U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1731008268  14 PSYFLCPISLQLMRDPVTISTGITYDRSSIEKWLFSFNKTvCPITKQPLSSD 65
Cdd:cd16664     1 PEEFICPISLELMKDPVILATGQTYERAAIEKWLDSGNNT-CPITGQPLTHT 51

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1731008268  14 PSYFLCPISLQLMRDPVTISTGITYDRSSIEKWLFSFNKTvCPITKQPLSSD 65
Cdd:cd16664     1 PEEFICPISLELMKDPVILATGQTYERAAIEKWLDSGNNT-CPITGQPLTHT 51

U-box domain; The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the beta-beta-alpha-beta-alpha- fold typical of U-box and RING domains. The central alpha helix is flanked by two prominent surface-exposed loop regions. This domain is one class of E3 ligases, involved in the ubiquitination process. This domain is related to the Ring finger pfam00097 but lacks the zinc binding residues.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1731008268  13 VPSYFLCPISLQLMRDPVTISTGITYDRSSIEKWLFSFNKTvCPITKQPLssDPDLLTPNHTLRRLIQSW 82
Cdd:pfam04564   1 IPDEFLDPITFELMTDPVILPSGITYDRSTIERHLLSVDPT-DPFTREPL--THDQLIPNLELKAKIDAW 67

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1731008268  14 PSYFLCPISLQLMRDPVTISTGITYDRSSIEKWLFSFNKTvCPITKQPLSSD 65
Cdd:cd16664     1 PEEFICPISLELMKDPVILATGQTYERAAIEKWLDSGNNT-CPITGQPLTHT 51

U-box domain; The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the beta-beta-alpha-beta-alpha- fold typical of U-box and RING domains. The central alpha helix is flanked by two prominent surface-exposed loop regions. This domain is one class of E3 ligases, involved in the ubiquitination process. This domain is related to the Ring finger pfam00097 but lacks the zinc binding residues.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1731008268  13 VPSYFLCPISLQLMRDPVTISTGITYDRSSIEKWLFSFNKTvCPITKQPLssDPDLLTPNHTLRRLIQSW 82
Cdd:pfam04564   1 IPDEFLDPITFELMTDPVILPSGITYDRSTIERHLLSVDPT-DPFTREPL--THDQLIPNLELKAKIDAW 67

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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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1731008268  13 VPSYFLCPISLQLMRDPVTISTGITYDRSSIEKWLFSfNKTVCPITKQPLSsdPDLLTPNHTLRRLIQSWCTLN 86
Cdd:cd16654     1 VPDYLCCKISFELMRDPVITPSGITYERKDIEEHLQR-VGHFDPITREPLT--QDQLIPNLALKEAIEAFLEEN 71

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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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1731008268  17 FLCPISLQLMRDPVTISTGITYDRSSIEKWLfsFNKTVCPITKQPLSSDPdlLTPNHTL 75
Cdd:cd23149     1 FTCPITSGFMEDPVITPSGFSYERSAIERWL--ETKPEDPQTREPLTAKD--LQPNREL 55

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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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1731008268  12 EVPSYFLCPISLQLMRDPVTISTGITYDRSSIEKWLFSFNKTvcPITKQPLSSdpDLLTPNHTLRRLIQSW 82
Cdd:cd16658     3 DAPDEFLDPLMDTLMTDPVILPSGTIMDRSIILRHLLNSQTD--PFNRQPLTE--DMLEPVPELKERIQAW 69

SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress. Moreover, NSE2 together with its partner proteins SMC6 and SMC5 form a tight subcomplex of the structural maintenance of chromosomes SMC5-6 complex, which includes another two subcomplexes, NSE1-NSE3-NSE4 and NSE5-NSE6. SMC6 and NSE3 are sumoylated in an NSE2-dependent manner, but SMC5 and NSE1 are not. NSE2-dependent E3 SUMO ligase activity is required for efficient DNA repair, but not for SMC5-6 complex stability. NSE2 contains a RING variant known as a Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)-like RING (SPL-RING) finger that is likely shared by the SP-RING type SUMO E3 ligases, such as PIAS family proteins. The SPL-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It harbors only one Zn binding site and is required for the sumoylating activity.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1731008268  17 FLCPISLQLMRDPVTIST-GITYDRSSIEKWLFSFNKTV-CPIT--KQPLS-SDpdlLTPNHTLRRLIQ 80
Cdd:cd16651     1 LKCPITQQLMVDPVRNKKcGHTYEKAAILQYLQSRKKKAkCPVAgcRNTVSkSD---LVPDPELKRRIE 66

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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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1731008268  17 FLCPISLQLMRDPVtIS--TGITYDRSSIEKWLFSFNKtvCPITKQPLSSDpDLL 69
Cdd:cd16656     1 MVCAISGEVPEEPV-VSpkSGHVFEKRLIEKYIAENGT--DPVTGEPLTEE-DLI 51

Zinc-finger of the MIZ type in Nse subunit; Nse1 and Nse2 are novel non-SMC subunits of the fission yeast Smc5-6 DNA repair complex. This family is the zinc-finger domain similar to the MIZ type of zinc-finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1731008268  19 CPISLQLMRDPVTiST--GITYDRSSIEKWLFSFNKTVCPI 57
Cdd:pfam11789  14 CPLTLQPFVEPVT-SKkcNHVFEKDAILEMLKRNPTVKCPV 53

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1731008268  14 PSYFLCPISLQLMRDPVTIS-TGITYDRSSIEKWLFSfNKTVCPITKQPLSSDPDL 68
Cdd:cd16620     1 PDELKCPICKDLMKDAVLTPcCGNSFCDECIRTALLE-EDFTCPTCKEPDVSPDAL 55

U-box domain 1, a modified RING finger, found in nitric oxide synthase-interacting protein (NOSIP) and similar proteins; NOSIP, also known as endothelial NO synthase (eNOS)-interacting protein, p33RUL, is an E3 ubiquitin-protein ligase implicated in the control of airway and vascular diameter, mucosal secretion, NO synthesis in ciliated epithelium, and, therefore, of mucociliary and bronchial function. The loss of NOSIP may cause holoprosencephaly and facial anomalies, including cleft lip/palate, cyclopia, and facial midline clefting. NOSIP interacts with neuronal nitric oxide synthase (nNOS) and eNOS by inhibiting the nitric oxide (NO) production. It acts as a novel type of modulator that promotes translocation of eNOS from the plasma membrane to intracellular sites, thereby uncoupling eNOS from plasma membrane caveolae and inhibiting NO synthesis. NOSIP also interacts with protein phosphatase PP2A and mediates the monoubiquitination of the PP2A catalytic subunit. Thus, it is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans. Moreover, NOSIP associates with the erythropoietin (Epo) receptor (EpoR), mediates ubiquitination of EpoR, and plays an essential role in erythropoietin-induced proliferation. NOSIP contains an atypical N-terminal RING-like U-box domain that is split into two parts by an interjacent stretch of 104 amino acid residues, as well as a C-terminal RING-like U-box domain. This model corresponds to the first U-box domain.

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                  ....*....|....*....|....*....|....*....|....
gi 1731008268  19 CPISLQLMRDPVTISTGITYDRSSIEKWLFSfNKTVCPITKQPL 62
Cdd:cd16661     4 CCLTLQPCRDPVVTPDGYLYDKEAILEYILH-QKKECPMSGKPL 46

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1731008268  19 CPISLQLMRDPVTISTGITYDRSSIEKWLFSFNKTVCPITKQPLSSDP 66
Cdd:cd16568     7 CIICHEYLYEPMVTTCGHTYCYTCLNTWFKSNRSLSCPDCRTKITTQP 54