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Conserved domains on  [gi|1034671657|ref|XP_016870718|]
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aminopeptidase O isoform X1 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
GluZincin super family cl14813
Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, ...
244-652 4.04e-40

Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, M2, M3, M4, M13, M32 and M36 (fungalysins); The Gluzincin family (thermolysin-like peptidases or TLPs) includes several zinc-dependent metallopeptidases such as M1, M2, M3, M4, M13, M32, M36 peptidases (MEROPS classification), which contain the HEXXH motif as part of their active site. Peptidases in this family bind a single catalytic zinc ion which is tetrahedrally co-ordinated by three amino acid ligands and a water molecule that forms the nucleophile on activation during catalysis. The M1 family includes aminopeptidase N (APN) and leukotriene A4 hydrolase (LTA4H). APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and is present in a variety of human tissues and cell types. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity such that the two activities occupy different, but overlapping sites. The M3_like peptidases include the M2_ACE, M3 or neurolysin-like family (subfamilies M3B_PepF and M3A) and M32_Taq peptidases. The M2 peptidase angiotensin converting enzyme (ACE, EC 3.4.15.1) catalyzes the conversion of decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II. ACE is a key component of the renin-angiotensin system that regulates blood pressure, thus ACE inhibitors are important for the treatment of hypertension. M3A includes thimet oligopeptidase (TOP; endopeptidase 3.4.24.15), neurolysin (3.4.24.16), and the mitochondrial intermediate peptidase; and M3B includes oligopeptidase F. The M32 family includes eukaryotic enzymes from protozoa Trypanosoma cruzi, a causative agent of Chagas' disease, and from Leishmania major, a parasite that causes leishmaniasis, making these enzymes attractive targets for drug development. The M4 family includes secreted protease thermolysin (EC 3.4.24.27), pseudolysin, aureolysin, and neutral protease as well as bacillolysin (EC 3.4.24.28) that degrade extracellular proteins and peptides for bacterial nutrition, especially prior to sporulation. Thermolysin is widely used as a nonspecific protease to obtain fragments for peptide sequencing as well as in production of the artificial sweetener aspartame. The M13 family includes neprilysin (EC 3.4.24.11) and endothelin-converting enzyme I (ECE-1, EC 3.4.24.71), which fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity and are prime therapeutic targets for selective inhibition. The peptidase M36 fungalysin family includes endopeptidases from pathogenic fungi. Fungalysin hydrolyzes extracellular matrix proteins such as elastin and keratin. Aspergillus fumigatus causes the pulmonary disease aspergillosis by invading the lungs of immuno-compromised animals and secreting fungalysin that possibly breaks down proteinaceous structural barriers.


The actual alignment was detected with superfamily member cd09599:

Pssm-ID: 449360 [Multi-domain]  Cd Length: 442  Bit Score: 154.15  E-value: 4.04e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 244 IRIWYKTKPEGRSVTW-----TSDQSgRPCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAAASFVVLMSGENSAKPtq 318
Cdd:cd09599    98 VKIEYSTTPQATALQWltpeqTAGKK-HPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALMSALRTGEK-- 174
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 319 lwEECSSWYYYVTM--PMPASTFTIAVGcwtemkmetwssnDLAtERPFSPseanfrHVGVCShmeypcrfqnasattqE 396
Cdd:cd09599   175 --EEAGTGTYTFEQpvPIPSYLIAIAVG-------------DLE-SREIGP------RSGVWA----------------E 216
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 397 iiPHRVfapvcltgACQETLLRLIPPCLSAAHSVLGAHPFSRLDVLIVPANFPSLGMASPHIMFLSQSILTGGNHLCGTr 476
Cdd:cd09599   217 --PSVV--------DAAAEEFADTEKFLKAAEKLYGPYVWGRYDLLVLPPSFPYGGMENPCLTFATPTLIAGDRSLVDV- 285
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 477 LCHEIAHAWFGLAIGARDWTEEWLSEGFATHLEdvfwataqqlapyeaR---------EQQELRACLRWRRLQDEMQCSP 547
Cdd:cd09599   286 IAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLE---------------RrilerlygeEYRQFEAILGWKDLQESIKEFG 350
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 548 EEM--QVLRPskdktghtsdsgasvIKHGLNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQD 625
Cdd:cd09599   351 EDPpyTLLVP---------------DLKGVDPDDAFSSVPYEKGFQFLYYLEQLGGREVFDPFLRAYFKKFAFQSIDTED 415
                         410       420
                  ....*....|....*....|....*..
gi 1034671657 626 FLQMLLENIPEEKRLELSVENIyQDWL 652
Cdd:cd09599   416 FKDFLLEYFAEDKPEILDKIDW-DAWL 441
Leuk-A4-hydro_C super family cl08525
Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of ...
721-771 1.75e-12

Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of two layers of parallel alpha-helices, five in the inner layer and four in the outer, arranged in an antiparallel manner, with perpendicular loops containing short helical segments on top. They are required for the formation of a deep cleft harbouring the catalytic Zn2+ site in Leukotriene A4 hydrolase.


The actual alignment was detected with superfamily member pfam09127:

Pssm-ID: 430422  Cd Length: 112  Bit Score: 64.43  E-value: 1.75e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034671657 721 QKTLSPRTLQSLQRTYHLQD-QDAEVRHRWCELIVKHKFTKAYKSVERFLQE 771
Cdd:pfam09127  16 FSPLSPEQLKALDEVYKLSEsKNAEIRFRWLRLALKAKYEPAYPEVAEFLGE 67
 
Name Accession Description Interval E-value
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
244-652 4.04e-40

Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents the N-terminal catalytic domain of leukotriene A4 hydrolase (LTA4H; E.C. 3.3.2.6) and the close homolog cold-active aminopeptidase (Colwellia psychrerythraea-type peptidase; ColAP), both members of the aminopeptidase M1 family. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase is poorly understood while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals. It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives. The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase. Thermodynamic characterization using different biophysical methods shows that structurally distinct inhibitors of the LTA4H occupy different regions of the binding site; while some (RB202, ARM1 and SC57461A) bind to the hydrophobic hydrolase side, both bestatin and captopril are located at the hydrophilic peptidase side. LTB4H overexpression is associated with different pathological conditions and diseases such as cystic fibrosis, coronary heart disease, sepsis, shock, connective tissue disease, and chronic obstructive pulmonary disease. It is also overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well-known red wine polyphenolic compound with cancer chemopreventive activity.


Pssm-ID: 341062 [Multi-domain]  Cd Length: 442  Bit Score: 154.15  E-value: 4.04e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 244 IRIWYKTKPEGRSVTW-----TSDQSgRPCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAAASFVVLMSGENSAKPtq 318
Cdd:cd09599    98 VKIEYSTTPQATALQWltpeqTAGKK-HPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALMSALRTGEK-- 174
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 319 lwEECSSWYYYVTM--PMPASTFTIAVGcwtemkmetwssnDLAtERPFSPseanfrHVGVCShmeypcrfqnasattqE 396
Cdd:cd09599   175 --EEAGTGTYTFEQpvPIPSYLIAIAVG-------------DLE-SREIGP------RSGVWA----------------E 216
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 397 iiPHRVfapvcltgACQETLLRLIPPCLSAAHSVLGAHPFSRLDVLIVPANFPSLGMASPHIMFLSQSILTGGNHLCGTr 476
Cdd:cd09599   217 --PSVV--------DAAAEEFADTEKFLKAAEKLYGPYVWGRYDLLVLPPSFPYGGMENPCLTFATPTLIAGDRSLVDV- 285
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 477 LCHEIAHAWFGLAIGARDWTEEWLSEGFATHLEdvfwataqqlapyeaR---------EQQELRACLRWRRLQDEMQCSP 547
Cdd:cd09599   286 IAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLE---------------RrilerlygeEYRQFEAILGWKDLQESIKEFG 350
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 548 EEM--QVLRPskdktghtsdsgasvIKHGLNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQD 625
Cdd:cd09599   351 EDPpyTLLVP---------------DLKGVDPDDAFSSVPYEKGFQFLYYLEQLGGREVFDPFLRAYFKKFAFQSIDTED 415
                         410       420
                  ....*....|....*....|....*..
gi 1034671657 626 FLQMLLENIPEEKRLELSVENIyQDWL 652
Cdd:cd09599   416 FKDFLLEYFAEDKPEILDKIDW-DAWL 441
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
244-771 7.03e-25

leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive subset within the zinc metallopeptidase family M1 (pfam01433). The majority of the members of pfam01433 are aminopeptidases, but the sequences in this family for which the function is known are leukotriene A-4 hydrolase. A dual epoxide hydrolase and aminopeptidase activity at the same active site is indicated. The physiological substrate for aminopeptidase activity is not known.


Pssm-ID: 274120 [Multi-domain]  Cd Length: 602  Bit Score: 110.25  E-value: 7.03e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 244 IRIWYKTKPEGRSVTW-TSDQ-SGR--PCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAaaSFVVLMSGENSAKPTql 319
Cdd:TIGR02411  97 LNISFSTTPKCTALQWlNPEQtSGKkhPYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVES--PLPVLMSGIRDGETS-- 172
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 320 wEECSSWYYYVTMPMPASTFTIAVGcwtemkmetwssnDLATeRPFSPseanfrhvgvcshmeypcrfqNASATTQEIIP 399
Cdd:TIGR02411 173 -NDPGKYLFKQKVPIPAYLIAIASG-------------DLAS-APIGP---------------------RSTVYSEPEQL 216
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 400 HrvfapvcltgACQETLLRLIPPCLSAAHSVLGAHPFSRLDVLIVPANFPSLGMASPHIMFLSQSILTGGNHLCGTrLCH 479
Cdd:TIGR02411 217 E----------KCQYEFENDTEKFIKTAEDLIFPYEWGQYDLLVLPPSFPYGGMENPNLTFATPTLIAGDRSNVDV-IAH 285
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 480 EIAHAWFGLAIGARDWTEEWLSEGFATHLEdvfwatAQQLAPYEAREQQELRACLRWRRLQDE---MQCSPEEMQVLRPS 556
Cdd:TIGR02411 286 ELAHSWSGNLVTNCSWEHFWLNEGWTVYLE------RRIIGRLYGEKTRHFSALIGWGDLQESvktLGETPEFTKLVVDL 359
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 557 KDKtghtsdsgasvikhglNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFS-FLRKFVHTFHGQLILSQDFLQMLLEN-I 634
Cdd:TIGR02411 360 KDN----------------DPDDAFSSVPYEKGFNFLFYLEQLLGGPAEFDpFLRHYFKKFAYKSLDTYQFKDALYEYfK 423
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 635 PEEKRLELSVENiYQDWLESSGIP--KPlqrerraGAECGLARQVRAEVTKWIGVNRRPRKRK-RREKEEVFEKLLPDQL 711
Cdd:TIGR02411 424 DKKKVDKLDAVD-WETWLYSPGMPpvKP-------NFDTTLADECYALADRWVDAAKADDLSSfNAKDIKDFSSHQLVLF 495
                         490       500       510       520       530       540
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034671657 712 VLLLEHLLEQKTLSPRTLQSLQRTYHL-QDQDAEVRHRWCELIVKHKFTKAYKSVERFLQE 771
Cdd:TIGR02411 496 LETLTERGGDWALPEGHIKRLGDIYNFaASKNAEVRFRWFRLAIQAKLEDEYPLLADWLGT 556
PepN COG0308
Aminopeptidase N [Amino acid transport and metabolism];
265-659 7.95e-16

Aminopeptidase N [Amino acid transport and metabolism];


Pssm-ID: 223385 [Multi-domain]  Cd Length: 859  Bit Score: 82.14  E-value: 7.95e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 265 GRPCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAAASFVVLMSGeNSAKPTQLWEECSSWYYYVTMPMPASTFTIAVG 344
Cdd:COG0308   132 GKPYLITQCEAEGARRIFPCIDEPDVKATFTLTIRADKGPKLISNG-NLIDGGTLVDGRKIVKFEDTPPMPTYLFALVAG 210
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 345 cwtemkmetwssndlaterpfspseanfrhvgvcshmEYPCrFQNASATTQEIIPHRVFAPVCLTGACQ---ETLLRLIP 421
Cdd:COG0308   211 -------------------------------------DLEV-FRDKFDTRSRDVPLEIYVPPGVLDRAKyalDETKRSIE 252
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 422 pclsAAHSVLGAHPFSRLDVLIVPaNFPSLGMASPHIM-FLSQSILTGGNHLCGTR-------LCHEIAHAWFGLAIGAR 493
Cdd:COG0308   253 ----FYEEYFGLPYALPIDIVAVP-DFSAGAMENWGLVtFREKYLLADPETATDSDyenveevIAHELAHQWFGNLVTMK 327
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 494 DWTEEWLSEGFATHLEdVFWATAQQLAPYEAREqqelraclRWRRLQDEMQcspeemqvLRpskdktghtSDSGASV--- 570
Cdd:COG0308   328 WWDDLWLNEGFATFRE-VLWSEDLGGRAWKRWE--------DFRTLRTSIA--------LA---------EDSLPSShpi 381
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 571 ---IKHGLNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQDFLQMLlenipeEKRLELSVENI 647
Cdd:COG0308   382 rvdVYDPKEINDFFDAIVYEKGASVLRMLETLLGEEAFRKGLSLYFKRHAGGNATTMDLWKAL------EDASGKDLSAF 455
                         410
                  ....*....|..
gi 1034671657 648 YQDWLESSGIPK 659
Cdd:COG0308   456 FESWLSQAGYPV 467
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
435-632 6.42e-15

Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ widely in specificity, hydrolysing acidic, basic or neutral N-terminal residues. This family includes leukotriene-A4 hydrolase, this enzyme also has an aminopeptidase activity.


Pssm-ID: 426262 [Multi-domain]  Cd Length: 219  Bit Score: 74.63  E-value: 6.42e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 435 PFSRLDVLIVPaNFPSLGMASPH-IMFLSQSILTGGNHLCGTRL-------CHEIAHAWFGLAIGARDWTEEWLSEGFAT 506
Cdd:pfam01433  22 PLPKYDLVALP-DFSAGAMENWGlITYRETLLLYDPGNSSTSDKqrvasviAHELAHQWFGNLVTMKWWDDLWLNEGFAT 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 507 HLEDVFwatAQQLAPyEAREQQELRACLRWRRLQdeMQCSPEEmqvlRPSKDKTGHTSDsgasvikhglnPEKIFMQVHY 586
Cdd:pfam01433 101 YMEYLG---TDALFP-EWNIWEQFLLDEVQNAMA--RDALDSS----HPITQNVNDPSE-----------IDDIFDAIPY 159
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1034671657 587 LKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQDFLQMLLE 632
Cdd:pfam01433 160 EKGASVLRMLETLLGEEVFQKGLRSYLKKFQYGNATTEDLWDALSE 205
Leuk-A4-hydro_C pfam09127
Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of ...
721-771 1.75e-12

Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of two layers of parallel alpha-helices, five in the inner layer and four in the outer, arranged in an antiparallel manner, with perpendicular loops containing short helical segments on top. They are required for the formation of a deep cleft harbouring the catalytic Zn2+ site in Leukotriene A4 hydrolase.


Pssm-ID: 430422  Cd Length: 112  Bit Score: 64.43  E-value: 1.75e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034671657 721 QKTLSPRTLQSLQRTYHLQD-QDAEVRHRWCELIVKHKFTKAYKSVERFLQE 771
Cdd:pfam09127  16 FSPLSPEQLKALDEVYKLSEsKNAEIRFRWLRLALKAKYEPAYPEVAEFLGE 67
 
Name Accession Description Interval E-value
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
244-652 4.04e-40

Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents the N-terminal catalytic domain of leukotriene A4 hydrolase (LTA4H; E.C. 3.3.2.6) and the close homolog cold-active aminopeptidase (Colwellia psychrerythraea-type peptidase; ColAP), both members of the aminopeptidase M1 family. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase is poorly understood while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals. It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives. The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase. Thermodynamic characterization using different biophysical methods shows that structurally distinct inhibitors of the LTA4H occupy different regions of the binding site; while some (RB202, ARM1 and SC57461A) bind to the hydrophobic hydrolase side, both bestatin and captopril are located at the hydrophilic peptidase side. LTB4H overexpression is associated with different pathological conditions and diseases such as cystic fibrosis, coronary heart disease, sepsis, shock, connective tissue disease, and chronic obstructive pulmonary disease. It is also overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well-known red wine polyphenolic compound with cancer chemopreventive activity.


Pssm-ID: 341062 [Multi-domain]  Cd Length: 442  Bit Score: 154.15  E-value: 4.04e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 244 IRIWYKTKPEGRSVTW-----TSDQSgRPCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAAASFVVLMSGENSAKPtq 318
Cdd:cd09599    98 VKIEYSTTPQATALQWltpeqTAGKK-HPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALMSALRTGEK-- 174
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 319 lwEECSSWYYYVTM--PMPASTFTIAVGcwtemkmetwssnDLAtERPFSPseanfrHVGVCShmeypcrfqnasattqE 396
Cdd:cd09599   175 --EEAGTGTYTFEQpvPIPSYLIAIAVG-------------DLE-SREIGP------RSGVWA----------------E 216
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 397 iiPHRVfapvcltgACQETLLRLIPPCLSAAHSVLGAHPFSRLDVLIVPANFPSLGMASPHIMFLSQSILTGGNHLCGTr 476
Cdd:cd09599   217 --PSVV--------DAAAEEFADTEKFLKAAEKLYGPYVWGRYDLLVLPPSFPYGGMENPCLTFATPTLIAGDRSLVDV- 285
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 477 LCHEIAHAWFGLAIGARDWTEEWLSEGFATHLEdvfwataqqlapyeaR---------EQQELRACLRWRRLQDEMQCSP 547
Cdd:cd09599   286 IAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLE---------------RrilerlygeEYRQFEAILGWKDLQESIKEFG 350
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 548 EEM--QVLRPskdktghtsdsgasvIKHGLNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQD 625
Cdd:cd09599   351 EDPpyTLLVP---------------DLKGVDPDDAFSSVPYEKGFQFLYYLEQLGGREVFDPFLRAYFKKFAFQSIDTED 415
                         410       420
                  ....*....|....*....|....*..
gi 1034671657 626 FLQMLLENIPEEKRLELSVENIyQDWL 652
Cdd:cd09599   416 FKDFLLEYFAEDKPEILDKIDW-DAWL 441
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
244-771 7.03e-25

leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive subset within the zinc metallopeptidase family M1 (pfam01433). The majority of the members of pfam01433 are aminopeptidases, but the sequences in this family for which the function is known are leukotriene A-4 hydrolase. A dual epoxide hydrolase and aminopeptidase activity at the same active site is indicated. The physiological substrate for aminopeptidase activity is not known.


Pssm-ID: 274120 [Multi-domain]  Cd Length: 602  Bit Score: 110.25  E-value: 7.03e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 244 IRIWYKTKPEGRSVTW-TSDQ-SGR--PCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAaaSFVVLMSGENSAKPTql 319
Cdd:TIGR02411  97 LNISFSTTPKCTALQWlNPEQtSGKkhPYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVES--PLPVLMSGIRDGETS-- 172
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 320 wEECSSWYYYVTMPMPASTFTIAVGcwtemkmetwssnDLATeRPFSPseanfrhvgvcshmeypcrfqNASATTQEIIP 399
Cdd:TIGR02411 173 -NDPGKYLFKQKVPIPAYLIAIASG-------------DLAS-APIGP---------------------RSTVYSEPEQL 216
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 400 HrvfapvcltgACQETLLRLIPPCLSAAHSVLGAHPFSRLDVLIVPANFPSLGMASPHIMFLSQSILTGGNHLCGTrLCH 479
Cdd:TIGR02411 217 E----------KCQYEFENDTEKFIKTAEDLIFPYEWGQYDLLVLPPSFPYGGMENPNLTFATPTLIAGDRSNVDV-IAH 285
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 480 EIAHAWFGLAIGARDWTEEWLSEGFATHLEdvfwatAQQLAPYEAREQQELRACLRWRRLQDE---MQCSPEEMQVLRPS 556
Cdd:TIGR02411 286 ELAHSWSGNLVTNCSWEHFWLNEGWTVYLE------RRIIGRLYGEKTRHFSALIGWGDLQESvktLGETPEFTKLVVDL 359
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 557 KDKtghtsdsgasvikhglNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFS-FLRKFVHTFHGQLILSQDFLQMLLEN-I 634
Cdd:TIGR02411 360 KDN----------------DPDDAFSSVPYEKGFNFLFYLEQLLGGPAEFDpFLRHYFKKFAYKSLDTYQFKDALYEYfK 423
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 635 PEEKRLELSVENiYQDWLESSGIP--KPlqrerraGAECGLARQVRAEVTKWIGVNRRPRKRK-RREKEEVFEKLLPDQL 711
Cdd:TIGR02411 424 DKKKVDKLDAVD-WETWLYSPGMPpvKP-------NFDTTLADECYALADRWVDAAKADDLSSfNAKDIKDFSSHQLVLF 495
                         490       500       510       520       530       540
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034671657 712 VLLLEHLLEQKTLSPRTLQSLQRTYHL-QDQDAEVRHRWCELIVKHKFTKAYKSVERFLQE 771
Cdd:TIGR02411 496 LETLTERGGDWALPEGHIKRLGDIYNFaASKNAEVRFRWFRLAIQAKLEDEYPLLADWLGT 556
M1 cd09595
Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 ...
241-627 2.08e-20

Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 hydrolase; The model represents the catalytic domains of M1 peptidase family members including aminopeptidase N (APN) and leukotriene A4 hydrolase (LTA4H). All peptidases in this family bind a single catalytic zinc ion which is tetrahedrally co-ordinated by three amino acid ligands and a water molecule that forms the nucleophile upon activation during catalysis. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and is present in a variety of human tissues and cell types. APN expression is dysregulated in many inflammatory diseases and is enhanced in numerous tumor cells, making it a lead target in the development of anti-cancer and anti-inflammatory drugs. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase in LTA4H is as yet unknown, while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals.


Pssm-ID: 341058 [Multi-domain]  Cd Length: 413  Bit Score: 94.82  E-value: 2.08e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 241 PHAIRIWYKTKPEGRSVTWTSDQSG---RPCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAAASFVVLMSG----ENS 313
Cdd:cd09595    76 TFTVRISFEAKPSKNLLGWLWEQTAgkeKPYLFTQFEATHARRIFPCIDHPAVKATFTVTITTPKKDLLASNGalvgEET 155
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 314 AKPTQLWeecssWYYYVTMPMPASTFTIAVGcwtemkmetwssnDLaterpfspseanfrhvgvcshmeypcRFQNASAT 393
Cdd:cd09595   156 GANGRKT-----YRFEDTPPIPTYLVAVVVG-------------DL--------------------------EFKYVTVK 191
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 394 TQEIIPHRVFAPVcltgacqETLLRLIPPcLSAAHSVL--------GAHPFSRLDVLIVPaNFPSLGMASPH-IMFLSQS 464
Cdd:cd09595   192 SQPRVGLSVYSEP-------LQVDQAQYA-FDATRAALawfedyfgGPYPLPKYDLLAVP-DFNSGAMENPGlITFRTTY 262
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 465 ILTGGNHLCGTR-----LCHEIAHAWFGLAIGARDWTEEWLSEGFATHLEDVFWATAQQLapyeareqqelraclrWRRL 539
Cdd:cd09595   263 LLRSKVTDTGARsienvIAHELAHQWFGNLVTMRWWNDLWLNEGFAVYYENRIMDATFGT----------------SSRH 326
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 540 QDEMQCSPEEMQVLRPskDKTGHTSDSgasvIKHGLNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQ 619
Cdd:cd09595   327 LDQLSGSSDLNTEQLL--EDSSPTSTP----VRSPADPDVAYDGVTYAKGALVLRMLEELVGEEAFDKGVQAYFNRHKFK 400

                  ....*...
gi 1034671657 620 LILSQDFL 627
Cdd:cd09595   401 NATTDDFI 408
M1_APN_like cd09603
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly ...
220-630 4.65e-17

Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly bacterial and some archaeal M1 peptidases with smilarity to the catalytic domain of aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341066 [Multi-domain]  Cd Length: 410  Bit Score: 84.17  E-value: 4.65e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 220 FDTDTWSLQIRKTGAQTATDfPHAIRIWYKTKP-EGRSVTW--TSDQSGRPCVYTVGSPINNRALFPCQEPPVAMSTWQA 296
Cdd:cd09603    58 FTHDGDKLVITLPRPLAAGE-TFTVTVRYSGKPrPAGYPPGdgGGWEEGDDGVWTAGQPEGASTWFPCNDHPDDKATYDI 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 297 TVRAAASFVV-----LMSGENSAKPTqlweecSSWYYYVTMPMPASTFTIAVGcwtemkmetwssndlaterpfspsean 371
Cdd:cd09603   137 TVTVPAGLTVvsngrLVSTTTNGGGT------TTWHWKMDYPIATYLVTLAVG--------------------------- 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 372 frhvgvcshmeypcRFQNASATTQEIIPHRVFAPVCLTGAcQETLLRLIPPCLSAAHSVLGAHPFSRLDVLIVPANFpsL 451
Cdd:cd09603   184 --------------RYAVVEDGSGGGIPLRYYVPPGDAAK-AKASFARTPEMLDFFEELFGPYPFEKYGQVVVPDLG--G 246
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 452 GMasPHimflsQSILT-GGNHLCGTR-----LCHEIAHAWFGLAIGARDWTEEWLSEGFATHLEDVFWAtaqqlapyEAR 525
Cdd:cd09603   247 GM--EH-----QTATTyGNNFLNGDRgserlIAHELAHQWFGDSVTCADWADIWLNEGFATYAEWLWSE--------HKG 311
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 526 EQQELRAclrwrRLQDEMQcspeemQVLRPSKdktghtsdsgasVIKHGLNPEKIFMQVHYLKGYFLLRFLAKRLGDETY 605
Cdd:cd09603   312 GADAYRA-----YLAGQRQ------DYLNADP------------GPGRPPDPDDLFDRDVYQKGALVLHMLRNLLGDEAF 368
                         410       420
                  ....*....|....*....|....*
gi 1034671657 606 FSFLRKFVHTFHGQLILSQDFLQML 630
Cdd:cd09603   369 FAALRAYLARYAHGNVTTEDFIAAA 393
PepN COG0308
Aminopeptidase N [Amino acid transport and metabolism];
265-659 7.95e-16

Aminopeptidase N [Amino acid transport and metabolism];


Pssm-ID: 223385 [Multi-domain]  Cd Length: 859  Bit Score: 82.14  E-value: 7.95e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 265 GRPCVYTVGSPINNRALFPCQEPPVAMSTWQATVRAAASFVVLMSGeNSAKPTQLWEECSSWYYYVTMPMPASTFTIAVG 344
Cdd:COG0308   132 GKPYLITQCEAEGARRIFPCIDEPDVKATFTLTIRADKGPKLISNG-NLIDGGTLVDGRKIVKFEDTPPMPTYLFALVAG 210
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 345 cwtemkmetwssndlaterpfspseanfrhvgvcshmEYPCrFQNASATTQEIIPHRVFAPVCLTGACQ---ETLLRLIP 421
Cdd:COG0308   211 -------------------------------------DLEV-FRDKFDTRSRDVPLEIYVPPGVLDRAKyalDETKRSIE 252
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 422 pclsAAHSVLGAHPFSRLDVLIVPaNFPSLGMASPHIM-FLSQSILTGGNHLCGTR-------LCHEIAHAWFGLAIGAR 493
Cdd:COG0308   253 ----FYEEYFGLPYALPIDIVAVP-DFSAGAMENWGLVtFREKYLLADPETATDSDyenveevIAHELAHQWFGNLVTMK 327
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 494 DWTEEWLSEGFATHLEdVFWATAQQLAPYEAREqqelraclRWRRLQDEMQcspeemqvLRpskdktghtSDSGASV--- 570
Cdd:COG0308   328 WWDDLWLNEGFATFRE-VLWSEDLGGRAWKRWE--------DFRTLRTSIA--------LA---------EDSLPSShpi 381
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 571 ---IKHGLNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQDFLQMLlenipeEKRLELSVENI 647
Cdd:COG0308   382 rvdVYDPKEINDFFDAIVYEKGASVLRMLETLLGEEAFRKGLSLYFKRHAGGNATTMDLWKAL------EDASGKDLSAF 455
                         410
                  ....*....|..
gi 1034671657 648 YQDWLESSGIPK 659
Cdd:COG0308   456 FESWLSQAGYPV 467
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
435-632 6.42e-15

Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ widely in specificity, hydrolysing acidic, basic or neutral N-terminal residues. This family includes leukotriene-A4 hydrolase, this enzyme also has an aminopeptidase activity.


Pssm-ID: 426262 [Multi-domain]  Cd Length: 219  Bit Score: 74.63  E-value: 6.42e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 435 PFSRLDVLIVPaNFPSLGMASPH-IMFLSQSILTGGNHLCGTRL-------CHEIAHAWFGLAIGARDWTEEWLSEGFAT 506
Cdd:pfam01433  22 PLPKYDLVALP-DFSAGAMENWGlITYRETLLLYDPGNSSTSDKqrvasviAHELAHQWFGNLVTMKWWDDLWLNEGFAT 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 507 HLEDVFwatAQQLAPyEAREQQELRACLRWRRLQdeMQCSPEEmqvlRPSKDKTGHTSDsgasvikhglnPEKIFMQVHY 586
Cdd:pfam01433 101 YMEYLG---TDALFP-EWNIWEQFLLDEVQNAMA--RDALDSS----HPITQNVNDPSE-----------IDDIFDAIPY 159
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1034671657 587 LKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQDFLQMLLE 632
Cdd:pfam01433 160 EKGASVLRMLETLLGEEVFQKGLRSYLKKFQYGNATTEDLWDALSE 205
M1_APN_like cd09604
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains ...
431-652 8.88e-15

Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains bacterial M1 peptidases with smilarity to the catalytic domain of aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341067  Cd Length: 440  Bit Score: 77.70  E-value: 8.88e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 431 LGAHPFSRLDvlIVPANFPSLGMASPHIMFLSQSILTGGNHLCGTrLCHEIAHAWFGLAIG--ARDWTeeWLSEGFATHL 508
Cdd:cd09604   254 FGPYPYPELD--VVQGPFGGGGMEYPGLVFIGSRLYDPKRSLEGV-VVHEIAHQWFYGIVGndERREP--WLDEGLATYA 328
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 509 EDVFwataqqlapYEAREQQELRACLRWRRLQDEMQCSPEEmQVLRPSkDKTGHTSDSGASVikhglnpekifmqvhYLK 588
Cdd:cd09604   329 ESLY---------LEEKYGKEAADELLGRRYYRAYARGPGG-PINLPL-DTFPDGSYYSNAV---------------YSK 382
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034671657 589 GYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQDFLQMLlenipeEKRLELSVENIYQDWL 652
Cdd:cd09604   383 GALFLEELREELGDEAFDKALREYYRRYKFKHPTPEDFFRTA------EEVSGKDLDWFFRGWL 440
Leuk-A4-hydro_C pfam09127
Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of ...
721-771 1.75e-12

Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of two layers of parallel alpha-helices, five in the inner layer and four in the outer, arranged in an antiparallel manner, with perpendicular loops containing short helical segments on top. They are required for the formation of a deep cleft harbouring the catalytic Zn2+ site in Leukotriene A4 hydrolase.


Pssm-ID: 430422  Cd Length: 112  Bit Score: 64.43  E-value: 1.75e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1034671657 721 QKTLSPRTLQSLQRTYHLQD-QDAEVRHRWCELIVKHKFTKAYKSVERFLQE 771
Cdd:pfam09127  16 FSPLSPEQLKALDEVYKLSEsKNAEIRFRWLRLALKAKYEPAYPEVAEFLGE 67
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
275-653 2.02e-12

Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), aminopeptidase Q (APQ), tricorn interacting factor F3, and endoplasmic reticulum aminopeptidase 1 (ERAP1); This M1 peptidase family includes eukaryotic and bacterial members: the catalytic domains of aminopeptidase N (APN), aminopeptidase Q (APQ, laeverin), endoplasmic reticulum aminopeptidase 1 (ERAP1) as well as tricorn interacting factor F3. Aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease, preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is considered a marker of differentiation since it is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. ERAP1, also known as endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP), adipocyte derived leucine aminopeptidase (A-LAP), or aminopeptidase regulating tumor necrosis factor receptor I (THFRI) shedding (ARTS-1), associates with the closely related ER aminopeptidase ERAP2, for the final trimming of peptides within the ER for presentation by MHC class I molecules. ERAP1 is associated with ankylosing spondylitis (AS), an inflammatory arthritis that predominantly affects the spine. ERAP1 also aids in the shedding of membrane-bound cytokine receptors. The tricorn interacting factor F3, together with factors F1 and F2, degrades the tricorn protease products, producing free amino acids, thus completing the proteasomal degradation pathway. F3 is homologous to F2, but not F1, and shows a strong preference for glutamate in the P1' position. APQ, also known as laeverin, is specifically expressed in human embryo-derived extravillous trophoblasts (EVTs) that invade the uterus during early placentation. It cleaves the N-terminal amino acid of various peptides such as angiotensin III, endokinin C, and kisspeptin-10, all expressed in the placenta in large quantities. APN is a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs are also putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341064 [Multi-domain]  Cd Length: 442  Bit Score: 70.30  E-value: 2.02e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 275 PINNRALFPCQ-EPpvAM-STWQATVRAAASFVVL--MSGENSAKPTQLWEEcssWYYYVTMPMPASTFTIAVGcwtemk 350
Cdd:cd09601   122 PTDARRAFPCFdEP--AFkATFDITITHPKGYTALsnMPPVESTELEDGWKT---TTFETTPPMSTYLVAFVVG------ 190
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 351 metwssndlaterpfspseanfrhvgvcshmeypcRFQNASATTQEIIPHRVFAPVCLTGACQETLlRLIPPCLSAAHSV 430
Cdd:cd09601   191 -----------------------------------DFEYIESTTKSGVPVRVYARPGKIEQGDFAL-EVAPKILDFYEDY 234
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 431 LG-AHPFSRLDVLIVPaNFPSLGMASP-HIMFLSQSILTGGNHLCGTRL-------CHEIAHAWFG-LaIGARDWTEEWL 500
Cdd:cd09601   235 FGiPYPLPKLDLVAIP-DFAAGAMENWgLITYRETALLYDPKTSSASDKqrvaeviAHELAHQWFGnL-VTMKWWDDLWL 312
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 501 SEGFATHLEdvfWATAQQLAP-YEAREQQelraclrwrrLQDEMQcspeemQVLRpskdktghtSDSGASV------IKH 573
Cdd:cd09601   313 NEGFATYME---YLAVDKLFPeWNMWDQF----------VVDELQ------SALE---------LDSLASShpievpVES 364
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 574 GLNPEKIFMQVHYLKGYFLLRFLAKRLGDETYFSFLRKFVHTFHGQLILSQDFLQMLLENIPEEKrlELSVENIYQDWLE 653
Cdd:cd09601   365 PSEISEIFDAISYSKGASVLRMLENFLGEEVFRKGLRKYLKKHAYGNATTDDLWEALQEASGESK--PLDVKEIMDSWTL 442
M1_APN cd09602
Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the ...
433-506 6.34e-03

Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the catalytic domain of bacterial and eukaryotic aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341065 [Multi-domain]  Cd Length: 440  Bit Score: 39.81  E-value: 6.34e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671657 433 AHPFSRLDVLIVPAnFPSLGMASP-------HIMFLS---QSILTGgnhLCGTRLcHEIAHAWFGLAIGARDWTEEWLSE 502
Cdd:cd09602   241 PYPFGKYDQVFVPE-FNFGAMENPgavtfreSYLFREeptRAQRLR---RANTIL-HEMAHMWFGDLVTMKWWDDLWLNE 315

                  ....
gi 1034671657 503 GFAT 506
Cdd:cd09602   316 SFAD 319
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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