E3 ubiquitin-protein ligase CHIP; antigen NY-CO-7; CLL-associated antigen KW-8; carboxy terminus of Hsp70-interacting protein; STIP1 homology & U box-containing protein 1 (STUB1 CHIP PP1131)

Function: 1) E3 ubiquitin protein ligase activity a) targets misfolded chaperone substrates towards proteasomal degradation b) mediates transfer of non-canonical short ubiquitin chains to HSPA8 without effect on HSPA8 degradation c) ubiquitinates NOS1 in concert with Hsp70 & Hsp40 d) mediates polyubiquitination of DNA polymerase beta (POLB) at Lys-41, Lys-61 & Lys-81, thus playing a role in base-excision repair - catalyzes polyubiquitination by amplifying HUWE1/ARF-BP1- dependent monoubiquitination, leading to POLB-degradation by the proteasome e) mediates polyubiquitination of CYP3A4 f) ubiquitinates EPHA2 & may regulate the receptor stability & activity through proteasomal degradation 2) modulates activity of several chaperone complexes, - Hsp70, Hsc70, Hsp90 - collaborates with ATXN3 in the degradation of misfolded chaperone substrates - ATXN3 restricts the length of ubiquitin chain attached to STUB1/CHIP substrates & preventing further chain extension 3) occurs in a ternary complex containing STUB1, HSPA1A, HSPBP1 4) auto-ubiquitinated (in vitro) - monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3 (putative) - auto-ubiquitination mediated by UBE2D1 & UBE2D2 5) phosphorylated upon DNA damage, probably by ATM or ATR 6) interacts with BAG2, UBE2D1, UBE2D2, UBE2D3, HSPA8, HSPA1A 7) interacts (via TPR repeats) with HSP90AA1 8) interacts (when monoubiquitinated) with ATXN3 9) interacts with UBE2W 10) interacts (via the U-box domain) with the UBE2V2-UBE2N heterodimer - the complex has a specific Lys-63-linked polyubiquitination activity 11) interacts with DNAJB6 Structure: - the TPR domain is essential for ubiquitination mediated by UBE2D1 - contains 3 TPR repeats - contains 1 U-box domain Compartment: cytoplasm Alternative splicing: named isoforms=2 Expression: - expressed in skeletal muscle, heart,pancreas, brain, placenta > kidney, liver, lung Pathology: - antibodies against STUB1 are found in patients with chronic lymphocytic leukemia (CLL) & in colorectal cancer

General

nuclear protein phosphoprotein zinc finger protein

Properties

SIZE: entity length = 303 aa MW = 35 kD COMPARTMENT: cytoplasm MOTIF: Ser phosphorylation site {S19} Ser phosphorylation site {S23} Ser phosphorylation site {S25} tetratricopeptide repeat {26-59} tetratricopeptide repeat {60-93} tetratricopeptide repeat {95-127} U-box {226-300} MOTIF: Ser phosphorylation site {S273} Thr phosphorylation site {T276}

Database Correlations

OMIM 607207 UniProt Q9UNE7 PFAM correlations Entrez Gene 10273 Kegg hsa:10273

References

UniProt :accession Q9UNE7