Q9NZP8 (C1RL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	487 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Complement pathway Immunity Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 35	35	Potential
	Chain	36 – 487	452	Complement C1r subcomponent-like protein		PRO_0000318678
Regions
	Domain	39 – 163	125	CUB
	Domain	245 – 484	240	Peptidase S1
Sites
	Active site	283	1	Charge relay system By similarity
	Active site	339	1	Charge relay system By similarity
	Active site	436	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	147	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	166	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	242	1	N-linked (GlcNAc...) Ref.6 Ref.7
	Glycosylation	296	1	N-linked (GlcNAc...) Ref.6 Ref.7
	Glycosylation	363	1	N-linked (GlcNAc...) Potential
	Disulfide bond	94 ↔ 112		By similarity
	Disulfide bond	402 ↔ 421		By similarity
	Disulfide bond	432 ↔ 462		By similarity
Natural variations
	Natural variant	285	1	I → V. Ref.1 Corresponds to variant rs3742089 [ dbSNP | Ensembl ].		VAR_038852
Experimental info
	Mutagenesis	436	1	S → A: Unable to cleave HP. Ref.5
	Sequence conflict	94	1	C → R in BAD96522. Ref.3
	Sequence conflict	99	1	V → A in BAD96522. Ref.3
	Sequence conflict	349	1	I → M in BAD96522. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9NZP8 [UniParc]. Last modified February 26, 2008. Version 2. Checksum: 6DE7CE9EA08C7990	FASTA	487	53,498
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Liver.
+	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.
IPI	IPI00009793.
RefSeq	NP_057630.2. NM_016546.2.
UniGene	Hs.631730.
3D structure databases
ProteinModelPortal	Q9NZP8.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000266542.
Protein family/group databases
MEROPS	S01.189.
PTM databases
PhosphoSite	Q9NZP8.
Polymorphism databases
DMDM	182705204.
Proteomic databases
PaxDb	Q9NZP8.
PRIDE	Q9NZP8.
Protocols and materials databases
DNASU	51279.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000266542; ENSP00000266542; ENSG00000139178.
GeneID	51279.
KEGG	hsa:51279.
UCSC	uc001qsn.3. human.
Organism-specific databases
CTD	51279.
GeneCards	GC12M007247.
H-InvDB	HIX0010393.
HGNC	HGNC:21265. C1RL.
HPA	HPA011338.
MIM	608974. gene.
neXtProt	NX_Q9NZP8.
PharmGKB	PA134957759.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5640.
HOGENOM	HOG000237311.
HOVERGEN	HBG000559.
InParanoid	Q9NZP8.
OMA	LTTELKY.
Gene expression databases
ArrayExpress	Q9NZP8.
Bgee	Q9NZP8.
CleanEx	HS_C1RL.
Genevestigator	Q9NZP8.
Family and domain databases
Gene3D	2.60.120.290. 1 hit.
InterPro	IPR000859. CUB_dom. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR000436. Sushi_SCR_CCP. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00431. CUB. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00042. CUB. 1 hit. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF57535. Complement_control_module. 1 hit. SSF49854. CUB. 1 hit. SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS01180. CUB. 1 hit. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. False negative. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	C1RL. human.
GenomeRNAi	51279.
NextBio	54501.
SOURCE	Search...

Entry information

Entry name

C1RL_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.