Affinage

HSCB

Iron-sulfur cluster co-chaperone protein HscB · UniProt Q8IWL3

Length
235 aa
Mass
27.4 kDa
Annotated
2026-06-10
41 papers in source corpus 28 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSCB (HSC20/Jac1) is a J-type co-chaperone that drives iron-sulfur (Fe-S) cluster biogenesis by coupling the scaffold protein ISCU to the Hsp70 chaperone HscA/HSPA9 (PMID:9144776, PMID:11171977, PMID:11273703, PMID:20668094). Structurally it is an L-shaped, rigid two-domain protein: an N-terminal J-domain joined to a C-terminal three-helix bundle that bears the ISCU-binding surface mapping to a conserved hydrophobic patch (L92/L96/F153 and an acidic cluster), mutation of which abolishes ISCU binding and ternary-complex allostery (PMID:11124030, PMID:18702525, PMID:21269500, PMID:22306468). HSCB selectively binds the structured (S) conformational state of ISCU and targets it to the ATP-bound state of HscA, synergistically stimulating Hsp70 ATPase activity by hundreds-fold and acting as a substrate-targeting factor independent of ISCU's own Hsp70-binding LPPVK motif (PMID:10869428, PMID:12871959, PMID:15485839, PMID:19492851, PMID:22782893). ATP hydrolysis and the accompanying Hsp70 conformational transition convert ISCU to the disordered (D) state, transiently distort the bound [2Fe-2S] cluster, release HSCB, and drive ATP-dependent cluster transfer to apo-acceptor proteins such as ferredoxin (PMID:16964969, PMID:18986169, PMID:22782893, PMID:23940031). Because the cysteine desulfurase NFS1/IscS competes with HSCB for the same ISCU surface, HSCB binding marks the handoff from cluster assembly to Hsp70-mediated cluster transfer (PMID:23946486, PMID:23940031). The human protein localizes predominantly to mitochondria, interacts with ISCU, HSPA9, NFS1 and frataxin, and its depletion lowers both mitochondrial and cytosolic Fe-S enzyme activities and perturbs cellular iron homeostasis (PMID:20668094, PMID:22171070); a cytosolic pool additionally bridges ISC components (ISCU1, NFS1) to the CIA targeting complex (CIAO1, FAM96B, MMS19) for cytosolic and nuclear Fe-S delivery (PMID:29309586). Human HSCB is distinguished by an N-terminal tetracysteine zinc-finger that coordinates a single Zn2+ ion with high affinity and is required for structural integrity and function (PMID:18713742, PMID:37871810). Beyond Fe-S biology, phosphorylated HSCB binds TACC3 to promote its proteasomal degradation, relieving cytoplasmic retention of FOG1 and enabling FOG1 nuclear translocation during erythropoiesis (PMID:38757931). Mutations in HSCB cause congenital sideroblastic anemia, with loss of HSCB impairing red-cell hemoglobinization and hematopoiesis across human cells, zebrafish, and mouse models (PMID:32634119).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Established that HscB is a regulatory co-chaperone, not an independent chaperone, defining its mechanistic class: it stimulates Hsp70 ATPase activity but lacks intrinsic aggregation-suppression activity.

    Evidence ATPase cross-stimulation and aggregation-suppression assays with purified proteins and model substrates

    PMID:9144776 PMID:9852006

    Open questions at the time
    • Did not identify the physiological substrate targeted by HscB
    • Functional readout limited to in vitro ATPase modulation
  2. 1999 High

    Placed HscB in the Fe-S cluster assembly pathway by showing genetic loss partially impairs holoferredoxin production in E. coli, linking the co-chaperone to a defined biosynthetic process.

    Evidence Genetic inactivation of isc operon genes with reporter ferredoxin assays in E. coli

    PMID:10544286

    Open questions at the time
    • Only partial requirement, leaving the molecular role ambiguous
    • No direct substrate identified
  3. 2001 High

    Generalized the Fe-S role to eukaryotes, showing the yeast ortholog Jac1 partners with Hsp70 Ssq1 and its loss reduces Fe-S enzyme activity and causes mitochondrial iron accumulation.

    Evidence Genetic analysis of jac1/ssq1 mutants with Fe-S enzyme assays and mitochondrial iron measurement

    PMID:11171977 PMID:11273703

    Open questions at the time
    • Mechanism of cluster transfer not resolved
    • Iron accumulation linkage to assembly defect inferred not proven biochemically
  4. 2003 High

    Defined HscB as a substrate-targeting factor by demonstrating it binds IscU directly, lowers the Km for IscU-dependent ATPase stimulation, and can target IscU to Hsc66 even when IscU's own Hsc66-binding LPPVK motif is impaired.

    Evidence SPR, ITC, ATPase assays and alanine scanning of the IscU LPPVK motif

    PMID:10869428 PMID:12871959

    Open questions at the time
    • Did not define the HscB surface mediating IscU recognition
    • Cluster-transfer consequences not yet measured
  5. 2004 High

    Resolved how HscB couples substrate delivery to the chaperone cycle: it binds the ATP-bound (T) state of HscA and, with IscU, synergistically accelerates both ATP hydrolysis and the T→R conformational transition.

    Evidence Single-turnover and rapid-mixing ATPase kinetics with affinity-sensor binding studies

    PMID:15485839

    Open questions at the time
    • Did not directly show cluster transfer is driven by this cycle
    • Structural basis of synergy not defined
  6. 2008 High

    Demonstrated that ATP hydrolysis by HscA, promoted by HscB, is required for [2Fe-2S] transfer from IscU to apo-acceptors and transiently distorts the bound cluster, directly linking the chaperone cycle to cluster handoff.

    Evidence In vitro cluster transfer assays with CD/EPR spectroscopy and an ATPase-dead HscA(T212V) mutant

    PMID:16964969 PMID:18986169

    Open questions at the time
    • Conformational state of IscU during distortion inferred indirectly
    • Acceptor selectivity not addressed
  7. 2008 High

    Provided the structural framework: high-resolution E. coli and human crystal structures plus solution NMR define a rigid L-shaped scaffold and map the IscU-binding hydrophobic patch, while revealing a metazoan-specific N-terminal tetracysteine metal-binding domain.

    Evidence X-ray crystallography of E. coli and human HscB, NMR structure with mutagenesis-validated binding-surface mapping

    PMID:11124030 PMID:18702525 PMID:18713742

    Open questions at the time
    • Functional role of the human tetracysteine domain not yet tested
    • Identity of coordinated metal not established in structure
  8. 2012 High

    Established the conformational-selection mechanism: HscB binds the structured (S) state of IscU while Hsp70 binds and stabilizes the disordered (D) state, so cluster transfer is coupled to ATP hydrolysis, IscU D-state conversion, and HscB release.

    Evidence NMR monitoring of IscU conformational states with state-stabilizing mutants, plus yeast crystal structure with in vivo rescue

    PMID:19492851 PMID:22306468 PMID:22782893

    Open questions at the time
    • Kinetic ordering of release versus transfer not fully resolved
    • Acceptor-protein engagement step not characterized
  9. 2013 High

    Identified the assembly-to-transfer switch: Jac1/HscB and the cysteine desulfurase Nfs1/IscS compete for the same IscU surface, providing a mechanism for transitioning from cluster assembly to Hsp70-mediated transfer; human proteins recapitulate the conformational-selection logic.

    Evidence Competition binding assays with IscU patch mutants and NMR with human ISCU/HSC20/HSPA9/NFS1

    PMID:23940031 PMID:23946486

    Open questions at the time
    • Regulation of the competition in vivo not defined
    • Timing relative to cluster maturation unresolved
  10. 2011 Medium

    Connected human HSC20 to physiological iron and Fe-S homeostasis by showing it localizes to mitochondria, interacts with ISCU, HSPA9, NFS1 and frataxin, and that its depletion lowers Fe-S enzyme activity and dysregulates iron pools.

    Evidence Yeast complementation, co-IP, localization, and RNAi knockdown with Fe-S enzyme and iron-pool assays

    PMID:20668094 PMID:22171070

    Open questions at the time
    • Frataxin interaction not mechanistically integrated into the transfer cycle
    • Co-IP interactions not all reciprocally validated
  11. 2013 High

    Extended the in vivo Fe-S requirement to a metazoan organism, showing Drosophila Hsc20 loss causes growth arrest, reduced Fe-S enzyme activity, and mitochondrial iron accumulation.

    Evidence Drosophila piggyBac loss-of-function mutants with enzyme activity and iron-staining analyses

    PMID:23444034

    Open questions at the time
    • Organismal phenotype not linked to specific molecular interactions
    • Tissue-specific roles not dissected
  12. 2018 Medium

    Revealed a non-mitochondrial role: a cytosolic HSC20 pool bridges ISC components to the CIA targeting complex (CIAO1, FAM96B, MMS19), defining a parallel route for cytosolic and nuclear Fe-S delivery.

    Evidence Co-IP, subcellular fractionation, and knockdown with Fe-S enzyme assays

    PMID:29309586

    Open questions at the time
    • Mechanism of cytosolic versus mitochondrial partitioning unknown
    • Single-lab co-IP based, not reconstituted
  13. 2020 High

    Linked HSCB to human disease, showing loss-of-function mutations cause congenital sideroblastic anemia and that HSCB loss impairs Fe-S biogenesis and red-cell hemoglobinization across multiple models.

    Evidence Patient genetics, engineered K562 cells, siRNA/CRISPR, zebrafish and mouse models with hematological phenotyping

    PMID:32634119

    Open questions at the time
    • Whether anemia is fully explained by Fe-S deficiency versus additional roles not resolved at this stage
    • Genotype-phenotype relationships across variants limited
  14. 2023 Medium

    Defined the human N-terminal zinc finger biochemically, showing HSCB binds a single Zn2+ with high affinity required for structural integrity, while retaining HSPA9 ATPase-stimulating activity as a monomer.

    Evidence SAXS, SEC-MALS, metal chelation, denaturation, and ATPase stimulation assays

    PMID:37871810

    Open questions at the time
    • Functional consequence of Zn2+ loss on Fe-S transfer not tested
    • Single-lab biophysical characterization
  15. 2024 Medium

    Uncovered an Fe-S-independent function: phosphorylated HSCB binds TACC3 to promote its proteasomal degradation, relieving cytoplasmic retention of FOG1 and enabling FOG1 nuclear translocation during erythropoiesis.

    Evidence Co-IP, phosphorylation and proteasome-inhibitor experiments, and HSCB knockdown with differentiation and fractionation assays in K562 and HSCs

    PMID:38757931

    Open questions at the time
    • Direct kinase and phosphosite identity within HSCB not fully defined
    • Single-lab study without structural validation of the HSCB-TACC3 interface

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HSCB's two distinct activities — Fe-S cluster co-chaperone and TACC3-degradation-linked erythroid regulator — are integrated, and whether the zinc finger or cytosolic localization gates this switch, remains unresolved.
  • No unifying model linking the Fe-S and TACC3/FOG1 functions
  • Signaling input (PI3K) coupling to subcellular pool not mapped
  • Relative contribution of each function to sideroblastic anemia unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 4 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-392499 Metabolism of proteins 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1643685 Disease 1
Partners
CIAO1FAM96BFXNHSPA9ISCUMMS19NFS1TACC3
Complex memberships
CIA targeting complex (CIAO1-FAM96B-MMS19)HscA-HscB-IscU chaperone complexISC assembly complex (ISCU-NFS1)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 HscB (Hsc20) is a J-type co-chaperone that stimulates the ATPase activity of Hsc66 (HscA) up to 3.8-fold in a concentration-dependent manner, establishing it as a regulatory cochaperone rather than an independent chaperone. ATPase activity assay with purified proteins; protein purification and characterization Protein science High 9144776
1998 Hsc20 (HscB) functions solely as a regulatory cochaperone for Hsc66 and lacks intrinsic chaperone activity; it does not suppress protein aggregation unlike DnaJ. The nucleotide exchange factor GrpE does not stimulate Hsc66 ATPase, indicating Hsc66/Hsc20 and DnaK/DnaJ/GrpE are separate systems with nonoverlapping functions. Aggregation suppression assays with model substrates (rhodanese, citrate synthase, luciferase); ATPase cross-stimulation experiments Journal of bacteriology High 9852006
1999 HscB (hscB gene product) is partially required for Fe-S cluster assembly in E. coli; inactivation of hscB had a partial but appreciable effect on production of some ferredoxins, while iscS, iscA, hscA, and fdx were strictly required. Genetic inactivation (truncation or stop-codon insertion) of individual isc operon genes; coexpression with reporter ferredoxins; holoferredoxin production assay Journal of biochemistry High 10544286
2000 HscB (Hsc20) directly binds IscU (and IscU-Fe/S complex), enhances binding of IscU to Hsc66, and decreases the apparent Km for IscU stimulation of Hsc66 ATPase activity; together IscU and Hsc20 increase Hsc66 ATPase activity up to 480-fold. Surface plasmon resonance; isothermal titration calorimetry; steady-state ATPase assay Proceedings of the National Academy of Sciences of the United States of America High 10869428
2000 Crystal structure of Hsc20 (HscB) from E. coli determined at 1.8 Å resolution: the protein consists of an N-terminal J-domain (residues 1–75) connected to a unique C-terminal three-helix bundle (residues 84–171) via a short loop; the two domains are held in fixed orientation by an extensive hydrophobic interface (~650 Ų), suggesting Hsc20 functions as a rigid scaffold for substrate targeting to Hsc66. X-ray crystallography (SIR + MAD phasing, 1.8 Å resolution) Journal of molecular biology High 11124030
2001 Yeast Jac1 (ortholog of HscB/HSCB) is the J-protein partner of Ssq1 in mitochondrial Fe-S cluster biogenesis; reduced Jac1 activity decreases activities of Fe-S-containing enzymes and causes mitochondrial iron accumulation independent of oxidative damage, indicating a direct role in Fe-S cluster assembly. Genetic analysis of jac1 and ssq1 mutants; enzyme activity assays for Fe-S proteins; iron measurement in mitochondria Proceedings of the National Academy of Sciences of the United States of America High 11171977 11273703
2003 The LPPVK motif of IscU (residues 99–103) is the primary recognition sequence for Hsc66 (HscA); alanine scanning mutagenesis showed Pro101, Val102, and Lys103 are most critical for Hsc66 binding and ATPase stimulation; Hsc20 (HscB) can target IscU mutants to Hsc66 even when their direct Hsc66-binding affinity is reduced, indicating HscB acts as a targeting factor independent of IscU's Hsc66-binding motif. Alanine mutagenesis scan; ATPase stimulation assays; isothermal titration calorimetry; affinity sensor (SPR) The Journal of biological chemistry High 12871959
2004 HscB (Hsc20) interacts selectively with the ATP-bound (T-state) conformation of HscA; together with IscU it synergistically stimulates both the rate of ATP hydrolysis (~500-fold) and the T→R conformational transition (~60-fold) of HscA, establishing a mechanism for substrate capture; IscU also accelerates the R→T transition (~50-fold) to regenerate the low-affinity T-state. Single-turnover and rapid-mixing ATPase kinetics; affinity sensor binding studies; steady-state ATPase assays The Journal of biological chemistry High 15485839
2006 HscA and HscB together stimulate [2Fe-2S] cluster transfer from IscU to apo-ferredoxin more than 20-fold in an ATP-dependent manner; cluster transfer requires both HscB and MgATP; HscB alone or MgADP does not stimulate transfer, demonstrating that ATP hydrolysis by HscA is required. In vitro cluster transfer assay monitored by CD and EPR spectroscopy; phosphate production measurement; KCl stimulation of ATPase Biochemistry High 16964969
2008 ATP hydrolysis by HscA and the accompanying T→R conformational transition are required for catalysis of Fe-S cluster transfer; an ATPase-dead HscA(T212V) mutant cannot accelerate cluster transfer; addition of HscA+HscB+ATP causes a transient distortion of the IscU-bound [2Fe-2S] cluster CD spectrum coupled to ATP hydrolysis; a 1:1:1 HscA-HscB-IscU complex and a single ATP hydrolysis event are sufficient to elicit full chaperone effect on the cluster. Visible-region CD spectroscopy; in vitro cluster transfer assay; site-directed mutagenesis (HscA T212V); concentration-dependence studies under limiting conditions Biochemistry High 18986169
2008 NMR-based solution structure of HscB (Hsc20) confirms it faithfully resembles the crystal structure; the IscU binding surface on HscB maps to a conserved hydrophobic patch in the C-terminal domain (L92, M93, L96, E97, E100, E104, F153); triple alanine mutants HscB(L92A,M93A,F153A) and HscB(E97A,E100A,E104A) showed decreased IscU binding; L92A,M93A,F153A also disrupted the allosteric interaction within the HscA·IscU·HscB ternary complex. NMR spectroscopy (15N relaxation, 1H-15N HSQC perturbation mapping, RDCs); site-directed mutagenesis; ITC for binding affinity; HscA ATPase stimulation assay Biochemistry High 18702525
2008 Crystal structure of human HscB (HSCB/HSC20) at 3.0 Å resolution reveals an L-shaped protein resembling E. coli HscB; uniquely, human HscB has an N-terminal tetracysteine metal-binding domain (CWXCX(9-13)FCXXCXXXQ) that coordinates a metal ion in a rubredoxin-like structural fold; normal mode analysis indicates a scissors-like domain motion. X-ray crystallography (3.0 Å resolution); normal mode analysis The Journal of biological chemistry High 18713742
2009 HscB (Hsc20) binds to and stabilizes the ordered (S) conformational state of IscU, as determined by NMR; the IscU-HscB binding interface involves the N-terminal beta-strands and C-terminal alpha-helix of IscU; the complex interconverts between two or more states at a rate faster than complex dissociation. NMR spectroscopy (1H-15N HSQC perturbation mapping of IscU upon HscB addition); use of stabilizing IscU D39A mutant as surrogate for ordered state Biochemistry High 19492851
2010 Human HSC20 (HSCB) complements yeast Jac1p functionally; it localizes primarily to mitochondria in HeLa cells (with small extra-mitochondrial fraction); it interacts with human ISCU and HSPA9 (hHSP70); RNAi depletion of hHSC20 reduces activities of both mitochondrial and cytosolic Fe-S enzymes; the N-terminal cysteine-rich domain unique to metazoan HSC20 is important for its integrity and function. Yeast complementation; subcellular fractionation/immunofluorescence; co-immunoprecipitation; RNAi knockdown with enzyme activity assays; domain deletion analysis Human molecular genetics High 20668094
2011 Human HSC20 interacts with frataxin in an iron-dependent manner; it also interacts with the ISCU/NFS1 ISC biogenesis complex and GRP75; knockdown of HSC20 reduces mitochondrial ISC enzyme activities and alters cytosolic and mitochondrial iron homeostasis (increased transferrin receptor 1 and IRP2 expression). Co-immunoprecipitation; siRNA knockdown with enzyme activity assays; iron pool measurements; western blotting Human molecular genetics Medium 22171070
2011 Three hydrophobic residues in the C-terminal domain of E. coli HscB (L92, L96, F153) make the greatest individual contributions to IscU binding affinity; triple alanine substitution L92A/L96A/F153A would reduce HscB-IscU binding affinity by ~15,000-fold (ΔΔGb ≅ 5.7 kcal/mol). Isothermal titration calorimetry; NMR spectroscopy (binding confirmation); site-directed mutagenesis of individual residues BMC biochemistry High 21269500
2012 Crystal structure of yeast Jac1 (HscB ortholog) determined; eight surface-exposed residues form the Isu1-binding surface; variants with all eight residues replaced by alanine cannot support growth of jac1-Δ yeast; replacement of three key residues causes partial loss of function with slow growth and reduced Fe-S enzyme activities, establishing that Jac1-Isu1 interaction is indispensable in vivo. X-ray crystallography; site-directed mutagenesis; yeast growth complementation assay; Fe-S enzyme activity assays; in vitro binding assays Journal of molecular biology High 22306468
2012 HscB (J-protein) preferentially binds the structured (S) conformational state of IscU, whereas HscA (Hsp70) preferentially binds and stabilizes the dynamically disordered (D) state of IscU; HscA releases IscU upon ATP binding. This establishes a mechanism where cluster transfer is coupled to ATP hydrolysis, IscU conversion to the D-state, and HscB release. NMR spectroscopy (15N-HSQC monitoring of IscU conformational states upon chaperone binding); use of IscU conformational state-stabilizing mutants The Journal of biological chemistry High 22782893
2013 Yeast Jac1 and cysteine desulfurase Nfs1 compete for binding to the same hydrophobic surface patch on Isu, indicating their binding is mutually exclusive; this competition is proposed to mediate the transition from Fe-S cluster assembly (Nfs1 bound) to Hsp70-mediated cluster transfer (Jac1 bound). In vitro binding assays with Isu hydrophobic patch mutants; competition binding assays between Jac1 and Nfs1; in vivo functional assays in yeast The Journal of biological chemistry High 23946486
2013 Human HSC20 (HscB) binds preferentially to the structured (S) state of ISCU; human mtHSP70 (HSPA9) binds preferentially to the disordered (D) state; HSC20 accelerates the ATPase activity of mtHSP70 and this is further enhanced by ISCU; NFS1 also binds preferentially to the D-state of ISCU. NMR spectroscopy with ISCU conformational state-stabilizing mutants (D39V, N90A, D39A, H105A); ATPase activity assays The Journal of biological chemistry High 23940031
2013 Drosophila Hsc20 loss-of-function (piggyBac insertion mutants) causes larval growth arrest, reduced aconitase and succinate dehydrogenase activities (Fe-S enzymes), and disrupted iron homeostasis with apparent mitochondrial iron accumulation, establishing an in vivo role for Hsc20 in Fe-S cluster biogenesis and iron homeostasis. Drosophila genetic mutant analysis; enzyme activity assays (aconitase, succinate dehydrogenase, isocitrate dehydrogenase); iron staining/ferritin expression analysis Journal of biological inorganic chemistry High 23444034
2015 HscB binding to apoIscU slows the rate (but not equilibrium) of [2Fe-2S] cluster formation on IscU; this slowing depends on a 1:1 HscB:IscU complex and requires HscB residues that mediate IscU binding; in the presence of HscA and ATP, cluster transfer from HscB-bound IscU is rescued; HscB may modulate cluster biosynthesis rate depending on acceptor protein availability. Circular dichroism spectroscopy monitoring cluster assembly; Fe-S cluster reconstitution experiments; HscB mutant analysis; cluster transfer to apoferredoxin Journal of biological inorganic chemistry Medium 26246371
2016 HscB interacts weakly with the cysteine desulfurase IscS; the binding site on HscB involves a region in the longer stem of the L-shaped molecule; the interacting surface on IscS overlaps with sites involved in binding ferredoxin and frataxin. Co-immunoprecipitation/pulldown; NMR/biophysical binding assays Frontiers in molecular biosciences Low 27730125
2018 Cytosolic HSC20 (C-HSC20) facilitates Fe-S cluster delivery to cytosolic and nuclear Fe-S proteins by mediating complex formation between ISC components (ISCU1, NFS1) and the CIA targeting complex (CIAO1, FAM96B, MMS19), demonstrating a novel cytosolic de novo Fe-S biogenesis pathway in parallel to the mitochondrial ISC pathway. Co-immunoprecipitation; protein interaction studies; knockdown experiments with Fe-S enzyme activity assays; subcellular fractionation Human molecular genetics Medium 29309586
2020 Mutations in HSCB (frameshift and rare promoter variant) cause congenital sideroblastic anemia (CSA); reduced HSCB expression impairs Fe-S cluster biogenesis; HSCB knockdown/deletion in K562 cells, zebrafish, and mice results in defective RBC hemoglobinization, siderocyte formation, and broader hematopoiesis defects. Patient genetic analysis; engineered K562 cells with patient-specific promoter variant; siRNA knockdown and CRISPR deletion; zebrafish and mouse models; Fe-S enzyme activity assays; hematological phenotyping The Journal of clinical investigation High 32634119
2023 Human DjC20/HscB (HSCB) behaves as a slightly elongated monomer in solution; it binds one Zn2+ ion with very high affinity (1:1 stoichiometry) via its N-terminal zinc-finger domain; Zn2+ removal destabilizes the protein and is required for structural integrity; recombinant hDjC20 stimulates HSPA9 ATPase activity. Small-angle X-ray scattering (SAXS); SEC-MALS; metal chelation (EDTA/DTPA); thermal and chemical denaturation; ATPase stimulation assay Biochimica et biophysica acta. Proteins and proteomics Medium 37871810
2024 HSCB can be phosphorylated by PI3K and in its phosphorylated form binds to TACC3, mediating proteasomal degradation of TACC3; this relieves TACC3-mediated cytoplasmic retention of FOG1, facilitating FOG1 nuclear translocation during erythropoiesis and megakaryopoiesis. This represents a Fe-S cluster delivery-independent function of HSCB. Co-immunoprecipitation; phosphorylation assays; proteasome inhibitor experiments; knockdown of HSCB in K562 cells and CD34+CD90+ HSCs; nuclear/cytoplasmic fractionation; differentiation assays eLife Medium 38757931

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Functional assignment of the ORF2-iscS-iscU-iscA-hscB-hscA-fdx-ORF3 gene cluster involved in the assembly of Fe-S clusters in Escherichia coli. Journal of biochemistry 228 10544286
2000 Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 193 10869428
1999 Hyperproduction of recombinant ferredoxins in escherichia coli by coexpression of the ORF1-ORF2-iscS-iscU-iscA-hscB-hs cA-fdx-ORF3 gene cluster. Journal of biochemistry 173 10393315
2007 Molecular chaperones HscA/Ssq1 and HscB/Jac1 and their roles in iron-sulfur protein maturation. Critical reviews in biochemistry and molecular biology 144 17453917
2006 HscA and HscB stimulate [2Fe-2S] cluster transfer from IscU to apoferredoxin in an ATP-dependent reaction. Biochemistry 140 16964969
2003 The Caenorhabditis elegans p120 catenin homologue, JAC-1, modulates cadherin-catenin function during epidermal morphogenesis. The Journal of cell biology 117 12847081
2001 The mitochondrial proteins Ssq1 and Jac1 are required for the assembly of iron sulfur clusters in mitochondria. Journal of molecular biology 110 11273703
2001 Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe/S clusters in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 107 11171977
1997 Hsc66 and Hsc20, a new heat shock cognate molecular chaperone system from Escherichia coli. Protein science : a publication of the Protein Society 86 9144776
2008 Studies on the mechanism of catalysis of iron-sulfur cluster transfer from IscU[2Fe2S] by HscA/HscB chaperones. Biochemistry 82 18986169
2009 Structure and dynamics of the iron-sulfur cluster assembly scaffold protein IscU and its interaction with the cochaperone HscB. Biochemistry 79 19492851
2004 Regulation of the HscA ATPase reaction cycle by the co-chaperone HscB and the iron-sulfur cluster assembly protein IscU. The Journal of biological chemistry 79 15485839
2010 Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis. Human molecular genetics 74 20668094
2003 Contributions of the LPPVK motif of the iron-sulfur template protein IscU to interactions with the Hsc66-Hsc20 chaperone system. The Journal of biological chemistry 74 12871959
1998 The Hsc66-Hsc20 chaperone system in Escherichia coli: chaperone activity and interactions with the DnaK-DnaJ-grpE system. Journal of bacteriology 74 9852006
2000 Crystal structure of Hsc20, a J-type Co-chaperone from Escherichia coli. Journal of molecular biology 56 11124030
2013 Binding of the chaperone Jac1 protein and cysteine desulfurase Nfs1 to the iron-sulfur cluster scaffold Isu protein is mutually exclusive. The Journal of biological chemistry 51 23946486
2012 Interaction of J-protein co-chaperone Jac1 with Fe-S scaffold Isu is indispensable in vivo and conserved in evolution. Journal of molecular biology 51 22306468
2013 Human mitochondrial chaperone (mtHSP70) and cysteine desulfurase (NFS1) bind preferentially to the disordered conformation, whereas co-chaperone (HSC20) binds to the structured conformation of the iron-sulfur cluster scaffold protein (ISCU). The Journal of biological chemistry 47 23940031
2018 Cytosolic HSC20 integrates de novo iron-sulfur cluster biogenesis with the CIAO1-mediated transfer to recipients. Human molecular genetics 39 29309586
2012 Specialized Hsp70 chaperone (HscA) binds preferentially to the disordered form, whereas J-protein (HscB) binds preferentially to the structured form of the iron-sulfur cluster scaffold protein (IscU). The Journal of biological chemistry 39 22782893
2011 HSC20 interacts with frataxin and is involved in iron-sulfur cluster biogenesis and iron homeostasis. Human molecular genetics 39 22171070
2008 Solution structure of the iron-sulfur cluster cochaperone HscB and its binding surface for the iron-sulfur assembly scaffold protein IscU. Biochemistry 39 18702525
2008 Structure of human J-type co-chaperone HscB reveals a tetracysteine metal-binding domain. The Journal of biological chemistry 39 18713742
2011 Three hydrophobic amino acids in Escherichia coli HscB make the greatest contribution to the stability of the HscB-IscU complex. BMC biochemistry 32 21269500
2016 Mammalian Fe-S proteins: definition of a consensus motif recognized by the co-chaperone HSC20. Metallomics : integrated biometal science 28 27714045
2022 JAC1 targets YY1 mediated JWA/p38 MAPK signaling to inhibit proliferation and induce apoptosis in TNBC. Cell death discovery 26 35383155
2020 Mutations in the iron-sulfur cluster biogenesis protein HSCB cause congenital sideroblastic anemia. The Journal of clinical investigation 25 32634119
2015 Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches. Proteins 24 25973573
2021 JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling. Cell death discovery 22 33875644
2003 Identification of a novel candidate gene in the iron-sulfur pathway implicated in ataxia-susceptibility: human gene encoding HscB, a J-type co-chaperone. Journal of human genetics 21 12938016
2013 Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron-sulfur cluster enzyme activities and impaired iron homeostasis. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 19 23444034
2015 Functional implications of the interaction between HscB and IscU in the biosynthesis of FeS clusters. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 15 26246371
2018 Role of the HSPA9/HSC20 chaperone pair in promoting directional human iron-sulfur cluster exchange involving monothiol glutaredoxin 5. Journal of inorganic biochemistry 12 29689452
2017 Regulation of human Nfu activity in Fe-S cluster delivery-characterization of the interaction between Nfu and the HSPA9/Hsc20 chaperone complex. The FEBS journal 10 29211945
2016 A New Tessera into the Interactome of the isc Operon: A Novel Interaction between HscB and IscS. Frontiers in molecular biosciences 10 27730125
2022 Interaction of client-the scaffold on which FeS clusters are build-with J-domain protein Hsc20 and its evolving Hsp70 partners. Frontiers in molecular biosciences 9 36310602
1997 Crystallization and preliminary X-ray crystallographic properties of Hsc20, a J-motif co-chaperone protein from Escherichia coli. Protein science : a publication of the Protein Society 5 9300502
2024 PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis. eLife 2 38757931
2023 Structural characterization of the human DjC20/HscB cochaperone in solution. Biochimica et biophysica acta. Proteins and proteomics 2 37871810
2026 High-Throughput Platform for Discovery of Chemical Inhibitors of Heat Shock Protein 70 (Hsp70): Adaptation for the Specialized Bacterial HscA-HscB-IscU Complex. Chemical biology & drug design 0 41883185

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