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 1034588052  51 YKCEKCHLVLCSPKQTECGHRFCESCMAALLSSSSPKCTACQ 92
Cdd:cd16640     1 YKCEKCRLVLCNPKQTECGHRFCESCMNALLSSSNPQCPACE 42

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 258 QHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEI 337
Cdd:TIGR04523 335 KIISQLNEQISQLKKELTNSESENSEKQRELEEKQNEIEKLKKENQSYKQEIKNLESQINDLESKIQNQEKLNQQKDEQI 414

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1034588052 338 RPFRQNWE----EADSMKSSVESLQNRVTELESVD 368
Cdd:TIGR04523 415 KKLQQEKEllekEIERLKETIIKNNSEIKDLTNQD 449

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 1034588052  51 YKCEKCHLVLCSPKQTECGHRFCESCMAALLSSSSPKCTACQ 92
Cdd:cd16640     1 YKCEKCRLVLCNPKQTECGHRFCESCMNALLSSSNPQCPACE 42

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052  417 VLIWKIRDYKRrkqeavMGKTLSLYSQPFYTgyFGYKMCARVYLNGDgmgkgtHLSLFFVIMRGEYDALlPWPFKQKVTL 496
Cdd:smart00061   1 VLSHTFKNVSR------LEEGESYFSPSEEH--FNIPWRLKIYRKNG------FLSLYLHCEKEECDSR-KWSIEAEFTL 65

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1034588052  497 MLMDQGSSRRhlgdafkPDPNSSSFKKPTGemniaSGCPVFV 538
Cdd:smart00061  66 KLVSQNGKSL-------SKKDKHVFEKPSG-----WGFSKFI 95

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 244 TNQQikaheaSSAVQHVNLLKEWSNSLEKKVSLLQNES--------------VEKNKSIQSLHNQICSFEIEIERQKEML 309
Cdd:pfam10174 316 TNQN------SDCKQHIEVLKESLTAKEQRAAILQTEVdalrlrleekesflNKKTKQLQDLTEEKSTLAGEIRDLKDML 389

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 310 RNNESKILHLQRVIDSQAEKLKELDKEIrpfrqnweeaDSMKSSVESLQ----NRVTELESVDKSAGQVARNTGLLESQL 385
Cdd:pfam10174 390 DVKERKINVLQKKIENLQEQLRDKDKQL----------AGLKERVKSLQtdssNTDTALTTLEEALSEKERIIERLKEQR 459

                  ....*
gi 1034588052 386 SRHDQ 390
Cdd:pfam10174 460 EREDR 464

TRAF-type zinc finger;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034588052 197 CPCVVVSCPHKCSVQTLLRSELSAHLSE-CVNAPSTCSFKRYGC--VFQGTNQQ 247
Cdd:pfam02176   5 CPFFPIPCPNGCCKKKILREDLPDHLELdCPKAEVPCPFKVFGCkeDVKREALQ 58

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034588052  52 KCEKCHLVLCSPKQTE-CGHRFCESCMAALLSSSSPKCTACQ-ESIVKDKVFKDNCCKREI 110
Cdd:COG5222   276 KCPLCHCLLRNPMKTPcCGHTFCDECIGTALLDSDFKCPNCSrKDVLLDGLTPDIDKKLEV 336

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052  52 KCEKCHLVLCSPKQTECGHRFCESCMAALLsSSSPKCTACQESIvKDKVFKDNCCKREIL------------ALQIYCR- 118
Cdd:COG5432    27 RCRICDCRISIPCETTCGHTFCSLCIRRHL-GTQPFCPVCREDP-CESRLRGSSGSREINesharnrdllrkVLESLCRl 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 119 ----NESRGCAEQLMLGHllVHLKNDCHFEELPCVRPDcKEKVLRKDLRDHVEKAckyRE--ATCSHCKSQVPMIALQKH 192
Cdd:COG5432   105 prpiKEERPCRWETVIAQ--DSASGDEEWEDDLASNSS-PASIAKKTSRDSKKRK---REdlVHCPACSNLVPHNQINQH 178

                  ...
gi 1034588052 193 EDT 195
Cdd:COG5432   179 LDS 181

family of the cytolysin A (ClyA) family alpha pore-forming toxins (alpha-PFT) including Bacillus cereus HblB, Aeromonas hydrophila AhlB, Bacillus thuringiensis Cry6Aa and similar proteins; This family belongs to the ClyA family of alpha-PFT bacterial toxins. PFTs form the major group of virulence factors in many pathogenic bacteria and in general are critical components of the molecular offensive and defensive machinery of cells in all kingdoms of life. Bacterial PFTs facilitate the takeover of host resources by puncturing holes in the membrane. PFTs can be classified as alpha-PFTs and beta-PFTs depending on the secondary structures of their membrane component. Alpha-PFTs use a ring of amphipathic helices while beta-PFTs use a beta-barrel to construct the pore. Members of this family include the toxins: Bacillus cereus hemolysin binding component B (HblB or HBL-B) of the diarrheal enterotoxin hemolysin BL, Aeromonas hydrophila hemolytic (Ahl) component B (AhlB) of the tripartite AhlABC toxin, Vibrio cholerae cytotoxin motility associated killing factor A (MakA) cytotoxin, Xenorhabdus nematophila alpha-xenorhabdolysin (XaxA), Bacillus thuringiensis crystal 6Aa (Cry6Aa) parasporal crystal (Cry) toxin, and Bacillus cereus non-hemolytic enterotoxin (Nhe) component A (NheA) of the non-hemolytic enterotoxin Nhe, which, despite its name, is hemolytic, among others. In solution, ClyA proteins have an elongated, almost entirely alpha-helical structure, except for a short hydrophobic beta-hairpin known as the beta-tongue. Pore formation by ClyA requires circular oligomerization of the toxin by a sequential mechanism. This, in turn, concentrates the amphipathic helices in the center of the ring-like structure, forming a helical barrel that inserts into the membrane by a wedge-like mechanism. Compared with ClyA, NheA is almost entirely alpha-helical with an enlarged "head" domain, and an enlarged beta-tongue; it has been proposed that NheA could even form beta-barrel pores. Alpha-PFTs with similar structures are increasingly being found in eukaryotes, in particular as components of the immune systems of animals. This family may be distantly related to Escherichia coli alpha-PFT hemolysin E (HlyE, also known as ClyA or SheA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 264 KEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILH-LQRVIDSQAEKLKELDKEIRPFRQ 342
Cdd:cd21116    47 LEWLNEIKPKLLSLPNDIIGYNNTFQSYYPDLIELADNLIKGDQGAKQQLLQGLEaLQSQVTKKQTSVTSFINELTTFKN 126

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034588052 343 NWEE-ADSMKSSVESLQNRVTELESVDKSAGQVARNTGLLESQLSRHDQMLSV 394
Cdd:cd21116   127 DLDDdSRNLQTDATKAQAQVAVLNALKNQLNSLAEQIDAAIDALEKLSNDWQT 179

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 280 ESVEKN--KSIQSLHNQICSFEIEIERQ---KEMLRNNESKILHLQRVIDSQAEKLKELDKEIRPFRQNWEEADSMKSSV 354
Cdd:PRK03918  161 ENAYKNlgEVIKEIKRRIERLEKFIKRTeniEELIKEKEKELEEVLREINEISSELPELREELEKLEKEVKELEELKEEI 240

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1034588052 355 ESLQnrvTELESVDKSAGQVARNTGLLESQL 385
Cdd:PRK03918  241 EELE---KELESLEGSKRKLEEKIRELEERI 268

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link cell surface TNFRs and receptors of the interleukin-1/Toll-like family to downstream kinase signaling 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. There are at least six mammalian and three Drosophila proteins containing TRAF domains. The mammalian TRAFs display varying expression profiles, indicating independent and cell type-specific regulation. They display distinct, as well as overlapping functions and interactions with receptors. Most TRAFs, except TRAF1, share N-terminal homology and contain a RING domain, multiple zinc finger domains, and a TRAF domain. TRAFs form homo- and heterotrimers through its 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 1034588052 416 GVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVT 495
Cdd:cd00270     1 GVLIWKIKDYSRKLQEAVAGSNTVLYSPPFYTSRYGYKLCLRLYLNGDGTGKGTHLSLFVHVMKGEYDALLEWPFRGKIT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034588052 496 LMLMDQG--SSRRHLGDAFKPDPNSSSFKK-PTGEMNIASGCPVFVAQTVLENGTYIKDDTIFIKVIVD 561
Cdd:cd00270    81 LTLLDQSddSKRKHITETFMPDPNSSAFQRpPTGENNIGFGYPEFVPLEKLESRGYVKDDTLFIKVEVD 149

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 1034588052 400 ADMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMR 479
Cdd:cd03778     3 ADLEQKVLE*EASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 480 GEYDALLPWPFKQKVTLMLMDQgSSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVF--VAQTVLENgTYIKDDTIFIK 557
Cdd:cd03778    83 GPNDALLRWPFNQKVTLMLLDQ-NNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFcpVSK*EAKN-SYVRDDAIFIK 160

                  ....
gi 1034588052 558 VIVD 561
Cdd:cd03778   161 AIVD 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 1034588052 416 GVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVT 495
Cdd:cd03781     1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034588052 496 LMLMDQG----SSRRHLGDAFKPDPNSSSFKKPTG----EMNIASGCPVFVAQTVLENGTYIKDDTIFIKVIVD 561
Cdd:cd03781    81 FTLLDQSdpslSKPQHITETFTPDPTWKNFQKPSAsrldESTLGFGYPKFISHEDLKKRNYIKDDAIFLRASVE 154

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 1034588052  51 YKCEKCHLVLCSPKQTECGHRFCESCMAALLSSSSPKCTACQ 92
Cdd:cd16640     1 YKCEKCRLVLCNPKQTECGHRFCESCMNALLSSSNPQCPACE 42

TRAF-type zinc finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034588052 136 HLKNdCHFEELPCVRPDCKEKVLRKDLRDHVEKACKYREATCSH----CKSQVPMIALQKH 192
Cdd:pfam02176   1 HLET-CPFFPIPCPNGCCKKKILREDLPDHLELDCPKAEVPCPFkvfgCKEDVKREALQRH 60

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 1034588052  50 KYKCEKCHLVLCSPKQTECGHRFCESCMAALLSSSSPKCTACQESIVKDKVFKDNCCK 107
Cdd:cd16643     1 KYECPICLMALREPVQTPCGHRFCKACILKSIREAGHKCPVDNEPLLENQLFPDNFAK 58

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 1034588052 419 IWKIRDYKRRKQEAvmGKTLSLYSQPFY--TGYfGYKMcaRVYLNGdGMGKGTHLSLFFVIMRGEYDALLPWP-FKQKVT 495
Cdd:cd03771     5 VWRVRNFSQLLETT--PKGTKIYSPRFYspEGY-AFQV--GLYPNG-TESYPGYTGLYFHLCSGENDDVLEWPcPNRQAT 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 496 LMLMDQGSS-RRHLGDA--FKPDPNSSS-----------------FKKPTGEM---NIASGCPVFVAQTVLENGTYIK-D 551
Cdd:cd03771    79 MTLLDQDPDiQQRMSNQrsFTTDPSMTSsdngeyfwdrpskvgsyDTDTNGCTcyrGPGYGWSTFISHSRLRRRDFLKgD 158

                  ....
gi 1034588052 552 DTIF 555
Cdd:cd03771   159 DLII 162

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 258 QHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEI 337
Cdd:TIGR04523 335 KIISQLNEQISQLKKELTNSESENSEKQRELEEKQNEIEKLKKENQSYKQEIKNLESQINDLESKIQNQEKLNQQKDEQI 414

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1034588052 338 RPFRQNWE----EADSMKSSVESLQNRVTELESVD 368
Cdd:TIGR04523 415 KKLQQEKEllekEIERLKETIIKNNSEIKDLTNQD 449

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 1034588052  48 EDKYKCEKCHLVLCSPKQTECGHRFCESCMAALL-SSSSPKCTACQE 93
Cdd:cd23125     2 EEKYLCCNCKNVLKKAQQTLCGHRYCLACLSWIVrNNKNPICQKCKE 48

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 1034588052  51 YKCEKCHLVLCSPKQTECGHRFCESCMAALLSSSSPKCTAC 91
Cdd:cd16449     1 LECPICLERLKDPVLLPCGHVFCRECIRRLLESGSIKCPIC 41

Chromosome segregation protein NDC80, interacts with SMC proteins [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 245 NQQIKAHEASSAVQHVNLLKEWSNSLEKKVSLLQ---NESVEKN---KSIQSLHNQICSFEI--EIERQKemlRNNESKI 316
Cdd:COG5185   262 NTDLRLEKLGENAESSKRLNENANNLIKQFENTKekiAEYTKSIdikKATESLEEQLAAAEAeqELEESK---RETETGI 338

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 317 LHLQRVIDSQAEKLKELDKEIRP----------FRQNWEEADSMK----SSVESLQNRVTELESVDKS-AGQVARNTGLL 381
Cdd:COG5185   339 QNLTAEIEQGQESLTENLEAIKEeienivgeveLSKSSEELDSFKdtieSTKESLDEIPQNQRGYAQEiLATLEDTLKAA 418

                  ....*..
gi 1034588052 382 ESQLSRH 388
Cdd:COG5185   419 DRQIEEL 425

TRAF-type zinc finger;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034588052 197 CPCVVVSCPHKCSVQTLLRSELSAHLSE-CVNAPSTCSFKRYGC--VFQGTNQQ 247
Cdd:pfam02176   5 CPFFPIPCPNGCCKKKILREDLPDHLELdCPKAEVPCPFKVFGCkeDVKREALQ 58

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 246 QQIKAhEASSAVQHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQrvIDS 325
Cdd:TIGR04523 242 NEKTT-EISNTQTQLNQLKDEQNKIKKQLSEKQKELEQNNKKIKELEKQLNQLKSEISDLNNQKEQDWNKELKSE--LKN 318

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1034588052 326 QAEKLKELDKEIrpfRQNWEEADSMKSSVESLQNRVTELES 366
Cdd:TIGR04523 319 QEKKLEEIQNQI---SQNNKIISQLNEQISQLKKELTNSES 356

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034588052  51 YKCEKCHLVLCSPKQTECGHRFCESCMAALLSSSSPKCTACQ 92
Cdd:cd16542     2 FDCAVCLEVLHQPVRTRCGHVFCRPCIATSLRNNTWTCPYCR 43

RING finger, HC subclass, found in radiation sensitivity protein 5 (RAD5) and similar proteins; RAD5, also known as revertibility protein 2 (REV2), or DNA repair protein RAD5, is a probable helicase, and a member of the UBC2/RAD6 epistasis group. It functions with the DNA repair protein RAD18 in error-free postreplication DNA repair. It is involved in the maintenance of wild-type rates of instability of simple repetitive sequences such as poly(GT) repeats. It may also be involved in maintaining a balance which acts in favor of error-prone non-homologous joining during DNA double-strand breaks repairs. It recruits the UBC13-MMS2 dimer to chromatin for DNA repair. RAD5 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034588052  66 TECGHRFCESCMAALL-----SSSSPKCTACQESIVKDKVFK 102
Cdd:cd23131    22 TECGHSFCEDCLLEYIefqnkKKLDLKCPNCREPISKYRLLK 63

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 234 FKRYGCVFQGTNQQIKA-----HEASSAVQHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKem 308
Cdd:COG4717    59 FKPQGRKPELNLKELKEleeelKEAEEKEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEA-- 136

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 309 lrnneskilhLQRVIDSQAEKLKELDKEIRPFRQNWEEADSMKSSVESLQNRVTELE-----SVDKSAGQVARNTGLLES 383
Cdd:COG4717   137 ----------LEAELAELPERLEELEERLEELRELEEELEELEAELAELQEELEELLeqlslATEEELQDLAEELEELQQ 206

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034588052 384 QLSRHDQMLSVHDIRLADMDLRFQVLETASyngvliWKIRDYKRRKQEAVMGKTLSL 440
Cdd:COG4717   207 RLAELEEELEEAQEELEELEEELEQLENEL------EAAALEERLKEARLLLLIAAA 257

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 1034588052 419 IWKIRDYKRRKQEAVmgKTLSLYSQPFYTGYfGYKMCARVY-LNGDGMGKGTHLSLFFVIMRGEYDALLPWP-FKQKVTL 496
Cdd:cd03783     5 VWRVRNFSQILENTT--KGDVLQSPRFYSPE-GYGYGVSLYpLSNESDYSGNYTGLYFHLCSGENDAVLEWPaLNRQAII 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 497 MLMDQ--------GSSRRHLGDAFKPDP---NSSSFKKPT--GEMNIASGC--------PVFVAQTVLENGTYIKDDTIF 555
Cdd:cd03783    82 TVLDQdpdvrlrmSSSRSFTTDKSQTSSainGTLRWDRPSrvGTYDTSCDCfrgidfgwSTFISHSQLRRRSFLKNDDLI 161

                  ...
gi 1034588052 556 IKV 558
Cdd:cd03783   162 IFV 164

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 1034588052  271 EKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKEL-DKEIRPFRqnwEEADS 349
Cdd:TIGR02169  222 EYEGYELLKEKEALERQKEAIERQLASLEEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLgEEEQLRVK---EKIGE 298

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1034588052  350 MKSSVESLQNRVTELES-VDKSAGQVARNTGLLESQLSRHDQM 391
Cdd:TIGR02169  299 LEAEIASLERSIAEKEReLEDAEERLAKLEAEIDKLLAEIEEL 341

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034588052 269 SLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEI-------ERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEIrpfr 341
Cdd:TIGR04523 444 DLTNQDSVKELIIKNLDNTRESLETQLKVLSRSInkikqnlEQKQKELKSKEKELKKLNEEKKELEEKVKDLTKKI---- 519

                          90       100
                  ....*....|....*....|....*
gi 1034588052 342 qnweeaDSMKSSVESLQNRVTELES 366
Cdd:TIGR04523 520 ------SSLKEKIEKLESEKKEKES 538

RING finger, HC subclass, found in ligand of numb protein X 3 (LNX3); LNX3, also known as PDZ domain-containing RING finger protein 3 (PDZRN3), or Semaphorin cytoplasmic domain-associated protein 3 (SEMACAP3), is an E3 ubiquitin-protein ligase that was first identified as a Semaphorin-binding partner. It is also 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. LNX3 acts as a negative regulator of osteoblast differentiation by inhibiting Wnt-beta-catenin signaling. LNX3 also plays an important role in neuromuscular junction formation. It interacts with and ubiquitinates the muscle specific tyrosine kinase (MuSK), thus promoting its endocytosis and negatively regulating the cell surface expression of this key regulator of postsynaptic assembly. LNX3 contains an N-terminal C3HC4-type RING-HC finger, two PDZ domains, and a C-terminal LNX3 homology (LNX3H) domain.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1034588052  47 VEDKYKCEKCHLVLCSPKQTECGHRFCESCM 77
Cdd:cd16718     1 VDPDFKCNLCNKVLEDPLTTPCGHVFCAGCV 31