Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 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. TRAF2 associates with the receptors TNFR-1, TNFR-2, RANK (which mediates differentiation and maturation of osteoclasts) and CD40 (which is important for the proliferation and activation of B cells), among others. It regulates distinct pathways that lead to the activation of nuclear factor-kappaB and Jun NH2-terminal kinases. TRAF2 also indirectly associates with death receptors through its interaction with TRADD (TNFR-associated death domain protein). It is involved in regulating oxidative stress or ROS-induced cell death and in the preconditioning of cells by sublethal stress for protection from subsequent injury. TRAF2 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 594150400 341 AMADLEQKVSELEVSTYDGVFIWKISDFTRKRQEAVAGRTPAIFSPAFYTSRYGYKMCLRVYLNGDGTGRGTHLSLFFVV 420
Cdd:cd03778    1 A*ADLEQKVLE*EASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400 421 MKGPNDALLQWPFNQKVTLMLLDHNNREHVIDAFRPDVTSSSFQRPVSDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIK 500
Cdd:cd03778   81 MKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSK*EAKNSYVRDDAIFIK 160

                 ....
gi 594150400 501 AIVD 504
Cdd:cd03778  161 AIVD 164

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400  185 HYEVCPKFPLTC-DGCGKKKIPRETFQDHVR-ACSKCRVLCRFHTVGCSEMVETENLQDH 242
Cdd:pfam02176   1 HLETCPFFPIPCpNGCCKKKILREDLPDHLElDCPKAEVPCPFKVFGCKEDVKREALQRH 60

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 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. TRAF2 associates with the receptors TNFR-1, TNFR-2, RANK (which mediates differentiation and maturation of osteoclasts) and CD40 (which is important for the proliferation and activation of B cells), among others. It regulates distinct pathways that lead to the activation of nuclear factor-kappaB and Jun NH2-terminal kinases. TRAF2 also indirectly associates with death receptors through its interaction with TRADD (TNFR-associated death domain protein). It is involved in regulating oxidative stress or ROS-induced cell death and in the preconditioning of cells by sublethal stress for protection from subsequent injury. TRAF2 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 594150400 341 AMADLEQKVSELEVSTYDGVFIWKISDFTRKRQEAVAGRTPAIFSPAFYTSRYGYKMCLRVYLNGDGTGRGTHLSLFFVV 420
Cdd:cd03778    1 A*ADLEQKVLE*EASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400 421 MKGPNDALLQWPFNQKVTLMLLDHNNREHVIDAFRPDVTSSSFQRPVSDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIK 500
Cdd:cd03778   81 MKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSK*EAKNSYVRDDAIFIK 160

                 ....
gi 594150400 501 AIVD 504
Cdd:cd03778  161 AIVD 164

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400  185 HYEVCPKFPLTC-DGCGKKKIPRETFQDHVR-ACSKCRVLCRFHTVGCSEMVETENLQDH 242
Cdd:pfam02176   1 HLETCPFFPIPCpNGCCKKKILREDLPDHLElDCPKAEVPCPFKVFGCKEDVKREALQRH 60

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400   360 VFIWKISDFTRkrqeavAGRTPAIFSPAFYtsRYGYKMCLRVYLNGDgtgrgtHLSLFFVVMKGPNDALlQWPFNQKVTL 439
Cdd:smart00061   1 VLSHTFKNVSR------LEEGESYFSPSEE--HFNIPWRLKIYRKNG------FLSLYLHCEKEECDSR-KWSIEAEFTL 65

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 594150400   440 MLLDHNNREHvidafrPDVTSSSFQRPVSdmniaSGCPLFC 480
Cdd:smart00061  66 KLVSQNGKSL------SKKDKHVFEKPSG-----WGFSKFI 95

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400 247 LREHLALLLSSFLEAQASPGTLNQVGPELLQrcqiLEQKIATfenivcvLNREVERVAVTAEACSRQHRLDQDKIEALSN 326
Cdd:COG4942    1 MRKLLLLALLLALAAAAQADAAAEAEAELEQ----LQQEIAE-------LEKELAALKKEEKALLKQLAALERRIAALAR 69

                         90       100
                 ....*....|....*....|....*..
gi 594150400 327 KVQQLERSIGLKDLAMADLEQKVSELE 353
Cdd:COG4942   70 RIRALEQELAALEAELAELEKEIAELR 96

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 594150400   34 CSACKNILRRPFQA-QCGHRYCSFCLTSILRcasilssSGPQNCAAC 79
Cdd:pfam00097   1 CPICLEEPKDPVTLlPCGHLFCSKCIRSWLE-------SGNVTCPLC 40

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 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. TRAF2 associates with the receptors TNFR-1, TNFR-2, RANK (which mediates differentiation and maturation of osteoclasts) and CD40 (which is important for the proliferation and activation of B cells), among others. It regulates distinct pathways that lead to the activation of nuclear factor-kappaB and Jun NH2-terminal kinases. TRAF2 also indirectly associates with death receptors through its interaction with TRADD (TNFR-associated death domain protein). It is involved in regulating oxidative stress or ROS-induced cell death and in the preconditioning of cells by sublethal stress for protection from subsequent injury. TRAF2 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 594150400 341 AMADLEQKVSELEVSTYDGVFIWKISDFTRKRQEAVAGRTPAIFSPAFYTSRYGYKMCLRVYLNGDGTGRGTHLSLFFVV 420
Cdd:cd03778    1 A*ADLEQKVLE*EASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400 421 MKGPNDALLQWPFNQKVTLMLLDHNNREHVIDAFRPDVTSSSFQRPVSDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIK 500
Cdd:cd03778   81 MKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSK*EAKNSYVRDDAIFIK 160

                 ....
gi 594150400 501 AIVD 504
Cdd:cd03778  161 AIVD 164

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 594150400 321 IEALSNKVQQLERSIGLKDLAMADLEQKVSELEVSTYDGVFIWKISDFTRKRQEAVAGRTPAIFSPAFYTSRYGYKMCLR 400
Cdd:cd03777    1 TGLLESQLSRHDQMLSVHDIRLADMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCAR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400 401 VYLNGDGTGRGTHLSLFFVVMKGPNDALLQWPFNQKVTLMLLDHN-NREHVIDAFRPDVTSSSFQRPVSDMNIASGCPLF 479
Cdd:cd03777   81 VYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVTLMLMDQGsSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVF 160

                        170       180
                 ....*....|....*....|....*..
gi 594150400 480 CPVSKMEaKNSYVRDDAIFIKAIVDLT 506
Cdd:cd03777  161 VAQTVLE-NGTYIKDDTIFIKVIVDTS 186

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 594150400 359 GVFIWKISDFTRKRQEAVAGRTPAIFSPAFYTSRYGYKMCLRVYLNGDGTGRGTHLSLFFVVMKGPNDALLQWPFNQKVT 438
Cdd:cd03780    1 GKLIWKVTDYKMKKKEAVDGHTVSIFSQPFYTSRCGYRLCARAYLNGDGSGKGTHLSLYFVVMRGEFDSLLQWPFRQRVT 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 594150400 439 LMLLDHNN-REHVIDAFRPDVTSSSFQRPVSDMNIASGCPLFCPVSKME-AKNSYVRDDAIFIKAIVD 504
Cdd:cd03780   81 LMLLDQSGkKNHIMETFKADPNSSSFKRPDGEMNIASGCPRFVAHSVLEnAKNTYIKDDTLFLKVAVD 148

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 594150400 359 GVFIWKISDFTRKRQEAVAGRTPAIFSPAFYTSRYGYKMCLRVYLNGDGTGRGTHLSLFFVVMKGPNDALLQWPFNQKVT 438
Cdd:cd03776    1 GIYVWKIKNFSNLRRSMEAGSPVVIHSPGFYTSPPGYKLCARLNLSLPEARCPNYISLFVHLMQGENDSHLDWPFQGTIT 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400 439 LMLLDHNNREH----VIDAfRPDVtsSSFQRPVSDMNIAS-GCPLFCPVSKMEAKnSYVRDDAIFIKAIV 503
Cdd:cd03776   81 LTLLDQSEPRQniheTMMS-KPEL--LAFQRPTTDRNPKGfGYVEFAHIEDLLQR-GFVKNDTLLIKIEV 146

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 594150400 359 GVFIWKISDFTRKRQEAvagrtpaIFSPAFYtsRYGYKMCLRVYLNGDGTgRGTHLSLFFVVMKGPNDaLLQWPFNQKVT 438
Cdd:cd00121    1 GKHTWKIVNFSELEGES-------IYSPPFE--VGGYKWRIRIYPNGDGE-SGDYLSLYLELDKGESD-LEKWSVRAEFT 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 594150400 439 LMLLDHNNREHVIDAFRPDVTSSSfqrpvsdmNIASGCPLFCPVSKMEaKNSYVRDDAIFIKAIVD 504
Cdd:cd00121   70 LKLVNQNGGKSLSKSFTHVFFSEK--------GSGWGFPKFISWDDLE-DSYYLVDDSLTIEVEVK 126

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 594150400  31 KYLCSACKNILRRPFQAQCGHRYCSFCLTSILrcasilsSSGPQNCAACV 80
Cdd:cd16639    1 KYLCSDCRNILRRPFQAQCGHRYCSYCLKKIL-------SSGPQKCAACI 43

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 594150400 361 FIWKISDFTRKRQEAVAGRtpAIFSPAFYTSR-YGYKMclRVYLNGdGTGRGTHLSLFFVVMKGPNDALLQWP-FNQKVT 438
Cdd:cd03771    4 AVWRVRNFSQLLETTPKGT--KIYSPRFYSPEgYAFQV--GLYPNG-TESYPGYTGLYFHLCSGENDDVLEWPcPNRQAT 78

                 ....*..
gi 594150400 439 LMLLDHN 445
Cdd:cd03771   79 MTLLDQD 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 594150400  29 EAKYLCSACKNILRRPFQAQCGHRYCSFCLTSILRC 64
Cdd:cd23125    2 EEKYLCCNCKNVLKKAQQTLCGHRYCLACLSWIVRN 37

Modified RING finger, HC subclass (C3HC3D-type), found in uncharacterized proteins similar to tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4); This subfamily corresponds to a group of uncharacterized proteins that shows high sequence similarity with tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4). TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, or metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of TRAF protein family, which mainly function in the immune system, where they mediate signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a critical role in the nervous system, as well as in carcinogenesis. Like TRAF4, members of this subfamily contain a modified C3HC3D-type RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 594150400  28 LEAKYLCSACKNILRRPFQAQ-CGHRYCSFCLTSILR 63
Cdd:cd23126    1 LDKKYECPVCCQVLRYPVQFEeCGHRVCSSCLPELLR 37

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 594150400  31 KYLCSACKNILRRPFQAQCGHRYCSFCltsILRCasiLSSSGPQncaaCVYEGlyeegiSILESSSAFPDNAAR 104
Cdd:cd16643    1 KYECPICLMALREPVQTPCGHRFCKAC---ILKS---IREAGHK----CPVDN------EPLLENQLFPDNFAK 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 594150400   28 LEAKYLCSACKNILRRPFQAQCGHRYCSFCltsILRCasiLSSSGpqNCAACVYE 82
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLC---IRRC---LSNQP--KCPLCRAE 69

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400   243 ELQRLREHLALL---LSSFLEAQASpgtLNQVGPELLQRCQILEQKIATFENIVCVLNREVERVAVTAEACSRQHRLDQD 319
Cdd:TIGR02169  675 ELQRLRERLEGLkreLSSLQSELRR---IENRLDELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQ 751

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 594150400   320 KIEALSNKVQQLERSIGLKDLAMADLEQKVSELEVStYDGVFIWKISDFTRKRQEAVA 377
Cdd:TIGR02169  752 EIENVKSELKELEARIEELEEDLHKLEEALNDLEAR-LSHSRIPEIQAELSKLEEEVS 808

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 594150400  34 CSACKNILRRPFQAQCGHRYCSFCLTSILR 63
Cdd:cd16568    7 CIICHEYLYEPMVTTCGHTYCYTCLNTWFK 36

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594150400  243 ELQRLREHLALLLSSFLEAQASPGTLNQVGPELL-------QRCQILEQKIATFENIVCVLNREVERVAVTAEACSRQHR 315
Cdd:pfam07888  88 ELRQSREKHEELEEKYKELSASSEELSEEKDALLaqraaheARIRELEEDIKTLTQRVLERETELERMKERAKKAGAQRK 167

                          90
                  ....*....|....*..
gi 594150400  316 LDQDKIEALSNKVQQLE 332
Cdd:pfam07888 168 EEEAERKQLQAKLQQTE 184

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.

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gi 594150400  33 LCSACKNILRRPFQAQCGHRYCSFCLT 59
Cdd:cd16601    3 SCSLCKEYLKDPVIIECGHNFCRACIT 29

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 594150400  26 TRLEAKYLCSACKNILRRP-FQAQCGHRYCSFCLTSIL 62
Cdd:cd16507    4 LNLLQSLTCGICQNLFKDPnTLIPCGHAFCLDCLTTNA 41