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 189065290  51 DFGGIFHTRYEQIHLVPAEPPEACGELSNGFFIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDNAVDNDSFYVEMIQ 130
Cdd:cd02127    1 DFGTIFNTRYKHVPLVPADPLEACEELRNIHDINGNIALIERGGCSFLTKAINAQKAGALAVIITDVNNDSDEYYVEMIQ 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 189065290 131 DSTQRTADIPALFLLGRDGYMIRRSLEQHGLPWAIISI 168
Cdd:cd02127   81 DDSSRRADIPAAFLLGKNGYMIRKTLERLGLPYAIINI 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 189065290  51 DFGGIFHTRYEQIHLVPAEPPEACGELSNGFFIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDNAVDNDSFYVEMIQ 130
Cdd:cd02127    1 DFGTIFNTRYKHVPLVPADPLEACEELRNIHDINGNIALIERGGCSFLTKAINAQKAGALAVIITDVNNDSDEYYVEMIQ 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 189065290 131 DSTQRTADIPALFLLGRDGYMIRRSLEQHGLPWAIISI 168
Cdd:cd02127   81 DDSSRRADIPAAFLLGKNGYMIRKTLERLGLPYAIINI 118

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 189065290  32 FQVLSPGDIRYIFTATPAKdFGGIFHTryEQI--HLVPAE-----PPEACGELSNGFFIQDQIALVERGGCSFLSKTRVV 104
Cdd:NF038113 412 LQVNAPGSLAGRYPGVRAG-FGPRLPD--APItgDLALATdsspdPNDGCDPILNAAALAGKIAVIRRGSCEFAVKVLNA 488

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 189065290 105 QEHGGRAVIISDNAVDNDSFyveMIQDSTQRTADIPALFLLGRDGYMIRRSLEQhglpwaiiSIPVNVT 173
Cdd:NF038113 489 QNAGAIAVIIVNNVPGEPIV---MGGGDTGPPITIPSIMISQADGEAIITALNN--------GETVNVT 546

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 189065290  51 DFGGIFHTRYEQIHLVPAEPPEACGELSNGFFIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDNAVDNDSFYVEMIQ 130
Cdd:cd02127    1 DFGTIFNTRYKHVPLVPADPLEACEELRNIHDINGNIALIERGGCSFLTKAINAQKAGALAVIITDVNNDSDEYYVEMIQ 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 189065290 131 DSTQRTADIPALFLLGRDGYMIRRSLEQHGLPWAIISI 168
Cdd:cd02127   81 DDSSRRADIPAAFLLGKNGYMIRKTLERLGLPYAIINI 118

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189065290  45 TATPAK---DFGGIFHTRYEqihLVPAEPPEACGELSNGFFIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDNaVDN 121
Cdd:cd02126    1 TAGPAQfgmDLTGDKAGVGR---VVKAKPYRACSEITNAEEVKGKIAIMERGDCMFVEKARRVQKAGAIGGIVIDN-NEG 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 189065290 122 DSF----YVEMIQDStQRTAD--IPALFLLGRDGYMIRRSLEQHG 160
Cdd:cd02126   77 SSSdtapMFAMSGDG-DSTDDvtIPVVFLFSKEGSKLLAAIKEHQ 120

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189065290   65 LVPAEPPEACGELSNGFFIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDNAVDNDSFYVEMIQDSTQRTADIPALFL 144
Cdd:pfam02225   4 LVLAPGCYAGDGIPADFDVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPGAGGNELYPDGIYIPAVGV 83

                  ....*...
gi 189065290  145 LGRDGYMI 152
Cdd:pfam02225  84 SRADGEAL 91

PA_1: Protease-associated (PA) domain subgroup 1. A subgroup of PA-domain containing proteins. Proteins in this subgroup contain a RING-finger (Really Interesting New Gene) domain C-terminal to this 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 in this group contain a C-terminal RING-finger domain. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases: such as hSPPL2a and 2b, ii) various E3 ubiquitin ligases similar to human GRAIL (gene related to anergy in lymphocytes) protein, iii) various proteins containing a RING finger motif such as Arabidopsis ReMembR-H2 protein, iv) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), v) various plant vacuolar sorting receptors such as Pisum sativum BP-80, vi) prostate-specific membrane antigen (PSMA), vii) yeast aminopeptidase Y viii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, ix) various subtilisin-like proteases such as Cucumisin from the juice of melon fruits, and x) human TfR (transferrin receptor) 1 and human TfR2. The proteins listed above belong to other subgroups; relatively little is known about proteins in this subgroup.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 189065290  62 QIHLVPAEppeACGeLSNGFFIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDN 117
Cdd:cd04813   21 SYKVSPTD---ACS-LQEHAEIDGKVALVLRGGCGFLDKVMWAQRRGAKAVIVGDD 72

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 189065290   31 YFQVLSPGDIRYIFTATPAkDFGgifHTRYE---QIHLVPAE---PPEACGELSNGFFIQDQIALVERGGCSFLSKTRVV 104
Cdd:NF038112  490 TLTVTAPASLAGVYEAGSA-SFG---PQAFDvtgDVVLAPDGtgsDTDGCTPFTNAAEVAGKIALIDRGTCDFTVKALNA 565

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 189065290  105 QEHGGRAVIISDNAvdnDSFYVEMIQDSTQRTadIPALFLLGRDGYMIRRSLEQHGL 161
Cdd:NF038112  566 QNAGAIGVIIANNA---AGAAPGLGGTDPAVT--IPALSITQADGNAWKAALANGPV 617

PA _GRAIL_like: Protease-associated (PA) domain GRAIL-like. This group includes PA domain containing E3 (ubiquitin ligases) similar to human GRAIL (gene related to anergy in lymphocytes) protein. Proteins in this group contain a C3H2C3 RING finger. E3 ubiquitin ligase is part of an enzymic cascade, the end result of which is the ubiquitination of proteins. In this cascade, E1 activates the ubiquitin, the activated ubiquitin is carried by E2, and E3 recognizes the acceptor protein as well as catalyzes the transfer of the activated ubiquitin from E2 to this acceptor. GRAIL, a transmembrane protein localized in the endosomes, controls the development of T cell clonal anergy, and may ubiquitinate membrane-associated targets for T cell activation. GRAIL1 is associated with, and regulated by, two isoforms of otubain 1 (the ubiquitin-specific protease). Additional E3s belonging to this group include human (h)Goliath and Xenopus GREUL1 (Goliath Related E3 Ubiquitin Ligase 1). hGoliath and GRAIL both have the property of self-ubiquitination. hGoliath is expressed in leukocytes; its expression and localization is not modified in leukemia. GREUL1 may play a role in the generation of anterior ectoderm. 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 189065290  65 LVPAEPP---EACGELSNgFFIQDQ----IALVERGGCSFLSKTRVVQEHGGRAVIISDN 117
Cdd:cd02122   35 VVVPDPPndhYGCDPDTR-FPIPPNgepwIALIQRGNCTFEEKIKLAAERNASAVVIYNN 93

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
                 ....*....|....*....|....*....|..
gi 189065290  87 IALVERGGCSFLSKTRVVQEHGGRAVIISDNA 118
Cdd:cd04816   46 IVLVDRGGCPFADKQKVAAARGAVAVIVVNNS 77

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 189065290  67 PAEPPEACGELSNgFFIQDQ--------IALVERGGCSFLSKTRVVQEHGGRAVIISDNAVD--------NDSFYVEMIQ 130
Cdd:cd02125   18 PKENRTGCKEFDV-FFKPKKsepgrrpvILLLDRGGCFFTLKAWNAQQAGAAAVLVADNVDEplltmdtpEESGSADYIE 96

                         90       100
                 ....*....|....*....|....*..
gi 189065290 131 DSTqrtadIPALFLLGRDGYMIRRSLE 157
Cdd:cd02125   97 KIT-----IPSALITKAFGEKLKKAIS 118

PA_PoS1_like: Protease-associated (PA) domain PoS1-like. This group includes various PA domain-containing proteins similar to Pleurotus ostreatus (Po)S1. PoSl, the main extracellular protease in P. ostreatus is a subtilisin-like serine protease belonging to the peptidase S8 family. Ca2+ and Mn2+ both stimulate the protease activity of (Po)S1. Ca2+ protects PoS1 from autolysis. PoS1 is a monomeric glycoprotein, which may play a role in the regulation of laccases in lignin formation. (Po)S1 participates in the degradation of POXA1b, and in the activation of POXA3, (POXA1b and POXA3 are laccase isoenzymes), but its effect may be indirect. The significance of the PA domain to PoS1 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 189065290  73 ACGELSNGF-FIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDNA 118
Cdd:cd02124   43 ACQPLPDDTpDLSGYIVLVRRGTCTFATKAANAAAKGAKYVLIYNNG 89