IC1_HUMAN
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 03-AUG-2022, entry version 245.
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 HAE
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=10.1016/s0022-5347(01)66050-6;
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 HAE 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 HAE 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 HAE 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 HAE 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 HAE 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 HAE 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 HAE 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 HAE 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 HAE 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 HAE 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 HAE 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 HAE.
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 HAE 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 HAE 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 HAE 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 HAE 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 (HAE) [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 ---------------------------------------------------------------------------
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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 SMR; P05155; -.
DR BioGRID; 107171; 49.
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 GlyGen; P05155; 25 sites, 56 N-linked glycans (5 sites), 8 O-linked glycans (11 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; P05155; -.
DR PeptideAtlas; P05155; -.
DR PRIDE; P05155; -.
DR ProteomicsDB; 51806; -. [P05155-1]
DR ProteomicsDB; 5752; -.
DR ProteomicsDB; 5757; -.
DR TopDownProteomics; P05155-1; -. [P05155-1]
DR Antibodypedia; 14214; 594 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 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; EFFDFTY; -.
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; 12 hits in 1073 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 206 other tissues.
DR ExpressionAtlas; P05155; baseline and differential.
DR Genevisible; P05155; 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; 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:0007568; P:aging; IEA:Ensembl.
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 GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR015553; C1-inh.
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; PTHR11461; 1.
DR PANTHER; PTHR11461:SF159; PTHR11461:SF159; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
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 HAE; phenotype consistent with hereditary
FT 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 HAE; 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 HAE; dbSNP:rs200534715)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068832"
FT VARIANT 130
FT /note="C -> Y (in HAE; phenotype consistent with hereditary
FT angioedema type 1)"
FT /evidence="ECO:0000269|PubMed:14635117"
FT /id="VAR_027379"
FT VARIANT 154
FT /note="Y -> C (in HAE; dbSNP:rs281875168)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068833"
FT VARIANT 170
FT /note="S -> F (in HAE; dbSNP:rs281875169)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068834"
FT VARIANT 184
FT /note="G -> R (in HAE; dbSNP:rs281875170)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068835"
FT VARIANT 230
FT /note="L -> P (in HAE; dbSNP:rs281875171)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068836"
FT VARIANT 232
FT /note="I -> K (in HAE; dbSNP:rs281875172)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068837"
FT VARIANT 265
FT /note="W -> R (in HAE)"
FT /evidence="ECO:0000269|PubMed:24456027"
FT /id="VAR_071702"
FT VARIANT 272
FT /note="Missing (in HAE)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068838"
FT VARIANT 273
FT /note="Missing (in HAE; 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 HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|PubMed:24456027"
FT /id="VAR_071703"
FT VARIANT 299
FT /note="W -> R (in HAE; 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 HAE; phenotype consistent with hereditary
FT angioedema type 1)"
FT /evidence="ECO:0000269|PubMed:16409206"
FT /id="VAR_027376"
FT VARIANT 394
FT /note="T -> P (in HAE; phenotype consistent with hereditary
FT angioedema type 1)"
FT /evidence="ECO:0000269|PubMed:14635117"
FT /id="VAR_027380"
FT VARIANT 408
FT /note="D -> V (in HAE; phenotype consistent with hereditary
FT angioedema type 1)"
FT /evidence="ECO:0000269|PubMed:14635117"
FT /id="VAR_027381"
FT VARIANT 429
FT /note="G -> R (in HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|PubMed:8172583"
FT /id="VAR_007013"
FT VARIANT 430
FT /note="L -> Q (in HAE; dbSNP:rs281875174)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068840"
FT VARIANT 441
FT /note="M -> T (in HAE; dbSNP:rs281875175)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068841"
FT VARIANT 447
FT /note="L -> P (in HAE; dbSNP:rs281875176)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068842"
FT VARIANT 454
FT /note="V -> E (in HAE; phenotype consistent with hereditary
FT angioedema type 2; dbSNP:rs121907949)"
FT /evidence="ECO:0000269|PubMed:1363816"
FT /id="VAR_007014"
FT VARIANT 456
FT /note="A -> E (in HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|Ref.41"
FT /id="VAR_007015"
FT VARIANT 458
FT /note="A -> T (in HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|Ref.41"
FT /id="VAR_007017"
FT VARIANT 465
FT /note="A -> V (in HAE; phenotype consistent with hereditary
FT angioedema type 2; dbSNP:rs121907950)"
FT /evidence="ECO:0000269|PubMed:7883978"
FT /id="VAR_007018"
FT VARIANT 466
FT /note="R -> C (in HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|PubMed:8529136"
FT /id="VAR_007023"
FT VARIANT 473
FT /note="V -> E (in HAE; phenotype consistent with hereditary
FT angioedema type 1)"
FT /evidence="ECO:0000269|PubMed:14635117"
FT /id="VAR_027382"
FT VARIANT 473
FT /note="V -> G (in HAE; dbSNP:rs281875177)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068843"
FT VARIANT 473
FT /note="V -> M (in HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|PubMed:7814636"
FT /id="VAR_007028"
FT VARIANT 481
FT /note="L -> R (in HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|PubMed:7814636"
FT /id="VAR_007029"
FT VARIANT 489
FT /note="P -> R (in HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|PubMed:7814636"
FT /id="VAR_007030"
FT VARIANT 493
FT /note="G -> E (in HAE; phenotype consistent with hereditary
FT 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 HAE; phenotype consistent with hereditary
FT angioedema type 2)"
FT /evidence="ECO:0000269|PubMed:24456027"
FT /id="VAR_071704"
FT VARIANT 497
FT /note="D -> G (in HAE; dbSNP:rs281875178)"
FT /evidence="ECO:0000269|PubMed:22994404"
FT /id="VAR_068844"
FT VARIANT 498
FT /note="P -> R (in HAE; phenotype consistent with hereditary
FT angioedema type 1)"
FT /evidence="ECO:0000269|PubMed:14635117"
FT /id="VAR_027384"
FT VARIANT 498
FT /note="P -> S (in HAE; phenotype consistent with hereditary
FT 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
