Reviewed, UniProtKB/Swiss-Prot P02741 (CRP_HUMAN)

Names and origin

Protein names

Recommended name:
    C-reactive protein
Cleaved into the following chain:
    1- Recommended name:
            C-reactive protein(1-205)

Gene names

Name:	CRP
Synonyms:	PTX1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	224 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	Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells.
Cofactor	Binds 2 calcium ions per subunit.
Subunit structure	Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.
Subcellular location	Secreted.
Tissue specificity	Found in plasma.
Induction	The concentration of CRP in plasma increases greatly during acute phase response to tissue injury, infection or other inflammatory stimuli. It is induced by IL-1 and IL-6.
Miscellaneous	This protein owes its name to its ability precipitate pneumococcal C-polysaccharide in the presence of calcium.
Sequence similarities	Belongs to the pentaxin family. Contains 1 pentaxin domain.
Mass spectrometry	Molecular weight is 23028 Da from positions 19 - 224. Determined by MALDI. Ref.13 Molecular weight is 22930 Da from positions 19 - 223. Determined by MALDI. Ref.13

Ontologies

Keywords
Biological process	Acute phase
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Ligand	Calcium Metal-binding
PTM	Pyrrolidone carboxylic acid
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	acute-phase response Inferred from electronic annotation. Source: UniProtKB-KW opsonization Traceable author statement. Source: UniProtKB
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	Gram-positive bacterial cell surface binding Traceable author statement. Source: UniProtKB calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW choline binding Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FCGR2A	P12318	1	EBI-1395983,EBI-1395970
FCGR2C	P31995	2	EBI-1395983,EBI-1396036

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P02741-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P02741-2)

The sequence of this isoform differs from the canonical sequence as follows:
     67-199: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Chain

19 – 224

206

C-reactive protein

PRO_0000023526

Chain

19 – 223

205

C-reactive protein(1-205)

PRO_0000023527

Regions

Domain

19 – 224

206

Pentaxin

Sites

Metal binding

78

1

Calcium 1

Metal binding

79

1

Calcium 1

Metal binding

156

1

Calcium 1

Metal binding

156

1

Calcium 2

Metal binding

157

1

Calcium 1; via carbonyl oxygen

Metal binding

158

1

Calcium 1

Metal binding

158

1

Calcium 2

Metal binding

168

1

Calcium 2

Amino acid modifications

Modified residue

19

1

Pyrrolidone carboxylic acid

Disulfide bond

54 ↔ 115

Natural variations

Alternative sequence

67 – 199

133

Missing in isoform 2.

VSP_004656

Experimental info

Sequence conflict

49

1

K → G AA sequence Ref.12

Sequence conflict

52

1

T → G AA sequence Ref.12

Sequence conflict

67 – 82

16

YSIFS…DNEIL → TVFSRMPPRDKTMRFF in CAA39671. Ref.4

Sequence conflict

80 – 98

19

Missing AA sequence Ref.11

Sequence conflict

170

1

L → V in AAA52074. Ref.10

Secondary structure

1

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224

Helix Strand Turn

Details...

Beta strand

25 – 29

5

Beta strand

37 – 40

4

Beta strand

48 – 58

11

Helix

61 – 63

3

Beta strand

67 – 73

7

Beta strand

80 – 86

7

Turn

87 – 89

3

Beta strand

90 – 95

6

Beta strand

98 – 103

6

Beta strand

112 – 119

8

Turn

120 – 122

3

Beta strand

124 – 129

6

Beta strand

150 – 155

6

Helix

166 – 168

3

Beta strand

172 – 182

11

Helix

186 – 194

9

Beta strand

201 – 203

3

Helix

205 – 207

3

Beta strand

210 – 215

6

Beta strand

217 – 220

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 669228636A8544F6	FASTA	224	25,039
	10 20 30 40 50 60 MEKLLCFLVL TSLSHAFGQT DMSRKAFVFP KESDTSYVSL KAPLTKPLKA FTVCLHFYTE 70 80 90 100 110 120 LSSTRGYSIF SYATKRQDNE ILIFWSKDIG YSFTVGGSEI LFEVPEVTVA PVHICTSWES 130 140 150 160 170 180 ASGIVEFWVD GKPRVRKSLK KGYTVGAEAS IILGQEQDSF GGNFEGSQSL VGDIGNVNMW 190 200 210 220 DFVLSPDEIN TIYLGGPFSP NVLNWRALKY EVQGEVFTKP QLWP
	Isoform 2 [UniParc]. Checksum: A5E24599540DAA05		91	10,415
	10 20 30 40 50 60 MEKLLCFLVL TSLSHAFGQT DMSRKAFVFP KESDTSYVSL KAPLTKPLKA FTVCLHFYTE 70 80 90 LSSTRGPNVL NWRALKYEVQ GEVFTKPQLW P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genomic DNA sequence for human C-reactive protein." Lei K.-J., Liu T., Zon G., Soravia E., Liu T.-Y., Goldman N.D. J. Biol. Chem. 260:13377-13383(1985) [PubMed: 2997165] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Characterization of genomic and complementary DNA sequence of human C-reactive protein, and comparison with the complementary DNA sequence of serum amyloid P component." Woo P., Korenberg J.R., Whitehead A.S. J. Biol. Chem. 260:13384-13388(1985) [PubMed: 3840479] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Extrahepetic transcription of human C-reactive protein." Murphy T.M., Baum L., Beaman K. Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	Tenchini M.L., Marchetti L., Bossi E., Malcovati M., Lorenzetti R. Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[5]	"Controlled gene expression using acute phase response elements." Harraghy N. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	SeattleSNPs program for genomic applications Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Liver.
[9]	"Biosynthesis and postsynthetic processing of human C-reactive protein." Tucci A., Goldberger G., Whitehead A.S., Kay R.M., Woods D.E., Colten H.R. J. Immunol. 131:2416-2419(1983) [PubMed: 6685157] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-26.
[10]	"Isolation of human C-reactive protein complementary DNA and localization of the gene to chromosome 1." Whitehead A.S., Bruns G.A.P., Markham A.F., Colten H.R., Woods D.E. Science 221:69-71(1983) [PubMed: 6857266] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 144-175.
[11]	"Primary structure of human C-reactive protein." Oliveira E.B., Gotschlich E.C., Liu T.-Y. J. Biol. Chem. 254:489-502(1979) [PubMed: 762075] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-224.
[12]	"Partial amino-acid sequences of human and rabbit C-reactive proteins: homology with immunoglobulins and histocompatibility antigens." Osmand A.P., Gewurz H., Friedenson B. Proc. Natl. Acad. Sci. U.S.A. 74:1214-1218(1977) [PubMed: 403526] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-55.
[13]	"Selected expression profiling of full-length proteins and their variants in human plasma." Kiernan U.A., Nedelkov D., Tubbs K.A., Niederkofler E.E., Nelson R.W. Clin. Proteomics 1:7-16(2004) Cited for: MASS SPECTROMETRY.
[14]	"Comparative analyses of pentraxins: implications for protomer assembly and ligand binding." Srinivasan N., White H.E., Emsley J., Wood S.P., Pepys M.B., Blundell T.L. Structure 2:1017-1027(1994) [PubMed: 7881902] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[15]	"Three dimensional structure of human C-reactive protein." Shrive A.K., Cheetham G.M.T., Holden D., Myles D.A.A., Turnell W.G., Volanakis J.E., Pepys M.B., Bloomer A.C., Greenhough T.J. Nat. Struct. Biol. 3:346-353(1996) [PubMed: 8599761] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[16]	"The physiological structure of human C-reactive protein and its complex with phosphocholine." Thompson D., Pepys M.B., Wood S.P. Structure 7:169-177(1999) [PubMed: 10368284] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Wikipedia

C-reactive protein entry

SeattleSNPs

Protein Spotlight

No more Christmas pudding? - Issue 30 of January 2003

Cross-references

Sequence databases

EMBLGenBankDDBJ

M11880 Genomic DNA. Translation: AAB59526.1.
M11725 Genomic DNA. Translation: AAA52075.1.
X56692 mRNA. Translation: CAA40020.1.
X56214 mRNA. Translation: CAA39671.1.
AF442818 Genomic DNA. Translation: AAL48218.2.
AF449713 Genomic DNA. Translation: AAL40835.1.
AL445528 Genomic DNA. Translation: CAH73654.1.
AL445528 Genomic DNA. Translation: CAH73656.1.
BC020766 mRNA. Translation: AAH20766.1.
BC125135 mRNA. Translation: AAI25136.1.
M35163 mRNA. Translation: AAA52076.1.
K00518 mRNA. Translation: AAA52074.1.

PIR

CJHU. A24515.

RefSeq

NP_000558.2.

UniGene

Hs.695960
Hs.76452

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B09	X-ray	2.50	A/B/C/D/E	19-224	[»]
1CRV	model	-	A/B/C/D/E	19-224	[»]
1GNH	X-ray	3.00	A/B/C/D/E/F/G/H/I/J	19-224	[»]
1LJ7	X-ray	3.15	A/B/C/D/E/F/G/H/I/J	19-224	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P02741.

2-D gel databases

SWISS-2DPAGE

P02741.

DOSAC-COBS-2DPAGE

P02741.

Proteomic databases

PeptideAtlas

P02741.

Genome annotation databases

Ensembl

ENSG00000132693. Homo sapiens. [Contig view]

GeneID

1401.