ILEU_HORSE
ID ILEU_HORSE Reviewed; 379 AA.
AC P05619;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Leukocyte elastase inhibitor;
DE Short=LEI;
DE AltName: Full=Serpin B1;
GN Name=SERPINB1; Synonyms=ELANH2;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND INTERACTION WITH TMSB4.
RC TISSUE=Leukocyte;
RX PubMed=1551869; DOI=10.1016/s0021-9258(19)50466-5;
RA Dubin A., Travis J., Enghild J.J., Potempa J.;
RT "Equine leukocyte elastase inhibitor. Primary structure and identification
RT as a thymosin-binding protein.";
RL J. Biol. Chem. 267:6576-6583(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7687128; DOI=10.1042/bj2930187;
RA Kordula T., Dubin A., Schooltink H., Koj A., Heinrich P.C., Rose-John S.;
RT "Molecular cloning and expression of an intracellular serpin: an elastase
RT inhibitor from horse leucocytes.";
RL Biochem. J. 293:187-193(1993).
RN [3]
RP PROTEIN SEQUENCE OF 343-362.
RX PubMed=3366785; DOI=10.1016/s0021-9258(18)68651-x;
RA Potempa J., Dubin A., Watorek W., Travis J.;
RT "An elastase inhibitor from equine leukocyte cytosol belongs to the serpin
RT superfamily. Further characterization and amino acid sequence of the
RT reactive center.";
RL J. Biol. Chem. 263:7364-7369(1988).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
RX PubMed=1518052; DOI=10.1016/0022-2836(92)91062-t;
RA Baumann U., Bode W., Huber R., Travis J., Potempa J.;
RT "Crystal structure of cleaved equine leucocyte elastase inhibitor
RT determined at 1.95-A resolution.";
RL J. Mol. Biol. 226:1207-1218(1992).
CC -!- FUNCTION: Neutrophil serine protease inhibitor that plays an essential
CC role in the regulation of the innate immune response, inflammation and
CC cellular homeostasis. Acts primarily to protect the cell from proteases
CC released in the cytoplasm during stress or infection. These proteases
CC are important in killing microbes but when released from granules,
CC these potent enzymes also destroy host proteins and contribute to
CC mortality. Regulates the activity of the neutrophil proteases elastase,
CC cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3.
CC Acts also as a potent intracellular inhibitor of GZMH by directly
CC blocking its proteolytic activity. During inflammation, limits the
CC activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing
CC their caspase-recruitment domain (CARD) oligomerization and enzymatic
CC activation. When secreted, promotes the proliferation of beta-cells via
CC its protease inhibitory function. {ECO:0000250|UniProtKB:P30740}.
CC -!- SUBUNIT: Monomer. Interacts (via C-terminus) with CASP1; CASP4 (via
CC CARD domain) and CASP5; these interactions regulate the activity of
CC inflammatory caspases. Interacts with PRTN3. Interacts with GZMH (By
CC similarity). Interacts with TMSB4 (PubMed:1551869).
CC {ECO:0000250|UniProtKB:P30740, ECO:0000269|PubMed:1551869}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P30740}.
CC Cytoplasm {ECO:0000250|UniProtKB:P30740}. Cytolytic granule
CC {ECO:0000250|UniProtKB:P30740}. Early endosome
CC {ECO:0000250|UniProtKB:P30740}.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC {ECO:0000305}.
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DR EMBL; M91161; AAA97513.1; -; mRNA.
DR PIR; A28060; A28060.
DR PIR; A42421; A42421.
DR RefSeq; NP_001075416.1; NM_001081947.1.
DR RefSeq; XP_005603556.1; XM_005603499.2.
DR RefSeq; XP_005603557.1; XM_005603500.2.
DR PDB; 1HLE; X-ray; 1.95 A; A=1-344, B=349-379.
DR PDBsum; 1HLE; -.
DR AlphaFoldDB; P05619; -.
DR SMR; P05619; -.
DR STRING; 9796.ENSECAP00000043372; -.
DR MEROPS; I04.006; -.
DR PaxDb; P05619; -.
DR PeptideAtlas; P05619; -.
DR PRIDE; P05619; -.
DR GeneID; 100049797; -.
DR KEGG; ecb:100049797; -.
DR CTD; 1992; -.
DR HOGENOM; CLU_023330_0_2_1; -.
DR InParanoid; P05619; -.
DR OMA; CMAIEED; -.
DR OrthoDB; 1124079at2759; -.
DR TreeFam; TF352619; -.
DR EvolutionaryTrace; P05619; -.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0044194; C:cytolytic granule; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IBA:GO_Central.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR015557; Serpin_B1.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR InterPro; IPR036186; Serpin_sf.
DR InterPro; IPR042178; Serpin_sf_1.
DR InterPro; IPR042185; Serpin_sf_2.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR PANTHER; PTHR11461:SF180; PTHR11461:SF180; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Endosome;
KW Lysosome; Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor.
FT CHAIN 1..379
FT /note="Leukocyte elastase inhibitor"
FT /id="PRO_0000094100"
FT REGION 351..379
FT /note="CARD-binding motif (CBM)"
FT /evidence="ECO:0000250|UniProtKB:P30740"
FT SITE 344..345
FT /note="Reactive bond"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P30740"
FT MOD_RES 137
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30740"
FT MOD_RES 177
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30740"
FT HELIX 2..22
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 32..44
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 48..57
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 66..77
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 83..95
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:1HLE"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 125..139
FT /evidence="ECO:0007829|PDB:1HLE"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 157..173
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 181..190
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 192..209
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 214..221
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 224..235
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 238..242
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 244..248
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 252..259
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 265..274
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 276..283
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 285..291
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:1HLE"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:1HLE"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 313..326
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 328..343
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 358..364
FT /evidence="ECO:0007829|PDB:1HLE"
FT TURN 365..368
FT /evidence="ECO:0007829|PDB:1HLE"
FT STRAND 369..376
FT /evidence="ECO:0007829|PDB:1HLE"
SQ SEQUENCE 379 AA; 43006 MW; 72DED1999371427A CRC64;
MEQLSTANTH FAVDLFRALN ESDPTGNIFI SPLSISSALA MIFLGTRGNT AAQVSKALYF
DTVEDIHSRF QSLNADINKP GAPYILKLAN RLYGEKTYNF LADFLASTQK MYGAELASVD
FQQAPEDARK EINEWVKGQT EGKIPELLVK GMVDNMTKLV LVNAIYFKGN WQEKFMKEAT
RDAPFRLNKK DTKTVKMMYQ KKKFPYNYIE DLKCRVLELP YQGKELSMII LLPDDIEDES
TGLEKIEKQL TLEKLREWTK PENLYLAEVN VHLPRFKLEE SYDLTSHLAR LGVQDLFNRG
KADLSGMSGA RDLFVSKIIH KSFVDLNEEG TEAAAATAGT IMLAMLMPEE NFNADHPFIF
FIRHNPSANI LFLGRFSSP
