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 40806196 260 PEEFLDPITLEIMPCPMLLPSGKVIDQSTLEKCNRSEATWGRVPSDPFTGVAF 312
Cdd:cd16660   1 PEEFLDPITCELMTLPVLLPSGKVVDQSTLEKYIKEEATWGRLPSDPFTGVPF 53

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 40806196 260 PEEFLDPITLEIMPCPMLLPSGKVIDQSTLEKCNRSEATWGRVPSDPFTGVAF 312
Cdd:cd16660   1 PEEFLDPITCELMTLPVLLPSGKVVDQSTLEKYIKEEATWGRLPSDPFTGVPF 53

RING finger, HC subclass, 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, and 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 RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 40806196 427 PECASCKRVFSPYFKKEPVYQLPCGHLLCRPCLGEKQRSLPMTCTACQRPVA 478
Cdd:cd16537   1 QGCASCSRAFSPYFKTEPVYRLPCGHLLCRPCLAEKQKSLAILCPTCNRPVA 52

zinc-RING finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 40806196   432 CKRVFSPYFKKEPVYQLPCGHLLCRPCLGEKQRslPMTCTACQR 475
Cdd:pfam14634   2 CNKCFKELSKTRPFYLTSCGHIFCEECLTRLLQ--ERQCPICKK 43

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 40806196 260 PEEFLDPITLEIMPCPMLLPSGKVIDQSTLEKCNRSEATWGRVPSDPFTGVAF 312
Cdd:cd16660   1 PEEFLDPITCELMTLPVLLPSGKVVDQSTLEKYIKEEATWGRLPSDPFTGVPF 53

RING finger, HC subclass, 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, and 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 RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 40806196 427 PECASCKRVFSPYFKKEPVYQLPCGHLLCRPCLGEKQRSLPMTCTACQRPVA 478
Cdd:cd16537   1 QGCASCSRAFSPYFKTEPVYRLPCGHLLCRPCLAEKQKSLAILCPTCNRPVA 52

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40806196 258 DVPEEFLDPITLEIMPCPMLLPSGKVIDQSTLEKCNRSEatwgrvPSDPFTgvaftphSQPL------PHPSLKARIDHF 331
Cdd:cd16658   3 DAPDEFLDPLMDTLMTDPVILPSGTIMDRSIILRHLLNS------QTDPFN-------RQPLtedmlePVPELKERIQAW 69

                .
gi 40806196 332 L 332
Cdd:cd16658  70 I 70

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 40806196 261 EEFLDPITLEIMPCPMLLPSGKV-IDQSTLEKCNRSEATwgrvpsDPFTGVAFTPhSQPLPHPSLKARIDHFLLQH 335
Cdd:cd16657   1 DEFLDPIMYTLMKDPVILPSSKVtVDRSTIKRHLLSDQT------DPFNRSPLTL-DMVIPNEELKQKIEEFLAEK 69

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 40806196 259 VPEEFLDPITLEIMPCPMLLPSGKVIDQSTLEKCNRSEATWgrvpsDPFTGVAFTPhSQPLPHPSLKARIDHFLLQH 335
Cdd:cd16654   1 VPDYLCCKISFELMRDPVITPSGITYERKDIEEHLQRVGHF-----DPITREPLTQ-DQLIPNLALKEAIEAFLEEN 71

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
                ....*....|....*....|....*....|..
gi 40806196 260 PEEFLDPITLEIMPCPMLLPSGKVIDQSTLEK 291
Cdd:cd16664   1 PEEFICPISLELMKDPVILATGQTYERAAIEK 32

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 40806196 428 ECASCKRVFspyfkKEPVYQLPCGHLLCRPCLGEKQRSLPMTCTACQRPVAS 479
Cdd:cd16544   4 TCPVCQEVL-----KDPVELPPCRHIFCKACILLALRSSGARCPLCRGPVGK 50

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 40806196 428 ECASCKRVFspyfkKEPVyQLPCGHLLCRPCLGEKQRSLPMTCTAC 473
Cdd:cd16449   2 ECPICLERL-----KDPV-LLPCGHVFCRECIRRLLESGSIKCPIC 41