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 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPGLAKPQHVTETFHPDPNWKNFQKPGTWRgsLDESSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd03781  81 FTLLDQSDPSLSKPQHITETFTPDPTWKNFQKPSASR--LDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   210 HQYQCPRLPVACPNQCGVGTVAREDLPGHLKDSCNTALVLCPFKDSGCKHRCPKLAMARH 269
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60

PRLI-interacting factor K; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622  113 CPnrCPMKLSRRDLPAHLQHDCPKRRLKCEFCG--CDFSGEAYESHE---GMCPQESVycenkcgarmmrrllaqhatse 187
Cdd:PLN03086 481 CP--CGVVLEKEQMVQHQASTCPLRLITCRFCGdmVQAGGSAMDVRDrlrGMSEHESI---------------------- 536

                         90       100
                 ....*....|....*....|....
gi 22027622  188 CPKRTQPCTYCTKEFVFDTIQSHQ 211
Cdd:PLN03086 537 CGSRTAPCDSCGRSVMLKEMDIHQ 560

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 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPGLAKPQHVTETFHPDPNWKNFQKPGTWRgsLDESSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd03781  81 FTLLDQSDPSLSKPQHITETFTPDPTWKNFQKPSASR--LDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   210 HQYQCPRLPVACPNQCGVGTVAREDLPGHLKDSCNTALVLCPFKDSGCKHRCPKLAMARH 269
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622    327 KPNLECFSPAFYTHKYGYKLQVSaflngngsGEGTHLSLYIRVLPGAFDNLlEWPFARRVTFSLLDQSDPglakpqhvte 406
Cdd:smart00061  13 EEGESYFSPSEEHFNIPWRLKIY--------RKNGFLSLYLHCEKEECDSR-KWSIEAEFTLKLVSQNGK---------- 73

                           90       100       110
                   ....*....|....*....|....*....|....
gi 22027622    407 tFHPDPNWKNFQKPGTWrgsldesslgfGYPKFI 440
Cdd:smart00061  74 -SLSKKDKHVFEKPSGW-----------GFSKFI 95

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
                   ....*....|....*....|....*....|....*...
gi 22027622     18 CPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCP 38

PRLI-interacting factor K; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622  113 CPnrCPMKLSRRDLPAHLQHDCPKRRLKCEFCG--CDFSGEAYESHE---GMCPQESVycenkcgarmmrrllaqhatse 187
Cdd:PLN03086 481 CP--CGVVLEKEQMVQHQASTCPLRLITCRFCGdmVQAGGSAMDVRDrlrGMSEHESI---------------------- 536

                         90       100
                 ....*....|....*....|....
gi 22027622  188 CPKRTQPCTYCTKEFVFDTIQSHQ 211
Cdd:PLN03086 537 CGSRTAPCDSCGRSVMLKEMDIHQ 560

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 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03781   1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22027622 388 FSLLDQSDPGLAKPQHVTETFHPDPNWKNFQKPGTWRgsLDESSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAVE 463
Cdd:cd03781  81 FTLLDQSDPSLSKPQHITETFTPDPTWKNFQKPSASR--LDESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF5 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. TRAF5 was identified as an activator of nuclear factor-kappaB and a regulator of lymphotoxin-beta receptor and CD40 signaling. Its interaction with CD40 is indirect, involving hetero-oligomerization with TRAF3. In addition, TRAF5 has been shown to associate with other TNFRs including CD27, CD30, OX40 and GITR (glucocorticoid-induced TNFR). It plays a role in modulating Th2 immune responses (driven by OX40 costimulation) and T-cell activation (triggered by GITR). It is also involved in osteoclastogenesis. TRAF5 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 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03780   1 GKLIWKVTDYKMKKKEAVDGHTVSIFSQPFYTSRCGYRLCARAYLNGDGSGKGTHLSLYFVVMRGEFDSLLQWPFRQRVT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22027622 388 FSLLDQSdpglAKPQHVTETFHPDPNWKNFQKPGtwrgslDESSLGFGYPKFISHQDIR--KRNYVRDDAVFIRAAVE 463
Cdd:cd03780  81 LMLLDQS----GKKNHIMETFKADPNSSSFKRPD------GEMNIASGCPRFVAHSVLEnaKNTYIKDDTLFLKVAVD 148

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 22027622 294 ELRRELEElSVGSDGVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGA 373
Cdd:cd03777  26 DLRFQVLE-TASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGE 104

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 374 FDNLLEWPFARRVTFSLLDQsDPGlakPQHVTETFHPDPNWKNFQKPGTwrgsldESSLGFGYPKFISHQDIRKRNYVRD 453
Cdd:cd03777 105 YDALLPWPFKQKVTLMLMDQ-GSS---RRHLGDAFKPDPNSSSFKKPTG------EMNIASGCPVFVAQTVLENGTYIKD 174

                       170
                ....*....|
gi 22027622 454 DAVFIRAAVE 463
Cdd:cd03777 175 DTIFIKVIVD 184

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. 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. TRAF6 is the most divergent in its TRAF domain among the mammalian TRAFs. In addition to mediating TNFR family signaling, it is also an essential signaling molecule of the interleukin-1/Toll-like receptor superfamily. Whereas other TRAF molecules display similar and overlapping TNFR-binding specificities, TRAF6 binds completely different sites on receptors such as CD40 and RANK. TRAF6 serves as a molecular bridge between innate and adaptive immunity and plays a central role in osteoimmunology. DTRAF2, as an activator of nuclear factor-kappaB, plays a pivotal role in Drosophila development and innate immunity. TRAF6 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 22027622 308 GVLIWKIGSYGRRLQEAKAKPNLECFSPAFYTHKYGYKLQVSAFLNGNGSGEGTHLSLYIRVLPGAFDNLLEWPFARRVT 387
Cdd:cd03776   1 GIYVWKIKNFSNLRRSMEAGSPVVIHSPGFYTSPPGYKLCARLNLSLPEARCPNYISLFVHLMQGENDSHLDWPFQGTIT 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22027622 388 FSLLDQSDPGlakpQHVTETFHPDPNWKNFQKPGTWRgsldeSSLGFGYPKFISHQDIRKRNYVRDDAVFIRAAV 462
Cdd:cd03776  81 LTLLDQSEPR----QNIHETMMSKPELLAFQRPTTDR-----NPKGFGYVEFAHIEDLLQRGFVKNDTLLIKIEV 146

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622   210 HQYQCPRLPVACPNQCGVGTVAREDLPGHLKDSCNTALVLCPFKDSGCKHRCPKLAMARH 269
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFKVFGCKEDVKREALQRH 60

Meprin family, MATH domain; Meprins are multidomain, highly glycosylated extracellular metalloproteases, which are either anchored to the membrane or secreted into extracellular spaces. They are expressed in renal and intestinal brush border membranes, leukocytes, and cancer cells, and are capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. Meprin proteases are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. Despite their similarity, the two subunits differ in their ability to self-associate, in proteolytic processing during biosynthesis and in substrate specificity. Both subunits are synthesized as membrane spanning proteins, however, the alpha subunit is cleaved during biosynthesis and loses its transmembrane domain. Meprin beta forms homodimers or heterotetramers while meprin alpha oligomerizes into large complexes containing 10-100 subunits. 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 22027622 311 IWKIGSYGRRLQeaKAKPNLECFSPAFYTHKyGYKLQVSAFLNGNGSgEGTHLSLYIRVLPGAFDNLLEWPFARR-VTFS 389
Cdd:cd03771   5 VWRVRNFSQLLE--TTPKGTKIYSPRFYSPE-GYAFQVGLYPNGTES-YPGYTGLYFHLCSGENDDVLEWPCPNRqATMT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 390 LLDQsDPGLAKPQHVTETFHPDPN----------WKNFQKPGTWRGSLDES----SLGFGYPKFISHQDIRKRNYVRDDA 455
Cdd:cd03771  81 LLDQ-DPDIQQRMSNQRSFTTDPSmtssdngeyfWDRPSKVGSYDTDTNGCtcyrGPGYGWSTFISHSRLRRRDFLKGDD 159

                ....*...
gi 22027622 456 VFIRAAVE 463
Cdd:cd03771 160 LIILLDFE 167

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 22027622 311 IWKIGSYGRRLqeAKAKPNLECFSPAFYTHKyGYKLQVSAFLNGNGSGEGtHLSLYIRVLPGAFDNLLEWPFA-RRVTFS 389
Cdd:cd03782   5 IWHIRNFTQLL--ATTPPNGKIYSPPFLSST-GYSFQVGLYLNGTDDYPG-NLAIYLHLTSGPNDDQLQWPCPwQQATMM 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22027622 390 LLDQsDPGLAKPQHVTETFHPDPN----------WKNFQKPGT----------WRGSldesslGFGYPKFISHQDIRKRN 449
Cdd:cd03782  81 LLDQ-HPDIRQRMSNQRSVTTDPNmtstdsdeyfWDDPRKVGSevtdtdgstfYRGP------GYGTSAFITHLRLRSRD 153

                       170
                ....*....|....
gi 22027622 450 YVRDDAVFIRAAVE 463
Cdd:cd03782 154 FIKGDDVIFLLTME 167

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 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        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22027622  15 RLLCPLCGKPMREPVQvSTCGHRFCDTCLQEFLSEGVFKCPEDQLPLDYAKIYPD 69
Cdd:cd16643   1 KYECPICLMALREPVQ-TPCGHRFCKACILKSIREAGHKCPVDNEPLLENQLFPD 54

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22027622  12 PKRRLLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPE--------DQLPLDYakiypDPELEVQ 75
Cdd:COG5222 271 PNISLKCPLCHCLLRNPMKTPCCGHTFCDECIGTALLDSDFKCPNcsrkdvllDGLTPDI-----DKKLEVE 337

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16620   4 LKCPICKDLMKDAVLTPCCGNSFCDECIRTALLEEDFTCP 43

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 22027622  16 LLCPLCGKPMREPVqVSTCGHRFCDTCLQEFLSEGVFKCPED 57
Cdd:cd16449   1 LECPICLERLKDPV-LLPCGHVFCRECIRRLLESGSIKCPIC 41

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 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).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16544   3 LTCPVCQEVLKDPVELPPCRHIFCKACILLALRSSGARCP 42

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
                  ....*....|....*....|....*....|....*....
gi 22027622    18 CPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCPE 56
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPL 39

Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation protein-1 (Nrdp1) and similar proteins; Nrdp1 (referred to as FLRF in mice), also known as RING finger protein 41 (RNF41), is an E3 ubiquitin-protein ligase that plays a critical role in the regulation of cell growth and apoptosis, inflammation and production of reactive oxygen species (ROS), as well as in doxorubicin (DOX)-induced cardiac injury. It promotes the degradation of the epidermal growth factor receptor (EGFR/ErbB) family member, ErbB3, which is independent of growth factor stimulation. It also promotes M2 macrophage polarization by ubiquitinating and activating transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) via Lys-63-linked ubiquitination. Moreover, Nrdp1 interacts with and modulates the activity of Parkin, a causative protein for early onset recessive juvenile parkinsonism (AR-JP). It also interacts with ubiquitin-specific protease 8 (USP8), which is involved in trafficking of various transmembrane proteins. Furthermore, Nrdp1 inhibits basal lysosomal degradation and enhances ectodomain shedding of JAK2-associated cytokine receptors. Its phosphorylation by the kinase Par-1b (also known as MARK2) is required for epithelial cell polarity. Nrdp1 contains an N-terminal modified C3HC3D-type RING-HC finger required for enhancing ErbB3 degradation, a B-box, a coiled-coil domain responsible for Nrdp1 oligomerization, and a C-terminal ErbB3-binding domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVfKCPEDQ 58
Cdd:cd16634   2 LICPICSGVLEEPLQAPHCEHAFCNACITEWLSRQQ-TCPVDR 43

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  17 LCPLCGKPMREPVQvSTCGHRFCDTCL----QEFLSEGVFKCP 55
Cdd:cd16583   7 VCPICQEPLKEAVS-TDCGHLFCRMCLtqhaKKASASGVFSCP 48

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVQVsTCGHRFCDTCLQEFLSE--GVFKCPE 56
Cdd:cd16601   2 ASCSLCKEYLKDPVII-ECGHNFCRACITRFWEEldGDFPCPQ 43

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                        10        20        30
                ....*....|....*....|....*....|....
gi 22027622  16 LLCPLCGKPMREPVqvST-CGHRFCDTCLQEFLS 48
Cdd:cd16498  17 LECPICLELLKEPV--STkCDHQFCRFCILKLLQ 48

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 22027622  16 LLCPLCGKPMREPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16531   2 LMCPICLGIIKNTMTVKECLHRFCAECIEKALRLGNKECP 41

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at the mitochondria.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22027622  10 EKPKRRLLCPLCGKPMREPVQVStCGHRFCDTCLQEFLSE--GVFKCPEDQLPLDYAKIYPD 69
Cdd:cd16590   1 EDIQEELTCPICLDYFQDPVSIE-CGHNFCRGCLHRNWAPggGPFPCPECRHPSAPAALRPN 61

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 22027622     16 LLCPLCGKPMREPVqVSTCGHRFCDTCLQEFLSEgVFKCPEDQLPLDYAKIYPDPEL 72
Cdd:smart00504   2 FLCPISLEVMKDPV-ILPSGQTYERSAIEKWLLS-HGTDPVTGQPLTHEDLIPNLAL 56

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22027622  18 CPLCGKPM---REPVQVSTCGHRFCDTCLQEFLSEGVFKCP 55
Cdd:cd16464   2 CPVCLEDLftsREPVHVLPCGHLMHSTCFEEYLKSGNYRCP 42

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 2 (LNX2); LNX2, also known as numb-binding protein 2, or PDZ domain-containing RING finger protein 1 (PDZRN1), is a PDZ domain-containing RING-type E3 ubiquitin ligase responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. It interacts with contactin-associated protein 4 (Caspr4, also known as CNTNAP4) in a PDZ domain-dependent manner, which modulates the proliferation and neuronal differentiation of neural progenitor cells (NPCs). LNX2 contains an N-terminal modified C3HC3D-type RING-HC finger, a NPAF motif for Numb/ Numblike-LNX interaction, and four PDZ domains necessary for the binding of substrates, including ErbB2, RhoC, the presynaptic protein CAST, the melanoma/cancer-testis antigen MAGEB18 and several proteins associated with cell junctions, such as JAM4 and the Coxsackievirus and adenovirus receptor (CAR).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22027622  16 LLCPLCGKPMREPVQvSTCGHRFCDTCLQEFLSEGVFkCPEDQ 58
Cdd:cd16780   4 LVCHICLQPLLQPLD-TPCGHTFCFKCLRNFLQEKDF-CPLDR 44

CDK-activating kinase assembly factor MAT1; All proteins in this family for which functions are known are cyclin dependent protein kinases that are components of TFIIH, a complex that is involved in nucleotide excision repair and transcription initiation. Also known as MAT1 (menage a trois 1). 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22027622    18 CPLC-GKPMREP---VQVSTCGHRFCDTCLQEFLSEGVFKCPEDQLPLDYAK----IYPDPELEVQV 76
Cdd:TIGR00570   6 CPRCkTTKYRNPslkLMVNVCGHTLCESCVDLLFVRGSGSCPECDTPLRKNNfrvqLFEDPTVEKEV 72

RING finger, HC subclass, found in tripartite motif-containing protein TRIM58 and similar proteins; TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization. TRIM58 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 22027622  18 CPLCGKPMREPVQVStCGHRFCDTCLQEFLSE------GVFKCPEDQLP 60
Cdd:cd16606   5 CPVCLDFLQEPVSVD-CGHSFCLRCISEFCEKsdsaqgGVYACPQCRGP 52

RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates Tumor necrosis factor alpha (TNF-alpha)- and interleukin-1beta-triggered Nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome. TRIM38 belongs the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 22027622  18 CPLCGKPMREPVQVStCGHRFCDTCLQEFL--------SEGVFKCPEDQLP 60
Cdd:cd16600   8 CSICLQLMTEPVSIN-CGHSYCKRCIVSFLenqsqlepGLETFSCPQCRAP 57

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30
                ....*....|....*....|....*....|.
gi 22027622  13 KRRLLCPLCGKPMREPVQVStCGHRFCDTCL 43
Cdd:cd16599   2 KEELLCPICYEPFREAVTLR-CGHNFCKGCV 31

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        40
                ....*....|....*....|....*....|....*....|....
gi 22027622  15 RLLCPLCGKPMREPVQvSTCGHRFCDTCLQEFLSE-GVFKCPED 57
Cdd:cd16642   4 RYKCATCHFVLHNPHQ-TGCGHRFCQHCILSLLELnTTPICPID 46