KLKB1_MOUSE
ID KLKB1_MOUSE Reviewed; 638 AA.
AC P26262; Q8R0P5;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 189.
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 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, Pk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=2264928; DOI=10.1089/dna.1990.9.737;
RA Seidah N.G., Sawyer N., Hamelin J., Mion P., Beaubien G., Brachpapa L.,
RA Rochemont J., Mbikay M., Chretien M.;
RT "Mouse plasma kallikrein: cDNA structure, enzyme characterization, and
RT comparison of protein and mRNA levels among species.";
RL DNA Cell Biol. 9:737-748(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-127.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-127; ASN-396 AND ASN-494.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=17330941; DOI=10.1021/pr0604559;
RA Bernhard O.K., Kapp E.A., Simpson R.J.;
RT "Enhanced analysis of the mouse plasma proteome using cysteine-containing
RT tryptic glycopeptides.";
RL J. Proteome Res. 6:987-995(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Plasma kallikrein
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; M58588; AAA63393.1; -; mRNA.
DR EMBL; BC026555; AAH26555.1; -; mRNA.
DR CCDS; CCDS22275.1; -.
DR PIR; A36557; KQMSPL.
DR RefSeq; NP_032481.2; NM_008455.3.
DR PDB; 5GVT; X-ray; 2.61 A; A/B=391-638.
DR PDB; 6A8O; X-ray; 2.77 A; A/B=391-638.
DR PDBsum; 5GVT; -.
DR PDBsum; 6A8O; -.
DR AlphaFoldDB; P26262; -.
DR SMR; P26262; -.
DR BioGRID; 200983; 1.
DR STRING; 10090.ENSMUSP00000112174; -.
DR BindingDB; P26262; -.
DR ChEMBL; CHEMBL1250359; -.
DR MEROPS; S01.212; -.
DR GlyGen; P26262; 5 sites.
DR iPTMnet; P26262; -.
DR PhosphoSitePlus; P26262; -.
DR SwissPalm; P26262; -.
DR CPTAC; non-CPTAC-5603; -.
DR MaxQB; P26262; -.
DR PaxDb; P26262; -.
DR PeptideAtlas; P26262; -.
DR PRIDE; P26262; -.
DR ProteomicsDB; 263662; -.
DR Antibodypedia; 850; 385 antibodies from 36 providers.
DR DNASU; 16621; -.
DR Ensembl; ENSMUST00000026907; ENSMUSP00000026907; ENSMUSG00000109764.
DR GeneID; 16621; -.
DR KEGG; mmu:16621; -.
DR UCSC; uc009lot.4; mouse.
DR CTD; 3818; -.
DR MGI; MGI:102849; Klkb1.
DR VEuPathDB; HostDB:ENSMUSG00000109764; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000161669; -.
DR HOGENOM; CLU_031604_0_0_1; -.
DR InParanoid; P26262; -.
DR OMA; RGEKCKC; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P26262; -.
DR TreeFam; TF343687; -.
DR BRENDA; 3.4.21.34; 3474.
DR Reactome; R-MMU-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR BioGRID-ORCS; 16621; 3 hits in 40 CRISPR screens.
DR PRO; PR:P26262; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P26262; protein.
DR Bgee; ENSMUSG00000109764; Expressed in left lobe of liver and 31 other tissues.
DR Genevisible; P26262; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; ISO:MGI.
DR GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0031639; P:plasminogen activation; ISO:MGI.
DR GO; GO:0051919; P:positive regulation of fibrinolysis; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR GO; GO:0031638; P:zymogen activation; ISO:MGI.
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; Disulfide bond;
KW Fibrinolysis; Glycoprotein; Hemostasis; Hydrolase; Inflammatory response;
KW Protease; Reference proteome; Repeat; Secreted; Serine protease; Signal;
KW Zymogen.
FT SIGNAL 1..19
FT CHAIN 20..390
FT /note="Plasma kallikrein heavy chain"
FT /id="PRO_0000028023"
FT CHAIN 391..638
FT /note="Plasma kallikrein light chain"
FT /id="PRO_0000028024"
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:16944957,
FT ECO:0000269|PubMed:17330941"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17330941"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17330941"
FT DISULFID 21..104
FT /evidence="ECO:0000250"
FT DISULFID 47..77
FT /evidence="ECO:0000250"
FT DISULFID 51..57
FT /evidence="ECO:0000250"
FT DISULFID 111..194
FT /evidence="ECO:0000250"
FT DISULFID 137..166
FT /evidence="ECO:0000250"
FT DISULFID 141..147
FT /evidence="ECO:0000250"
FT DISULFID 201..284
FT /evidence="ECO:0000250"
FT DISULFID 227..256
FT /evidence="ECO:0000250"
FT DISULFID 231..237
FT /evidence="ECO:0000250"
FT DISULFID 292..375
FT /evidence="ECO:0000250"
FT DISULFID 318..347
FT /evidence="ECO:0000250"
FT DISULFID 322..328
FT /evidence="ECO:0000250"
FT DISULFID 340..345
FT /evidence="ECO:0000250"
FT DISULFID 383..503
FT /evidence="ECO:0000250"
FT DISULFID 419..435
FT /evidence="ECO:0000250"
FT DISULFID 517..584
FT /evidence="ECO:0000250"
FT DISULFID 548..563
FT /evidence="ECO:0000250"
FT DISULFID 574..602
FT /evidence="ECO:0000250"
FT CONFLICT 603
FT /note="A -> G (in Ref. 1; AAA63393)"
FT /evidence="ECO:0000305"
FT STRAND 405..423
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 425..431
FT /evidence="ECO:0007829|PDB:5GVT"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:5GVT"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 445..448
FT /evidence="ECO:0007829|PDB:5GVT"
FT HELIX 454..456
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 466..471
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 485..491
FT /evidence="ECO:0007829|PDB:5GVT"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 517..523
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 525..528
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 536..539
FT /evidence="ECO:0007829|PDB:5GVT"
FT HELIX 545..551
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 561..564
FT /evidence="ECO:0007829|PDB:5GVT"
FT TURN 567..569
FT /evidence="ECO:0007829|PDB:6A8O"
FT STRAND 581..586
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 589..596
FT /evidence="ECO:0007829|PDB:5GVT"
FT STRAND 600..603
FT /evidence="ECO:0007829|PDB:6A8O"
FT STRAND 609..613
FT /evidence="ECO:0007829|PDB:5GVT"
FT HELIX 614..617
FT /evidence="ECO:0007829|PDB:5GVT"
FT HELIX 618..624
FT /evidence="ECO:0007829|PDB:5GVT"
SQ SEQUENCE 638 AA; 71383 MW; CC27C93F4B57C599 CRC64;
MILFNRVGYF VSLFATVSCG CMTQLYKNTF FRGGDLAAIY TPDAQYCQKM CTFHPRCLLF
SFLAVTPPKE TNKRFGCFMK ESITGTLPRI HRTGAISGHS LKQCGHQISA CHRDIYKGLD
MRGSNFNISK TDNIEECQKL CTNNFHCQFF TYATSAFYRP EYRKKCLLKH SASGTPTSIK
SADNLVSGFS LKSCALSEIG CPMDIFQHSA FADLNVSQVI TPDAFVCRTI CTFHPNCLFF
TFYTNEWETE SQRNVCFLKT SKSGRPSPPI PQENAISGYS LLTCRKTRPE PCHSKIYSGV
DFEGEELNVT FVQGADVCQE TCTKTIRCQF FIYSLLPQDC KEEGCKCSLR LSTDGSPTRI
TYGMQGSSGY SLRLCKLVDS PDCTTKINAR IVGGTNASLG EWPWQVSLQV KLVSQTHLCG
GSIIGRQWVL TAAHCFDGIP YPDVWRIYGG ILSLSEITKE TPSSRIKELI IHQEYKVSEG
NYDIALIKLQ TPLNYTEFQK PICLPSKADT NTIYTNCWVT GWGYTKEQGE TQNILQKATI
PLVPNEECQK KYRDYVINKQ MICAGYKEGG TDACKGDSGG PLVCKHSGRW QLVGITSWGE
GCARKDQPGV YTKVSEYMDW ILEKTQSSDV RALETSSA
