SPRY domain at N-terminus of Really Interesting New Gene (RING) finger domain; This SPRY domain is found at the N-terminus of RING finger domains which are present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RING-finger domain is a type of Zn-finger that binds two Zn atoms and is identified in proteins with a wide range of functions such as viral replication, signal transduction, and development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370469427 390 GVWYYEVTVVTSGVMQIGWATRDSKFLNHEGYGIGDDEYSCAYDGCRQLIWYNARSKPHIHPCWKEGDTVGFLLDLNEKQ 469
Cdd:cd12883     1 GVWYYEVTVLTSGVMQIGWATKDSKFLNHEGYGIGDDEYSCAYDGCRQLIWYNAKSKPHTHPRWKPGDVLGCLLDLNKKQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1370469427 470 MIFFLNGNQLPPEKQVFSSTVSGFFAAASFMSYQQCEFNFG 510
Cdd:cd12883    81 MIFSLNGNRLPPERQVFTSAKSGFFAAASFMSFQQCEFNFG 121

SPRY domain at N-terminus of Really Interesting New Gene (RING) finger domain; This SPRY domain is found at the N-terminus of RING finger domains which are present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RING-finger domain is a type of Zn-finger that binds two Zn atoms and is identified in proteins with a wide range of functions such as viral replication, signal transduction, and development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370469427 390 GVWYYEVTVVTSGVMQIGWATRDSKFLNHEGYGIGDDEYSCAYDGCRQLIWYNARSKPHIHPCWKEGDTVGFLLDLNEKQ 469
Cdd:cd12883     1 GVWYYEVTVLTSGVMQIGWATKDSKFLNHEGYGIGDDEYSCAYDGCRQLIWYNAKSKPHTHPRWKPGDVLGCLLDLNKKQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1370469427 470 MIFFLNGNQLPPEKQVFSSTVSGFFAAASFMSYQQCEFNFG 510
Cdd:cd12883    81 MIFSLNGNRLPPERQVFTSAKSGFFAAASFMSFQQCEFNFG 121

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 1370469427 391 VWYYEVTV--VTSGVMQIGWATRDSKFLNHEGygIGDDEYSCAYDGCRQLIWYNARSKPHIHPCWKEGDTVGFLLDLNEK 468
Cdd:pfam00622   1 RHYFEVEIfgQDGGGWRVGWATKSVPRKGERF--LGDESGSWGYDGWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1370469427 469 QMIFFLNGNQLPPEKQVFSSTvSGFFAAASFMSYQQCEFNFG 510
Cdd:pfam00622  79 TISFTKNGKSLGYAFRDVPFA-GPLFPAVSLGAGEGLKFNFG 119

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370469427 554 RENCCSLCCDEVADTQLKPCGHSDLCMDCALQLE----TCPLCRKEIVSR 599
Cdd:pfam13920   1 EDLLCVICLDRPRNVVLLPCGHLCLCEECAERLLrkkkKCPICRQPIESV 50

SPRY domain at N-terminus of Really Interesting New Gene (RING) finger domain; This SPRY domain is found at the N-terminus of RING finger domains which are present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RING-finger domain is a type of Zn-finger that binds two Zn atoms and is identified in proteins with a wide range of functions such as viral replication, signal transduction, and development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370469427 390 GVWYYEVTVVTSGVMQIGWATRDSKFLNHEGYGIGDDEYSCAYDGCRQLIWYNARSKPHIHPCWKEGDTVGFLLDLNEKQ 469
Cdd:cd12883     1 GVWYYEVTVLTSGVMQIGWATKDSKFLNHEGYGIGDDEYSCAYDGCRQLIWYNAKSKPHTHPRWKPGDVLGCLLDLNKKQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1370469427 470 MIFFLNGNQLPPEKQVFSSTVSGFFAAASFMSYQQCEFNFG 510
Cdd:cd12883    81 MIFSLNGNRLPPERQVFTSAKSGFFAAASFMSFQQCEFNFG 121

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 1370469427 380 SVRCTFCVDAGVWYYEVTVVTSGVMQIGWATRDSKFLNHEgyGIGDDEYSCAYDGCRQLIWyNARSKPHIHPcWKEGDTV 459
Cdd:cd12882     1 SIRANACVYKGKWMYEVTLGTKGIMQIGWATISCRFTQEE--GVGDTRDSYAYDGNRVRKW-NVSTQKYGEP-WVAGDVI 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370469427 460 GFLLDLNEKQMIFFLNGNQLPPE-KQVFSSTVSGFFAAASFMSYQQCEFNFG 510
Cdd:cd12882    77 GCCIDLDKGTISFYRNGRSLGVAfDNVRRGPGLAYFPAVSLSFGERLELNFG 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 1370469427 391 VWYYEVTV--VTSGVMQIGWATRDSKFLNHEGygIGDDEYSCAYDGCRQLIWYNARSKPHIHPCWKEGDTVGFLLDLNEK 468
Cdd:pfam00622   1 RHYFEVEIfgQDGGGWRVGWATKSVPRKGERF--LGDESGSWGYDGWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1370469427 469 QMIFFLNGNQLPPEKQVFSSTvSGFFAAASFMSYQQCEFNFG 510
Cdd:pfam00622  79 TISFTKNGKSLGYAFRDVPFA-GPLFPAVSLGAGEGLKFNFG 119

SPRY domain 2 (SPRY2) of ryanodine receptor (RyR); This SPRY domain (SPRY2) is the second of three structural repeats in all three isoforms of the ryanodine receptor (RyR), which are the major Ca2+ release channels in the membranes of sarcoplasmic reticulum (SR). There are three RyR genes in mammals; the skeletal RyR1, the cardiac RyR2 and the brain RyR3. The three SPRY domains are located in the N-terminal part of the cytoplasmic region of the RyRs, The SPRY2 domain has been shown to bind to the dihydropryidine receptor (DHPR) II-III loop and the ASI region of RyR1

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370469427 384 TFCVDAGVWYYEVTVVTSGVMQIGWATRDSkflnHEGYGIGDDEYSCAYDGCRQLIWYNARSkpHIHPCWKEGDTVGFLL 463
Cdd:cd12878     8 TYAVTSGKWYFEFEVLTSGYMRVGWARPGF----RPDLELGSDDLSYAFDGFLARKWHQGSE--SFGKQWQPGDVVGCML 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370469427 464 DLNEKQMIFFLNGNQLppEKQVFSSTV-------SGFFAAASFMSYQQCEFNFG 510
Cdd:cd12878    82 DLVDRTISFTLNGELL--IDSSGSEVAfkdieigEGFVPACSLGVGQKGRLNLG 133

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 1370469427 353 LNSNDVSEYLKISPHGLEARC-DASSFESVRCTFCV-DAGVWYYEVTVVTSGVMQIGWATRDSKFlnhegyGIGDDEYSC 430
Cdd:cd12873     1 MNPYDRDAALAISPDGLLCQSrEEKGWQGCRATKGVkGKGKYYYEVTVTDEGLCRVGWSTEDASL------DLGTDKFGF 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370469427 431 AYDG------CRQLIWYnarSKPHIHpcwkeGDTVGFLLDLNEKQMIFFLNGNQLPPEKQVFSSTV-SGFFAAASfMSYQ 503
Cdd:cd12873    75 GYGGtgkkshGRQFDDY---GEPFGL-----GDVIGCYLDLDNGTISFSKNGKDLGKAFDIPPHLRnSALFPAVC-LKNA 145

                         170
                  ....*....|
gi 1370469427 504 QCEFNFGAKP 513
Cdd:cd12873   146 EVEFNFGDKP 155

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370469427 554 RENCCSLCCDEVADTQLKPCGHSDLCMDCALQLE----TCPLCRKEIVSR 599
Cdd:pfam13920   1 EDLLCVICLDRPRNVVLLPCGHLCLCEECAERLLrkkkKCPICRQPIESV 50

RING finger, HC subclass, found in myosin regulatory light chain interacting protein (MYLIP) and similar proteins; MYLIP, also known as inducible degrader of the low-density lipoprotein (LDL)-receptor (IDOL), or MIR, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR, and LRP8. Its activity depends on E2 ubiquitin-conjugating enzymes of the UBE2D family. MYLIP stimulates clathrin-independent endocytosis and acts as a sterol-dependent inhibitor of cellular cholesterol uptake by binding directly to the cytoplasmic tail of the LDLR and promoting its ubiquitination via the UBE2D1/E1 complex. The ubiquitinated LDLR then enters the multivesicular body (MVB) protein-sorting pathway and is shuttled to the lysosome for degradation. Moreover, MYLIP has been identified as a novel ERM-like protein that affects cytoskeleton interactions regulating cell motility, such as neurite outgrowth. The ERM proteins includes ezrin, radixin, and moesin, which are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. MYLIP contains an ERM-homology domain and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQLETCPLCRKEI 596
Cdd:cd16523     5 CMVCCEEEINSAFCPCGHMVCCESCAAQLQSCPVCRSRV 43

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 1370469427 556 NCCSLCCDEVADTQLKPCGHSDLCMDCALQLETCPLCRKEIVSRIR 601
Cdd:cd16500     1 DLCKICMDAAIDCVLLECGHMVTCTDCGKKLSECPICRQYVVRVVH 46

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 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQLETCPLCRKEIVSRIR 601
Cdd:cd16515     4 CVVCMDAESQVIFLPCGHVCCCQTCSSSLSTCPLCRADITQRVR 47

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQL----ETCPLCRKEIVSRIR 601
Cdd:cd23129     5 CVVCMDAPRDAVCVPCGHVAGCMSCLKALmqssPLCPICRAPVRQVIK 52

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1370469427 555 ENCCSLCCDEVADTQLKPCGHSDLCMDCALQLETCPLCRKEIVSRI 600
Cdd:cd16706     4 DNLCRICMDAVIDCVLLECGHMVTCTKCGKRMSECPICRQYVVRAV 49

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 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQLE-----TCPLCRKEIVSRIR 601
Cdd:cd16786     5 CTVCFDSEVDTVIYTCGHMCLCNSCGLKLKrqinaCCPICRRVIKDVIK 53

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1370469427 555 ENCCSLCCDEVADTQLKPCGHSDLCMDCALQLETCPLCRKEIVSRI 600
Cdd:cd16707     2 ENLCKICMDSPIDCVLLECGHMVTCTKCGKRMSECPICRQYVIRAV 47

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQL-----ETCPLCRKEIVSRIRQIS 604
Cdd:cd16721     7 CSICFESEVIAALVPCGHNLFCMECANRIceknePQCPVCHAAVTQAIRIFS 58

RING finger, HC subclass, found in RNA-binding proteins of the evolutionarily-conserved MEX-3 family; MEX-3 phosphoproteins are found in vertebrates. They are mediators of post-transcriptional regulation in different organisms, and have been implicated in many core biological processes, including embryonic development, epithelial homeostasis, immune responses, metabolism, and cancer. They contain two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. They shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway. The RNA-binding protein MEX-3 from nematode Caenorhabditis elegans is the founding member of the MEX-3 family. Due to the lack of a RING-HC finger, it is not included here.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQL-----ETCPLCRKEIVSRIR 601
Cdd:cd16518     3 CVVCFESEVVAALVPCGHNLFCMECANRIceksdPECPVCHTPVTQAIR 51

RING finger, HC subclass, found in RNA-binding protein MEX3D; MEX3D, also known as RING finger and KH domain-containing protein 1 (RKHD1), RING finger protein 193 (RNF193), or TINO, is an RNA-binding phosphoprotein that controls the stability of the transcripts coding for the anti-apoptotic protein BCL-2, and negatively regulates BCL-2 in HeLa cells. MEX3D 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, MEX3D shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370469427 552 SIREncCSLCCDEVADTQLKPCGHSDLCMDCALQL-----ETCPLCRKEIVSRIRQIS 604
Cdd:cd16723     9 SARE--CVVCFESEVIAALVPCGHNLFCMECAIRIcgksePECPACHTPATQAIHIFS 64

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and similar proteins; Tripartite motif-containing proteins TRIM9 and TRIM67 belong to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, consisting of three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also known as TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H, also known as glucosidase II beta, a protein kinase C substrate.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1370469427 558 CSLCCDEVADTQLKPCGHSdLCMDCALQLE-TCPLCRK 594
Cdd:cd16576     6 CPVCGSLFTEPVILPCSHN-LCLGCALNIQlTCPICHK 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQ-----LETCPLCRKEIVSRIR 601
Cdd:cd16722     4 CVICFENEVIAALVPCGHNLFCMECANKicekeTPSCPVCQTAVTQAIQ 52

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370469427 558 CSLCCDEVAD-TQLKPCGHSdLCMDCAL----QLETCPLCRKEIVSRIRQ 602
Cdd:cd23130     3 CPICLDDPEDeAITLPCLHQ-FCYTCILrwlqTSPTCPLCKTPVTSIIHS 51

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.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQL--ETCPLCR 593
Cdd:cd16649     3 CVVCLENPASVLLLPCRHLCLCEVCAKGLrgKTCPICR 40

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 1370469427 558 CSLCCDEVADTQLKPCGHSDLCMDCALQLET----CPLCR 593
Cdd:cd16789     3 CVICLSDPRDTAVLPCRHLCLCSDCAEVLRYqsnkCPICR 42

RING finger, HC subclass, found in mind bomb MIB1, MIB2, RGLG1, RGLG2, and similar proteins; MIBs are large, multi-domain E3 ubiquitin-protein ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. They are also responsible for TBK1 K63-linked ubiquitination and activation, promoting interferon production and controlling antiviral immunity. Moreover, MIBs selectively control responses to cytosolic RNA and regulate type I interferon transcription. Both MIB1 and MIB2 have similar domain architectures, which consist of 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, where MIB1 and MIB2 contain three and two C3HC4-type RING-HC fingers, respectively. This model corresponds to the third RING-HC finger of MIB1, as well as the second RING-HC finger of MIB2. In addition to MIB1 and MIB2, the RING-HC fingers of RING domain ligase RGLG1, RGLG2 and similar proteins from plant are also included in this model. RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. All RGLG proteins contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

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gi 1370469427 557 CCSLCCDEVADTQLKpCGHSdLCMDCALQLETCPLCRKEI 596
Cdd:cd16520     2 LCPICMERKKNVVFL-CGHG-TCQKCAEKLKKCPICRKPI 39

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370469427 381 VRCTFCVDAGVWYYEVTVV-----TSgvMQIGWATRDSKfLNHEGY----GIGDDEYSC--AYDGcrqLIWYNARSKPHI 449
Cdd:cd12876    35 VRGTKPLTNGQHYWEIKMSspvygTD--MMVGVGTKKAD-LHAYRYefcsLLGEDEESWglSYKG---LLWHDGQSRPYT 108

                          90       100
                  ....*....|....*....|....*..
gi 1370469427 450 HPCWKEGDTVGFLLDLNEKQMIFFLNG 476
Cdd:cd12876   109 SPFGNQGTIIGVHLDMWRGTLTFYKNG 135

RING finger, HC subclass, found in zinc finger protein 598 (ZNF598) and similar proteins; ZNF598 associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammals (m4EHP) by binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian. ZNF598 harbors a C3HC4-type RING-HC finger at its N-terminus.

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gi 1370469427 556 NCCSLCCDEVADTQLKPCGHSdLCMDCALQLET------CPLCRKEI 596
Cdd:cd16615     1 ETCVICCEEIEYFAVGPCNHP-VCYKCSLRMRVlykdkyCPICRTEL 46

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

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                  ....*....|....*....|....*....|....*....|....*.
gi 1370469427 558 CSLCCDEVADTQLKPCGHSdLCMDCALQ-LE----TCPLCRKEIVS 598
Cdd:cd16550     3 CPICLEILVEPVTLPCNHT-LCMPCFQStVEkaslCCPLCRLRISS 47

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).

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gi 1370469427 558 CSLCCDEVADTQLKPCGHSdLCMDC--ALQ---LETCPLCRKEIVSR 599
Cdd:cd16710    16 CKICAERDKDVRIEPCGHL-LCSCClaAWQhsdSQTCPFCRCEIKGR 61

Ring finger domain;

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gi 1370469427 556 NCCSLCCDEV---ADTQLKPCGHSdLCMDCALQL----ETCPLCR 593
Cdd:pfam13639   1 DECPICLEEFeegDKVVVLPCGHH-FHRECLDKWlrssNTCPLCR 44

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

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gi 1370469427 557 CCSLCCDEVADTQLKPCGHSDLCMDCALQLE-----TCPLCRKEIVS 598
Cdd:cd16620     5 KCPICKDLMKDAVLTPCCGNSFCDECIRTALleedfTCPTCKEPDVS 51

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370469427 374 DASSfesVRCTFCVDA--GVWYYEVTVVTSGV---MQIGWATRDSKfLNH------EGYGI-GDD--EYSCAYDGcrqli 439
Cdd:cd12909    10 DAAA---VRANHPIPPqcGIYYFEVKIISKGRdgyIGIGFSTKDVN-LNRlpgwepHSWGYhGDDghSFCSSGTG----- 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1370469427 440 wynarsKPHiHPCWKEGDTVGFLLDLNEKQMIFFLNGNQLP 480
Cdd:cd12909    81 ------KPY-GPTFTTGDVIGCGINFRDNTAFYTKNGVNLG 114

second 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. Especially, 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 second RING-HC finger.

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                  ....*....|....*....|....*....|....*....|....
gi 1370469427 558 CSLCCDEVADTQLKpCGHSDlCMDCALQLETCPLCRKEIVSRIR 601
Cdd:cd16728     7 CPICIDNHIKLVFQ-CGHGS-CIECSSALKACPICRQAIRERIQ 48