MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1073718822 309 SPGYF---FGYRIEPIIRFKTHGKNVRMHFGL--QVLRGEHDEQLLWPFHHNVRLWMMVPSGQASG---GCPLEINAESv 380
Cdd:cd00270    27 SPPFYtsrYGYKLCLRLYLNGDGTGKGTHLSLfvHVMKGEYDALLEWPFRGKITLTLLDQSDDSKRkhiTETFMPDPNS- 105

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1073718822 381 cKRFYDRP-ADGTRGNG-PCFSSssvdLKALESGGFVENDRLRLRFEVL 427
Cdd:cd00270   106 -SAFQRPPtGENNIGFGyPEFVP----LEKLESRGYVKDDTLFIKVEVD 149

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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 different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1073718822  27 VCSLCGLIPEATVQLPCAHILCRPCYEGCLQQGGVC 62
Cdd:cd16550     2 LCPICLEILVEPVTLPCNHTLCMPCFQSTVEKASLC 37

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 1073718822 309 SPGYF---FGYRIEPIIRFKTHGKNVRMHFGL--QVLRGEHDEQLLWPFHHNVRLWMMVPSGQASG---GCPLEINAESv 380
Cdd:cd00270    27 SPPFYtsrYGYKLCLRLYLNGDGTGKGTHLSLfvHVMKGEYDALLEWPFRGKITLTLLDQSDDSKRkhiTETFMPDPNS- 105

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1073718822 381 cKRFYDRP-ADGTRGNG-PCFSSssvdLKALESGGFVENDRLRLRFEVL 427
Cdd:cd00270   106 -SAFQRPPtGENNIGFGyPEFVP----LEKLESRGYVKDDTLFIKVEVD 149

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1073718822  27 VCSLCGLIPEATVQLPCAHILCRPCYEGCLQQGGVC 62
Cdd:cd16550     2 LCPICLEILVEPVTLPCNHTLCMPCFQSTVEKASLC 37

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 1073718822 309 SPGYF---FGYRIEPIIRFKTHGKNVRMHFGL--QVLRGEHDEQLLWPFHHNVRLWMMVPSGQASG---GCPLEINAESv 380
Cdd:cd00270    27 SPPFYtsrYGYKLCLRLYLNGDGTGKGTHLSLfvHVMKGEYDALLEWPFRGKITLTLLDQSDDSKRkhiTETFMPDPNS- 105

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1073718822 381 cKRFYDRP-ADGTRGNG-PCFSSssvdLKALESGGFVENDRLRLRFEVL 427
Cdd:cd00270   106 -SAFQRPPtGENNIGFGyPEFVP----LEKLESRGYVKDDTLFIKVEVD 149

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1073718822 157 ESLTERIKEIAETRKALIEAVAALEE----AKAQKTSLEASLKELKELLAQSFAVLATMERRSSEGGSEAGDTIRKRHNS 232
Cdd:COG1196   305 ARLEERRRELEERLEELEEELAELEEeleeLEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEEL 384

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1073718822 233 KQRDANGSSEAKQLREGIGEVLRAWKDYQIR 263
Cdd:COG1196   385 AEELLEALRAAAELAAQLEELEEAEEALLER 415

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
                  ....*....|....*....|....*....|....*
gi 1073718822  28 CSLCGLIPEATVQLPCAHILCRPCYEGCLQQGGVC 62
Cdd:cd16449     3 CPICLERLKDPVLLPCGHVFCRECIRRLLESGSIK 37

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1073718822 157 ESLTERIKEIAETRKALIEAVAALEEAKAQKTSLEASLKELKELLAQSFAVLATMERRSSE----GGSEAGDTIRKRHNS 232
Cdd:COG4942    62 RRIAALARRIRALEQELAALEAELAELEKEIAELRAELEAQKEELAELLRALYRLGRQPPLalllSPEDFLDAVRRLQYL 141

                          90
                  ....*....|....*.
gi 1073718822 233 KQRDANGSSEAKQLRE 248
Cdd:COG4942   142 KYLAPARREQAEELRA 157

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1073718822 163 IKEIAETRKALIEAVAA-LEEAKAQKTSLEASLKELKELLAQSFAVLATMERRSSEGGSEAGDTIRKRHNSKQRDANGSS 241
Cdd:COG4942   141 LKYLAPARREQAEELRAdLAELAALRAELEAERAELEALLAELEEERAALEALKAERQKLLARLEKELAELAAELAELQQ 220

                          90
                  ....*....|....*
gi 1073718822 242 EAKQLREGIGEVLRA 256
Cdd:COG4942   221 EAEELEALIARLEAE 235