ID   KAIN_HUMAN              Reviewed;         427 AA.
AC   P29622; Q53XB5; Q86TR9; Q96BZ5;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   21-JUN-2005, sequence version 3.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=Kallistatin;
DE   AltName: Full=Kallikrein inhibitor;
DE   AltName: Full=Peptidase inhibitor 4;
DE            Short=PI-4;
DE   AltName: Full=Serpin A4;
DE   Flags: Precursor;
GN   Name=SERPINA4; Synonyms=KST, PI4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=8227002; DOI=10.1016/s0021-9258(20)80553-5;
RA   Chai K.X., Chen L.-M., Chao J., Chao L.;
RT   "Kallistatin: a novel human serine proteinase inhibitor. Molecular cloning,
RT   tissue distribution, and expression in Escherichia coli.";
RL   J. Biol. Chem. 268:24498-24505(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7835886; DOI=10.1006/geno.1994.1513;
RA   Chai K.X., Ward D.C., Chao J., Chao L.;
RT   "Molecular cloning, sequence analysis, and chromosomal localization of the
RT   human protease inhibitor 4 (kallistatin) gene (PI4).";
RL   Genomics 23:370-378(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Fetal liver;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PROTEIN SEQUENCE OF 388-403.
RC   TISSUE=Plasma;
RX   PubMed=1334488; DOI=10.1016/s0021-9258(18)35690-4;
RA   Zhou G.X., Chao L., Chao J.;
RT   "Kallistatin: a novel human tissue kallikrein inhibitor. Purification,
RT   characterization, and reactive center sequence.";
RL   J. Biol. Chem. 267:25873-25880(1992).
RN   [6]
RP   GLYCOSYLATION AT ASN-157.
RX   PubMed=12754519; DOI=10.1038/nbt827;
RA   Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT   "Identification and quantification of N-linked glycoproteins using
RT   hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL   Nat. Biotechnol. 21:660-666(2003).
RN   [7]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-108; ASN-157 AND ASN-238.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [8]
RP   GLYCOSYLATION AT ASN-238.
RX   PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA   Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA   Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA   Ying W.T., He S.M., Qian X.H.;
RT   "A strategy for precise and large scale identification of core fucosylated
RT   glycoproteins.";
RL   Mol. Cell. Proteomics 8:913-923(2009).
CC   -!- FUNCTION: Inhibits human amidolytic and kininogenase activities of
CC       tissue kallikrein. Inhibition is achieved by formation of an equimolar,
CC       heat- and SDS-stable complex between the inhibitor and the enzyme, and
CC       generation of a small C-terminal fragment of the inhibitor due to
CC       cleavage at the reactive site by tissue kallikrein.
CC       {ECO:0000269|PubMed:8227002}.
CC   -!- SUBUNIT: Monomer and some homodimers.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC   -!- PTM: The N-terminus is blocked.
CC   -!- MISCELLANEOUS: Heparin blocks kallistatin's complex formation with
CC       tissue kallikrein and abolishes its inhibitory effect on tissue
CC       kallikrein's activity.
CC   -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAD66567.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; L19684; AAA59454.1; -; mRNA.
DR   EMBL; L28101; AAC41706.1; -; Genomic_DNA.
DR   EMBL; BX248009; CAD62337.1; -; mRNA.
DR   EMBL; BX248760; CAD66567.1; ALT_INIT; mRNA.
DR   EMBL; BC014992; AAH14992.1; -; mRNA.
DR   CCDS; CCDS9927.1; -.
DR   PIR; A49518; A49518.
DR   RefSeq; NP_001275961.1; NM_001289032.1.
DR   RefSeq; NP_001275962.1; NM_001289033.1.
DR   RefSeq; NP_006206.2; NM_006215.3.
DR   PDB; 6F02; X-ray; 3.00 A; A/C=45-427.
DR   PDBsum; 6F02; -.
DR   AlphaFoldDB; P29622; -.
DR   SMR; P29622; -.
DR   BioGRID; 111285; 21.
DR   IntAct; P29622; 13.
DR   MINT; P29622; -.
DR   STRING; 9606.ENSP00000451172; -.
DR   DrugBank; DB09130; Copper.
DR   DrugBank; DB01593; Zinc.
DR   DrugBank; DB14487; Zinc acetate.
DR   MEROPS; I04.003; -.
DR   GlyConnect; 1429; 17 N-Linked glycans (3 sites).
DR   GlyCosmos; P29622; 4 sites, 20 glycans.
DR   GlyGen; P29622; 4 sites, 20 N-linked glycans (3 sites).
DR   iPTMnet; P29622; -.
DR   PhosphoSitePlus; P29622; -.
DR   BioMuta; SERPINA4; -.
DR   DMDM; 68067608; -.
DR   CPTAC; CPTAC-672; -.
DR   CPTAC; non-CPTAC-1135; -.
DR   jPOST; P29622; -.
DR   MassIVE; P29622; -.
DR   PaxDb; 9606-ENSP00000450838; -.
DR   PeptideAtlas; P29622; -.
DR   ProteomicsDB; 54602; -.
DR   TopDownProteomics; P29622; -.
DR   Antibodypedia; 118; 262 antibodies from 30 providers.
DR   DNASU; 5267; -.
DR   Ensembl; ENST00000298841.5; ENSP00000298841.5; ENSG00000100665.12.
DR   Ensembl; ENST00000555095.5; ENSP00000451172.1; ENSG00000100665.12.
DR   Ensembl; ENST00000557004.6; ENSP00000450838.1; ENSG00000100665.12.
DR   GeneID; 5267; -.
DR   KEGG; hsa:5267; -.
DR   MANE-Select; ENST00000557004.6; ENSP00000450838.1; NM_006215.4; NP_006206.2.
DR   UCSC; uc001ydk.5; human.
DR   AGR; HGNC:8948; -.
DR   CTD; 5267; -.
DR   DisGeNET; 5267; -.
DR   GeneCards; SERPINA4; -.
DR   HGNC; HGNC:8948; SERPINA4.
DR   HPA; ENSG00000100665; Tissue enriched (liver).
DR   MIM; 147935; gene.
DR   neXtProt; NX_P29622; -.
DR   OpenTargets; ENSG00000100665; -.
DR   PharmGKB; PA35514; -.
DR   VEuPathDB; HostDB:ENSG00000100665; -.
DR   eggNOG; KOG2392; Eukaryota.
DR   GeneTree; ENSGT00940000160877; -.
DR   HOGENOM; CLU_023330_2_1_1; -.
DR   InParanoid; P29622; -.
DR   OMA; LWFNRPF; -.
DR   OrthoDB; 3218836at2759; -.
DR   PhylomeDB; P29622; -.
DR   TreeFam; TF343201; -.
DR   PathwayCommons; P29622; -.
DR   Reactome; R-HSA-114608; Platelet degranulation.
DR   SignaLink; P29622; -.
DR   BioGRID-ORCS; 5267; 3 hits in 1143 CRISPR screens.
DR   ChiTaRS; SERPINA4; human.
DR   GeneWiki; SERPINA4; -.
DR   GenomeRNAi; 5267; -.
DR   Pharos; P29622; Tbio.
DR   PRO; PR:P29622; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; P29622; Protein.
DR   Bgee; ENSG00000100665; Expressed in right lobe of liver and 63 other cell types or tissues.
DR   ExpressionAtlas; P29622; baseline and differential.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0031089; C:platelet dense granule lumen; TAS:Reactome.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR   CDD; cd19552; serpinA4_KST; 1.
DR   Gene3D; 2.30.39.10; Alpha-1-antitrypsin, domain 1; 1.
DR   Gene3D; 3.30.497.10; Antithrombin, subunit I, domain 2; 1.
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:SF194; KALLISTATIN; 1.
DR   PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1.
DR   Pfam; PF00079; Serpin; 1.
DR   SMART; SM00093; SERPIN; 1.
DR   SUPFAM; SSF56574; Serpins; 1.
DR   PROSITE; PS00284; SERPIN; 1.
DR   Genevisible; P29622; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Glycoprotein; Protease inhibitor;
KW   Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..427
FT                   /note="Kallistatin"
FT                   /id="PRO_0000032425"
FT   SITE            388..389
FT                   /note="Reactive bond"
FT   CARBOHYD        33
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        108
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:12754519,
FT                   ECO:0000269|PubMed:16335952"
FT   CARBOHYD        238
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952,
FT                   ECO:0000269|PubMed:19139490"
FT   CONFLICT        382
FT                   /note="S -> T (in Ref. 1 and 2)"
FT                   /evidence="ECO:0000305"
FT   TURN            48..50
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           52..69
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          75..77
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           79..89
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   TURN            90..92
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           96..104
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   TURN            109..111
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           114..128
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          136..149
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           153..163
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          166..170
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           175..189
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   TURN            190..192
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          207..216
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          218..221
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           225..227
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          229..233
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          235..238
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          241..248
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          250..257
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          259..281
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           286..291
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           295..304
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           308..310
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          311..313
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          315..319
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          321..328
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           329..332
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   HELIX           333..336
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   TURN            339..341
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   TURN            349..351
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          353..355
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          361..370
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          372..375
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          396..398
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          403..409
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   TURN            410..413
FT                   /evidence="ECO:0007829|PDB:6F02"
FT   STRAND          414..422
FT                   /evidence="ECO:0007829|PDB:6F02"
SQ   SEQUENCE   427 AA;  48542 MW;  68EBE7AF956BFB77 CRC64;
     MHLIDYLLLL LVGLLALSHG QLHVEHDGES CSNSSHQQIL ETGEGSPSLK IAPANADFAF
     RFYYLIASET PGKNIFFSPL SISAAYAMLS LGACSHSRSQ ILEGLGFNLT ELSESDVHRG
     FQHLLHTLNL PGHGLETRVG SALFLSHNLK FLAKFLNDTM AVYEAKLFHT NFYDTVGTIQ
     LINDHVKKET RGKIVDLVSE LKKDVLMVLV NYIYFKALWE KPFISSRTTP KDFYVDENTT
     VRVPMMLQDQ EHHWYLHDRY LPCSVLRMDY KGDATVFFIL PNQGKMREIE EVLTPEMLMR
     WNNLLRKRNF YKKLELHLPK FSISGSYVLD QILPRLGFTD LFSKWADLSG ITKQQKLEAS
     KSFHKATLDV DEAGTEAAAA TSFAIKFFSA QTNRHILRFN RPFLVVIFST STQSVLFLGK
     VVDPTKP
//