KNG1_BOVIN
ID KNG1_BOVIN Reviewed; 621 AA.
AC P01044; P01046; Q2KJ62;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Kininogen-1;
DE AltName: Full=Kininogen I;
DE AltName: Full=Thiol proteinase inhibitor;
DE Contains:
DE RecName: Full=Kininogen-1 heavy chain;
DE Contains:
DE RecName: Full=Bradykinin;
DE AltName: Full=Kallidin I;
DE Contains:
DE RecName: Full=Lysyl-bradykinin;
DE AltName: Full=Kallidin II;
DE Contains:
DE RecName: Full=Kininogen-1 light chain;
DE Flags: Precursor;
GN Name=KNG1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HMW).
RX PubMed=6571699; DOI=10.1038/305545a0;
RA Kitamura N., Takagaki Y., Furuto S., Tanaka T., Nawa H., Nakanishi S.;
RT "A single gene for bovine high molecular weight and low molecular weight
RT kininogens.";
RL Nature 305:545-549(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LMW).
RX PubMed=6572010; DOI=10.1073/pnas.80.1.90;
RA Nawa H., Kitamura N., Hirose T., Asai M., Inayama S., Nakanishi S.;
RT "Primary structures of bovine liver low molecular weight kininogen
RT precursors and their two mRNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:90-94(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM HMW).
RC STRAIN=Hereford; TISSUE=Fetal liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 19-378, AND GLYCOSYLATION AT ASN-87; THR-136; ASN-168;
RP ASN-169; ASN-197 AND ASN-204.
RX PubMed=3546295; DOI=10.1016/s0021-9258(18)61573-x;
RA Sueyoshi T., Miyata T., Hashimoto N., Kato H., Hayashida H., Miyata T.,
RA Iwanaga S.;
RT "Bovine high molecular weight kininogen. The amino acid sequence, positions
RT of carbohydrate chains and disulfide bridges in the heavy chain portion.";
RL J. Biol. Chem. 262:2768-2779(1987).
RN [5]
RP PROTEIN SEQUENCE OF 378-393.
RX PubMed=4986212; DOI=10.1093/oxfordjournals.jbchem.a129254;
RA Kato H., Nagasawa S., Suzuki T.;
RT "Studies on the structure of bovine kininogen: cleavages of disulfide bonds
RT and of methionyl bonds in kininogen-II.";
RL J. Biochem. 67:313-323(1970).
RN [6]
RP PROTEIN SEQUENCE OF 458-498.
RX PubMed=1169237;
RA Han Y.N., Komiya M., Iwanaga S., Suzuki T.;
RT "Studies on the primary structure of bovine high-molecular-weight
RT kininogen. Amino acid sequence of a fragment ('histidine-rich peptide')
RT released by plasma kallikrein.";
RL J. Biochem. 77:55-68(1975).
RN [7]
RP GLYCOSYLATION AT THR-136 AND SER-581, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19674964; DOI=10.1074/mcp.m900211-mcp200;
RA Darula Z., Medzihradszky K.F.;
RT "Affinity enrichment and characterization of mucin core-1 type
RT glycopeptides from bovine serum.";
RL Mol. Cell. Proteomics 8:2515-2526(2009).
CC -!- FUNCTION: Kininogens are inhibitors of thiol proteases. HMW-kininogen
CC plays an important role in blood coagulation by helping to position
CC optimally prekallikrein and factor XI next to factor XII; HMW-kininogen
CC inhibits the thrombin- and plasmin-induced aggregation of thrombocytes.
CC LMW-kininogen inhibits the aggregation of thrombocytes. LMW-kininogen
CC is in contrast to HMW-kininogen not involved in blood clotting.
CC -!- FUNCTION: [Bradykinin]: The active peptide bradykinin is a potent
CC vasodilatator that is released from HMW-kininogen shows a variety of
CC physiological effects: (A) influence in smooth muscle contraction, (B)
CC induction of hypotension, (C) natriuresis and diuresis, (D) decrease in
CC blood glucose level, (E) it is a mediator of inflammation and causes
CC (E1) increase in vascular permeability, (E2) stimulation of nociceptors
CC (4E3) release of other mediators of inflammation (e.g. prostaglandins),
CC (F) it has a cardioprotective effect (directly via bradykinin action,
CC indirectly via endothelium-derived relaxing factor action).
CC {ECO:0000250|UniProtKB:P01042}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=HMW;
CC IsoId=P01044-1; Sequence=Displayed;
CC Name=LMW;
CC IsoId=P01044-2; Sequence=VSP_013562, VSP_013563;
CC -!- TISSUE SPECIFICITY: Plasma.
CC -!- PTM: Bradykinin is released from kininogen by plasma kallikrein.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P01042}.
CC -!- PTM: [Bradykinin]: Bradykinin is inactivated by ACE, which removes the
CC dipeptide Arg-Phe from its C-terminus. {ECO:0000250|UniProtKB:P01042}.
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DR EMBL; V01491; CAA24735.1; -; mRNA.
DR EMBL; V00426; CAA23709.1; -; mRNA.
DR EMBL; BC105499; AAI05500.1; -; mRNA.
DR PIR; A01281; KGBOH1.
DR PIR; A01283; KGBOL1.
DR RefSeq; NP_786968.2; NM_175774.3.
DR AlphaFoldDB; P01044; -.
DR SMR; P01044; -.
DR STRING; 9913.ENSBTAP00000048995; -.
DR MEROPS; I25.016; -.
DR MEROPS; I25.017; -.
DR MEROPS; I25.950; -.
DR GlyConnect; 785; 1 O-Linked glycan (2 sites).
DR iPTMnet; P01044; -.
DR PaxDb; P01044; -.
DR PeptideAtlas; P01044; -.
DR PRIDE; P01044; -.
DR GeneID; 280833; -.
DR CTD; 3827; -.
DR eggNOG; ENOG502RYAC; Eukaryota.
DR HOGENOM; CLU_029531_0_0_1; -.
DR InParanoid; P01044; -.
DR OrthoDB; 740995at2759; -.
DR TreeFam; TF351852; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0030195; P:negative regulation of blood coagulation; IBA:GO_Central.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0042311; P:vasodilation; IEA:UniProtKB-KW.
DR CDD; cd00042; CY; 3.
DR InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR002395; Kininogen.
DR InterPro; IPR027358; Kininogen-type_cystatin_dom.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR Pfam; PF00031; Cystatin; 3.
DR PRINTS; PR00334; KININOGEN.
DR SMART; SM00043; CY; 3.
DR SUPFAM; SSF54403; SSF54403; 3.
DR PROSITE; PS00287; CYSTATIN; 2.
DR PROSITE; PS51647; CYSTATIN_KININOGEN; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Blood coagulation; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hemostasis; Inflammatory response;
KW Phosphoprotein; Protease inhibitor; Reference proteome; Repeat; Secreted;
KW Signal; Thiol protease inhibitor; Vasoactive; Vasodilator.
FT SIGNAL 1..18
FT /evidence="ECO:0000305|PubMed:3546295"
FT CHAIN 19..621
FT /note="Kininogen-1"
FT /id="PRO_0000006675"
FT CHAIN 19..378
FT /note="Kininogen-1 heavy chain"
FT /id="PRO_0000006676"
FT PEPTIDE 379..388
FT /note="Lysyl-bradykinin"
FT /id="PRO_0000006677"
FT PEPTIDE 380..388
FT /note="Bradykinin"
FT /id="PRO_0000006678"
FT CHAIN 389..621
FT /note="Kininogen-1 light chain"
FT /id="PRO_0000006679"
FT DOMAIN 27..131
FT /note="Cystatin kininogen-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DOMAIN 150..253
FT /note="Cystatin kininogen-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DOMAIN 272..375
FT /note="Cystatin kininogen-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT REGION 396..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..435
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..491
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 378..379
FT /note="Cleavage; by kallikrein"
FT SITE 386..387
FT /note="Cleavage; by ACE"
FT /evidence="ECO:0000250|UniProtKB:P01042"
FT SITE 388..389
FT /note="Cleavage; by kallikrein"
FT SITE 498..499
FT /note="Cleavage; by kallikrein"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01042"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3546295"
FT CARBOHYD 136
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:19674964,
FT ECO:0000269|PubMed:3546295"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3546295"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3546295"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:3546295"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3546295"
FT CARBOHYD 398
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 399
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 400
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 406
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 512
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 520
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 524
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 536
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 548
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 553
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 570
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 581
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:19674964"
FT DISULFID 27..591
FT /note="Interchain (between heavy and light chains)"
FT DISULFID 82..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT DISULFID 106..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT DISULFID 141..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT DISULFID 205..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT DISULFID 228..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT DISULFID 263..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT DISULFID 327..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT DISULFID 350..369
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979,
FT ECO:0000269|PubMed:3546295"
FT VAR_SEQ 401..436
FT /note="VSLPHSAMSPVQDEERDSGKEQGPTHGHGWDHGKQI -> THVKSCEYKGRP
FT QEAGAEPAPQGEVSLPAESPQLAR (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:6572010"
FT /id="VSP_013562"
FT VAR_SEQ 437..621
FT /note="Missing (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:6572010"
FT /id="VSP_013563"
FT CONFLICT 295
FT /note="A -> T (in Ref. 2; CAA23709)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="P -> S (in Ref. 3; AAI05500)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="L -> V (in Ref. 3; AAI05500)"
FT /evidence="ECO:0000305"
FT CONFLICT 457
FT /note="G -> R (in Ref. 3; AAI05500)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 621 AA; 68890 MW; D16850BEFE3C55CD CRC64;
MKLITILFLC SRLLPSLTQE SSQEIDCNDQ DVFKAVDAAL TKYNSENKSG NQFVLYRITE
VARMDNPDTF YSLKYQIKEG DCPFQSNKTW QDCDYKDSAQ AATGECTATV AKRGNMKFSV
AIQTCLITPA EGPVVTAQYE CLGCVHPIST KSPDLEPVLR YAIQYFNNNT SHSHLFDLKE
VKRAQRQVVS GWNYEVNYSI AQTNCSKEEF SFLTPDCKSL SSGDTGECTD KAHVDVKLRI
SSFSQKCDLY PVKDFVQPPT RLCAGCPKPI PVDSPDLEEP LSHSIAKLNA EHDGAFYFKI
DTVKKATVQV VAGLKYSIVF IARETTCSKG SNEELTKSCE INIHGQILHC DANVYVVPWE
EKVYPTVNCQ PLGQTSLMKR PPGFSPFRSV QVMKTEGSTT VSLPHSAMSP VQDEERDSGK
EQGPTHGHGW DHGKQIKLHG LGLGHKHKHD QGHGHHGSHG LGHGHQKQHG LGHGHKHGHG
HGKHKNKGKN NGKHYDWRTP YLASSYEDST TSSAQTQEKT EETTLSSLAQ PGVAITFPDF
QDSDLIATVM PNTLPPHTES DDDWIPDIQT EPNSLAFKLI SDFPETTSPK CPSRPWKPVN
GVNPTVEMKE SHDFDLVDAL L
