P05155 (IC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Plasma protease C1 inhibitor
Short name=C1 Inh
Short name=C1Inh

Alternative name(s):
C1 esterase inhibitor
C1-inhibiting factor
Serpin G1

Gene names

Name:	SERPING1
Synonyms:	C1IN, C1NH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	500 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Activation of the C1 complex is under control of the C1-inhibitor. It forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases. May play a potentially crucial role in regulating important physiological pathways including complement activation, blood coagulation, fibrinolysis and the generation of kinins. Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein. Ref.21
Subunit structure	Binds to E.coli stcE which allows localization of SERPING1 to cell membranes thus protecting the bacteria against complement-mediated lysis. Interacts with MASP1. Ref.22 Ref.23 Ref.25
Subcellular location	Secreted.
Post-translational modification	Highly glycosylated (49%) with N- and O-glycosylation. O-glycosylated with core 1 or possibly core 8 glycans. N-glycan heterogeneity at Asn-25: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor). Ref.2 Ref.24 Ref.27 Ref.31 Ref.32 Ref.33 Can be proteolytically cleaved by E.coli stcE. Ref.23 Ref.25
Polymorphism	Chymotrypsin uses Ala-465 as its reactive site in normal plasma protease C1 inhibitor, and His-466 as its reactive site in the variant His-466.
Involvement in disease	Hereditary angioedema (HAE) [MIM:106100]: An autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In hereditary angioedema type 1, serum levels of C1 esterase inhibitor are decreased, while in type 2, the levels are normal or elevated, but the protein is non-functional. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.20 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48
Sequence similarities	Belongs to the serpin family.
Sequence caution	The sequence AAA53096.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Blood coagulation Complement pathway Fibrinolysis Hemostasis Immunity Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood circulation Traceable author statement Ref.36PubMed 2563376. Source: ProtInc blood coagulation, intrinsic pathway Traceable author statement. Source: Reactome complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW fibrinolysis Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of complement activation, lectin pathway Inferred from direct assay Ref.22. Source: UniProtKB platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome
Cellular_component	extracellular space Inferred from Biological aspect of Ancestor. Source: RefGenome platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	serine-type endopeptidase inhibitor activity Inferred from direct assay PubMed 11527969. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.15

Chain

23 – 500

478

Plasma protease C1 inhibitor Ref.2

PRO_0000032514

Regions

Repeat

85 – 88

4

1

Repeat

89 – 92

4

2

Repeat

93 – 96

4

3

Repeat

97 – 100

4

4

Repeat

101 – 104

4

5

Repeat

105 – 108

4

6

Repeat

116 – 119

4

7

Region

85 – 119

35

7 X 4 AA tandem repeats of [QE]-P-T-[TQ]

Sites

Site

465 – 466

2

Reactive bond for chymotrypsin

Site

466 – 467

2

Reactive bond

Amino acid modifications

Glycosylation

25

1

N-linked (GlcNAc...) (complex) Ref.2 Ref.26 Ref.27 Ref.28 Ref.31

Glycosylation

47

1

O-linked (GalNAc...) Ref.31 Ref.32

Glycosylation

48

1

O-linked (GalNAc...) Ref.2 Ref.31 Ref.32

Glycosylation

64

1

O-linked (GalNAc...) Ref.2

Glycosylation

69

1

N-linked (GlcNAc...) Ref.2 Ref.28 Ref.29

Glycosylation

71

1

O-linked (GalNAc...) Ref.2

Glycosylation

81

1

N-linked (GlcNAc...) Ref.2 Ref.29

Glycosylation

83

1

O-linked (GalNAc...) Ref.2

Glycosylation

88

1

O-linked (GalNAc...) Ref.2

Glycosylation

92

1

O-linked (GalNAc...) Ref.2

Glycosylation

96

1

O-linked (GalNAc...) Ref.2

Glycosylation

238

1

N-linked (GlcNAc...) Ref.2 Ref.26 Ref.28 Ref.29 Ref.33

Glycosylation

253

1

N-linked (GlcNAc...) Ref.2 Ref.24 Ref.26 Ref.28 Ref.29

Glycosylation

272

1

N-linked (GlcNAc...); in variant TA

Glycosylation

352

1

N-linked (GlcNAc...) (complex) Ref.2 Ref.26 Ref.28 Ref.29 Ref.30

Disulfide bond

123 ↔ 428

Ref.2 Ref.33

Disulfide bond

130 ↔ 205

Ref.2 Ref.33

Natural variations

Natural variant

39

1

D → E.
Corresponds to variant rs11229062 [ dbSNP | Ensembl ].

VAR_027374

Natural variant

56

1

V → A. Ref.47 Ref.48
Corresponds to variant rs11546660 [ dbSNP | Ensembl ].

VAR_027375

Natural variant

84 – 138

55

Missing in HAE; type 2.

VAR_046202

Natural variant

118

1

T → A in HAE. Ref.48

VAR_068832

Natural variant

130

1

C → Y in HAE; type 1. Ref.46

VAR_027379

Natural variant

154

1

Y → C in HAE. Ref.48

VAR_068833

Natural variant

170

1

S → F in HAE. Ref.48

VAR_068834

Natural variant

184

1

G → R in HAE. Ref.48

VAR_068835

Natural variant

230

1

L → P in HAE. Ref.48

VAR_068836

Natural variant

232

1

I → K in HAE. Ref.48

VAR_068837

Natural variant

272

1

Missing in HAE. Ref.48

VAR_068838

Natural variant

273

1

Missing in HAE; type 2; TA; creates a new glycosylation site. Ref.38

VAR_007012

Natural variant

299

1

W → R in HAE. Ref.48

VAR_068839

Natural variant

308

1

T → S.
Corresponds to variant rs1803212 [ dbSNP | Ensembl ].

VAR_011751

Natural variant

345

1

G → R in HAE; type 1. Ref.47

VAR_027376

Natural variant

394

1

T → P in HAE; type 1. Ref.46

VAR_027380

Natural variant

408

1

D → V in HAE; type 1. Ref.46

VAR_027381

Natural variant

429

1

G → R in HAE; type 2. Ref.42

VAR_007013

Natural variant

430

1

L → Q in HAE. Ref.48

VAR_068840

Natural variant

441

1

M → T in HAE. Ref.48

VAR_068841

Natural variant

447

1

L → P in HAE. Ref.48

VAR_068842

Natural variant

454

1

V → E in HAE; type 2; WE. Ref.41

VAR_007014

Natural variant

456

1

A → E in HAE; type 2; MA. Ref.39

VAR_007015

Natural variant

458

1

A → T in HAE; type 2; MO. Ref.37 Ref.41

VAR_007016

Natural variant

458

1

A → V in HAE; type 2. Ref.39

VAR_007017

Natural variant

465

1

A → V in HAE; type 2. Ref.43

VAR_007018

Natural variant

466

1

R → C in HAE; type 2; DA. Ref.46 Ref.48
Corresponds to variant rs28940870 [ dbSNP | Ensembl ].

VAR_007019

Natural variant

466

1

R → H in HAE; type 2; AT. Ref.35

VAR_007020

Natural variant

466

1

R → L in HAE; type 2. Ref.40 Ref.48

VAR_007021

Natural variant

466

1

R → S in HAE; type 2. Ref.36 Ref.48
Corresponds to variant rs28940870 [ dbSNP | Ensembl ].

VAR_007022

Natural variant

467

1

T → P in HAE; type 2. Ref.44

VAR_007023

Natural variant

473

1

V → E in HAE; type 1. Ref.46

VAR_027382

Natural variant

473

1

V → G in HAE. Ref.48

VAR_068843

Natural variant

473

1

V → M in HAE; type 2. Ref.20

VAR_007024

Natural variant

474

1

Q → E.

VAR_007025

Natural variant

477

1

F → S in HAE; type 2.

VAR_007026

Natural variant

480

1

V → M. Ref.7 Ref.8 Ref.9 Ref.12 Ref.47 Ref.48
Corresponds to variant rs4926 [ dbSNP | Ensembl ].

VAR_007027

Natural variant

481

1

L → P in HAE; type 2. Ref.20

VAR_007028

Natural variant

481

1

L → R in HAE; type 2. Ref.20

VAR_007029

Natural variant

489

1

P → R in HAE; type 2. Ref.20

VAR_007030

Natural variant

493

1

G → E in HAE; type 1. Ref.46

VAR_027383

Natural variant

497

1

D → G in HAE. Ref.48

VAR_068844

Natural variant

498

1

P → R in HAE; type 1. Ref.46

VAR_027384

Natural variant

498

1

P → S in HAE; type 2. Ref.20

VAR_007031

Experimental info

Sequence conflict

103

1

T → S in BAF85743. Ref.6

Sequence conflict

187

1

E → Q in AAB59387. Ref.2

Sequence conflict

306

1

K → R in AAA35613. Ref.1

Sequence conflict

314 – 320

7

HFKNSVI → QLQKLSY AA sequence Ref.19

Sequence conflict

322

1

V → M AA sequence Ref.19

Sequence conflict

332

1

V → L AA sequence Ref.19

Sequence conflict

370 – 375

6

MEQALS → TGTGSQ AA sequence Ref.19

Sequence conflict

417

1

E → V AA sequence Ref.19

Sequence conflict

439

1

S → F AA sequence Ref.19

Secondary structure

1

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500

Helix Strand Turn

Details...

Helix

135 – 157

23

Beta strand

167 – 169

3

Helix

171 – 183

13

Helix

187 – 197

11

Helix

206 – 211

6

Beta strand

216 – 226

11

Helix

234 – 244

11

Helix

255 – 268

14

Turn

269 – 272

4

Beta strand

287 – 301

15

Beta strand

309 – 313

5

Beta strand

320 – 337

18

Turn

338 – 341

4

Beta strand

342 – 350

9

Beta strand

353 – 362

10

Helix

367 – 373

7

Helix

376 – 387

12

Beta strand

391 – 399

9

Beta strand

402 – 408

7

Helix

409 – 413

5

Helix

414 – 416

3

Beta strand

417 – 419

3

Helix

421 – 424

4

Turn

428 – 430

3

Beta strand

441 – 449

9

Beta strand

451 – 463

13

Beta strand

468 – 470

3

Beta strand

477 – 483

7

Turn

484 – 487

4

Beta strand

488 – 495

8

Sequences

	Sequence		Length	Mass (Da)
	P05155 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: 8B5E874833EA6C05	FASTA	500	55,154
	10 20 30 40 50 60 MASRLTLLTL LLLLLAGDRA SSNPNATSSS SQDPESLQDR GEGKVATTVI SKMLFVEPIL 70 80 90 100 110 120 EVSSLPTTNS TTNSATKITA NTTDEPTTQP TTEPTTQPTI QPTQPTTQLP TDSPTQPTTG 130 140 150 160 170 180 SFCPGPVTLC SDLESHSTEA VLGDALVDFS LKLYHAFSAM KKVETNMAFS PFSIASLLTQ 190 200 210 220 230 240 VLLGAGENTK TNLESILSYP KDFTCVHQAL KGFTTKGVTS VSQIFHSPDL AIRDTFVNAS 250 260 270 280 290 300 RTLYSSSPRV LSNNSDANLE LINTWVAKNT NNKISRLLDS LPSDTRLVLL NAIYLSAKWK 310 320 330 340 350 360 TTFDPKKTRM EPFHFKNSVI KVPMMNSKKY PVAHFIDQTL KAKVGQLQLS HNLSLVILVP 370 380 390 400 410 420 QNLKHRLEDM EQALSPSVFK AIMEKLEMSK FQPTLLTLPR IKVTTSQDML SIMEKLEFFD 430 440 450 460 470 480 FSYDLNLCGL TEDPDLQVSA MQHQTVLELT ETGVEAAAAS AISVARTLLV FEVQQPFLFV 490 500 LWDQQHKFPV FMGRVYDPRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and analysis of a cDNA coding for human C1 inhibitor." Que B.G., Petra P.H. Biochem. Biophys. Res. Commun. 137:620-625(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization." Bock S.C., Skriver K., Nielsen E., Thoegersen H.-C., Wiman B., Donaldson V.H., Eddy R.L., Marrinan J., Radziejewska E., Huber R., Shows T.B., Magnusson S. Biochemistry 25:4292-4301(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-25; THR-48; SER-64; ASN-69; THR-71; ASN-81; THR-83; THR-88; THR-92; THR-96; ASN-238; ASN-253 AND ASN-352.
[3]	"Genomic and cDNA cloning of the human C1 inhibitor. Intron-exon junctions and comparison with other serpins." Carter P.E., Dunbar B., Fothergill J.E. Eur. J. Biochem. 173:163-169(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	"Complete nucleotide sequence of the gene for human C1 inhibitor with an unusually high density of Alu elements." Carter P.E., Duponchel C., Tosi M., Fothergill J.E. Eur. J. Biochem. 197:301-308(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Production of recombinant human C1 inhibitor in milk of transgenic rabbits for potential use in enzyme replacement therapy for hereditary angioedema." Heus J., Platenburg-Kootwijk E., Meershoek E., De Winter R., Knijnenburg J., Kupers L., Habex H., Renaers I., Samuel C., Bonnarens L., Hoffman S., Brouwer M., Hack E., Horbach D., Timmermans M., Nuijens J., Pieper F. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Foreskin.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart and Uterus.
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-480.
[8]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-480. Tissue: Brain.
[9]	SeattleSNPs variation discovery resource Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-480.
[10]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-480. Tissue: Brain.
[13]	"Molecular cloning of the cDNA coding for human C1 inhibitor." Rauth G., Schumacher G., Buckel P., Mueller-Esterl W. Protein Seq. Data Anal. 1:251-257(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-500.
[14]	"The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant." Bos I.G.A., Lubbers Y.T.P., Roem D., Abrahams J.P., Hack C.E., Eldering E. J. Biol. Chem. 278:29463-29470(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 18-188, VARIANT HAE 84-ASP--THR-138 DEL. Tissue: Blood.
[15]	"Human C1 inhibitor: improved isolation and preliminary structural characterization." Harrison R.A. Biochemistry 22:5001-5007(1983) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-62.
[16]	"Clusters of intragenic Alu repeats predispose the human C1 inhibitor locus to deleterious rearrangements." Stoppa-Lyonnet D., Carter P.E., Meo T., Tosi M. Proc. Natl. Acad. Sci. U.S.A. 87:1551-1555(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-228.
[17]	"Molecular cloning of human C1 inhibitor: sequence homologies with alpha 1-antitrypsin and other members of the serpins superfamily." Tosi M., Duponchel C., Bourgarel P., Colomb M., Meo T. Gene 42:265-272(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 213-500.
[18]	"Molecular weights and isoelectric points of sperm antigens relevant to autoimmune infertility in men." Pillai S., Wright D., Gupta A., Zhou G., Hull G., Jiang H., Zhang H. J. Urol. 155:1928-1933(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 217-233.
[19]	"Human inhibitor of the first component of complement, C1: characterization of cDNA clones and localization of the gene to chromosome 11." Davis A.E. III, Whitehead A.S., Harrison R.A., Dauphinias A., Bruns G.A., Cicardi M., Rosen F.S. Proc. Natl. Acad. Sci. U.S.A. 83:3161-3165(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 241-458, PARTIAL PROTEIN SEQUENCE.
[20]	"Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function." Verpy E., Couture-Tosi E., Eldering E., Lopez-Trascasa M., Spath P., Meo T., Tosi M. J. Clin. Invest. 95:350-359(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 418-500, VARIANTS HAE MET-473; ARG-481; PRO-481; ARG-489 AND SER-498.
[21]	"Chymotrypsin inhibitory activity of normal C1-inhibitor and a P1 Arg to His mutant: evidence for the presence of overlapping reactive centers." Aulak K.S., Davis A.E. III, Donaldson V.H., Harrison R.A. Protein Sci. 2:727-732(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 464-481, FUNCTION, REACTIVE SITE FOR CHYMOTRYPSIN. Tissue: Plasma.
[22]	"Proteolytic activities of two types of mannose-binding lectin-associated serine protease." Matsushita M., Thiel S., Jensenius J.C., Terai I., Fujita T. J. Immunol. 165:2637-2642(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MASP1.
[23]	"StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor." Lathem W.W., Grys T.E., Witowski S.E., Torres A.G., Kaper J.B., Tarr P.I., Welch R.A. Mol. Microbiol. 45:277-288(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH E.COLI STCE, PROTEOLYTIC PROCESSING BY E.COLI STCE.
[24]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-253.
[25]	"Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7." Lathem W.W., Bergsbaken T., Welch R.A. J. Exp. Med. 199:1077-1087(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH E.COLI STCE, PROTEOLYTIC PROCESSING BY E.COLI STCE.
[26]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-25; ASN-238; ASN-253 AND ASN-352, MASS SPECTROMETRY. Tissue: Plasma.
[27]	"N-linked glycosylation at Asn3 and the positively charged residues within the amino-terminal domain of the c1 inhibitor are required for interaction of the C1 Inhibitor with Salmonella enterica serovar typhimurium lipopolysaccharide and lipid A." Liu D., Cramer C.C., Scafidi J., Davis A.E. III Infect. Immun. 73:4478-4487(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-25.
[28]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-25; ASN-69; ASN-238; ASN-253 AND ASN-352, MASS SPECTROMETRY. Tissue: Plasma.
[29]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-69; ASN-81; ASN-238; ASN-253 AND ASN-352, MASS SPECTROMETRY. Tissue: Liver.
[30]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-352, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[31]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-25; THR-47 AND THR-48, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
[32]	"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins." Halim A., Ruetschi U., Larson G., Nilsson J. J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-47 AND THR-48, MASS SPECTROMETRY.
[33]	"C1 inhibitor serpin domain structure reveals the likely mechanism of heparin potentiation and conformational disease." Beinrohr L., Harmat V., Dobo J., Loerincz Z., Gal P., Zavodszky P. J. Biol. Chem. 282:21100-21109(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 119-500, DISULFIDE BONDS, GLYCOSYLATION AT ASN-238.
[34]	"What do dysfunctional serpins tell us about molecular mobility and disease?" Stein P.E., Carrell R.W. Nat. Struct. Biol. 2:96-113(1995) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[35]	"Dysfunctional C1-inhibitor(At), isolated from a type II hereditary-angio-oedema plasma, contains a P1 'reactive centre' (Arg444-->His) mutation." Aulak K.S., Pemberton P.A., Rosen F.S., Carrell R.W., Lachmann P.J., Harrison R.A. Biochem. J. 253:615-618(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE HIS-466.
[36]	"Identification of a new P1 residue mutation (444Arg-->Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma." Aulak K.S., Cicardi M., Harrison R.A. FEBS Lett. 266:13-16(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE SER-466.
[37]	"Type II hereditary angioneurotic edema that may result from a single nucleotide change in the codon for alanine-436 in the C1 inhibitor gene." Levy N.J., Ramesh N., Cicardi M., Harrison R.A., Davis A.E. III Proc. Natl. Acad. Sci. U.S.A. 87:265-268(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE THR-458.
[38]	"Dysfunctional C1 inhibitor Ta: deletion of Lys-251 results in acquisition of an N-glycosylation site." Parad R.B., Kramer J., Strunk R.C., Rosen F.S., Davis A.E. III Proc. Natl. Acad. Sci. U.S.A. 87:6786-6790(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE LYS-273 DEL.
[39]	"Identification of type II hereditary angio-oedema (HAE) mutations." Siddique Z.M., McPhaden A.R., Whaley K. Clin. Exp. Immunol. 86:11-12(1991) Cited for: VARIANTS HAE GLU-456 AND VAL-458.
[40]	"A dysfunctional C1 inhibitor protein with a new reactive center mutation (Arg-444-->Leu)." Frange D., Aulak K.S., Cicardi M., Harrison R.A., Davis A.E. III FEBS Lett. 301:34-36(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE LEU-466.
[41]	"C1 inhibitor hinge region mutations produce dysfunction by different mechanisms." Davis A.E. III, Aulak K., Parad R.B., Stecklein H.P., Eldering E., Hack C.E., Kramer J., Strunk R.C., Bissler J., Rosen F.S. Nat. Genet. 1:354-358(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HAE GLU-454 AND THR-458.
[42]	"Mutations in the C1 inhibitor gene that result in hereditary angioneurotic edema." Davis A.E. III, Bissler J.J., Cicardi M. Behring Inst. Mitt. 93:313-320(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE ARG-429.
[43]	"Unique C1 inhibitor dysfunction in a kindred without angioedema. II. Identification of an Ala443-->Val substitution and functional analysis of the recombinant mutant protein." Zahedi R., Bissler J.J., Davis A.E. III, Andreadis C., Wisnieski J.J. J. Clin. Invest. 95:1299-1305(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE VAL-465.
[44]	"A mutation unique in serine protease inhibitors (serpins) identified in a family with type II hereditary angioneurotic edema." Ocejo-Vinyals J.G., Leyva-Cobian F., Fernandez-Luna J.L. Mol. Med. 1:700-705(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE PRO-467.
[45]	"Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema." Verpy E., Biasotto M., Brai M., Misiano G., Meo T., Tosi M. Am. J. Hum. Genet. 59:308-319(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HAE.
[46]	"Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema." Kalmar L., Bors A., Farkas H., Vas S., Fandl B., Varga L., Fuest G., Tordai A. Hum. Mutat. 22:498-498(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HAE TYR-130; PRO-394; VAL-408; CYS-466; GLU-473; GLU-493 AND ARG-498.
[47]	"Normal C1 inhibitor mRNA expression level in type I hereditary angioedema patients: newly found C1 inhibitor gene mutations." Kang H.-R., Yim E.-Y., Oh S.-Y., Chang Y.-S., Kim Y.-K., Cho S.-H., Min K.-U., Kim Y.-Y. Allergy 61:260-264(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HAE ARG-345, VARIANTS ALA-56 AND MET-480.
[48]	"Mutational spectrum and geno-phenotype correlation in Chinese families with Hereditary Angioedema." Xu Y.Y., Zhi Y.X., Yin J., Wang L.L., Wen L.P., Gu J.Q., Guan K., Craig T., Zhang H.Y. Allergy 67:1430-1436(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HAE ALA-118; CYS-154; PHE-170; ARG-184; PRO-230; LYS-232; ASN-272 DEL; ARG-299; GLN-430; THR-441; PRO-447; SER-466; CYS-466; LEU-466; GLY-473 AND GLY-497, VARIANTS ALA-56 AND MET-480.
+	Additional computationally mapped references.

Web resources

Wikipedia

C1-inhibitor entry

SERPING1base

SERPING1 mutation db

GeneReviews

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13690 mRNA. Translation: AAA35613.1.
M13656 mRNA. Translation: AAB59387.1.
X07427 , X07428, X07429, X07430, X07431, X07432, X07433 Genomic DNA. Translation: CAA30314.1.
X07577 mRNA. Translation: CAA30469.1.
X54486 Genomic DNA. Translation: CAA38358.1.
AF435921 Genomic DNA. Translation: AAM21515.1.
AK293054 mRNA. Translation: BAF85743.1.
AK312626 mRNA. Translation: BAG35512.1.
BT006966 mRNA. Translation: AAP35612.1.
AB209826 mRNA. Translation: BAD93063.1.
AY904027 Genomic DNA. Translation: AAW69393.1.
AP000662 Genomic DNA. No translation available.
AP002893 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW73764.1.
BC011171 mRNA. Translation: AAH11171.1.
AY291075 Genomic DNA. Translation: AAQ19269.1.
M30688 Genomic DNA. Translation: AAA53096.1. Sequence problems.
M14036 mRNA. Translation: AAA51848.1.
M13203 mRNA. Translation: AAA51849.1.
S76944 Genomic DNA. Translation: AAB33044.2.

IPI

IPI00291866.

PIR

ITHUC1. S15386.

RefSeq

NP_000053.2. NM_000062.2.
NP_001027466.1. NM_001032295.1.

UniGene

Hs.384598.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M6Q	model	-	A	138-500	[»]
2OAY	X-ray	2.35	A	119-500	[»]

ProteinModelPortal

P05155.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-45635N.

IntAct

P05155. 5 interactions.

Protein family/group databases

MEROPS

I04.024.

PTM databases

PhosphoSite

P05155.

Polymorphism databases

DMDM

124096.

Proteomic databases

PaxDb

P05155.

PeptideAtlas

P05155.

PRIDE

P05155.

Protocols and materials databases

DNASU

710.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000278407; ENSP00000278407; ENSG00000149131.

GeneID

710.

KEGG

hsa:710.

UCSC

uc001nkp.1. human.

Organism-specific databases

CTD

710.

GeneCards

GC11P057364.

HGNC

HGNC:1228. SERPING1.

HPA

CAB026161.

MIM

106100. phenotype.
606860. gene.

neXtProt

NX_P05155.

Orphanet

100050. Hereditary angioedema type 1.
100051. Hereditary angioedema type 2.
169147. Immunodeficiency due to an early component of complement deficiency.

PharmGKB

PA35029.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4826.

HOVERGEN

HBG104060.

KO

K04001.

PhylomeDB

P05155.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P05155.

Bgee

P05155.

Genevestigator

P05155.

GermOnline

ENSG00000149131. Homo sapiens.

Family and domain databases

InterPro

IPR015553. Protease_inhib_I4_serpin_C1.
IPR023795. Protease_inhib_I4_serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]

PANTHER

PTHR11461. PTHR11461. 1 hit.
PTHR11461:SF21. PTHR11461:SF21. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

SUPFAM

SSF56574. Prot_inh_serpin. 1 hit.

PROSITE

PS00284. SERPIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SERPING1. human.

EvolutionaryTrace

P05155.

GenomeRNAi

710.

NextBio

2886.

PMAP-CutDB

P05155.

SOURCE

Search...

Entry information

Entry name

IC1_HUMAN

Accession

Primary (citable) accession number: P05155
Secondary accession number(s): A6NMU0 , A8KAI9, B2R6L5, Q16304, Q547W3, Q59EI5, Q7Z455, Q96FE0, Q9UC49, Q9UCF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 168 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.