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 24-JAN-2024, entry version 244. 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 {ECO:0000303|PubMed:3366244}; 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 its RT 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; DOI=10.1016/s0021-9258(17)39515-7; RA Takagaki Y., Kitamura N., Nakanishi S.; RT "Cloning and sequence analysis of cDNAs for human high molecular weight and RT low molecular weight prekininogens. Primary structures of two human RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 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., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., 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., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 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 project: RT 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 LACK RP 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 evidence RT 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 DEL. RC TISSUE=Ascites; RX PubMed=3828072; DOI=10.1515/bchm3.1986.367.2.1231; 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; DOI=10.1515/bchm3.1990.371.2.977; 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 human RT 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., Mueller-Esterl W.; RT "The amino acid sequence of the light chain of human high-molecular-mass RT kininogen."; RL Eur. J. Biochem. 152:307-314(1985). RN [13] RP PROTEIN SEQUENCE OF 380-389 (BRADYKININ), 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 bradykinin in RT 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., Nabet P., RA Belleville F.; RT "Purification from human plasma of a tetrapeptide that potentiates insulin- RT like growth factor-I activity in chick embryo cartilage."; RL FEBS Lett. 373:207-211(1995). RN [16] RP FUNCTION (BRADYKININ), AND DEGRADATION (BRADYKININ). RX PubMed=6055465; DOI=10.1038/2151402a0; RA Yang H.Y., Erdoes E.G.; RT "Second kininase in human blood plasma."; RL Nature 215:1402-1403(1967). RN [17] RP FUNCTION (BRADYKININ), AND DEGRADATION (BRADYKININ). RX PubMed=4322742; DOI=10.1016/0005-2795(70)90017-6; RA Yang H.Y., Erdoes E.G., Levin Y.; RT "A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates RT bradykinin."; RL Biochim. Biophys. Acta 214:374-376(1970). RN [18] 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 [19] RP GENE STRUCTURE. RX PubMed=2989294; DOI=10.1016/s0021-9258(17)39516-9; 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 its RT evolution."; RL J. Biol. Chem. 260:8610-8617(1985). RN [20] RP AMINO-ACID COMPOSITION OF 381-389, AND HYDROXYLATION AT PRO-383. RX PubMed=3182782; DOI=10.1016/s0021-9258(18)37555-0; RA Maeda H., Matsumura Y., Kato H.; RT "Purification and identification of [hydroxyprolyl3]bradykinin in ascitic RT fluid from a patient with gastric cancer."; RL J. Biol. Chem. 263:16051-16054(1988). RN [21] RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION). RX PubMed=8760820; DOI=10.1084/jem.184.2.665; RA Herwald H., Collin M., Mueller-Esterl W., Bjoerck L.; RT "Streptococcal cysteine proteinase releases kinins: a virulence RT mechanism."; RL J. Exp. Med. 184:665-673(1996). RN [22] 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 [23] 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 [24] 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., Moore R.J., RA 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 [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION BY RP 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., Liotta L.A., RA Petricoin E.F. III; RT "An initial characterization of the serum phosphoproteome."; RL J. Proteome Res. 8:5523-5531(2009). RN [26] 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 multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [27] 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., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [28] 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., Brinkmalm G., RA Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION BY RP 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., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [30] 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 phosphoproteome."; RL Cell 161:1619-1632(2015). RN [31] RP VARIANT HAE6 LYS-379, AND INVOLVEMENT IN HAE6. RX PubMed=31087670; DOI=10.1111/all.13869; RA Bork K., Wulff K., Rossmann H., Steinmueller-Magin L., Braenne I., RA Witzke G., Hardt J.; RT "Hereditary angioedema cosegregating with a novel kininogen 1 gene mutation RT changing the N-terminal cleavage site of bradykinin."; RL Allergy 74:2479-2481(2019). RN [32] RP VARIANT HAE6 ALA-574, AND INVOLVEMENT IN HAE6. RX PubMed=33114181; DOI=10.3390/jcm9113402; RA Loules G., Parsopoulou F., Zamanakou M., Csuka D., Bova M., RA Gonzalez-Quevedo T., Psarros F., Porebski G., Speletas M., Firinu D., RA Del Giacco S., Suffritti C., Makris M., Vatsiou S., Zanichelli A., RA Farkas H., Germenis A.E.; RT "Deciphering the genetics of primary angioedema with normal levels of C1 RT inhibitor."; RL J. Clin. Med. 9:0-0(2020). 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:0000305|PubMed:4322742, ECO:0000305|PubMed:6055465}. CC -!- INTERACTION: CC P01042; Q07021: C1QBP; NbExp=4; IntAct=EBI-6378713, EBI-347528; CC P01042; Q10714: Ance; Xeno; NbExp=2; IntAct=EBI-6378713, EBI-115736; CC PRO_0000006687; P46663: BDKRB1; NbExp=2; IntAct=EBI-6623250, EBI-6623218; CC PRO_0000006688; Q9BYF1: ACE2; NbExp=5; IntAct=EBI-6623273, EBI-7730807; CC PRO_0000006688; P30411: BDKRB2; NbExp=2; IntAct=EBI-6623273, EBI-6623386; 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 -!- 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]: Bradykinin is inactivated by ACE, which removes the CC dipeptide Arg-Phe from its C-terminus. {ECO:0000269|PubMed:4322742, CC ECO:0000269|PubMed:6055465}. CC -!- PTM: Bradykinin is released from kininogen by plasma kallikrein. CC {ECO:0000305|PubMed:3366244}. CC -!- PTM: Hydroxylation of Pro-383 occurs prior to the release of CC bradykinin. {ECO:0000269|PubMed:3182782, 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 core CC 8 glycans. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, CC ECO:0000269|PubMed:3484703}. CC -!- PTM: (Microbial infection) Bradykinin is generated upon proteolytic CC cleavage by S.pyogenes SpeB to produce hypotension during septic shock. CC {ECO:0000269|PubMed:8760820}. CC -!- POLYMORPHISM: The T-kinin peptide is missing residues 378 to 380, CC probably as a result of a naturally occurring variant. The complete CC sequence of the T-kinin peptide is therefore ISRPPGFSPFR. This peptide CC is associated with malignant tumors but not with benign ones. CC {ECO:0000269|PubMed:3828072}. CC -!- DISEASE: High molecular weight kininogen deficiency (HMWK deficiency) CC [MIM:228960]: Autosomal recessive coagulation defect. Patients with CC HWMK deficiency do not have a hemorrhagic tendency, but they exhibit CC abnormal surface-mediated activation of fibrinolysis. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Angioedema, hereditary, 6 (HAE6) [MIM:619363]: A form of CC angioedema, a disorder characterized by episodic local swelling CC involving subcutaneous or submucous tissue of the upper respiratory and CC gastrointestinal tracts, face, extremities, and genitalia. HAE6 is an CC autosomal dominant form with onset in adulthood. CC {ECO:0000269|PubMed:31087670, ECO:0000269|PubMed:33114181}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 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 PDB; 7EIB; EM; 3.00 A; D=380-388. DR PDB; 7F2O; EM; 2.90 A; D=381-389. DR PDB; 7F6H; EM; 2.90 A; L=381-389. DR PDB; 7F6I; EM; 2.80 A; L=380-389. DR PDB; 7QOT; X-ray; 3.24 A; C/D=583-613. DR PDB; 7QOX; X-ray; 2.32 A; C/D=582-609. 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 PDBsum; 7EIB; -. DR PDBsum; 7F2O; -. DR PDBsum; 7F6H; -. DR PDBsum; 7F6I; -. DR PDBsum; 7QOT; -. DR PDBsum; 7QOX; -. DR AlphaFoldDB; P01042; -. DR BMRB; P01042; -. DR EMDB; EMD-15972; -. DR EMDB; EMD-31480; -. DR EMDB; EMD-31481; -. DR SMR; P01042; -. DR BioGRID; 110026; 50. DR IntAct; P01042; 32. DR MINT; P01042; -. DR STRING; 9606.ENSP00000493985; -. DR BindingDB; P01042; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR MEROPS; I25.016; -. DR MEROPS; I25.017; -. DR MEROPS; I25.950; -. DR CarbonylDB; P01042; -. DR GlyConnect; 810; 60 N-Linked glycans (5 sites), 1 O-Linked glycan (1 site). DR GlyCosmos; P01042; 26 sites, 88 glycans. DR GlyGen; P01042; 28 sites, 86 N-linked glycans (5 sites), 14 O-linked glycans (20 sites). DR iPTMnet; P01042; -. DR PhosphoSitePlus; P01042; -. DR BioMuta; KNG1; -. DR DMDM; 124056474; -. DR CPTAC; CPTAC-687; -. DR CPTAC; non-CPTAC-1138; -. DR EPD; P01042; -. DR jPOST; P01042; -. DR MassIVE; P01042; -. DR PaxDb; 9606-ENSP00000265023; -. DR PeptideAtlas; P01042; -. DR ProteomicsDB; 51315; -. [P01042-1] DR ProteomicsDB; 51316; -. [P01042-2] DR ProteomicsDB; 9908; -. DR Antibodypedia; 888; 920 antibodies from 43 providers. DR DNASU; 3827; -. DR Ensembl; ENST00000287611.8; ENSP00000287611.2; ENSG00000113889.14. [P01042-2] DR Ensembl; ENST00000447445.1; ENSP00000396025.1; ENSG00000113889.14. [P01042-3] DR Ensembl; ENST00000644859.2; ENSP00000493985.1; ENSG00000113889.14. [P01042-1] DR GeneID; 3827; -. DR KEGG; hsa:3827; -. DR MANE-Select; ENST00000644859.2; ENSP00000493985.1; NM_001102416.3; NP_001095886.1. DR UCSC; uc003fqr.4; human. [P01042-1] DR AGR; HGNC:6383; -. DR CTD; 3827; -. DR DisGeNET; 3827; -. DR GeneCards; KNG1; -. DR HGNC; HGNC:6383; KNG1. DR HPA; ENSG00000113889; Tissue enriched (liver). DR MalaCards; KNG1; -. DR MIM; 228960; phenotype. DR MIM; 612358; gene. DR MIM; 619363; phenotype. DR neXtProt; NX_P01042; -. DR OpenTargets; ENSG00000113889; -. DR Orphanet; 483; Congenital high-molecular-weight kininogen deficiency. DR Orphanet; 599418; Hereditary angioedema with normal C1Inh not related to F12 or PLG variant. DR PharmGKB; PA225; -. DR VEuPathDB; HostDB:ENSG00000113889; -. DR eggNOG; ENOG502RYAC; Eukaryota. DR GeneTree; ENSGT00950000182930; -. DR HOGENOM; CLU_029531_0_0_1; -. DR InParanoid; P01042; -. DR OMA; DQGHGHQ; -. DR OrthoDB; 5223498at2759; -. DR PhylomeDB; P01042; -. DR TreeFam; TF351852; -. DR PathwayCommons; P01042; -. 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 SignaLink; P01042; -. DR SIGNOR; P01042; -. DR BioGRID-ORCS; 3827; 11 hits in 1150 CRISPR screens. DR ChiTaRS; KNG1; human. DR EvolutionaryTrace; P01042; -. DR GeneWiki; Kininogen_1; -. DR GenomeRNAi; 3827; -. DR Pharos; P01042; Tbio. DR PRO; PR:P01042; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P01042; Protein. DR Bgee; ENSG00000113889; Expressed in renal medulla and 95 other cell types or tissues. 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:0005179; F:hormone activity; IDA:UniProt. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB. 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; IDA:UniProtKB. DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB. 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:0042311; P:vasodilation; IDA:UniProt. DR CDD; cd00042; CY; 3. DR DisProt; DP01861; -. DR Gene3D; 3.10.450.10; -; 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 PANTHER; PTHR13814; FETUIN; 1. DR PANTHER; PTHR13814:SF12; KININOGEN-1; 1. DR Pfam; PF00031; Cystatin; 3. DR PRINTS; PR00334; KININOGEN. DR SMART; SM00043; CY; 3. DR SUPFAM; SSF54403; Cystatin/monellin; 3. DR PROSITE; PS00287; CYSTATIN; 2. DR PROSITE; PS51647; CYSTATIN_KININOGEN; 3. DR SWISS-2DPAGE; P01042; -. DR Genevisible; P01042; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Blood coagulation; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Hemostasis; Hydroxylation; Inflammatory response; Phosphoprotein; KW Protease inhibitor; Pyrrolidone carboxylic acid; Reference proteome; KW Repeat; Secreted; Signal; Thiol protease inhibitor; Vasoactive; KW Vasodilator. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:2989293, FT ECO:0000269|PubMed:3484703" FT CHAIN 19..644 FT /note="Kininogen-1" FT /id="PRO_0000006685" FT CHAIN 19..380 FT /note="Kininogen-1 heavy chain" FT /id="PRO_0000006686" FT PEPTIDE 376..389 FT /note="T-kinin" FT /id="PRO_0000372485" FT PEPTIDE 380..389 FT /note="Lysyl-bradykinin" FT /id="PRO_0000006687" FT PEPTIDE 381..389 FT /note="Bradykinin" FT /evidence="ECO:0000269|PubMed:3182782, FT ECO:0000269|PubMed:4952632" FT /id="PRO_0000006688" FT CHAIN 390..644 FT /note="Kininogen-1 light chain" FT /id="PRO_0000006689" FT PEPTIDE 431..434 FT /note="Low molecular weight growth-promoting factor" FT /id="PRO_0000006690" 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 REPEAT 420..449 FT REPEAT 450..479 FT REPEAT 480..510 FT REGION 120..153 FT /note="O-glycosylated at one site only" FT REGION 387..555 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 411..430 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 445..491 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 492..514 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 524..545 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 48 FT /note="Not glycosylated" FT /evidence="ECO:0000269|PubMed:3484703" FT SITE 379..380 FT /note="Cleavage; by kallikrein" FT /evidence="ECO:0000303|PubMed:3366244" FT SITE 387..388 FT /note="Cleavage; by ACE" FT /evidence="ECO:0000269|PubMed:4322742, FT ECO:0000269|PubMed:6055465" FT SITE 389..390 FT /note="Cleavage; by kallikrein" FT /evidence="ECO:0000303|PubMed:3366244" FT MOD_RES 19 FT /note="Pyrrolidone carboxylic acid; in mature form" FT /evidence="ECO:0000250|UniProtKB:P01045" FT MOD_RES 332 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039, FT ECO:0007744|PubMed:19824718, ECO:0007744|PubMed:24275569" FT MOD_RES 383 FT /note="4-hydroxyproline; partial" FT /evidence="ECO:0000269|PubMed:3182782, FT ECO:0000269|PubMed:3366244" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490" FT CARBOHYD 169 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:3484703" FT CARBOHYD 205 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:3484703" FT CARBOHYD 294 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169" FT CARBOHYD 401 FT /note="O-linked (GalNAc...) threonine" FT CARBOHYD 533 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:4054110" FT CARBOHYD 542 FT /note="O-linked (GalNAc...) threonine" FT CARBOHYD 546 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:4054110" FT CARBOHYD 557 FT /note="O-linked (GalNAc...) threonine" FT CARBOHYD 571 FT /note="O-linked (GalNAc...) threonine" FT CARBOHYD 577 FT /note="O-linked (GalNAc...) serine" FT CARBOHYD 628 FT /note="O-linked (GalNAc...) threonine" FT DISULFID 28..614 FT /note="Interchain (between heavy and light chains)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 83..94 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 107..126 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 142..145 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 206..218 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 229..248 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 264..267 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 328..340 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT DISULFID 351..370 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00979, FT ECO:0000269|Ref.18" FT VAR_SEQ 189..224 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_047307" FT VAR_SEQ 402..643 FT /note="VSPPHTSMAPAQDEERDSGKEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGH FT GHQRGHGLGHGHEQQHGLGHGHKFKLDDDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKK FT NGKHNGWKTEHLASSSEDSTTPSAQTQEKTEGPTPIPSLAKPGVTVTFSDFQDSDLIAT FT MMPPISPAPIQSDDDWIPDIQIDPNGLSFNPISDFPDTTSPKCPGRPWKSVSEINPTTQ FT MKESYYFDLTDGL -> SHLRSCEYKGRPPKAGAEPASEREV (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_047308" FT VAR_SEQ 402..427 FT /note="VSPPHTSMAPAQDEERDSGKEQGHTR -> SHLRSCEYKGRPPKAGAEPASE FT REVS (in isoform LMW)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:6441591, FT ECO:0000303|Ref.4" FT /id="VSP_001261" FT VAR_SEQ 428..644 FT /note="Missing (in isoform LMW)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:6441591, FT ECO:0000303|Ref.4" FT /id="VSP_001262" FT VARIANT 163 FT /note="G -> S (in dbSNP:rs5030015)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_019277" FT VARIANT 178 FT /note="M -> T (in dbSNP:rs1656922)" FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.5, FT ECO:0000269|Ref.7" FT /id="VAR_019278" FT VARIANT 197 FT /note="I -> M (in dbSNP:rs2304456)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_028937" FT VARIANT 212 FT /note="L -> P (in dbSNP:rs5030024)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_019279" FT VARIANT 378..380 FT /note="Missing (in T-kinin peptide)" FT /evidence="ECO:0000269|PubMed:2076202, FT ECO:0000269|PubMed:3828072" FT /id="VAR_055233" FT VARIANT 379 FT /note="M -> K (in HAE6)" FT /evidence="ECO:0000269|PubMed:31087670" FT /id="VAR_085817" FT VARIANT 430 FT /note="D -> E (in dbSNP:rs5030084)" FT /id="VAR_048853" FT VARIANT 574 FT /note="P -> A (in HAE6; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33114181" FT /id="VAR_085818" FT VARIANT 581 FT /note="I -> T (in dbSNP:rs710446)" FT /id="VAR_048854" FT VARIANT 642 FT /note="G -> A (in dbSNP:rs5030087)" FT /id="VAR_048855" FT CONFLICT 33 FT /note="L -> F (in Ref. 3; BAF83528)" FT /evidence="ECO:0000305" FT CONFLICT 311 FT /note="V -> A (in Ref. 3; BAF83528)" FT /evidence="ECO:0000305" FT CONFLICT 593 FT /note="I -> T (in Ref. 5; AAO61092 and 12; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 385..387 FT /evidence="ECO:0007829|PDB:7F6I" 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 //