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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 926512797  38 LEERYKCAYCHLVLHNPHQTGCGHRFCQQCILSLRELNAVPTCPVDKETIKMHEVF 93
Cdd:cd16642    1 LEDRYKCATCHFVLHNPHQTGCGHRFCQHCILSLLELNTTPICPIDKETIKSDEVF 56

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 926512797  127 HLQQCLFESVQCTNDGCCDQVLRKDLKDHLSQHCKFREEMCQY----CNKYVVLINIKNH 182
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 926512797  38 LEERYKCAYCHLVLHNPHQTGCGHRFCQQCILSLRELNAVPTCPVDKETIKMHEVF 93
Cdd:cd16642    1 LEDRYKCATCHFVLHNPHQTGCGHRFCQHCILSLLELNTTPICPIDKETIKSDEVF 56

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 926512797   426 SIFSQPFYTSRCGYRLCARaylngdgsGKGTHVSLYFVVMRGEFDSLlPWPFKQKVTLMLLDQSGKKnhivevfRADPNS 505
Cdd:smart00061  17 SYFSPSEEHFNIPWRLKIY--------RKNGFLSLYLHCEKEECDSR-KWSIEAEFTLKLVSQNGKS-------LSKKDK 80

                           90       100
                   ....*....|....*....|
gi 926512797   506 SSFKRPDGemniaSGCPRFV 525
Cdd:smart00061  81 HVFEKPSG-----WGFSKFI 95

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 926512797  39 EERYKCAYCHLVLHNPHQTGCGHRFCQQCILSLRELNAVPTCPVDKETIKMHEV 92
Cdd:COG5574  213 LADYKCFLCLEEPEVPSCTPCGHLFCLSCLLISWTKKKYEFCPLCRAKVYPKKV 266

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 926512797    44 CAYCH-LVLHNPHQTGCGHRFCQQCILSLRElNAVPTCPV 82
Cdd:smart00184   1 CPICLeEYLKDPVILPCGHTFCRSCIRKWLE-SGNNTCPI 39

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 926512797 365 LVVLEGQSNKHDLQINIHKAQLNKNEERFKLLEGTCYNGKLIWKIMDYKMKKKEAVEGRVLSIFSQPFYTSRCGYRLCAR 444
Cdd:cd03777    1 TGLLESQLSRHDQMLSVHDIRLADMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCAR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 926512797 445 AYLNGDGSGKGTHVSLYFVVMRGEFDSLLPWPFKQKVTLMLLDQSGKKNHIVEVFRADPNSSSFKRPDGEMNIASGCPRF 524
Cdd:cd03777   81 VYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVTLMLMDQGSSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVF 160

                        170       180
                 ....*....|....*....|....*...
gi 926512797 525 VPHTVLENtkNTYIKDDTLFLKVVVDLT 552
Cdd:cd03777  161 VAQTVLEN--GTYIKDDTIFIKVIVDTS 186

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 926512797 385 QLNKNEERFKLLEGTCYNGKLIWKIMDYKMKKKEAVEGRVLSIFSQPFYTSRCGYRLCARAYLNGDGSGKGTHVSLYFVV 464
Cdd:cd03778    1 A*ADLEQKVLE*EASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 926512797 465 MRGEFDSLLPWPFKQKVTLMLLDQSGKKnHIVEVFRADPNSSSFKRPDGEMNIASGCPRFVPHTVLEnTKNTYIKDDTLF 544
Cdd:cd03778   81 MKGPNDALLRWPFNQKVTLMLLDQNNRE-HVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSK*E-AKNSYVRDDAIF 158

                 ....*.
gi 926512797 545 LKVVVD 550
Cdd:cd03778  159 IKAIVD 164

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 926512797 403 GKLIWKIMDYKMKKKEAVEGRVLSIFSQPFYTSRCGYRLCARAYLNGDGSGKGTHVSLYFVVMRGEFDSLLPWPFKQKVT 482
Cdd:cd03781    1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 926512797 483 LMLLDQS----GKKNHIVEVFRADPNSSSFKRP----DGEMNIASGCPRFVPHTVLEntKNTYIKDDTLFLKVVVD 550
Cdd:cd03781   81 FTLLDQSdpslSKPQHITETFTPDPTWKNFQKPsasrLDESTLGFGYPKFISHEDLK--KRNYIKDDAIFLRASVE 154

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 926512797  38 LEERYKCAYCHLVLHNPHQTGCGHRFCQQCILSLRELNAVPTCPVDKETIKMHEVF 93
Cdd:cd16642    1 LEDRYKCATCHFVLHNPHQTGCGHRFCQHCILSLLELNTTPICPIDKETIKSDEVF 56

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 926512797  41 RYKCAYCHLVLHNPHQTGCGHRFCQQCIL-SLRElnAVPTCPVDKETIKMHEVFKDNCCK 99
Cdd:cd16643    1 KYECPICLMALREPVQTPCGHRFCKACILkSIRE--AGHKCPVDNEPLLENQLFPDNFAK 58

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 926512797  42 YKCAYCHLVLHNPHQTGCGHRFCQQCILSLRElNAVPTCPVD 83
Cdd:cd16640    1 YKCEKCRLVLCNPKQTECGHRFCESCMNALLS-SSNPQCPAC 41

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 926512797  127 HLQQCLFESVQCTNDGCCDQVLRKDLKDHLSQHCKFREEMCQY----CNKYVVLINIKNH 182
Cdd:pfam02176   1 HLETCPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60

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        40
                 ....*....|....*....|....*....|....*....|....*..
gi 926512797  39 EERYKCAYCHLVLHNPHQTGCGHRFCQQCILSLRELNAVPTCPVDKE 85
Cdd:cd23125    2 EEKYLCCNCKNVLKKAQQTLCGHRYCLACLSWIVRNNKNPICQKCKE 48

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 926512797  39 EERYKCAYCHLVLHNPHQTGCGHRFCQQCILSLRELNAVPTCPVDKETIKMHEV 92
Cdd:COG5574  213 LADYKCFLCLEEPEVPSCTPCGHLFCLSCLLISWTKKKYEFCPLCRAKVYPKKV 266

RING finger, HC subclass, found in ligand of Numb protein LNX3, LNX4, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4, or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for the substrate-binding. This family corresponds to LNX3/LNX4-like proteins, which contains a C3HC4-type RING-HC finger and two PDZ domains.

                         10        20
                 ....*....|....*....|....*..
gi 926512797  43 KCAYCHLVLHNPHQTGCGHRFCQQCIL 69
Cdd:cd16512    2 KCKLCLGVLEEPLATPCGHVFCAGCVL 28

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 926512797  42 YKCAYCHLVLHNPHQTGCGHRFCQQCILSLRELNAvPTCPVD 83
Cdd:cd16449    1 LECPICLERLKDPVLLPCGHVFCRECIRRLLESGS-IKCPIC 41

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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 926512797  40 ERYKCAYCHLVLHNPHQTG-CGHRFCQQCILSLReLNAVPTCPVDKETIKM 89
Cdd:cd16620    2 DELKCPICKDLMKDAVLTPcCGNSFCDECIRTAL-LEEDFTCPTCKEPDVS 51

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) and similar proteins; TRAF7, also known as RING finger and WD repeat-containing protein 1 or RING finger protein 119 (RNF119), is an E3 ubiquitin-protein ligase involved in signal transduction pathways that lead either to activation or repression of NF-kappaB transcription factor by promoting K29-linked ubiquitination of several cellular targets, including the NF-kappaB essential modulator (NEMO) and the p65 subunit of NF-kappaB transcription factor. It is also involved in K29-linked polyubiquitination that has been implicated in lysosomal degradation of proteins. Moreover, TRAF7 is required for K48-linked ubiquitination of p53, a key tumor suppressor and a master regulator of various signaling pathways, such as those related to apoptosis, cell cycle and DNA repair. It is also required for tumor necrosis factor alpha (TNFalpha)-induced Jun N-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein. Furthermore, TRAF7 functions as small ubiquitin-like modifier (SUMO) E3 ligase involved in other post-translational modification, such as sumoylation. It binds to and stimulates sumoylation of the proto-oncogene product c-Myb, a transcription factor regulating proliferation and differentiation of hematopoietic cells. It potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. Meanwhile, TRAF7 mediates MyoD1 regulation of the pathway and cell-cycle progression in myoblasts. It also plays a role in Toll-like receptors (TLR) signaling. TRAF7 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and an adjacent zinc finger, and a unique C-terminal domain that comprises a coiled coil domain and seven WD40 repeats.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 926512797  44 CAYCHLVLHNPHQTGCGHRFCQQCILSlrelNAVPTCPVDK 84
Cdd:cd16644    8 CPLCQRVFKDPVITSCGHTFCRRCALT----APGEKCPVDN 44

Meprin family, Alpha 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 alpha subunit is synthesized as a membrane spanning protein, however, it is cleaved during biosynthesis and loses its transmembrane domain. It oligomerizes into large complexes, containing 10-100 subunits (dimers that associate noncovalently), which are secreted as latent proteases and can move through extracellular spaces in a nondestructive manner. This allows delivery of the concentrated protease to sites containing activating enzymes, such as sites of inflammation, infection or cancerous growth. Meprin alpha shows preference for small or hydrophobic residues at the P1 and P1' sites of its substrate. 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 926512797 400 CYNGklIWKIMDYKMKKKEAVEGRVLSifSQPFYTSRcGYRLCARAY-LNGDGSGKGTHVSLYFVVMRGEFDSLLPWP-F 477
Cdd:cd03783    1 CPNA--VWRVRNFSQILENTTKGDVLQ--SPRFYSPE-GYGYGVSLYpLSNESDYSGNYTGLYFHLCSGENDAVLEWPaL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 926512797 478 KQKVTLMLLDQ--------SGKKNHIVEVFRADP---NSSSFKRPD--GEMNIASGCPR--------FVPHTVLEntKNT 536
Cdd:cd03783   76 NRQAIITVLDQdpdvrlrmSSSRSFTTDKSQTSSainGTLRWDRPSrvGTYDTSCDCFRgidfgwstFISHSQLR--RRS 153

                        170
                 ....*....|.
gi 926512797 537 YIKDDTLFLKV 547
Cdd:cd03783  154 FLKNDDLIIFV 164

RING finger, HC subclass, found in peroxin-2 (PEX2) and similar proteins; PEX2, also known as peroxisome biogenesis factor 2, 35 kDa peroxisomal membrane protein, peroxisomal membrane protein 3, peroxisome assembly factor 1 (PAF-1), or RING finger protein 72 (RNF72), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It may be involved in the biogenesis of peroxisomes, as well as in peroxisomal matrix protein import. Mutations in the PEX2 gene are the primary defect in a subset of patients with Zellweger syndrome and related peroxisome biogenesis disorders. Moreover, PEX2 functions as an E3-ubiquitin ligase that mediates the UBC4-dependent polyubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 926512797  43 KCAYCHLV-LHNPHQTGCGHRFCQQCILSLRELNAVPTCP 81
Cdd:cd16526    3 ECAICGEWpTNNPYSTGCGHVYCYYCIKSNLLADDSFTCP 42

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 926512797   43 KCAYCHLVLHNPHQ-TGCGHRFCQQCIL-SLRELNAVPTC 80
Cdd:pfam13923   1 MCPICMDMLKDPSTtTPCGHVFCQDCILrALRAGNECPLC 40

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 926512797  38 LEERYKCAYCHLVLHNPHQTGCGHRFCQQCIlsLRELNAVPTCPV 82
Cdd:COG5432   22 LDSMLRCRICDCRISIPCETTCGHTFCSLCI--RRHLGTQPFCPV 64

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 926512797  43 KCAYCHLVLHNPHQTGCGHRFCQQCILSLreLNAVPTCPVDKETIKMHEV 92
Cdd:cd16527    2 KCSLCLEERRHPTATPCGHLFCWSCITEW--CNEKPECPLCREPFQPQRL 49

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) and similar proteins; TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of the 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 nervous system, as well as in carcinogenesis. TRAF4 promotes the growth and invasion of colon cancer through the Wnt/beta-catenin pathway. It contributes to the TNFalpha-induced activation of the 70 kDa ribosomal protein S6 kinase (p70s6k) signaling pathway, and activation of transforming growth factor beta (TGF-beta)-induced SMAD-dependent signaling and non-SMAD signaling in breast cancer. It also enhances osteosarcoma cell proliferation and invasion by the Akt signaling pathway. Moreover, TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration. TRAF4 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 926512797  41 RYKCAYCHLVLHNPHQ-TGCGHRFCQQCILS-LRElnAVPTCPVDK 84
Cdd:cd16641    1 RLLCPLCRLPMREPVQiSTCGHRFCDTCLQEfLSE--GVFKCPEDQ 44

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 926512797  44 CAYCHLVLHNPHQTGCGHRFCQQCIlsLRELNAVPTCPVDKETI 87
Cdd:cd16514    4 CSLCLRLLYEPVTTPCGHTFCRACL--ERCLDHSPKCPLCRTSL 45

RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar proteins; TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM10 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        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 926512797  37 SLEERYKCAYCHLVLHNPHQTGCGHRFCQQCILSLRE-----LNAVPTCPVDKE 85
Cdd:cd16593    1 SLADEVNCPICQGTLREPVTIDCGHNFCRACLTRYCEipgpdLEEPPTCPLCKE 54

RING finger, HC subclass, found in RING finger protein 180 (RNF180) and similar proteins; RNF180, also known as Rines, is a membrane-bound E3 ubiquitin-protein ligase well conserved among vertebrates. It is a critical regulator of the monoaminergic system, as well as emotional and social behavior. It interacts with brain monoamine oxidase A (MAO-A) and targets it for ubiquitination and degradation. It also functions as a novel tumor suppressor in gastric carcinogenesis. The hypermethylated CpG site count of the RNF180 DNA promoter can be used to predict survival of gastric cancer. RNF180 contains a novel conserved dual specificity protein phosphatase Rines conserved (DSPRC) domain, a basic coiled-coil domain, a C3HC4-type RING-HC finger, and a C-terminal hydrophobic region that is predicted to be a transmembrane domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 926512797  40 ERYKCAYCHLVLHNPHQ-TGCGHRFCQQCILSLRELN-AVPTCPVDKETIK 88
Cdd:cd16554    1 ESLTCPVCLDLYYDPYMcYPCGHIFCEPCLRQLAKSSpKNTPCPLCRTTIR 51