4GA7


Conserved Protein Domain Family
serpinB1_LEI

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cd19560: serpinB1_LEI 
Click on image for an interactive view with Cn3D
serpin family B member 1 (serpin B1), leukocyte elastase inhibitor (LEI)
Leukocyte elastase inhibitor (LEI , also known as proteinase inhibitor 2/PI2, monocyte neutrophil elastase inhibitor/MNEI, EI, or ELANH2) is a member of the clade B serpins or ov-serpins (ovalbumin related serpins) that in humans is encoded by the SERPINB1 gene. Human SERPINB1 is a potent intracellular inhibitor for granzyme H (GzmH) which is constitutively expressed in NK cells and induces target cell death. GzmH cleaves SERPINB1 at Phe343 in the RCL to mediate suicide inhibition. Equine leukocyte elastase inhibitor (HLEI) in contrast to other serpins contains no carbohydrate and has a blocked amino terminus. HLEI is a thymosin beta4-binding protein suggesting a physiological role for cytoplasmic elastase inhibitors in the thymosin B4-regulated rearrangement of the cytoskeleton of leukocytes. HLEI has been proposed to be involved with the control of intracellular protein turnover or the control of elastinolytic activity during inflammation. Ov-serpins are a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.
Statistics
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PSSM-Id: 381028
View PSSM: cd19560
Aligned: 20 rows
Threshold Bit Score: 646.34
Threshold Setting Gi: 661567837
Created: 28-Jun-2017
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
reactive center
Conserved site includes 30 residues -Click on image for an interactive view with Cn3D
Feature 1:reactive center loop (RCL)
Evidence:
  • Comment:depending on the conformational state, RCL is surface accessible in the active form or buried and inserted as the central beta strand in the inactive form
  • Structure:4GA7_A: Human serpinB1 RCL, exposed to solvent
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                        
4GA7_A        11 MEQLSSANTRFALDLFLALSENnpaGNIFISPFSISSAMAMVFLGTRGNTAAQLSKTFHfn---------tvEEVHSRFQ 81  human
NP_001089382   1 MENLSSACTHFCFDLFKKINENnstGNLFFSPISLSTALAMVFLGTKGKTAEQMSKTLHfd---------avKDLHSNFQ 71  African clawed ...
XP_006007367   1 MEKVSAANTLFTLDLFKNINETnptGNIFFSPLSISSALAMVYLGAKGSTADQMQKVLHfd---------kaGEIHPSFQ 71  coelacanth
XP_006888771   1 MEEMSRANNHFTLDLFHVLNKKdptGNIFFSPFSISCAAAMLLVGAKGNSEAQLSKAFHld---------kvEEVHSKFQ 71  Cape elephant s...
XP_007900824   1 MEDLSRVNTHFTLDVFRKLSETnqvGNIFFSPLSISTALAMVYHGAKNNTASQMAKVLHfd---------qvADLHSGFQ 71  elephant shark
KFO04593       1 MENLCNANSRFALDLLRRFNETnptGNVFFSPVSVSAALAMVLLGAKGNTEAQVLKVTNslplfqtlhfdkvEGIHSRFQ 80  Balearica pavon...
KYO35471     293 MEKLRNANTCFALALLKKLNETnptGNIFFSPISISAALAMILLGAKGNTKTQMLKALHyd---------daEDLHSRFQ 363 American alligator
Q5I0S8         1 MENLSSACTHFSFDLFRKINENnatGNVFFSPISISTALAMVLLGARGNTAQQISRILHfd---------avKDLHSNFQ 71  western clawed ...
Q52L45         1 MENLSSACTHFCFDLFKKINENnstGNLFFSPISLSTALAMVFLGTKGKTAEQMSKTLHfd---------avKDLHSNFQ 71  African clawed ...
AIE16052       1 MDAVTAANTEFALDLFRELSTAsgaGNVFFSPASVSAALAMVLLGAKEETAAQMSKSLHld---------gvEDVHGGYQ 71  European river ...
Feature 1                                                                                        
4GA7_A        82 SLNADINKr-GASYILKLANRLYGEKTYNFLPEFLVSTQktyGADLASVDFqhaSEDARKTINQWVKGQTEGKIPELLAS 160 human
NP_001089382  72 TLNAEINKkdVSTYALNLANRLFGEKTFNFLPNFLSSVKkqySADLGTVDFisaLEDARKEINKWVSEQTKGKIPEVLST 151 African clawed ...
XP_006007367  72 SLNTEINK--PGECLLKLANRLYTEKTYNFLPEFLNSATkfyKADLPTVDFknaAEKVRQQINQWVEAQTEGKIQNLLTE 149 coelacanth
XP_006888771  72 CLQAEINKr-DTSYMLKLANRLYGEKTYHYLPDFLATIQkfyGADLASVDFqhaSEEVRKEINQWVKDQTEGKIPDLLPS 150 Cape elephant s...
XP_007900824  72 TLQSDINKa-GALYVLKTANRLYGEKTFNFFEEFIQTCVklyGANLLPVNFlsaADEARQEINKWVEDQTEGKIQDLLAH 150 elephant shark
KFO04593      81 TLTMDINRs-NAPYLLRLANRLYGEKSYSFLPDFLTNTQklyGADLAAVDFlqgYDEARKEINQWVEEKTEGKIPDLLSE 159 Balearica pavon...
KYO35471     364 TLTSDVNRq-GAPYLLKLANRLYGEKTCIFLPDFLANTQksyGASLAMVDFlhaSDEARKHINQWVEEQTEGKIPNLLSE 442 American alligator
Q5I0S8        72 TLNAEINKknVSSYALNLANRLFGEKSFKFLPDFLSSVKkqyNADLGTVDFisaAEDARKEINTWVSEQTKGKIPEVLSA 151 western clawed ...
Q52L45        72 TLNAEINKkdVSTYALNLANRLFGEKTFNFLPNFLSSVKkqySADLGTVDFisaLEDARKEINKWVSEQTKGKIPEVLST 151 African clawed ...
AIE16052      72 SLLGAFSSt-TQGSVLRMANRLYGEKGYNFLQDFLDSSAkyyQAELAAVNFkeaFEEARKEINAWVEGQTEGKIQDLLAS 150 European river ...
Feature 1                                                                                        
4GA7_A       161 gMVDNMTKLVLVNAIYFKGNWKDKFMKEATTNAPFRLNkKDRKTVKMMYQKKKFAYGYIedLKCRVLELPYQgeeLSMVI 240 human
NP_001089382 152 gTVDRSTKLVLVNAIYFKGDWAKKFNAEHTTDMPFQLNkKEQKTVKMMYQKEKLPFNYIpdINCRILELPYVdyeLSMII 231 African clawed ...
XP_006007367 150 gTVTSLTRMVLVNAIYFKGSWVHKFNDQATKEMPFRLNkSKSIPVQMMYQKEKLNFNNVdgMKLKVLELPYVgkeLSMII 229 coelacanth
XP_006888771 151 gVVNNLTKLVLVNAIYFMGKWQKVFHRGNTKEAQFYLNkKDKKMVNMMFQKKPFPYGYIdeVKCHVLVLPYEdneLSMVI 230 Cape elephant s...
XP_007900824 151 gSVDHLTKLVLVNAIYFKGSWAEKFDEKLTEEMPFKLNkNESRTVKMMYLMKKFRFNYIpeVKCKVLELPYVgkeLSMII 230 elephant shark
KFO04593     160 gSVDNMTRLVLVNAIYFKGDWAEKFNEADTTDMPFRLNkNERKTVKMMYQKKKFRFGYIpeVKVRVLELPYDgreLSMII 239 Balearica pavon...
KYO35471     443 gLLNNTTRLVLVNAIYFKGKWGEKFEEQNTKEMPFHLNkNETKTVKMMYQKKKFPFGYIceLECRVLELPYDgdeLSMII 522 American alligator
Q5I0S8       152 gAVNSFTKLVLVNAIYFKGDWAKKFKAEHTKDMPFQLNkKEQKTVKMMYQMEKLPFNYIpeINCRVLELPYVdyeLSMVI 231 western clawed ...
Q52L45       152 gTVDRSTKLVLVNAIYFKGDWAKKFNAEHTTDMPFQLNkKEQKTVKMMYQKEKLPFNYIpdINCRILELPYVdyeLSMII 231 African clawed ...
AIE16052     151 gVVTSLTRLVLVNAVYFKGSWAAKFDPEVTRDAEFKINkNEKKPVKMMYKKAKYNFSHVdeLSVNIVELPYEgnkLSMLL 230 European river ...
Feature 1                                                                                        
4GA7_A       241 LLPDDIEdestGLKKIEEQLTLEKLHEWTkpenldfiEVNVSLPRFKLEESYTLNSDLARLGVQDLFNsSKADLSGMSGA 320 human
NP_001089382 232 ILPDNINddttGLQQLEKELSLEKIHEWTenm--mptDVHIHLPKFKLEDSYKLKSQLAGMGMVDLFNsGSADLSGMSGS 309 African clawed ...
XP_006007367 230 LLPDDISddstGLQQVEKKITLENIQKWTqpgkmrnvEVQVHLPKFKLEDMYDLKSSLTKLGMLDVFLdGQADLSGMTGK 309 coelacanth
XP_006888771 231 LLPRDIEddstGLKKIEEQLTLDKLNEWIssnnvkvnHVNVSLPRFKLEESYNLKDHLASLDVQDILDpSKADLSGISGA 310 Cape elephant s...
XP_007900824 231 MLPDDNEdgspGLKQLETMLTLENLQEWTklnc-mpvEVHVRLPKFKLEDNYELKPILSSLGMQDVFDsAKVDLSGMSGC 309 elephant shark
KFO04593     240 LLPDDIEddstGLQKLEKQLTLENLQEWTcpehlystDVRVRLPKFKLEESYDLKSDLAAMGLLDVFDsGKSDLSGMSGA 319 Balearica pavon...
KYO35471     523 LLPDEIKddttGLQQLEKQLTFEKLCEWTklqnmqpiDVHVHLPKFKLEDSYDLKSALSGLGFLDIFDsGKADLSGMSGA 602 American alligator
Q5I0S8       232 VLPDNINddttGLQQLEKELSLEKINEWTenm--mpiDVHVHLPKFKLEDSYKLKSQLAGMGMADLFEaGSADLSGMSGS 309 western clawed ...
Q52L45       232 ILPDNINddttGLQQLEKELSLEKIHEWTenm--mptDVHIHLPKFKLEDSYKLKSQLAGMGMVDLFNsGSADLSGMSGS 309 African clawed ...
AIE16052     231 LVPLAIEdettGLEKLESALTLKSLNEWTspenmsnlEVKLHLPRFRLENSYTLNDHLQRLGMSSIFTqGKADFSGIDGT 310 European river ...
Feature 1                        ###################      ###########                      
4GA7_A       321 RDifISKIVHKSFVEVNEEGTEAAAATAGIATFCMd-----DPEENFTADHPFLFFIRHNssGSILFLGRFSSP 389 human
NP_001089382 310 NNlfLSEVIHKSFVEVNEEGTEAAAASAGIAMMCM------MREEEFNADHPFLFLIRHNatKSILFFGRYSSP 377 African clawed frog
XP_006007367 310 PGlhVSEVIHKSFVEVNEEGTEAAAATAAIVAFCAfi---pEETVHFTADHPFLFFIRHNssNSVLFFGRYCSP 380 coelacanth
XP_006888771 311 KDlyVSEFVHKSFVEVNEEGTVAAAATAAGRVLCAl-----VHPKNFNANHPFLFFIQHNasKCILFFGRFSSP 379 Cape elephant shrew
XP_007900824 310 RDlyMSRVVHKSFLEVNEEGTEAAAATAAIASFCMl-----TREEIFTADRPFLFFIRHTktNSILFFGRVSSP 378 elephant shark
KFO04593     320 RDlfLSKIVHKAFVEVNEEGTEAAAAGRPPPATAGiamlcmVMEEDFNADHPFLFFIRHNptQSILFFGRYASP 393 Balearica pavonina gi...
KYO35471     603 RNlfLSKIVHKSFVEVNEEGTEAAAATAGMIANCM------FMEEHFTANHPFLFFIRHNptQSILFFGRGNPE 670 American alligator
Q5I0S8       310 NDlyLSEVIHKSFVEVNEEGTEAAAASAGIAMMCL------MREEEFNANHPFLFFIRHNatKSILFFGRYSSP 377 western clawed frog
Q52L45       310 NNlfLSEVIHKSFVEVNEEGTEAAAASAGIAMMCM------MREEEFNADHPFLFLIRHNatKSILFFGRYSSP 377 African clawed frog
AIE16052     311 RDlyVSHVAHKAFVEVNEEGTEAAAATAAIMMMRCa-----RMGPVVRADHPFIFFIRENssGSVLFLGRFASP 379 European river lamprey

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