RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and similar proteins; TRAF2, also known as tumor necrosis factor type 2 receptor-associated protein 3, is an E3 ubiquitin-protein ligase that was identified as a 75 kDa tumor necrosis factor receptor (TNF-R2)-associated signaling protein. It interacts with members of the TNF receptor superfamily and connects the receptors to downstream signaling proteins. It also mediates K63-linked polyubiquitination of RIP1, a kinase pivotal in TNFalpha-induced NF-kappaB activation. Moreover, TRAF2 regulates peripheral CD8(+) T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15. It also acts as an important biological suppressor of necroptosis. It inhibits TNF-related apoptosis inducing ligand (TRAIL)- and CD95L-induced apoptosis and necroptosis. TRAF2 contains an N-terminal domain with a typical C3HC4-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 16549281  31 KYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAACV 73
Cdd:cd16639   1 KYLCSDCRNILRRPFQAQCGHRYCSYCLKKILSSGPQKCAACI 43

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281    28 LEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPqNCAACVHEgiyeegisilESSSAFPDNAARRE-VESLPAV 106
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQP-KCPLCRAE----------DQESKLRSNWLVSEiVESFKNL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281   107 CPSdgctwkgtLKEYeVKMPACGMVtEAPAVGSrPRSPSSYDLVlhvpltgAEACLMSVEEETELLLRSCHEGR------ 180
Cdd:TIGR00599  92 RPS--------LLEF-LRIPKTTPV-ENPDLAG-PENSSKIELI-------EESESDGVDAEDEDLQRSATSSRalaars 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 16549281   181 --CPLM---------------------LTECPACKGLVRLGEKERHLEHECP 209
Cdd:TIGR00599 154 taDILQlssdpskrndadyrseppnegLVQCPICQQRMPEKAVERHLDSECL 205

RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and similar proteins; TRAF2, also known as tumor necrosis factor type 2 receptor-associated protein 3, is an E3 ubiquitin-protein ligase that was identified as a 75 kDa tumor necrosis factor receptor (TNF-R2)-associated signaling protein. It interacts with members of the TNF receptor superfamily and connects the receptors to downstream signaling proteins. It also mediates K63-linked polyubiquitination of RIP1, a kinase pivotal in TNFalpha-induced NF-kappaB activation. Moreover, TRAF2 regulates peripheral CD8(+) T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15. It also acts as an important biological suppressor of necroptosis. It inhibits TNF-related apoptosis inducing ligand (TRAIL)- and CD95L-induced apoptosis and necroptosis. TRAF2 contains an N-terminal domain with a typical C3HC4-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 16549281  31 KYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAACV 73
Cdd:cd16639   1 KYLCSDCRNILRRPFQAQCGHRYCSYCLKKILSSGPQKCAACI 43

TNF receptor-associated factor BIRC3 binding domain; This domain is found in TNF receptor-associated factor 1 and 2 (TRAF1 and TRAF2), where it binds to Baculoviral IAP repeat-containing protein 3 (BIRC3) (cIAP2).

                          10        20
                  ....*....|....*....|....*.
gi 16549281   251 REKFQDQDKIEALSSKVQQLERSIGL 276
Cdd:pfam16673  39 RQRRLDQDKIESLENKIRQLERSIAL 64

TRAF-type zinc finger;

                          10        20
                  ....*....|....*....|....*...
gi 16549281   230 HHEVCPKFPLTC-DGCGKKKIPREKFQD 256
Cdd:pfam02176   1 HLETCPFFPIPCpNGCCKKKILREDLPD 28

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 16549281    34 CSACRNVLRRPFQA-QCGHRYCSFCLASILSSGPQNCAAC 72
Cdd:pfam00097   1 CPICLEEPKDPVTLlPCGHLFCSKCIRSWLESGNVTCPLC 40

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 16549281     34 CSACRNV-LRRPFQAQCGHRYCSFCLASILSSGPQNCAAC 72
Cdd:smart00184   1 CPICLEEyLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF1 subfamily, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF1 expression is the most restricted among the TRAFs. It is found exclusively in activated lymphocytes, dendritic cells and certain epithelia. TRAF1 associates, directly or indirectly through heterodimerization with TRAF2, with the TNFR family receptors TNFR-2, CD30, RANK, CD40 and LMP1, among others. It also binds the intracellular proteins TRADD, TANK, TRIP, RIP1, RIP2 and FLIP. TRAF1 is unique among the TRAFs in that it lacks a RING domain, which is critical for the activation of nuclear factor-kappaB and Jun NH2-terminal kinase. Studies on TRAF1-deficient mice suggest that TRAF1 has a negative regulatory role in TNFR-mediated signaling events. TRAF1 contains one zinc finger and one TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281 298 GVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVT 377
Cdd:cd03779   1 GTFLWKITDVSQKQRESSHGRDVSLCSPAFYTAKYGYKVCLRLYLNGDGAGKGTHISLFFVIMKGEYDALLPWPFRHKVT 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 16549281 378 LMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEA-KNSYVRDDAIFIKAIVD 443
Cdd:cd03779  81 FMLLDQNNREHVIDAFRPDLSSASFQRPVSDMNVASGCPLFFPLKKLQSpKHAYCKDDTIYIKCVVD 147

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF3 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF3 was first described as a molecule that binds the cytoplasmic tail of CD40. However, it is not required for CD40 signaling. More recently, TRAF3 has been identified as a key regulator of type I interferon (IFN) production and the mammalian innate antiviral immunity. It mediates IFN responses in Toll-like receptor (TLR)-dependent as well as TLR-independent viral recognition pathways. It is also a key element in immunological homeostasis through its regulation of the anti-inflammatory cytokine interleukin-10. TRAF3 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281 260 IEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLR 339
Cdd:cd03777   1 TGLLESQLSRHDQMLSVHDIRLADMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCAR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281 340 IYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVTLMLLDQN-NREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLF 418
Cdd:cd03777  81 VYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVTLMLMDQGsSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVF 160

                       170       180
                ....*....|....*....|....*..
gi 16549281 419 CPVSKMEaKNSYVRDDAIFIKAIVDLT 445
Cdd:cd03777 161 VAQTVLE-NGTYIKDDTIFIKVIVDTS 186

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF4 is highly expressed during embryogenesis, especially in the central and peripheral nervous system. Studies using TRAF4-deficient mice show that TRAF4 is required for neurogenesis, as well as the development of the trachea and the axial skeleton. In addition, TRAF4 augments nuclear factor-kappaB activation triggered by GITR (glucocorticoid-induced TNFR), a receptor expressed in T-cells, B-cells and macrophages. It also participates in counteracting the signaling mediated by Toll-like receptors through its association with TRAF6 and TRIF. DTRAF1 plays a pivotal role in the development of eye imaginal discs and photosensory neuron arrays in Drosophila. TRAF4 contains a RING finger domain, seven zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281 298 GVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVT 377
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 16549281 378 LMLLDQNN-----REHVIDAFRPDVTSSSFQRPVNDMNIAS----GCPLFcpVSKMEAK-NSYVRDDAIFIKAIVD 443
Cdd:cd03781  81 FTLLDQSDpslskPQHITETFTPDPTWKNFQKPSASRLDEStlgfGYPKF--ISHEDLKkRNYIKDDAIFLRASVE 154

MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281 298 GVFIWKISDFARKRQEAvagripaIFSPAFYtsRYGYKMCLRIYLNGDGTgRGTHLSLFFVVMKGPNDaLLRWPFNQKVT 377
Cdd:cd00121   1 GKHTWKIVNFSELEGES-------IYSPPFE--VGGYKWRIRIYPNGDGE-SGDYLSLYLELDKGESD-LEKWSVRAEFT 69

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 16549281 378 LMLLDQNNREHVIDAFRPDVTSSSfqrpvndmNIASGCPLFCPVSKMEaKNSYVRDDAIFIKAIVD 443
Cdd:cd00121  70 LKLVNQNGGKSLSKSFTHVFFSEK--------GSGWGFPKFISWDDLE-DSYYLVDDSLTIEVEVK 126

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281    299 VFIWKISDFARkrqeavAGRIPAIFSPAFYtsRYGYKMCLRIYLNGDgtgrgtHLSLFFVVMKGPNDALlRWPFNQKVTL 378
Cdd:smart00061   1 VLSHTFKNVSR------LEEGESYFSPSEE--HFNIPWRLKIYRKNG------FLSLYLHCEKEECDSR-KWSIEAEFTL 65

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 16549281    379 MLLDQNNREHvidafrPDVTSSSFQRPvndmnIASGCPLFC 419
Cdd:smart00061  66 KLVSQNGKSL------SKKDKHVFEKP-----SGWGFSKFI 95

Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. The beta subunit is a type I membrane protein, which forms homodimers or heterotetramers (alpha2beta2 or alpha3beta). Meprin beta shows preference for acidic residues at the P1 and P1' sites of its substrate. Among its best substrates are growth factors and chemokines such as gastrin and osteopontin. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281 300 FIWKISDFARKRQEAVAGRipAIFSPAFYTSRyGYKMCLRIYLNGDgTGRGTHLSLFFVVMKGPNDALLRWPFN-QKVTL 378
Cdd:cd03782   4 HIWHIRNFTQLLATTPPNG--KIYSPPFLSST-GYSFQVGLYLNGT-DDYPGNLAIYLHLTSGPNDDQLQWPCPwQQATM 79

                ....*.
gi 16549281 379 MLLDQN 384
Cdd:cd03782  80 MLLDQH 85

RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1)-like and similar proteins; TRAF1, also known as Epstein-Barr virus-induced protein 6 (EBI6), is an adapter molecule that regulates the activation of NF-kappa-B and JNK. It plays a role in the regulation of cell survival and apoptosis. The heterotrimer formed by TRAF1 and TRAF2 is part of an E3 ubiquitin-protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14. The TRAF1/TRAF2 complex recruits the antiapoptotic E3 protein-ubiquitin ligases BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This subfamily corresponds a group of TRAF1-like proteins that contains an N-terminal domain with a typical C3HC4-type RING-HC finger.

                        10        20        30
                ....*....|....*....|....*....|....
gi 16549281  29 EAKYLCSACRNVLRRPFQAQCGHRYCSFCLASIL 62
Cdd:cd23125   2 EEKYLCCNCKNVLKKAQQTLCGHRYCLACLSWIV 35

RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) and similar proteins; TRAF3, also known as CAP-1, CD40 receptor-associated factor 1 (CRAF1), CD40-binding protein (CD40BP), or LMP1-associated protein 1 (LAP1), is a member of the TRAF protein family, which mainly functions in the immune system, where it mediates signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a unique cell type-specific and critical role in the restraint of B-cell homeostatic survival, a role with important implications for both B-cell differentiation and the pathogenesis of B-cell malignancies. TRAF3 differentially regulates differentiation of specific T cell subsets. It is required for iNKT cell development, restrains Treg cell development in the thymus, and plays an essential role in the homeostasis of central memory CD8+ T cells. TRAF3 contains an N-terminal domain with a typical C3HC4-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain, and a conserved TRAF-C domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 16549281  32 YLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAAC 72
Cdd:cd16640   1 YKCEKCRLVLCNPKQTECGHRFCESCMNALLSSSNPQCPAC 41

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) and similar proteins; TRAF5, also known as RING finger protein 84 (RNF84), is an important signal transducer for a wide range of TNF receptor superfamily members, including tumor necrosis factor receptor 1 (TNFR1), TNFR2, CD40, and other lymphocyte costimulatory receptors, RANK/TRANCE-R, ectodysplasin-A Receptor (EDAR), lymphotoxin-beta receptor (LT-betaR), latent membrane protein 1 (LMP1), and IRE1. It functions as an activator of NF-kappaB, MAPK, and JNK, and is involved in both RANKL- and TNFalpha-induced osteoclastogenesis. It mediates CD40 signaling by associating with the cytoplasmic tail of CD40. It also negatively regulates Toll-like receptor (TLR) signaling and functions as a negative regulator of the interleukin 6 (IL-6) receptor signaling pathway that limits the differentiation of inflammatory CD4(+) T cells. TRAF5 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 16549281  28 LEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASIL 62
Cdd:cd16642   1 LEDRYKCATCHFVLHNPHQTGCGHRFCQHCILSLL 35

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281    28 LEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPqNCAACVHEgiyeegisilESSSAFPDNAARRE-VESLPAV 106
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQP-KCPLCRAE----------DQESKLRSNWLVSEiVESFKNL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281   107 CPSdgctwkgtLKEYeVKMPACGMVtEAPAVGSrPRSPSSYDLVlhvpltgAEACLMSVEEETELLLRSCHEGR------ 180
Cdd:TIGR00599  92 RPS--------LLEF-LRIPKTTPV-ENPDLAG-PENSSKIELI-------EESESDGVDAEDEDLQRSATSSRalaars 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 16549281   181 --CPLM---------------------LTECPACKGLVRLGEKERHLEHECP 209
Cdd:TIGR00599 154 taDILQlssdpskrndadyrseppnegLVQCPICQQRMPEKAVERHLDSECL 205

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281  28 LEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPqNCAACvhegIYEEGISILESSSafpdnAARREVESLPAVC 107
Cdd:COG5432  22 LDSMLRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQP-FCPVC----REDPCESRLRGSS-----GSREINESHARNR 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16549281 108 PSDgctwkgtLKEYEVKMPacgmvTEAPAVGSRprsPSSYDLVLHVPLTGAEAC----LMSVEEETELLLRSCHE--GRC 181
Cdd:COG5432  92 DLL-------RKVLESLCR-----LPRPIKEER---PCRWETVIAQDSASGDEEweddLASNSSPASIAKKTSRDskKRK 156

                       170       180
                ....*....|....*....|....*..
gi 16549281 182 PLMLTECPACKGLVRLGEKERHLEhEC 208
Cdd:COG5432 157 REDLVHCPACSNLVPHNQINQHLD-SC 182

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 16549281    34 CSACRNVLRRPFQA-QCGHRYCSFCLASILSSGPQNCAAC 72
Cdd:pfam00097   1 CPICLEEPKDPVTLlPCGHLFCSKCIRSWLESGNVTCPLC 40

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                        10        20        30
                ....*....|....*....|....*....|.
gi 16549281  34 CSACRNVLRRPFQAQCGHRYCSFCLASILSS 64
Cdd:cd16568   7 CIICHEYLYEPMVTTCGHTYCYTCLNTWFKS 37

RING finger, HC subclass, found in bifunctional apoptosis regulator (BAR); BAR, also known as RING finger protein 47, was originally identified as an inhibitor of Bax-induced apoptosis. It participates in the block of apoptosis induced by TNF-family death receptors (extrinsic pathway) and mitochondria-dependent apoptosis (intrinsic pathway). BAR is predominantly expressed by neurons in the central nervous system and is involved in the regulation of neuronal survival. It is an endoplasmic reticulum (ER)-associated RING-type E3 ubiquitin ligase that interacts with BI-1 protein and post-translationally regulates its stability, as well as functioning in ER stress. BAR contains an N-terminal C3HC4-type RING-HC finger, a SAM domain, a coiled-coil domain, and a C-terminal transmembrane (TM) domain. This model corresponds to the RING-HC finger responsible for the binding of ubiquitin conjugating enzymes (E2s).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 16549281  32 YLCSACRNVLRRPFQAQCGHRYCSFCLAS-ILSSGPQNCAAC 72
Cdd:cd16497   2 FLCHCCYDLLVNPTTLNCGHSFCRHCLALwWKSSKKTECPEC 43

RING finger, HC subclass, found in RING finger protein 125 (RNF125); RNF125, also known as T-cell RING activation protein 1 (TRAC-1), is an E3 ubiquitin-protein ligase that is predominantly expressed in lymphoid cells, and functions as a positive regulator of T cell activation. It also down-modulates HIV replication and inhibits pathogen-induced cytokine production. It negatively regulates type I interferon signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. Further, RNF125 conjugates ubiquitin to melanoma differentiation-associated gene 5 (MDA5), a family protein of RIG-I. It thus acts as a negative regulator of RIG-I signaling, and is a direct target of miR-15b in the context of Japanese encephalitis virus (JEV) infection. Moreover, RNF125 binds to and ubiquitinates JAK1, prompting its degradation and inhibition of receptor tyrosine kinase (RTK) expression. It also negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. Mutations in RNF125 may lead to overgrowth syndromes (OGS). RNF125, together with three closely related proteins: RNF114, RNF138 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM). The UIM of RNF125 binds K48-linked poly-ubiquitin chains and is, together with the RING domain, required for auto-ubiquitination.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 16549281  34 CSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAAC 72
Cdd:cd16542   4 CAVCLEVLHQPVRTRCGHVFCRPCIATSLRNNTWTCPYC 42

RING finger, HC subclass, found in Dictyostelium discoideum Ras guanine nucleotide exchange factor O (RasGEFO) and similar proteins; RasGEFO, also known as RasGEF domain-containing protein O, functions as a Ras guanine-nucleotide exchange factor (RasGEFs), activating Ras by catalyzing the replacement of GDP with GTP. RasGEFs are particularly important for signaling in development and chemotaxis in many organisms, including Dictyostelium. RasGEFO contains a C3HC4-type RING-HC finger that may be responsible for E3 ubiquitin ligase activity.

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gi 16549281  26 TKLEAKYLCSACRNVLRRP-FQAQCGHRYCSFCLASILsSGPqNCAAC 72
Cdd:cd16507   4 LNLLQSLTCGICQNLFKDPnTLIPCGHAFCLDCLTTNA-SIK-NCIQC 49

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1); UHRF1, also known as inverted CCAAT box-binding protein of 90 kDa, nuclear protein 95, nuclear zinc finger protein Np95 (Np95), RING finger protein 106, transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also a N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) domain, a SET and RING finger associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitylation has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD domain targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-HC finger exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

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gi 16549281  27 KLEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAACVHE 75
Cdd:cd16769   8 KVEETFQCICCQELVFRPITTVCQHNVCKDCLDRSFRAQVFSCPACRYD 56

second RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; This subfamily includes Arabidopsis thaliana ORTHRUS 1-5. They are E3 ubiquitin-protein ligases that may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing. ORTHRUS 1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologs (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTHRUS 2 and 5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTHRUS 1 and 2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this subfamily contain two typical C3HC4-type RING-HC fingers. This model corresponds to the second one.

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gi 16549281  27 KLEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASI 61
Cdd:cd23139   1 RLLKEFGCQICKKVLSLPVSTPCGHNFCKACLEAK 35