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P00736 (C1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 179. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement C1r subcomponent

EC=3.4.21.41
Alternative name(s):
Complement component 1 subcomponent r
Gene names
Name:C1R
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length705 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 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).

Subunit structure

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.

Post-translational modification

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).

Sequence similarities

Belongs to the peptidase S1 family.

Contains 2 CUB domains.

Contains 1 EGF-like domain.

Contains 1 peptidase S1 domain.

Contains 2 Sushi (CCP/SCR) domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

C1SP098713EBI-3926504,EBI-2810045

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Ref.7
Chain18 – 705688Complement C1r subcomponent
PRO_0000027577
Chain18 – 463446Complement C1r subcomponent heavy chain
PRO_0000027578
Chain464 – 705242Complement C1r subcomponent light chain
PRO_0000027579

Regions

Domain18 – 141124CUB 1
Domain142 – 19049EGF-like; calcium-binding Potential
Domain193 – 305113CUB 2
Domain307 – 37367Sushi 1
Domain374 – 44976Sushi 2
Domain464 – 702239Peptidase S1

Sites

Active site5021Charge relay system
Active site5571Charge relay system
Active site6541Charge relay system

Amino acid modifications

Modified residue1671(3R)-3-hydroxyasparagine
Modified residue2061Phosphoserine; by CK2 Ref.10
Glycosylation1251N-linked (GlcNAc...) Ref.11
Glycosylation2211N-linked (GlcNAc...) Ref.11
Glycosylation5141N-linked (GlcNAc...) Ref.11 Ref.12
Glycosylation5811N-linked (GlcNAc...)
Disulfide bond71 ↔ 89 Probable
Disulfide bond146 ↔ 165
Disulfide bond161 ↔ 174
Disulfide bond176 ↔ 189
Disulfide bond193 ↔ 220 Probable
Disulfide bond250 ↔ 268 Probable
Disulfide bond309 ↔ 358
Disulfide bond338 ↔ 371
Disulfide bond376 ↔ 429
Disulfide bond406 ↔ 447
Disulfide bond451 ↔ 577Interchain (between heavy and light chains)
Disulfide bond620 ↔ 639
Disulfide bond650 ↔ 680

Natural variations

Natural variant1311Y → H. Ref.3
VAR_018667
Natural variant1521S → L Common polymorphism. Ref.2 Ref.3 Ref.6 Ref.16
Corresponds to variant rs1801046 [ dbSNP | Ensembl ].
VAR_016103
Natural variant1631H → Y. Ref.3
VAR_018668
Natural variant1841E → K Polymorphism confirmed at protein level. Ref.3 Ref.17
Corresponds to variant rs1126605 [ dbSNP | Ensembl ].
VAR_018669
Natural variant1861T → R. Ref.1 Ref.2 Ref.3 Ref.6
Corresponds to variant rs4519167 [ dbSNP | Ensembl ].
VAR_047933
Natural variant2611G → R Polymorphism confirmed at protein level. Ref.3 Ref.17
Corresponds to variant rs3813728 [ dbSNP | Ensembl ].
VAR_018670

Secondary structure

...................................................................................... 705
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00736 [UniParc].

Last modified December 16, 2008. Version 2.
Checksum: B45D120201061462

FASTA70580,119
        10         20         30         40         50         60 
MWLLYLLVPA LFCRAGGSIP IPQKLFGEVT SPLFPKPYPN NFETTTVITV PTGYRVKLVF 

        70         80         90        100        110        120 
QQFDLEPSEG CFYDYVKISA DKKSLGRFCG QLGSPLGNPP GKKEFMSQGN KMLLTFHTDF 

       130        140        150        160        170        180 
SNEENGTIMF YKGFLAYYQA VDLDECASRS KSGEEDPQPQ CQHLCHNYVG GYFCSCRPGY 

       190        200        210        220        230        240 
ELQEDTHSCQ AECSSELYTE ASGYISSLEY PRSYPPDLRC NYSIRVERGL TLHLKFLEPF 

       250        260        270        280        290        300 
DIDDHQQVHC PYDQLQIYAN GKNIGEFCGK QRPPDLDTSS NAVDLLFFTD ESGDSRGWKL 

       310        320        330        340        350        360 
RYTTEIIKCP QPKTLDEFTI IQNLQPQYQF RDYFIATCKQ GYQLIEGNQV LHSFTAVCQD 

       370        380        390        400        410        420 
DGTWHRAMPR CKIKDCGQPR NLPNGDFRYT TTMGVNTYKA RIQYYCHEPY YKMQTRAGSR 

       430        440        450        460        470        480 
ESEQGVYTCT AQGIWKNEQK GEKIPRCLPV CGKPVNPVEQ RQRIIGGQKA KMGNFPWQVF 

       490        500        510        520        530        540 
TNIHGRGGGA LLGDRWILTA AHTLYPKEHE AQSNASLDVF LGHTNVEELM KLGNHPIRRV 

       550        560        570        580        590        600 
SVHPDYRQDE SYNFEGDIAL LELENSVTLG PNLLPICLPD NDTFYDLGLM GYVSGFGVME 

       610        620        630        640        650        660 
EKIAHDLRFV RLPVANPQAC ENWLRGKNRM DVFSQNMFCA GHPSLKQDAC QGDSGGVFAV 

       670        680        690        700 
RDPNTDRWVA TGIVSWGIGC SRGYGFYTKV LNYVDWIKKE MEEED 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the cDNA coding for human complement C1r."
Leytus S.P., Kurachi K., Sakariassen K.S., Davie E.W.
Biochemistry 25:4855-4863(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-186.
[2]"Cloning and sequencing of full-length cDNA encoding the precursor of human complement component C1r."
Journet A., Tosi M.
Biochem. J. 240:783-787(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-152 AND ARG-186.
[3]"The human complement component C1R gene: the exon-intron structure and the molecular basis of allelic diversity."
Nakagawa M., Yuasa I., Irizawa Y., Umetsu K.
Ann. Hum. Genet. 67:207-215(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-131; LEU-152; TYR-163; LYS-184; ARG-186 AND ARG-261.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon endothelium.
[5]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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], VARIANTS LEU-152 AND ARG-186.
Tissue: Skin.
[7]"Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r."
Arlaud G.J., Willis A.C., Gagnon J.
Biochem. J. 241:711-720(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-463.
[8]"Complete amino acid sequence of the catalytic chain of human complement subcomponent C1-r."
Arlaud G.J., Gagnon J.
Biochemistry 22:1758-1764(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 464-705.
[9]"Identification of erythro-beta-hydroxyasparagine in the EGF-like domain of human C1r."
Arlaud G.J., van Dorsselaer A., Bell A., Mancini M., Aude C., Gagnon J.
FEBS Lett. 222:129-134(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 152-186, HYDROXYLATION.
[10]"Identification of a cryptic protein kinase CK2 phosphorylation site in human complement protease Clr, and its use to probe intramolecular interaction."
Pelloux S., Thielens N.M., Hudry-Clergeon G., Petillot Y., Filhol O., Arlaud G.J.
FEBS Lett. 386:15-20(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 133-137; 187-211 AND 609-613, PHOSPHORYLATION AT SER-206 BY CK2.
[11]"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-125; ASN-221 AND ASN-514.
Tissue: Plasma.
[12]"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-514.
Tissue: Liver.
[13]"Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family."
Bersch B., Hernandez J.-F., Marion D., Arlaud G.J.
Biochemistry 37:1204-1214(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 140-192.
[14]"The crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex."
Budayova-Spano M., Lacroix M., Thielens N.M., Arlaud G.J., Fontecilla-Camps J.-C., Gaboriaud C.
EMBO J. 21:231-239(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 307-702.
[15]"Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism."
Budayova-Spano M., Grabarse W., Thielens N.M., Hillen H., Lacroix M., Schmidt M., Fontecilla-Camps J.-C., Arlaud G.J., Gaboriaud C.
Structure 10:1509-1519(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 375-702.
[16]"A common amino acid polymorphism in complement component C1R."
Nothen M.M., Dewald G.
Hum. Mol. Genet. 3:217-217(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-152.
[17]"Quantitative detection of single amino acid polymorphisms by targeted proteomics."
Su Z.D., Sun L., Yu D.X., Li R.X., Li H.X., Yu Z.J., Sheng Q.H., Lin X., Zeng R., Wu J.R.
J. Mol. Cell Biol. 3:309-315(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-184 AND ARG-261, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRC1HURB. A24170.
RefSeqNP_001724.3. NM_001733.4.
UniGeneHs.524224.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
DisProtDP00621.
ProteinModelPortalP00736.
SMRP00736. Positions 25-703.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107176. 6 interactions.
IntActP00736. 3 interactions.
MINTMINT-8045732.
STRING9606.ENSP00000290575.

Chemistry

BindingDBP00736.
ChEMBLCHEMBL4611.
DrugBankDB00054. Abciximab.
DB00051. Adalimumab.
DB00092. Alefacept.
DB00087. Alemtuzumab.
DB00074. Basiliximab.
DB00112. Bevacizumab.
DB00002. Cetuximab.
DB00111. Daclizumab.
DB00095. Efalizumab.
DB00005. Etanercept.
DB00056. Gemtuzumab ozogamicin.
DB00078. Ibritumomab.
DB00028. Immune globulin.
DB00075. Muromonab.
DB00108. Natalizumab.
DB00110. Palivizumab.
DB00073. Rituximab.
DB00081. Tositumomab.
DB00072. Trastuzumab.

Protein family/group databases

MEROPSS01.192.

PTM databases

PhosphoSiteP00736.

Polymorphism databases

DMDM218511956.

Proteomic databases

PaxDbP00736.
PeptideAtlasP00736.
PRIDEP00736.

Protocols and materials databases

DNASU715.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290575; ENSP00000290575; ENSG00000159403.
GeneID715.
KEGGhsa:715.

Organism-specific databases

CTD715.
GeneCardsGC12M007187.
HGNCHGNC:1246. C1R.
HPAHPA001551.
MIM216950. phenotype.
613785. gene.
neXtProtNX_P00736.
Orphanet169147. Immunodeficiency due to an early component of complement deficiency.
PharmGKBPA25635.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOVERGENHBG000559.
KOK01330.
OrthoDBEOG7W6WK4.
PhylomeDBP00736.
TreeFamTF330373.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP00736.
CleanExHS_C1R.
GenevestigatorP00736.

Family and domain databases

Gene3D2.60.120.290. 2 hits.
InterProIPR000859. CUB_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024175. Pept_S1A_C1r/C1S/mannan-bd.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00431. CUB. 2 hits.
PF00084. Sushi. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF001155. C1r_C1s_MASP. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00032. CCP. 2 hits.
SM00042. CUB. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF49854. SSF49854. 2 hits.
SSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEPS00010. 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]
ProtoNetSearch...

Other

ChiTaRSC1R. human.
EvolutionaryTraceP00736.
GeneWikiC1R_(gene).
GenomeRNAi715.
NextBio2906.
PROP00736.
SOURCESearch...

Entry information

Entry nameC1R_HUMAN
AccessionPrimary (citable) accession number: P00736
Secondary accession number(s): A6NJQ8, Q68D77, Q8J012
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 16, 2008
Last modified: June 11, 2014
This is version 179 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM