KNG2_BOVIN
ID KNG2_BOVIN Reviewed; 619 AA.
AC P01045; P01047;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Kininogen-2;
DE AltName: Full=Kininogen II;
DE AltName: Full=Thiol proteinase inhibitor;
DE Contains:
DE RecName: Full=Kininogen-2 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-2 light chain;
DE Flags: Precursor;
GN Name=KNG2;
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 PROTEIN SEQUENCE OF 19-376, PYROGLUTAMATE FORMATION AT GLN-19, AND
RP GLYCOSYLATION AT ASN-87; THR-136; ASN-168; ASN-169; ASN-197; ASN-204 AND
RP ASN-280.
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 [4]
RP PROTEIN SEQUENCE OF 376-391.
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 [5]
RP PROTEIN SEQUENCE OF 387-455.
RX PubMed=956151; DOI=10.1093/oxfordjournals.jbchem.a131175;
RA Han Y.N., Kato H., Iwanaga S., Suzuki T.;
RT "Primary structure of bovine plasma high-molecular-weight kininogen. The
RT amino acid sequence of a glycopeptide portion (fragment 1) following the C-
RT terminus ot the bradykinin moiety.";
RL J. Biochem. 79:1201-1222(1976).
RN [6]
RP PROTEIN SEQUENCE OF 456-496.
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.
RA Iwanaga S., Kato H., Sugo T., Ikari N., Hasimoto N., Fuji S.;
RL (In) Tschesche H., Hotzer H. (eds.);
RL Biological functions of Proteinases, pp.243-259, Springer-Verlag, Berlin
RL (1979).
CC -!- FUNCTION: (1) Kininogens are inhibitors of thiol proteases; (2) HMW-
CC kininogen plays an important role in blood coagulation by helping to
CC position optimally prekallikrein and factor XI next to factor XII; (3)
CC HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of
CC thrombocytes; (4) the active peptide bradykinin that is released from
CC HMW-kininogen shows a variety of physiological effects: (4A) influence
CC in smooth muscle contraction, (4B) induction of hypotension, (4C)
CC natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it
CC is a mediator of inflammation and causes (4E1) increase in vascular
CC permeability, (4E2) stimulation of nociceptors (4E3) release of other
CC mediators of inflammation (e.g. prostaglandins), (4F) it has a
CC cardioprotective effect (directly via bradykinin action, indirectly via
CC endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits
CC the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to
CC HMW-kininogen not involved in blood clotting.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=HMW;
CC IsoId=P01045-1; Sequence=Displayed;
CC Name=LMW;
CC IsoId=P01045-2; Sequence=VSP_013564, VSP_013565;
CC -!- TISSUE SPECIFICITY: Plasma.
CC -!- PTM: Bradykinin is released from kininogen by plasma kallikrein.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; V01492; CAA24736.1; -; mRNA.
DR EMBL; V00427; CAA23710.1; -; mRNA.
DR PIR; A01282; KGBOH2.
DR PIR; A01284; KGBOL2.
DR RefSeq; NP_001106748.1; NM_001113277.1. [P01045-1]
DR AlphaFoldDB; P01045; -.
DR SMR; P01045; -.
DR MEROPS; I25.016; -.
DR MEROPS; I25.017; -.
DR MEROPS; I25.950; -.
DR iPTMnet; P01045; -.
DR PeptideAtlas; P01045; -.
DR PRIDE; P01045; -.
DR GeneID; 280833; -.
DR KEGG; bta:280833; -.
DR CTD; 3827; -.
DR InParanoid; P01045; -.
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; Hydroxylation;
KW Inflammatory response; Protease inhibitor; Pyrrolidone carboxylic acid;
KW Reference proteome; Repeat; Secreted; Signal; Thiol protease inhibitor;
KW Vasoactive; Vasodilator.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:3546295"
FT CHAIN 19..619
FT /note="Kininogen-2"
FT /id="PRO_0000006680"
FT CHAIN 19..376
FT /note="Kininogen-2 heavy chain"
FT /id="PRO_0000006681"
FT PEPTIDE 377..386
FT /note="Lysyl-bradykinin"
FT /evidence="ECO:0000269|PubMed:956151"
FT /id="PRO_0000006682"
FT PEPTIDE 378..386
FT /note="Bradykinin"
FT /evidence="ECO:0000269|PubMed:956151"
FT /id="PRO_0000006683"
FT CHAIN 387..619
FT /note="Kininogen-2 light chain"
FT /id="PRO_0000006684"
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 270..373
FT /note="Cystatin kininogen-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT REGION 394..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..433
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..489
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 47
FT /note="Not glycosylated"
FT SITE 376..377
FT /note="Cleavage; by kallikrein"
FT SITE 386..387
FT /note="Cleavage; by kallikrein"
FT SITE 496..497
FT /note="Cleavage; by kallikrein"
FT MOD_RES 19
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:3546295"
FT MOD_RES 380
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250"
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: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 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3546295"
FT CARBOHYD 396
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 397
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 398
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 400
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 404
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 510
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 518
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 522
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 534
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 546
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 551
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT CARBOHYD 568
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.7"
FT DISULFID 27..589
FT /note="Interchain (between heavy and light chains)"
FT DISULFID 82..93
FT DISULFID 106..125
FT DISULFID 141..144
FT DISULFID 205..217
FT DISULFID 228..247
FT DISULFID 261..264
FT DISULFID 325..337
FT DISULFID 348..367
FT VAR_SEQ 399..434
FT /note="VSLPHSAMSPVQDEERDSGKEQGPTHGHGWDHGKQI -> THVKSCEYKGRP
FT QEAGAEPAPQGEVSLPAESPQLAR (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:6572010"
FT /id="VSP_013564"
FT VAR_SEQ 435..619
FT /note="Missing (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:6572010"
FT /id="VSP_013565"
FT VARIANT 398
FT /note="T -> P"
FT VARIANT 401
FT /note="L -> V"
FT VARIANT 454
FT /note="H -> K"
SQ SEQUENCE 619 AA; 68710 MW; F04320A8EB0EE0DA CRC64;
MKLITILFLC SRLLPSLTQE SSQEIDCNDQ DVFKAVDAAL TKYNSENKSG NQFVLYRITE
VARMDNPDTF YSLKYQIKEG DCPFQSNKTW QDCDYKDSAQ AATGQCTATV AKRGNMKFSV
AIQTCLITPA EGPVVTAQYE CLGCVHPIST KSPDLEPVLR YAIQYFNNNT SHSHLFDLKE
VKRAQKQVVS GWNYEVNYSI AQTNCSKEEF SFLTPDCKSL SSGDTGECTD KAHVDVKLRI
SSFSQKCDLY PGEDFLPPMV CVGCPKPIPV DSPDLEEALN HSIAKLNAEH DGTFYFKIDT
VKKATVQVVG GLKYSIVFIA RETTCSKGSN EELTKSCEIN IHGQILHCDA NVYVVPWEEK
VYPTVNCQPL GQTSLMKRPP GFSPFRSVQV MKTEGSTTVS LPHSAMSPVQ DEERDSGKEQ
GPTHGHGWDH GKQIKLHGLG LGHKHKHDQG HGHHRSHGLG HGHQKQHGLG HGHKHGHGHG
KHKNKGKNNG KHYDWRTPYL ASSYEDSTTS SAQTQEKTEE TTLSSLAQPG VAITFPDFQD
SDLIATVMPN TLPPHTESDD DWIPDIQTEP NSLAFKLISD FPETTSPKCP SRPWKPVNGV
NPTVEMKESH DFDLVDALL
