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Details on Person UniProt:P00736 C1R
| Class:Id | ReferenceGeneProduct:51072 |
|---|---|
| _chainChangeLog | signal peptide:1-17 added on Fri February 6 2015;chain:18-705 added on Fri February 6 2015;chain:18-463 added on Fri February 6 2015;chain:464-705 added on Fri February 6 2015 |
| _displayName | UniProt:P00736 C1R |
| _timestamp | 2025-08-15 21:21:13 |
| chain | signal peptide:1-17 chain:18-705 chain:18-463 chain:464-705 |
| checksum | B45D120201061462 |
| comment | FUNCTION Serine protease component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:17996945, PubMed:19473974, PubMed:29449492). C1R catalyzes the first enzymatic step in the classical complement pathway: it is activated by the C1Q subcomplex of the C1 complex, which associates with IgG or IgM immunoglobulins complexed with antigens to form antigen-antibody complexes on the surface of pathogens (PubMed:29449492, PubMed:34155115). Immunoglobulin-binding promotes the autocatalytic cleavage and activation of C1R (PubMed:11445589, PubMed:11673533, PubMed:17996945, PubMed:20178990, PubMed:6254570, PubMed:6271784). Activated C1R then cleaves and activates C1S, the second protease of the classical complement pathway (PubMed:11445589, PubMed:11673533, PubMed:6271784). It is unclear if C1R activates C1S within single, strained C1 complexes or between neighboring C1 complexes on surfaces (PubMed:28104818, PubMed:29311313, PubMed:29449492).CATALYTIC ACTIVITY Selective cleavage of Lys(or Arg)-|-Ile bond in complement subcomponent C1s to form the active form of C1s (EC 3.4.21.42).ACTIVITY REGULATION Activated by the C1Q subcomplex of the C1 complex following C1Q binding to immunoglobulins (IgG or IgM) complexed with antigens to form antigen-antibody complexes on the surface of pathogens (PubMed:17996945, PubMed:20178990, PubMed:6254570). Immunoglobulin-binding promotes autoactivation of C1R, which results in the cleavage of the Arg-Ile bond in the catalytic domain (PubMed:17996945, PubMed:20178990).SUBUNIT Core component of the complement C1 complex, a calcium-dependent complex composed of 1 molecule of the C1Q subcomplex, 2 molecules of C1R and 2 molecules of C1S (PubMed:19473974, PubMed:28104818, PubMed:29311313, PubMed:2988513, PubMed:2989825, PubMed:34155115, PubMed:6952210). The C1Q subcomplex is composed 18 subunits: 3 chains of C1QA, C1QB, and C1QC trimerize to form 6 collagen-like triple helices connected to six globular ligand-recognition modules (PubMed:2988513, PubMed:6952210). Within the C1 complex, C1R is a dimer of identical chains, each of which is activated by cleavage into two chains, heavy and light, connected by disulfide bonds (PubMed:2988513, PubMed:6952210).INTERACTION Recruited to the surface of pathogens by the C1Q subcomplex.DOMAIN The CUB domain 2 shows a compact folded structure in the presence of Ca(2+), whereas it has a flexible, disordered conformation in the absence of Ca(2+) (PubMed:20178990). Ca(2+) could provide a switch between the folded and disordered forms; low Ca(2+) could provide flexibility to promote autoprocessing and activation of CIR (PubMed:20178990).PTM Cleaved and activated by autocatalytic processing to generate Complement C1r subcomponent heavy and light chains that are connected by disulfide bonds.PTM The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.POLYMORPHISM Complement component C1r deficiency [MIM:216950] leads to the failure of the classical complement system activation pathway (C1 deficiency). Individuals with C1 deficiency are highly susceptible to infections by microorganisms and have greater risk in developing autoimmune diseases such as systemic lupus erythematosus (SLE).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the peptidase S1 family. |
| description | recommendedName: fullName evidence="39"Complement C1r subcomponent ecNumber evidence="5 6 30"3.4.21.41 alternativeName: Complement component 1 subcomponent r component recommendedName: Complement C1r subcomponent heavy chain alternativeName: fullName evidence="38"Complement C1r subcomponent chain A /component component recommendedName: Complement C1r subcomponent light chain alternativeName: fullName evidence="38"Complement C1r subcomponent chain B /component |
| geneName | C1R |
| identifier | P00736 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Autocatalytic cleavage Complement pathway Direct protein sequencing Disease variant Disulfide bond EGF-like domain Ehlers-Danlos syndrome Glycoprotein Hydrolase Hydroxylation Immunity Innate immunity Phosphoprotein Protease Proteomics identification Reference proteome Repeat Secreted Serine protease Signal Sushi |
| modified | [InstanceEdit:84067] Schmidt, EE, 2003-12-18 04:29:09 [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8856987] Weiser, JD [InstanceEdit:8964659] Weiser, JD [InstanceEdit:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | C1R |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989996] ENSEMBL:ENSG00000159403 C1R [Homo sapiens] |
| secondaryIdentifier | C1R_HUMAN A6NJQ8 Q68D77 Q8J012 |
| sequenceLength | 705 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:173554] C1R(18-705) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:173603] C1R C-terminal fragment [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:173606] C1R N-terminal fragment [extracellular region] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P00736 C1R (51072)
