KNG1_RAT
ID KNG1_RAT Reviewed; 639 AA.
AC P08934; P08933;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Kininogen-1;
DE Contains:
DE RecName: Full=Kininogen-1 heavy chain;
DE Contains:
DE RecName: Full=Bradykinin;
DE Contains:
DE RecName: Full=Kininogen-1 light chain;
DE Flags: Precursor;
GN Name=Kng1; Synonyms=Kng;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HMW AND LMW).
RX PubMed=3029068; DOI=10.1016/s0021-9258(18)61638-2;
RA Kitagawa H., Kitamura N., Hayashida H., Miyata T., Nakanishi S.;
RT "Differing expression patterns and evolution of the rat kininogen gene
RT family.";
RL J. Biol. Chem. 262:2190-2198(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LMW).
RX PubMed=2413018; DOI=10.1016/s0021-9258(17)38984-6;
RA Furuto-Kato S., Matsumoto A., Kitamura N., Nakanishi S.;
RT "Primary structures of the mRNAs encoding the rat precursors for bradykinin
RT and T-kinin. Structural relationship of kininogens with major acute phase
RT protein and alpha 1-cysteine proteinase inhibitor.";
RL J. Biol. Chem. 260:12054-12059(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65.
RC STRAIN=Buffalo;
RX PubMed=2439509; DOI=10.1016/s0021-9258(18)48080-5;
RA Fung W.-P., Schreiber G.;
RT "Structure and expression of the genes for major acute phase alpha 1-
RT protein (thiostatin) and kininogen in the rat.";
RL J. Biol. Chem. 262:9298-9308(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=3818598; DOI=10.1016/s0021-9258(18)61660-6;
RA Kageyama R., Kitamura N., Ohkubo H., Nakanishi S.;
RT "Differing utilization of homologous transcription initiation sites of rat
RT K and T kininogen genes under inflammation condition.";
RL J. Biol. Chem. 262:2345-2351(1987).
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=P08934-1; Sequence=Displayed;
CC Name=LMW;
CC IsoId=P08934-2; Sequence=VSP_001265, VSP_001266;
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}.
CC -!- MISCELLANEOUS: Rats express four types of kininogens: the classical
CC HMW/LMW kininogens and two additional LMW-like kininogens: T-I and T-
CC II.
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DR EMBL; L29428; AAA41486.1; -; mRNA.
DR EMBL; M11884; AAA41487.1; -; mRNA.
DR EMBL; M14369; AAA41484.1; -; Genomic_DNA.
DR EMBL; M14369; AAA41485.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M16455; AAA41482.1; -; Genomic_DNA.
DR PIR; A25486; A25486.
DR PIR; A28055; A28055.
DR PIR; C25486; C25486.
DR RefSeq; NP_036873.1; NM_012741.1. [P08934-1]
DR AlphaFoldDB; P08934; -.
DR SMR; P08934; -.
DR IntAct; P08934; 1.
DR STRING; 10116.ENSRNOP00000065146; -.
DR MEROPS; I25.018; -.
DR MEROPS; I25.019; -.
DR MEROPS; I25.950; -.
DR GlyGen; P08934; 5 sites.
DR PhosphoSitePlus; P08934; -.
DR jPOST; P08934; -.
DR PaxDb; P08934; -.
DR PRIDE; P08934; -.
DR GeneID; 25087; -.
DR KEGG; rno:25087; -.
DR UCSC; RGD:2980; rat. [P08934-1]
DR CTD; 25087; -.
DR RGD; 2980; Kng1.
DR eggNOG; ENOG502RYAC; Eukaryota.
DR InParanoid; P08934; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:P08934; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:RGD.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IPI:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0002542; P:Factor XII activation; IDA:RGD.
DR GO; GO:0006954; P:inflammatory response; IEP:RGD.
DR GO; GO:0030195; P:negative regulation of blood coagulation; ISO:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:RGD.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0050672; P:negative regulation of lymphocyte proliferation; IDA:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:RGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:RGD.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:RGD.
DR GO; GO:0052548; P:regulation of endopeptidase activity; IDA:RGD.
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 2: Evidence at transcript level;
KW Alternative splicing; Blood coagulation; Disulfide bond; Glycoprotein;
KW Hemostasis; Inflammatory response; Phosphoprotein; Protease inhibitor;
KW Reference proteome; Repeat; Secreted; Signal; Thiol protease inhibitor;
KW Vasoactive; Vasodilator.
FT SIGNAL 1..18
FT CHAIN 19..639
FT /note="Kininogen-1"
FT /id="PRO_0000006695"
FT CHAIN 19..380
FT /note="Kininogen-1 heavy chain"
FT /id="PRO_0000006696"
FT PEPTIDE 381..389
FT /note="Bradykinin"
FT /id="PRO_0000006697"
FT CHAIN 390..639
FT /note="Kininogen-1 light chain"
FT /id="PRO_0000006698"
FT DOMAIN 28..132
FT /note="Cystatin kininogen-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DOMAIN 151..254
FT /note="Cystatin kininogen-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DOMAIN 273..376
FT /note="Cystatin kininogen-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT REGION 438..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..459
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..500
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 501..516
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 517..543
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 387..388
FT /note="Cleavage; by ACE"
FT /evidence="ECO:0000250|UniProtKB:P01042"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01042"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..609
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 83..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 107..126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 142..145
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 206..218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 229..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 264..267
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 328..340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 351..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT VAR_SEQ 402..433
FT /note="VSPSYIARVQEERDPGNEQGPIHGHGWLHAKQ -> RLLNSCEYKGRLLKAG
FT AGPAPERQAEASTVTP (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:2413018,
FT ECO:0000303|PubMed:3029068"
FT /id="VSP_001265"
FT VAR_SEQ 434..639
FT /note="Missing (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:2413018,
FT ECO:0000303|PubMed:3029068"
FT /id="VSP_001266"
FT CONFLICT 61
FT /note="E -> K (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 639 AA; 70933 MW; D3172DF94FF56AF5 CRC64;
MKLITILLLC SRLLPSLAQE EDAQEMDCND ESLFQAVDTA LKKYNAGLKS GNQFVLYQVT
EGTKKDGSKT FYSFKYQIKE GNCSVQSGFA WQDCDFKDAE EAATGECTAT LEKRRNNKFS
IATQICNITP GKGPIVTNEY HCLGCMHPIS VDSPELGPVL KHAVEHFNNN TKHTHLFALG
EVKSADRQVV AGMNYQIIYS IVQTNCSKED FPSLHEDCVP LPSGDDGECK GNAFVDIHKT
IAGFSDSCEF YPGDDLFELL PEDCPGCPRN IPVDSPELKE ALGHSIAQLN AENNHTFYFK
IDTVKKATSQ VVAGTKYVIE FIARETKCSK ESNAELTADC ETKRLGQSLN CNANVYMRPW
ENKVVPTVKC KVLDMTSVIR RPPGFSPFRA PRVKKPKEST TVSPSYIARV QEERDPGNEQ
GPIHGHGWLH AKQIKNKNHQ GHKHGHGIGH GHQKPHGLGH GHQLKLDDLK QQREDGYDHR
HPVGHGHGQR HGHGHGHGHG RDKHTNKDKN NVKHTDQRRA PLTSSSEDNT TSTQIQGRTE
GFTLNPPLAQ PAVISRGFQD SGFTEGVIAT TSPYDTETHD DLIPDIHVQP DSLSFKLISD
FPEATSHKCP GRPWKPVSRK DPTIETTEFS DFDLLDALS
