RING finger, H2 subclass, found in ubiquitin-protein ligase E3-alpha-2 (UBR2) and similar proteins; UBR2, also known as N-recognin-2 or E3alpha-II, is an E3 ubiquitin-protein ligase that plays an important role in maintaining genome integrity and in homologous recombination repair. It regulates the level of the transcription factor Rpn4 (also known as Son1 and Ufd5) through ubiquitylation. The ubiquitin-conjugating enzyme Rad6, another binding partner of URB2, and an additional factor Mub1, are required for the ubiquitin-dependent degradation of Rpn4. UBR2 associates with Mub1 to form a Mub1/Ubr2 complex that regulates the conserved Dsn1 kinetochore protein levels, which is a part of a quality control system that monitors kinetochore integrity, thus ensuring genomic stability. As the recognition component of a major cellular proteolytic system, UBR2 is associated with chromatin and controls chromatin dynamics and gene expression in both spermatocytes and somatic cells. UBR2 also mediates transcriptional silencing during spermatogenesis via histone ubiquitination. It functions as a scaffold E3 promoting HR6B/UbcH2-dependent ubiquitylation of H2A and H2B, but not H3 and H4. It also binds to Tex19.1, also known as Tex19, a germ cell-specific protein, and metabolically stabilizes it during spermatogenesis. Furthermore, UBR2 is involved in skeletal muscle (SKM) atrophy. Its expression can be modulated by the mouse ether-a-gogo-related gene 1a (MERG1a) potassium channel. In addition, UBR2 up-regulation in cachectic muscle is mediated by the p38beta-CCAAT/enhancer binding protein (C/EBP)-beta signaling pathway responsible for the bulk of tumor-induced muscle proteolysis. UBR2 contains an N-terminal ubiquitin-recognin (UBR) box involved in binding type-1 (basic) N-end rule substrate, an N-domain (also known as ClpS domain) required for type-2 (bulky hydrophobic) N-end rule substrate recognition, a C3H2C3-type RING-H2 finger, and a C-terminal UBR-specific autoinhibitory (UAIN) domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27597061 1107 TCILCQEEQEVKVESRAMVLAAFVQRSTVLSKNRSKFIQDPEKYDPLFMHPDLSCGTHTSSCGHIMHAHCWQRYFDSVQA 1186
Cdd:cd16686    1 TCILCQEEQEIKVDNKAMVLAAFVQRSTVMSKNRSRVIHDPEKYDPLFMHPDLSCGTHTGSCGHIMHAHCWQRYFDAVQA 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 27597061 1187 KEQRRQQRLRLHTSYDVENGEFLCPLCECLSNTVIP 1222
Cdd:cd16686   81 KEQRRQQRLRVHTSYDVENGEFLCPLCECLSNTVIP 116

ATP-dependent Clp protease adaptor protein ClpS; In the bacterial cytosol, ATP-dependent protein degradation is performed by several different chaperone-protease pairs, including ClpAP. ClpS directly influences the ClpAP machine by binding to the N-terminal domain of the chaperone ClpA. The degradation of ClpAP substrates, both SsrA-tagged proteins and ClpA itself, is specifically inhibited by ClpS. ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27597061    222 EKSDTYYCMLFNDEVHTYEQVIYTLQKAVNCTQKEAIGFATTVDRDGRRSVRYGDFQYCEQAKSVIVRNTSRQTKPLKV 300
Cdd:pfam02617    1 KEPPMYKVILLNDDYTTMEFVVEVLQRVFGKSEEEATEIMLQVHREGRAVVGVYTYDIAETKVAQVHQLARENGFPLRC 79

RING finger, H2 subclass, found in ubiquitin-protein ligase E3-alpha-2 (UBR2) and similar proteins; UBR2, also known as N-recognin-2 or E3alpha-II, is an E3 ubiquitin-protein ligase that plays an important role in maintaining genome integrity and in homologous recombination repair. It regulates the level of the transcription factor Rpn4 (also known as Son1 and Ufd5) through ubiquitylation. The ubiquitin-conjugating enzyme Rad6, another binding partner of URB2, and an additional factor Mub1, are required for the ubiquitin-dependent degradation of Rpn4. UBR2 associates with Mub1 to form a Mub1/Ubr2 complex that regulates the conserved Dsn1 kinetochore protein levels, which is a part of a quality control system that monitors kinetochore integrity, thus ensuring genomic stability. As the recognition component of a major cellular proteolytic system, UBR2 is associated with chromatin and controls chromatin dynamics and gene expression in both spermatocytes and somatic cells. UBR2 also mediates transcriptional silencing during spermatogenesis via histone ubiquitination. It functions as a scaffold E3 promoting HR6B/UbcH2-dependent ubiquitylation of H2A and H2B, but not H3 and H4. It also binds to Tex19.1, also known as Tex19, a germ cell-specific protein, and metabolically stabilizes it during spermatogenesis. Furthermore, UBR2 is involved in skeletal muscle (SKM) atrophy. Its expression can be modulated by the mouse ether-a-gogo-related gene 1a (MERG1a) potassium channel. In addition, UBR2 up-regulation in cachectic muscle is mediated by the p38beta-CCAAT/enhancer binding protein (C/EBP)-beta signaling pathway responsible for the bulk of tumor-induced muscle proteolysis. UBR2 contains an N-terminal ubiquitin-recognin (UBR) box involved in binding type-1 (basic) N-end rule substrate, an N-domain (also known as ClpS domain) required for type-2 (bulky hydrophobic) N-end rule substrate recognition, a C3H2C3-type RING-H2 finger, and a C-terminal UBR-specific autoinhibitory (UAIN) domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27597061 1107 TCILCQEEQEVKVESRAMVLAAFVQRSTVLSKNRSKFIQDPEKYDPLFMHPDLSCGTHTSSCGHIMHAHCWQRYFDSVQA 1186
Cdd:cd16686    1 TCILCQEEQEIKVDNKAMVLAAFVQRSTVMSKNRSRVIHDPEKYDPLFMHPDLSCGTHTGSCGHIMHAHCWQRYFDAVQA 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 27597061 1187 KEQRRQQRLRLHTSYDVENGEFLCPLCECLSNTVIP 1222
Cdd:cd16686   81 KEQRRQQRLRVHTSYDVENGEFLCPLCECLSNTVIP 116

ATP-dependent Clp protease adaptor protein ClpS; In the bacterial cytosol, ATP-dependent protein degradation is performed by several different chaperone-protease pairs, including ClpAP. ClpS directly influences the ClpAP machine by binding to the N-terminal domain of the chaperone ClpA. The degradation of ClpAP substrates, both SsrA-tagged proteins and ClpA itself, is specifically inhibited by ClpS. ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27597061    222 EKSDTYYCMLFNDEVHTYEQVIYTLQKAVNCTQKEAIGFATTVDRDGRRSVRYGDFQYCEQAKSVIVRNTSRQTKPLKV 300
Cdd:pfam02617    1 KEPPMYKVILLNDDYTTMEFVVEVLQRVFGKSEEEATEIMLQVHREGRAVVGVYTYDIAETKVAQVHQLARENGFPLRC 79

Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway; Domain is involved in recognition of N-end rule substrates in yeast Ubr1p

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27597061      98 LCGRVFKVGEPTYSCRDCAVDPTCVLCMECFLGSIHRDHRYRMTTSGGGGFCDCGDTEAWKEGPYCQKHE 167
Cdd:smart00396    2 VCGYKFTGGEVIYRCKTCGLDPTCVLCSDCFRPSCHKGHDVSLKTSRGSGICDCGDKEAWNEDLKCKAHE 71

RING finger, H2 subclass, found in ubiquitin-protein ligase E3-alpha-2 (UBR2) and similar proteins; UBR2, also known as N-recognin-2 or E3alpha-II, is an E3 ubiquitin-protein ligase that plays an important role in maintaining genome integrity and in homologous recombination repair. It regulates the level of the transcription factor Rpn4 (also known as Son1 and Ufd5) through ubiquitylation. The ubiquitin-conjugating enzyme Rad6, another binding partner of URB2, and an additional factor Mub1, are required for the ubiquitin-dependent degradation of Rpn4. UBR2 associates with Mub1 to form a Mub1/Ubr2 complex that regulates the conserved Dsn1 kinetochore protein levels, which is a part of a quality control system that monitors kinetochore integrity, thus ensuring genomic stability. As the recognition component of a major cellular proteolytic system, UBR2 is associated with chromatin and controls chromatin dynamics and gene expression in both spermatocytes and somatic cells. UBR2 also mediates transcriptional silencing during spermatogenesis via histone ubiquitination. It functions as a scaffold E3 promoting HR6B/UbcH2-dependent ubiquitylation of H2A and H2B, but not H3 and H4. It also binds to Tex19.1, also known as Tex19, a germ cell-specific protein, and metabolically stabilizes it during spermatogenesis. Furthermore, UBR2 is involved in skeletal muscle (SKM) atrophy. Its expression can be modulated by the mouse ether-a-gogo-related gene 1a (MERG1a) potassium channel. In addition, UBR2 up-regulation in cachectic muscle is mediated by the p38beta-CCAAT/enhancer binding protein (C/EBP)-beta signaling pathway responsible for the bulk of tumor-induced muscle proteolysis. UBR2 contains an N-terminal ubiquitin-recognin (UBR) box involved in binding type-1 (basic) N-end rule substrate, an N-domain (also known as ClpS domain) required for type-2 (bulky hydrophobic) N-end rule substrate recognition, a C3H2C3-type RING-H2 finger, and a C-terminal UBR-specific autoinhibitory (UAIN) domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27597061 1107 TCILCQEEQEVKVESRAMVLAAFVQRSTVLSKNRSKFIQDPEKYDPLFMHPDLSCGTHTSSCGHIMHAHCWQRYFDSVQA 1186
Cdd:cd16686    1 TCILCQEEQEIKVDNKAMVLAAFVQRSTVMSKNRSRVIHDPEKYDPLFMHPDLSCGTHTGSCGHIMHAHCWQRYFDAVQA 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 27597061 1187 KEQRRQQRLRLHTSYDVENGEFLCPLCECLSNTVIP 1222
Cdd:cd16686   81 KEQRRQQRLRVHTSYDVENGEFLCPLCECLSNTVIP 116

UBR-box found in ubiquitin-protein ligase E3-alpha-2 (UBR2) and similar proteins; UBR2 (EC 2.3.2.27), also called ubiquitin-protein ligase E3-alpha-II (E3alpha-II), or N-recognin-2, is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR2 is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. It plays an important role in spermatogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27597061   98 LCGRVFKVGEPTYSCRDCAVDPTCVLCMECFLGSIHRDHRYRMTTSGGGGFCDCGDTEAWKEGPYCQKHE 167
Cdd:cd19679    1 LCGRVFKVGEPTYSCRDCAVDPTCVLCMECFLGSIHRDHRYRMTTSGGGGFCDCGDTEAWKEGPYCQKHE 70

RING finger, H2 subclass, found in ubiquitin-protein ligase E3-alpha-1 (UBR1), E3-alpha-2 (UBR2), and similar proteins; Two UBR family members, UBR1 and UBR2, are major N-recognin ubiquitin ligases that both function in the N-end rule degradation pathway. They can recognize substrate proteins with type-1 (basic) and type-2 (bulky hydrophobic) N-terminal residues as part of N-degrons and an internal lysine residue for ubiquitin conjugation. They also function in a quality control pathway for degradation of unfolded cytosolic proteins. Their action is stimulated by Hsp70. Moreover, UBR1 and UBR2 are negative regulators of the leucine-mTOR signaling pathway. Leucine might activate this pathway in part through inhibition of their ubiquitin ligase activity. In yeast, only one E3, encoded by UBR1, mediates the recognition of substrates by the N-end rule pathway. Saccharomyces cerevisiae UBR1 also functions as an additional E3 ligase in the endoplasmic reticulum-associated protein degradation (ERAD). It can provide ubiquitin ligation activity for the ERAD substrate mutated Ste6 (sterile). Schizosaccharomyces pombe UBR1 is a critical regulator that influences the oxidative stress response via degradation of active Pap1 basic leucine zipper (bZIP) transcription factor in the nucleus. Both UBR1 and UBR2 contain an N-terminal ubiquitin-recognin (UBR) box involved in binding type-1 (basic) N-end rule substrate, an N-domain (also known as ClpS domain) required for type-2 (bulky hydrophobic) N-end rule substrate recognition, a C3H2C3-type RING-H2 finger, and a C-terminal UBR-specific autoinhibitory (UAIN) domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27597061 1162 GTHTSSCGHIMHAHCWQRYFDSVQAKEQRRQQRLRLHtSYDVENGEFLCPLCECLSNTVIP 1222
Cdd:cd16482    8 GLHISSCGHVMHYDCWQRYFDSVRLREQRRPAFRRHH-SEDVSKGEFLCPLCKSLSNTVLP 67

ATP-dependent Clp protease adaptor protein ClpS; In the bacterial cytosol, ATP-dependent protein degradation is performed by several different chaperone-protease pairs, including ClpAP. ClpS directly influences the ClpAP machine by binding to the N-terminal domain of the chaperone ClpA. The degradation of ClpAP substrates, both SsrA-tagged proteins and ClpA itself, is specifically inhibited by ClpS. ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27597061    222 EKSDTYYCMLFNDEVHTYEQVIYTLQKAVNCTQKEAIGFATTVDRDGRRSVRYGDFQYCEQAKSVIVRNTSRQTKPLKV 300
Cdd:pfam02617    1 KEPPMYKVILLNDDYTTMEFVVEVLQRVFGKSEEEATEIMLQVHREGRAVVGVYTYDIAETKVAQVHQLARENGFPLRC 79

Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway; Domain is involved in recognition of N-end rule substrates in yeast Ubr1p

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27597061      98 LCGRVFKVGEPTYSCRDCAVDPTCVLCMECFLGSIHRDHRYRMTTSGGGGFCDCGDTEAWKEGPYCQKHE 167
Cdd:smart00396    2 VCGYKFTGGEVIYRCKTCGLDPTCVLCSDCFRPSCHKGHDVSLKTSRGSGICDCGDKEAWNEDLKCKAHE 71

UBR-box found in ubiquitin-protein ligase E3-alpha-1 (UBR1), E3-alpha-2 (UBR2), E3-alpha-3 (UBR3) and similar proteins; This family includes UBR1, UBR2, and UBR3 (all belonging to EC 2.3.2.27). Both UBR1 (also called E3alpha-I or N-recognin-1) and UBR2 (also called E3-alpha-II or N-recognin-2), are RING-type E3 ubiquitin ligases of the Arg/N-end rule degradation pathway. They recognize and bind to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Deficiency of UBR1 causes Johanson-Blizzard syndrome. UBR2 is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. It plays an important role in spermatogenesis. UBR3, also called ubiquitin-protein ligase E3-alpha-III (E3alpha-III), or N-recognin-3, or zinc finger protein 650, is a RING-type E3 ubiquitin ligase with a function in olfactory and other sensory systems. It negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. It acts as a positive regulator of Hedgehog (Hh) signaling in Drosophila and vertebrates. It also plays an important role for genome stability by controlling cellular levels of the essential DNA repair protein APE1.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27597061   99 CGRVFKVGEPTYSCRDCAVDPTCVLCMECFLGSIHRDHRYRMTTSGGGGFCDCGDTEAWKEGPYCQKH 166
Cdd:cd19670    1 CGKSLKKGELYYRCLDCSLDPSSCICEECFLNGNHEGHNYSLRTSSGGGVCDCGDSEAWKPSGFCSKH 68

UBR-box found in UBR family of E3 ubiquitin ligases (UBR1-7) and similar proteins; The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases (UBR1-7, also called N-recognins) that directly binds N-terminal degradation signals (N-degrons) in substrate proteins to facilitate substrate ubiquitination and proteasomal degradation via the ubiquitin-proteasome system (UPS). UBR1 and UBR2 bind all type-1 and type-2 N-degrons. They mediate ubiquitination and proteolysis of short-lived regulators and misfolded proteins. UBR4 binds both type-1 and type-2 N-degrons and is involved in proteome-wide turnover of cell surface proteins. UBR5 preferentially binds type-1 N-degrons and mediates ubiquitination of short-lived proteins. UBR3, UBR6 (also called FBXO11), and UBR7 may not bind efficiently to N-degrons. UBR3 is a RING-type E3 ubiquitin ligase with a function in olfactory and other sensory systems. UBR6 is an E3 ubiquitin ligase and a type II methyltransferase, which functions as a key regulator of tumor initiation and progression. It does not bind N-terminal signals. UBR7 is a RING-type E3 ubiquitin ligase that may play an important role in spermiogenesis and fertilization.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 27597061   99 CGRVF-KVGEPTYSCRDCAVDPTCVLCMECFLgSIHRDHRYRMTTS 143
Cdd:cd19669    1 CTFSItGINQVMYHCLTCSLDDNSGICEECAK-KCHEGHDVVYIGS 45

RING finger, H2 subclass, found in RING finger protein 25 (RNF25) and similar proteins; RNF25, also known as AO7, is a putative E3 ubiquitin-protein ligase that was initially identified as an interacting protein of the E2 ubiquitin-conjugating enzyme, Ubc5B. It is ubiquitously expressed in various tissues and predominantly localized in the nucleus. RNF25 activates the nuclear factor (NF)-kappaB-dependent gene expression upon stimulation with Interleukin-1 beta (IL-1beta), or tumor necrosis factor (TNF), or overexpression of NF-kappaB-inducing kinase. It interacts with the p65 transactivation domain (TAD) and modulates its transcriptional activity. RNF25 contains an N-terminal RWD domain, a C3H2C3-type RING-H2 finger, and a C-terminal Pro-rich region. Both the RING-H2 finger and the C-terminal regions of RNF25 are necessary for transcriptional activation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 27597061 1166 SSCGHIMHAHCWQRYFDSVQA--KEQRRQQRLRLHTSYDVENGEFLCPLC 1213
Cdd:cd16470   21 TPCYHYFHSHCLARYIQHMEEnlKEEQEEQEERPRAQTEQEQFQVLCPVC 70