ID IC1_HUMAN Reviewed; 500 AA. AC P05155; A6NMU0; A8KAI9; B2R6L5; B4E1F0; B4E1H2; Q16304; Q547W3; Q59EI5; AC Q7Z455; Q96FE0; Q9UC49; Q9UCF9; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 2. DT 27-MAR-2024, entry version 254. DE RecName: Full=Plasma protease C1 inhibitor; DE Short=C1 Inh; DE Short=C1Inh; DE AltName: Full=C1 esterase inhibitor; DE AltName: Full=C1-inhibiting factor; DE AltName: Full=Serpin G1; DE Flags: Precursor; GN Name=SERPING1; Synonyms=C1IN, C1NH; 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 1). RX PubMed=3488058; DOI=10.1016/0006-291x(86)91123-x; RA Que B.G., Petra P.H.; RT "Isolation and analysis of a cDNA coding for human C1 inhibitor."; RL Biochem. Biophys. Res. Commun. 137:620-625(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND RP GLYCOSYLATION AT ASN-25; THR-48; SER-64; ASN-69; THR-71; ASN-81; THR-83; RP THR-88; THR-92; THR-96; ASN-238; ASN-253 AND ASN-352. RX PubMed=3756141; DOI=10.1021/bi00363a018; RA Bock S.C., Skriver K., Nielsen E., Thoegersen H.-C., Wiman B., RA Donaldson V.H., Eddy R.L., Marrinan J., Radziejewska E., Huber R., RA Shows T.B., Magnusson S.; RT "Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal RT localization."; RL Biochemistry 25:4292-4301(1986). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX PubMed=3267220; DOI=10.1111/j.1432-1033.1988.tb13980.x; RA Carter P.E., Dunbar B., Fothergill J.E.; RT "Genomic and cDNA cloning of the human C1 inhibitor. Intron-exon junctions RT and comparison with other serpins."; RL Eur. J. Biochem. 173:163-169(1988). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2026152; DOI=10.1111/j.1432-1033.1991.tb15911.x; RA Carter P.E., Duponchel C., Tosi M., Fothergill J.E.; RT "Complete nucleotide sequence of the gene for human C1 inhibitor with an RT unusually high density of Alu elements."; RL Eur. J. Biochem. 197:301-308(1991). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Foreskin; RA Heus J., Platenburg-Kootwijk E., Meershoek E., De Winter R., RA Knijnenburg J., Kupers L., Habex H., Renaers I., Samuel C., Bonnarens L., RA Hoffman S., Brouwer M., Hack E., Horbach D., Timmermans M., Nuijens J., RA Pieper F.; RT "Production of recombinant human C1 inhibitor in milk of transgenic rabbits RT for potential use in enzyme replacement therapy for hereditary RT angioedema."; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Heart, Liver, Ovary, and Uterus; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-480. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-480. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-480. RG SeattleSNPs variation discovery resource; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-480. RC TISSUE=Brain; 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 [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-500 (ISOFORM 1). RX PubMed=3393514; RA Rauth G., Schumacher G., Buckel P., Mueller-Esterl W.; RT "Molecular cloning of the cDNA coding for human C1 inhibitor."; RL Protein Seq. Data Anal. 1:251-257(1988). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 18-188, AND VARIANT HAE1 RP 84-ASP--THR-138 DEL. RC TISSUE=Blood; RX PubMed=12773530; DOI=10.1074/jbc.m302977200; RA Bos I.G.A., Lubbers Y.T.P., Roem D., Abrahams J.P., Hack C.E., Eldering E.; RT "The functional integrity of the serpin domain of C1-inhibitor depends on RT the unique N-terminal domain, as revealed by a pathological mutant."; RL J. Biol. Chem. 278:29463-29470(2003). RN [15] RP PROTEIN SEQUENCE OF 23-62. RX PubMed=6416294; DOI=10.1021/bi00290a019; RA Harrison R.A.; RT "Human C1 inhibitor: improved isolation and preliminary structural RT characterization."; RL Biochemistry 22:5001-5007(1983). RN [16] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-228. RX PubMed=2154751; DOI=10.1073/pnas.87.4.1551; RA Stoppa-Lyonnet D., Carter P.E., Meo T., Tosi M.; RT "Clusters of intragenic Alu repeats predispose the human C1 inhibitor locus RT to deleterious rearrangements."; RL Proc. Natl. Acad. Sci. U.S.A. 87:1551-1555(1990). RN [17] RP NUCLEOTIDE SEQUENCE [MRNA] OF 213-500 (ISOFORM 1/2/3). RX PubMed=3089875; DOI=10.1016/0378-1119(86)90230-1; RA Tosi M., Duponchel C., Bourgarel P., Colomb M., Meo T.; RT "Molecular cloning of human C1 inhibitor: sequence homologies with alpha 1- RT antitrypsin and other members of the serpins superfamily."; RL Gene 42:265-272(1986). RN [18] RP PROTEIN SEQUENCE OF 217-233. RX PubMed=8618290; DOI=10.1097/00005392-199606000-00030; RA Pillai S., Wright D., Gupta A., Zhou G., Hull G., Jiang H., Zhang H.; RT "Molecular weights and isoelectric points of sperm antigens relevant to RT autoimmune infertility in men."; RL J. Urol. 155:1928-1933(1996). RN [19] RP NUCLEOTIDE SEQUENCE [MRNA] OF 241-458 (ISOFORM 1/2/3), AND PARTIAL PROTEIN RP SEQUENCE. RX PubMed=3458172; DOI=10.1073/pnas.83.10.3161; RA Davis A.E. III, Whitehead A.S., Harrison R.A., Dauphinias A., Bruns G.A., RA Cicardi M., Rosen F.S.; RT "Human inhibitor of the first component of complement, C1: characterization RT of cDNA clones and localization of the gene to chromosome 11."; RL Proc. Natl. Acad. Sci. U.S.A. 83:3161-3165(1986). RN [20] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 418-500, AND VARIANTS HAE1 MET-473; RP ARG-481; PRO-481; ARG-489 AND SER-498. RX PubMed=7814636; DOI=10.1172/jci117663; RA Verpy E., Couture-Tosi E., Eldering E., Lopez-Trascasa M., Spath P., RA Meo T., Tosi M.; RT "Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by RT pathogenic mutants impaired in secretion or function."; RL J. Clin. Invest. 95:350-359(1995). RN [21] RP PROTEIN SEQUENCE OF 464-481, FUNCTION, AND REACTIVE SITE FOR CHYMOTRYPSIN. RC TISSUE=Plasma; RX PubMed=8495195; DOI=10.1002/pro.5560020504; RA Aulak K.S., Davis A.E. III, Donaldson V.H., Harrison R.A.; RT "Chymotrypsin inhibitory activity of normal C1-inhibitor and a P1 Arg to RT His mutant: evidence for the presence of overlapping reactive centers."; RL Protein Sci. 2:727-732(1993). RN [22] RP INTERACTION WITH MASP1. RX PubMed=10946292; DOI=10.4049/jimmunol.165.5.2637; RA Matsushita M., Thiel S., Jensenius J.C., Terai I., Fujita T.; RT "Proteolytic activities of two types of mannose-binding lectin-associated RT serine protease."; RL J. Immunol. 165:2637-2642(2000). RN [23] RP INTERACTION WITH E.COLI STCE, AND PROTEOLYTIC PROCESSING BY E.COLI STCE. RX PubMed=12123444; DOI=10.1046/j.1365-2958.2002.02997.x; RA Lathem W.W., Grys T.E., Witowski S.E., Torres A.G., Kaper J.B., Tarr P.I., RA Welch R.A.; RT "StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically RT cleaves C1 esterase inhibitor."; RL Mol. Microbiol. 45:277-288(2002). RN [24] RP GLYCOSYLATION AT ASN-253. 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 [25] RP INTERACTION WITH E.COLI STCE, AND PROTEOLYTIC PROCESSING BY E.COLI STCE. RX PubMed=15096536; DOI=10.1084/jem.20030255; RA Lathem W.W., Bergsbaken T., Welch R.A.; RT "Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted RT by Escherichia coli O157:H7."; RL J. Exp. Med. 199:1077-1087(2004). RN [26] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-25; ASN-238; ASN-253 AND RP ASN-352. 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 [27] RP GLYCOSYLATION AT ASN-25. RX PubMed=16040958; DOI=10.1128/iai.73.8.4478-4487.2005; RA Liu D., Cramer C.C., Scafidi J., Davis A.E. III; RT "N-linked glycosylation at Asn3 and the positively charged residues within RT the amino-terminal domain of the c1 inhibitor are required for interaction RT of the C1 Inhibitor with Salmonella enterica serovar typhimurium RT lipopolysaccharide and lipid A."; RL Infect. Immun. 73:4478-4487(2005). RN [28] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-25; ASN-69; ASN-238; ASN-253 RP AND ASN-352. 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 [29] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-69; ASN-81; ASN-238; ASN-253 RP AND ASN-352. 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 [30] RP GLYCOSYLATION AT ASN-238; ASN-253 AND ASN-352. 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 [31] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-352, 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 [32] RP GLYCOSYLATION AT ASN-25; THR-47 AND THR-48, STRUCTURE OF CARBOHYDRATES, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=22171320; DOI=10.1074/mcp.m111.013649; RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.; RT "Human urinary glycoproteomics; attachment site specific analysis of N- and RT O-linked glycosylations by CID and ECD."; RL Mol. Cell. Proteomics 11:1-17(2012). RN [33] RP GLYCOSYLATION AT THR-47 AND THR-48, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=23234360; DOI=10.1021/pr300963h; RA Halim A., Ruetschi U., Larson G., Nilsson J.; RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures RT of human cerebrospinal fluid glycoproteins."; RL J. Proteome Res. 12:573-584(2013). RN [34] RP IDENTIFICATION 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., 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 [35] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 119-500, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-238. RX PubMed=17488724; DOI=10.1074/jbc.m700841200; RA Beinrohr L., Harmat V., Dobo J., Loerincz Z., Gal P., Zavodszky P.; RT "C1 inhibitor serpin domain structure reveals the likely mechanism of RT heparin potentiation and conformational disease."; RL J. Biol. Chem. 282:21100-21109(2007). RN [36] RP REVIEW ON VARIANTS. RX PubMed=7749926; DOI=10.1038/nsb0295-96; RA Stein P.E., Carrell R.W.; RT "What do dysfunctional serpins tell us about molecular mobility and RT disease?"; RL Nat. Struct. Biol. 2:96-113(1995). RN [37] RP VARIANT HAE1 HIS-466. RX PubMed=3178731; DOI=10.1042/bj2530615; RA Aulak K.S., Pemberton P.A., Rosen F.S., Carrell R.W., Lachmann P.J., RA Harrison R.A.; RT "Dysfunctional C1-inhibitor(At), isolated from a type II hereditary-angio- RT oedema plasma, contains a P1 'reactive centre' (Arg444-->His) mutation."; RL Biochem. J. 253:615-618(1988). RN [38] RP VARIANT HAE1 SER-466. RX PubMed=2365061; DOI=10.1016/0014-5793(90)81494-9; RA Aulak K.S., Cicardi M., Harrison R.A.; RT "Identification of a new P1 residue mutation (444Arg-->Ser) in a RT dysfunctional C1 inhibitor protein contained in a type II hereditary RT angioedema plasma."; RL FEBS Lett. 266:13-16(1990). RN [39] RP VARIANT HAE1 THR-458. RX PubMed=2296585; DOI=10.1073/pnas.87.1.265; RA Levy N.J., Ramesh N., Cicardi M., Harrison R.A., Davis A.E. III; RT "Type II hereditary angioneurotic edema that may result from a single RT nucleotide change in the codon for alanine-436 in the C1 inhibitor gene."; RL Proc. Natl. Acad. Sci. U.S.A. 87:265-268(1990). RN [40] RP VARIANT HAE1 LYS-273 DEL. RX PubMed=2118657; DOI=10.1073/pnas.87.17.6786; RA Parad R.B., Kramer J., Strunk R.C., Rosen F.S., Davis A.E. III; RT "Dysfunctional C1 inhibitor Ta: deletion of Lys-251 results in acquisition RT of an N-glycosylation site."; RL Proc. Natl. Acad. Sci. U.S.A. 87:6786-6790(1990). RN [41] RP VARIANTS HAE1 GLU-456 AND VAL-458. RA Siddique Z.M., McPhaden A.R., Whaley K.; RT "Identification of type II hereditary angio-oedema (HAE) mutations."; RL Clin. Exp. Immunol. 86:11-12(1991). RN [42] RP VARIANT HAE1 LEU-466. RX PubMed=1451784; DOI=10.1016/0014-5793(92)80204-t; RA Frange D., Aulak K.S., Cicardi M., Harrison R.A., Davis A.E. III; RT "A dysfunctional C1 inhibitor protein with a new reactive center mutation RT (Arg-444-->Leu)."; RL FEBS Lett. 301:34-36(1992). RN [43] RP VARIANTS HAE1 GLU-454 AND THR-458. RX PubMed=1363816; DOI=10.1038/ng0892-354; RA Davis A.E. III, Aulak K., Parad R.B., Stecklein H.P., Eldering E., RA Hack C.E., Kramer J., Strunk R.C., Bissler J., Rosen F.S.; RT "C1 inhibitor hinge region mutations produce dysfunction by different RT mechanisms."; RL Nat. Genet. 1:354-358(1992). RN [44] RP VARIANT HAE1 ARG-429. RX PubMed=8172583; RA Davis A.E. III, Bissler J.J., Cicardi M.; RT "Mutations in the C1 inhibitor gene that result in hereditary angioneurotic RT edema."; RL Behring Inst. Mitt. 93:313-320(1993). RN [45] RP VARIANT HAE1 VAL-465. RX PubMed=7883978; DOI=10.1172/jci117780; RA Zahedi R., Bissler J.J., Davis A.E. III, Andreadis C., Wisnieski J.J.; RT "Unique C1 inhibitor dysfunction in a kindred without angioedema. II. RT Identification of an Ala443-->Val substitution and functional analysis of RT the recombinant mutant protein."; RL J. Clin. Invest. 95:1299-1305(1995). RN [46] RP VARIANT HAE1 PRO-467. RX PubMed=8529136; DOI=10.1007/bf03401610; RA Ocejo-Vinyals J.G., Leyva-Cobian F., Fernandez-Luna J.L.; RT "A mutation unique in serine protease inhibitors (serpins) identified in a RT family with type II hereditary angioneurotic edema."; RL Mol. Med. 1:700-705(1995). RN [47] RP VARIANTS HAE1. RX PubMed=8755917; RA Verpy E., Biasotto M., Brai M., Misiano G., Meo T., Tosi M.; RT "Exhaustive mutation scanning by fluorescence-assisted mismatch analysis RT discloses new genotype-phenotype correlations in angiodema."; RL Am. J. Hum. Genet. 59:308-319(1996). RN [48] RP VARIANTS HAE1 TYR-130; PRO-394; VAL-408; CYS-466; GLU-473; GLU-493 AND RP ARG-498. RX PubMed=14635117; DOI=10.1002/humu.9202; RA Kalmar L., Bors A., Farkas H., Vas S., Fandl B., Varga L., Fuest G., RA Tordai A.; RT "Mutation screening of the C1 inhibitor gene among Hungarian patients with RT hereditary angioedema."; RL Hum. Mutat. 22:498-498(2003). RN [49] RP VARIANT HAE1 ARG-345, AND VARIANTS ALA-56 AND MET-480. RX PubMed=16409206; DOI=10.1111/j.1398-9995.2006.01010.x; RA Kang H.-R., Yim E.-Y., Oh S.-Y., Chang Y.-S., Kim Y.-K., Cho S.-H., RA Min K.-U., Kim Y.-Y.; RT "Normal C1 inhibitor mRNA expression level in type I hereditary angioedema RT patients: newly found C1 inhibitor gene mutations."; RL Allergy 61:260-264(2006). RN [50] RP VARIANTS HAE1 ALA-118; CYS-154; PHE-170; ARG-184; PRO-230; LYS-232; ASN-272 RP DEL; ARG-299; GLN-430; THR-441; PRO-447; SER-466; CYS-466; LEU-466; GLY-473 RP AND GLY-497, AND VARIANTS ALA-56 AND MET-480. RX PubMed=22994404; DOI=10.1111/all.12024; RA Xu Y.Y., Zhi Y.X., Yin J., Wang L.L., Wen L.P., Gu J.Q., Guan K., Craig T., RA Zhang H.Y.; RT "Mutational spectrum and geno-phenotype correlation in Chinese families RT with Hereditary Angioedema."; RL Allergy 67:1430-1436(2012). RN [51] RP VARIANTS HAE1 ARG-11; ARG-265; VAL-274; THR-458; CYS-466; HIS-466; ARG-493 RP AND GLU-493. RX PubMed=24456027; DOI=10.1111/ahg.12052; RA Bafunno V., Bova M., Loffredo S., Divella C., Petraroli A., Marone G., RA Montinaro V., Margaglione M., Triggiani M.; RT "Mutational spectrum of the c1 inhibitor gene in a cohort of Italian RT patients with hereditary angioedema: description of nine novel mutations."; RL Ann. Hum. Genet. 78:73-82(2014). CC -!- FUNCTION: Activation of the C1 complex is under control of the C1- CC inhibitor. It forms a proteolytically inactive stoichiometric complex CC with the C1r or C1s proteases. May play a potentially crucial role in CC regulating important physiological pathways including complement CC activation, blood coagulation, fibrinolysis and the generation of CC kinins. Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and CC kallikrein. {ECO:0000269|PubMed:8495195}. CC -!- SUBUNIT: Binds to E.coli stcE which allows localization of SERPING1 to CC cell membranes thus protecting the bacteria against complement-mediated CC lysis. Interacts with MASP1. {ECO:0000269|PubMed:10946292, CC ECO:0000269|PubMed:12123444, ECO:0000269|PubMed:15096536}. CC -!- INTERACTION: CC P05155; P00736: C1R; NbExp=2; IntAct=EBI-1223454, EBI-3926504; CC P05155; P09871: C1S; NbExp=5; IntAct=EBI-1223454, EBI-2810045; CC P05155; O43889-2: CREB3; NbExp=3; IntAct=EBI-1223454, EBI-625022; CC P05155; O00187: MASP2; NbExp=3; IntAct=EBI-1223454, EBI-7965040; CC P05155; A0A7D5SLD3: MSP-3; Xeno; NbExp=4; IntAct=EBI-1223454, EBI-27104100; CC P05155; PRO_0000037310 [P0C6X7]: rep; Xeno; NbExp=2; IntAct=EBI-1223454, EBI-25474098; CC P05155; PRO_0000037320 [P0C6X7]: rep; Xeno; NbExp=2; IntAct=EBI-1223454, EBI-25487328; CC P05155; O82882: stcE; Xeno; NbExp=3; IntAct=EBI-1223454, EBI-15979286; CC P05155; Q79GN7: vag8; Xeno; NbExp=3; IntAct=EBI-1223454, EBI-27104360; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P05155-1; Sequence=Displayed; CC Name=2; CC IsoId=P05155-2; Sequence=VSP_056662; CC Name=3; CC IsoId=P05155-3; Sequence=VSP_056663; CC -!- PTM: Highly glycosylated (49%) with N- and O-glycosylation. O- CC glycosylated with core 1 or possibly core 8 glycans. N-glycan CC heterogeneity at Asn-25: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (minor), CC Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor). CC {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, CC ECO:0000269|PubMed:16040958, ECO:0000269|PubMed:16335952, CC ECO:0000269|PubMed:17488724, ECO:0000269|PubMed:19139490, CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, CC ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:23234360, CC ECO:0000269|PubMed:3756141}. CC -!- PTM: Can be proteolytically cleaved by E.coli stcE. CC {ECO:0000269|PubMed:12123444, ECO:0000269|PubMed:15096536}. CC -!- POLYMORPHISM: Chymotrypsin uses Ala-465 as its reactive site in normal CC plasma protease C1 inhibitor, and His-466 as its reactive site in the CC variant His-466. CC -!- DISEASE: Angioedema, hereditary, 1 (HAE1) [MIM:106100]: An autosomal CC dominant disorder characterized by episodic local swelling involving CC subcutaneous or submucous tissue of the upper respiratory and CC gastrointestinal tracts, face, extremities, and genitalia. Hereditary CC angioedema due to C1 esterase inhibitor deficiency is comprised of two CC clinically indistinguishable forms. In hereditary angioedema type 1, CC serum levels of C1 esterase inhibitor are decreased, while in type 2, CC the levels are normal or elevated, but the protein is non-functional. CC {ECO:0000269|PubMed:12773530, ECO:0000269|PubMed:1363816, CC ECO:0000269|PubMed:1451784, ECO:0000269|PubMed:14635117, CC ECO:0000269|PubMed:16409206, ECO:0000269|PubMed:2118657, CC ECO:0000269|PubMed:2296585, ECO:0000269|PubMed:22994404, CC ECO:0000269|PubMed:2365061, ECO:0000269|PubMed:24456027, CC ECO:0000269|PubMed:3178731, ECO:0000269|PubMed:7814636, CC ECO:0000269|PubMed:7883978, ECO:0000269|PubMed:8172583, CC ECO:0000269|PubMed:8529136, ECO:0000269|PubMed:8755917, CC ECO:0000269|Ref.41}. Note=The disease is caused by variants affecting CC the gene represented in this entry. CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA53096.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=C1-inhibitor entry; CC URL="https://en.wikipedia.org/wiki/C1-inhibitor"; CC -!- WEB RESOURCE: Name=SERPING1base; Note=SERPING1 mutation db; CC URL="http://structure.bmc.lu.se/idbase/SERPING1base/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/serping1/"; 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; M13690; AAA35613.1; -; mRNA. DR EMBL; M13656; AAB59387.1; -; mRNA. DR EMBL; X07427; CAA30314.1; -; Genomic_DNA. DR EMBL; X07428; CAA30314.1; JOINED; Genomic_DNA. DR EMBL; X07429; CAA30314.1; JOINED; Genomic_DNA. DR EMBL; X07430; CAA30314.1; JOINED; Genomic_DNA. DR EMBL; X07431; CAA30314.1; JOINED; Genomic_DNA. DR EMBL; X07432; CAA30314.1; JOINED; Genomic_DNA. DR EMBL; X07433; CAA30314.1; JOINED; Genomic_DNA. DR EMBL; X07577; CAA30469.1; -; mRNA. DR EMBL; X54486; CAA38358.1; -; Genomic_DNA. DR EMBL; AF435921; AAM21515.1; -; Genomic_DNA. DR EMBL; AK293054; BAF85743.1; -; mRNA. DR EMBL; AK303809; BAG64762.1; -; mRNA. DR EMBL; AK303840; BAG64784.1; -; mRNA. DR EMBL; AK312626; BAG35512.1; -; mRNA. DR EMBL; BT006966; AAP35612.1; -; mRNA. DR EMBL; AB209826; BAD93063.1; -; mRNA. DR EMBL; AY904027; AAW69393.1; -; Genomic_DNA. DR EMBL; AP000662; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP002893; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW73764.1; -; Genomic_DNA. DR EMBL; BC011171; AAH11171.1; -; mRNA. DR EMBL; AY291075; AAQ19269.1; -; Genomic_DNA. DR EMBL; M30688; AAA53096.1; ALT_SEQ; Genomic_DNA. DR EMBL; M14036; AAA51848.1; -; mRNA. DR EMBL; M13203; AAA51849.1; -; mRNA. DR EMBL; S76944; AAB33044.2; -; Genomic_DNA. DR CCDS; CCDS7962.1; -. [P05155-1] DR PIR; S15386; ITHUC1. DR RefSeq; NP_000053.2; NM_000062.2. [P05155-1] DR RefSeq; NP_001027466.1; NM_001032295.1. [P05155-1] DR PDB; 2OAY; X-ray; 2.35 A; A=119-500. DR PDB; 5DU3; X-ray; 2.10 A; A/B=119-500. DR PDB; 5DUQ; X-ray; 2.90 A; A/B=118-500. DR PDB; 7AKV; EM; 3.60 A; A=98-500. DR PDBsum; 2OAY; -. DR PDBsum; 5DU3; -. DR PDBsum; 5DUQ; -. DR PDBsum; 7AKV; -. DR AlphaFoldDB; P05155; -. DR EMDB; EMD-11814; -. DR SMR; P05155; -. DR BioGRID; 107171; 51. DR DIP; DIP-45635N; -. DR IntAct; P05155; 24. DR MINT; P05155; -. DR STRING; 9606.ENSP00000278407; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB05961; PPL-100. DR MEROPS; I04.024; -. DR GlyConnect; 749; 41 N-Linked glycans (5 sites), 7 O-Linked glycans (3 sites). DR GlyCosmos; P05155; 24 sites, 60 glycans. DR GlyGen; P05155; 26 sites, 58 N-linked glycans (5 sites), 9 O-linked glycans (12 sites). DR iPTMnet; P05155; -. DR PhosphoSitePlus; P05155; -. DR BioMuta; SERPING1; -. DR DMDM; 124096; -. DR CPTAC; CPTAC-1305; -. DR CPTAC; CPTAC-684; -. DR CPTAC; non-CPTAC-1147; -. DR CPTAC; non-CPTAC-1148; -. DR EPD; P05155; -. DR jPOST; P05155; -. DR MassIVE; P05155; -. DR PaxDb; 9606-ENSP00000278407; -. DR PeptideAtlas; P05155; -. DR ProteomicsDB; 51806; -. [P05155-1] DR ProteomicsDB; 5752; -. DR ProteomicsDB; 5757; -. DR TopDownProteomics; P05155-1; -. [P05155-1] DR Antibodypedia; 14214; 633 antibodies from 39 providers. DR DNASU; 710; -. DR Ensembl; ENST00000278407.9; ENSP00000278407.4; ENSG00000149131.17. [P05155-1] DR Ensembl; ENST00000378323.8; ENSP00000367574.4; ENSG00000149131.17. [P05155-3] DR Ensembl; ENST00000378324.6; ENSP00000367575.2; ENSG00000149131.17. [P05155-2] DR Ensembl; ENST00000676670.1; ENSP00000504807.1; ENSG00000149131.17. [P05155-1] DR GeneID; 710; -. DR KEGG; hsa:710; -. DR MANE-Select; ENST00000278407.9; ENSP00000278407.4; NM_000062.3; NP_000053.2. DR UCSC; uc001nkp.2; human. [P05155-1] DR AGR; HGNC:1228; -. DR CTD; 710; -. DR DisGeNET; 710; -. DR GeneCards; SERPING1; -. DR HGNC; HGNC:1228; SERPING1. DR HPA; ENSG00000149131; Tissue enhanced (liver). DR MalaCards; SERPING1; -. DR MIM; 106100; phenotype. DR MIM; 606860; gene. DR neXtProt; NX_P05155; -. DR OpenTargets; ENSG00000149131; -. DR Orphanet; 100050; Hereditary angioedema type 1. DR Orphanet; 100051; Hereditary angioedema type 2. DR PharmGKB; PA35029; -. DR VEuPathDB; HostDB:ENSG00000149131; -. DR eggNOG; KOG2392; Eukaryota. DR GeneTree; ENSGT00940000159681; -. DR HOGENOM; CLU_023330_3_0_1; -. DR InParanoid; P05155; -. DR OMA; FELSSCT; -. DR OrthoDB; 4007596at2759; -. DR PhylomeDB; P05155; -. DR TreeFam; TF317350; -. DR PathwayCommons; P05155; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation. DR Reactome; R-HSA-9657689; Defective SERPING1 causes hereditary angioedema. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P05155; -. DR SIGNOR; P05155; -. DR BioGRID-ORCS; 710; 13 hits in 1153 CRISPR screens. DR ChiTaRS; SERPING1; human. DR EvolutionaryTrace; P05155; -. DR GeneWiki; C1-inhibitor; -. DR GenomeRNAi; 710; -. DR Pharos; P05155; Tbio. DR PRO; PR:P05155; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P05155; Protein. DR Bgee; ENSG00000149131; Expressed in right lobe of liver and 208 other cell types or tissues. DR ExpressionAtlas; P05155; baseline and differential. 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; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB. DR GO; GO:0008015; P:blood circulation; TAS:ProtInc. DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW. DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW. DR GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0001869; P:negative regulation of complement activation, lectin pathway; IDA:UniProtKB. DR CDD; cd02050; serpinG1_C1-INH; 1. DR Gene3D; 2.30.39.10; Alpha-1-antitrypsin, domain 1; 1. DR Gene3D; 3.30.497.10; Antithrombin, subunit I, domain 2; 1. DR InterPro; IPR023795; Serpin_CS. DR InterPro; IPR023796; Serpin_dom. DR InterPro; IPR000215; Serpin_fam. DR InterPro; IPR036186; Serpin_sf. DR InterPro; IPR042178; Serpin_sf_1. DR InterPro; IPR042185; Serpin_sf_2. DR PANTHER; PTHR11461:SF159; PLASMA PROTEASE C1 INHIBITOR; 1. DR PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1. DR Pfam; PF00079; Serpin; 1. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; Serpins; 1. DR PROSITE; PS00284; SERPIN; 1. DR Genevisible; P05155; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Blood coagulation; Complement pathway; KW Direct protein sequencing; Disease variant; Disulfide bond; Fibrinolysis; KW Glycoprotein; Hemostasis; Immunity; Innate immunity; Protease inhibitor; KW Reference proteome; Repeat; Secreted; Serine protease inhibitor; Signal. FT SIGNAL 1..22 FT /evidence="ECO:0000269|PubMed:6416294" FT CHAIN 23..500 FT /note="Plasma protease C1 inhibitor" FT /evidence="ECO:0000269|PubMed:3756141" FT /id="PRO_0000032514" FT REPEAT 85..88 FT /note="1" FT REPEAT 89..92 FT /note="2" FT REPEAT 93..96 FT /note="3" FT REPEAT 97..100 FT /note="4" FT REPEAT 101..104 FT /note="5" FT REPEAT 105..108 FT /note="6" FT REPEAT 116..119 FT /note="7" FT REGION 20..43 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 65..118 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 85..119 FT /note="7 X 4 AA tandem repeats of [QE]-P-T-[TQ]" FT COMPBIAS 20..36 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 465..466 FT /note="Reactive bond for chymotrypsin" FT SITE 466..467 FT /note="Reactive bond" FT CARBOHYD 25 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16040958, ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:3756141" FT CARBOHYD 47 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:22171320, FT ECO:0000269|PubMed:23234360" FT CARBOHYD 48 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:22171320, FT ECO:0000269|PubMed:23234360, ECO:0000269|PubMed:3756141" FT CARBOHYD 64 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000269|PubMed:3756141" FT CARBOHYD 69 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:3756141" FT CARBOHYD 71 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:3756141" FT CARBOHYD 81 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:3756141" FT CARBOHYD 83 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:3756141" FT CARBOHYD 88 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:3756141" FT CARBOHYD 92 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:3756141" FT CARBOHYD 96 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:3756141" FT CARBOHYD 238 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:17488724, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:3756141" FT CARBOHYD 253 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:3756141" FT CARBOHYD 272 FT /note="N-linked (GlcNAc...) asparagine; in variant TA" FT CARBOHYD 352 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, FT ECO:0000269|PubMed:3756141" FT DISULFID 123..428 FT /evidence="ECO:0000269|PubMed:17488724, FT ECO:0000269|PubMed:3756141" FT DISULFID 130..205 FT /evidence="ECO:0000269|PubMed:17488724, FT ECO:0000269|PubMed:3756141" FT VAR_SEQ 1..52 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056662" FT VAR_SEQ 17 FT /note="G -> GFLEPQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056663" FT VARIANT 11 FT /note="L -> R (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:24456027" FT /id="VAR_071701" FT VARIANT 39 FT /note="D -> E (in dbSNP:rs11229062)" FT /id="VAR_027374" FT VARIANT 56 FT /note="V -> A (in dbSNP:rs11546660)" FT /evidence="ECO:0000269|PubMed:16409206, FT ECO:0000269|PubMed:22994404" FT /id="VAR_027375" FT VARIANT 84..138 FT /note="Missing (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:12773530" FT /id="VAR_046202" FT VARIANT 118 FT /note="T -> A (in HAE1; dbSNP:rs200534715)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068832" FT VARIANT 130 FT /note="C -> Y (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:14635117" FT /id="VAR_027379" FT VARIANT 154 FT /note="Y -> C (in HAE1; dbSNP:rs281875168)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068833" FT VARIANT 170 FT /note="S -> F (in HAE1; dbSNP:rs281875169)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068834" FT VARIANT 184 FT /note="G -> R (in HAE1; dbSNP:rs281875170)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068835" FT VARIANT 230 FT /note="L -> P (in HAE1; dbSNP:rs281875171)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068836" FT VARIANT 232 FT /note="I -> K (in HAE1; dbSNP:rs281875172)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068837" FT VARIANT 265 FT /note="W -> R (in HAE1)" FT /evidence="ECO:0000269|PubMed:24456027" FT /id="VAR_071702" FT VARIANT 272 FT /note="Missing (in HAE1)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068838" FT VARIANT 273 FT /note="Missing (in HAE1; phenotype consistent with FT hereditary angioedema type 2; creates a new glycosylation FT site)" FT /evidence="ECO:0000269|PubMed:2118657" FT /id="VAR_007012" FT VARIANT 274 FT /note="I -> V (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:24456027" FT /id="VAR_071703" FT VARIANT 299 FT /note="W -> R (in HAE1; dbSNP:rs281875173)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068839" FT VARIANT 308 FT /note="T -> S (in dbSNP:rs1803212)" FT /id="VAR_011751" FT VARIANT 345 FT /note="G -> R (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:16409206" FT /id="VAR_027376" FT VARIANT 394 FT /note="T -> P (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:14635117" FT /id="VAR_027380" FT VARIANT 408 FT /note="D -> V (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:14635117" FT /id="VAR_027381" FT VARIANT 429 FT /note="G -> R (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:8172583" FT /id="VAR_007013" FT VARIANT 430 FT /note="L -> Q (in HAE1; dbSNP:rs281875174)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068840" FT VARIANT 441 FT /note="M -> T (in HAE1; dbSNP:rs281875175)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068841" FT VARIANT 447 FT /note="L -> P (in HAE1; dbSNP:rs281875176)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068842" FT VARIANT 454 FT /note="V -> E (in HAE1; phenotype consistent with FT hereditary angioedema type 2; dbSNP:rs121907949)" FT /evidence="ECO:0000269|PubMed:1363816" FT /id="VAR_007014" FT VARIANT 456 FT /note="A -> E (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|Ref.41" FT /id="VAR_007015" FT VARIANT 458 FT /note="A -> T (in HAE1; phenotype consistent with FT hereditary angioedema type 2; dbSNP:rs121907947)" FT /evidence="ECO:0000269|PubMed:1363816, FT ECO:0000269|PubMed:2296585, ECO:0000269|PubMed:24456027" FT /id="VAR_007016" FT VARIANT 458 FT /note="A -> V (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|Ref.41" FT /id="VAR_007017" FT VARIANT 465 FT /note="A -> V (in HAE1; phenotype consistent with FT hereditary angioedema type 2; dbSNP:rs121907950)" FT /evidence="ECO:0000269|PubMed:7883978" FT /id="VAR_007018" FT VARIANT 466 FT /note="R -> C (in HAE1; phenotype consistent with FT hereditary angioedema type 2; dbSNP:rs28940870)" FT /evidence="ECO:0000269|PubMed:14635117, FT ECO:0000269|PubMed:22994404, ECO:0000269|PubMed:24456027" FT /id="VAR_007019" FT VARIANT 466 FT /note="R -> H (in HAE1; phenotype consistent with FT hereditary angioedema type 2; dbSNP:rs121907948)" FT /evidence="ECO:0000269|PubMed:24456027, FT ECO:0000269|PubMed:3178731" FT /id="VAR_007020" FT VARIANT 466 FT /note="R -> L (in HAE1; phenotype consistent with FT hereditary angioedema type 2; dbSNP:rs121907948)" FT /evidence="ECO:0000269|PubMed:1451784, FT ECO:0000269|PubMed:22994404" FT /id="VAR_007021" FT VARIANT 466 FT /note="R -> S (in HAE1; phenotype consistent with FT hereditary angioedema type 2; dbSNP:rs28940870)" FT /evidence="ECO:0000269|PubMed:22994404, FT ECO:0000269|PubMed:2365061" FT /id="VAR_007022" FT VARIANT 467 FT /note="T -> P (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:8529136" FT /id="VAR_007023" FT VARIANT 473 FT /note="V -> E (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:14635117" FT /id="VAR_027382" FT VARIANT 473 FT /note="V -> G (in HAE1; dbSNP:rs281875177)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068843" FT VARIANT 473 FT /note="V -> M (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:7814636" FT /id="VAR_007024" FT VARIANT 474 FT /note="Q -> E" FT /id="VAR_007025" FT VARIANT 477 FT /note="F -> S (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /id="VAR_007026" FT VARIANT 480 FT /note="V -> M (in dbSNP:rs4926)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:16409206, ECO:0000269|PubMed:22994404, FT ECO:0000269|Ref.7, ECO:0000269|Ref.8, ECO:0000269|Ref.9" FT /id="VAR_007027" FT VARIANT 481 FT /note="L -> P (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:7814636" FT /id="VAR_007028" FT VARIANT 481 FT /note="L -> R (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:7814636" FT /id="VAR_007029" FT VARIANT 489 FT /note="P -> R (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:7814636" FT /id="VAR_007030" FT VARIANT 493 FT /note="G -> E (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:14635117, FT ECO:0000269|PubMed:24456027" FT /id="VAR_027383" FT VARIANT 493 FT /note="G -> R (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:24456027" FT /id="VAR_071704" FT VARIANT 497 FT /note="D -> G (in HAE1; dbSNP:rs281875178)" FT /evidence="ECO:0000269|PubMed:22994404" FT /id="VAR_068844" FT VARIANT 498 FT /note="P -> R (in HAE1; phenotype consistent with FT hereditary angioedema type 1)" FT /evidence="ECO:0000269|PubMed:14635117" FT /id="VAR_027384" FT VARIANT 498 FT /note="P -> S (in HAE1; phenotype consistent with FT hereditary angioedema type 2)" FT /evidence="ECO:0000269|PubMed:7814636" FT /id="VAR_007031" FT CONFLICT 103 FT /note="T -> S (in Ref. 6; BAF85743)" FT /evidence="ECO:0000305" FT CONFLICT 187 FT /note="E -> Q (in Ref. 2; AAB59387)" FT /evidence="ECO:0000305" FT CONFLICT 306 FT /note="K -> R (in Ref. 1; AAA35613)" FT /evidence="ECO:0000305" FT CONFLICT 314..320 FT /note="HFKNSVI -> QLQKLSY (in Ref. 19; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 322 FT /note="V -> M (in Ref. 19; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 332 FT /note="V -> L (in Ref. 19; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 370..375 FT /note="MEQALS -> TGTGSQ (in Ref. 19; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 417 FT /note="E -> V (in Ref. 19; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 439 FT /note="S -> F (in Ref. 19; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 132..137 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 139..160 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 167..169 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 171..182 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 187..197 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 206..212 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 218..226 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 234..244 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 255..269 FT /evidence="ECO:0007829|PDB:5DU3" FT TURN 270..272 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 287..295 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 305..307 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 309..315 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 318..337 FT /evidence="ECO:0007829|PDB:5DU3" FT TURN 338..341 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 342..350 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 353..362 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 367..373 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 376..387 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 392..399 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 401..408 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 409..415 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 417..419 FT /evidence="ECO:0007829|PDB:2OAY" FT TURN 420..422 FT /evidence="ECO:0007829|PDB:5DU3" FT TURN 428..430 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 440..449 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 453..455 FT /evidence="ECO:0007829|PDB:5DU3" FT HELIX 458..461 FT /evidence="ECO:0007829|PDB:5DUQ" FT STRAND 469..472 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 477..483 FT /evidence="ECO:0007829|PDB:5DU3" FT TURN 484..487 FT /evidence="ECO:0007829|PDB:5DU3" FT STRAND 488..496 FT /evidence="ECO:0007829|PDB:5DU3" SQ SEQUENCE 500 AA; 55154 MW; 8B5E874833EA6C05 CRC64; MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKVGQLQLS HNLSLVILVP QNLKHRLEDM EQALSPSVFK AIMEKLEMSK FQPTLLTLPR IKVTTSQDML SIMEKLEFFD FSYDLNLCGL TEDPDLQVSA MQHQTVLELT ETGVEAAAAS AISVARTLLV FEVQQPFLFV LWDQQHKFPV FMGRVYDPRA //