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- EMDB-80082: Cryo-EM structure of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432... -

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Basic information

Entry
Database: EMDB / ID: EMD-80082
TitleCryo-EM structure of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432) complex
Map dataRegarding the half-maps (Issue 1): The half-maps were generated by a 3D Flexible Refinement (3DFlex) job in cryoSPARC. As per the algorithm's design, the reconstruction is performed in real-space within a user-provided solvent mask, resulting in half-maps that are zero outside this mask. This is inherent to the 3DFlex method, not a result of post-processing. We have included a soft mask for FSC calculation that is fully contained within the defined solvent region, which is standard practice for 3DFlex outputs. Regarding the FSC curve (Issue 2): The plateauing of the FSC curve at high resolution is a known phenomenon for 3DFlex maps and is often indicative of the need for more optimization iterations. While we have already used a high number of BFGS iterations (e.g., 60) to optimize convergence, the flexible nature of the KICSTOR complex may contribute to this behavior. Nevertheless, the map quality is sufficient for de novo model building, as evidenced by the clear secondary structure features and the model's validation statistics.
Sample
  • Complex: Complex of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432)
    • Protein or peptide: KICSTOR complex protein kaptin
    • Protein or peptide: KICSTOR subunit 2
    • Protein or peptide: KICSTOR complex protein ITFG2
    • Protein or peptide: KICSTOR complex protein SZT2
KeywordsComplex / lysosome / mTORC1 / SIGNALING PROTEIN
Function / homology
Function and homology information


KICSTOR complex / regulation of superoxide dismutase activity / corpus callosum morphogenesis / protein localization to lysosome / Amino acids regulate mTORC1 / stereocilium / post-embryonic development / postsynaptic actin cytoskeleton / regulation of TOR signaling / cellular response to glucose starvation ...KICSTOR complex / regulation of superoxide dismutase activity / corpus callosum morphogenesis / protein localization to lysosome / Amino acids regulate mTORC1 / stereocilium / post-embryonic development / postsynaptic actin cytoskeleton / regulation of TOR signaling / cellular response to glucose starvation / negative regulation of TORC1 signaling / cellular response to amino acid starvation / actin filament organization / central nervous system development / actin filament binding / peroxisome / lamellipodium / lysosomal membrane / glutamatergic synapse / nucleoplasm / cytosol
Similarity search - Function
KICSTOR subunit 2 / KICSTOR complex protein C12orf66-like, central domain superfamily / KICSTOR complex C12orf66 like / Kaptin / Integrin-alpha FG-GAP repeat-containing protein 2 / Integrin-alpha FG-GAP repeat-containing protein 2 / Protein SZT2 / Integrin alpha, N-terminal / WD40-repeat-containing domain superfamily
Similarity search - Domain/homology
KICSTOR complex protein SZT2 / KICSTOR complex protein ITFG2 / KICSTOR subunit 2 / KICSTOR complex protein kaptin
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.81 Å
AuthorsYang A / Liang L
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32571452 China
CitationJournal: To Be Published
Title: Mechanistic insights into GATOR1 inhibition by GATOR2 and KICSTOR
Authors: Yang A / Liang L
History
DepositionApr 1, 2026-
Header (metadata) releaseAug 26, 2026-
Map releaseAug 26, 2026-
UpdateAug 26, 2026-
Current statusAug 26, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_80082.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationRegarding the half-maps (Issue 1): The half-maps were generated by a 3D Flexible Refinement (3DFlex) job in cryoSPARC. As per the algorithm's design, the reconstruction is performed in real-space within a user-provided solvent mask, resulting in half-maps that are zero outside this mask. This is inherent to the 3DFlex method, not a result of post-processing. We have included a soft mask for FSC calculation that is fully contained within the defined solvent region, which is standard practice for 3DFlex outputs. Regarding the FSC curve (Issue 2): The plateauing of the FSC curve at high resolution is a known phenomenon for 3DFlex maps and is often indicative of the need for more optimization iterations. While we have already used a high number of BFGS iterations (e.g., 60) to optimize convergence, the flexible nature of the KICSTOR complex may contribute to this behavior. Nevertheless, the map quality is sufficient for de novo model building, as evidenced by the clear secondary structure features and the model's validation statistics.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.03 Å/pix.
x 400 pix.
= 413.696 Å
1.03 Å/pix.
x 400 pix.
= 413.696 Å
1.03 Å/pix.
x 400 pix.
= 413.696 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.03424 Å
Density
Contour LevelBy AUTHOR: 0.012
Minimum - Maximum-0.026917577 - 0.07057975
Average (Standard dev.)0.00008510924 (±0.0014177373)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 413.696 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_80082_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_80082_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Complex of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432)

EntireName: Complex of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432)
Components
  • Complex: Complex of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432)
    • Protein or peptide: KICSTOR complex protein kaptin
    • Protein or peptide: KICSTOR subunit 2
    • Protein or peptide: KICSTOR complex protein ITFG2
    • Protein or peptide: KICSTOR complex protein SZT2

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Supramolecule #1: Complex of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432)

SupramoleculeName: Complex of the human KPTN-ITFG2-C12orf66-SZT2(2189-3432)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: KICSTOR complex protein kaptin

MacromoleculeName: KICSTOR complex protein kaptin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 48.185355 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GMMGEAAVAA GPCPLREDSF TRFSSQSNVY GLAGGAGGRG ELLAATLKGK VLGFRYQDLR QKIRPVAKEL QFNYIPVDAE IVSIDTFNK SPPKRGLVVG ITFIKDSGDK GSPFLNIYCD YEPGSEYNLD SIAQSCLNLE LQFTPFQLCH AEVQVGDQLE T VFLLSGND ...String:
GMMGEAAVAA GPCPLREDSF TRFSSQSNVY GLAGGAGGRG ELLAATLKGK VLGFRYQDLR QKIRPVAKEL QFNYIPVDAE IVSIDTFNK SPPKRGLVVG ITFIKDSGDK GSPFLNIYCD YEPGSEYNLD SIAQSCLNLE LQFTPFQLCH AEVQVGDQLE T VFLLSGND PAIHLYKENE GLHQFEEQPV ENLFPELTNL TSSVLWLDVH NFPGTSRRLS ALGCQSGYVR VAHVDQRSRE VL QMWSVLQ DGPISRVIVF SLSAAKETKD RPLQDEYSVL VASMLEPAVV YRDLLNRGLE DQLLLPGSDQ FDSVLCSLVT DVD LDGRPE VLVATYGQEL LCYKYRGPES GLPEAQHGFH LLWQRSFSSP LLAMAHVDLT GDGLQELAVV SLKGVHILQH SLIQ ASELV LTRLRHQVEQ RRRRLQGLED GAGAGPAENA AS

UniProtKB: KICSTOR complex protein kaptin

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Macromolecule #2: KICSTOR subunit 2

MacromoleculeName: KICSTOR subunit 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 50.469758 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGESIPLAAP VPVEQAVLET FFSHLGIFSY DKAKDNVEKE REANKSAGGS WLSLLAALAH LAAAEKVYHS LTYLGQKLGG QSFFSRKDS IRTIYTSLHN ELKKVVTGRG ALGGTAPHVE ELLSHLSEQL CFFVQARMEI ADFYEKMYTL STQKFINAEE L VGLLDAIM ...String:
MGESIPLAAP VPVEQAVLET FFSHLGIFSY DKAKDNVEKE REANKSAGGS WLSLLAALAH LAAAEKVYHS LTYLGQKLGG QSFFSRKDS IRTIYTSLHN ELKKVVTGRG ALGGTAPHVE ELLSHLSEQL CFFVQARMEI ADFYEKMYTL STQKFINAEE L VGLLDAIM KKYSSRFHHP ILSPLESSFQ LEVDVLCHLL KAQAQVSEWK FLPSLVNLHS AHTKLQTWGQ IFEKQRETKK HL FGGQSQK AVQPPHLFLW LMKLKNMLLA KFSFYFHEAL SRQTTASEMK TLTAKANPDF FGKISSFIRK YDAANVSLIF DNR GSESFQ GHGYHHPHSY REAPKGVDQY PAVVSLPSDR PVMHWPNVIM IMTDRTSDLN SLEKVVHFYD DKVQSTYFLT RPEP HFTIV IIFESKKSER DSHFISFLNE VSLALKNPKV FASLKPGAKG

UniProtKB: KICSTOR subunit 2

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Macromolecule #3: KICSTOR complex protein ITFG2

MacromoleculeName: KICSTOR complex protein ITFG2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 49.365742 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MRSVSYVQRV ALEFSGSLFP HAICLGDVDN DTLNELVVGD TSGKVSVYKN DDSRPWLTCS CQGMLTCVGV GDVCNKGKNL LVAVSAEGW FHLFDLTPAK VLDASGHHET LIGEEQRPVF KQHIPANTKV MLISDIDGDG CRELVVGYTD RVVRAFRWEE L GEGPEHLT ...String:
MRSVSYVQRV ALEFSGSLFP HAICLGDVDN DTLNELVVGD TSGKVSVYKN DDSRPWLTCS CQGMLTCVGV GDVCNKGKNL LVAVSAEGW FHLFDLTPAK VLDASGHHET LIGEEQRPVF KQHIPANTKV MLISDIDGDG CRELVVGYTD RVVRAFRWEE L GEGPEHLT GQLVSLKKWM LEGQVDSLSV TLGPLGLPEL MVSQPGCAYA ILLCTWKKDT GSPPASEGPT DGSRETPAAR DV VLHQTSG RIHNKNVSTH LIGNIKQGHG TESSGSGLFA LCTLDGTLKL MEEMEEADKL LWSVQVDHQL FALEKLDVTG NGH EEVVAC AWDGQTYIID HNRTVVRFQV DENIRAFCAG LYACKEGRNS PCLVYVTFNQ KIYVYWEVQL ERMESTNLVK LLET KPEYH SLLQELGVDP DDLPVTRALL HQTLYHPDQP PQCAPSSLQD PT

UniProtKB: KICSTOR complex protein ITFG2

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Macromolecule #4: KICSTOR complex protein SZT2

MacromoleculeName: KICSTOR complex protein SZT2 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 137.96625 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GTLDVITVML VRNCKLTPAD VEFIQPPGSL PSEVLHLALP TSCRPWLPAL AWYLRQNLLI FLHSPKYTDS NSRNHFQHPL PPQGGLPDL DIYLYNKPGG QGTGGKGVAC ITLAFVDEGG APLSLALWPP SSPGPPDPLR EEEFEQLTQV IRCPVVVDSS S AQNGAPRL ...String:
GTLDVITVML VRNCKLTPAD VEFIQPPGSL PSEVLHLALP TSCRPWLPAL AWYLRQNLLI FLHSPKYTDS NSRNHFQHPL PPQGGLPDL DIYLYNKPGG QGTGGKGVAC ITLAFVDEGG APLSLALWPP SSPGPPDPLR EEEFEQLTQV IRCPVVVDSS S AQNGAPRL RLDVWEKGNI SIVQLEEKLR GAARQALADA IIELQLLPAS LCTEDTPTGS LRNGSLETKS SAGRASTFPP AP VPGEPVT PPSKAGRRSF WDMLSKTECG DLGSPKTTDD IVLDRPEDTR GRRRHKTESV RTPGGAERAP GSDSGAQRQK RRT TQLEEG EVGTLHPVFA RVAQRWMEFM VQIGCASVSR SSAHMVSRFL LPSILSEFTA LVTSMAGDTS VRIFEQHLGS EPEI FGPCS PGQLGPSPRP AAERHLLLLG RNFLQWRRPT QQAAKAMQRF EPGGDGSSGR NAPRQRLLLL EVVDKKLQLL TYNWA PDLG AALGRALVRL VQWQNARAHL IFCLLSQKLG LFHHYGQLDF PVRDEKEPNP FLLPTMEVET LIRSASPPLS REQGRL SGS SRGGGPLPLD TFPFDEALRD ITAARPSSVL GPVPRPPDPV TYHGQQFLEI KMAERRELER QMKMENLFVT WQQRSTP AT MPISAGELET LKQSSRLVHY CATAMLFDPA AWLHGPPETS GPPDGQRRHR PESGSGSREA PTSCESLDVS PPGAREEP W LKELSLAFLQ QYVQYLQSIG FVLVPLRPPS PARSTSRPRA MAILGTEGRG SFSCPKTKTD GSPKSTSSPV TTYHLQRAL PGGIILMELA FQGCYFCVKQ FALECSRIPM GQAVNSQLSM LFTEECDKVR DLMHVHSFSY DFHLRLVHQH VLGAHLVLRH GYHLTTFLR HFLAHHPDGP HFGRNHIYQG TLELPTPLIA AHQLYNYVAD HASSYHMKPL RMARPGGPEH NEYALVSAWH S SGSYLDSE GLRHQDDFDV SLLVCHCAAP FEEQGEAERH VLRLQFFVVL TSQRELFPRL TADMRRFRKP PRLPPEPEAP GS SAGSPGE ASGLILAPGP APLFPPLAAE VGMARARLAQ LVRLAGGHCR RDTLWKRLFL LEPPGPDRLR LGGRLALAEL EEL LEAVHA KSIGDIDPQL DCFLSMTVSW YQSLIKVLLS RFPQSCRHFQ SPDLGTQYLV VLNQKFTDCF VLVFLDSHLG KTSL TVVFR EPFPVQPQDS ESPPAQLVST YHHLESVINT ACFTLWTRLL

UniProtKB: KICSTOR complex protein SZT2

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.9 mg/mL
BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.81 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Software - details: 3Dflex / Number images used: 51000
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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