SASDCL6: Lys63-linked dimer ubiquitin (Polyubiquitin-C, ubiquitin)

Basic information

Entry

Database: SASBDB / ID: SASDCL6

Sample

Lys63-linked dimer ubiquitin

• Polyubiquitin-C (protein), ubiquitin, Homo sapiens

Function / homology

Function:

Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / IRAK2 mediated activation of TAK1 complex / Prevention of phagosomal-lysosomal fusion / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / Negative regulation of FLT3 / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Constitutive Signaling by NOTCH1 HD Domain Mutants / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Regulation of FZD by ubiquitination / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / p75NTR recruits signalling complexes / InlA-mediated entry of Listeria monocytogenes into host cells / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / NF-kB is activated and signals survival / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Regulation of pyruvate metabolism / Pexophagy / Regulation of innate immune responses to cytosolic DNA / NRIF signals cell death from the nucleus / Downregulation of ERBB2:ERBB3 signaling / Regulation of PTEN localization / VLDLR internalisation and degradation / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / TICAM1, RIP1-mediated IKK complex recruitment / Regulation of BACH1 activity / Translesion synthesis by POLK / InlB-mediated entry of Listeria monocytogenes into host cell / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Downregulation of TGF-beta receptor signaling / Translesion synthesis by POLI / Josephin domain DUBs / IKK complex recruitment mediated by RIP1 / Gap-filling DNA repair synthesis and ligation in GG-NER / PINK1-PRKN Mediated Mitophagy / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / Regulation of activated PAK-2p34 by proteasome mediated degradation / TNFR1-induced NF-kappa-B signaling pathway / TCF dependent signaling in response to WNT / Regulation of NF-kappa B signaling / activated TAK1 mediates p38 MAPK activation / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / Regulation of signaling by CBL / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Ubiquitin-dependent degradation of Cyclin D / NOTCH3 Activation and Transmission of Signal to the Nucleus / Negative regulators of DDX58/IFIH1 signaling / Fanconi Anemia Pathway / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / AUF1 (hnRNP D0) binds and destabilizes mRNA / Negative regulation of FGFR3 signaling / Peroxisomal protein import / TNFR2 non-canonical NF-kB pathway / Deactivation of the beta-catenin transactivating complex / Stabilization of p53 / Assembly of the pre-replicative complex / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / Vpu mediated degradation of CD4 / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Negative regulation of FGFR1 signaling / Termination of translesion DNA synthesis / EGFR downregulation / Regulation of TNFR1 signaling / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of DVL / Degradation of AXIN / Assembly Of The HIV Virion / Degradation of CRY and PER proteins / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / G2/M Checkpoints / Spry regulation of FGF signaling / Iron uptake and transport / Late endosomal microautophagy / Degradation of GLI1 by the proteasome

Domain/homology:

: / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily

Component:

Polyubiquitin-C

• Biological species: Homo sapiens (human)
• Citation: Journal: Elife / Year: 2015; Title: Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition.; Authors: Zhu Liu / Zhou Gong / Wen-Xue Jiang / Ju Yang / Wen-Kai Zhu / Da-Chuan Guo / Wei-Ping Zhang / Mai-Li Liu / Chun Tang / ; Abstract: A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, polyubiquitins are found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2). Refining against inter-subunit paramagnetic NMR data, we show that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states. The quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways. When binding to a target protein, one of the preexisting quaternary states is selected and stabilized. A point mutation that shifts the equilibrium between the different states modulates the binding affinities towards K63-Ub2 ligands. This conformational selection mechanism at the quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition.

Contact author

• Zhu [e-mail] (Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences)

Models

Sample

• Sample: Name: Lys63-linked dimer ubiquitin / Specimen concentration: 5.1 mg/ml
• Buffer: Name: 100mM NaCl, 10mM sodium acetate / pH: 6

Entity #757

Name: ubiquitin / Type: protein / Description: Polyubiquitin-C / Formula weight: 8.565 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P0CG48
Sequence:

MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG

Experimental information

• Beam: Instrument name: Shanghai Synchrotron Radiation Facility (SSRF) BL19U2; City: Shanghai / 国: China / Type of source: X-ray synchrotron / Wavelength: 0.1033 Å / Dist. spec. to detc.: 2.126 mm
• Detector: Name: Pilatus 1M

Scan

Title: Lys63-linked dimer ubiquitin / Measurement date: Mar 24, 2016 / Storage temperature: 4 °C / Cell temperature: 25 °C / Exposure time: 1 sec. / Number of frames: 20 / Unit: 1/A /

	Min	Max
Q	0.0123	0.4699

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 410 /

	Min	Max
Q	0.0270648	0.228209
P(R) point	1	410
R	0	65

Result

Type of curve: single_conc /

	Experimental	Porod
MW	14 kDa	14 kDa
Volume	-	23.8 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	69	0.07	69.0664	0.01
Radius of gyration, Rg	2.115 nm	0.024	2.084 nm	0.01

	Min	Max
D	-	6.5
Guinier point	31	101