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P04003 (C4BPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. 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·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C4b-binding protein alpha chain

Short name=C4bp
Alternative name(s):
Proline-rich protein
Short name=PRP
Gene names
Name:C4BPA
Synonyms:C4BP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length597 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. Alpha chain binds C4b. It interacts also with anticoagulant protein S and with serum amyloid P component.

Subunit structure

Disulfide-linked complex of alpha and beta chains of 3 possible sorts: a 570 kDa complex of 7 alpha chains and 1 beta chain, a 530 kDa homoheptamer of alpha chains or a 500 kDa complex of 6 alpha chains and 1 beta chain. The central body of the alpha chain homopolymer supports tentacles, each with the binding site for C4b at the end.

Subcellular location

Secreted.

Tissue specificity

Chylomicrons in the plasma.

Sequence similarities

Contains 8 Sushi (CCP/SCR) domains.

Caution

It is uncertain whether Met-1 or Met-17 is the initiator.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

arp4P130505EBI-978348,EBI-978341From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4848 Ref.9
Chain49 – 597549C4b-binding protein alpha chain
PRO_0000005888

Regions

Domain49 – 11062Sushi 1
Domain111 – 17262Sushi 2
Domain173 – 23664Sushi 3
Domain237 – 29660Sushi 4
Domain297 – 36266Sushi 5
Domain363 – 42462Sushi 6
Domain425 – 48258Sushi 7
Domain483 – 54058Sushi 8

Amino acid modifications

Glycosylation2211N-linked (GlcNAc...) Ref.8 Ref.11 Ref.12
Glycosylation5061N-linked (GlcNAc...) Ref.8 Ref.10 Ref.11 Ref.12
Glycosylation5281N-linked (GlcNAc...) Ref.8 Ref.10
Disulfide bond50 ↔ 96 Ref.14
Disulfide bond81 ↔ 108 Ref.14
Disulfide bond113 ↔ 154 Ref.14
Disulfide bond140 ↔ 170 Ref.14
Disulfide bond175 ↔ 217 By similarity
Disulfide bond203 ↔ 234 By similarity
Disulfide bond239 ↔ 281 By similarity
Disulfide bond267 ↔ 294 By similarity
Disulfide bond299 ↔ 348 By similarity
Disulfide bond332 ↔ 360 By similarity
Disulfide bond365 ↔ 409 By similarity
Disulfide bond399 ↔ 422 By similarity
Disulfide bond426 ↔ 468 By similarity
Disulfide bond454 ↔ 480 By similarity
Disulfide bond484 ↔ 525 By similarity
Disulfide bond511 ↔ 538 By similarity
Disulfide bond546Interchain (with beta chain) Potential
Disulfide bond558Interchain (with beta chain) Potential

Natural variations

Natural variant41P → Q.
Corresponds to variant rs55867570 [ dbSNP | Ensembl ].
VAR_061123
Natural variant601A → V.
Corresponds to variant rs17020956 [ dbSNP | Ensembl ].
VAR_048815
Natural variant2401R → H.
Corresponds to variant rs45574833 [ dbSNP | Ensembl ].
VAR_061124
Natural variant3001I → T.
Corresponds to variant rs4844573 [ dbSNP | Ensembl ].
VAR_024420
Natural variant3571Y → H.
VAR_001978
Natural variant4731W → L.
Corresponds to variant rs1801341 [ dbSNP | Ensembl ].
VAR_012038

Secondary structure

.................. 597
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P04003 [UniParc].

Last modified October 1, 1993. Version 2.
Checksum: 67E03F2EA85A16DD

FASTA59767,033
        10         20         30         40         50         60 
MHPPKTPSGA LHRKRKMAAW PFSRLWKVSD PILFQMTLIA ALLPAVLGNC GPPPTLSFAA 

        70         80         90        100        110        120 
PMDITLTETR FKTGTTLKYT CLPGYVRSHS TQTLTCNSDG EWVYNTFCIY KRCRHPGELR 

       130        140        150        160        170        180 
NGQVEIKTDL SFGSQIEFSC SEGFFLIGST TSRCEVQDRG VGWSHPLPQC EIVKCKPPPD 

       190        200        210        220        230        240 
IRNGRHSGEE NFYAYGFSVT YSCDPRFSLL GHASISCTVE NETIGVWRPS PPTCEKITCR 

       250        260        270        280        290        300 
KPDVSHGEMV SGFGPIYNYK DTIVFKCQKG FVLRGSSVIH CDADSKWNPS PPACEPNSCI 

       310        320        330        340        350        360 
NLPDIPHASW ETYPRPTKED VYVVGTVLRY RCHPGYKPTT DEPTTVICQK NLRWTPYQGC 

       370        380        390        400        410        420 
EALCCPEPKL NNGEITQHRK SRPANHCVYF YGDEISFSCH ETSRFSAICQ GDGTWSPRTP 

       430        440        450        460        470        480 
SCGDICNFPP KIAHGHYKQS SSYSFFKEEI IYECDKGYIL VGQAKLSCSY SHWSAPAPQC 

       490        500        510        520        530        540 
KALCRKPELV NGRLSVDKDQ YVEPENVTIQ CDSGYGVVGP QSITCSGNRT WYPEVPKCEW 

       550        560        570        580        590 
ETPEGCEQVL TGKRLMQCLP NPEDVKMALE VYKLSLEIEQ LELQRDSARQ STLDKEL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the cDNA coding for proline-rich protein (PRP): identity of PRP as C4b-binding protein."
Matsuguchi T., Okamura S., Aso T., Sata T., Niho Y.
Biochem. Biophys. Res. Commun. 165:138-144(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Genomic organization of the alpha chain of the human C4b-binding protein gene."
Aso T., Okamura S., Matsuguchi T., Sakamoto N., Sata T., Niho Y.
Biochem. Biophys. Res. Commun. 174:222-227(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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].
Tissue: Lung.
[6]"Derivation of the sequence of the signal peptide in human C4b-binding protein and interspecies cross-hybridisation of the C4bp cDNA sequence."
Lintin S.J., Lewin A.R., Reid K.B.M.
FEBS Lett. 232:328-332(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-81.
[7]"Studies on the structure of the human C4b-binding protein gene."
Lintin S.J., Reid K.B.M.
FEBS Lett. 204:77-81(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 203-288.
[8]"Molecular cloning and characterization of the cDNA coding for C4b-binding protein, a regulatory protein of the classical pathway of the human complement system."
Chung L.P., Bentley D.R., Reid K.B.M.
Biochem. J. 230:133-141(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 80-597.
[9]"Amino acid sequence studies of human C4b-binding protein: N-terminal sequence analysis and alignment of the fragments produced by limited proteolysis with chymotrypsin and the peptides produced by cyanogen bromide treatment."
Chung L.P., Gagnon J., Reid K.B.M.
Mol. Immunol. 22:427-435(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 49-88.
[10]"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-506 AND ASN-528.
Tissue: Plasma.
[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-221 AND ASN-506.
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-221 AND ASN-506.
Tissue: Liver.
[13]"Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b."
Dahlback B., Smith C.A., Mueller-Eberhard H.J.
Proc. Natl. Acad. Sci. U.S.A. 80:3461-3465(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY ELECTRON MICROSCOPY, LIGAND-BINDING.
[14]"Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor."
Jenkins H.T., Mark L., Ball G., Persson J., Lindahl G., Uhrin D., Blom A.M., Barlow P.N.
J. Biol. Chem. 281:3690-3697(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 49-172, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M31452 mRNA. Translation: AAA36507.1.
M62486 expand/collapse EMBL AC list , M62475, M62476, M62477, M62478, M62479, M62480, M62481, M62482, M62484, M62485 Genomic DNA. Translation: AAA36506.1.
AK313164 mRNA. Translation: BAG35982.1.
CH471100 Genomic DNA. Translation: EAW93502.1.
CH471100 Genomic DNA. Translation: EAW93503.1.
BC022312 mRNA. Translation: AAH22312.1.
X07853 mRNA. Translation: CAA30701.1.
X04284 Genomic DNA. Translation: CAB51244.1.
X04296 Genomic DNA. Translation: CAA27839.1.
X02865 mRNA. Translation: CAA26617.1.
CCDSCCDS1477.1.
PIRNBHUC4. A33568.
RefSeqNP_000706.1. NM_000715.3.
XP_005273308.1. XM_005273251.1.
XP_005273309.1. XM_005273252.2.
UniGeneHs.1012.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2A55NMR-A49-172[»]
4B0FX-ray2.80A/B/C/D/E/F/G540-597[»]
ProteinModelPortalP04003.
SMRP04003. Positions 49-597.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107183. 8 interactions.
IntActP04003. 6 interactions.
STRING9606.ENSP00000356037.

PTM databases

PhosphoSiteP04003.

Polymorphism databases

DMDM416733.

Proteomic databases

MaxQBP04003.
PaxDbP04003.
PeptideAtlasP04003.
PRIDEP04003.

Protocols and materials databases

DNASU722.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367070; ENSP00000356037; ENSG00000123838.
GeneID722.
KEGGhsa:722.
UCSCuc001hfo.3. human.

Organism-specific databases

CTD722.
GeneCardsGC01P207277.
HGNCHGNC:1325. C4BPA.
HPAHPA000926.
HPA001578.
MIM120830. gene.
neXtProtNX_P04003.
PharmGKBPA25905.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG150577.
HOGENOMHOG000015324.
HOVERGENHBG004657.
InParanoidP04003.
KOK04002.
OMAVENETIG.
OrthoDBEOG725DH2.
PhylomeDBP04003.
TreeFamTF334137.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP04003.
BgeeP04003.
CleanExHS_C4BPA.
GenevestigatorP04003.

Family and domain databases

InterProIPR000436. Sushi_SCR_CCP.
[Graphical view]
PfamPF00084. Sushi. 8 hits.
[Graphical view]
SMARTSM00032. CCP. 8 hits.
[Graphical view]
SUPFAMSSF57535. SSF57535. 8 hits.
PROSITEPS50923. SUSHI. 8 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP04003.
GenomeRNAi722.
NextBio2938.
PROP04003.
SOURCESearch...

Entry information

Entry nameC4BPA_HUMAN
AccessionPrimary (citable) accession number: P04003
Secondary accession number(s): Q5VVQ8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 23, 1986
Last sequence update: October 1, 1993
Last modified: July 9, 2014
This is version 146 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

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 1

Human chromosome 1: entries, gene names and cross-references to MIM