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 2077861559  56 MLGVHFpdgaNKTFRNLEMVLADPVHGCEALRN-EIFAPSVILMERGECSFTVKALNGEKAGATVIMVTDSQNYEYsyhQ 134
Cdd:cd02127     1 DFGTIF----NTRYKHVPLVPADPLEACEELRNiHDINGNIALIERGGCSFLTKAINAQKAGALAVIITDVNNDSD---E 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2077861559 135 YYVNMIPDESLDRANVPCVYVAPVTGRYFRDHLEEGGTIKLDIPV 179
Cdd:cd02127    74 YYVEMIQDDSSRRADIPAAFLLGKNGYMIRKTLERLGLPYAIINI 118

PA_hPAP21_like: Protease-associated domain containing proteins like the human secreted glycoprotein hPAP21 (human protease-associated domain-containing protein, 21kDa). This group contains various PA domain-containing proteins similar to hPAP21. Complex N-glycosylation may be required for the secretion of hPAP21. The significance of the PA domain to hPAP21 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 2077861559  56 MLGVHFpdgaNKTFRNLEMVLADPVHGCEALRN-EIFAPSVILMERGECSFTVKALNGEKAGATVIMVTDSQNYEYsyhQ 134
Cdd:cd02127     1 DFGTIF----NTRYKHVPLVPADPLEACEELRNiHDINGNIALIERGGCSFLTKAINAQKAGALAVIITDVNNDSD---E 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2077861559 135 YYVNMIPDESLDRANVPCVYVAPVTGRYFRDHLEEGGTIKLDIPV 179
Cdd:cd02127    74 YYVEMIQDDSSRRADIPAAFLLGKNGYMIRKTLERLGLPYAIINI 118

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 2077861559   34 NMLFTVTEPYTLAYTYQMKHAfMLGvhfPDGANKTfrnLEMVLA-----DPVHGCEALRNE-IFAPSVILMERGECSFTV 107
Cdd:NF038112   488 EQTLTVTAPASLAGVYEAGSA-SFG---PQAFDVT---GDVVLApdgtgSDTDGCTPFTNAaEVAGKIALIDRGTCDFTV 560

                           90
                   ....*....|....*...
gi 2077861559  108 KALNGEKAGATVIMVTDS 125
Cdd:NF038112   561 KALNAQNAGAIGVIIANN 578

PA_hPAP21_like: Protease-associated domain containing proteins like the human secreted glycoprotein hPAP21 (human protease-associated domain-containing protein, 21kDa). This group contains various PA domain-containing proteins similar to hPAP21. Complex N-glycosylation may be required for the secretion of hPAP21. The significance of the PA domain to hPAP21 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 2077861559  56 MLGVHFpdgaNKTFRNLEMVLADPVHGCEALRN-EIFAPSVILMERGECSFTVKALNGEKAGATVIMVTDSQNYEYsyhQ 134
Cdd:cd02127     1 DFGTIF----NTRYKHVPLVPADPLEACEELRNiHDINGNIALIERGGCSFLTKAINAQKAGALAVIITDVNNDSD---E 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2077861559 135 YYVNMIPDESLDRANVPCVYVAPVTGRYFRDHLEEGGTIKLDIPV 179
Cdd:cd02127    74 YYVEMIQDDSSRRADIPAAFLLGKNGYMIRKTLERLGLPYAIINI 118

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 2077861559  53 HAFMLGVHFPDGANKTFRNLEMVLADPVhGCEALRNEIFAPS----VILMERGECSFTVKALNGEKAGATVIMVTDSQNY 128
Cdd:cd00538     4 LATTGYAGSALLFNPPSSPVGVVAGPLV-GCGYGTTDDSGADvkgkIVLVRRGGCSFSEKVKNAQKAGAKAVIIYNNGDD 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2077861559 129 EYSYHQYyvnmiPDESLDRANVPCVYVAPVTGRYFRDHLEEGGTIKLDI 177
Cdd:cd00538    83 PGPQMGS-----VGLESTDPSIPTVGISYADGEALLSLLEAGKTVTVDL 126

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 2077861559   34 NMLFTVTEPYTLAYTYQMKHAfMLGvhfPDGANKTfrnLEMVLA-----DPVHGCEALRNE-IFAPSVILMERGECSFTV 107
Cdd:NF038112   488 EQTLTVTAPASLAGVYEAGSA-SFG---PQAFDVT---GDVVLApdgtgSDTDGCTPFTNAaEVAGKIALIDRGTCDFTV 560

                           90
                   ....*....|....*...
gi 2077861559  108 KALNGEKAGATVIMVTDS 125
Cdd:NF038112   561 KALNAQNAGAIGVIIANN 578

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 2077861559  75 VLADPVHGCEALRNEIFAPS-----VILMERGECSFTVKALNGEKAGATVIMVtdsqnYEYSYHQYYVNMIPDESLDRAN 149
Cdd:cd02123    45 VVAEPLNACSPIENPPLNSNasgsfIVLIRRGNCSFETKVRNAQRAGYKAAIV-----YNDESNDLISMSGNDQEIKGID 119

                          90
                  ....*....|....*...
gi 2077861559 150 VPCVYVAPVTGRYFRDHL 167
Cdd:cd02123   120 IPSVFVGKSTGEILKKYA 137

PA_EDEM3_like: protease associated domain (PA) domain-containing EDEM3-like proteins. This group contains various PA domain-containing proteins similar to mouse EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein). EDEM3 contains a region, similar to Class I alpha-mannosidases (gylcosyl hydrolase family 47), N-terminal to the PA domain. EDEM3 accelerates glycoprotein ERAD (ER-associated degradation). In transfected mammalian cells, overexpression of EDEM3 enhances the mannose trimming from the N-glycans, of a model misfolded protein [alpha1-antitrypsin null (Hong Kong)] as well as, from total glycoproteins. Mannose trimming appears to be involved in the selection of ERAD substrates. EDEM3 has a different specificity of trimming than ER alpha-mannosidase 1. The significance of the PA domain to EDEM3 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2077861559  75 VLADPVHGCEALRN-EIFAPSVILMERGECSFTVKALNGEKAGATVIMVTD 124
Cdd:cd02126    22 VKAKPYRACSEITNaEEVKGKIAIMERGDCMFVEKARRVQKAGAIGGIVID 72

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2077861559  95 VILMERGECSFTVKALNGEKAGATVIMV---TDSqnyeysyhqyYVNMIPDESLDranVPCVYVAPVTGRYFRDHLEEGG 171
Cdd:cd02133    50 IALIQRGEITFVEKIANAKAAGAVGVIIynnVDG----------LIPGTLGEAVF---IPVVFISKEDGEALKAALESSK 116

                          90
                  ....*....|
gi 2077861559 172 TIKLDIPVER 181
Cdd:cd02133   117 KLTFNTKKEK 126

PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae aminopeptidase Y (ScAPY). This group contains various PA domain-containing proteins similar to the S. cerevisiae APY, including Trichophyton rubrum leucine aminopeptidase 1(LAP1). Proteins in this group belong to the peptidase M28 family. ScAPY hydrolyzes amino acid-4-methylcoumaryl-7-amides (MCAs). ScAPY more rapidly hydrolyzes dipeptidyl-MCAs. Hydrolysis of amino acid-MCAs or dipeptides is stimulated by Co2+ while the hydrolysis of dipeptidyl-MCAs, tripeptides, and longer peptides is inhibited by Co2+. ScAPY is vacuolar and is activated by proteolytic processing. LAP1 is a secreted leucine aminopeptidase. 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
                  ....*....|....*....|....*....|....*....|....*
gi 2077861559  82 GCEAlrnEIFAPSV----ILMERGECSFTVKALNGEKAGAT-VIM 121
Cdd:cd02130    33 GCDA---ADYPASVagniALIERGECPFGDKSALAGAAGAAaAII 74