ID KNG1_HUMAN Reviewed; 644 AA. AC P01042; A8K474; B2RCR2; C9JEX1; P01043; Q53EQ0; Q6PAU9; Q7M4P1; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 13-FEB-2019, entry version 216. DE RecName: Full=Kininogen-1; DE AltName: Full=Alpha-2-thiol proteinase inhibitor; DE AltName: Full=Fitzgerald factor; DE AltName: Full=High molecular weight kininogen; DE Short=HMWK; DE AltName: Full=Williams-Fitzgerald-Flaujeac factor; DE Contains: DE RecName: Full=Kininogen-1 heavy chain; DE Contains: DE RecName: Full=T-kinin; DE AltName: Full=Ile-Ser-Bradykinin; 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 Contains: DE RecName: Full=Low molecular weight growth-promoting factor; DE Flags: Precursor; GN Name=KNG1; Synonyms=BDK, KNG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LMW). RX PubMed=6441591; DOI=10.1021/bi00319a005; RA Ohkubo I., Kurachi K., Takasawa T., Shiokawa H., Sasaki M.; RT "Isolation of a human cDNA for alpha 2-thiol proteinase inhibitor and RT its identity with low molecular weight kininogen."; RL Biochemistry 23:5691-5697(1984). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS HMW AND LMW). RC TISSUE=Liver; RX PubMed=2989293; RA Takagaki Y., Kitamura N., Nakanishi S.; RT "Cloning and sequence analysis of cDNAs for human high molecular RT weight and low molecular weight prekininogens. Primary structures of RT two human prekininogens."; RL J. Biol. Chem. 260:8601-8609(1985). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LMW). RC TISSUE=Liver; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LMW), AND VARIANT RP THR-178. RC TISSUE=Kidney; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-163; THR-178 AND RP PRO-212. RG SeattleSNPs variation discovery resource; RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-178. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LMW), AND VARIANT RP MET-197. RC 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 19-380, GLYCOSYLATION AT ASN-169 AND ASN-205, AND RP LACK OF GLYCOSYLATION AT ASN-48. RX PubMed=3484703; DOI=10.1111/j.1432-1033.1986.tb09421.x; RA Kellermann J., Lottspeich F., Henschen A., Muller-Esterl W.; RT "Completion of the primary structure of human high-molecular-mass RT kininogen. The amino acid sequence of the entire heavy chain and RT evidence for its evolution by gene triplication."; RL Eur. J. Biochem. 154:471-478(1986). RN [10] RP PROTEIN SEQUENCE OF 376-389 (T-KININ), AND VARIANT 378-LEU--LYS-380 RP DEL. RC TISSUE=Ascites; RX PubMed=3828072; RA Wunderer G., Walter I., Mueller E., Henschen A.; RT "Human Ile-Ser-bradykinin, identical with rat T-kinin, is a major RT permeability factor in ovarian carcinoma ascites."; RL Biol. Chem. Hoppe-Seyler 367:1231-1234(1986). RN [11] RP PROTEIN SEQUENCE OF 376-389 (T-KININ), TISSUE SPECIFICITY, AND VARIANT RP 378-LEU--LYS-380 DEL. RX PubMed=2076202; RA Wunderer G., Walter I., Eschenbacher B., Lang M., Kellermann J., RA Kindermann G.; RT "Ile-Ser-bradykinin is an aberrant permeability factor in various RT human malignant effusions."; RL Biol. Chem. Hoppe-Seyler 371:977-981(1990). RN [12] RP PROTEIN SEQUENCE OF 379-644. RX PubMed=4054110; DOI=10.1111/j.1432-1033.1985.tb09199.x; RA Lottspeich F., Kellermann J., Henschen A., Foertsch B., RA Mueller-Esterl W.; RT "The amino acid sequence of the light chain of human high-molecular- RT mass kininogen."; RL Eur. J. Biochem. 152:307-314(1985). RN [13] RP PROTEIN SEQUENCE OF 380-389, AND HYDROXYLATION AT PRO-383. RX PubMed=3366244; DOI=10.1016/0014-5793(88)80427-7; RA Kato H., Matsumura Y., Maeda H.; RT "Isolation and identification of hydroxyproline analogues of RT bradykinin in human urine."; RL FEBS Lett. 232:252-254(1988). RN [14] RP PROTEIN SEQUENCE OF 381-389. RX PubMed=4952632; RA Pierce J.V.; RT "Structural features of plasma kinins and kininogens."; RL Fed. Proc. 27:52-57(1968). RN [15] RP PROTEIN SEQUENCE OF 431-434, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=7589467; DOI=10.1016/0014-5793(95)01037-F; RA Straczek J., Maachi F., Le Nguyen D., Becchi M., Heulin M.H., RA Nabet P., Belleville F.; RT "Purification from human plasma of a tetrapeptide that potentiates RT insulin-like growth factor-I activity in chick embryo cartilage."; RL FEBS Lett. 373:207-211(1995). RN [16] RP DISULFIDE BONDS. RA Sueyoshi T., Miyata T., Kato H., Iwanaga S.; RT "Disulfide bonds in bovine HMW kininogens."; RL Seikagaku 56:808-808(1984). RN [17] RP GENE STRUCTURE. RX PubMed=2989294; RA Kitamura N., Kitagawa H., Fukushima D., Takagaki Y., Miyata T., RA Nakanishi S.; RT "Structural organization of the human kininogen gene and a model for RT its evolution."; RL J. Biol. Chem. 260:8610-8617(1985). RN [18] RP AMINO-ACID COMPOSITION OF 381-389, AND HYDROXYLATION AT PRO-383. RX PubMed=3182782; RA Maeda H., Matsumura Y., Kato H.; RT "Purification and identification of [hydroxyprolyl3]bradykinin in RT ascitic fluid from a patient with gastric cancer."; RL J. Biol. Chem. 263:16051-16054(1988). RN [19] RP GLYCOSYLATION AT ASN-294. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-169 AND ASN-294. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [21] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-48; ASN-169; ASN-205 AND RP ASN-294. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Serum; RX PubMed=19824718; DOI=10.1021/pr900603n; RA Zhou W., Ross M.M., Tessitore A., Ornstein D., Vanmeter A., RA Liotta L.A., Petricoin E.F. III; RT "An initial characterization of the serum phosphoproteome."; RL J. Proteome Res. 8:5523-5531(2009). RN [23] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-169; ASN-205 AND ASN-294. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [24] RP GLYCOSYLATION AT ASN-48; ASN-205 AND ASN-294. RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core RT fucosylated glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [25] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-294, AND STRUCTURE OF RP CARBOHYDRATES. RC TISSUE=Cerebrospinal fluid; RX PubMed=19838169; DOI=10.1038/nmeth.1392; RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., RA Brinkmalm G., Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [27] RP PHOSPHORYLATION AT SER-332. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted RT phosphoproteome."; RL Cell 161:1619-1632(2015). CC -!- FUNCTION: (1) Kininogens are inhibitors of thiol proteases; (2) CC HMW-kininogen plays an important role in blood coagulation by CC helping to position optimally prekallikrein and factor XI next to CC factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin- CC induced aggregation of thrombocytes; (4) the active peptide CC bradykinin that is released from HMW-kininogen shows a variety of CC physiological effects: (4A) influence in smooth muscle CC contraction, (4B) induction of hypotension, (4C) natriuresis and CC diuresis, (4D) decrease in blood glucose level, (4E) it is a CC mediator of inflammation and causes (4E1) increase in vascular CC permeability, (4E2) stimulation of nociceptors (4E3) release of CC other mediators of inflammation (e.g. prostaglandins), (4F) it has CC a cardioprotective effect (directly via bradykinin action, CC indirectly via endothelium-derived relaxing factor action); (5) CC LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW- CC kininogen is in contrast to HMW-kininogen not involved in blood CC clotting. CC -!- INTERACTION: CC Q10714:Ance (xeno); NbExp=2; IntAct=EBI-6378713, EBI-115736; CC P46663:BDKRB1; NbExp=2; IntAct=EBI-6623250, EBI-6623218; CC P30411:BDKRB2; NbExp=2; IntAct=EBI-6623273, EBI-6623386; CC Q07021:C1QBP; NbExp=4; IntAct=EBI-6378713, EBI-347528; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=HMW; CC IsoId=P01042-1; Sequence=Displayed; CC Name=LMW; CC IsoId=P01042-2; Sequence=VSP_001261, VSP_001262; CC Name=3; CC IsoId=P01042-3; Sequence=VSP_047307, VSP_047308; CC Note=Gene prediction based on EST data.; CC -!- TISSUE SPECIFICITY: Secreted in plasma. T-kinin is detected in CC malignant ovarian, colon and breast carcinomas, but not in benign CC tumors. {ECO:0000269|PubMed:2076202}. CC -!- PTM: Bradykinin is released from kininogen by plasma kallikrein. CC -!- PTM: Hydroxylation of Pro-383 occurs prior to the release of CC bradykinin. {ECO:0000269|PubMed:3182782, CC ECO:0000269|PubMed:3366244}. CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium. CC {ECO:0000269|PubMed:26091039}. CC -!- PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly CC core 8 glycans. {ECO:0000269|PubMed:12754519, CC ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, CC ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, CC ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:3484703}. CC -!- POLYMORPHISM: The T-kinin peptide is missing residues 378 to 380, CC probably as a result of a naturally occurring variant. The CC complete sequence of the T-kinin peptide is therefore ISRPPGFSPFR. CC This peptide is associated with malignant tumors but not with CC benign ones. {ECO:0000269|PubMed:3828072}. CC -!- DISEASE: High molecular weight kininogen deficiency (HMWK CC deficiency) [MIM:228960]: Autosomal recessive coagulation defect. CC Patients with HWMK deficiency do not have a hemorrhagic tendency, CC but they exhibit abnormal surface-mediated activation of CC fibrinolysis. Note=The disease is caused by mutations affecting CC the gene represented in this entry. CC -!- WEB RESOURCE: Name=Wikipedia; Note=High molecular weight kininogen CC entry; CC URL="https://en.wikipedia.org/wiki/High-molecular_weight_kininogen"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/kng/"; 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; K02566; AAA35497.1; -; mRNA. DR EMBL; M11437; AAB59550.1; -; Genomic_DNA. DR EMBL; M11438; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11521; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11522; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11523; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11524; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11525; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11526; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11527; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11528; AAB59550.1; JOINED; Genomic_DNA. DR EMBL; M11437; AAB59551.1; -; Genomic_DNA. DR EMBL; M11438; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11521; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11522; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11523; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11524; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11525; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11526; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11527; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; M11528; AAB59551.1; JOINED; Genomic_DNA. DR EMBL; AK315230; BAG37659.1; -; mRNA. DR EMBL; AK290839; BAF83528.1; -; mRNA. DR EMBL; AK223589; BAD97309.1; -; mRNA. DR EMBL; AY248697; AAO61092.1; -; Genomic_DNA. DR EMBL; AC109780; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC112907; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW78179.1; -; Genomic_DNA. DR EMBL; BC060039; AAH60039.1; -; mRNA. DR CCDS; CCDS3281.1; -. [P01042-2] DR CCDS; CCDS43183.1; -. [P01042-1] DR CCDS; CCDS54695.1; -. [P01042-3] DR PIR; A01279; KGHUH1. DR PIR; A01280; KGHUL1. DR PIR; S13279; S13279. DR RefSeq; NP_000884.1; NM_000893.3. [P01042-2] DR RefSeq; NP_001095886.1; NM_001102416.2. [P01042-1] DR RefSeq; NP_001159923.1; NM_001166451.1. [P01042-3] DR UniGene; Hs.77741; -. DR PDB; 1NY2; X-ray; 2.30 A; 4=381-385. DR PDB; 2WOK; X-ray; 1.70 A; B=381-389. DR PDB; 4ASQ; X-ray; 1.99 A; P=381-389. DR PDB; 4ASR; X-ray; 1.90 A; P=381-389. DR PDB; 4ECB; X-ray; 2.20 A; A/B=498-507. DR PDB; 4ECC; X-ray; 2.20 A; A=498-510. DR PDB; 5I25; X-ray; 2.85 A; B=601-608. DR PDB; 6F27; NMR; -; A=380-388. DR PDB; 6F3V; NMR; -; A=381-389. DR PDB; 6F3W; NMR; -; A=381-389. DR PDB; 6F3X; NMR; -; A=380-388. DR PDB; 6F3Y; NMR; -; A=380-388. DR PDBsum; 1NY2; -. DR PDBsum; 2WOK; -. DR PDBsum; 4ASQ; -. DR PDBsum; 4ASR; -. DR PDBsum; 4ECB; -. DR PDBsum; 4ECC; -. DR PDBsum; 5I25; -. DR PDBsum; 6F27; -. DR PDBsum; 6F3V; -. DR PDBsum; 6F3W; -. DR PDBsum; 6F3X; -. DR PDBsum; 6F3Y; -. DR ProteinModelPortal; P01042; -. DR SMR; P01042; -. DR BioGrid; 110026; 33. DR IntAct; P01042; 13. DR MINT; P01042; -. DR STRING; 9606.ENSP00000265023; -. DR BindingDB; P01042; -. DR ChEMBL; CHEMBL3638337; -. DR MEROPS; I25.016; -. DR CarbonylDB; P01042; -. DR GlyConnect; 810; -. DR iPTMnet; P01042; -. DR PhosphoSitePlus; P01042; -. DR BioMuta; KNG1; -. DR DMDM; 124056474; -. DR SWISS-2DPAGE; P01042; -. DR EPD; P01042; -. DR jPOST; P01042; -. DR PaxDb; P01042; -. DR PeptideAtlas; P01042; -. DR PRIDE; P01042; -. DR ProteomicsDB; 51315; -. DR ProteomicsDB; 51316; -. [P01042-2] DR DNASU; 3827; -. DR Ensembl; ENST00000265023; ENSP00000265023; ENSG00000113889. [P01042-1] DR Ensembl; ENST00000287611; ENSP00000287611; ENSG00000113889. [P01042-2] DR Ensembl; ENST00000447445; ENSP00000396025; ENSG00000113889. [P01042-3] DR Ensembl; ENST00000644859; ENSP00000493985; ENSG00000113889. [P01042-1] DR Ensembl; ENST00000645909; ENSP00000496167; ENSG00000113889. [P01042-2] DR GeneID; 3827; -. DR KEGG; hsa:3827; -. DR UCSC; uc003fqr.4; human. [P01042-1] DR CTD; 3827; -. DR DisGeNET; 3827; -. DR EuPathDB; HostDB:ENSG00000113889.11; -. DR GeneCards; KNG1; -. DR HGNC; HGNC:6383; KNG1. DR HPA; CAB009809; -. DR HPA; HPA001616; -. DR HPA; HPA001645; -. DR MalaCards; KNG1; -. DR MIM; 228960; phenotype. DR MIM; 612358; gene. DR neXtProt; NX_P01042; -. DR OpenTargets; ENSG00000113889; -. DR Orphanet; 483; Congenital high-molecular-weight kininogen deficiency. DR PharmGKB; PA225; -. DR eggNOG; ENOG410IKIQ; Eukaryota. DR eggNOG; ENOG4111ZQ8; LUCA. DR GeneTree; ENSGT00940000154051; -. DR HOGENOM; HOG000113239; -. DR HOVERGEN; HBG006224; -. DR InParanoid; P01042; -. DR KO; K03898; -. DR OMA; DWIPDIQ; -. DR OrthoDB; 740995at2759; -. DR PhylomeDB; P01042; -. DR TreeFam; TF351852; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR ChiTaRS; KNG1; human. DR EvolutionaryTrace; P01042; -. DR GeneWiki; Kininogen_1; -. DR GenomeRNAi; 3827; -. DR PMAP-CutDB; P01042; -. DR PRO; PR:P01042; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; ENSG00000113889; Expressed in 72 organ(s), highest expression level in liver. DR Genevisible; P01042; HS. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; NAS:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB. DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB. DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; TAS:Reactome. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0031640; P:killing of cells of other organism; IDA:UniProtKB. DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:UniProtKB. DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central. DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0043065; P:positive regulation of apoptotic process; NAS:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0042311; P:vasodilation; IEA:UniProtKB-KW. DR CDD; cd00042; CY; 3. DR InterPro; IPR000010; Cystatin_dom. 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 PROSITE; PS00287; CYSTATIN; 2. DR PROSITE; PS51647; CYSTATIN_KININOGEN; 3. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Blood coagulation; KW Complete proteome; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Hemostasis; Hydroxylation; Inflammatory response; KW Phosphoprotein; Polymorphism; Protease inhibitor; KW Pyrrolidone carboxylic acid; Reference proteome; Repeat; Secreted; KW Signal; Thiol protease inhibitor; Vasoactive; Vasodilator. FT SIGNAL 1 18 {ECO:0000269|PubMed:2989293, FT ECO:0000269|PubMed:3484703}. FT CHAIN 19 644 Kininogen-1. FT /FTId=PRO_0000006685. FT CHAIN 19 380 Kininogen-1 heavy chain. FT /FTId=PRO_0000006686. FT PEPTIDE 376 389 T-kinin. FT /FTId=PRO_0000372485. FT PEPTIDE 380 389 Lysyl-bradykinin. FT /FTId=PRO_0000006687. FT PEPTIDE 381 389 Bradykinin. FT /FTId=PRO_0000006688. FT CHAIN 390 644 Kininogen-1 light chain. FT /FTId=PRO_0000006689. FT PEPTIDE 431 434 Low molecular weight growth-promoting FT factor. FT /FTId=PRO_0000006690. FT DOMAIN 28 132 Cystatin kininogen-type 1. FT {ECO:0000255|PROSITE-ProRule:PRU00979}. FT DOMAIN 151 254 Cystatin kininogen-type 2. FT {ECO:0000255|PROSITE-ProRule:PRU00979}. FT DOMAIN 273 376 Cystatin kininogen-type 3. FT {ECO:0000255|PROSITE-ProRule:PRU00979}. FT REPEAT 420 449 FT REPEAT 450 479 FT REPEAT 480 510 FT REGION 120 153 O-glycosylated at one site only. FT COMPBIAS 420 510 His-rich. FT SITE 48 48 Not glycosylated. FT {ECO:0000269|PubMed:3484703}. FT SITE 379 380 Cleavage; by kallikrein. FT SITE 389 390 Cleavage; by kallikrein. FT MOD_RES 19 19 Pyrrolidone carboxylic acid; in mature FT form. {ECO:0000250|UniProtKB:P01045}. FT MOD_RES 332 332 Phosphoserine; by FAM20C. FT {ECO:0000244|PubMed:19824718, FT ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:26091039}. FT MOD_RES 383 383 4-hydroxyproline; partial. FT {ECO:0000269|PubMed:3182782, FT ECO:0000269|PubMed:3366244}. FT CARBOHYD 48 48 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490}. FT CARBOHYD 169 169 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:3484703}. FT CARBOHYD 205 205 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:3484703}. FT CARBOHYD 294 294 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169}. FT CARBOHYD 401 401 O-linked (GalNAc...) threonine. FT CARBOHYD 533 533 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:4054110}. FT CARBOHYD 542 542 O-linked (GalNAc...) threonine. FT CARBOHYD 546 546 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:4054110}. FT CARBOHYD 557 557 O-linked (GalNAc...) threonine. FT CARBOHYD 571 571 O-linked (GalNAc...) threonine. FT CARBOHYD 577 577 O-linked (GalNAc...) serine. FT CARBOHYD 628 628 O-linked (GalNAc...) threonine. FT DISULFID 28 614 Interchain (between heavy and light FT chains). {ECO:0000255|PROSITE- FT ProRule:PRU00979, ECO:0000269|Ref.16}. FT DISULFID 83 94 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT DISULFID 107 126 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT DISULFID 142 145 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT DISULFID 206 218 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT DISULFID 229 248 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT DISULFID 264 267 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT DISULFID 328 340 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT DISULFID 351 370 {ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.16}. FT VAR_SEQ 189 224 Missing (in isoform 3). {ECO:0000305}. FT /FTId=VSP_047307. FT VAR_SEQ 402 643 VSPPHTSMAPAQDEERDSGKEQGHTRRHDWGHEKQRKHNLG FT HGHKHERDQGHGHQRGHGLGHGHEQQHGLGHGHKFKLDDDL FT EHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGWKTEHL FT ASSSEDSTTPSAQTQEKTEGPTPIPSLAKPGVTVTFSDFQD FT SDLIATMMPPISPAPIQSDDDWIPDIQIDPNGLSFNPISDF FT PDTTSPKCPGRPWKSVSEINPTTQMKESYYFDLTDGL -> FT SHLRSCEYKGRPPKAGAEPASEREV (in isoform 3). FT {ECO:0000305}. FT /FTId=VSP_047308. FT VAR_SEQ 402 427 VSPPHTSMAPAQDEERDSGKEQGHTR -> SHLRSCEYKGR FT PPKAGAEPASEREVS (in isoform LMW). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:6441591, FT ECO:0000303|Ref.4}. FT /FTId=VSP_001261. FT VAR_SEQ 428 644 Missing (in isoform LMW). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:6441591, FT ECO:0000303|Ref.4}. FT /FTId=VSP_001262. FT VARIANT 163 163 G -> S (in dbSNP:rs5030015). FT {ECO:0000269|Ref.5}. FT /FTId=VAR_019277. FT VARIANT 178 178 M -> T (in dbSNP:rs1656922). FT {ECO:0000269|Ref.4, ECO:0000269|Ref.5, FT ECO:0000269|Ref.7}. FT /FTId=VAR_019278. FT VARIANT 197 197 I -> M (in dbSNP:rs2304456). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_028937. FT VARIANT 212 212 L -> P (in dbSNP:rs5030024). FT {ECO:0000269|Ref.5}. FT /FTId=VAR_019279. FT VARIANT 378 380 Missing (in T-kinin peptide). FT {ECO:0000269|PubMed:2076202, FT ECO:0000269|PubMed:3828072}. FT /FTId=VAR_055233. FT VARIANT 430 430 D -> E (in dbSNP:rs5030084). FT /FTId=VAR_048853. FT VARIANT 581 581 I -> T (in dbSNP:rs710446). FT /FTId=VAR_048854. FT VARIANT 642 642 G -> A (in dbSNP:rs5030087). FT /FTId=VAR_048855. FT CONFLICT 33 33 L -> F (in Ref. 3; BAF83528). FT {ECO:0000305}. FT CONFLICT 311 311 V -> A (in Ref. 3; BAF83528). FT {ECO:0000305}. FT CONFLICT 593 593 I -> T (in Ref. 5; AAO61092 and 12; AA FT sequence). {ECO:0000305}. FT TURN 383 385 {ECO:0000244|PDB:6F3V}. SQ SEQUENCE 644 AA; 71957 MW; 3132B4DF2954C24E CRC64; MKLITILFLC SRLLLSLTQE SQSEEIDCND KDLFKAVDAA LKKYNSQNQS NNQFVLYRIT EATKTVGSDT FYSFKYEIKE GDCPVQSGKT WQDCEYKDAA KAATGECTAT VGKRSSTKFS VATQTCQITP AEGPVVTAQY DCLGCVHPIS TQSPDLEPIL RHGIQYFNNN TQHSSLFMLN EVKRAQRQVV AGLNFRITYS IVQTNCSKEN FLFLTPDCKS LWNGDTGECT DNAYIDIQLR IASFSQNCDI YPGKDFVQPP TKICVGCPRD IPTNSPELEE TLTHTITKLN AENNATFYFK IDNVKKARVQ VVAGKKYFID FVARETTCSK ESNEELTESC ETKKLGQSLD CNAEVYVVPW EKKIYPTVNC QPLGMISLMK RPPGFSPFRS SRIGEIKEET TVSPPHTSMA PAQDEERDSG KEQGHTRRHD WGHEKQRKHN LGHGHKHERD QGHGHQRGHG LGHGHEQQHG LGHGHKFKLD DDLEHQGGHV LDHGHKHKHG HGHGKHKNKG KKNGKHNGWK TEHLASSSED STTPSAQTQE KTEGPTPIPS LAKPGVTVTF SDFQDSDLIA TMMPPISPAP IQSDDDWIPD IQIDPNGLSF NPISDFPDTT SPKCPGRPWK SVSEINPTTQ MKESYYFDLT DGLS //