KNG1_MOUSE
ID KNG1_MOUSE Reviewed; 661 AA.
AC O08677; O08676; Q32MX7; Q6S9I1; Q91XK5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 188.
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 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] (ISOFORMS HMW AND LMW).
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=9199253; DOI=10.1016/s0167-4781(97)00018-3;
RA Takano M., Kondo J., Yayama K., Otani M., Sano K., Okamoto H.;
RT "Molecular cloning of cDNAs for mouse low-molecular-weight and high-
RT molecular-weight prekininogens.";
RL Biochim. Biophys. Acta 1352:222-230(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC STRAIN=FVB/N;
RX PubMed=15134344; DOI=10.1515/bc.2004.025;
RA Cardoso C.C., Garrett T., Cayla C., Meneton P., Pesquero J.B., Bader M.;
RT "Structure and expression of two kininogen genes in mice.";
RL Biol. Chem. 385:295-301(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J;
RA Merkulov S.M., Komar A.A., McCrae K.R.;
RT "Characterization of high molecular weight kininogen gene duplication in
RT mice.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LMW).
RC STRAIN=C57BL/6J; TISSUE=Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS HMW AND LMW).
RC STRAIN=FVB/N; TISSUE=Liver;
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 [6]
RP PROTEIN SEQUENCE OF 21-35 AND 389-403 (ISOFORM LMW), AND INTERACTION WITH
RP CRISP3.
RC TISSUE=Serum;
RX PubMed=20116414; DOI=10.1016/j.bbagen.2010.01.011;
RA Udby L., Johnsen A.H., Borregaard N.;
RT "Human CRISP-3 binds serum alpha1B-glycoprotein across species.";
RL Biochim. Biophys. Acta 1800:481-485(2010).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-168.
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 [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82; ASN-168; ASN-204 AND
RP ASN-242.
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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: 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 -!- SUBUNIT: Isoform LMW interacts with CRISP3.
CC {ECO:0000269|PubMed:20116414}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=HMW;
CC IsoId=O08677-1; Sequence=Displayed;
CC Name=LMW;
CC IsoId=O08677-2; Sequence=VSP_001263, VSP_001264;
CC Name=3;
CC IsoId=O08677-3; Sequence=VSP_037159;
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; D84415; BAA19742.1; -; mRNA.
DR EMBL; D84435; BAA19743.1; -; mRNA.
DR EMBL; AY462058; AAR88632.1; -; mRNA.
DR EMBL; AY660571; AAT70087.1; -; mRNA.
DR EMBL; AK005547; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC018158; AAH18158.1; -; mRNA.
DR EMBL; BC108936; AAI08937.1; -; mRNA.
DR CCDS; CCDS28073.1; -. [O08677-2]
DR CCDS; CCDS49803.1; -. [O08677-3]
DR CCDS; CCDS49804.1; -. [O08677-1]
DR RefSeq; NP_001095881.1; NM_001102411.1.
DR RefSeq; NP_075614.1; NM_023125.3. [O08677-2]
DR AlphaFoldDB; O08677; -.
DR SMR; O08677; -.
DR BioGRID; 201005; 6.
DR IntAct; O08677; 4.
DR STRING; 10090.ENSMUSP00000023589; -.
DR MEROPS; I25.018; -.
DR MEROPS; I25.019; -.
DR MEROPS; I25.950; -.
DR GlyConnect; 2451; 1 N-Linked glycan (1 site).
DR GlyGen; O08677; 4 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O08677; -.
DR PhosphoSitePlus; O08677; -.
DR SwissPalm; O08677; -.
DR REPRODUCTION-2DPAGE; IPI00129225; -.
DR CPTAC; non-CPTAC-3506; -.
DR jPOST; O08677; -.
DR MaxQB; O08677; -.
DR PaxDb; O08677; -.
DR PeptideAtlas; O08677; -.
DR PRIDE; O08677; -.
DR ProteomicsDB; 263640; -. [O08677-1]
DR ProteomicsDB; 263641; -. [O08677-2]
DR ProteomicsDB; 263642; -. [O08677-3]
DR DNASU; 16644; -.
DR Ensembl; ENSMUST00000039492; ENSMUSP00000040485; ENSMUSG00000022875. [O08677-2]
DR GeneID; 16644; -.
DR KEGG; mmu:16644; -.
DR UCSC; uc007ytb.1; mouse. [O08677-1]
DR UCSC; uc007ytc.1; mouse. [O08677-2]
DR CTD; 3827; -.
DR MGI; MGI:1097705; Kng1.
DR VEuPathDB; HostDB:ENSMUSG00000022875; -.
DR eggNOG; ENOG502RYAC; Eukaryota.
DR GeneTree; ENSGT00950000182930; -.
DR InParanoid; O08677; -.
DR OMA; SEENKHW; -.
DR OrthoDB; 740995at2759; -.
DR PhylomeDB; O08677; -.
DR TreeFam; TF351852; -.
DR BioGRID-ORCS; 16644; 1 hit in 71 CRISPR screens.
DR PRO; PR:O08677; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; O08677; protein.
DR Bgee; ENSMUSG00000022875; Expressed in left lobe of liver and 43 other tissues.
DR ExpressionAtlas; O08677; baseline and differential.
DR Genevisible; O08677; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; ISO:MGI.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; ISO:MGI.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; ISO:MGI.
DR GO; GO:0030195; P:negative regulation of blood coagulation; ISO:MGI.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:MGI.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
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; 1.
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..20
FT CHAIN 21..661
FT /note="Kininogen-1"
FT /id="PRO_0000006691"
FT CHAIN 21..379
FT /note="Kininogen-1 heavy chain"
FT /id="PRO_0000006692"
FT PEPTIDE 380..388
FT /note="Bradykinin"
FT /id="PRO_0000006693"
FT CHAIN 389..661
FT /note="Kininogen-1 light chain"
FT /id="PRO_0000006694"
FT DOMAIN 28..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 405..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 626..661
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 406..434
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 435..469
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..526
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 537..583
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 386..387
FT /note="Cleavage; by ACE"
FT /evidence="ECO:0000250|UniProtKB:P01042"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01042"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17330941"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957,
FT ECO:0000269|PubMed:17330941"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17330941"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17330941"
FT DISULFID 28..631
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..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 141..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 205..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 228..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 263..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 327..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT DISULFID 350..369
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979"
FT VAR_SEQ 401..581
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15134344, ECO:0000303|Ref.3"
FT /id="VSP_037159"
FT VAR_SEQ 401..432
FT /note="VSPPYIAREQEERDAETEQGPTHGHGWLHEKQ -> RLLRACEYKGRLSKAG
FT AEPAPERQAESSQVKQ (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:9199253"
FT /id="VSP_001263"
FT VAR_SEQ 433..661
FT /note="Missing (in isoform LMW)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:9199253"
FT /id="VSP_001264"
FT CONFLICT 642
FT /note="E -> K (in Ref. 5; AAI08937)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 661 AA; 73102 MW; 774460258D58796E CRC64;
MKLITTLLLC SGLLLTLTQG EEAQEIDCND EAVFQAVDFS LKQFNPGVKS GNQYMLHRVI
EGTKTDGSPT FYSFKYLIKE GNCSAQSGLA WQDCDFKDAE EAATGECTAT VGKRENEFFI
VTQTCKIAPS KAPILKAYFP CIGCVHAIST DSPDLEPVLK HSIEHFNNNT DHSHLFTLRK
VKSAHRQVVA GLNFDITYTI VQTNCSKERF PSLHGDCVAL PNGDDGECRG NLFMDINNKI
ANFSQSCTLY SGDDLVEALP KPCPGCPRDI PVDSPELKEV LGHSIAQLNA ENDHPFYYKI
DTVKKATSQV VAGTKYVIEF IARETKCSKE SNTELAEDCE IKHLGQSLDC NANVYMRPWE
NKVVPTVKCQ ALDMTEMARR PPGFSPFRSV TVQETKEGRT VSPPYIAREQ EERDAETEQG
PTHGHGWLHE KQIKANKNHR GHKHGHDHGH WSPRRHGLGH GHQKPHGLGH GHQLKLDYLR
HQREDGDDHT HTVGHGHGHG HGHGHGHGHG HGHGHGHGHG HGHGKHTNKD KNSVKQTTQR
TESLASSSEY STTSTQMQGR TEGPTLTPPR AQPTVTSSGF QDSDFIEDVV ATTPPYDTGA
HDDLIPDIHV QPDSLSFKLI SDFPEATSPK CPGRPWKPAS WEDPNTETTE FSDFDLLDAL
S
