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Protein

Complement C1r subcomponent

Gene

C1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.

Catalytic activityi

Selective cleavage of Lys(or Arg)-|-Ile bond in complement subcomponent C1s to form the active form of C1s (EC 3.4.21.42).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei502Charge relay system1
Active sitei557Charge relay system1
Active sitei654Charge relay system1

GO - Molecular functioni

  • calcium ion binding Source: CAFA
  • serine-type endopeptidase activity Source: Reactome
  • serine-type peptidase activity Source: ProtInc

GO - Biological processi

  • complement activation Source: Reactome
  • complement activation, classical pathway Source: Reactome
  • immune response Source: ProtInc
  • innate immune response Source: UniProtKB-KW
  • regulation of complement activation Source: Reactome
  • zymogen activation Source: CAFA

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processComplement pathway, Immunity, Innate immunity

Enzyme and pathway databases

BRENDAi3.4.21.41 2681
ReactomeiR-HSA-166663 Initial triggering of complement
R-HSA-173623 Classical antibody-mediated complement activation
R-HSA-977606 Regulation of Complement cascade
SABIO-RKiP00736
SIGNORiP00736

Protein family/group databases

MEROPSiS01.192

Names & Taxonomyi

Protein namesi
Recommended name:
Complement C1r subcomponent (EC:3.4.21.41)
Alternative name(s):
Complement component 1 subcomponent r
Cleaved into the following 2 chains:
Gene namesi
Name:C1R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000159403.15
HGNCiHGNC:1246 C1R
MIMi613785 gene
neXtProtiNX_P00736

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Ehlers-Danlos syndrome, periodontal type, 1 (EDSPD1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD1 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. EDSPD1 inheritance is autosomal dominant.
See also OMIM:130080
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07710650V → D in EDSPD1; requires 2 nucleotide substitutions; the mutant is not secreted but retained intracellularly. 1 Publication1
Natural variantiVAR_077107290D → G in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077108297G → D in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077109300L → P in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077110301R → P in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077111302Y → C in EDSPD1. 1 Publication1
Natural variantiVAR_077112306 – 309IIKC → RR in EDSPD1. 1 Publication4
Natural variantiVAR_077113309C → W in EDSPD1; the mutant is not secreted but retained intracellularly. 1 Publication1
Natural variantiVAR_077114338C → R in EDSPD1. 1 Publication1
Natural variantiVAR_077115358C → F in EDSPD1. 1 Publication1
Natural variantiVAR_077116364W → C in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077117371C → W in EDSPD1; the mutant is not secreted but retained intracellularly. 1 Publication1
Natural variantiVAR_077118401 – 405RIQYY → HVI in EDSPD1; unknown pathological significance. 1 Publication5
Natural variantiVAR_077119435W → R in EDSPD1; unknown pathological significance. 1 Publication1

Keywords - Diseasei

Disease mutation, Ehlers-Danlos syndrome

Organism-specific databases

DisGeNETi715
MalaCardsiC1R
MIMi130080 phenotype
216950 phenotype
Orphaneti169147 Immunodeficiency due to an early component of complement deficiency
PharmGKBiPA25635

Chemistry databases

ChEMBLiCHEMBL4611
DrugBankiDB00054 Abciximab
DB00051 Adalimumab
DB00092 Alefacept
DB00087 Alemtuzumab
DB00074 Basiliximab
DB00112 Bevacizumab
DB06404 C1 Esterase Inhibitor (Human)
DB09228 C1 Esterase Inhibitor (Recombinant)
DB00002 Cetuximab
DB00111 Daclizumab
DB00095 Efalizumab
DB00005 Etanercept
DB00056 Gemtuzumab ozogamicin
DB00078 Ibritumomab tiuxetan
DB00075 Muromonab
DB00108 Natalizumab
DB00110 Palivizumab
DB00073 Rituximab
DB00081 Tositumomab
DB00072 Trastuzumab
GuidetoPHARMACOLOGYi2334

Polymorphism and mutation databases

BioMutaiC1R
DMDMi218511956

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 171 PublicationAdd BLAST17
ChainiPRO_000002757718 – 705Complement C1r subcomponentAdd BLAST688
ChainiPRO_000002757818 – 463Complement C1r subcomponent heavy chainAdd BLAST446
ChainiPRO_0000027579464 – 705Complement C1r subcomponent light chainAdd BLAST242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi71 ↔ 89Curated
Glycosylationi125N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi146 ↔ 165
Disulfide bondi161 ↔ 174
Modified residuei167(3R)-3-hydroxyasparagine1 Publication1
Disulfide bondi176 ↔ 189
Disulfide bondi193 ↔ 220Curated
Modified residuei206Phosphoserine; by CK21 Publication1
Glycosylationi221N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi250 ↔ 268Curated
Disulfide bondi309 ↔ 358
Disulfide bondi338 ↔ 371
Disulfide bondi376 ↔ 429
Disulfide bondi406 ↔ 447
Disulfide bondi451 ↔ 577Interchain (between heavy and light chains)
Glycosylationi514N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi581N-linked (GlcNAc...) asparagine1
Disulfide bondi620 ↔ 639
Disulfide bondi650 ↔ 680

Post-translational modificationi

The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Hydroxylation, Phosphoprotein

Proteomic databases

EPDiP00736
PeptideAtlasiP00736
PRIDEiP00736
ProteomicsDBi51270

PTM databases

GlyConnecti713
iPTMnetiP00736
PhosphoSitePlusiP00736

Expressioni

Gene expression databases

BgeeiENSG00000159403
CleanExiHS_C1R
ExpressionAtlasiP00736 baseline and differential
GenevisibleiP00736 HS

Organism-specific databases

HPAiHPA001251
HPA001551

Interactioni

Subunit structurei

C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. C1r is a dimer of identical chains, each of which is activated by cleavage into two chains, A and B, connected by disulfide bonds.

Binary interactionsi

WithEntry#Exp.IntActNotes
C1SP098714EBI-3926504,EBI-2810045

Protein-protein interaction databases

BioGridi107176, 10 interactors
IntActiP00736, 3 interactors
MINTiP00736

Chemistry databases

BindingDBiP00736

Structurei

Secondary structure

1705
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni145 – 147Combined sources3
Turni150 – 152Combined sources3
Beta strandi156 – 158Combined sources3
Beta strandi162 – 168Combined sources7
Beta strandi171 – 175Combined sources5
Beta strandi196 – 198Combined sources3
Beta strandi200 – 206Combined sources7
Turni208 – 211Combined sources4
Beta strandi219 – 225Combined sources7
Beta strandi230 – 236Combined sources7
Beta strandi246 – 250Combined sources5
Beta strandi254 – 259Combined sources6
Beta strandi262 – 267Combined sources6
Beta strandi269 – 271Combined sources3
Beta strandi281 – 288Combined sources8
Beta strandi299 – 306Combined sources8
Beta strandi319 – 322Combined sources4
Beta strandi326 – 328Combined sources3
Beta strandi333 – 338Combined sources6
Beta strandi342 – 346Combined sources5
Beta strandi349 – 352Combined sources4
Beta strandi355 – 358Combined sources4
Beta strandi364 – 366Combined sources3
Beta strandi370 – 373Combined sources4
Beta strandi385 – 392Combined sources8
Beta strandi401 – 406Combined sources6
Turni408 – 410Combined sources3
Beta strandi411 – 413Combined sources3
Beta strandi426 – 429Combined sources4
Beta strandi433 – 437Combined sources5
Turni438 – 440Combined sources3
Beta strandi447 – 449Combined sources3
Beta strandi478 – 492Combined sources15
Turni493 – 495Combined sources3
Beta strandi496 – 499Combined sources4
Helixi501 – 504Combined sources4
Beta strandi518 – 522Combined sources5
Helixi526 – 532Combined sources7
Beta strandi537 – 542Combined sources6
Beta strandi548 – 552Combined sources5
Beta strandi559 – 565Combined sources7
Beta strandi571 – 573Combined sources3
Helixi582 – 585Combined sources4
Beta strandi590 – 595Combined sources6
Beta strandi600 – 602Combined sources3
Beta strandi608 – 614Combined sources7
Helixi617 – 626Combined sources10
Beta strandi637 – 641Combined sources5
Helixi643 – 650Combined sources8
Turni651 – 655Combined sources5
Beta strandi657 – 661Combined sources5
Turni663 – 665Combined sources3
Beta strandi668 – 676Combined sources9
Beta strandi678 – 683Combined sources6
Beta strandi685 – 689Combined sources5
Helixi690 – 693Combined sources4
Helixi694 – 700Combined sources7

3D structure databases

DisProtiDP00621
ProteinModelPortaliP00736
SMRiP00736
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00736

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 141CUB 1PROSITE-ProRule annotationAdd BLAST124
Domaini142 – 190EGF-like; calcium-bindingSequence analysisAdd BLAST49
Domaini193 – 305CUB 2PROSITE-ProRule annotationAdd BLAST113
Domaini307 – 373Sushi 1PROSITE-ProRule annotationAdd BLAST67
Domaini374 – 449Sushi 2PROSITE-ProRule annotationAdd BLAST76
Domaini464 – 702Peptidase S1PROSITE-ProRule annotationAdd BLAST239

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Sushi

Phylogenomic databases

HOVERGENiHBG000559
InParanoidiP00736
KOiK01330
PhylomeDBiP00736
TreeFamiTF330373

Family and domain databases

CDDicd00033 CCP, 2 hits
cd00041 CUB, 2 hits
cd00190 Tryp_SPc, 1 hit
Gene3Di2.60.120.290, 2 hits
InterProiView protein in InterPro
IPR035707 Complement_subcomponent_C1r
IPR000859 CUB_dom
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR035914 Sperma_CUB_dom_sf
IPR035976 Sushi/SCR/CCP_sf
IPR000436 Sushi_SCR_CCP_dom
IPR001254 Trypsin_dom
IPR033116 TRYPSIN_SER
PANTHERiPTHR45206 PTHR45206, 1 hit
PfamiView protein in Pfam
PF00431 CUB, 2 hits
PF00084 Sushi, 2 hits
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00032 CCP, 2 hits
SM00042 CUB, 2 hits
SM00181 EGF, 1 hit
SM00179 EGF_CA, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF49854 SSF49854, 2 hits
SSF50494 SSF50494, 1 hit
SSF57535 SSF57535, 2 hits
PROSITEiView protein in PROSITE
PS00010 ASX_HYDROXYL, 1 hit
PS01180 CUB, 2 hits
PS01186 EGF_2, 1 hit
PS01187 EGF_CA, 1 hit
PS50923 SUSHI, 2 hits
PS50240 TRYPSIN_DOM, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P00736-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWLLYLLVPA LFCRAGGSIP IPQKLFGEVT SPLFPKPYPN NFETTTVITV
60 70 80 90 100
PTGYRVKLVF QQFDLEPSEG CFYDYVKISA DKKSLGRFCG QLGSPLGNPP
110 120 130 140 150
GKKEFMSQGN KMLLTFHTDF SNEENGTIMF YKGFLAYYQA VDLDECASRS
160 170 180 190 200
KSGEEDPQPQ CQHLCHNYVG GYFCSCRPGY ELQEDTHSCQ AECSSELYTE
210 220 230 240 250
ASGYISSLEY PRSYPPDLRC NYSIRVERGL TLHLKFLEPF DIDDHQQVHC
260 270 280 290 300
PYDQLQIYAN GKNIGEFCGK QRPPDLDTSS NAVDLLFFTD ESGDSRGWKL
310 320 330 340 350
RYTTEIIKCP QPKTLDEFTI IQNLQPQYQF RDYFIATCKQ GYQLIEGNQV
360 370 380 390 400
LHSFTAVCQD DGTWHRAMPR CKIKDCGQPR NLPNGDFRYT TTMGVNTYKA
410 420 430 440 450
RIQYYCHEPY YKMQTRAGSR ESEQGVYTCT AQGIWKNEQK GEKIPRCLPV
460 470 480 490 500
CGKPVNPVEQ RQRIIGGQKA KMGNFPWQVF TNIHGRGGGA LLGDRWILTA
510 520 530 540 550
AHTLYPKEHE AQSNASLDVF LGHTNVEELM KLGNHPIRRV SVHPDYRQDE
560 570 580 590 600
SYNFEGDIAL LELENSVTLG PNLLPICLPD NDTFYDLGLM GYVSGFGVME
610 620 630 640 650
EKIAHDLRFV RLPVANPQAC ENWLRGKNRM DVFSQNMFCA GHPSLKQDAC
660 670 680 690 700
QGDSGGVFAV RDPNTDRWVA TGIVSWGIGC SRGYGFYTKV LNYVDWIKKE

MEEED
Length:705
Mass (Da):80,119
Last modified:December 16, 2008 - v2
Checksum:iB45D120201061462
GO

Polymorphismi

Complement component C1r deficiency [MIMi: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).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07710650V → D in EDSPD1; requires 2 nucleotide substitutions; the mutant is not secreted but retained intracellularly. 1 Publication1
Natural variantiVAR_018667131Y → H1 Publication1
Natural variantiVAR_016103152S → L Common polymorphism. 4 PublicationsCorresponds to variant dbSNP:rs1801046Ensembl.1
Natural variantiVAR_018668163H → Y1 Publication1
Natural variantiVAR_018669184E → K Polymorphism; confirmed at protein level. 2 PublicationsCorresponds to variant dbSNP:rs1126605Ensembl.1
Natural variantiVAR_047933186T → R4 PublicationsCorresponds to variant dbSNP:rs4519167Ensembl.1
Natural variantiVAR_018670261G → R Polymorphism; confirmed at protein level. 2 PublicationsCorresponds to variant dbSNP:rs3813728Ensembl.1
Natural variantiVAR_077107290D → G in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077108297G → D in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077109300L → P in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077110301R → P in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077111302Y → C in EDSPD1. 1 Publication1
Natural variantiVAR_077112306 – 309IIKC → RR in EDSPD1. 1 Publication4
Natural variantiVAR_077113309C → W in EDSPD1; the mutant is not secreted but retained intracellularly. 1 Publication1
Natural variantiVAR_077114338C → R in EDSPD1. 1 Publication1
Natural variantiVAR_077115358C → F in EDSPD1. 1 Publication1
Natural variantiVAR_077116364W → C in EDSPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_077117371C → W in EDSPD1; the mutant is not secreted but retained intracellularly. 1 Publication1
Natural variantiVAR_077118401 – 405RIQYY → HVI in EDSPD1; unknown pathological significance. 1 Publication5
Natural variantiVAR_077119435W → R in EDSPD1; unknown pathological significance. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14058 mRNA Translation: AAA51851.1
X04701 mRNA Translation: CAA28407.1
AB083037 Genomic DNA Translation: BAC19850.2
AC094008 Genomic DNA No translation available.
AC140077 Genomic DNA No translation available.
CR749540 mRNA Translation: CAH18343.1
BC035220 mRNA Translation: AAH35220.1
CCDSiCCDS81658.1
PIRiA24170 C1HURB
RefSeqiNP_001724.3, NM_001733.4
UniGeneiHs.524224
Hs.731679

Genome annotation databases

EnsembliENST00000542285; ENSP00000438615; ENSG00000159403
GeneIDi715
KEGGihsa:715
UCSCiuc031ysf.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiC1R_HUMAN
AccessioniPrimary (citable) accession number: P00736
Secondary accession number(s): A6NJQ8, Q68D77, Q8J012
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 16, 2008
Last modified: July 18, 2018
This is version 218 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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