Plasma protease C1 inhibitor (SERPING1)
The protein contains 500 amino acids for an estimated molecular weight of 55154 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
Biological Process
Aging
Blood circulation
Blood coagulation
Blood coagulation, intrinsic pathway
Complement activation, classical pathway
Fibrinolysis
Innate immune response
Negative regulation of blood coagulation, intrinsic pathway
Negative regulation of complement activation, lectin pathway
Negative regulation of endopeptidase activity
Platelet activation
Platelet degranulation
Regulation of complement activation
The reference OMIM entry for this protein is 106100
Angioedema, hereditary, type i; hae1
Angioneurotic edema, hereditary; hane
C1 esterase inhibitor, deficiency of angioedema, hereditary, type ii, included; hae2, included
A number sign (#) is used with this entry because hereditary angioedema types I and II are caused by heterozygous mutation in the C1 inhibitor gene (C1NH, SERPING1; 606860) on chromosome 11q. Another type of hereditary angioedema, HAE type III (610618), is caused by mutation in the gene encoding coagulation factor XII (F12; 610619) on chromosome 5q.
DESCRIPTION
Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. There are 2 classic types of the disorder. In type I, representing 85% of patients, serum levels of C1NH are less than 35% of normal (Cicardi and Agostoni, 1996; Bowen et al., 2001). In type II, the levels are normal or elevated, but the protein is nonfunctional. The 2 types are clinically indistinguishable. See 300145 for a discussion of angioedema induced by ACE inhibitors. Zuraw (2008) provided a detailed review of the clinical features, management, and pathogenesis of hereditary angioedema.CLINICAL FEATURES
Edema of the larynx and other portions of the airways is the most fearsome feature of this disorder. Visceral involvement with abdominal pain can lead to unnecessary laparotomy (Weinstock et al., 1987; Waytes et al., 1996). Weinstock et al. (1987) described a family in which lifelong abdominal pain was the only manifestation of hereditary angioedema. A 40-year-old man, 2 of his brothers, his mother, and his daughter were affected. In addition to abdominal pain, nausea, diarrhea, and vomiting occurred, but there were no cutaneous, oropharyngeal, or respiratory manifestations. Barium studies during painful attacks showed transient intestinal wall edema. In rare patients the deficiency is acquired, with symptoms first emerging well into adulthood. Jackson et al. (1986), Alsenz et al. (1987), and Malbran et al. (1988) described patients with acquired C1 inhibitor deficiency resulting from anti-C1NH autoantibodies. These patients had no evidence of an underlying disease, followed a benign course, and showed variable responses to therapy. Frigas (1989) described a patient with acquired C1 inhibitor deficiency who had no evidence of underlying disease 11 years after onset. Muhlemann et al. (1987) found an increased frequency of thyroglobulin antibodies and thyroid microsomal antibodies in patients with hereditary angioedema. They reported the occurrence of systemic lupus erythematosus and glomerulonephritis in patients with this disorder. Perricone et al. (1992) concluded that polycystic ovaries (PCO syndrome; 184700) or multifollicular ovaries occur with unusually high frequency in women with HANE. Weidenbach et al. (1993) reported a 25-year-old woman, with no family history of the disorder, in whom infectious mononucleosis appeared to precipitate the acute onset of HAE. Yakushiji et al. (2007) reported a 35-year-old woman who presented with rapid onset of severe numbness and weakness of all 4 extremities. Detailed laboratory investigations revealed decreased serum levels of several complement components, including C2, C4, C1q, and C1INH. Nerve conduction studies indicated a sensorimotor axonal peripheral neuropathy. Peripheral nerve biopsies showed enlarged nerves with vasculitis and lymphocytic infiltration; most of the proliferating capillaries were strongly positive for anti-C1q, consistent with activation of the classic complement pathway. There was also a dec ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 106100 was added.