sujigwak/NVAR huggingface dataset:
UniProt ID: Q9UNE0
Variant: R -> Q at position 420-420
Variant annotation: in ECTD10A and ECTD10B; abolishes NF-kappa-B activation and reduces JNK activation; dbSNP:rs121908453
Protein function: Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase-independent cell death.
Reference sequence:
MAHVGDCTQTPWLPVLVVSLMCSARAEYSNCGENEYYNQTTGLCQECPPCGPGEEPYLSCGYGTKDEDYGCVPCPAEKFSKGGYQICRRHKDCEGFFRATVLTPGDMENDAECGPCLPGYYMLENRPRNIYGMVCYSCLLAPPNTKECVGATSGASANFPGTSGSSTLSPFQHAHKELSGQGHLATALIIAMSTIFIMAIAIVLIIMFYILKTKPSAPACCTSHPGKSVEAQVSKDEEKKEAPDNVVMFSEKDEFEKLTATPAKPTKSENDASSENEQLLSRSVDSDEEPAPDKQGSPELCLLSLVHLAREKSATSNKSAGIQSRRKKILDVYANVCGVVEGLSPTELPFDCLEKTSRMLSSTYNSEKAVVKTWRHLAESFGLKRDEIGGMTDGMQLFDRISTAGYSIPELLTKLVQIERLDAVESLCADILEWAGVVPPASQPHAAS
UniProt ID: Q9UNE0
Variant: W -> C at position 434-434
Variant annotation: in ECTD10B; dbSNP:rs528478080
Protein function: Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase-independent cell death.
Reference sequence:
MAHVGDCTQTPWLPVLVVSLMCSARAEYSNCGENEYYNQTTGLCQECPPCGPGEEPYLSCGYGTKDEDYGCVPCPAEKFSKGGYQICRRHKDCEGFFRATVLTPGDMENDAECGPCLPGYYMLENRPRNIYGMVCYSCLLAPPNTKECVGATSGASANFPGTSGSSTLSPFQHAHKELSGQGHLATALIIAMSTIFIMAIAIVLIIMFYILKTKPSAPACCTSHPGKSVEAQVSKDEEKKEAPDNVVMFSEKDEFEKLTATPAKPTKSENDASSENEQLLSRSVDSDEEPAPDKQGSPELCLLSLVHLAREKSATSNKSAGIQSRRKKILDVYANVCGVVEGLSPTELPFDCLEKTSRMLSSTYNSEKAVVKTWRHLAESFGLKRDEIGGMTDGMQLFDRISTAGYSIPELLTKLVQIERLDAVESLCADILEWAGVVPPASQPHAAS
UniProt ID: Q9UNE0
Variant: W -> R at position 434-434
Variant annotation: in ECTD10B; dbSNP:rs773885029
Protein function: Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase-independent cell death.
Reference sequence:
MAHVGDCTQTPWLPVLVVSLMCSARAEYSNCGENEYYNQTTGLCQECPPCGPGEEPYLSCGYGTKDEDYGCVPCPAEKFSKGGYQICRRHKDCEGFFRATVLTPGDMENDAECGPCLPGYYMLENRPRNIYGMVCYSCLLAPPNTKECVGATSGASANFPGTSGSSTLSPFQHAHKELSGQGHLATALIIAMSTIFIMAIAIVLIIMFYILKTKPSAPACCTSHPGKSVEAQVSKDEEKKEAPDNVVMFSEKDEFEKLTATPAKPTKSENDASSENEQLLSRSVDSDEEPAPDKQGSPELCLLSLVHLAREKSATSNKSAGIQSRRKKILDVYANVCGVVEGLSPTELPFDCLEKTSRMLSSTYNSEKAVVKTWRHLAESFGLKRDEIGGMTDGMQLFDRISTAGYSIPELLTKLVQIERLDAVESLCADILEWAGVVPPASQPHAAS
UniProt ID: Q9UNE7
Variant: E -> K at position 28-28
Variant annotation: in SCAR16; reduces protein level; does not reduce ubiquitin ligase activity and autoubiquitination
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: P -> S at position 57-57
Variant annotation: found in a patient with progressive myoclonus epilepsy; uncertain significance
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: N -> S at position 65-65
Variant annotation: in SCAR16; reduces protein level; reduces ubiquitin ligase activity; does not change autoubiquitination; dbSNP:rs690016544
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: A -> D at position 79-79
Variant annotation: in SCAR16; dbSNP:rs587777347
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: A -> T at position 79-79
Variant annotation: in SCAR16; dbSNP:rs587777346
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: L -> V at position 123-123
Variant annotation: in SCAR16; dbSNP:rs587777344
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: N -> I at position 130-130
Variant annotation: in SCAR16; dbSNP:rs587777341
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: K -> Q at position 145-145
Variant annotation: in SCAR16; dbSNP:rs146251364
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY
UniProt ID: Q9UNE7
Variant: W -> C at position 147-147
Variant annotation: in SCAR16; dbSNP:rs587777342
Protein function: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation . Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension . Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 . Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 . Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation . Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome . Mediates polyubiquitination of CYP3A4 . Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation . Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation . Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner . Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome . Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity . Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation . May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation . Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation .
Reference sequence:
MKGKEEKEGGARLGAGGGSPEKSPSAQELKEQGNRLFVGRKYPEAAACYGRAITRNPLVAVYYTNRALCYLKMQQHEQALADCRRALELDGQSVKAHFFLGQCQLEMESYDEAIANLQRAYSLAKEQRLNFGDDIPSALRIAKKKRWNSIEERRIHQESELHSYLSRLIAAERERELEECQRNHEGDEDDSHVRAQQACIEAKHDKYMADMDELFSQVDEKRKKRDIPDYLCGKISFELMREPCITPSGITYDRKDIEEHLQRVGHFDPVTRSPLTQEQLIPNLAMKEVIDAFISENGWVEDY