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Protein

Complement C1r subcomponent

Gene

C1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei502 – 5021Charge relay system
Active sitei557 – 5571Charge relay system
Active sitei654 – 6541Charge relay system

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Complement 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.
SABIO-RKP00736.

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

HGNCiHGNC:1246. C1R.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

MalaCardsiC1R.
MIMi216950. phenotype.
Orphaneti169147. Immunodeficiency due to an early component of complement deficiency.
PharmGKBiPA25635.

Chemistry

ChEMBLiCHEMBL4611.
DrugBankiDB00054. Abciximab.
DB00051. Adalimumab.
DB00092. Alefacept.
DB00087. Alemtuzumab.
DB00074. Basiliximab.
DB00112. Bevacizumab.
DB00002. Cetuximab.
DB00111. Daclizumab.
DB00095. Efalizumab.
DB00005. Etanercept.
DB00056. Gemtuzumab ozogamicin.
DB00078. Ibritumomab.
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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 17171 PublicationAdd
BLAST
Chaini18 – 705688Complement C1r subcomponentPRO_0000027577Add
BLAST
Chaini18 – 463446Complement C1r subcomponent heavy chainPRO_0000027578Add
BLAST
Chaini464 – 705242Complement C1r subcomponent light chainPRO_0000027579Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi71 ↔ 89Curated
Glycosylationi125 – 1251N-linked (GlcNAc...)1 Publication
Disulfide bondi146 ↔ 165
Disulfide bondi161 ↔ 174
Modified residuei167 – 1671(3R)-3-hydroxyasparagine1 Publication
Disulfide bondi176 ↔ 189
Disulfide bondi193 ↔ 220Curated
Modified residuei206 – 2061Phosphoserine; by CK21 Publication
Glycosylationi221 – 2211N-linked (GlcNAc...)1 Publication
Disulfide bondi250 ↔ 268Curated
Disulfide bondi309 ↔ 358
Disulfide bondi338 ↔ 371
Disulfide bondi376 ↔ 429
Disulfide bondi406 ↔ 447
Disulfide bondi451 ↔ 577Interchain (between heavy and light chains)
Glycosylationi514 – 5141N-linked (GlcNAc...)2 Publications
Glycosylationi581 – 5811N-linked (GlcNAc...)
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

PeptideAtlasiP00736.
PRIDEiP00736.

PTM databases

iPTMnetiP00736.
PhosphoSiteiP00736.

Expressioni

Gene expression databases

CleanExiHS_C1R.
ExpressionAtlasiP00736. baseline and differential.
GenevisibleiP00736. HS.

Organism-specific databases

HPAiHPA001551.

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. 9 interactions.
IntActiP00736. 3 interactions.
MINTiMINT-8045732.

Chemistry

BindingDBiP00736.

Structurei

Secondary structure

1
705
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni145 – 1473Combined sources
Turni150 – 1523Combined sources
Beta strandi156 – 1583Combined sources
Beta strandi162 – 1687Combined sources
Beta strandi171 – 1755Combined sources
Beta strandi319 – 3224Combined sources
Beta strandi326 – 3283Combined sources
Beta strandi333 – 3386Combined sources
Beta strandi342 – 3465Combined sources
Beta strandi349 – 3524Combined sources
Beta strandi355 – 3584Combined sources
Beta strandi364 – 3663Combined sources
Beta strandi370 – 3734Combined sources
Beta strandi385 – 3928Combined sources
Beta strandi401 – 4066Combined sources
Turni408 – 4103Combined sources
Beta strandi411 – 4133Combined sources
Beta strandi426 – 4294Combined sources
Beta strandi433 – 4375Combined sources
Turni438 – 4403Combined sources
Beta strandi447 – 4493Combined sources
Beta strandi478 – 49215Combined sources
Turni493 – 4953Combined sources
Beta strandi496 – 4994Combined sources
Helixi501 – 5044Combined sources
Beta strandi518 – 5225Combined sources
Helixi526 – 5327Combined sources
Beta strandi537 – 5426Combined sources
Beta strandi548 – 5525Combined sources
Beta strandi559 – 5657Combined sources
Beta strandi571 – 5733Combined sources
Helixi582 – 5854Combined sources
Beta strandi590 – 5956Combined sources
Beta strandi600 – 6023Combined sources
Beta strandi608 – 6147Combined sources
Helixi617 – 62610Combined sources
Beta strandi637 – 6415Combined sources
Helixi643 – 6508Combined sources
Turni651 – 6555Combined sources
Beta strandi657 – 6615Combined sources
Turni663 – 6653Combined sources
Beta strandi668 – 6769Combined sources
Beta strandi678 – 6836Combined sources
Beta strandi685 – 6895Combined sources
Helixi690 – 6934Combined sources
Helixi694 – 7007Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1APQNMR-A140-192[»]
1GPZX-ray2.90A/B307-705[»]
1MD7X-ray3.20A375-702[»]
1MD8X-ray2.80A375-703[»]
2QY0X-ray2.60A/C309-463[»]
B/D464-705[»]
DisProtiDP00621.
ProteinModelPortaliP00736.
SMRiP00736. Positions 25-703.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00736.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 141124CUB 1PROSITE-ProRule annotationAdd
BLAST
Domaini142 – 19049EGF-like; calcium-bindingSequence analysisAdd
BLAST
Domaini193 – 305113CUB 2PROSITE-ProRule annotationAdd
BLAST
Domaini307 – 37367Sushi 1PROSITE-ProRule annotationAdd
BLAST
Domaini374 – 44976Sushi 2PROSITE-ProRule annotationAdd
BLAST
Domaini464 – 702239Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 2 CUB domains.PROSITE-ProRule annotation
Contains 1 EGF-like domain.Curated
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation
Contains 2 Sushi (CCP/SCR) domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Sushi

Phylogenomic databases

HOVERGENiHBG000559.
InParanoidiP00736.
KOiK01330.
PhylomeDBiP00736.
TreeFamiTF330373.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di2.60.120.290. 2 hits.
InterProiIPR000859. 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.
IPR024175. Pept_S1A_C1r/C1S/mannan-bd.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP_dom.
IPR001254. Trypsin_dom.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00431. CUB. 2 hits.
PF00084. Sushi. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001155. C1r_C1s_MASP. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00032. CCP. 2 hits.
SM00042. CUB. 2 hits.
SM00181. EGF. 1 hit.
SM00179. EGF_CA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEiPS00010. 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.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1311Y → H.1 Publication
VAR_018667
Natural varianti152 – 1521S → L Common polymorphism. 4 Publications
Corresponds to variant rs1801046 [ dbSNP | Ensembl ].
VAR_016103
Natural varianti163 – 1631H → Y.1 Publication
VAR_018668
Natural varianti184 – 1841E → K Polymorphism; confirmed at protein level. 2 Publications
Corresponds to variant rs1126605 [ dbSNP | Ensembl ].
VAR_018669
Natural varianti186 – 1861T → R.4 Publications
Corresponds to variant rs4519167 [ dbSNP | Ensembl ].
VAR_047933
Natural varianti261 – 2611G → R Polymorphism; confirmed at protein level. 2 Publications
Corresponds to variant rs3813728 [ dbSNP | Ensembl ].
VAR_018670

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.
PIRiA24170. C1HURB.
RefSeqiNP_001724.3. NM_001733.4.
UniGeneiHs.524224.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

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.
PIRiA24170. C1HURB.
RefSeqiNP_001724.3. NM_001733.4.
UniGeneiHs.524224.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1APQNMR-A140-192[»]
1GPZX-ray2.90A/B307-705[»]
1MD7X-ray3.20A375-702[»]
1MD8X-ray2.80A375-703[»]
2QY0X-ray2.60A/C309-463[»]
B/D464-705[»]
DisProtiDP00621.
ProteinModelPortaliP00736.
SMRiP00736. Positions 25-703.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107176. 9 interactions.
IntActiP00736. 3 interactions.
MINTiMINT-8045732.

Chemistry

BindingDBiP00736.
ChEMBLiCHEMBL4611.
DrugBankiDB00054. Abciximab.
DB00051. Adalimumab.
DB00092. Alefacept.
DB00087. Alemtuzumab.
DB00074. Basiliximab.
DB00112. Bevacizumab.
DB00002. Cetuximab.
DB00111. Daclizumab.
DB00095. Efalizumab.
DB00005. Etanercept.
DB00056. Gemtuzumab ozogamicin.
DB00078. Ibritumomab.
DB00075. Muromonab.
DB00108. Natalizumab.
DB00110. Palivizumab.
DB00073. Rituximab.
DB00081. Tositumomab.
DB00072. Trastuzumab.
GuidetoPHARMACOLOGYi2334.

Protein family/group databases

MEROPSiS01.192.

PTM databases

iPTMnetiP00736.
PhosphoSiteiP00736.

Polymorphism and mutation databases

BioMutaiC1R.
DMDMi218511956.

Proteomic databases

PeptideAtlasiP00736.
PRIDEiP00736.

Protocols and materials databases

DNASUi715.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi715.
GeneCardsiC1R.
HGNCiHGNC:1246. C1R.
HPAiHPA001551.
MalaCardsiC1R.
MIMi216950. phenotype.
613785. gene.
neXtProtiNX_P00736.
Orphaneti169147. Immunodeficiency due to an early component of complement deficiency.
PharmGKBiPA25635.
GenAtlasiSearch...

Phylogenomic databases

HOVERGENiHBG000559.
InParanoidiP00736.
KOiK01330.
PhylomeDBiP00736.
TreeFamiTF330373.

Enzyme and pathway databases

BRENDAi3.4.21.41. 2681.
ReactomeiR-HSA-166663. Initial triggering of complement.
R-HSA-173623. Classical antibody-mediated complement activation.
SABIO-RKP00736.

Miscellaneous databases

ChiTaRSiC1R. human.
EvolutionaryTraceiP00736.
GeneWikiiC1R_(gene).
GenomeRNAii715.
PROiP00736.
SOURCEiSearch...

Gene expression databases

CleanExiHS_C1R.
ExpressionAtlasiP00736. baseline and differential.
GenevisibleiP00736. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di2.60.120.290. 2 hits.
InterProiIPR000859. 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.
IPR024175. Pept_S1A_C1r/C1S/mannan-bd.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP_dom.
IPR001254. Trypsin_dom.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00431. CUB. 2 hits.
PF00084. Sushi. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001155. C1r_C1s_MASP. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00032. CCP. 2 hits.
SM00042. CUB. 2 hits.
SM00181. EGF. 1 hit.
SM00179. EGF_CA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEiPS00010. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiC1R_HUMAN
AccessioniPrimary (citable) accession number: P00736
Secondary accession number(s): A6NJQ8, Q68D77, Q8J012
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 16, 2008
Last modified: September 7, 2016
This is version 199 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.