U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 B (UBE4B) and similar proteins; UBE4B, also known as UFD2a, is a U-box-type ubiquitin-protein ligase that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor, which catalyzes formation of Lys27- and Lys33-linked polyubiquitin chains rather than the Lys48-linked chain. It is a mammalian homolog of yeast UFD2 ubiquitination factor and it participates in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. It is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. UBE4B has contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. It is essential for Hdm2 (also known as Mdm2)-mediated p53 degradation. It mediates p53 polyubiquitination and degradation, as well as inhibits p53-dependent transactivation and apoptosis, and thus plays an important role in regulating phosphorylated p53 following DNA damage. UBE4B is also associated with other pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration, both of which are critical in neurodegenerative diseases. Moreover, UBE4B acts as a regulator of epidermal growth factor receptor (EGFR) degradation. It is recruited to endosomes in response to EGFR activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0, and then regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. UBE4B contains a ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
3L1Z_B       23 YSDAPDEFRDPLMDTLMTDPVRLPSGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPVPELKEQIQAWMREKQ 96
Cdd:cd16658   1 LGDAPDEFLDPLMDTLMTDPVILPSGTIMDRSIILRHLLNSQTDPFNRQPLTEDMLEPVPELKERIQAWIREKQ 74

U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 B (UBE4B) and similar proteins; UBE4B, also known as UFD2a, is a U-box-type ubiquitin-protein ligase that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor, which catalyzes formation of Lys27- and Lys33-linked polyubiquitin chains rather than the Lys48-linked chain. It is a mammalian homolog of yeast UFD2 ubiquitination factor and it participates in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. It is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. UBE4B has contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. It is essential for Hdm2 (also known as Mdm2)-mediated p53 degradation. It mediates p53 polyubiquitination and degradation, as well as inhibits p53-dependent transactivation and apoptosis, and thus plays an important role in regulating phosphorylated p53 following DNA damage. UBE4B is also associated with other pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration, both of which are critical in neurodegenerative diseases. Moreover, UBE4B acts as a regulator of epidermal growth factor receptor (EGFR) degradation. It is recruited to endosomes in response to EGFR activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0, and then regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. UBE4B contains a ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.

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3L1Z_B       23 YSDAPDEFRDPLMDTLMTDPVRLPSGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPVPELKEQIQAWMREKQ 96
Cdd:cd16658   1 LGDAPDEFLDPLMDTLMTDPVILPSGTIMDRSIILRHLLNSQTDPFNRQPLTEDMLEPVPELKERIQAWIREKQ 74

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.

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3L1Z_B          29 EFRDPLMDTLMTDPVRLPSGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPVPELKEQIQAW 91
Cdd:smart00504   1 EFLCPISLEVMKDPVILPSGQTYERSAIEKWLLSHGTDPVTGQPLTHEDLIPNLALKSAIQEW 63

U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 B (UBE4B) and similar proteins; UBE4B, also known as UFD2a, is a U-box-type ubiquitin-protein ligase that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor, which catalyzes formation of Lys27- and Lys33-linked polyubiquitin chains rather than the Lys48-linked chain. It is a mammalian homolog of yeast UFD2 ubiquitination factor and it participates in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. It is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. UBE4B has contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. It is essential for Hdm2 (also known as Mdm2)-mediated p53 degradation. It mediates p53 polyubiquitination and degradation, as well as inhibits p53-dependent transactivation and apoptosis, and thus plays an important role in regulating phosphorylated p53 following DNA damage. UBE4B is also associated with other pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration, both of which are critical in neurodegenerative diseases. Moreover, UBE4B acts as a regulator of epidermal growth factor receptor (EGFR) degradation. It is recruited to endosomes in response to EGFR activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0, and then regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. UBE4B contains a ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.

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3L1Z_B       23 YSDAPDEFRDPLMDTLMTDPVRLPSGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPVPELKEQIQAWMREKQ 96
Cdd:cd16658   1 LGDAPDEFLDPLMDTLMTDPVILPSGTIMDRSIILRHLLNSQTDPFNRQPLTEDMLEPVPELKERIQAWIREKQ 74

U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 A (UBE4A) and similar proteins; This subfamily includes yeast ubiquitin fusion degradation protein 2 (UFD2p) and its mammalian homolog, UBE4A. Yeast UFD2p, also known as ubiquitin conjugation factor E4 or UB fusion protein 2, is a polyubiquitin chain conjugation factor (E4) in the ubiquitin fusion degradation (UFD) pathway which catalyzes elongation of the ubiquitin chain through Lys48 linkage. It binds to substrates conjugated with one to three ubiquitin molecules and catalyzes the addition of further ubiquitin moieties in the presence of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3), yielding multiubiquitylated substrates that are targets for the 26S proteasome. UFD2p is implicated in cell survival under stress conditions and is essential for homoeostasis of unsaturated fatty acids. It interacts with UBL-UBA proteins Rad23 and Dsk2, which are involved in the endoplasmic reticulum-associated degradation, ubiquitin fusion degradation, and OLE-1 gene induction pathways. UBE4A is a U-box-type ubiquitin-protein ligase that is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. It may have a specific role in different biochemical processes other than ubiquitination, including growth or differentiation. Members of this family contain an N-terminal ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.

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3L1Z_B       28 DEFRDPLMDTLMTDPVRLP-SGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPVPELKEQIQAWMREKQ 96
Cdd:cd16657   1 DEFLDPIMYTLMKDPVILPsSKVTVDRSTIKRHLLSDQTDPFNRSPLTLDMVIPNEELKQKIEEFLAEKK 70

Ubiquitin fusion degradation protein 2 [Posttranslational modification, protein turnover, chaperones];

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3L1Z_B        5 FAEKVEEIVAKNARAEIDYSDAPDEFRDPLMDTLMTDPVRLP-SGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPVPE 83
Cdd:COG5113 830 FINRLEKVRVIEAVEEEDMGDVPDEFLDPLMFTIMKDPVKLPtSRITIDRSTIKAHLLSDGTDPFNRMPLTLDDVTPNAE 909

                        90
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3L1Z_B       84 LKEQIQAWMREKQN 97
Cdd:COG5113 910 LREKINRFYKCKGQ 923

U-box domain, a modified RING finger, found in carboxyl terminus of HSP70-interacting protein (CHIP) and similar proteins; CHIP, also known as STIP1 homology and U box-containing protein 1 (STUB1), CLL-associated antigen KW-8, or Antigen NY-CO-7, is a multifunctional protein that functions both as a co-chaperone and an E3 ubiquitin-protein ligase. It couples protein folding and proteasome mediated degradation by interacting with heat shock proteins (e.g. HSC70) and ubiquitinating their misfolded client proteins, thereby targeting them for proteasomal degradation. It is also important for cellular differentiation and survival (or apoptosis), as well as susceptibility to stress. It targets a wide range of proteins, such as expanded ataxin-1, ataxin-3, huntingtin, and androgen receptor, which play roles in glucocorticoid response, tau degradation, and both p53 and cAMP signaling. CHIP contains an N-terminal tetratricopeptide repeat (TPR) domain responsible for protein-protein interaction, a highly charged middle coiled-coil (CC), and a C-terminal RING-like U-box domain acting as an ubiquitin ligase.

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3L1Z_B       26 APDEFRDPLMDTLMTDPVRLPSGTIMDRSIILRHLL-NSPTDPFNRQTLTESMLEPVPELKEQIQAWMRE 94
Cdd:cd16654   1 VPDYLCCKISFELMRDPVITPSGITYERKDIEEHLQrVGHFDPITREPLTQDQLIPNLALKEAIEAFLEE 70

first U-box domain, a modified RING finger, found in Legionella pneumophila U-box protein LubX and similar proteins; LubX, also called RING-type E3 ubiquitin transferase LubX, is part of the large arsenal of effectors in Legionella pneumophila that are translocated into the host cytosol during infection. LubX acts as an E3 ubiquitin-protein ligase (EC 2.3.2.27) that interferes with the host's ubiquitination pathway. LubX contains two RING-like U-box domains. U-box 1 is critical to the ubiquitin ligase activity, and U-box 2 mediates interaction with host target. This model corresponds to the first one.

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3L1Z_B       33 PLMDTLMTDPVRLPSGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPVPEL 84
Cdd:cd23149   4 PITSGFMEDPVITPSGFSYERSAIERWLETKPEDPQTREPLTAKDLQPNREL 55

U-box domain, a modified RING finger, found in WD repeat, SAM and U-box domain-containing protein 1 (WDSUB1) and similar proteins; WDSUB1 is an uncharacterized protein containing seven WD40 repeats and a SAM domain in addition to the U-box. Its biological role remains unclear. This subfamily also includes many uncharacterized kinase domain-containing U-box (AtPUB) proteins and several MIF4G motif-containing AtPUB proteins from Arabidopsis.

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3L1Z_B       27 PDEFRDPLMDTLMTDPVRLPSGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEP 80
Cdd:cd16655   1 PDEFLCPITQELMRDPVVAADGHTYERSAIEEWLETHNTSPMTRLPLSSTDLVP 54

U-box domain, a modified RING finger, found in pre-mRNA-processing factor 19 (Prp19) and similar proteins; Prp19, also known as nuclear matrix protein 200 (NMP200), senescence evasion factor (SNEV), or DNA repair protein Pso4 (psoralen-sensitive mutant 4), is a ubiquitously expressed multifunctional E3 ubiquitin ligase with pleiotropic activities in DNA damage signaling, repair, and replicative senescence. It functions as a critical component of DNA repair and DNA damage checkpoint complexes. It senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, and regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex. Prp19 contains an N-terminal E3 ubiquitin ligase U-box domain with E2 recruitment function that facilitates dimerization and is essential for its auto-ubiquitination activity in vitro or when overexpressed, a coiled-coil Prp19 homology region that mediates its tetramerization and interaction with CDC5L and SPF27, and a C-terminal seven-bladed WD40 beta-propeller type of leucine-rich architectural repeats that form an asymmetrical barrel-shaped structure important for substrate recognition and recruitment.

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3L1Z_B       47 SGTIMDRSIILRHLLNSPTDPFNRQTLTESMLEPV 81
Cdd:cd16656  19 SGHVFEKRLIEKYIAENGTDPVTGEPLTEEDLIEI 53