Zinc finger, C3HC4 type (RING finger);

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                  ....*....|....*....|....*....|....*....|....*....|
gi 71987791   167 RLQCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPlLCPICHMHVQSF 216
Cdd:pfam13920   2 DLLCVICLDRPRNVVLLPCGHLCLCEECAERLLRKKK-KCPICRQPIESV 50

Zinc finger, C3HC4 type (RING finger);

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                  ....*....|....*....|....*....|....*....|....*....|
gi 71987791   167 RLQCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPlLCPICHMHVQSF 216
Cdd:pfam13920   2 DLLCVICLDRPRNVVLLPCGHLCLCEECAERLLRKKK-KCPICRQPIESV 50

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

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                ....*....|....*....|....*....|....*....|....*....|....*....
gi 71987791 162 SINEARLQCFLCKLTEKRVLLRPCNHLcFCEPC-NDTFQKQIPLLCPICHMHVQSFEIV 219
Cdd:COG5574 210 FIPLADYKCFLCLEEPEVPSCTPCGHL-FCLSClLISWTKKKYEFCPLCRAKVYPKKVI 267

Zinc finger, C3HC4 type (RING finger);

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                  ....*....|....*....|....*....|....*....|....*....|
gi 71987791   167 RLQCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPlLCPICHMHVQSF 216
Cdd:pfam13920   2 DLLCVICLDRPRNVVLLPCGHLCLCEECAERLLRKKK-KCPICRQPIESV 50

Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 (CGRRF1), RNF156 (MGRN1), RNF157 and similar proteins; This subfamily corresponds to a group of RING finger proteins containing a 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. Cell growth regulator with RING finger domain protein 1 (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. 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 after viral infection and promoting degradation of IRF3, another important component required for virus-triggered interferon induction. Mahogunin ring finger-1 (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. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase 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.

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                ....*....|....*....|....*....|....*....|
gi 71987791 170 CFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIpllCPIC 209
Cdd:cd16649   3 CVVCLENPASVLLLPCRHLCLCEVCAKGLRGKT---CPIC 39

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.

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                ....*....|....*....|....*....|....*....|...
gi 71987791 168 LQCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKqipllCPICH 210
Cdd:cd16614   1 KKCMKCEERNRSVAVLPCQHYVLCEQCAETATE-----CPYCH 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.

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                ....*....|....*....|....*....|....*....|
gi 71987791 170 CFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPlLCPIC 209
Cdd:cd16789   3 CVICLSDPRDTAVLPCRHLCLCSDCAEVLRYQSN-KCPIC 41

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1B (NEURL1B); NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling through working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. NEURL1B contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger 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 71987791 169 QCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPLLCPIC 209
Cdd:cd16786   4 ECTVCFDSEVDTVIYTCGHMCLCNSCGLKLKRQINACCPIC 44

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.

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                ....*....|....*....|....*....|....*....|..
gi 71987791 168 LQCFLCKLTEKRVLLRPCNHLcFCEPCNDTFQKQIPLLCPIC 209
Cdd:cd16449   1 LECPICLERLKDPVLLPCGHV-FCRECIRRLLESGSIKCPIC 41

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and similar proteins; XBAT35, also known as ankyrin repeat domain and RING finger-containing protein XBAT35, or RING-type E3 ubiquitin transferase XBAT35, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. It contains a typical C3HC4-type RING-HC finger.

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                ....*....|....*....|....*....|....*....|....*..
gi 71987791 169 QCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPLlCPICHMHVQS 215
Cdd:cd23129   4 ECVVCMDAPRDAVCVPCGHVAGCMSCLKALMQSSPL-CPICRAPVRQ 49

RING finger, HC subclass, found in RNA-binding protein MEX3B; MEX3B, also known as RING finger and KH domain-containing protein 3 (RKHD3), or RING finger protein 195 (RNF195), is an RNA-binding phosphoprotein that localizes in P-bodies and stress granules, which are two structures involved in the storage and turnover of mRNAs. It regulates the spatial organization of the Rap1 pathway that orchestrates Sertoli cell functions. It has a 3' long conserved untranslated region (3'LCU)-mediated fine-tuning system for mRNA regulation in early vertebrate development such as anteroposterior (AP) patterning and signal transduction. MEX3B 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, MEX3B shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

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                ....*....|....*....|....*....|....*....|....*
gi 71987791 169 QCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPLLCPICHMHV 213
Cdd:cd16721   6 DCSICFESEVIAALVPCGHNLFCMECANRICEKNEPQCPVCHAAV 50

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1A (NEURL1A) and similar proteins; NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in the medulloblastoma. NEURL1A contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger 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.

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                ....*....|....*....|....*....|....*....|.
gi 71987791 169 QCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKQIPLLCPIC 209
Cdd:cd16785   6 ECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNACCPIC 46

RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor protein family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity, which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-c, as well as two invertebrate Cbl-family proteins, D-Cbl in Drosophila and Sli-1 in C. elegans. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating activated tyrosine kinases and targeting them for degradation. D-Cbl associates with the Drosophila epidermal growth factor receptor (EGFR) and overexpression of D-Cbl in the eye of Drosophila embryos inhibits EGFR-dependent photoreceptor cell development. Sli-1 is a negative regulator of the Let-23 receptor tyrosine kinase, an EGFR homolog, in vulva development. Cbl proteins in this subfamily consist of a highly conserved N-terminal half that includes 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) and a C3HC4-type RING-HC finger, both of which are required for Cbl-mediated downregulation of RTKs, and a divergent C-terminal region.

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                ....*....|....*....|....*....|....*....|
gi 71987791 170 CFLCKLTEKRVLLRPCNHLcFCEPCNDTFQKQIPLLCPIC 209
Cdd:cd16502   4 CKICAENDKDVRIEPCGHL-LCTPCLTSWQDSDGQTCPFC 42

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.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 71987791 170 CFLCKLTEKRVLLRPCNHLCFCEPC-NDTFQKQIPlLCPICHMHV-QSFEI 218
Cdd:cd16722   4 CVICFENEVIAALVPCGHNLFCMECaNKICEKETP-SCPVCQTAVtQAIQI 53

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 71987791 169 QCFLCKLTEKRVLLRPCNHLCFCEPCNDTFQKqipllCPIC 209
Cdd:cd16772   2 KCIVCQERDRSIVLQPCQHYVLCEHCAASKPE-----CPYC 37