cytoskeleton. Yeast two-hybrid, co-localization, biochemical interaction assays Nature genetics High 9140394
2001 HIP1 co-purifies with clathrin-coated vesicles from brain, directly binds the terminal domain of clathrin heavy chain and the AP-2 adaptor complex (predominantly through amino acids 276–335 containing consensus clathrin- and AP2-binding sites), and its coiled-coil domain cooperates with these sites to target HIP1 to CCVs. Expression of HIP1 fragments potently blocks clathrin-mediated endocytosis. CCV purification, co-immunoprecipitation, direct binding assays, deletion mapping, dominant-negative overexpression with endocytosis block readout The Journal of biological chemistry High 11517213 11532990 11577110
2001 HIP1 binds both AP-2 and clathrin via discrete modular interaction sequences analogous to those in epsin and AP180; anchored to a phosphoinositide-containing membrane via its ENTH domain, HIP1 associates with AP-2 and together they efficiently recruit clathrin to the bilayer, implicating HIP1 in lipid-regulated clathrin lattice biogenesis. In vitro binding assays, liposome recruitment assays, clathrin assembly assays, CCV co-purification The Journal of biological chemistry High 11577110
2002 Free Hip-1 (released from huntingtin upon polyglutamine expansion) binds the novel protein Hippi via their pseudo-death-effector domains to form a heterodimer; this Hip-1/Hippi heterodimer recruits procaspase-8 into a ternary complex, initiating apoptosis through the extrinsic caspase-8 pathway independent of death receptors. Co-immunoprecipitation, yeast two-hybrid, caspase-8 recruitment assay, apoptosis assays Nature cell biology High 11788820
2002 HIP1 and its paralogue HIP12 are major components of the clathrin coat; HIP1 contains a clathrin-box and AP2 consensus-binding sites mediating high-affinity binding to clathrin heavy chain terminal domain and AP2 alpha-ear, respectively. Both HIP1 and HIP12 stimulate clathrin assembly through their central helical domain, which binds directly to clathrin light chain. HIP12 (unlike HIP1) co-sediments with F-actin while HIP1 does not bind actin in vitro. In vitro binding assays, clathrin assembly assays, F-actin co-sedimentation, deletion/mutation mapping The Journal of biological chemistry High 11889126
2003 HIP1 knockout mice (HIP1−/−) develop neurological deficits (tremor, gait ataxia, kyphosis), decreased assembly of endocytic protein complexes on liposomal membranes, and a dose-dependent defect in clathrin-mediated internalization of GluR1-containing AMPA receptors in hippocampal neurons, demonstrating that HIP1 is required for AMPA receptor trafficking via clathrin-mediated endocytosis. Targeted gene knockout in mice, internalization assays in primary neurons, liposome-based endocytic complex assembly assay The EMBO journal High 12839988
2004 HIP1 (and HIP1R) directly interact with the conserved 22-amino-acid regulatory sequence of clathrin light chains (CLC); the regulatory N-terminal residues of this CLC sequence mediate the interaction and are required for HIP1/HIP1R stimulation of clathrin assembly in vitro. In vivo overexpression of the Hip1R-binding fragment of CLC disrupts actin distribution. In vitro binding assays with CLC mutants, clathrin assembly assay, in vivo actin distribution analysis upon overexpression The Journal of biological chemistry High 15533940 15533941
2004 Residues Leu-451, Leu-452, and Arg-453 within HIP1's central helical domain (aa 450–456) are required for clathrin light chain (CLC) binding; CLC-binding mutants fail to promote clathrin assembly in vitro, are unable to target to clathrin-coated pits and vesicles in cells, but still support HIP1 homodimerization and heterodimerization with HIP1R. Site-directed mutagenesis, in vitro clathrin assembly assay, subcellular localization by fluorescence microscopy, dimerization assays The Journal of biological chemistry High 15533941
2004 HIP1 binds 3-phosphate-containing inositol lipids (PI(3,4)P2 and PI(3,5)P2) preferentially via its ENTH domain; this ENTH domain is necessary for lipid binding, and ENTH-deleted HIP1 induces apoptosis. Full-length HIP1 stabilizes pools of growth factor receptors (receptor tyrosine kinases) by prolonging their half-life following ligand-induced endocytosis. Lipid-binding assays with ENTH domain mutants, receptor half-life measurements after ligand stimulation, apoptosis assays The Journal of biological chemistry Medium 14732715
2004 The I/LWEQ module (C-terminal actin-binding domain) of HIP1 binds F-actin, but actin binding is regulated by intrasteric inhibition: a conserved structural element within the I/LWEQ module occludes the primary actin-binding determinants of HIP1 and other family members (Talin1, Talin2, Hip12). The I/LWEQ module also contains a dimerization motif and stabilizes actin filaments against depolymerization. F-actin co-sedimentation assays, affinity measurements, truncation/mutagenesis analysis Biochemistry Medium 15581353
2006 Crystal structure of the HIP1 coiled-coil domain (residues 482–586) at 2.8 Å reveals a partially splayed-open dimeric coiled-coil; structural analysis identified a hydrophobic surface path (S3) proposed as the clathrin light chain interaction surface. X-ray crystallography Journal of molecular biology Medium 17257618
2007 Crystal structure of HIP1 subfragment 371–481 at 2.8 Å reveals a partially opened coiled-coil with a basic surface near residues F432 and K474 proposed as the HIPPI-binding site, and a highly negatively charged adjacent region. This structure rules out a death-effector domain fold for the HIPPI-interaction module. X-ray crystallography, structural comparison Journal of molecular biology Medium 18155047
2007 HIP1 colocalizes with NMDARs in hippocampal and cortical neurons and affinity-purifies with NMDARs by GST pull-down and co-immunoprecipitation. In HIP1−/− neurons, NMDA-induced AMPA receptor internalization is reduced by 75%, long-term depression is impaired, and neurons are partially protected from NMDA-induced excitotoxicity. HIP1 also modulates NMDA-induced phosphorylation of Akt and huntingtin. GST pull-down, co-immunoprecipitation, quantitative AMPA receptor internalization assay in KO neurons, LTD electrophysiology in brain slices, LDH/TUNEL/caspase-3 excitotoxicity assays The Journal of neuroscience High 17329427
2008 Clathrin light chain (CLC) binding to Hip1 (and Hip1R) induces a compact conformation of their coiled-coil domains and significantly reduces actin binding by their THATCH (I/LWEQ) domains; thus clathrin light chain acts as a negative regulator of Hip1-actin interactions. Hip1 coiled-coil homodimers do not heterodimerize with Hip1R in vitro. Biophysical analysis (calorimetry, analytical ultracentrifugation, CD), actin co-sedimentation assay, conformational analysis The Journal of biological chemistry High 18790740
2009 Live-cell imaging shows HIP1 is recruited early to clathrin-coated pits at the plasma membrane and is absent from newly internalized vesicles (after vesicle closure); shRNA knockdown of clathrin compromises HIP1 membrane localization. An HIP1 fragment lacking ANTH and Talin-like domains inhibits transferrin internalization while retaining membrane clathrin co-localization, placing HIP1 function in pit maturation and coated vesicle formation. Live-cell fluorescence imaging, pHluorin-tagged transferrin receptor assay, shRNA knockdown, dominant-negative fragment expression Cellular and molecular life sciences Medium 19626275
2009 The HIP1/Hippi heterodimer (via HIP-1 as nuclear transporter) accumulates in the nucleus and the pseudo-death-effector domain of HIPPI binds to specific promoter motifs of caspase-1, -8, and -10 genes, increasing their transcription. Residue R393 of HIPPI is critical for promoter binding; HIP-1 nuclear localization signal is required for HIPPI nuclear translocation and consequent caspase-1 upregulation. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), mutagenesis (R393E), HIP-1 NLS deletion, HIP-1 knockdown Nucleic acids research Medium 19934260
2011 HIPPI (HIP-1 protein interactor) directly binds the promoter of REST/NRSF and activates its transcription; this activation requires HIP1 as the nuclear transporter of HIPPI. In a HD cell model, reduced interaction of mutant huntingtin with HIP1 leads to increased nuclear accumulation of HIPPI/HIP1, greater REST promoter occupancy, REST upregulation, and consequent repression of BDNF and proenkephalin. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, HIP1 overexpression/knockdown, NLS mutation, huntingtin polyQ model The Journal of biological chemistry Medium 21832040
2014 HIP1 is identified as a fusion partner of ALK (anaplastic lymphoma kinase) in NSCLC; the HIP1-ALK fusion protein (exon 28 of HIP1 fused to exon 20 of ALK) is constitutively active and drives tumor growth in a patient-derived xenograft model that is sensitive to the ALK inhibitor crizotinib in vivo. RNA-seq, RT-PCR, genomic sequencing, in vivo PDX efficacy study with crizotinib Journal of thoracic oncology Medium 24496003 24518094
2014 HIP1 mediates HGF-induced c-Met signaling by promoting β1-integrin turnover (increased endocytosis), which is required for c-Met-driven mesenchymal-type cell invasion. siRNA screen identified HIP1 as a crucial c-Met effector for this morphological/invasive outcome. High-throughput siRNA screen, integrin trafficking assay, invasion assay, c-Met activation assay Journal of cell science Medium 24790222
2018 HIP1 is required for PDGFR-mediated RAC1 activation and lamellipodia formation in fibroblast-like synoviocytes; knockdown of HIP1 reduces receptor tyrosine kinase responses, RAC1 activation, and invasiveness. HIP1 knockout mice are protected in KRN serum-induced arthritis, demonstrating an in vivo role for HIP1 in joint disease severity via RTK/Rac1 signaling. siRNA knockdown, RAC1 activation assay, invasion assay, HIP1 KO mouse model with arthritis induction Annals of the rheumatic diseases Medium 30049830
2018 In HIP1-deficient mice, phosphocholine levels are low and Gdpd3 (lysophospholipase D) expression is reduced. Brain-specific rescue of HIP1 expression does not rescue the phenotype, whereas expression in kidney, spleen, and liver does, indicating the degenerative phenotype is not brain-autonomous. Double knockout of Gdpd3 and Hip1 worsens the Hip1 phenotype, suggesting Gdpd3 compensates for Hip1 loss in choline metabolism. Conditional knockout (Cre/lox), tissue-specific rescue with Cre drivers, metabolomics (phosphocholine), microarray, double KO genetic interaction Molecular and cellular biology Medium 30224518
2022 UGT2B28 physically associates with HIP1, stabilizing it and priming AR and EGFR signaling pathways leading to ERK1/2 activation, cell proliferation, and EMT in prostate cancer; HIP1 knockdown in UGT2B28-positive cells abolishes these proliferative advantages. Co-immunoprecipitation (protein-protein interaction), siRNA knockdown, signaling pathway assays (ERK1/2, AR, EGFR), cell proliferation assay Cancer letters Medium 36343786

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nature genetics 306 9140394
1990 Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site. Molecular and cellular biology 245 2300058
2003 Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung. Genes & development 244 12569124
2002 Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi. Nature cell biology 232 11788820
1992 The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter. Molecular and cellular biology 178 1545788
2001 HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2. The Journal of biological chemistry 155 11517213
1985 The histidine permease gene (HIP1) of Saccharomyces cerevisiae. Gene 146 3905514
2001 The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. Human molecular genetics 129 11532990
2001 Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins. The Journal of biological chemistry 110 11577110
2004 Huntingtin-interacting protein 1 (Hip1) and Hip1-related protein (Hip1R) bind the conserved sequence of clathrin light chains and thereby influence clathrin assembly in vitro and actin distribution in vivo. The Journal of biological chemistry 96 15533940
2003 Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking. The EMBO journal 94 12839988
2002 HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain. The Journal of biological chemistry 89 11889126
1989 Nucleotide sequence of the Saccharomyces cerevisiae PUT4 proline-permease-encoding gene: similarities between CAN1, HIP1 and PUT4 permeases. Gene 89 2687114
2004 Huntingtin interacting protein 1 (HIP1) regulates clathrin assembly through direct binding to the regulatory region of the clathrin light chain. The Journal of biological chemistry 87 15533941
2014 HIP1-ALK, a novel ALK fusion variant that responds to crizotinib. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 83 24496003
2014 Identification of a novel HIP1-ALK fusion variant in Non-Small-Cell Lung Cancer (NSCLC) and discovery of ALK I1171 (I1171N/S) mutations in two ALK-rearranged NSCLC patients with resistance to Alectinib. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 81 25393796
2008 Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain. The Journal of biological chemistry 68 18790740
2004 Intrasteric inhibition mediates the interaction of the I/LWEQ module proteins Talin1, Talin2, Hip1, and Hip12 with actin. Biochemistry 67 15581353
2004 The Schizosaccharomyces pombe HIRA-like protein Hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres. Molecular and cellular biology 65 15121850
2014 HIP1-ALK, a novel fusion protein identified in lung adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 59 24518094
2004 HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains. The Journal of biological chemistry 59 14732715
2014 Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1. Journal of immunology (Baltimore, Md. : 1950) 56 24659689
2010 Recurrent distal 7q11.23 deletion including HIP1 and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems. American journal of human genetics 56 21109226
1995 Singular over-representation of an octameric palindrome, HIP1, in DNA from many cyanobacteria. Nucleic acids research 56 7708486
1993 Deletion within the metallothionein locus of cadmium-tolerant Synechococcus PCC 6301 involving a highly iterated palindrome (HIP1). Molecular microbiology 53 8446026
2004 HIP1: trafficking roles and regulation of tumorigenesis. Trends in molecular medicine 49 15059611
1992 The HIP1 initiator element plays a role in determining the in vitro requirement of the dihydrofolate reductase gene promoter for the C-terminal domain of RNA polymerase II. Molecular and cellular biology 47 1569952
2008 Crystal structures of fission yeast histone chaperone Asf1 complexed with the Hip1 B-domain or the Cac2 C terminus. The Journal of biological chemistry 46 18334479
2011 Mycobacterium tuberculosis Hip1 dampens macrophage proinflammatory responses by limiting toll-like receptor 2 activation. Infection and immunity 45 21947769
2006 Hip3 interacts with the HIRA proteins Hip1 and Slm9 and is required for transcriptional silencing and accurate chromosome segregation. The Journal of biological chemistry 44 16428807
2016 Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis. ACS infectious diseases 43 27739665
1998 Cloning, expression analysis, and chromosomal localization of HIP1R, an isolog of huntingtin interacting protein (HIP1). Journal of human genetics 41 9852681
2000 HIP12 is a non-proapoptotic member of a gene family including HIP1, an interacting protein with huntingtin. Mammalian genome : official journal of the International Mammalian Genome Society 40 11063258
2019 White matter DNA methylation profiling reveals deregulation of HIP1, LMAN2, MOBP, and other loci in multiple system atrophy. Acta neuropathologica 39 31535203
2007 NMDA receptor function and NMDA receptor-dependent phosphorylation of huntingtin is altered by the endocytic protein HIP1. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 17329427
2007 Degenerative phenotypes caused by the combined deficiency of murine HIP1 and HIP1r are rescued by human HIP1. Human molecular genetics 36 17452370
2003 Two potato proteins, including a novel RING finger protein (HIP1), interact with the potyviral multifunctional protein HCpro. Molecular plant-microbe interactions : MPMI 36 12744511
2014 Mycobacterium tuberculosis Hip1 modulates macrophage responses through proteolysis of GroEL2. PLoS pathogens 35 24830429
2008 Huntington's disease: roles of huntingtin-interacting protein 1 (HIP-1) and its molecular partner HIPPI in the regulation of apoptosis and transcription. The FEBS journal 35 18637945
2005 The novel fission yeast protein Pal1p interacts with Hip1-related Sla2p/End4p and is involved in cellular morphogenesis. Molecular biology of the cell 34 15975911
2004 Hip1-related mutant mice grow and develop normally but have accelerated spinal abnormalities and dwarfism in the absence of HIP1. Molecular and cellular biology 32 15121852
2014 Distinct c-Met activation mechanisms induce cell rounding or invasion through pathways involving integrins, RhoA and HIP1. Journal of cell science 31 24790222
2010 The Sla2p/HIP1/HIP1R family: similar structure, similar function in endocytosis? Biochemical Society transactions 31 20074057
2018 Huntingtin-interacting protein 1 (HIP1) regulates arthritis severity and synovial fibroblast invasiveness by altering PDGFR and Rac1 signalling. Annals of the rheumatic diseases 29 30049830
1998 A PCR technique based on the Hip1 interspersed repetitive sequence distinguishes cyanobacterial species and strains. Microbiology (Reading, England) 28 9802020
2007 Structural abnormalities in spermatids together with reduced sperm counts and motility underlie the reproductive defect in HIP1-/- mice. Molecular reproduction and development 26 16967501
2020 Long non-coding RNA DNM3OS/miR-204-5p/HIP1 axis modulates oral cancer cell viability and migration. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 25 32463958
2005 Induction of apoptosis in cells expressing exogenous Hippi, a molecular partner of huntingtin-interacting protein Hip1. Neurobiology of disease 24 16364650
2011 Regulation of RE1 protein silencing transcription factor (REST) expression by HIP1 protein interactor (HIPPI). The Journal of biological chemistry 19 21832040
2006 Crystal structure at 2.8 A of the DLLRKN-containing coiled-coil domain of huntingtin-interacting protein 1 (HIP1) reveals a surface suitable for clathrin light chain binding. Journal of molecular biology 18 17257618
1997 HIP1 propagates in cyanobacterial DNA via nucleotide substitutions but promotes excision at similar frequencies in Escherichia coli and Synechococcus PCC 7942. Molecular microbiology 18 9140975
2017 Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses. Journal of leukocyte biology 15 29345365
2007 Crystal structure at 2.8 A of Huntingtin-interacting protein 1 (HIP1) coiled-coil domain reveals a charged surface suitable for HIP1 protein interactor (HIPPI). Journal of molecular biology 15 18155047
2021 MOBP and HIP1 in multiple system atrophy: New α-synuclein partners in glial cytoplasmic inclusions implicated in the disease pathogenesis. Neuropathology and applied neurobiology 14 33368549
1998 IRS-PCR-based genetic mapping of the huntingtin interacting protein gene (HIP1) on mouse chromosome 5. Mammalian genome : official journal of the International Mammalian Genome Society 14 9434941
2001 Regulation of the Src homology 2-containing inositol 5-phosphatase SHIP1 in HIP1/PDGFbeta R-transformed cells. The Journal of biological chemistry 12 11287412
2020 miR-1272 Exerts Tumor-Suppressive Functions in Prostate Cancer via HIP1 Suppression. Cells 11 32069895
2017 Knockdown of HIP1 expression promotes ligand‑induced endocytosis of EGFR in HeLa cells. Oncology reports 11 29039605
2009 Transcription regulation of caspase-1 by R393 of HIPPI and its molecular partner HIP-1. Nucleic acids research 11 19934260
2006 Partially overlapping distribution of epsin1 and HIP1 at the synapse: analysis by immunoelectron microscopy. The Journal of comparative neurology 11 16320245
2002 Hip1 and Hippi participate in a novel cell death-signaling pathway. Developmental cell 11 11832235
2023 Y-box protein-1 modulates circSPECC1 to promote glioma tumorigenesis via miR-615-5p/HIP1/AKT axis. Acta biochimica et biophysica Sinica 10 37994157
2017 Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c). Biochemistry 10 28346784
2009 HIP1 exhibits an early recruitment and a late stage function in the maturation of coated pits. Cellular and molecular life sciences : CMLS 10 19626275
2007 Interactions of HIPPI, a molecular partner of Huntingtin interacting protein HIP1, with the specific motif present at the putative promoter sequence of the caspase-1, caspase-8 and caspase-10 genes. The FEBS journal 10 17623017
2022 UGT2B28 accelerates prostate cancer progression through stabilization of the endocytic adaptor protein HIP1 regulating AR and EGFR pathways. Cancer letters 8 36343786
2021 Clinicopathological features and resistance mechanisms in HIP1-ALK-rearranged lung cancer: A multicenter study. Genes, chromosomes & cancer 8 34687488
2024 Targeted inhibition of NRF2 reduces the invasive and metastatic ability of HIP1 depleted lung cancer cells. Biochemical and biophysical research communications 5 39303527
2018 Deficiency of the Endocytic Protein Hip1 Leads to Decreased Gdpd3 Expression, Low Phosphocholine, and Kypholordosis. Molecular and cellular biology 5 30224518
2011 Abundance and distribution of the highly iterated palindrome 1 (HIP1) among prokaryotes. Mobile genetic elements 5 22312590
2019 Association of single nucleotide polymorphism in NLRC3, NLRC5, HIP1, and LRP8 genes with fecal egg counts in goats naturally infected with Haemonchus contortus. Tropical animal health and production 4 31828571
2025 Identification and functional characterization of hub genes CLTA, EDIL3, HAPLN1, and HIP1 as diagnostic biomarkers and therapeutic targets in thyroid cancer and Hashimoto's thyroiditis. Clinical and experimental medicine 3 40372556
2023 An advanced NSCLC patient with ALK-RNF144A and HIP1-ALK fusions treated with ALK-TKI combination therapy: a case report. Translational lung cancer research 3 38205210
2021 Identification of triple gene fusion ALK-LRRN2, LTBP1-ALK, and HIP1-ALK in advanced lung adenocarcinoma and response to alectinib: A case report. Medicine 3 34941039
2018 Selection, periodicity and potential function for Highly Iterative Palindrome-1 (HIP1) in cyanobacterial genomes. Nucleic acids research 3 29432573
2025 NSUN2-mediated RNA m5C modification drives multiple myeloma progression by enhancing the stability of HIP1 mRNA. Scientific reports 2 40739289
2024 Successful treatment of a non-small-cell lung cancer patient harboring HIP1-ALK (H28:A20) and CTNNB1 p.S45del with alectinib. Thoracic cancer 2 39318178
2022 2.1 Å crystal structure of the Mycobacterium tuberculosis serine hydrolase, Hip1, in its anhydro-form (Anhydrohip1). Biochemical and biophysical research communications 2 36148729
2012 Replacement of charged and polar residues in the coiled-coiled interface of huntingtin-interacting protein 1 (HIP1) causes aggregation and cell death. FEBS letters 2 22835334
2009 Two Distantly Spaced Basic Patches in the Flexible Domain of Huntingtin-Interacting Protein 1 (HIP1) Are Essential for the Binding of Clathrin Light Chain. Research letters in biochemistry 1 22820750
2006 Cloning, expression, purification, crystallization and preliminary crystallographic analysis of pseudo death-effector domain of HIPPI, a molecular partner of Huntingtin-interacting protein HIP-1. Acta crystallographica. Section F, Structural biology and crystallization communications 1 17142908
2026 Distinction of dental mesenchymal cell populations during molar tooth germ development via analysis of the spatiotemporal expression patterns of mRNAs for Shh ligand receptors Ptch1 and Hip1 using in situ hybridization. Developmental dynamics : an official publication of the American Association of Anatomists 0 42204835
2023 HIP1-ALK-Rearranged Lung Cancer in a Young Adult With BRAF V600E Mutation Detected After ALK Tyrosine Kinase Inhibitor Therapy: A Case Report. JTO clinical and research reports 0 38229767
2022 Genetic interaction of the histone chaperone hip1 with double strand break repair genes in Schizosaccharomyces pombe. microPublication biology 0 35622511

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