EMDB-32281: Structure of USP14-bound human 26S proteasome in substrate-inhibi...

Basic information

Entry

Database: EMDB / ID: EMD-32281

• Title: Structure of USP14-bound human 26S proteasome in substrate-inhibited state SB_USP14
• Map data: Complete map of the human proteasome holoenzyme in state SB_USP14, with the RP/CP low-pass filtered to 4.4/3.0 angstrom and sharpened by a B-factor of -50/0

Sample

• Complex: 26S proteasome
  • Complex: 26S proteasome
    • Protein or peptide: x 32 types
  • Complex: USP14
    • Protein or peptide: x 2 types
• Ligand: x 3 types

• Keywords: Proteasome / AAA-ATPase / Deubiquitinase / USP14 / HYDROLASE

Function / homology

Function:

negative regulation of ERAD pathway / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / proteasome accessory complex / integrator complex / regulation of chemotaxis / deubiquitinase activity / purine ribonucleoside triphosphate binding / meiosis I / protein K48-linked deubiquitination / proteasome regulatory particle / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / metal-dependent deubiquitinase activity / negative regulation of programmed cell death / regulation of endopeptidase activity / protein K63-linked deubiquitination / hypothalamus gonadotrophin-releasing hormone neuron development / Homologous DNA Pairing and Strand Exchange / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / female meiosis I / Resolution of D-loop Structures through Holliday Junction Intermediates / positive regulation of protein monoubiquitination / Cross-presentation of soluble exogenous antigens (endosomes) / fat pad development / : / mitochondrion transport along microtubule / K63-linked deubiquitinase activity / Somitogenesis / Impaired BRCA2 binding to RAD51 / endopeptidase inhibitor activity / myofibril / immune system process / proteasome binding / female gonad development / transcription factor binding / regulation of protein catabolic process / seminiferous tubule development / male meiosis I / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / blastocyst development / general transcription initiation factor binding / NF-kappaB binding / endopeptidase activator activity / polyubiquitin modification-dependent protein binding / proteasome assembly / protein deubiquitination / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / mRNA export from nucleus / negative regulation of ubiquitin-dependent protein catabolic process / enzyme regulator activity / regulation of neuron apoptotic process / regulation of proteasomal protein catabolic process / energy homeostasis / inclusion body / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / TICAM1,TRAF6-dependent induction of TAK1 complex / Negative regulation of FLT3 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Constitutive Signaling by NOTCH1 HD Domain Mutants / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / Regulation of FZD by ubiquitination / APC/C:Cdc20 mediated degradation of Cyclin B / Downregulation of ERBB4 signaling / p75NTR recruits signalling complexes / APC-Cdc20 mediated degradation of Nek2A / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex

Domain/homology:

Ubiquitin carboxyl-terminal hydrolase 14-like / : / Ubiquitin interaction motif / : / 26S proteasome regulatory subunit RPN7/PSMD6 C-terminal helix / 26S proteasome non-ATPase regulatory subunit Rpn12 / 26S proteasome regulatory subunit, C-terminal / Proteasome regulatory subunit C-terminal / DSS1/SEM1 / 26S proteasome regulatory subunit RPN5, C-terminal domain / : / DSS1/SEM1 family / 26S proteasome regulatory subunit RPN5 C-terminal domain / PSD13 N-terminal repeats / DSS1_SEM1 / 26S proteasome regulatory subunit Rpn6, N-terminal / 6S proteasome subunit Rpn6, C-terminal helix domain / 26S proteasome regulatory subunit RPN6 N-terminal domain / 26S proteasome subunit RPN6 C-terminal helix domain / 26S Proteasome non-ATPase regulatory subunit 13 / : / 26S proteasome subunit RPN2, N-terminal domain / 26S proteasome regulatory complex, non-ATPase subcomplex, Rpn2/Psmd1 subunit / 26S proteasome regulatory subunit RPN2, C-terminal / 26S proteasome regulatory subunit RPN2 C-terminal domain / 26S Proteasome non-ATPase regulatory subunit 7/8 / 26S proteasome regulatory complex, non-ATPase subcomplex, Rpn1 subunit / RPN1, N-terminal / 26S proteasome non-ATPase regulatory subunit RPN1, C-terminal / : / RPN1 N-terminal domain / 26S proteasome non-ATPase regulatory subunit RPN1 C-terminal / 26S proteasome regulatory subunit 7, OB domain / : / : / PSMD12/CSN4, N-terminal / 26S proteasome regulatory subunit Rpn7/COP9 signalosome complex subunit 1 / 26S proteasome regulatory subunit Rpn7, N-terminal / 26S proteasome subunit RPN7 / 26S Proteasome non-ATPase regulatory subunit 12/COP9 signalosome complex subunit 4 / Proteasome/cyclosome repeat / Proteasome/cyclosome repeat / Ubiquitin-interacting motif. / PCI/PINT associated module / : / von Willebrand factor type A domain / Proteasome subunit alpha 1 / HEAT repeats / Proteasomal ATPase OB C-terminal domain / Proteasomal ATPase OB C-terminal domain / CSN8/PSMD8/EIF3K / CSN8/PSMD8/EIF3K family / Rpn11/EIF3F, C-terminal / Maintenance of mitochondrial structure and function / Ubiquitin specific protease (USP) domain signature 2. / : / Ubiquitin specific protease (USP) domain signature 1. / Ubiquitin specific protease, conserved site / motif in proteasome subunits, Int-6, Nip-1 and TRIP-15 / PCI domain / Proteasome component (PCI) domain / PCI domain profile. / Peptidase C19, ubiquitin carboxyl-terminal hydrolase / Ubiquitin carboxyl-terminal hydrolase / Ubiquitin specific protease domain / Ubiquitin specific protease (USP) domain profile. / Ubiquitin interacting motif / Ubiquitin-interacting motif (UIM) domain profile. / JAB1/Mov34/MPN/PAD-1 ubiquitin protease / Proteasome beta subunit, C-terminal / Proteasome beta subunits C terminal / Proteasome subunit beta 4 / Proteasome subunit beta 2 / Proteasome beta 3 subunit / Proteasome subunit alpha6 / Proteasome subunit alpha5 / Proteasome beta-type subunits signature. / Peptidase T1A, proteasome beta-subunit / Proteasome beta-type subunit, conserved site / Proteasome subunit A N-terminal signature / Proteasome alpha-type subunits signature. / Proteasome alpha-subunit, N-terminal domain / Proteasome subunit A N-terminal signature Add an annotation / von Willebrand factor (vWF) type A domain / : / Proteasome alpha-type subunit / Proteasome alpha-type subunit profile. / VWFA domain profile. / Proteasome B-type subunit / Proteasome beta-type subunit profile. / Proteasome subunit / Proteasome, subunit alpha/beta / von Willebrand factor, type A / AAA ATPase, AAA+ lid domain / AAA+ lid domain / ATPase, AAA-type, conserved site / AAA-protein family signature. / JAB/MPN domain / JAB1/MPN/MOV34 metalloenzyme domain / MPN domain

Component:

Proteasome 26S subunit, ATPase 6 / 26S proteasome non-ATPase regulatory subunit 11 / 26S proteasome non-ATPase regulatory subunit 12 / 26S proteasome non-ATPase regulatory subunit 14 / Proteasome subunit alpha type-7 / 26S proteasome non-ATPase regulatory subunit 3 / Polyubiquitin-B / 26S proteasome regulatory subunit 6A / Proteasome subunit beta type-1 / Proteasome subunit alpha type-1 / Proteasome subunit alpha type-2 / Proteasome subunit alpha type-3 / Proteasome subunit alpha type-4 / Proteasome subunit alpha type-5 / Proteasome subunit beta type-4 / Proteasome subunit beta type-6 / Proteasome subunit beta type-5 / 26S proteasome regulatory subunit 7 / 26S proteasome regulatory subunit 6B / 26S proteasome non-ATPase regulatory subunit 8 / Proteasome subunit beta type-3 / Proteasome subunit beta type-2 / 26S proteasome non-ATPase regulatory subunit 7 / Ubiquitin carboxyl-terminal hydrolase 14 / 26S proteasome non-ATPase regulatory subunit 4 / 26S proteasome complex subunit SEM1 / Proteasome subunit alpha type-6 / 26S proteasome regulatory subunit 4 / 26S proteasome regulatory subunit 8 / 26S proteasome non-ATPase regulatory subunit 2 / 26S proteasome non-ATPase regulatory subunit 6 / Proteasome subunit beta type-7 / 26S proteasome non-ATPase regulatory subunit 1 / 26S proteasome non-ATPase regulatory subunit 13

• Biological species: Homo sapiens (human)
• Method: single particle reconstruction / cryo EM / Resolution: 3.5 Å
• Authors: Zhang S / Zou S / Yin D / Wu Z / Mao Y

Funding support

China, 1 items

Organization	Grant number	Country
National Natural Science Foundation of China (NSFC)	11774012	China

• Citation: Journal: Nature / Year: 2022; Title: USP14-regulated allostery of the human proteasome by time-resolved cryo-EM.; Authors: Shuwen Zhang / Shitao Zou / Deyao Yin / Lihong Zhao / Daniel Finley / Zhaolong Wu / Youdong Mao / ; Abstract: Proteasomal degradation of ubiquitylated proteins is tightly regulated at multiple levels. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating enzyme ubiquitin-specific protease 14 (USP14), which reversibly binds the proteasome and confers the ability to edit and reject substrates. How USP14 is activated and regulates proteasome function remain unknown. Here we present high-resolution cryo-electron microscopy structures of human USP14 in complex with the 26S proteasome in 13 distinct conformational states captured during degradation of polyubiquitylated proteins. Time-resolved cryo-electron microscopy analysis of the conformational continuum revealed two parallel pathways of proteasome state transitions induced by USP14, and captured transient conversion of substrate-engaged intermediates into substrate-inhibited intermediates. On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate, enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding. Dynamic USP14-ATPase interactions decouple the ATPase activity from RPN11-catalysed deubiquitylation and kinetically introduce three regulatory checkpoints on the proteasome, at the steps of ubiquitin recognition, substrate translocation initiation and ubiquitin chain recycling. These findings provide insights into the complete functional cycle of the USP14-regulated proteasome and establish mechanistic foundations for the discovery of USP14-targeted therapies.

History

Deposition	Nov 25, 2021	-
Header (metadata) release	May 18, 2022	-
Map release	May 18, 2022	-
Update	Oct 23, 2024	-
Current status	Oct 23, 2024	Processing site: PDBj / Status: Released

Map

• File: Download / File: emd_32281.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
• Annotation: Complete map of the human proteasome holoenzyme in state SB_USP14, with the RP/CP low-pass filtered to 4.4/3.0 angstrom and sharpened by a B-factor of -50/0
• Voxel size: X=Y=Z: 0.685 Å

Density

Contour Level	By AUTHOR: 0.005
Minimum - Maximum	-0.004620825 - 0.020436777
Average (Standard dev.)	-0.00005505522 (±0.0016008122)

• Symmetry: Space group: 1

Details

EMDB XML:

Map geometry	Axis order X Y Z Origin 0 0 0 Dimensions 640 640 640 Spacing 640 640 640
Cell	A=B=C: 438.4 Å α=β=γ: 90.0 °

Supplemental data

Additional map: Map of the human proteasome in state SB USP14...

• File: emd_32281_additional_1.map
• Annotation: Map of the human proteasome in state SB_USP14 after CP-masked refinement, low-pass filtered to 3.0 angstrom with no sharpening B-factor applied

Additional map: Unfiltered, unsharpened raw map of the human proteasome...

• File: emd_32281_additional_2.map
• Annotation: Unfiltered, unsharpened raw map of the human proteasome in state SB_USP14 after CP-masked refinement

Additional map: Map of the human proteasome in state SB USP14...

• File: emd_32281_additional_3.map
• Annotation: Map of the human proteasome in state SB_USP14 after RP-masked refinement, low-pass filtered to 4.4 angstrom and sharpened by a B-factor of -50

Additional map: Unfiltered, unsharpened raw map of the human proteasome...

• File: emd_32281_additional_4.map
• Annotation: Unfiltered, unsharpened raw map of the human proteasome in state SB_USP14 after RP-masked refinement

Sample components

Entire : 26S proteasome

• Entire: Name: 26S proteasome

Components

• Complex: 26S proteasome
  • Complex: 26S proteasome
    • Protein or peptide: 26S protease regulatory subunit 7
    • Protein or peptide: 26S protease regulatory subunit 4
    • Protein or peptide: Isoform 2 of 26S proteasome regulatory subunit 8
    • Protein or peptide: 26S protease regulatory subunit 6B
    • Protein or peptide: 26S proteasome regulatory subunit 10B
    • Protein or peptide: 26S protease regulatory subunit 6A
    • Protein or peptide: Proteasome subunit alpha type-6
    • Protein or peptide: Proteasome subunit alpha type-2
    • Protein or peptide: Proteasome subunit alpha type-4
    • Protein or peptide: Proteasome subunit alpha type-7
    • Protein or peptide: Proteasome subunit alpha type-5
    • Protein or peptide: Isoform Long of Proteasome subunit alpha type-1
    • Protein or peptide: Proteasome subunit alpha type-3
    • Protein or peptide: Proteasome subunit beta type-6
    • Protein or peptide: Proteasome subunit beta type-7
    • Protein or peptide: Proteasome subunit beta type-3
    • Protein or peptide: Proteasome subunit beta type-2
    • Protein or peptide: Proteasome subunit beta type-5
    • Protein or peptide: Proteasome subunit beta type-1
    • Protein or peptide: Proteasome subunit beta type-4
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 1
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 3
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 12
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 11
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 6
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 7
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 13
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 4
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 14
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 8
    • Protein or peptide: 26S proteasome non-ATPase regulatory subunit 2
    • Protein or peptide: 26S proteasome complex subunit DSS1
  • Complex: USP14
    • Protein or peptide: Ubiquitin carboxyl-terminal hydrolase 14
    • Protein or peptide: Ubiquitin
• Ligand: ADENOSINE-5'-TRIPHOSPHATE
• Ligand: ADENOSINE-5'-DIPHOSPHATE
• Ligand: ZINC ION

Supramolecule #1: 26S proteasome

• Supramolecule: Name: 26S proteasome / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#34
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 1.6 MDa

Supramolecule #2: 26S proteasome

• Supramolecule: Name: 26S proteasome / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2-#21, #23-#34
• Source (natural): Organism: Homo sapiens (human)

Supramolecule #3: USP14

• Supramolecule: Name: USP14 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1, #22

Macromolecule #1: Ubiquitin carboxyl-terminal hydrolase 14

• Macromolecule: Name: Ubiquitin carboxyl-terminal hydrolase 14 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: ubiquitinyl hydrolase 1
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 56.133926 KDa
• Recombinant expression: Organism: Escherichia coli BL21(DE3) (bacteria)

Sequence

String:

MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN IKIKNGMTLL MMGSADALPE EPSAKTVFV EDMTEEQLAS AMELPCGLTN LGNTCYMNAT VQCIRSVPEL KDALKRYAGA LRASGEMASA QYITAALRDL F DSMDKTSS SIPPIILLQF LHMAFPQFAE KGEQGQYLQQ DANECWIQMM RVLQQKLEAI EDDSVKETDS SSASAATPSK KK SLIDQFF GVEFETTMKC TESEEEEVTK GKENQLQLSC FINQEVKYLF TGLKLRLQEE ITKQSPTLQR NALYIKSSKI SRL PAYLTI QMVRFFYKEK ESVNAKVLKD VKFPLMLDMY ELCTPELQEK MVSFRSKFKD LEDKKVNQQP NTSDKKSSPQ KEVK YEPFS FADDIGSNNC GYYDLQAVLT HQGRSSSSGH YVSWVKRKQD EWIKFDDDKV SIVTPEDILR LSGGGDWHIA YVLLY GPRR VEIMEEESEQ

UniProtKB: Ubiquitin carboxyl-terminal hydrolase 14

Macromolecule #2: 26S protease regulatory subunit 7

• Macromolecule: Name: 26S protease regulatory subunit 7 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 48.700805 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MPDYLGADQR KTKEDEKDDK PIRALDEGDI ALLKTYGQST YSRQIKQVED DIQQLLKKIN ELTGIKESDT GLAPPALWDL AADKQTLQS EQPLQVARCT KIINADSEDP KYIINVKQFA KFVVDLSDQV APTDIEEGMR VGVDRNKYQI HIPLPPKIDP T VTMMQVEE KPDVTYSDVG GCKEQIEKLR EVVETPLLHP ERFVNLGIEP PKGVLLFGPP GTGKTLCARA VANRTDACFI RV IGSELVQ KYVGEGARMV RELFEMARTK KACLIFFDEI DAIGGARFDD GAGGDNEVQR TMLELINQLD GFDPRGNIKV LMA TNRPDT LDPALMRPGR LDRKIEFSLP DLEGRTHIFK IHARSMSVER DIRFELLARL CPNSTGAEIR SVCTEAGMFA IRAR RKIAT EKDFLEAVNK VIKSYAKFSA TPRYMTYN

UniProtKB: 26S proteasome regulatory subunit 7

Macromolecule #3: 26S protease regulatory subunit 4

• Macromolecule: Name: 26S protease regulatory subunit 4 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 49.260504 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MGQSQSGGHG PGGGKKDDKD KKKKYEPPVP TRVGKKKKKT KGPDAASKLP LVTPHTQCRL KLLKLERIKD YLLMEEEFIR NQEQMKPLE EKQEEERSKV DDLRGTPMSV GTLEEIIDDN HAIVSTSVGS EHYVSILSFV DKDLLEPGCS VLLNHKVHAV I GVLMDDTD PLVTVMKVEK APQETYADIG GLDNQIQEIK ESVELPLTHP EYYEEMGIKP PKGVILYGPP GTGKTLLAKA VA NQTSATF LRVVGSELIQ KYLGDGPKLV RELFRVAEEH APSIVFIDEI DAIGTKRYDS NSGGEREIQR TMLELLNQLD GFD SRGDVK VIMATNRIET LDPALIRPGR IDRKIEFPLP DEKTKKRIFQ IHTSRMTLAD DVTLDDLIMA KDDLSGADIK AICT EAGLM ALRERRMKVT NEDFKKSKEN VLYKKQEGTP EGLYL

UniProtKB: 26S proteasome regulatory subunit 4

Macromolecule #4: Isoform 2 of 26S proteasome regulatory subunit 8

• Macromolecule: Name: Isoform 2 of 26S proteasome regulatory subunit 8 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 44.852121 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MELEEGKAGS GLRQYYLSKI EELQLIVNDK SQNLRRLQAQ RNELNAKVRL LREELQLLQE QGSYVGEVVR AMDKKKVLVK VHPEGKFVV DVDKNIDIND VTPNCRVALR NDSYTLHKIL PNKVDPLVSL MMVEKVPDST YEMIGGLDKQ IKEIKEVIEL P VKHPELFE ALGIAQPKGV LLYGPPGTGK TLLARAVAHH TDCTFIRVSG SELVQKFIGE GARMVRELFV MAREHAPSII FM DEIDSIG SSRLEGGSGG DSEVQRTMLE LLNQLDGFEA TKNIKVIMAT NRIDILDSAL LRPGRIDRKI EFPPPNEEAR LDI LKIHSR KMNLTRGINL RKIAELMPGA SGAEVKGVCT EAGMYALRER RVHVTQEDFE MAVAKVMQKD SEKNMSIKKL WK

UniProtKB: 26S proteasome regulatory subunit 8

Macromolecule #5: 26S protease regulatory subunit 6B

• Macromolecule: Name: 26S protease regulatory subunit 6B / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 47.426141 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MEEIGILVEK AQDEIPALSV SRPQTGLSFL GPEPEDLEDL YSRYKKLQQE LEFLEVQEEY IKDEQKNLKK EFLHAQEEVK RIQSIPLVI GQFLEAVDQN TAIVGSTTGS NYYVRILSTI DRELLKPNAS VALHKHSNAL VDVLPPEADS SIMMLTSDQK P DVMYADIG GMDIQKQEVR EAVELPLTHF ELYKQIGIDP PRGVLMYGPP GCGKTMLAKA VAHHTTAAFI RVVGSEFVQK YL GEGPRMV RDVFRLAKEN APAIIFIDEI DAIATKRFDA QTGADREVQR ILLELLNQMD GFDQNVNVKV IMATNRADTL DPA LLRPGR LDRKIEFPLP DRRQKRLIFS TITSKMNLSE EVDLEDYVAR PDKISGADIN SICQESGMLA VRENRYIVLA KDFE KAYKT VIKKDEQEHE FYK

UniProtKB: 26S proteasome regulatory subunit 6B

Macromolecule #6: 26S proteasome regulatory subunit 10B

• Macromolecule: Name: 26S proteasome regulatory subunit 10B / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 45.867027 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MAIPGIPYER RLLIMADPRD KALQDYRKKL LEHKEIDGRL KELREQLKEL TKQYEKSEND LKALQSVGQI VGEVLKQLTE EKFIVKATN GPRYVVGCRR QLDKSKLKPG TRVALDMTTL TIMRYLPREV DPLVYNMSHE DPGNVSYSEI GGLSEQIREL R EVIELPLT NPELFQRVGI IPPKGCLLYG PPGTGKTLLA RAVASQLDCN FLKVVSSSIV DKYIGESARL IREMFNYARD HQ PCIIFMD EIDAIGGRRF SEGTSADREI QRTLMELLNQ MDGFDTLHRV KMIMATNRPD TLDPALLRPG RLDRKIHIDL PNE QARLDI LKIHAGPITK HGEIDYEAIV KLSDGFNGAD LRNVCTEAGM FAIRADHDFV VQEDFMKAVR KVADSKKLES KLDY KPV

UniProtKB: Proteasome 26S subunit, ATPase 6

Macromolecule #7: 26S protease regulatory subunit 6A

• Macromolecule: Name: 26S protease regulatory subunit 6A / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 49.266457 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MNLLPNIESP VTRQEKMATV WDEAEQDGIG EEVLKMSTEE IIQRTRLLDS EIKIMKSEVL RVTHELQAMK DKIKENSEKI KVNKTLPYL VSNVIELLDV DPNDQEEDGA NIDLDSQRKG KCAVIKTSTR QTYFLPVIGL VDAEKLKPGD LVGVNKDSYL I LETLPTEY DSRVKAMEVD ERPTEQYSDI GGLDKQIQEL VEAIVLPMNH KEKFENLGIQ PPKGVLMYGP PGTGKTLLAR AC AAQTKAT FLKLAGPQLV QMFIGDGAKL VRDAFALAKE KAPSIIFIDE LDAIGTKRFD SEKAGDREVQ RTMLELLNQL DGF QPNTQV KVIAATNRVD ILDPALLRSG RLDRKIEFPM PNEEARARIM QIHSRKMNVS PDVNYEELAR CTDDFNGAQC KAVC VEAGM IALRRGATEL THEDYMEGIL EVQAKKKANL QYYA

UniProtKB: 26S proteasome regulatory subunit 6A

Macromolecule #8: Proteasome subunit alpha type-6

• Macromolecule: Name: Proteasome subunit alpha type-6 / type: protein_or_peptide / ID: 8 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 27.432459 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MSRGSSAGFD RHITIFSPEG RLYQVEYAFK AINQGGLTSV AVRGKDCAVI VTQKKVPDKL LDSSTVTHLF KITENIGCVM TGMTADSRS QVQRARYEAA NWKYKYGYEI PVDMLCKRIA DISQVYTQNA EMRPLGCCMI LIGIDEEQGP QVYKCDPAGY Y CGFKATAA GVKQTESTSF LEKKVKKKFD WTFEQTVETA ITCLSTVLSI DFKPSEIEVG VVTVENPKFR ILTEAEIDAH LV ALAERD

UniProtKB: Proteasome subunit alpha type-6

Macromolecule #9: Proteasome subunit alpha type-2

• Macromolecule: Name: Proteasome subunit alpha type-2 / type: protein_or_peptide / ID: 9 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 25.927535 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MAERGYSFSL TTFSPSGKLV QIEYALAAVA GGAPSVGIKA ANGVVLATEK KQKSILYDER SVHKVEPITK HIGLVYSGMG PDYRVLVHR ARKLAQQYYL VYQEPIPTAQ LVQRVASVMQ EYTQSGGVRP FGVSLLICGW NEGRPYLFQS DPSGAYFAWK A TAMGKNYV NGKTFLEKRY NEDLELEDAI HTAILTLKES FEGQMTEDNI EVGICNEAGF RRLTPTEVKD YLAAIA

UniProtKB: Proteasome subunit alpha type-2

Macromolecule #10: Proteasome subunit alpha type-4

• Macromolecule: Name: Proteasome subunit alpha type-4 / type: protein_or_peptide / ID: 10 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 29.525842 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MSRRYDSRTT IFSPEGRLYQ VEYAMEAIGH AGTCLGILAN DGVLLAAERR NIHKLLDEVF FSEKIYKLNE DMACSVAGIT SDANVLTNE LRLIAQRYLL QYQEPIPCEQ LVTALCDIKQ AYTQFGGKRP FGVSLLYIGW DKHYGFQLYQ SDPSGNYGGW K ATCIGNNS AAAVSMLKQD YKEGEMTLKS ALALAIKVLN KTMDVSKLSA EKVEIATLTR ENGKTVIRVL KQKEVEQLIK KH EEEEAKA EREKKEKEQK EKDK

UniProtKB: Proteasome subunit alpha type-4

Macromolecule #11: Proteasome subunit alpha type-7

• Macromolecule: Name: Proteasome subunit alpha type-7 / type: protein_or_peptide / ID: 11 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 27.929891 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MSYDRAITVF SPDGHLFQVE YAQEAVKKGS TAVGVRGRDI VVLGVEKKSV AKLQDERTVR KICALDDNVC MAFAGLTADA RIVINRARV ECQSHRLTVE DPVTVEYITR YIASLKQRYT QSNGRRPFGI SALIVGFDFD GTPRLYQTDP SGTYHAWKAN A IGRGAKSV REFLEKNYTD EAIETDDLTI KLVIKALLEV VQSGGKNIEL AVMRRDQSLK ILNPEEIEKY VAEIEKEKEE NE KKKQKKA S

UniProtKB: Proteasome subunit alpha type-7

Macromolecule #12: Proteasome subunit alpha type-5

• Macromolecule: Name: Proteasome subunit alpha type-5 / type: protein_or_peptide / ID: 12 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 26.435977 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MFLTRSEYDR GVNTFSPEGR LFQVEYAIEA IKLGSTAIGI QTSEGVCLAV EKRITSPLME PSSIEKIVEI DAHIGCAMSG LIADAKTLI DKARVETQNH WFTYNETMTV ESVTQAVSNL ALQFGEEDAD PGAMSRPFGV ALLFGGVDEK GPQLFHMDPS G TFVQCDAR AIGSASEGAQ SSLQEVYHKS MTLKEAIKSS LIILKQVMEE KLNATNIELA TVQPGQNFHM FTKEELEEVI KD I

UniProtKB: Proteasome subunit alpha type-5

Macromolecule #13: Isoform Long of Proteasome subunit alpha type-1

• Macromolecule: Name: Isoform Long of Proteasome subunit alpha type-1 / type: protein_or_peptide / ID: 13 / Number of copies: 2 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 30.281473 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MQLSKVKFRN QYDNDVTVWS PQGRIHQIEY AMEAVKQGSA TVGLKSKTHA VLVALKRAQS ELAAHQKKIL HVDNHIGISI AGLTADARL LCNFMRQECL DSRFVFDRPL PVSRLVSLIG SKTQIPTQRY GRRPYGVGLL IAGYDDMGPH IFQTCPSANY F DCRAMSIG ARSQSARTYL ERHMSEFMEC NLNELVKHGL RALRETLPAE QDLTTKNVSI GIVGKDLEFT IYDDDDVSPF LE GLEERPQ RKAQPAQPAD EPAEKADEPM EH

UniProtKB: Proteasome subunit alpha type-1

Macromolecule #14: Proteasome subunit alpha type-3

• Macromolecule: Name: Proteasome subunit alpha type-3 / type: protein_or_peptide / ID: 14 / Number of copies: 2 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 28.469252 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MSSIGTGYDL SASTFSPDGR VFQVEYAMKA VENSSTAIGI RCKDGVVFGV EKLVLSKLYE EGSNKRLFNV DRHVGMAVAG LLADARSLA DIAREEASNF RSNFGYNIPL KHLADRVAMY VHAYTLYSAV RPFGCSFMLG SYSVNDGAQL YMIDPSGVSY G YWGCAIGK ARQAAKTEIE KLQMKEMTCR DIVKEVAKII YIVHDEVKDK AFELELSWVG ELTNGRHEIV PKDIREEAEK YA KESLKEE DESDDDNM

UniProtKB: Proteasome subunit alpha type-3

Macromolecule #15: Proteasome subunit beta type-6

• Macromolecule: Name: Proteasome subunit beta type-6 / type: protein_or_peptide / ID: 15 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 25.377652 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MAATLLAARG AGPAPAWGPE AFTPDWESRE VSTGTTIMAV QFDGGVVLGA DSRTTTGSYI ANRVTDKLTP IHDRIFCCRS GSAADTQAV ADAVTYQLGF HSIELNEPPL VHTAASLFKE MCYRYREDLM AGIIIAGWDP QEGGQVYSVP MGGMMVRQSF A IGGSGSSY IYGYVDATYR EGMTKEECLQ FTANALALAM ERDGSSGGVI RLAAIAESGV ERQVLLGDQI PKFAVATLPP A

UniProtKB: Proteasome subunit beta type-6

Macromolecule #16: Proteasome subunit beta type-7

• Macromolecule: Name: Proteasome subunit beta type-7 / type: protein_or_peptide / ID: 16 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 30.000418 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MAAVSVYAPP VGGFSFDNCR RNAVLEADFA KRGYKLPKVR KTGTTIAGVV YKDGIVLGAD TRATEGMVVA DKNCSKIHFI SPNIYCCGA GTAADTDMTT QLISSNLELH SLSTGRLPRV VTANRMLKQM LFRYQGYIGA ALVLGGVDVT GPHLYSIYPH G STDKLPYV TMGSGSLAAM AVFEDKFRPD MEEEEAKNLV SEAIAAGIFN DLGSGSNIDL CVISKNKLDF LRPYTVPNKK GT RLGRYRC EKGTTAVLTE KITPLEIEVL EETVQTMDTS

UniProtKB: Proteasome subunit beta type-7

Macromolecule #17: Proteasome subunit beta type-3

• Macromolecule: Name: Proteasome subunit beta type-3 / type: protein_or_peptide / ID: 17 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 22.972896 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MSIMSYNGGA VMAMKGKNCV AIAADRRFGI QAQMVTTDFQ KIFPMGDRLY IGLAGLATDV QTVAQRLKFR LNLYELKEGR QIKPYTLMS MVANLLYEKR FGPYYTEPVI AGLDPKTFKP FICSLDLIGC PMVTDDFVVS GTCAEQMYGM CESLWEPNMD P DHLFETIS QAMLNAVDRD AVSGMGVIVH IIEKDKITTR TLKARMD

UniProtKB: Proteasome subunit beta type-3

Macromolecule #18: Proteasome subunit beta type-2

• Macromolecule: Name: Proteasome subunit beta type-2 / type: protein_or_peptide / ID: 18 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 22.864277 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MEYLIGIQGP DYVLVASDRV AASNIVQMKD DHDKMFKMSE KILLLCVGEA GDTVQFAEYI QKNVQLYKMR NGYELSPTAA ANFTRRNLA DCLRSRTPYH VNLLLAGYDE HEGPALYYMD YLAALAKAPF AAHGYGAFLT LSILDRYYTP TISRERAVEL L RKCLEELQ KRFILNLPTF SVRIIDKNGI HDLDNISFPK QGS

UniProtKB: Proteasome subunit beta type-2

Macromolecule #19: Proteasome subunit beta type-5

• Macromolecule: Name: Proteasome subunit beta type-5 / type: protein_or_peptide / ID: 19 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 28.510248 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MALASVLERP LPVNQRGFFG LGGRADLLDL GPGSLSDGLS LAAPGWGVPE EPGIEMLHGT TTLAFKFRHG VIVAADSRAT AGAYIASQT VKKVIEINPY LLGTMAGGAA DCSFWERLLA RQCRIYELRN KERISVAAAS KLLANMVYQY KGMGLSMGTM I CGWDKRGP GLYYVDSEGN RISGATFSVG SGSVYAYGVM DRGYSYDLEV EQAYDLARRA IYQATYRDAY SGGAVNLYHV RE DGWIRVS SDNVADLHEK YSGSTP

UniProtKB: Proteasome subunit beta type-5

Macromolecule #20: Proteasome subunit beta type-1

• Macromolecule: Name: Proteasome subunit beta type-1 / type: protein_or_peptide / ID: 20 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 26.522396 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MLSSTAMYSA PGRDLGMEPH RAAGPLQLRF SPYVFNGGTI LAIAGEDFAI VASDTRLSEG FSIHTRDSPK CYKLTDKTVI GCSGFHGDC LTLTKIIEAR LKMYKHSNNK AMTTGAIAAM LSTILYSRRF FPYYVYNIIG GLDEEGKGAV YSFDPVGSYQ R DSFKAGGS ASAMLQPLLD NQVGFKNMQN VEHVPLSLDR AMRLVKDVFI SAAERDVYTG DALRICIVTK EGIREETVSL RK D

UniProtKB: Proteasome subunit beta type-1

Macromolecule #21: Proteasome subunit beta type-4

• Macromolecule: Name: Proteasome subunit beta type-4 / type: protein_or_peptide / ID: 21 / Number of copies: 2 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 29.231178 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MEAFLGSRSG LWAGGPAPGQ FYRIPSTPDS FMDPASALYR GPITRTQNPM VTGTSVLGVK FEGGVVIAAD MLGSYGSLAR FRNISRIMR VNNSTMLGAS GDYADFQYLK QVLGQMVIDE ELLGDGHSYS PRAIHSWLTR AMYSRRSKMN PLWNTMVIGG Y ADGESFLG YVDMLGVAYE APSLATGYGA YLAQPLLREV LEKQPVLSQT EARDLVERCM RVLYYRDARS YNRFQIATVT EK GVEIEGP LSTETNWDIA HMISGFE

UniProtKB: Proteasome subunit beta type-4

Macromolecule #22: Ubiquitin

• Macromolecule: Name: Ubiquitin / type: protein_or_peptide / ID: 22 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 8.576831 KDa
• Recombinant expression: Organism: Escherichia coli BL21(DE3) (bacteria)

Sequence

String:

MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG

UniProtKB: Polyubiquitin-B

Macromolecule #23: 26S proteasome non-ATPase regulatory subunit 1

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 1 / type: protein_or_peptide / ID: 23 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 105.958234 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MITSAAGIIS LLDEDEPQLK EFALHKLNAV VNDFWAEISE SVDKIEVLYE DEGFRSRQFA ALVASKVFYH LGAFEESLNY ALGAGDLFN VNDNSEYVET IIAKCIDHYT KQCVENADLP EGEKKPIDQR LEGIVNKMFQ RCLDDHKYKQ AIGIALETRR L DVFEKTIL ESNDVPGMLA YSLKLCMSLM QNKQFRNKVL RVLVKIYMNL EKPDFINVCQ CLIFLDDPQA VSDILEKLVK ED NLLMAYQ ICFDLYESAS QQFLSSVIQN LRTVGTPIAS VPGSTNTGTV PGSEKDSDSM ETEEKTSSAF VGKTPEASPE PKD QTLKMI KILSGEMAIE LHLQFLIRNN NTDLMILKNT KDAVRNSVCH TATVIANSFM HCGTTSDQFL RDNLEWLARA TNWA KFTAT ASLGVIHKGH EKEALQLMAT YLPKDTSPGS AYQEGGGLYA LGLIHANHGG DIIDYLLNQL KNASNDIVRH GGSLG LGLA AMGTARQDVY DLLKTNLYQD DAVTGEAAGL ALGLVMLGSK NAQAIEDMVG YAQETQHEKI LRGLAVGIAL VMYGRM EEA DALIESLCRD KDPILRRSGM YTVAMAYCGS GNNKAIRRLL HVAVSDVNDD VRRAAVESLG FILFRTPEQC PSVVSLL SE SYNPHVRYGA AMALGICCAG TGNKEAINLL EPMTNDPVNY VRQGALIASA LIMIQQTEIT CPKVNQFRQL YSKVINDK H DDVMAKFGAI LAQGILDAGG HNVTISLQSR TGHTHMPSVV GVLVFTQFWF WFPLSHFLSL AYTPTCVIGL NKDLKMPKV QYKSNCKPST FAYPAPLEVP KEKEKEKVST AVLSITAKAK KKEKEKEKKE EEKMEVDEAE KKEEKEKKKE PEPNFQLLDN PARVMPAQL KVLTMPETCR YQPFKPLSIG GIIILKDTSE DIEELVEPVA AHGPKIEEEE QEPEPPEPFE YIDD

UniProtKB: 26S proteasome non-ATPase regulatory subunit 1

Macromolecule #24: 26S proteasome non-ATPase regulatory subunit 3

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 3 / type: protein_or_peptide / ID: 24 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 61.0665 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MKQEGSARRR GADKAKPPPG GGEQEPPPPP APQDVEMKEE AATGGGSTGE ADGKTAAAAA EHSQRELDTV TLEDIKEHVK QLEKAVSGK EPRFVLRALR MLPSTSRRLN HYVLYKAVQG FFTSNNATRD FLLPFLEEPM DTEADLQFRP RTGKAASTPL L PEVEAYLQ LLVVIFMMNS KRYKEAQKIS DDLMQKISTQ NRRALDLVAA KCYYYHARVY EFLDKLDVVR SFLHARLRTA TL RHDADGQ ATLLNLLLRN YLHYSLYDQA EKLVSKSVFP EQANNNEWAR YLYYTGRIKA IQLEYSEARR TMTNALRKAP QHT AVGFKQ TVHKLLIVVE LLLGEIPDRL QFRQPSLKRS LMPYFLLTQA VRTGNLAKFN QVLDQFGEKF QADGTYTLII RLRH NVIKT GVRMISLSYS RISLADIAQK LQLDSPEDAE FIVAKAIRDG VIEASINHEK GYVQSKEMID IYSTREPQLA FHQRI SFCL DIHNMSVKAM RFPPKSYNKD LESAEERRER EQQDLEFAKE MAEDDDDSFP

UniProtKB: 26S proteasome non-ATPase regulatory subunit 3

Macromolecule #25: 26S proteasome non-ATPase regulatory subunit 12

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 12 / type: protein_or_peptide / ID: 25 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 52.979359 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MADGGSERAD GRIVKMEVDY SATVDQRLPE CAKLAKEGRL QEVIETLLSL EKQTRTASDM VSTSRILVAV VKMCYEAKEW DLLNENIML LSKRRSQLKQ AVAKMVQQCC TYVEEITDLP IKLRLIDTLR MVTEGKIYVE IERARLTKTL ATIKEQNGDV K EAASILQE LQVETYGSME KKERVEFILE QMRLCLAVKD YIRTQIISKK INTKFFQEEN TEKLKLKYYN LMIQLDQHEG SY LSICKHY RAIYDTPCIQ AESEKWQQAL KSVVLYVILA PFDNEQSDLV HRISGDKKLE EIPKYKDLLK LFTTMELMRW STL VEDYGM ELRKGSLESP ATDVFGSTEE GEKRWKDLKN RVVEHNIRIM AKYYTRITMK RMAQLLDLSV DESEAFLSNL VVNK TIFAK VDRLAGIINF QRPKDPNNLL NDWSQKLNSL MSLVNKTTHL IAKEEMIHNL Q

UniProtKB: 26S proteasome non-ATPase regulatory subunit 12

Macromolecule #26: 26S proteasome non-ATPase regulatory subunit 11

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 11 / type: protein_or_peptide / ID: 26 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 47.526688 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MAAAAVVEFQ RAQSLLSTDR EASIDILHSI VKRDIQENDE EAVQVKEQSI LELGSLLAKT GQAAELGGLL KYVRPFLNSI SKAKAARLV RSLLDLFLDM EAATGQEVEL CLECIEWAKS EKRTFLRQAL EARLVSLYFD TKRYQEALHL GSQLLRELKK M DDKALLVE VQLLESKTYH ALSNLPKARA ALTSARTTAN AIYCPPKLQA TLDMQSGIIH AAEEKDWKTA YSYFYEAFEG YD SIDSPKA ITSLKYMLLC KIMLNTPEDV QALVSGKLAL RYAGRQTEAL KCVAQASKNR SLADFEKALT DYRAELRDDP IIS THLAKL YDNLLEQNLI RVIEPFSRVQ IEHISSLIKL SKADVERKLS QMILDKKFHG ILDQGEGVLI IFDEPPVDKT YEAA LETIQ NMSKVVDSLY NKAKKLT

UniProtKB: 26S proteasome non-ATPase regulatory subunit 11

Macromolecule #27: 26S proteasome non-ATPase regulatory subunit 6

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 6 / type: protein_or_peptide / ID: 27 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 45.592285 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MPLENLEEEG LPKNPDLRIA QLRFLLSLPE HRGDAAVRDE LMAAVRDNNM APYYEALCKS LDWQIDVDLL NKMKKANEDE LKRLDEELE DAEKNLGESE IRDAMMAKAE YLCRIGDKEG ALTAFRKTYD KTVALGHRLD IVFYLLRIGL FYMDNDLITR N TEKAKSLI EEGGDWDRRN RLKVYQGLYC VAIRDFKQAA ELFLDTVSTF TSYELMDYKT FVTYTVYVSM IALERPDLRE KV IKGAEIL EVLHSLPAVR QYLFSLYECR YSVFFQSLAV VEQEMKKDWL FAPHYRYYVR EMRIHAYSQL LESYRSLTLG YMA EAFGVG VEFIDQELSR FIAAGRLHCK IDKVNEIVET NRPDSKNWQY QETIKKGDLL LNRVQKLSRV INM

UniProtKB: 26S proteasome non-ATPase regulatory subunit 6

Macromolecule #28: 26S proteasome non-ATPase regulatory subunit 7

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 7 / type: protein_or_peptide / ID: 28 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 37.086441 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MPELAVQKVV VHPLVLLSVV DHFNRIGKVG NQKRVVGVLL GSWQKKVLDV SNSFAVPFDE DDKDDSVWFL DHDYLENMYG MFKKVNARE RIVGWYHTGP KLHKNDIAIN ELMKRYCPNS VLVIIDVKPK DLGLPTEAYI SVEEVHDDGT PTSKTFEHVT S EIGAEEAE EVGVEHLLRD IKDTTVGTLS QRITNQVHGL KGLNSKLLDI RSYLEKVATG KLPINHQIIY QLQDVFNLLP DV SLQEFVK AFYLKTNDQM VVVYLASLIR SVVALHNLIN NKIANRDAEK KEGQEKEESK KDRKEDKEKD KDKEKSDVKK EEK KEKK

UniProtKB: 26S proteasome non-ATPase regulatory subunit 7

Macromolecule #29: 26S proteasome non-ATPase regulatory subunit 13

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 13 / type: protein_or_peptide / ID: 29 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 42.995359 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MKDVPGFLQQ SQNSGPGQPA VWHRLEELYT KKLWHQLTLQ VLDFVQDPCF AQGDGLIKLY ENFISEFEHR VNPLSLVEII LHVVRQMTD PNVALTFLEK TREKVKSSDE AVILCKTAIG ALKLNIGDLQ VTKETIEDVE EMLNNLPGVT SVHSRFYDLS S KYYQTIGN HASYYKDALR FLGCVDIKDL PVSEQQERAF TLGLAGLLGE GVFNFGELLM HPVLESLRNT DRQWLIDTLY AF NSGNVER FQTLKTAWGQ QPDLAANEAQ LLRKIQLLCL MEMTFTRPAN HRQLTFEEIA KSAKITVNEV ELLVMKALSV GLV KGSIDE VDKRVHMTWV QPRVLDLQQI KGMKDRLEFW CTDVKSMEML VEHQAHDILT

UniProtKB: 26S proteasome non-ATPase regulatory subunit 13

Macromolecule #30: 26S proteasome non-ATPase regulatory subunit 4

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 4 / type: protein_or_peptide / ID: 30 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 40.78159 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MVLESTMVCV DNSEYMRNGD FLPTRLQAQQ DAVNIVCHSK TRSNPENNVG LITLANDCEV LTTLTPDTGR ILSKLHTVQP KGKITFCTG IRVAHLALKH RQGKNHKMRI IAFVGSPVED NEKDLVKLAK RLKKEKVNVD IINFGEEEVN TEKLTAFVNT L NGKDGTGS HLVTVPPGPS LADALISSPI LAGEGGAMLG LGASDFEFGV DPSADPELAL ALRVSMEEQR QRQEEEARRA AA ASAAEAG IATTGTEDSD DALLKMTISQ QEFGRTGLPD LSSMTEEEQI AYAMQMSLQG AEFGQAESAD IDASSAMDTS EPA KEEDDY DVMQDPEFLQ SVLENLPGVD PNNEAIRNAM GSLASQATKD GKKDKKEEDK K

UniProtKB: 26S proteasome non-ATPase regulatory subunit 4

Macromolecule #31: 26S proteasome non-ATPase regulatory subunit 14

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 14 / type: protein_or_peptide / ID: 31 / Number of copies: 1 / Enantiomer: LEVO; EC number: Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 34.620023 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MDRLLRLGGG MPGLGQGPPT DAPAVDTAEQ VYISSLALLK MLKHGRAGVP MEVMGLMLGE FVDDYTVRVI DVFAMPQSGT GVSVEAVDP VFQAKMLDML KQTGRPEMVV GWYHSHPGFG CWLSGVDINT QQSFEALSER AVAVVVDPIQ SVKGKVVIDA F RLINANMM VLGHEPRQTT SNLGHLNKPS IQALIHGLNR HYYSITINYR KNELEQKMLL NLHKKSWMEG LTLQDYSEHC KH NESVVKE MLELAKNYNK AVEEEDKMTP EQLAIKNVGK QDPKRHLEEH VDVLMTSNIV QCLAAMLDTV VFK

UniProtKB: 26S proteasome non-ATPase regulatory subunit 14

Macromolecule #32: 26S proteasome non-ATPase regulatory subunit 8

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 8 / type: protein_or_peptide / ID: 32 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 39.667871 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MFIKGRAPRA PPRERRRATR GGLRQVVAPP RALGSTSRPH FRRASVCRRR CRKSGGLLAA SRKMAAAAVN GAAGFSSSGP AATSGAVLQ AATGMYEQLK GEWNRKSPNL SKCGEELGRL KLVLLELNFL PTTGTKLTKQ QLILARDILE IGAQWSILRK D IPSFERYM AQLKCYYFDY KEQLPESAYM HQLLGLNLLF LLSQNRVAEF HTELERLPAK DIQTNVYIKH PVSLEQYLME GS YNKVFLA KGNIPAESYT FFIDILLDTI RDEIAGCIEK AYEKILFTEA TRILFFNTPK KMTDYAKKRG WVLGPNNYYS FAS QQQKPE DTTIPSTELA KQVIEYARQL EMIV

UniProtKB: 26S proteasome non-ATPase regulatory subunit 8

Macromolecule #33: 26S proteasome non-ATPase regulatory subunit 2

• Macromolecule: Name: 26S proteasome non-ATPase regulatory subunit 2 / type: protein_or_peptide / ID: 33 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 100.313625 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MEEGGRDKAP VQPQQSPAAA PGGTDEKPSG KERRDAGDKD KEQELSEEDK QLQDELEMLV ERLGEKDTSL YRPALEELRR QIRSSTTSM TSVPKPLKFL RPHYGKLKEI YENMAPGENK RFAADIISVL AMTMSGEREC LKYRLVGSQE ELASWGHEYV R HLAGEVAK EWQELDDAEK VQREPLLTLV KEIVPYNMAH NAEHEACDLL MEIEQVDMLE KDIDENAYAK VCLYLTSCVN YV PEPENSA LLRCALGVFR KFSRFPEALR LALMLNDMEL VEDIFTSCKD VVVQKQMAFM LGRHGVFLEL SEDVEEYEDL TEI MSNVQL NSNFLALARE LDIMEPKVPD DIYKTHLENN RFGGSGSQVD SARMNLASSF VNGFVNAAFG QDKLLTDDGN KWLY KNKDH GMLSAAASLG MILLWDVDGG LTQIDKYLYS SEDYIKSGAL LACGIVNSGV RNECDPALAL LSDYVLHNSN TMRLG SIFG LGLAYAGSNR EDVLTLLLPV MGDSKSSMEV AGVTALACGM IAVGSCNGDV TSTILQTIME KSETELKDTY ARWLPL GLG LNHLGKGEAI EAILAALEVV SEPFRSFANT LVDVCAYAGS GNVLKVQQLL HICSEHFDSK EKEEDKDKKE KKDKDKK EA PADMGAHQGV AVLGIALIAM GEEIGAEMAL RTFGHLLRYG EPTLRRAVPL ALALISVSNP RLNILDTLSK FSHDADPE V SYNSIFAMGM VGSGTNNARL AAMLRQLAQY HAKDPNNLFM VRLAQGLTHL GKGTLTLCPY HSDRQLMSQV AVAGLLTVL VSFLDVRNII LGKSHYVLYG LVAAMQPRML VTFDEELRPL PVSVRVGQAV DVVGQAGKPK TITGFQTHTT PVLLAHGERA ELATEEFLP VTPILEGFVI LRKNPNYDL

UniProtKB: 26S proteasome non-ATPase regulatory subunit 2

Macromolecule #34: 26S proteasome complex subunit DSS1

• Macromolecule: Name: 26S proteasome complex subunit DSS1 / type: protein_or_peptide / ID: 34 / Number of copies: 1 / Enantiomer: LEVO
• Source (natural): Organism: Homo sapiens (human)
• Molecular weight: Theoretical: 8.284611 KDa
• Recombinant expression: Organism: Homo sapiens (human)

Sequence

String:

MSEKKQPVDL GLLEEDDEFE EFPAEDWAGL DEDEDAHVWE DNWDDDNVED DFSNQLRAEL EKHGYKMETS

UniProtKB: 26S proteasome complex subunit SEM1

Macromolecule #35: ADENOSINE-5'-TRIPHOSPHATE

• Macromolecule: Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 35 / Number of copies: 4 / Formula: ATP
• Molecular weight: Theoretical: 507.181 Da

Chemical component information

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

Macromolecule #36: ADENOSINE-5'-DIPHOSPHATE

• Macromolecule: Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 36 / Number of copies: 2 / Formula: ADP
• Molecular weight: Theoretical: 427.201 Da

Chemical component information

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Macromolecule #37: ZINC ION

• Macromolecule: Name: ZINC ION / type: ligand / ID: 37 / Number of copies: 1 / Formula: ZN
• Molecular weight: Theoretical: 65.409 Da

Experimental details

Structure determination

• Method: cryo EM
• Processing: single particle reconstruction
• Aggregation state: particle

Sample preparation

• Buffer: pH: 7
• Vitrification: Cryogen name: ETHANE

Electron microscopy

• Microscope: FEI TITAN KRIOS
• Image recording: Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Ų
• Electron beam: Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
• Electron optics: Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 0.4 µm
• Experimental equipment: Model: Titan Krios / Image courtesy: FEI Company

Image processing

Startup model

Type of model: EMDB MAP
EMDB ID:

9216

• Final reconstruction: Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 53225
• Initial angle assignment: Type: MAXIMUM LIKELIHOOD
• Final angle assignment: Type: MAXIMUM LIKELIHOOD