PA_C-RZF_ like: Protease-associated (PA) domain C_RZF-like. This group includes various PA domain-containing proteins similar to C-RZF (chicken embryo RING zinc finger) protein. These proteins contain a C3H2C3 RING finger. C-RZF is expressed in embryo cells and is restricted mainly to brain and heart, it is localized to both the nucleus and endosomes. Additional C3H2C3 RING finger proteins belonging to this group, include Arabidopsis ReMembR-H2 protein and mouse sperizin. ReMembR-H2 is likely to be an integral membrane protein, and to traffic through the endosomal pathway. Sperizin is expressed in haploid germ cells and localized in the cytoplasm, it may participate in spermatogenesis. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  17 SYVVDAGQVILVDSNITRSFVDMEADFSPSVT-TVETGVVYVAEPLNACRNLRNKPEQSPYGTSPLVLIIRGGCSFEYKV 95
Cdd:cd02123   5 SPLATADKLALADSNLTDEFDDLPANFGPIPPgSGLKGVLVVAEPLNACSPIENPPLNSNASGSFIVLIRRGNCSFETKV 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15219930  96 RNAQRSGFKAAIVYDNVDrNFLSAMGGDSD---GIKIQAVFVMKRAGEMLKKYAGSEEMeVMLVPPNT 160
Cdd:cd02123  85 RNAQRAGYKAAIVYNDES-NDLISMSGNDQeikGIDIPSVFVGKSTGEILKKYASYEKG-VILIPDLP 150

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930 163 SVWSLYASIALILSLAIFCVMVTCvfFYRYCSTIRnSTSQFNGMCRRTVKAMPsvTFTCAKIDNTTGFsCAICLEDYIVG 242
Cdd:COG5243 227 SLLFMYQFPYVRVPIYLIRQMYTC--FYALFRRIR-EHARFRRATKDLNAMYP--TATEEQLTNSDRT-CTICMDEMFHP 300

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930 243 D----------KLRVLPCSHKFHVACVDSWLISWRTfCPVCKRDarTTADEPLATESTPFLSSSIATSSLVCIDSPPLGS 312
Cdd:COG5243 301 DheplprgldmTPKRLPCGHILHLHCLKNWLERQQT-CPICRRP--VIFDQSSPTPASPNVRNTQIATQVPNPDNTPTTT 377

                ..
gi 15219930 313 SV 314
Cdd:COG5243 378 AV 379

PA_C-RZF_ like: Protease-associated (PA) domain C_RZF-like. This group includes various PA domain-containing proteins similar to C-RZF (chicken embryo RING zinc finger) protein. These proteins contain a C3H2C3 RING finger. C-RZF is expressed in embryo cells and is restricted mainly to brain and heart, it is localized to both the nucleus and endosomes. Additional C3H2C3 RING finger proteins belonging to this group, include Arabidopsis ReMembR-H2 protein and mouse sperizin. ReMembR-H2 is likely to be an integral membrane protein, and to traffic through the endosomal pathway. Sperizin is expressed in haploid germ cells and localized in the cytoplasm, it may participate in spermatogenesis. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  17 SYVVDAGQVILVDSNITRSFVDMEADFSPSVT-TVETGVVYVAEPLNACRNLRNKPEQSPYGTSPLVLIIRGGCSFEYKV 95
Cdd:cd02123   5 SPLATADKLALADSNLTDEFDDLPANFGPIPPgSGLKGVLVVAEPLNACSPIENPPLNSNASGSFIVLIRRGNCSFETKV 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15219930  96 RNAQRSGFKAAIVYDNVDrNFLSAMGGDSD---GIKIQAVFVMKRAGEMLKKYAGSEEMeVMLVPPNT 160
Cdd:cd02123  85 RNAQRAGYKAAIVYNDES-NDLISMSGNDQeikGIDIPSVFVGKSTGEILKKYASYEKG-VILIPDLP 150

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  82 VLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRNF------LSAMGGDSDGIKIQAVFVM------------KRAGEMLK 143
Cdd:COG5540 150 RCNRRGNETEEDPTRERRRTRFKGVIRGSERNGETfrlhymVAPDKVDPRSEGVEDPVTLttsinvtwdglgNTYQAPSQ 229

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930 144 KYAGSEEMEVMLVPpntedSVWSLYASIALILSLAIFCVMVTCVFFYRYCSTIR-----NSTSQFNGMCRRTVKAMPSVT 218
Cdd:COG5540 230 SAEAQDETGDMFWP-----RLSRFVGSRGFRVVFPRIPSQELRFLFLTQSKGSRfniilEIQINFDVGFYSSSEAIPTTT 304

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15219930 219 ----FTCAKIDNTT----GFSCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTFCPVCK 274
Cdd:COG5540 305 tkgsLKPLSIERAVeadkGVECAICMSNFIKNDRLRVLPCDHRFHVGCVDKWLLGYSNKCPVCR 368

T9SS-dependent M36 family metallopeptidase; Members of this family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal T9SS type A sorting domain (see TIGR04131).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930   29 DSNITRSFVDMEADFSPSVTTVE-TGVVYVAE-----PLNACRNLRNKPEQspygTSPLVLIIRGGCSFEYKVRNAQRSG 102
Cdd:NF038113 417 PGSLAGRYPGVRAGFGPRLPDAPiTGDLALATdsspdPNDGCDPILNAAAL----AGKIAVIRRGSCEFAVKVLNAQNAG 492

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 15219930  103 FKAAIVYDNVDRNFLSAMGGDSD-GIKIQAVFVMKRAGEMLK 143
Cdd:NF038113 493 AIAVIIVNNVPGEPIVMGGGDTGpPITIPSIMISQADGEAII 534

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930    41 ADFSPSVTTVeTGVVYVAE-----PLNACRNLRNkpeqSPYGTSPLVLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRN 115
Cdd:NF038112  508 ASFGPQAFDV-TGDVVLAPdgtgsDTDGCTPFTN----AAEVAGKIALIDRGTCDFTVKALNAQNAGAIGVIIANNAAGA 582

                          90       100
                  ....*....|....*....|....*...
gi 15219930   116 FLSaMGGDSDGIKIQAVFVMKRAGEMLK 143
Cdd:NF038112  583 APG-LGGTDPAVTIPALSITQADGNAWK 609

PA domain; The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor Swiss:O22925 and members of the RZF family Swiss:O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15219930    82 VLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRNFLSAMGG----DSDGIKIQAVFVMKRAGEML 142
Cdd:pfam02225  27 VLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPGAGgnelYPDGIYIPAVGVSRADGEAL 91

PA_C-RZF_ like: Protease-associated (PA) domain C_RZF-like. This group includes various PA domain-containing proteins similar to C-RZF (chicken embryo RING zinc finger) protein. These proteins contain a C3H2C3 RING finger. C-RZF is expressed in embryo cells and is restricted mainly to brain and heart, it is localized to both the nucleus and endosomes. Additional C3H2C3 RING finger proteins belonging to this group, include Arabidopsis ReMembR-H2 protein and mouse sperizin. ReMembR-H2 is likely to be an integral membrane protein, and to traffic through the endosomal pathway. Sperizin is expressed in haploid germ cells and localized in the cytoplasm, it may participate in spermatogenesis. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  17 SYVVDAGQVILVDSNITRSFVDMEADFSPSVT-TVETGVVYVAEPLNACRNLRNKPEQSPYGTSPLVLIIRGGCSFEYKV 95
Cdd:cd02123   5 SPLATADKLALADSNLTDEFDDLPANFGPIPPgSGLKGVLVVAEPLNACSPIENPPLNSNASGSFIVLIRRGNCSFETKV 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15219930  96 RNAQRSGFKAAIVYDNVDrNFLSAMGGDSD---GIKIQAVFVMKRAGEMLKKYAGSEEMeVMLVPPNT 160
Cdd:cd02123  85 RNAQRAGYKAAIVYNDES-NDLISMSGNDQeikGIDIPSVFVGKSTGEILKKYASYEKG-VILIPDLP 150

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTFCPVCKR 275
Cdd:cd16797   3 CAICLDEYEEGDKLRVLPCSHAYHSKCVDPWLTQTKKTCPVCKQ 46

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 15219930 231 SCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTFCPVCKRDA 277
Cdd:cd16473   6 ECAICLENYQNGDLLRGLPCGHVFHQNCIDVWLERDNHCCPVCRWPV 52

PA_subtilisin_1: Protease-associated domain containing subtilisin-like proteases, subgroup 1. A subgroup of PA domain-containing subtilisin-like proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following subtilisin-like proteases: i) melon cucumisin, ii) Arabidopsis thaliana Ara12, iii) Alnus glutinosa ag12, iv) members of the tomato P69 family, and v) tomato LeSBT2. However, these proteins belong to other subtilisin-like subgroups. Relatively little is known about proteins in this subgroup.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  40 EADFSPSVTTVETGVVYV----AEPLNACRNLRNKPEQspygTSPLVLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRN 115
Cdd:cd04818   2 SAGFGPALTNVTADVVLAgaapASNTDGCTAFTNAAAF----AGKIALIDRGTCNFTVKVLNAQNAGAIAVIVANNVAGG 77

                        90       100
                ....*....|....*....|....*...
gi 15219930 116 FLSAMGGDSDGIKIQAVFVMKRAGEMLK 143
Cdd:cd04818  78 APITMGGDDPDITIPAVMISQADGDALK 105

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVCK 274
Cdd:cd16468   2 CVICMADFVVGDPIRYLPCMHIYHVDCIDDWLMRSFT-CPSCM 43

RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. It functions as an important regulator of inositol-requiring transmembrane kinase/endonuclease IRE1alpha, mediating endoplasmic reticulum (ER) stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. Moreover, RNF13 is involved in the regulation of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex via the ubiquitination of snapin, a SNAP25-interacting protein, which thereby controls synaptic function. In addition, RNF13 participates in regulating the function of satellite cells by modulating cytokine composition. RNF13 is evolutionarily conserved among many metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTFCPVCKR 275
Cdd:cd16796  11 CAICLDEYEEGDKLRILPCSHAYHCKCVDPWLTKTKKTCPVCKQ 54

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISwRTFCPVCKRD 276
Cdd:cd16474   3 CTICLSDFEEGEDVRRLPCMHLFHQECVDQWLST-NKRCPICRVD 46

H2 subclass of RING (RING-H2) fingers 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 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). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger 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 serves as a scaffold 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 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTFCPVCK 274
Cdd:cd16448   1 CVICLEEFEEGDVVRLLPCGHVFHLACILRWLESGNNTCPLCR 43

Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3 and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination, and two modified RING-H2 fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This model corresponds to the second RING-H2 finger, which is not a canonical C3H2C3-type, but a modified C3H2C2D-type.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTFCPVC 273
Cdd:cd16486   2 CRICLKAFQLGQHVRTLPCRHKFHRDCIDNWLLHSRNSCPID 43

PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases including, hSPPL2a and 2b which catalyze the intramembrane proteolysis of tumor necrosis factor alpha, ii) various proteins containing a C3H2C3 RING finger including, Arabidopsis ReMembR-H2 protein and various E3 ubiquitin ligases such as human GRAIL (gene related to anergy in lymphocytes), iii) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), iv) various plant vacuolar sorting receptors such as Pisum sativum BP-80, v) glutamate carboxypeptidase II (GCPII), vi) yeast aminopeptidase Y, vii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, viii) lactocepin (a cell envelope-associated protease from Lactobacillus paracasei subsp. paracasei NCDO 151), ix) various subtilisin-like proteases such as melon Cucumisin, and x) human TfR (transferrin receptor) 1 and 2.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  40 EADFSPSVTTVETGVVYVAEPLNACRNLRNKPEQSPYGTSpLVLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRN--FL 117
Cdd:cd00538   9 YAGSALLFNPPSSPVGVVAGPLVGCGYGTTDDSGADVKGK-IVLVRRGGCSFSEKVKNAQKAGAKAVIIYNNGDDPgpQM 87

                        90       100       110
                ....*....|....*....|....*....|...
gi 15219930 118 SAMGGDSDGIKIQAVFVMKRAGEMLKKYAGSEE 150
Cdd:cd00538  88 GSVGLESTDPSIPTVGISYADGEALLSLLEAGK 120

RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that interacts with wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. RNF149 induces the ubiquitination of wild-type BRAF and promotes its proteasome-dependent degradation. Mutated RNF149 has been found in some human breast, ovarian, and colorectal cancers. RNF149 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 15219930 231 SCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVCKRD 276
Cdd:cd16804   1 NCAVCIENYKSKDVVRILPCKHVFHRICIDPWLLEHRT-CPMCKLD 45

RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 is a transmembrane E3 ubiquitin-protein ligase that plays an important role in frizzled (FZD)-dependent regulation of the Wnt/beta-catenin pathway. It functions as a tumor suppressor that inhibits Wnt/beta-catenin signaling by ubiquitinating FZD receptor and targeting it to the lysosomal pathway for degradation. miR-550a-5p directly targeted the 3'-UTR of gene RNF43 and regulated its expression. Moreover, RNF43 interacts with NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) and regulates p53-mediated transcription. It may also be involved in cell growth control through the interaction with HAP95, a chromatin-associated protein interfacing the nuclear envelope. Mutations of RNF43 have been identified in various tumors, including colorectal cancer (CRC), endometrial cancer, mucinous ovarian tumors, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, liver fluke-associated cholangiocarcinoma, hepatocellular carcinoma, and glioma. RNF43 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVC 273
Cdd:cd16798   6 CAICLEEFSEGQELRIISCSHEFHRECVDPWLHQHRT-CPLC 46

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. RNF6 also regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. It acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF12, also known as LIM domain-interacting RING finger protein, or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Both RNF6 and RNF12 contain a well conserved C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15219930 231 SCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLiSWRTFCPVCK 274
Cdd:cd16467   1 ECTICLGEYETGEKLRRLPCSHEFHSECVDRWL-KENSSCPICR 43

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 15219930 231 SCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLiSWRTFCPVCKR 275
Cdd:cd16673   2 TCSVCINEYATGNKLRRLPCAHEFHIHCIDRWL-SENSTCPICRQ 45

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVCKRDA 277
Cdd:cd16680  10 CVVCFSDFESRQLLRVLPCNHEFHTKCVDKWLKTNRT-CPICRADA 54

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 15219930   230 FSCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISwRTFCPVCK 274
Cdd:pfam13639   1 DECPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRS-SNTCPLCR 44

RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL). It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property, and controls the development of T cell clonal anergy by ubiquitination. RNF130 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLiSWRTFCPVCK 274
Cdd:cd16803   3 CAVCIEGYKQNDVVRILPCKHVFHKSCVDPWL-NEHCTCPMCK 44

RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; This subfamily includes RING finger proteins RNF126, RNF115, and similar proteins. RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation; this inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a cofactor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. RNF115 and RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. Both of them contain an N-terminal BCA2 Zinc-finger domain (BZF), AKT-phosphorylation sites, and a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVCK 274
Cdd:cd16667   2 CAVCKEDFEVGEEVRQLPCKHLFHPDCIVPWLELHNS-CPVCR 43

RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. It interacts with calcium-modulating cyclophilin ligand (CAML), which is not a substrate, but a stabilizer of RNF122. RNF122 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 15219930 231 SCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLiSWRTFCPVCKR 275
Cdd:cd16676   2 TCAVCLEDFKTKDELGVLPCQHAFHRKCLVKWL-EIRCVCPMCNK 45

RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; RNF150 is a RING finger protein and its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. Further studies with larger numbers of participants worldwide are needed for validation of the relationships between RNF150 genetic variants and the pathogenesis of COPD. RNF150 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15219930 231 SCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVCK 274
Cdd:cd16805   8 NCAVCIEGYKPNDVVRILPCRHLFHKSCVDPWLLDHRT-CPMCK 50

PA_VSR: Protease-associated (PA) domain-containing plant vacuolar sorting receptor (VSR). This group includes various PA domain-containing VSRs such as garden pea BP-80, pumpkin PV72, and various Arabidopsis VSRs including AtVSR1. In contrast to most eukaryotes, which only have one or two VSRs, plants have several. This may in part be a reflection of having a more complex vacuolar system with both lytic vacuoles and storage vacuoles. The lytic vacuole is thought to be equivalent to the mammalian lysosome and the yeast vacuole. Pea BP-80 is a type 1 transmembrane protein, involved in the targeting of proteins to the lytic vacuole; it has been suggested that this protein also mediates targeting to the storage vacuole. PV72 and AtVSR1 may mediate transport of seed storage proteins to protein storage vacuoles. The significance of the PA domain to VSRs has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  54 VVYVAEPLNACRNL--RNKPEQSPYGTSPLVLII-RGGCSFEYKVRNAQRSGFKAAIVYDNVDRNFLS----AMGGDSD- 125
Cdd:cd02125  15 VVYPKENRTGCKEFdvFFKPKKSEPGRRPVILLLdRGGCFFTLKAWNAQQAGAAAVLVADNVDEPLLTmdtpEESGSADy 94

                        90       100       110
                ....*....|....*....|....*....|..
gi 15219930 126 --GIKIQAVFVMKRAGEMLKKYAGSEEMEVML 155
Cdd:cd02125  95 ieKITIPSALITKAFGEKLKKAISNGEMVVIK 126

RING-like zinc finger;

                          10        20
                  ....*....|....*....|....*...
gi 15219930   232 CAICLEDYIVGDKLRVLPCSHKFHVACV 259
Cdd:pfam17123   2 CSICLDEFKPGQALFVLPCSHVFHYKCI 29

PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a peptidase. This group contains various PA domain-containing proteins similar to S. pyogenes C5a, including, i) Vpr, a minor extracellular serine protease from Bacillus subtilis, ii) a large molecular mass collagenolytic protease from Geobacillus collagenovorans MO-1, and iii) PrtS, a cell envelope protease from Streptococcus thermophilus CNRZ 385. Proteins in this group belong to the peptidase S8 family. C5a peptidase is a cell surface serine protease which specifically inactivates C5a [a chemotactic peptide, which attracts polymorphonuclear leukocytes (PMNs)], by cleaving it to release a 7-residue carboxy-terminal fragment which contains the PMN binding site. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15219930  81 LVLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRNFLSAMGGdsdGIKIQAVFVMKRAGEMLKK 144
Cdd:cd02133  50 IALIQRGEITFVEKIANAKAAGAVGVIIYNNVDGLIPGTLGE---AVFIPVVFISKEDGEALKA 110

RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation and its inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a co-factor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. Furthermore, RNF115 and the related protein, RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF115 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVCKR 275
Cdd:cd16800   3 CPVCKEDYTVGEQVRQLPCNHFFHSDCIVPWLELHDT-CPVCRK 45

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 15219930 232 CAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTfCPVCKRDART 279
Cdd:cd16681  13 CTICLSILEEGEDVRRLPCMHLFHQVCVDQWLITNKK-CPICRVDIEA 59

RING finger, H2 subclass, found in Saccharomyces cerevisiae RING-H2 zinc finger protein RHA2B and similar proteins; RHA2B is an E3 ubiquitin-protein ligase involved in the positive regulation of abscisic acid (ABA) signaling and responses to salt and osmotic stresses during seed germination and early seedling development. It acts additively with RHA2A in regulating ABA signaling and drought response. RHA2B contains a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 15219930 231 SCAICLEDYIVGDKLRVLPCSHKFHVACVDSWLISWRTFCPVCK 274
Cdd:cd23123   2 DCCICLDKLKTGEEVKKLDCRHKFHKQCIEGWLKHLNFNCPLCR 45

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 15219930    232 CAICLEDYIvgDKLRVLPCSHKFHVACVDSWLISWRTFCPVC 273
Cdd:smart00184   1 CPICLEEYL--KDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 15219930 225 DNTtgfsCAICLEDYIVGDKLrvLPCSHKFHVACVDSWLISWRTfCPVCK 274
Cdd:cd16479   1 DNT----CIICREEMTVGAKK--LPCGHIFHLSCLRSWLQRQQT-CPTCR 43

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930    41 ADFSPSVTTVeTGVVYVAE-----PLNACRNLRNkpeqSPYGTSPLVLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRN 115
Cdd:NF038112  508 ASFGPQAFDV-TGDVVLAPdgtgsDTDGCTPFTN----AAEVAGKIALIDRGTCDFTVKALNAQNAGAIGVIIANNAAGA 582

                          90       100
                  ....*....|....*....|....*...
gi 15219930   116 FLSaMGGDSDGIKIQAVFVMKRAGEMLK 143
Cdd:NF038112  583 APG-LGGTDPAVTIPALSITQADGNAWK 609

PA_GO-like: Protease-associated domain containing proteins like Arabidopsis thaliana growth-on protein GRO10. This group contains various PA domain-containing proteins similar to the functionally uncharacterized Arabidopsis GRO10. The PA domain may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930  28 VDSNITRSFVDMEADFSPSVTTVE-----TGVVyVAEPLNACRNLRNKPeqspygTSPLVLIIRGGCSFEYKVRNAQRSG 102
Cdd:cd02132  11 VDGDEGDELVGVTARFGASLPSKEdnankTRAV-LANPLDCCSPSTSKL------SGSIALVERGECAFTEKAKIAEAGG 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15219930 103 FKAAIVYDNVDRnfLSAMG-GDSD---GIKIQAVFVMKRAGEMLKK-YAGSEEMEVML 155
Cdd:cd02132  84 ASALLIINDQEE--LYKMVcEDNDtslNISIPVVMIPQSAGDALNKsLDQGKKVEVLL 139

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930 163 SVWSLYASIALILSLAIFCVMVTCvfFYRYCSTIRnSTSQFNGMCRRTVKAMPsvTFTCAKIDNTTGFsCAICLEDYIVG 242
Cdd:COG5243 227 SLLFMYQFPYVRVPIYLIRQMYTC--FYALFRRIR-EHARFRRATKDLNAMYP--TATEEQLTNSDRT-CTICMDEMFHP 300

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15219930 243 D----------KLRVLPCSHKFHVACVDSWLISWRTfCPVCKRDarTTADEPLATESTPFLSSSIATSSLVCIDSPPLGS 312
Cdd:COG5243 301 DheplprgldmTPKRLPCGHILHLHCLKNWLERQQT-CPICRRP--VIFDQSSPTPASPNVRNTQIATQVPNPDNTPTTT 377

                ..
gi 15219930 313 SV 314
Cdd:COG5243 378 AV 379

PA_SaNapH_like: Protease-associated domain containing proteins like Streptomyces anulatus N-acetylpuromycin N-acetylhydrolase (SaNapH).This group contains various PA domain-containing proteins similar SaNapH. Proteins in this group belong to the peptidase M28 family. NapH is a terminal enzyme in the puromycin biosynthetic pathway; NapH hydrolyzes N-acetylpuromycin to the active antibiotic. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15219930  81 LVLIIRGGCSFEYKVRNAQRSGFKAAIVYDNVDRNFLSA-MGGDSDGIKIQAVFVMKRAGEMLKKYAGSEE 150
Cdd:cd04816  46 IVLVDRGGCPFADKQKVAAARGAVAVIVVNNSDGGGTAGtLGAPNIDLKVPVGVITKAAGAALRRRLGAGE 116