SPRY domain at N-terminus of ring finger protein 123; This SPRY domain is found at the N-terminus of RING finger protein 123 domain (also known as E3 ubiquitin-protein ligase RNF123). The ring finger domain motif is present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RNF123 displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor p27 (Kip1).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916  102 TIRGTCCVFKGKWQYELMLGSKGVMQVGWVTSNCKFSQEKGVGDTQDSYAYDGNRVRKWNVSTYKYGEPWLAGDVIGCCL 181
Cdd:cd12882      1 SIRANACVYKGKWMYEVTLGTKGIMQIGWATISCRFTQEEGVGDTRDSYAYDGNRVRKWNVSTQKYGEPWVAGDVIGCCI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2015531916  182 DLDEGTVHFYRNGRSLGVAFDRVRAGPGLVYFPAVSLAFGENLVANFG 229
Cdd:cd12882     81 DLDKGTISFYRNGRSLGVAFDNVRRGPGLAYFPAVSLSFGERLELNFG 128

SPRY domain at N-terminus of ring finger protein 123; This SPRY domain is found at the N-terminus of RING finger protein 123 domain (also known as E3 ubiquitin-protein ligase RNF123). The ring finger domain motif is present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RNF123 displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor p27 (Kip1).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916  102 TIRGTCCVFKGKWQYELMLGSKGVMQVGWVTSNCKFSQEKGVGDTQDSYAYDGNRVRKWNVSTYKYGEPWLAGDVIGCCL 181
Cdd:cd12882      1 SIRANACVYKGKWMYEVTLGTKGIMQIGWATISCRFTQEEGVGDTRDSYAYDGNRVRKWNVSTQKYGEPWVAGDVIGCCI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2015531916  182 DLDEGTVHFYRNGRSLGVAFDRVRAGPGLVYFPAVSLAFGENLVANFG 229
Cdd:cd12882     81 DLDKGTISFYRNGRSLGVAFDNVRRGPGLAYFPAVSLSFGERLELNFG 128

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916   111 KGKWQYELMLGSKGVMQVGWVTSNCKFSQEKGVGDTQDSYAYDGNRVRKWNVSTYK-YGEPW-LAGDVIGCCLDLDEGTV 188
Cdd:smart00449    1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHNSTGPeYGLPLqEPGDVIGCFLDLEAGTI 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 2015531916   189 HFYRNGRSL-GVAFDRVRAGPGLvyFPAVSLAFGENLVANFG 229
Cdd:smart00449   81 SFYKNGKYLhGLAFFDVKFSGPL--YPAFSLGSGNSVRLNFG 120

Zinc finger, C3HC4 type (RING finger);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2015531916 1120 EDQLCTICYAQGNSVRFVPCGHQS-CQLCIMTHLVNNRECFFCKALIEKL 1168
Cdd:pfam13920    1 EDLLCVICLDRPRNVVLLPCGHLClCEECAERLLRKKKKCPICRQPIESV 50

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 2015531916  1124 CTICYAQ-GNSVRFVPCGHQSCQLCIMTHLVN-NRECFFC 1161
Cdd:smart00184    1 CPICLEEyLKDPVILPCGHTFCRSCIRKWLESgNNTCPIC 40

SPRY domain at N-terminus of ring finger protein 123; This SPRY domain is found at the N-terminus of RING finger protein 123 domain (also known as E3 ubiquitin-protein ligase RNF123). The ring finger domain motif is present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RNF123 displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor p27 (Kip1).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916  102 TIRGTCCVFKGKWQYELMLGSKGVMQVGWVTSNCKFSQEKGVGDTQDSYAYDGNRVRKWNVSTYKYGEPWLAGDVIGCCL 181
Cdd:cd12882      1 SIRANACVYKGKWMYEVTLGTKGIMQIGWATISCRFTQEEGVGDTRDSYAYDGNRVRKWNVSTQKYGEPWVAGDVIGCCI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2015531916  182 DLDEGTVHFYRNGRSLGVAFDRVRAGPGLVYFPAVSLAFGENLVANFG 229
Cdd:cd12882     81 DLDKGTISFYRNGRSLGVAFDNVRRGPGLAYFPAVSLSFGERLELNFG 128

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916  113 KWQYE--LMLGSKGVMQVGWVTSNCKFSQEKGVGDTQDSYAYDGNRVRKWNVSTY-KYGEP-WLAGDVIGCCLDLDEGTV 188
Cdd:pfam00622    1 RHYFEveIFGQDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWASTSpLTGLPlFEPGDVIGCFLDYEAGTI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2015531916  189 HFYRNGRSLGVAFDRVRAGPGLvyFPAVSLAFGENLVANFGAT 231
Cdd:pfam00622   81 SFTKNGKSLGYAFRDVPFAGPL--FPAVSLGAGEGLKFNFGLR 121

SPRY domain associated with DEAD box gene DDX1; This SPRY domain is associated with the DEAD box gene, DDX1, an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication. It is suggested that DDX1 acts as a cellular cofactor by promoting oligomerization of Rev on the Rev response element (RRE). DDX1 RNA is overexpressed in breast cancer, data showing a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1, thus potentially serving as an effective prognostic biomarker for early recurrence in primary breast cancer. DDX1 also interacts with RelA and enhances nuclear factor kappaB-mediated transcription. DEAD-box proteins are associated with all levels of RNA metabolism and function, and have been implicated in translation initiation, transcription, RNA splicing, ribosome assembly, RNA transport, and RNA decay.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916   84 TFIVDKDRLGVSSQSNF--NTIRGTCCVF-KGKWQYELMLGSKGVMQVGWVTSNCKFSqekgVGDTQDSYAYDGNRVRKW 160
Cdd:cd12873      9 ALAISPDGLLCQSREEKgwQGCRATKGVKgKGKYYYEVTVTDEGLCRVGWSTEDASLD----LGTDKFGFGYGGTGKKSH 84

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2015531916  161 NVSTYKYGEPWLAGDVIGCCLDLDEGTVHFYRNGRSLGVAFDRVRAGPGLVYFPAVSLAFGEnLVANFGATP 232
Cdd:cd12873     85 GRQFDDYGEPFGLGDVIGCYLDLDNGTISFSKNGKDLGKAFDIPPHLRNSALFPAVCLKNAE-VEFNFGDKP 155

SPRY domain in Ash2; This SPRY domain is found at the C-terminus of Ash2 (absent, small, or homeotic discs 2) -like proteins, core components of all mixed-lineage leukemia (MLL) family histone methyltransferases. Ash2 is a member of the trithorax group of transcriptional regulators of the Hox genes. Recent studies show that the SPRY domain of Ash2 mediates the interaction with RbBP5 and has an important role in regulating the methyltransferase activity of MLL complexes. In yeast, Ash2 is involved in histone methylation and is required for the earliest stages of embryogenesis.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916   87 VDKDRLGVSSQSNFNTIRGTCCVFKGKWQYELMLGSKGVMQVGWVtsNCKFSQEKG-----VGDTQDSYAY---DGNRVR 158
Cdd:cd12872      3 LSEDRLTVTGEKGYRMARANHGVREGKWYFEVKILEGGGTETGHV--RVGWSRREAslqapVGYDKYSYAIrdkDGSKFH 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2015531916  159 kwNVSTYKYGEPWL-AGDVIGCCLDLDEgtVHFYRNGRSLGVAFDRVraGPGLVYFPAVSLAFGENLVANFG 229
Cdd:cd12872     81 --QSRGKPYGEPGFkEGDVIGFLITLPK--IEFFKNGKSQGVAFEDI--YGTGGYYPAVSLYKGATVTINFG 146

RING finger, HC subclass, found in RING finger protein 123 (RNF123) and similar proteins; RNF123, also known as Kip1 ubiquitination-promoting complex protein 1 (KPC1), is an E3 ubiquitin-protein ligase that mediates ubiquitination and proteasomal processing of the nuclear factor-kappaB 1 (NF-kappaB1) precursor p105 to the p50 active subunit that restricts tumor growth. It also regulates degradation of heterochromatin protein 1alpha (HP1alpha) and 1beta (HP1beta) in lamin A/C knock-down cells. Moreover, RNF123, together with Kip1 ubiquitylation-promoting complex 2 (KPC2), forms the Kip1 ubiquitination-promoting complex (KPC), acting as a cytoplasmic ubiquitin ligase that regulates degradation of the cyclin-dependent kinase inhibitor p27 (Kip1) at the G1 phase of the cell cycle. RNF123 may also function as a clinically relevant, peripheral state marker of depression. RNF123 contains a C3HC4-type RING-HC finger at the C-terminus.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2015531916 1122 QLCTICYAQGNSVRFVPCGHQSCQLCIMTHLVNNRECFFCKALI 1165
Cdd:cd16541      1 DLCPICYAHPIDAVFLPCGHKSCRSCINRHLMNNKECFFCKATI 44

SPRY domain in heterogeneous nuclear ribonucleoprotein U-like (hnRNP) protein 1; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of heterogeneous nuclear ribonucleoprotein U-like (hnRNP) protein 1 (also known as HNRPUL1 ) which is a major constituent of nuclear matrix or scaffold and binds directly to DNA sequences through the N-terminal acidic region named serum amyloid P (SAP). Its function is specifically modulated by E1B-55kDa in adenovirus-infected cells. HNRPUL1 also participates in ATR protein kinase signaling pathways during adenovirus infection. Two transcript variants encoding different isoforms have been found for this gene. When associated with bromodomain-containing protein 7 (BRD7), it activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916   85 FIVDKDRLGVSSQSN--FNT----IRGTCCVFKGKWQYELMLGSK-------------GVMQVGWVTSNCKFSqekgVGD 145
Cdd:cd12884     12 LKISKDRYSASPLTDegFAYlwagARATYGVTKGKVCFEVKVTENlpvkhlpteetdpHVVRVGWSVDSSSLQ----LGE 87

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2015531916  146 TQDSYAYDGNRvRKW-NVSTYKYGEPWLAGDVIGCCLDLD--EGTVHFYRNGRSLGVAFD-RVRAGPGLVYFPAV 216
Cdd:cd12884     88 EEFSYGYGSTG-KKStNCKFEDYGEPFGENDVIGCYLDFEsePVEISFSKNGKDLGVAFKiSKEELGGKALFPHV 161

SPRY domain-like in bacteria; This family contains SPRY-like domains that are found only in bacterial and are mostly uncharacterized. SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 eukaryotic protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916  112 GKWQYELMLGSKGV---MQVGWVTSN-CKFSQEKGVGDTQDSYA---YDGNRVRKWNVSTYkYGEPWLAGDVIGCCLDLD 184
Cdd:cd12886      1 GKWYWEVTVVSSAAstyAGIGVANAAaTGNNGLNGIELSSIGYSlgvYSGNKLSNGSSVAT-YGAGFTAGDVIGVALDLD 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2015531916  185 EGTVHFYRNGRSLGV---AFDRVRAGPGLVYFPAVSL--AFGENLVANFG 229
Cdd:cd12886     80 AGKIWFYKNGVWQGGgdpAPGTNPAFAGTAMYPAVTGgsSTGGSFTANFG 129

SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2015531916  164 TYKYGEPW-LAGDVIGCCLDLDEGTVHFYRNGRSLGVAFDRVRAgpGLVYFPAVS 217
Cdd:cd12876    104 SRPYTSPFgNQGTIIGVHLDMWRGTLTFYKNGKPLGVAFTGLNG--VKPLYPMVS 156

SPRY domain in HERC1; This SPRY domain is found in the HERC1, a large protein related to chromosome condensation regulator RCC1. It is widely expressed in many tissues, playing an important role in intracellular membrane trafficking in the cytoplasm as well as Golgi apparatus. HERC1 also interacts with tuberous sclerosis 2 (TSC2, tuberin), which suppresses cell growth, and results in the destabilization of TSC2. However, the biological function of HERC1 has yet to be defined.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916   76 FDICTNvGTFIVDKDRLGVSSQSNFNTIRGTCCVFK-GKWQYELML-----GSKGV---MQVGWVTSNCkfsqekgVGDT 146
Cdd:cd12881      6 PEKSTN-CVVVENGGTLVHSSGGRGYGLAATWIGISsGCYQWKFYLvkenrGNEGTcvgVSRKPVTDFN-------YRTS 77

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2015531916  147 QDSY---AYDGN---RVRKWNVSTYKYGepwlAGDVIGCCLDLDEGTVHFYRNGRSLGVAFDRVragPGLVYFPAVS 217
Cdd:cd12881     78 SDMWlyrAYNGNlyhNGEQLLRLSSKFH----QGDYITVVLDMEEGTLSFGKNGEEPGVAFEDV---DATELYPCVM 147

SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4); The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but only SPSB1, SPSB2, and SPSB4 interact with prostate apoptosis response protein 4 (Par-4). They are negative regulators that recruit the ECS E3 ubiquitin ligase complex to polyubiquitinate inducible nitric-oxide synthase (iNOS), resulting in its proteasomal degradation, thus contributing to protection against the cytotoxic effect of iNOS in activated macrophages. It has been shown that SPSB1 and SPSB4 induce the degradation of iNOS more strongly than SPSB2. The Drosophila melanogaster SPSB1 homolog, GUSTAVUS, interacts with the DEAD box RNA helicase Vasa. Suppressor of cytokine signaling (SOCS) proteins negatively regulate signaling from JAK-associated cytokine receptor complexes, and play key roles in the regulation of immune homeostasis.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2015531916  143 VGDTQDSYAYDGNRVRKW----NVSTYKY------GEPWLAGDVIGCCLDLDEGTVHFYRNGRSLGVAFdrvRAGPGLVY 212
Cdd:cd12906     80 VGSNEESWGWDIGRNKLYhdskNQPGWTYpaflepDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAF---RGLKGKKL 156

                   ....*....
gi 2015531916  213 FPAVSLAFG 221
Cdd:cd12906    157 YPIVSAVWG 165

RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. RNF165 contains two serine rich domains, a nuclear localization signal, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is responsible for the enhancement of BMP-Smad1/5/8 signaling in the spinal cord.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2015531916 1119 DEDQLCTICYA---QGNSVRFVPCGHQSCQLCIMTHLVNNRECFFCKALIE 1166
Cdd:cd16682      5 DTDEKCTICLSmleDGEDVRRLPCMHLFHQLCVDQWLAMSKKCPICRVDIE 55

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
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2015531916 1118 LDEDQLCTICYAQGNSVRFVPCGHQ-SCQLCimTHLVNnrECFFCKALIEK 1167
Cdd:cd16714     11 LQEEKLCKICMDRNISIVFIPCGHLvTCKQC--AEALD--KCPICCTVITF 57

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2015531916 1120 EDQLCTICYAQGNSVRFVPCGHQSCQLCIMTHLVNNRECFFCKALI 1165
Cdd:cd16561      1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCRTEL 46

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 2015531916 1122 QLCTICYAQGNSVRFVPCGHQSCQLCIMT-HLVNNRECFFCKALIE 1166
Cdd:cd16710     14 ELCKICAERDKDVRIEPCGHLLCSCCLAAwQHSDSQTCPFCRCEIK 59

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
                   ....*....|....*....|....*....|....*....
gi 2015531916 1124 CTICYAQGNSVRFVPCGHQSCQLCIMTHL-VNNRECFFC 1161
Cdd:cd16449      3 CPICLERLKDPVLLPCGHVFCRECIRRLLeSGSIKCPIC 41

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2015531916 1119 DEDQLCTICYAQGNSVRFVPCGHQSCQLCI--MTHLVNNRECFFCK 1162
Cdd:COG5236     59 EENMNCQICAGSTTYSARYPCGHQICHACAvrLRALYMQKGCPLCR 104

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2015531916 1118 LDEDQLCTICYAQGNSVRFVPCGHQSCQLCIMTHLVNNRECFFCKA 1163
Cdd:COG5432     22 LDSMLRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCRE 67

SPRY domain in Fbxo45 and suppressors of cytokine signaling (SOCS) proteins; This family consists of the SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) as well as F-box protein 45 (Fbxo45), a novel synaptic E3 and ubiquitin ligase. The SPSB protein is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. SPSB1, SPSB2, and SPSB4 interact with prostate apoptosis response protein 4 (Par-4) and are negative regulators that recruit the ECS E3 ubiquitin ligase complex to polyubiquitinate inducible nitric-oxide synthase (iNOS), resulting in its proteasomal degradation. Fbxo45 is related to this family; it is located N-terminal to the SPRY domain, and known to induce the degradation of a synaptic vesicle-priming factor, Munc13-1, via the SPRY domain, thus playing an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse. Suppressor of cytokine signaling (SOCS) proteins negatively regulate signaling from JAK-associated cytokine receptor complexes, and play key roles in the regulation of immune homeostasis.

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gi 2015531916  173 AGDVIGCCLDLDEGTVHFYRNGRSLGVAFdrvRAGPGLVYFPAVSLAFG 221
Cdd:cd12875    115 VPDRILVILDMEDGTLAFEANGEYLGVAF---RGLPGKLLYPAVSAVYG 160

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.

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gi 2015531916 1122 QLCTIC---YAQGNSVRFVPCGHQSCQLCIMTHLVNNRECFFCK 1162
Cdd:cd16673      1 KTCSVCineYATGNKLRRLPCAHEFHIHCIDRWLSENSTCPICR 44

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. RNF12 also acts as a co-regulator for a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.

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gi 2015531916 1124 CTIC---YAQGNSVRFVPCGHQSCQLCIMTHLVNNRECFFCK 1162
Cdd:cd16674      3 CSVCiteYTEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICR 44

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

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gi 2015531916 1120 EDQLCTICYAQGNS---VRFVPCGHQSCQLCIMTHLVNNRECFFCKA 1163
Cdd:cd16680      6 EQTLCVVCFSDFESrqlLRVLPCNHEFHTKCVDKWLKTNRTCPICRA 52

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

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gi 2015531916 1121 DQLCTICYAQ-GNSVRFV-PCGHQSCQLCIMTHLVNNRECFFCKA 1163
Cdd:cd16574      1 DSSCPICLDRfENEKAFLdGCFHAFCFTCILEWSKVKNECPLCKQ 45

RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and similar proteins; This subfamily includes Arabidopsis thaliana MIP1, RING finger protein 4 (RF4) and RING finger protein 298 (RF298). MIP1 interacts with MND1, HOP2 and XRI1. RF4 and RF298 are putative E3 ubiquitin-protein ligase that may mediate E2-dependent protein ubiquitination. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

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gi 2015531916 1124 CTICYAQGNSVRFVPCGHQ-SCQLCIMTHLVNN-RECFFCKALIEK 1167
Cdd:cd23128      6 CVMCMEEERSVVFLPCAHQvVCSGCNDLHEKKGmRECPSCRGEIQE 51