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 1958783876  50 YKCEKCRLVLCNPKQTECGHRFCESCMAALLSSSSPKCTACQ 91
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 1958783876 257 QHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEI 336
Cdd:TIGR04523 335 KIISQLNEQISQLKKELTNSESENSEKQRELEEKQNEIEKLKKENQSYKQEIKNLESQINDLESKIQNQEKLNQQKDEQI 414

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958783876 337 RPFRQNWE----EADSMKSSVESLQNRVTELESVD 367
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 1958783876  50 YKCEKCRLVLCNPKQTECGHRFCESCMAALLSSSSPKCTACQ 91
Cdd:cd16640     1 YKCEKCRLVLCNPKQTECGHRFCESCMNALLSSSNPQCPACE 42

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876  416 VLIWKIRDYKRrkqeavMGKTLSLYSQPFYTgyFGYKMCARVYLNGDgmgkgtHLSLFFVIMRGEYDALlPWPFKQKVTL 495
Cdd:smart00061   1 VLSHTFKNVSR------LEEGESYFSPSEEH--FNIPWRLKIYRKNG------FLSLYLHCEKEECDSR-KWSIEAEFTL 65

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1958783876  496 MLMDQGSSRRhlgdafkPDPNSSSFKKPTGemniaSGCPVFV 537
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 1958783876 243 TNQQikaheaSSAVQHVNLLKEWSNSLEKKVSLLQNES--------------VEKNKSIQSLHNQICSFEIEIERQKEML 308
Cdd:pfam10174 316 TNQN------SDCKQHIEVLKESLTAKEQRAAILQTEVdalrlrleekesflNKKTKQLQDLTEEKSTLAGEIRDLKDML 389

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 309 RNNESKILHLQRVIDSQAEKLKELDKEIrpfrqnweeaDSMKSSVESLQ----NRVTELESVDKSAGQAARNTGLLESQL 384
Cdd:pfam10174 390 DVKERKINVLQKKIENLQEQLRDKDKQL----------AGLKERVKSLQtdssNTDTALTTLEEALSEKERIIERLKEQR 459

                  ....*
gi 1958783876 385 SRHDQ 389
Cdd:pfam10174 460 EREDR 464

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 244 NQQIKAHEASSAVQHVNLLKEWSNSLEKKVSLLQ---NESVEKN---KSIQSLHNQICSFEI--EIERQKemlRNNESKI 315
Cdd:COG5185   262 NTDLRLEKLGENAESSKRLNENANNLIKQFENTKekiAEYTKSIdikKATESLEEQLAAAEAeqELEESK---RETETGI 338

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 316 LHLQRVIDSQAEKLKELDKEIRPFRQNWEEADSMKSSVESLQNRVTELESVDKSAGQAARN----TGLLESQLSRHdqmL 391
Cdd:COG5185   339 QNLTAEIEQGQESLTENLEAIKEEIENIVGEVELSKSSEELDSFKDTIESTKESLDEIPQNqrgyAQEILATLEDT---L 415

                         170       180
                  ....*....|....*....|..
gi 1958783876 392 SVHDIRLADM--DLRFQVLETA 411
Cdd:COG5185   416 KAADRQIEELqrQIEQATSSNE 437

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 1958783876  55 CRLVLCNPKQ----TECGHRFCESCMAALLSSSSPKCTAC 90
Cdd:pfam00097   1 CPICLEEPKDpvtlLPCGHLFCSKCIRSWLESGNVTCPLC 40

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 1958783876  44 KTVEDKYKCEKCRLVLCNPKQTECGHRFCESCMAALLsSSSPKCTAC----QESIIK 96
Cdd:TIGR00599  21 YPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCL-SNQPKCPLCraedQESKLR 76

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 1958783876 415 GVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVT 494
Cdd:cd00270     1 GVLIWKIKDYSRKLQEAVAGSNTVLYSPPFYTSRYGYKLCLRLYLNGDGTGKGTHLSLFVHVMKGEYDALLEWPFRGKIT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958783876 495 LMLMDQG--SSRRHLGDAFKPDPNSSSFKK-PTGEMNIASGCPVFVAQTVLENGTYIKDDTIFIKVIVD 560
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 1958783876 399 ADMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMR 478
Cdd:cd03778     3 ADLEQKVLE*EASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 479 GEYDALLPWPFKQKVTLMLMDQgSSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVF--VAQTVLENgTYIKDDTIFIK 556
Cdd:cd03778    83 GPNDALLRWPFNQKVTLMLLDQ-NNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFcpVSK*EAKN-SYVRDDAIFIK 160

                  ....
gi 1958783876 557 VIVD 560
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 1958783876 415 GVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVT 494
Cdd:cd03781     1 GTLLWKITDYSRKLQEAKGRDNLELFSPPFYTHRYGYKLQVSAFLNGNGSGEGSHLSVYIRVLPGEYDNLLEWPFSHRIT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958783876 495 LMLMDQG----SSRRHLGDAFKPDPNSSSFKKPTG----EMNIASGCPVFVAQTVLENGTYIKDDTIFIKVIVD 560
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 1958783876  50 YKCEKCRLVLCNPKQTECGHRFCESCMAALLSSSSPKCTACQ 91
Cdd:cd16640     1 YKCEKCRLVLCNPKQTECGHRFCESCMNALLSSSNPQCPACE 42

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 1958783876  47 EDKYKCEKCRLVLCNPKQTECGHRFCESCMAALLS-SSSPKCTACQESIIKDKVF 100
Cdd:cd16642     2 EDRYKCATCHFVLHNPHQTGCGHRFCQHCILSLLElNTTPICPIDKETIKSDEVF 56

meprin and TRAF homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876  416 VLIWKIRDYKRrkqeavMGKTLSLYSQPFYTgyFGYKMCARVYLNGDgmgkgtHLSLFFVIMRGEYDALlPWPFKQKVTL 495
Cdd:smart00061   1 VLSHTFKNVSR------LEEGESYFSPSEEH--FNIPWRLKIYRKNG------FLSLYLHCEKEECDSR-KWSIEAEFTL 65

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1958783876  496 MLMDQGSSRRhlgdafkPDPNSSSFKKPTGemniaSGCPVFV 537
Cdd:smart00061  66 KLVSQNGKSL-------SKKDKHVFEKPSG-----WGFSKFI 95

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 1958783876 418 IWKIRDYKRRKQEAvmGKTLSLYSQPFY--TGYfGYKMcaRVYLNGdGMGKGTHLSLFFVIMRGEYDALLPWP-FKQKVT 494
Cdd:cd03771     5 VWRVRNFSQLLETT--PKGTKIYSPRFYspEGY-AFQV--GLYPNG-TESYPGYTGLYFHLCSGENDDVLEWPcPNRQAT 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 495 LMLMDQGSS-RRHLGDA--FKPDPNSSS-----------------FKKPTGEM---NIASGCPVFVAQTVLENGTYIK-D 550
Cdd:cd03771    79 MTLLDQDPDiQQRMSNQrsFTTDPSMTSsdngeyfwdrpskvgsyDTDTNGCTcyrGPGYGWSTFISHSRLRRRDFLKgD 158

                  ....
gi 1958783876 551 DTIF 554
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 1958783876 257 QHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEI 336
Cdd:TIGR04523 335 KIISQLNEQISQLKKELTNSESENSEKQRELEEKQNEIEKLKKENQSYKQEIKNLESQINDLESKIQNQEKLNQQKDEQI 414

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958783876 337 RPFRQNWE----EADSMKSSVESLQNRVTELESVD 367
Cdd:TIGR04523 415 KKLQQEKEllekEIERLKETIIKNNSEIKDLTNQD 449

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958783876  46 VEDKYKCEKCRLVLCNPKQ-TECGHRFCESCMAALLsSSSPKCTACQESIIKD 97
Cdd:cd23126     1 LDKKYECPVCCQVLRYPVQfEECGHRVCSSCLPELL-RVEPRCPIDQGPIDRD 52

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 418 IWKIRDYKRrkqeaVMGKTL---SLYSQPFYTGYfGYKMCARVYLNGDGMGKGtHLSLFFVIMRGEYDALLPWPFK-QKV 493
Cdd:cd03782     5 IWHIRNFTQ-----LLATTPpngKIYSPPFLSST-GYSFQVGLYLNGTDDYPG-NLAIYLHLTSGPNDDQLQWPCPwQQA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 494 TLMLMDQGSS-RRHLG-------DAFK--------------------PDPNSSSFKKPTGemniaSGCPVFVAQTVLENG 545
Cdd:cd03782    78 TMMLLDQHPDiRQRMSnqrsvttDPNMtstdsdeyfwddprkvgsevTDTDGSTFYRGPG-----YGTSAFITHLRLRSR 152

                         170
                  ....*....|
gi 1958783876 546 TYIKDDTIFI 555
Cdd:cd03782   153 DFIKGDDVIF 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 1958783876 267 NSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERqkemlrnneskilhLQRVIDSQAEKLKELDKEIRPFRQNWE-- 344
Cdd:TIGR04523 422 ELLEKEIERLKETIIKNNSEIKDLTNQDSVKELIIKN--------------LDNTRESLETQLKVLSRSINKIKQNLEqk 487

                          90       100
                  ....*....|....*....|..
gi 1958783876 345 --EADSMKSSVESLQNRVTELE 364
Cdd:TIGR04523 488 qkELKSKEKELKKLNEEKKELE 509

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 244 NQQIKAHEASSAVQHVNLLKEWSNSLEKKVSLLQ---NESVEKN---KSIQSLHNQICSFEI--EIERQKemlRNNESKI 315
Cdd:COG5185   262 NTDLRLEKLGENAESSKRLNENANNLIKQFENTKekiAEYTKSIdikKATESLEEQLAAAEAeqELEESK---RETETGI 338

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 316 LHLQRVIDSQAEKLKELDKEIRPFRQNWEEADSMKSSVESLQNRVTELESVDKSAGQAARN----TGLLESQLSRHdqmL 391
Cdd:COG5185   339 QNLTAEIEQGQESLTENLEAIKEEIENIVGEVELSKSSEELDSFKDTIESTKESLDEIPQNqrgyAQEILATLEDT---L 415

                         170       180
                  ....*....|....*....|..
gi 1958783876 392 SVHDIRLADM--DLRFQVLETA 411
Cdd:COG5185   416 KAADRQIEELqrQIEQATSSNE 437

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 1958783876 245 QQIKAhEASSAVQHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQrvIDS 324
Cdd:TIGR04523 242 NEKTT-EISNTQTQLNQLKDEQNKIKKQLSEKQKELEQNNKKIKELEKQLNQLKSEISDLNNQKEQDWNKELKSE--LKN 318

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958783876 325 QAEKLKELDKEIrpfRQNWEEADSMKSSVESLQNRVTELES 365
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 1958783876  50 YKCEKCRLVLCNPKQTECGHRFCESCMAALLSSSSPKCTACQ 91
Cdd:cd16542     2 FDCAVCLEVLHQPVRTRCGHVFCRPCIATSLRNNTWTCPYCR 43

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 1958783876  48 DKYKCEKCRLVLCNPKQTEC-GHRFCESCMAALLSSSSPKCTACQESIIKDKV 99
Cdd:cd16620     2 DELKCPICKDLMKDAVLTPCcGNSFCDECIRTALLEEDFTCPTCKEPDVSPDA 54

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958783876  52 CEKCRLVLCNPKQTECGHRFCESCMAALLSSSSPK--CTACQESIIK 96
Cdd:cd16498    19 CPICLELLKEPVSTKCDHQFCRFCILKLLQKKKKPapCPLCKKSVTK 65

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 1958783876 418 IWKIRDYKRRKQEAVmgKTLSLYSQPFYTGYfGYKMCARVY-LNGDGMGKGTHLSLFFVIMRGEYDALLPWP-FKQKVTL 495
Cdd:cd03783     5 VWRVRNFSQILENTT--KGDVLQSPRFYSPE-GYGYGVSLYpLSNESDYSGNYTGLYFHLCSGENDAVLEWPaLNRQAII 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 496 MLMDQ--------GSSRRHLGDAFKPDP---NSSSFKKPT--GEMNIASGC--------PVFVAQTVLENGTYIKDDTIF 554
Cdd:cd03783    82 TVLDQdpdvrlrmSSSRSFTTDKSQTSSainGTLRWDRPSrvGTYDTSCDCfrgidfgwSTFISHSQLRRRSFLKNDDLI 161

                  ...
gi 1958783876 555 IKV 557
Cdd:cd03783   162 IFV 164

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 1958783876  49 KYKCEKCRLVLCNPKQ-TECGHRFCESCMAALLSSSSPKC 87
Cdd:cd16641     1 RLLCPLCRLPMREPVQiSTCGHRFCDTCLQEFLSEGVFKC 40

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958783876  51 KCEKCRLVLCNPKQTE-CGHRFCESCMAALLSSSSPKCTACQ-ESIIKDKVFKDNCCKREI 109
Cdd:COG5222   276 KCPLCHCLLRNPMKTPcCGHTFCDECIGTALLDSDFKCPNCSrKDVLLDGLTPDIDKKLEV 336

RING finger, HC subclass, found in RING finger protein 114 (RNF114) and similar proteins; RNF114, also known as zinc finger protein 228 (ZNF228) or zinc finger protein 313 (ZNF313), is a p21(WAF1)-targeting ubiquitin E3 ligase that interacts with X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) and may play a role in p53-mediated cell-fate decisions. It is involved in the immune response to double-stranded RNA in disease pathogenesis. Moreover, RNF114 interacts with A20 and modulates its ubiquitylation. It negatively regulates nuclear factor-kappaB (NF-kappaB)-dependent transcription and positively regulates T-cell activation. RNF114 may play a putative role in the regulation of immune responses, since it corresponds to a novel psoriasis susceptibility gene, ZNF313. RNF114, together with three closely related proteins: RNF125, 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).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1958783876  49 KYKCEKCRLVLCNPKQTECGHRFCESCMAALLSSSSPKCTACQ 91
Cdd:cd16540     1 RFTCPVCLEIFETPVRVPCGHVFCNACLQECLKPKKPVCAVCR 43

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 1958783876 268 SLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEI-------ERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEIrpfr 340
Cdd:TIGR04523 444 DLTNQDSVKELIIKNLDNTRESLETQLKVLSRSInkikqnlEQKQKELKSKEKELKKLNEEKKELEEKVKDLTKKI---- 519

                          90       100
                  ....*....|....*....|....*
gi 1958783876 341 qnweeaDSMKSSVESLQNRVTELES 365
Cdd:TIGR04523 520 ------SSLKEKIEKLESEKKEKES 538

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 1958783876 270 EKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEIRPFRQNWEEADSM 349
Cdd:TIGR04523 553 ELKKENLEKEIDEKNKEIEELKQTQKSLKKKQEEKQELIDQKEKEKKDLIKEIEEKEKKISSLEKELEKAKKENEKLSSI 632

                          90
                  ....*....|....
gi 1958783876 350 KSSVESLQNRVTEL 363
Cdd:TIGR04523 633 IKNIKSKKNKLKQE 646

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783876 269 LEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILH---------LQRVIDSQAEKLKELDKEIRPF 339
Cdd:COG1579    36 LEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNvrnnkeyeaLQKEIESLKRRISDLEDEILEL 115

                          90       100
                  ....*....|....*....|....*.
gi 1958783876 340 rqnWEEADSMKSSVESLQNRVTELES 365
Cdd:COG1579   116 ---MERIEELEEELAELEAELAELEA 138

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 1958783876  46 VEDKYKCEKCRLVLCNPKQTECGHRFCESCM 76
Cdd:cd16718     1 VDPDFKCNLCNKVLEDPLTTPCGHVFCAGCV 31