KLKB1_HUMAN
ID KLKB1_HUMAN Reviewed; 638 AA.
AC P03952; A6NH96; B2R8H9; Q17RE8; Q17RE9; Q4W5C3;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-1986, sequence version 1.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Plasma kallikrein;
DE EC=3.4.21.34;
DE AltName: Full=Fletcher factor;
DE AltName: Full=Kininogenin;
DE AltName: Full=Plasma prekallikrein;
DE Short=PKK;
DE Contains:
DE RecName: Full=Plasma kallikrein heavy chain;
DE Contains:
DE RecName: Full=Plasma kallikrein light chain;
DE Flags: Precursor;
GN Name=KLKB1; Synonyms=KLK3;
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].
RX PubMed=3521732; DOI=10.1021/bi00357a017;
RA Chung D.W., Fujikawa K., McMullen B.A., Davie E.W.;
RT "Human plasma prekallikrein, a zymogen to a serine protease that contains
RT four tandem repeats.";
RL Biochemistry 25:2410-2417(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-143; GLN-202 AND
RP PRO-208.
RX PubMed=11031105; DOI=10.1006/geno.2000.6330;
RA Yu H., Anderson P.J., Freedman B.I., Rich S.S., Bowden D.W.;
RT "Genomic structure of the human plasma prekallikrein gene, identification
RT of allelic variants, and analysis in end-stage renal disease.";
RL Genomics 69:225-234(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-143; THR-178; GLN-202;
RP CYS-269; VAL-311; ALA-358; ALA-381; PRO-442 AND GLN-560.
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-560.
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 [8]
RP PARTIAL PROTEIN SEQUENCE, AND DISULFIDE BONDS.
RX PubMed=1998666; DOI=10.1021/bi00222a007;
RA McMullen B.A., Fujikawa K., Davie E.W.;
RT "Location of the disulfide bonds in human plasma prekallikrein: the
RT presence of four novel apple domains in the amino-terminal portion of the
RT molecule.";
RL Biochemistry 30:2050-2056(1991).
RN [9]
RP ACTIVITY REGULATION, AND HETERODIMER WITH SERPINA5.
RX PubMed=2844223; DOI=10.1021/bi00412a005;
RA Meijers J.C., Kanters D.H., Vlooswijk R.A., van Erp H.E., Hessing M.,
RA Bouma B.N.;
RT "Inactivation of human plasma kallikrein and factor XIa by protein C
RT inhibitor.";
RL Biochemistry 27:4231-4237(1988).
RN [10]
RP GLYCOSYLATION AT ASN-453.
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 [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-127; ASN-308; ASN-396; ASN-453
RP AND ASN-494.
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 [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-308; ASN-396; ASN-453 AND
RP ASN-494.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP VARIANT PKK DEFICIENCY TYR-548.
RX PubMed=14652634; DOI=10.1160/th03-05-0275;
RA Lombardi A.M., Sartori M.T., Cabrio L., Fadin M., Zanon E., Girolami A.;
RT "Severe prekallikrein (Fletcher factor) deficiency due to a compound
RT heterozygosis (383Trp stop codon and Cys529Tyr).";
RL Thromb. Haemost. 90:1040-1045(2003).
RN [14]
RP VARIANTS PKK DEFICIENCY ARG-123 AND SER-143.
RX PubMed=17598838; DOI=10.1111/j.1600-0609.2007.00871.x;
RA Katsuda I., Maruyama F., Ezaki K., Sawamura T., Ichihara Y.;
RT "A new type of plasma prekallikrein deficiency associated with homozygosity
RT for Gly104Arg and Asn124Ser in apple domain 2 of the heavy-chain region.";
RL Eur. J. Haematol. 79:59-68(2007).
CC -!- FUNCTION: The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates,
CC in a reciprocal reaction, factor XII after its binding to a negatively
CC charged surface. It also releases bradykinin from HMW kininogen and may
CC also play a role in the renin-angiotensin system by converting prorenin
CC into renin.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves selectively Arg-|-Xaa and Lys-|-Xaa bonds, including
CC Lys-|-Arg and Arg-|-Ser bonds in (human) kininogen to release
CC bradykinin.; EC=3.4.21.34;
CC -!- ACTIVITY REGULATION: Inhibited by SERPINA5.
CC {ECO:0000269|PubMed:2844223}.
CC -!- SUBUNIT: Forms a heterodimer with SERPINA5. The zymogen is activated by
CC factor XIIa, which cleaves the molecule into a light chain, which
CC contains the active site, and a heavy chain, which associates with HMW
CC kininogen. These chains are linked by one or more disulfide bonds.
CC -!- INTERACTION:
CC P03952; Q8TAB7: CCDC26; NbExp=3; IntAct=EBI-10087153, EBI-10271580;
CC P03952; Q9UI10: EIF2B4; NbExp=3; IntAct=EBI-10087153, EBI-2340132;
CC P03952; O00746: NME4; NbExp=3; IntAct=EBI-10087153, EBI-744871;
CC P03952; C9J082: NPHP1; NbExp=3; IntAct=EBI-10087153, EBI-25830675;
CC P03952; O14744: PRMT5; NbExp=3; IntAct=EBI-10087153, EBI-351098;
CC P03952; Q8TAS3: PRRG2; NbExp=3; IntAct=EBI-10087153, EBI-10272071;
CC P03952; O00233: PSMD9; NbExp=3; IntAct=EBI-10087153, EBI-750973;
CC P03952; Q8IYM2: SLFN12; NbExp=3; IntAct=EBI-10087153, EBI-2822550;
CC P03952; Q9UMY4: SNX12; NbExp=3; IntAct=EBI-10087153, EBI-1752602;
CC P03952; O43493-5: TGOLN2; NbExp=3; IntAct=EBI-10087153, EBI-25830716;
CC P03952; Q8NFB2: TMEM185A; NbExp=3; IntAct=EBI-10087153, EBI-21757569;
CC P03952; Q8N0U8: VKORC1L1; NbExp=3; IntAct=EBI-10087153, EBI-11337915;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DISEASE: Prekallikrein deficiency (PKK deficiency) [MIM:612423]: This
CC disorder is a blood coagulation defect. {ECO:0000269|PubMed:14652634,
CC ECO:0000269|PubMed:17598838}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Plasma kallikrein
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/klkb1/";
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DR EMBL; M13143; AAA60153.1; -; mRNA.
DR EMBL; AF232742; AAF79940.1; -; Genomic_DNA.
DR EMBL; AF232734; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AF232735; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AF232736; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AF232737; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AF232738; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AF232739; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AF232740; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AF232741; AAF79940.1; JOINED; Genomic_DNA.
DR EMBL; AK313378; BAG36176.1; -; mRNA.
DR EMBL; AY190920; AAN84794.1; -; Genomic_DNA.
DR EMBL; AC110771; AAY40900.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04623.1; -; Genomic_DNA.
DR EMBL; BC117349; AAI17350.1; -; mRNA.
DR EMBL; BC117351; AAI17352.1; -; mRNA.
DR CCDS; CCDS34120.1; -.
DR PIR; A00921; KQHUP.
DR RefSeq; NP_000883.2; NM_000892.4.
DR PDB; 2ANW; X-ray; 1.85 A; A=391-631.
DR PDB; 2ANY; X-ray; 1.40 A; A=391-631.
DR PDB; 4OGX; X-ray; 2.40 A; A=391-631.
DR PDB; 4OGY; X-ray; 2.10 A; A/B=391-631.
DR PDB; 5F8T; X-ray; 1.75 A; A=391-629.
DR PDB; 5F8X; X-ray; 1.55 A; A=391-629.
DR PDB; 5F8Z; X-ray; 1.50 A; A=391-629.
DR PDB; 5TJX; X-ray; 1.41 A; A=376-638.
DR PDB; 6I44; X-ray; 1.36 A; A=20-638.
DR PDB; 6O1G; X-ray; 2.20 A; A=1-638.
DR PDB; 6O1S; X-ray; 1.70 A; E=376-638.
DR PDB; 6T7P; X-ray; 1.42 A; A=391-632.
DR PDB; 7N7X; X-ray; 2.10 A; AAA=391-626.
DR PDBsum; 2ANW; -.
DR PDBsum; 2ANY; -.
DR PDBsum; 4OGX; -.
DR PDBsum; 4OGY; -.
DR PDBsum; 5F8T; -.
DR PDBsum; 5F8X; -.
DR PDBsum; 5F8Z; -.
DR PDBsum; 5TJX; -.
DR PDBsum; 6I44; -.
DR PDBsum; 6O1G; -.
DR PDBsum; 6O1S; -.
DR PDBsum; 6T7P; -.
DR PDBsum; 7N7X; -.
DR AlphaFoldDB; P03952; -.
DR SMR; P03952; -.
DR BioGRID; 110018; 10.
DR ComplexPortal; CPX-6234; Kallikrein complex.
DR IntAct; P03952; 19.
DR STRING; 9606.ENSP00000264690; -.
DR BindingDB; P03952; -.
DR ChEMBL; CHEMBL2000; -.
DR DrugBank; DB15982; Berotralstat.
DR DrugBank; DB09228; Conestat alfa.
DR DrugBank; DB05311; Ecallantide.
DR DrugBank; DB12831; Gabexate.
DR DrugBank; DB06404; Human C1-esterase inhibitor.
DR DrugBank; DB14597; Lanadelumab.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; P03952; -.
DR GuidetoPHARMACOLOGY; 2379; -.
DR MEROPS; S01.212; -.
DR GlyConnect; 714; 19 N-Linked glycans (8 sites).
DR GlyGen; P03952; 8 sites, 23 N-linked glycans (8 sites).
DR iPTMnet; P03952; -.
DR PhosphoSitePlus; P03952; -.
DR BioMuta; KLKB1; -.
DR DMDM; 125184; -.
DR CPTAC; CPTAC-682; -.
DR CPTAC; CPTAC-683; -.
DR jPOST; P03952; -.
DR MassIVE; P03952; -.
DR PaxDb; P03952; -.
DR PeptideAtlas; P03952; -.
DR PRIDE; P03952; -.
DR ProteomicsDB; 51622; -.
DR ABCD; P03952; 1 sequenced antibody.
DR Antibodypedia; 850; 385 antibodies from 36 providers.
DR DNASU; 3818; -.
DR Ensembl; ENST00000264690.11; ENSP00000264690.6; ENSG00000164344.16.
DR GeneID; 3818; -.
DR KEGG; hsa:3818; -.
DR UCSC; uc003iyy.4; human.
DR CTD; 3818; -.
DR DisGeNET; 3818; -.
DR GeneCards; KLKB1; -.
DR HGNC; HGNC:6371; KLKB1.
DR HPA; ENSG00000164344; Tissue enriched (liver).
DR MalaCards; KLKB1; -.
DR MIM; 229000; gene.
DR MIM; 612423; phenotype.
DR neXtProt; NX_P03952; -.
DR Orphanet; 749; Congenital prekallikrein deficiency.
DR PharmGKB; PA30160; -.
DR VEuPathDB; HostDB:ENSG00000164344; -.
DR eggNOG; KOG3627; Eukaryota.
DR HOGENOM; CLU_031604_0_0_1; -.
DR InParanoid; P03952; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P03952; -.
DR TreeFam; TF343687; -.
DR BRENDA; 3.4.21.34; 2681.
DR PathwayCommons; P03952; -.
DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-9657688; Defective factor XII causes hereditary angioedema.
DR Reactome; R-HSA-9657689; Defective SERPING1 causes hereditary angioedema.
DR SABIO-RK; P03952; -.
DR SignaLink; P03952; -.
DR SIGNOR; P03952; -.
DR BioGRID-ORCS; 3818; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; KLKB1; human.
DR EvolutionaryTrace; P03952; -.
DR GeneWiki; KLKB1; -.
DR GenomeRNAi; 3818; -.
DR Pharos; P03952; Tclin.
DR PRO; PR:P03952; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P03952; protein.
DR Bgee; ENSG00000164344; Expressed in right lobe of liver and 123 other tissues.
DR ExpressionAtlas; P03952; baseline and differential.
DR Genevisible; P03952; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IC:ComplexPortal.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; IDA:ComplexPortal.
DR GO; GO:0002542; P:Factor XII activation; TAS:BHF-UCL.
DR GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW.
DR GO; GO:0031639; P:plasminogen activation; IDA:BHF-UCL.
DR GO; GO:0051919; P:positive regulation of fibrinolysis; IDA:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal.
DR GO; GO:0031638; P:zymogen activation; IDA:ComplexPortal.
DR CDD; cd01100; APPLE_Factor_XI_like; 4.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR InterPro; IPR000177; Apple.
DR InterPro; IPR003609; Pan_app.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00024; PAN_1; 4.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00005; APPLEDOMAIN.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00223; APPLE; 4.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS00495; APPLE; 4.
DR PROSITE; PS50948; PAN; 4.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Blood coagulation; Direct protein sequencing;
KW Disease variant; Disulfide bond; Fibrinolysis; Glycoprotein; Hemostasis;
KW Hydrolase; Inflammatory response; Protease; Reference proteome; Repeat;
KW Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..19
FT CHAIN 20..390
FT /note="Plasma kallikrein heavy chain"
FT /id="PRO_0000028021"
FT CHAIN 391..638
FT /note="Plasma kallikrein light chain"
FT /id="PRO_0000028022"
FT DOMAIN 21..104
FT /note="Apple 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 111..194
FT /note="Apple 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 201..284
FT /note="Apple 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 292..375
FT /note="Apple 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 391..626
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 434
FT /note="Charge relay system"
FT ACT_SITE 483
FT /note="Charge relay system"
FT ACT_SITE 578
FT /note="Charge relay system"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:3521732"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:3521732"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:3521732"
FT CARBOHYD 453
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:3521732"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:3521732"
FT DISULFID 21..104
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 47..77
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 51..57
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 111..194
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 137..166
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 141..147
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 201..284
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 227..256
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 231..237
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 292..375
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 318..347
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 322..328
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 340..345
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 383..503
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 419..435
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 517..584
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 548..563
FT /evidence="ECO:0000269|PubMed:1998666"
FT DISULFID 574..602
FT /evidence="ECO:0000269|PubMed:1998666"
FT VARIANT 123
FT /note="G -> R (in PKK deficiency; reduces the binding
FT activity of Apple domain 2 to HMW kininogen;
FT dbSNP:rs121964952)"
FT /evidence="ECO:0000269|PubMed:17598838"
FT /id="VAR_054907"
FT VARIANT 143
FT /note="N -> S (in PKK deficiency; reduces the binding
FT activity of Apple domain 2 to HMW kininogen;
FT dbSNP:rs3733402)"
FT /evidence="ECO:0000269|PubMed:11031105,
FT ECO:0000269|PubMed:17598838, ECO:0000269|Ref.4"
FT /id="VAR_013598"
FT VARIANT 178
FT /note="A -> T (in dbSNP:rs4253257)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016280"
FT VARIANT 202
FT /note="H -> Q (in dbSNP:rs4253373)"
FT /evidence="ECO:0000269|PubMed:11031105, ECO:0000269|Ref.4"
FT /id="VAR_013599"
FT VARIANT 208
FT /note="H -> P (in dbSNP:rs145640112)"
FT /evidence="ECO:0000269|PubMed:11031105"
FT /id="VAR_013600"
FT VARIANT 210
FT /note="A -> E (in dbSNP:rs2278542)"
FT /id="VAR_020180"
FT VARIANT 269
FT /note="S -> C (in dbSNP:rs4253376)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016281"
FT VARIANT 311
FT /note="F -> V (in dbSNP:rs4253377)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016282"
FT VARIANT 358
FT /note="T -> A (in dbSNP:rs4253379)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016283"
FT VARIANT 381
FT /note="S -> A (in dbSNP:rs4253301)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016284"
FT VARIANT 442
FT /note="Q -> P (in dbSNP:rs4253316)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016285"
FT VARIANT 548
FT /note="C -> Y (in PKK deficiency; dbSNP:rs121964951)"
FT /evidence="ECO:0000269|PubMed:14652634"
FT /id="VAR_054908"
FT VARIANT 560
FT /note="R -> Q (in dbSNP:rs4253325)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_016286"
FT STRAND 25..31
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 44..53
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:6I44"
FT TURN 71..75
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 89..99
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 116..130
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 134..142
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 177..189
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 213..220
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 224..233
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 238..243
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:6O1G"
FT STRAND 270..279
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:6O1G"
FT STRAND 305..314
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 315..324
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 330..334
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 340..343
FT /evidence="ECO:0007829|PDB:6O1G"
FT STRAND 345..351
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 358..363
FT /evidence="ECO:0007829|PDB:6O1G"
FT STRAND 365..370
FT /evidence="ECO:0007829|PDB:6I44"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:4OGY"
FT STRAND 405..425
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 428..431
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 445..448
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 454..456
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 466..471
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 479..482
FT /evidence="ECO:0007829|PDB:2ANY"
FT STRAND 485..491
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:4OGY"
FT HELIX 511..513
FT /evidence="ECO:0007829|PDB:6T7P"
FT STRAND 517..523
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 525..528
FT /evidence="ECO:0007829|PDB:2ANW"
FT STRAND 536..539
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 545..551
FT /evidence="ECO:0007829|PDB:6I44"
FT TURN 552..554
FT /evidence="ECO:0007829|PDB:5TJX"
FT STRAND 561..564
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 581..586
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 589..598
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 600..603
FT /evidence="ECO:0007829|PDB:6I44"
FT STRAND 609..613
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 614..617
FT /evidence="ECO:0007829|PDB:6I44"
FT HELIX 618..628
FT /evidence="ECO:0007829|PDB:6I44"
SQ SEQUENCE 638 AA; 71370 MW; E62F9C1053838FB4 CRC64;
MILFKQATYF ISLFATVSCG CLTQLYENAF FRGGDVASMY TPNAQYCQMR CTFHPRCLLF
SFLPASSIND MEKRFGCFLK DSVTGTLPKV HRTGAVSGHS LKQCGHQISA CHRDIYKGVD
MRGVNFNVSK VSSVEECQKR CTNNIRCQFF SYATQTFHKA EYRNNCLLKY SPGGTPTAIK
VLSNVESGFS LKPCALSEIG CHMNIFQHLA FSDVDVARVL TPDAFVCRTI CTYHPNCLFF
TFYTNVWKIE SQRNVCLLKT SESGTPSSST PQENTISGYS LLTCKRTLPE PCHSKIYPGV
DFGGEELNVT FVKGVNVCQE TCTKMIRCQF FTYSLLPEDC KEEKCKCFLR LSMDGSPTRI
AYGTQGSSGY SLRLCNTGDN SVCTTKTSTR IVGGTNSSWG EWPWQVSLQV KLTAQRHLCG
GSLIGHQWVL TAAHCFDGLP LQDVWRIYSG ILNLSDITKD TPFSQIKEII IHQNYKVSEG
NHDIALIKLQ APLNYTEFQK PICLPSKGDT STIYTNCWVT GWGFSKEKGE IQNILQKVNI
PLVTNEECQK RYQDYKITQR MVCAGYKEGG KDACKGDSGG PLVCKHNGMW RLVGITSWGE
GCARREQPGV YTKVAEYMDW ILEKTQSSDG KAQMQSPA
