RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 914912722 596 LRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTFLS 652
Cdd:cd16713    1 LRRLQEERTCKVCMDKEVSIVFIPCGHLVVCTECAPSLRKCPICRATIKGTVRTFLS 57

Baculoviral inhibition of apoptosis protein repeat; Domain found in inhibitor of apoptosis proteins (IAPs) and other proteins. Acts as a direct inhibitor of caspase enzymes.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 914912722    76 CELYRMSTYSTFPSGVPVSERSLARAGFYYTGVKDKVKCFCCGLMLDNWKQGDNPIEKHKKLYPSCSFVQN 146
Cdd:smart00238   1 SEEARLKTFQNWPYNSKCTPEQLAEAGFYYTGVGDEVKCFFCGGELDNWEPGDDPWEEHKKWSPNCPFVRN 71

UBA domain found in baculoviral IAP repeat-containing protein BIRC2, BIRC3 and similar proteins; The subfamily includes cellular inhibitor of apoptosis protein 1 (c-IAP1) and c-IAP2. c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of the substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB)signaling, and oncogenesis. Unlike other apoptosis proteins (IAPs), such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also called baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also called BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of binds polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a RING domain at the carboxyl terminus that is required for ubiquitin ligase activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 914912722 425 MNTPVVKAALEMGFSRNLVKQTVQSKILTAGENYKTISDLVLDLLNAEDE 474
Cdd:cd14394    1 MNTPVVKSALEMGFNRRLVKQTVQSKILTSGENYKTVNDLVSDLLSAEDE 50

RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 914912722 596 LRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTFLS 652
Cdd:cd16713    1 LRRLQEERTCKVCMDKEVSIVFIPCGHLVVCTECAPSLRKCPICRATIKGTVRTFLS 57

Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. In yeast, BIR domains are involved in regulating cytokinesis. This novel fold is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues and resembles a classical zinc finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 914912722 304 AARFKTFFNWPSSVLVHPEQLASAGFYYVGHSDDVKCFCCDGGLRCWELGDDPWVEHAKWFPRCEYL 370
Cdd:cd00022    1 EARLKTFKNWPISLKVTPEKLAEAGFYYTGRGDEVKCFFCGLELKNWEPGDDPWEEHKRWSPNCPFV 67

Baculoviral inhibition of apoptosis protein repeat; Domain found in inhibitor of apoptosis proteins (IAPs) and other proteins. Acts as a direct inhibitor of caspase enzymes.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 914912722   216 TEKARLLTYQMWP-LTFLSPTELAKAGFYYIGPGDRVACFACGGKLSNWEPKDDAMSEHLRHFPNCPFVEN 285
Cdd:smart00238   1 SEEARLKTFQNWPyNSKCTPEQLAEAGFYYTGVGDEVKCFFCGGELDNWEPGDDPWEEHKKWSPNCPFVRN 71

Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. In yeast, BIR domains are involved in regulating cytokinesis. This novel fold is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues and resembles a classical zinc finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 914912722 218 KARLLTYQMWPLT-FLSPTELAKAGFYYIGPGDRVACFACGGKLSNWEPKDDAMSEHLRHFPNCPFVEN 285
Cdd:cd00022    1 EARLKTFKNWPISlKVTPEKLAEAGFYYTGRGDEVKCFFCGLELKNWEPGDDPWEEHKRWSPNCPFVLL 69

Inhibitor of Apoptosis domain; BIR stands for 'Baculovirus Inhibitor of apoptosis protein Repeat'. It is found repeated in inhibitor of apoptosis proteins (IAPs), and in fact it is also known as IAP repeat. These domains characteriztically have a number of invariant residues, including 3 conserved cysteines and one conserved histidine that coordinate a zinc ion. They are usually made up of 4-5 alpha helices and a three-stranded beta-sheet. BIR is also found in other proteins known as BIR-domain-containing proteins (BIRPs), such as Survivin.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 914912722   80 RMSTYSTFPSG--VPVSERSLARAGFYYTGVKDKVKCFCCGLMLDNWKQGDNPIEKHKKLYPSCSFVQ 145
Cdd:pfam00653   1 RLATFENWPHSnkSPPTPEELAEAGFYYTGTGDRVQCFYCGLELDGWEEGDDPWEEHKKHSPDCPFLK 68

UBA domain found in baculoviral IAP repeat-containing protein BIRC2, BIRC3 and similar proteins; The subfamily includes cellular inhibitor of apoptosis protein 1 (c-IAP1) and c-IAP2. c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of the substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB)signaling, and oncogenesis. Unlike other apoptosis proteins (IAPs), such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also called baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also called BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of binds polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a RING domain at the carboxyl terminus that is required for ubiquitin ligase activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 914912722 425 MNTPVVKAALEMGFSRNLVKQTVQSKILTAGENYKTISDLVLDLLNAEDE 474
Cdd:cd14394    1 MNTPVVKSALEMGFNRRLVKQTVQSKILTSGENYKTVNDLVSDLLSAEDE 50

Caspase recruitment domain; Motif contained in proteins involved in apoptotic signalling. Mediates homodimerisation. Structure consists of six antiparallel helices arranged in a topology homologue to the DEATH and the DED domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 914912722   488 ESGDLLLIRKNRMALFQHLTCViPILDSLLIARVINEQEHDVIKQKTQTSLQARELIDTILVKGNTAATVFKNSLQETDP 567
Cdd:smart00114   2 AERDKRLLRRNRVRLGEELGVD-GLLDYLVEKNVLTEKEIEAIKAATTKLRDKRELVDSLQKRGSQAFDTFLDSLQETDQ 80

                   ....*...
gi 914912722   568 MLYKHLFV 575
Cdd:smart00114  81 KLADFLEL 88

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 914912722   605 CKVCMDK-EVSIVFIPCGHlVVCKDCAPSL-----RKCPIC 639
Cdd:smart00184   1 CPICLEEyLKDPVILPCGH-TFCRSCIRKWlesgnNTCPIC 40

RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 914912722 596 LRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTFLS 652
Cdd:cd16713    1 LRRLQEERTCKVCMDKEVSIVFIPCGHLVVCTECAPSLRKCPICRATIKGTVRTFLS 57

Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. In yeast, BIR domains are involved in regulating cytokinesis. This novel fold is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues and resembles a classical zinc finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 914912722 304 AARFKTFFNWPSSVLVHPEQLASAGFYYVGHSDDVKCFCCDGGLRCWELGDDPWVEHAKWFPRCEYL 370
Cdd:cd00022    1 EARLKTFKNWPISLKVTPEKLAEAGFYYTGRGDEVKCFFCGLELKNWEPGDDPWEEHKRWSPNCPFV 67

Baculoviral inhibition of apoptosis protein repeat; Domain found in inhibitor of apoptosis proteins (IAPs) and other proteins. Acts as a direct inhibitor of caspase enzymes.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 914912722   216 TEKARLLTYQMWP-LTFLSPTELAKAGFYYIGPGDRVACFACGGKLSNWEPKDDAMSEHLRHFPNCPFVEN 285
Cdd:smart00238   1 SEEARLKTFQNWPyNSKCTPEQLAEAGFYYTGVGDEVKCFFCGGELDNWEPGDDPWEEHKKWSPNCPFVRN 71

Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. In yeast, BIR domains are involved in regulating cytokinesis. This novel fold is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues and resembles a classical zinc finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 914912722 218 KARLLTYQMWPLT-FLSPTELAKAGFYYIGPGDRVACFACGGKLSNWEPKDDAMSEHLRHFPNCPFVEN 285
Cdd:cd00022    1 EARLKTFKNWPISlKVTPEKLAEAGFYYTGRGDEVKCFFCGLELKNWEPGDDPWEEHKRWSPNCPFVLL 69

Inhibitor of Apoptosis domain; BIR stands for 'Baculovirus Inhibitor of apoptosis protein Repeat'. It is found repeated in inhibitor of apoptosis proteins (IAPs), and in fact it is also known as IAP repeat. These domains characteriztically have a number of invariant residues, including 3 conserved cysteines and one conserved histidine that coordinate a zinc ion. They are usually made up of 4-5 alpha helices and a three-stranded beta-sheet. BIR is also found in other proteins known as BIR-domain-containing proteins (BIRPs), such as Survivin.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 914912722   80 RMSTYSTFPSG--VPVSERSLARAGFYYTGVKDKVKCFCCGLMLDNWKQGDNPIEKHKKLYPSCSFVQ 145
Cdd:pfam00653   1 RLATFENWPHSnkSPPTPEELAEAGFYYTGTGDRVQCFYCGLELDGWEEGDDPWEEHKKHSPDCPFLK 68

UBA domain found in baculoviral IAP repeat-containing protein BIRC2, BIRC3 and similar proteins; The subfamily includes cellular inhibitor of apoptosis protein 1 (c-IAP1) and c-IAP2. c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of the substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB)signaling, and oncogenesis. Unlike other apoptosis proteins (IAPs), such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also called baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also called BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of binds polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a RING domain at the carboxyl terminus that is required for ubiquitin ligase activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 914912722 425 MNTPVVKAALEMGFSRNLVKQTVQSKILTAGENYKTISDLVLDLLNAEDE 474
Cdd:cd14394    1 MNTPVVKSALEMGFNRRLVKQTVQSKILTSGENYKTVNDLVSDLLSAEDE 50

RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins; XIAP, also known as baculoviral IAP repeat-containing protein 4 (BIRC4), IAP-like protein (ILP), inhibitor of apoptosis protein 3 (IAP-3), or X-linked inhibitor of apoptosis protein (X-linked IAP), is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases, including caspase-3, -7, and -9. It promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. The ubiquitin-protein ligase (E3) activity of XIAP also exhibits in the ubiquitination of second mitochondria-derived activator of caspases (Smac). The mitochondrial proteins, Smac/DIABLO and Omi/HtrA2, can inhibit the antiapoptotic activity of XIAP. XIAP has also been implicated in several intracellular signaling cascades involved in the cellular response to stress, such as the c-Jun N-terminal kinase (JNK), the nuclear factor-kappaB (NF-kappaB), and the transforming growth factor-beta (TGF-beta) pathways. Moreover, XIAP can regulate copper homeostasis by interacting with MURR1. BIRC8, also known as inhibitor of apoptosis-like protein 2, IAP-like protein 2, ILP-2, or testis-specific inhibitor of apoptosis, is a tissue-specific homolog of E3 ubiquitin-protein ligase XIAP. It has been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. Both XIAP and BIRC8 contain three N-terminal baculoviral IAP repeat (BIR) domains, a ubiquitin-association (UBA) domain and a C3HC4-type RING-HC finger at the carboxyl terminus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 914912722 589 DLPMEEQLRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTFLS 652
Cdd:cd16714    1 EISTEEKLRRLQEEKLCKICMDRNISIVFIPCGHLVTCKQCAEALDKCPICCTVITFKQKIFMS 64

Caspase recruitment domain; Motif contained in proteins involved in apoptotic signalling. Mediates homodimerisation. Structure consists of six antiparallel helices arranged in a topology homologue to the DEATH and the DED domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 914912722   488 ESGDLLLIRKNRMALFQHLTCViPILDSLLIARVINEQEHDVIKQKTQTSLQARELIDTILVKGNTAATVFKNSLQETDP 567
Cdd:smart00114   2 AERDKRLLRRNRVRLGEELGVD-GLLDYLVEKNVLTEKEIEAIKAATTKLRDKRELVDSLQKRGSQAFDTFLDSLQETDQ 80

                   ....*...
gi 914912722   568 MLYKHLFV 575
Cdd:smart00114  81 KLADFLEL 88

Caspase activation and recruitment domain: a protein-protein interaction domain; Caspase activation and recruitment domains (CARDs) are death domains (DDs) found associated with caspases. Caspases are aspartate-specific cysteine proteases with functions in apoptosis, immune signaling, inflammation, and host-defense mechanisms. In addition to caspases, proteins containing CARDs include adaptor proteins such as RAIDD, CARD9, and RIG-I-like helicases, which can form multiprotein complexes and play important roles in mediating the signals to induce immune and inflammatory responses. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 914912722 495 IRKNRMALFQHLtCVIPILDSLLIARVINEQEHDVIKQKTQTSLQARELIDTILVKGNTAATVFKNSLQETD-PMLYKHL 573
Cdd:cd01671    1 LRKNRVELVEDL-DVEDILDHLIQKGVLTEEDKEEILSEKTRQDKARKLLDILPRRGPKAFEVFCEALRETGqPHLAELL 79

RING finger, HC subclass, found in leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) and similar proteins; LRSAM1, also known as Tsg101-associated ligase (TAL), or RIFLE, is an E3 ubiquitin-protein ligase that physically associates with, and selectively ubiquitylates, Tsg101, an E2-like molecule that regulates vesicular trafficking processes in yeast and mammals. It regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane. LRSAM1 is a multidomain protein containing an N-terminal leucine-rich repeat (LRR), followed by several recognizable motifs, including an ezrin-radixin-moezin (ERM) domain, a coiled-coil (CC) region, a SAM domain, and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 914912722 605 CKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVR 648
Cdd:cd16515    4 CVVCMDAESQVIFLPCGHVCCCQTCSSSLSTCPLCRADITQRVR 47

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein CARP-1, CARP-2 and similar proteins; The CARP subfamily includes CARP-1 and CARP-2 proteins, both of which are E3 ubiquitin ligases that ubiquitinate apical caspases and target them for proteasome-mediated degradation. As a novel group of caspase regulators with a FYVE-type zinc finger domain, they do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8, and caspase 10. Moreover, they stabilize MDM2 by inhibiting MDM2 self-ubiquitination, as well as by targeting 14-3-3sigma for degradation. They work together with MDM2 to enhance p53 degradation, thereby inhibiting p53-mediated cell death. CARPs contain an N-terminal FYVE-like domain that can serve as a membrane-targeting or endosome localizing signal and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 914912722 604 TCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTF 650
Cdd:cd16500    2 LCKICMDAAIDCVLLECGHMVTCTDCGKKLSECPICRQYVVRVVHFF 48

RING finger, HC subclass, found in Dictyostelium discoideum Cbl-like protein A (CblA) and similar proteins; CblA is a Dictyostelium homolog of the Cbl proteins which are multi-domain proteins acting as key negative regulators of various receptor and non-receptor tyrosine kinase signaling. CblA upregulates STATc tyrosine phosphorylation by downregulating PTP3, the protein tyrosine phosphatase responsible for dephosphorylating STATc. STATc is a signal transducer and activator of transcription protein. Like other Cbl proteins, CblA contains a tyrosine-kinase-binding domain (TKB), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB, also known as a phosphotyrosine binding PTB domain, is composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain. This family also includes Drosophila melanogaster defense repressor 1 (Dnr1) that was identified as an inhibitor of Dredd activity in the absence of a microbial insult in Drosophila S2 cells. It inhibits the Drosophila initiator caspases Dredd and Dronc. Moreover, Dnr1 acts as a negative regulator of the Imd (immune deficiency) innate immune-response pathway. Its mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain. Dnr1 contains a FERM N-terminal domain followed by a region rich in glutamine and serine residues, a central FERM domain, and a C-terminal C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 914912722 605 CKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTF 650
Cdd:cd16501    8 CVVCMDAPIDTVFLECGHLACCRLCSKRLRVCPICRQPISRVVRIF 53

Modified RING finger, HC subclass (C3HC5-type), found in mitochondrial-anchored protein ligase (MAPL) and similar proteins; MAPL, also known as MULAN, mitochondrial ubiquitin ligase activator of NFKB 1, E3 SUMO-protein ligase MUL1, E3 ubiquitin-protein ligase MUL1, growth inhibition and death E3 ligase (GIDE), putative NF-kappa-B-activating protein 266, or RING finger protein 218 (RNF218), is a multifunctional mitochondrial outer membrane protein involved in several processes specific to metazoan (multicellular animal) cells, such as NF-kappaB activation, innate immunity and antiviral signaling, suppression of PINK1/parkin defects, mitophagy in skeletal muscle, and caspase-dependent apoptosis. MAPL contains a unique BAM (beside a membrane)/GIDE (growth inhibition death E3 ligase) domain and a C-terminal modified cytosolic C3HC5-type RING-HC finger which is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 914912722 605 CKVCMDKEVSIVFIPCGHLVVCKDC---APSLRKCPICRGTIK 644
Cdd:cd16648    4 CVICLSNPRSCVFLECGHVCSCIECyeaLPSPKKCPICRSFIK 46

UBA domain found in Xenopus tropicalis baculoviral IAP repeat-containing protein BIRC7, BIRC71A and similar proteins; X. tropicalis BIRC7, also called E3 ubiquitin-protein ligase EIAP, embryonic/Egg IAP (xEIAP/XLX), inhibitor of apoptosis (IAP)-like protein, XIAP homolog XLX, is a weak apoptosis inhibitor that exhibits caspase inhibition and autoubiquitylation. It is uniquely modified by MAPK- and Cdc2/Cyclin B-dependent phosphorylation during oocyte maturation. Its caspase-dependent cleavage is altered when it is phosphorylated. X. tropicalis BIRC7 contains two N-terminal baculoviral IAP repeats (BIRs) and a C-terminal RING domain. Based on sequence homology, it also harbors a ubiquitin-associated (UBA) domain which is not detected in human BIRC7.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 914912722 428 PVVKAALEMGFSRNLVKQTVQSKILTAGENYKTISDLVLDLLNA 471
Cdd:cd14396    1 SVVQAVLQMGFDQSLVESLVQNKYLLTGPAYTSVSQLVSDLLQE 44

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 2 (CARP-2) and similar proteins; CARP-2, also known as rififylin, caspase regulator CARP2, FYVE-RING finger protein Sakura (Fring), RING finger and FYVE-like domain-containing protein 1, RING finger protein 189 (RNF189), or RING finger protein 34-like, is an endosome-associated E3 ubiquitin-protein ligase that targets internalized receptor interacting kinase (RIP) for proteasome-mediated degradation. It acts as a negative regulator of tumor necrosis factor (TNF)-induced nuclear factor (NF)-kappaB activation. It also regulates the p53 signaling pathway by degrading 14-3-3sigma and stabilizing MDM2. As a caspase regulator, CARP2 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10. CARP2 contains an N-terminal FYVE-like domain and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 914912722 601 EERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTF 650
Cdd:cd16707    1 DENLCKICMDSPIDCVLLECGHMVTCTKCGKRMSECPICRQYVIRAVHVF 50

UBA domain found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins; XIAP, also called baculoviral IAP repeat-containing protein 4 (BIRC4), IAP-like protein (ILP), inhibitor of apoptosis protein 3 (IAP-3), or X-linked inhibitor of apoptosis protein (X-linked IAP), is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases, including caspase-3, -7, and -9. It promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. The ubiquitin-protein ligase (E3) activity of XIAP also exhibits in the ubiquitination of second mitochondria-derived activator of caspases (Smac). The mitochondrial proteins, Smac/DIABLO and Omi/HtrA2, can inhibit the antiapoptotic activity of XIAP. XIAP has also been implicated in several intracellular signaling cascades involved in the cellular response to stress, such as the c-Jun N-terminal kinase (JNK) pathway, the nuclear factor-kappaB (NF-kappaB) pathway, and the transforming growth factor-beta (TGF-beta) pathway. Moreover, XIAP can regulate copper homeostasis through interacting with MURR1. BIRC8, also called inhibitor of apoptosis-like protein 2 (IAP-like protein 2 or ILP-2), or testis-specific inhibitor of apoptosis, is a tissue-specific homolog of E3 ubiquitin-protein ligase XIAP. It has been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. Both XIAP and BIRC8 contain three N-terminal baculoviral IAP repeat (BIR) domains, a ubiquitin-association (UBA) domain and a RING domain at the carboxyl terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 914912722 424 MMNTPVVKAALEMGFSRNLVKQTVQSKILTAGENYKTISDLVLDLLNAE 472
Cdd:cd14395    1 ILQNPLVQEAIRMGFSFKEIKKIMEEKLKTSGSNYTSLEVLVADLVSAQ 49

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 1 (CARP1) and similar proteins; CARP1, also known as caspase regulator CARP1, FYVE-RING finger protein Momo, RING finger homologous to inhibitor of apoptosis protein (RFI), RING finger protein 34 (RNF34), or RING finger protein RIFF, is a nuclear protein that functions as a specific E3 ubiquitin ligase for the transcriptional coactivator PGC-1alpha, a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell which negatively regulates brown fat cell metabolism. It is preferentially expressed in esophageal, gastric, and colorectal cancers, suggesting a possible association with the development of digestive tract cancers. It regulates the p53 signaling pathway by degrading 14-3-3 sigma and stabilizing MDM2. CARP1 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10. CARP1 contains an N-terminal FYVE-like domain and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 914912722 600 QEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTIKGTVRTFLS 652
Cdd:cd16706    2 SDDNLCRICMDAVIDCVLLECGHMVTCTKCGKRMSECPICRQYVVRAVHVFKS 54

Modified RING finger, HC subclass (C3HC5-type), found in cell growth regulator with RING finger domain protein 1 (CGRRF1) and similar proteins; CGRRF1, also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. CGRRF1 contains a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 914912722 605 CKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICR 640
Cdd:cd16787    3 CVVCQNAPVNRVLLPCRHACVCDECFKRLQRCPMCR 38

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1), RING finger protein 157 (RNF157) and similar proteins; MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. MGRN1 also interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase mahogunin ring finger-1 (MGRN1). In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. Both MGRN1 and RNF157 contain a modified C3HC5-type RING-HC finger, and a functionally uncharacterized region, known as domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 914912722 603 RTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLR----KCPICR 640
Cdd:cd16789    1 SECVICLSDPRDTAVLPCRHLCLCSDCAEVLRyqsnKCPICR 42

second RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the second RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 914912722 605 CKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICR 640
Cdd:cd16725    3 CVVCSDKKASVLFKPCGHMCACEGCAALMKKCVQCR 38

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 914912722 604 TCKVCMDKEVSIVFIPCGHlVVCKDCAPSLR-----KCPIC 639
Cdd:cd16449    2 ECPICLERLKDPVLLPCGH-VFCRECIRRLLesgsiKCPIC 41

RING finger, HC subclass, found in RING finger protein unkempt-like (UNKL) and similar proteins; UNKL, also known as zinc finger CCCH domain-containing protein 5-like, is a putative E3 ubiquitin-protein ligase that may participate in a protein complex showing an E3 ligase activity regulated by RAC1. It shows high sequence similarity with RING finger protein unkempt (UNK), which is a metazoan-specific zinc finger protein enriched in embryonic brains, and may play a broad regulatory role during the formation of the central nervous system (CNS). UNKL contains several CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 914912722 603 RTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTI 643
Cdd:cd16772    1 KKCIVCQERDRSIVLQPCQHYVLCEHCAASKPECPYCKTKI 41

Prokaryotic RING finger family 4; RING finger family domain found sporadically in bacteria. The finger is fused to an N-terminal alpha-helical domain, ROT/Trove-like repeats and a C-terminal TerD domain. The architecture suggests a possible role in an RNA-processing complex.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 914912722  605 CKVCMDKEVSIVFIPCGHLvVCKDCAPS--LRKCPICRGTIKGT 646
Cdd:pfam14447   1 CVLCGRNGTVHALIPCGHL-VCRDCFDGsdFSACPICRRRIDAD 43

RING finger, HC subclass, found in RING finger protein unkempt (UNK), unkempt-like (UNKL), and similar proteins; UNK, also known as zinc finger CCCH domain-containing protein 5, is a metazoan-specific zinc finger protein enriched in embryonic brains. It may play a broad regulatory role during the formation of the central nervous system (CNS). It is a sequence-specific RNA-binding protein required for early neuronal morphology. UNK is a neurogenic component of the mTOR pathway, and functions as a negative regulator of the timing of photoreceptor differentiation. It also specifically binds to Brg/Brm-associated factor BAF60b and promotes its ubiquitination in a Rac1-dependent manner. UNKL, also known as zinc finger CCCH domain-containing protein 5-like, is a putative E3 ubiquitin-protein ligase that may participate in a protein complex showing an E3 ligase activity regulated by RAC1. Both UNK and UNKL contain several tandem CCCH-type zinc fingers at the N-terminus, and a C3HC4-type RING-HC finger at its C-terminus.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 914912722 605 CKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPIC 639
Cdd:cd16614    3 CMKCEERNRSVAVLPCQHYVLCEQCAETATECPYC 37

first RING finger, HC subclass, found in mind bomb 2 (MIB2) and similar proteins; MIB2, also known as novel zinc finger protein (Novelzin), putative NF-kappa-B-activating protein 002N, skeletrophin, or zinc finger ZZ type with ankyrin repeat domain protein 1, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands. It promotes Delta ubiquitylation and endocytosis in Notch activation. Overexpression of MIB2 activates NF-kappaB and interferon-stimulated response element (ISRE) reporter activity. Moreover, MIB2 acts as a novel component of the activated B-cell CLL/lymphoma 10 (BCL10) complex and controls BCL10-dependent NF-kappaB activation. It also functions as a founder myoblast-specific protein that regulates myoblast fusion and muscle stability. MIB2 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of two C3HC4-type RING-HC fingers. This model corresponds to the first RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 914912722 605 CKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPIC 639
Cdd:cd16726    3 CLVCSELAALVRFEPCQHSIVCEECARRMKKCIKC 37

Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 26 (RNF26) and similar proteins; RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination of MITA after viral infection, and promoting the degradation of IRF3, another important component required for virus-triggered interferon induction. Although RNF26 substrates of ubiquitination remain unclear at present, RNF26 upregulation in gastric cancer might be implicated in carcinogenesis through dysregulation of growth regulators. RNF26 contains an N-terminal leucine zipper domain and a C-terminal modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 914912722 600 QEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSL-------RKCPICRGTIKGTV 647
Cdd:cd16788    3 RDKKKCVICQDQSKTVLILPCRHMCLCRQCANILlqqpvyrRNCPLCRTMILQTL 57

RING finger, HC subclass, found in RING finger and SPRY domain-containing protein 1 (RSPRY1) and similar proteins; RSPRY1 is a hypothetical RING and SPRY domain-containing protein of unknown physiological function. Mutations in its corresponding gene RSPRY1 may associate with a distinct skeletal dysplasia syndrome. RSPRY1 contains a B30.2/SPRY domain and a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 914912722 602 ERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRGTI 643
Cdd:cd16566    2 EDSCTLCFDKVADTELRPCGHSGFCMECALQLETCPLCRQPI 43

RING finger, HC subclass, found in RNA-binding protein MEX3C; MEX3C, also known as RING finger and KH domain-containing protein 2 (RKHD2), or RING finger protein 194 (RNF194), is an RNA-binding phosphoprotein that acts as a suppressor of chromosomal instability. It functions as an ubiquitin E3 ligase responsible for the post-transcriptional, HLA-A allotype-specific regulation of MHC class I molecules (MHC-I). It also modifies retinoic acid inducible gene-1 (RIG-I) in stress granules and plays a critical role in eliciting antiviral immune responses. Moreover, MEX3C plays an essential role in normal postnatal growth via enhancing the local expression of insulin-like growth factor 1 (IGF1) in bone. It may also be involved in metabolic regulation of energy balance. MEX3C contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3C shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 914912722 602 ERTCKVCMDKEVSIVFIPCGHLVVCKDCA-----PSLRKCPICRGTI 643
Cdd:cd16722    1 KHDCVICFENEVIAALVPCGHNLFCMECAnkiceKETPSCPVCQTAV 47

third RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region consisting of three C3HC4-type RING-HC fingers. This model corresponds to the third RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 914912722 605 CKVCMDKEVSIVFIpCGHlVVCKDCAPSLRKCPICRGTIKGTVRTF 650
Cdd:cd16727    3 CPVCLDRLKNMIFL-CGH-GTCQLCGDRMSECPICRKAIEKRILLY 46

Caspase activation and recruitment domain found in Human ASC, NALP1, and similar proteins; Caspase activation and recruitment domain (CARD) similar to those found in human ASC (Apoptosis-associated speck-like protein containing a CARD) and NALP1 (CARD7, NLRP1). ASC, an adaptor molecule, and NALP1, a member of the Nod-like receptor (NLR) family, are involved in the assembly of the 'inflammasome', a multiprotein platform, which is responsible for caspase-1 activation and regulation of IL-1beta maturation. In general, CARDs are death domains (DDs) associated with caspases. They are known to be important in the signaling pathways for apoptosis, inflammation and host-defense mechanisms. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 914912722 495 IRKNRMALFQHLTCVIPILDSLLiARVINEQEHDVIKQKTQTSLQARELIDTILVKGNTAATVFKNSLQETDPML 569
Cdd:cd08330    3 VDRHREALIQRVTNVDPILDELR-GKVLTQEQYSSIRAERTNQEKMRKLYELVPSWGRTCKDLFYQALKETNPYL 76

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also known as Casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55 (RNF55), or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinase signaling. It contains a tyrosine kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70, and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with a SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through the RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 914912722 605 CKVCMDKEVSIVFIPCGHLvVCKDCAPSLRK-----CPICRGTIKGT 646
Cdd:cd16708   24 CKICAENDKDVKIEPCGHL-MCTSCLTSWQEsegqgCPFCRCEIKGT 69

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 914912722 596 LRRLQEERTCKVCMDKEVSIVFIPCGHlVVCKDCAPSLRK-----CPICR 640
Cdd:cd16596    3 LTMMWEEVTCPICLDPFVEPVSIECGH-SFCQECISQVGKgggsvCPVCR 51

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins; Cbl-c, also known as RING finger protein 57 (RNF57), SH3-binding protein Cbl-3, SH3-binding protein Cbl-c, or signal transduction protein Cbl-c, is an E3 ubiquitin-protein ligase expressed exclusively in epithelial cells. It contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a C3HC4-type RING-HC finger, and a short proline-rich region, but lacks the ubiquitin-associated (UBA) leucine zipper motif that are present in Cbl and Cbl-b. Cbl-c acts as a regulator of epidermal growth factor receptor (EGFR)-mediated signal transduction. It also suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Moreover, Cbl-c ubiquitinates and downregulates RETMEN2A and implicates Enigma (PDLIM7) as a positive regulator of RETMEN2A by blocking Cbl-mediated ubiquitination and degradation. The ubiquitin ligase activity of Cbl-c is increased via the interaction of its RING-HC finger domain with a LIM domain of the paxillin homolog, hydrogen peroxide induced construct 5 (Hic-5).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 914912722 605 CKVCMDKEVSIVFIPCGHLvVCKDCAPSL-----RKCPICRGTIKG 645
Cdd:cd16710   16 CKICAERDKDVRIEPCGHL-LCSCCLAAWqhsdsQTCPFCRCEIKG 60