KAIN_HUMAN
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 03-AUG-2022, entry version 183.
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; 20.
DR IntAct; P29622; 12.
DR MINT; P29622; -.
DR STRING; 9606.ENSP00000450838; -.
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 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; P29622; -.
DR PeptideAtlas; P29622; -.
DR PRIDE; P29622; -.
DR ProteomicsDB; 54602; -.
DR TopDownProteomics; P29622; -.
DR Antibodypedia; 118; 232 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 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; 1124079at2759; -.
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 1066 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 tissues.
DR ExpressionAtlas; P29622; baseline and differential.
DR Genevisible; P29622; HS.
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 GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 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; PTHR11461; 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; 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
