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Q9NZP8 (C1RL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement C1r subcomponent-like protein

Short name=C1r-LP
Short name=C1r-like protein
EC=3.4.21.-
Alternative name(s):
C1r-like serine protease analog protein
Short name=CLSPa
Gene names
Name:C1RL
Synonyms:C1RL1, C1RLP, CLSPA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length487 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates the proteolytic cleavage of HP/haptoglobin in the endoplasmic reticulum. Ref.1 Ref.2 Ref.5

Subcellular location

Secreted Ref.1.

Tissue specificity

Highly expressed in placenta, liver, kidney, pancreas, moderately in lung, spleen, prostate, ovary, colon, and PBL, and weakly in heart, skeletal muscle, thymus, testis, and small intestine. Expressed in PC-3 (prostate adenocarcinoma) and SK-OV-3 (ovary adenocarcinoma) cells, but not in LoVo and HT-29 (colon adenocarcinoma), SMMC7721 (hepatocellular carcinoma), CaoV-3 (ovary adenocarcinoma), HeLa (cervix epithelioid carcinoma), MCF-7 (breast adenocarcinoma), U-251MG (glioma) or A-549 (lung carcinoma) cells. Widely expressed in myeloid leukemia cell lines, including K-562 (chronic myelogenous leukemia), THP-1 (myelomonocytic leukemia), HL-60 and NB4 (promyelocytic leukemia), and KG-1 (acute myelogenous leukemia) cells. Expressed mainly in the liver and in serum (at protein level). Ref.1 Ref.2

Induction

Up-regulated in monocytes and dendritic cells (DC) undergoing maturation or activation. Ref.1

Sequence similarities

Belongs to the peptidase S1 family.

Contains 1 CUB domain.

Contains 1 peptidase S1 domain.

Caution

Does not associate with the C1 complex. According to Ref.5, doesn't cleave the proform of complement C1s.

Ontologies

Keywords
   Biological processComplement pathway
Immunity
Innate immunity
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcomplement activation, classical pathway

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionserine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Potential
Chain36 – 487452Complement C1r subcomponent-like protein
PRO_0000318678

Regions

Domain39 – 163125CUB
Domain245 – 484240Peptidase S1

Sites

Active site2831Charge relay system By similarity
Active site3391Charge relay system By similarity
Active site4361Charge relay system By similarity

Amino acid modifications

Glycosylation1471N-linked (GlcNAc...) Ref.7
Glycosylation1661N-linked (GlcNAc...) Ref.6
Glycosylation2421N-linked (GlcNAc...) (complex) Ref.6 Ref.7 Ref.8
Glycosylation2961N-linked (GlcNAc...) Ref.6 Ref.7
Glycosylation3631N-linked (GlcNAc...) Potential
Disulfide bond94 ↔ 112 By similarity
Disulfide bond402 ↔ 421 By similarity
Disulfide bond432 ↔ 462 By similarity

Natural variations

Natural variant2851I → V. Ref.1
Corresponds to variant rs3742089 [ dbSNP | Ensembl ].
VAR_038852

Experimental info

Mutagenesis4361S → A: Unable to cleave HP. Ref.5
Sequence conflict941C → R in BAD96522. Ref.3
Sequence conflict991V → A in BAD96522. Ref.3
Sequence conflict3491I → M in BAD96522. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9NZP8 [UniParc].

Last modified February 26, 2008. Version 2.
Checksum: 6DE7CE9EA08C7990

FASTA48753,498
        10         20         30         40         50         60 
MPGPRVWGKY LWRSPHSKGC PGAMWWLLLW GVLQACPTRG SVLLAQELPQ QLTSPGYPEP 

        70         80         90        100        110        120 
YGKGQESSTD IKAPEGFAVR LVFQDFDLEP SQDCAGDSVT ISFVGSDPSQ FCGQQGSPLG 

       130        140        150        160        170        180 
RPPGQREFVS SGRSLRLTFR TQPSSENKTA HLHKGFLALY QTVAVNYSQP ISEASRGSEA 

       190        200        210        220        230        240 
INAPGDNPAK VQNHCQEPYY QAAAAGALTC ATPGTWKDRQ DGEEVLQCMP VCGRPVTPIA 

       250        260        270        280        290        300 
QNQTTLGSSR AKLGNFPWQA FTSIHGRGGG ALLGDRWILT AAHTIYPKDS VSLRKNQSVN 

       310        320        330        340        350        360 
VFLGHTAIDE MLKLGNHPVH RVVVHPDYRQ NESHNFSGDI ALLELQHSIP LGPNVLPVCL 

       370        380        390        400        410        420 
PDNETLYRSG LLGYVSGFGM EMGWLTTELK YSRLPVAPRE ACNAWLQKRQ RPEVFSDNMF 

       430        440        450        460        470        480 
CVGDETQRHS VCQGDSGSVY VVWDNHAHHW VATGIVSWGI GCGEGYDFYT KVLSYVDWIK 


GVMNGKN 

« Hide

References

« Hide 'large scale' references
[1]"A novel human dendritic cell-derived C1r-like serine protease analog inhibits complement-mediated cytotoxicity."
Lin N., Liu S., Li N., Wu P., An H., Yu Y., Wan T., Cao X.
Biochem. Biophys. Res. Commun. 321:329-336(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, VARIANT VAL-285.
Tissue: Dendritic cell.
[2]"A novel human complement-related protein, C1r-like protease (C1r-LP), specifically cleaves pro-C1s."
Ligoudistianou C., Xu Y., Garnier G., Circolo A., Volanakis J.E.
Biochem. J. 387:165-173(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[4]"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].
[5]"Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1r-like protein."
Wicher K.B., Fries E.
Proc. Natl. Acad. Sci. U.S.A. 101:14390-14395(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-436.
[6]"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-166; ASN-242 AND ASN-296.
Tissue: Plasma.
[7]"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-147; ASN-242 AND ASN-296.
Tissue: Liver.
[8]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-242.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF178985 mRNA. Translation: AAF44349.1.
AK222802 mRNA. Translation: BAD96522.1.
AC018653 Genomic DNA. No translation available.
AC094008 Genomic DNA. No translation available.
AC233309 Genomic DNA. No translation available.
CCDSCCDS8573.1.
RefSeqNP_057630.2. NM_016546.2.
UniGeneHs.631730.

3D structure databases

ProteinModelPortalQ9NZP8.
SMRQ9NZP8. Positions 51-483.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119431. 2 interactions.
STRING9606.ENSP00000266542.

Protein family/group databases

MEROPSS01.189.

PTM databases

PhosphoSiteQ9NZP8.

Polymorphism databases

DMDM182705204.

Proteomic databases

PaxDbQ9NZP8.
PRIDEQ9NZP8.

Protocols and materials databases

DNASU51279.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266542; ENSP00000266542; ENSG00000139178.
GeneID51279.
KEGGhsa:51279.
UCSCuc001qsn.3. human.

Organism-specific databases

CTD51279.
GeneCardsGC12M007247.
H-InvDBHIX0010393.
HGNCHGNC:21265. C1RL.
HPAHPA011338.
MIM608974. gene.
neXtProtNX_Q9NZP8.
PharmGKBPA134957759.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000237311.
HOVERGENHBG000559.
InParanoidQ9NZP8.
OMAWQAFTSI.
PhylomeDBQ9NZP8.
TreeFamTF330373.

Gene expression databases

ArrayExpressQ9NZP8.
BgeeQ9NZP8.
CleanExHS_C1RL.
GenevestigatorQ9NZP8.

Family and domain databases

Gene3D2.60.120.290. 1 hit.
InterProIPR000859. CUB_dom.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00431. CUB. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00042. CUB. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF49854. SSF49854. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 1 hit.
PROSITEPS01180. CUB. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSC1RL. human.
GenomeRNAi51279.
NextBio54501.
PROQ9NZP8.
SOURCESearch...

Entry information

Entry nameC1RL_HUMAN
AccessionPrimary (citable) accession number: Q9NZP8
Secondary accession number(s): Q53GX9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: July 9, 2014
This is version 109 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

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