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 962248687 430 PEEFYCMInTGELMKDPVTTVTGQTYEREAIEEWFSRCKtagrpITDPATGVELKNTAL 488
Cdd:cd16664    1 PEEFICPI-SLELMKDPVILATGQTYERAAIEKWLDSGN-----NTCPITGQPLTHTDL 53

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 962248687   587 AFECPICGEIMEDPVMTPNGDSYERSEIVAWLEANPSDPKTRERTTVEDLVPNYHLKAVIENW 649
Cdd:smart00504   1 EFLCPISLEVMKDPVILPSGQTYERSAIEKWLLSHGTDPVTGQPLTHEDLIPNLALKSAIQEW 63

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 962248687   432 EFYCMInTGELMKDPVTTVTGQTYEREAIEEWFSrcktagRPITDPATGVELKNTALIPNRNLQDLIQEW 501
Cdd:smart00504   1 EFLCPI-SLEVMKDPVILPSGQTYERSAIEKWLL------SHGTDPVTGQPLTHEDLIPNLALKSAIQEW 63

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 962248687  430 PEEFYCMInTGELMKDPVTTVTGQTYEREAIEEWFSRCKTagrpiTDPATGVELKNTALIPNRNLQDLIQEWVIKH 505
Cdd:pfam04564   2 PDEFLDPI-TFELMTDPVILPSGITYDRSTIERHLLSVDP-----TDPFTREPLTHDQLIPNLELKAKIDAWLEEK 71

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 962248687   587 AFECPICGEIMEDPVMTPNGDSYERSEIVAWLEANPSDPKTRERTTVEDLVPNYHLKAVIENW 649
Cdd:smart00504   1 EFLCPISLEVMKDPVILPSGQTYERSAIEKWLLSHGTDPVTGQPLTHEDLIPNLALKSAIQEW 63

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 962248687 430 PEEFYCMInTGELMKDPVTTVTGQTYEREAIEEWFSRCKtagrpITDPATGVELKNTAL 488
Cdd:cd16664    1 PEEFICPI-SLELMKDPVILATGQTYERAAIEKWLDSGN-----NTCPITGQPLTHTDL 53

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 962248687 585 PLAFECPICGEIMEDPVMTPNGDSYERSEIVAWLEAN-PSDPKTRERTTVEDLVPNYHLKAVIENWQKAH 653
Cdd:cd16654    2 PDYLCCKISFELMRDPVITPSGITYERKDIEEHLQRVgHFDPITREPLTQDQLIPNLALKEAIEAFLEEN 71

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 962248687  585 PLAFECPICGEIMEDPVMTPNGDSYERSEIVAWL-EANPSDPKTRERTTVEDLVPNYHLKAVIENWQKAH 653
Cdd:pfam04564   2 PDEFLDPITFELMTDPVILPSGITYDRSTIERHLlSVDPTDPFTREPLTHDQLIPNLELKAKIDAWLEEK 71

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 962248687 429 PPEEFYCMInTGELMKDPVTTVTGQTYEREAIEEWFSRcktagRPITDPATGVELKNTALIPNRNLQDLIQEWVIKH 505
Cdd:cd16654    1 VPDYLCCKI-SFELMRDPVITPSGITYERKDIEEHLQR-----VGHFDPITREPLTQDQLIPNLALKEAIEAFLEEN 71

second 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 second one.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 962248687 585 PLAFECPICGEIMEDPVMTPNGDSYERSEIVAWLEANPSDPKTRERTTVEDLVPNYHLKAVIENW 649
Cdd:cd23150    1 PDIFLCPISKTLIKTPVITAQGKVYDQEALSNFLIATGNKDETGKKLSIDDVVVFDELYQQIKVY 65

U-box domain, a modified RING finger; The U-box protein family is a family of E3 enzymes that also includes the HECT family and the RING finger family. The E3 enzyme is ubiquitin-protein ligase that cooperates with a ubiquitin-activating enzyme (E1) and a ubiquitin-conjugating enzyme (E2), and plays a central role in determining the specificity of the ubiquitination system. It removes the ubiquitin molecule from the E2 enzyme and attaches it to the target substrate, forming a covalent bond between ubiquitin and the target. U-box proteins are characterized by the presence of a U-box domain of approximately 70 amino acids. The U-box is a modified form of the RING finger domain that lacks metal chelating cysteines and histidines. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 962248687 433 FYCMInTGELMKDPVTTVTGQTYEREAIEEWFSRCKtagrpiTDPATGVEL 483
Cdd:cd16453    1 FLCPI-SGELMKDPVITPSGITYDRSAIERWLLSDN------TDPFTREPL 44

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 962248687 583 ESPLAFECPICGEIMEDPVMTPNGDSYERSEIVAWLEANPSDPKTRERTTVEDLVPNYHLKAVIENWQK 651
Cdd:cd16658    3 DAPDEFLDPLMDTLMTDPVILPSGTIMDRSIILRHLLNSQTDPFNRQPLTEDMLEPVPELKERIQAWIR 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 962248687 433 FYCMInTGELMKDPVTTVTGQTYEREAIEEWFSrcktaGRPiTDPATGVELKNTALIPNRNL 494
Cdd:cd23149    1 FTCPI-TSGFMEDPVITPSGFSYERSAIERWLE-----TKP-EDPQTREPLTAKDLQPNREL 55

U-box domain, a modified RING finger, found in RING finger protein 37 (RNF37); RNF37, also known as KIAA0860, U-box domain-containing protein 5 (UBOX5), UbcM4-interacting protein 5 (UIP5), or ubiquitin-conjugating enzyme 7-interacting protein 5, is an E3 ubiquitin-protein ligase found exclusively in the nucleus as part of a nuclear dot-like structure. It interacts with the molecular chaperone VCP/p97 protein. RNF37 contains a U-box domain followed by a potential nuclear location signal (NLS), and a C-terminal C3HC4-type RING-HC finger. The U-box domain is a modified RING finger domain that lacks the hallmark metal-chelating cysteines and histidines of the latter, but is likely to adopt a RING finger-like conformation. The presence of the U-box, but not of the RING finger, is required for the E3 activity. The U-box domain can directly interact with several E2 enzymes, including UbcM2, UbcM3, UbcM4, UbcH5, and UbcH8, suggesting a similar function as the RING finger in the ubiquitination pathway. This model corresponds to the U-box domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 962248687 430 PEEFYCMInTGELMKDPVTTVTGQTYEREAIEEWFSRCKTAGRPITDPATGVEL 483
Cdd:cd16660    1 PEEFLDPI-TCELMTLPVLLPSGKVVDQSTLEKYIKEEATWGRLPSDPFTGVPF 53

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 962248687 590 CPICGEIMEDPVMTPN-GDSYERSEIVAWLEANPSD---PKT--RERTTVEDLVPNYHLKAVIEN 648
Cdd:cd16651    3 CPITQQLMVDPVRNKKcGHTYEKAAILQYLQSRKKKakcPVAgcRNTVSKSDLVPDPELKRRIER 67

U-box domain, a modified RING finger, found in erythroblast macrophage protein (Emp) and similar proteins; Emp, also known as cell proliferation-inducing gene 5 protein or macrophage erythroblast attacher (MAEA), is a key protein which functions in normal differentiation of erythroid cells and macrophages. It is a potential biomarker for hematopoietic evaluation of Hematopoietic stem cell transplantation (HSCT) patients. Emp was initially identified as a heparin-binding protein involved in the association of erythroblasts with macrophages. It promotes erythroid proliferation and maturation. It also plays an important role in erythroblastic island formation. Absence of Emp leads to failure of erythroblast nuclear extrusion. It is required in definitive erythropoiesis and plays a cell intrinsic role in the erythroid lineage. Emp contains a Lissencephaly type-1-like homology (LisH) motif, a C-terminal to LisH (CTLH) domain, and a RING-like U-box domain at the C-terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 962248687 590 CPICGEIMED---PVMTPNGDSYERSEIVAWLEANPS---DPKTRER 630
Cdd:cd16659    5 CRITGEVMNEhnpPLALPNGYVYSEKALEEMAEKNDGkvvCPRTGES 51

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 962248687 433 FYCMINTGELMKDPVTTVTGQTYEREAIEEWFSR----CKTAGRPI 474
Cdd:cd16661    1 FDCCCLTLQPCRDPVVTPDGYLYDKEAILEYILHqkkeCPMSGKPL 46

RING finger, HC subclass, found in constitutive photomorphogenesis protein 1 (COP1) and similar proteins; COP1, also known as RING finger and WD repeat domain protein 2 (RFWD2) or RING finger protein 200 (RNF200), is a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. It is localized predominantly in the nucleus, but may also be present in the cytosol. Mammalian COP1 functions as an E3 ubiquitin-protein ligase that interacts with Jun transcription factors and modulates their transcriptional activity. It also interacts with and negatively regulates the tumor-suppressor protein p53. Moreover, COP1 associates with COP9 signalosome subunit 6 (CSN6), and is involved in 14-3-3sigma ubiquitin-mediated degradation. The CSN6-COP1 link enhances ubiquitin-mediated degradation of p27(Kip1), a critical CDK inhibitor involved in cell cycle regulation, to promote cancer cell growth. Furthermore, COP1 functions as the negative regulator of ETV1 and influences prognosis in triple-negative breast cancer. COP1 contains an N-terminal extension, a C3HC4-type RING-HC finger, a coiled coil domain, and seven WD40 repeats. In human COP1, a classic leucine-rich NES, and a novel bipartite NLS is bridged by the RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 962248687 588 FECPICGEIMEDPVMTPNGDSYERSEIVAWLEANPSDPK 626
Cdd:cd16504    3 FLCPICFDIIKEAFVTKCGHSFCYKCIVKHLEQKNRCPK 41

U-box domain, a modified RING finger, found in RING finger protein 37 (RNF37); RNF37, also known as KIAA0860, U-box domain-containing protein 5 (UBOX5), UbcM4-interacting protein 5 (UIP5), or ubiquitin-conjugating enzyme 7-interacting protein 5, is an E3 ubiquitin-protein ligase found exclusively in the nucleus as part of a nuclear dot-like structure. It interacts with the molecular chaperone VCP/p97 protein. RNF37 contains a U-box domain followed by a potential nuclear location signal (NLS), and a C-terminal C3HC4-type RING-HC finger. The U-box domain is a modified RING finger domain that lacks the hallmark metal-chelating cysteines and histidines of the latter, but is likely to adopt a RING finger-like conformation. The presence of the U-box, but not of the RING finger, is required for the E3 activity. The U-box domain can directly interact with several E2 enzymes, including UbcM2, UbcM3, UbcM4, UbcH5, and UbcH8, suggesting a similar function as the RING finger in the ubiquitination pathway. This model corresponds to the U-box domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 962248687 591 PICGEIMEDPVMTPNGDSYERSEIVAWL--EAN----PSDPKT 627
Cdd:cd16660    7 PITCELMTLPVLLPSGKVVDQSTLEKYIkeEATwgrlPSDPFT 49