P04003 (C4BPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C4b-binding protein alpha chain
Short name=C4bp

Alternative name(s):
Proline-rich protein
Short name=PRP

Gene names

Name:	C4BPA
Synonyms:	C4BP

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	597 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	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.

Ontologies

Keywords
Biological process	Complement pathway Immunity Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Sushi
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome regulation of complement activation Traceable author statement. Source: Reactome
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
arp4	P13050	5	EBI-978348,EBI-978341	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 48

48

Ref.7

Chain

49 – 597

549

C4b-binding protein alpha chain

PRO_0000005888

Regions

Domain

49 – 110

62

Sushi 1

Domain

111 – 172

62

Sushi 2

Domain

173 – 236

64

Sushi 3

Domain

237 – 296

60

Sushi 4

Domain

297 – 362

66

Sushi 5

Domain

363 – 424

62

Sushi 6

Domain

425 – 482

58

Sushi 7

Domain

483 – 540

58

Sushi 8

Amino acid modifications

Glycosylation

221

1

N-linked (GlcNAc...) Ref.6 Ref.9 Ref.10

Glycosylation

506

1

N-linked (GlcNAc...) Ref.6 Ref.8 Ref.9 Ref.10

Glycosylation

528

1

N-linked (GlcNAc...) Ref.6 Ref.8

Disulfide bond

50 ↔ 96

By similarity

Disulfide bond

81 ↔ 108

By similarity

Disulfide bond

113 ↔ 154

By similarity

Disulfide bond

140 ↔ 170

By similarity

Disulfide bond

175 ↔ 217

By similarity

Disulfide bond

203 ↔ 234

By similarity

Disulfide bond

239 ↔ 281

By similarity

Disulfide bond

267 ↔ 294

By similarity

Disulfide bond

299 ↔ 348

By similarity

Disulfide bond

332 ↔ 360

By similarity

Disulfide bond

365 ↔ 409

By similarity

Disulfide bond

399 ↔ 422

By similarity

Disulfide bond

426 ↔ 468

By similarity

Disulfide bond

454 ↔ 480

By similarity

Disulfide bond

484 ↔ 525

By similarity

Disulfide bond

511 ↔ 538

By similarity

Disulfide bond

546

Interchain (with beta chain) Potential

Disulfide bond

558

Interchain (with beta chain) Potential

Natural variations

Natural variant

4

1

P → Q.
Corresponds to variant rs55867570 [ dbSNP | Ensembl ].

VAR_061123

Natural variant

60

1

A → V.
Corresponds to variant rs17020956 [ dbSNP | Ensembl ].

VAR_048815

Natural variant

240

1

R → H.
Corresponds to variant rs45574833 [ dbSNP | Ensembl ].

VAR_061124

Natural variant

300

1

I → T.
Corresponds to variant rs4844573 [ dbSNP | Ensembl ].

VAR_024420

Natural variant

357

1

Y → H.

VAR_001978

Natural variant

473

1

W → L.
Corresponds to variant rs1801341 [ dbSNP | Ensembl ].

VAR_012038

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

597

Helix Strand Turn

Details...

Beta strand

85 – 87

3

Beta strand

98 – 103

6

Beta strand

108 – 110

3

Beta strand

131 – 133

3

Beta strand

158 – 160

3

Helix

547 – 555

9

Beta strand

558 – 561

4

Helix

562 – 589

28

Helix

591 – 596

6

Sequences

	Sequence		Length	Mass (Da)
	P04003 [UniParc]. Last modified October 1, 1993. Version 2. Checksum: 67E03F2EA85A16DD	FASTA	597	67,033
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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, MASS SPECTROMETRY. Tissue: Plasma.
[9]	"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, MASS SPECTROMETRY. Tissue: Plasma.
[10]	"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, MASS SPECTROMETRY. Tissue: Liver.
[11]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M31452 mRNA. Translation: AAA36507.1.
M62486 , M62475, M62476, M62477, M62478, M62479, M62480, M62481, M62482, M62484, M62485 Genomic DNA. Translation: AAA36506.1.
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.

IPI

IPI00021727.

PIR

NBHUC4. A33568.

RefSeq

NP_000706.1. NM_000715.3.

UniGene

Hs.1012.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A55	NMR	-	A	49-172	[»]
4B0F	X-ray	2.80	A/B/C/D/E/F/G	540-597	[»]

ProteinModelPortal

P04003.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04003. 6 interactions.

STRING

9606.ENSP00000356037.

PTM databases

PhosphoSite

P04003.

Polymorphism databases

DMDM

416733.

Proteomic databases

PaxDb

P04003.

PeptideAtlas

P04003.

PRIDE

P04003.

Protocols and materials databases

DNASU

722.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367070; ENSP00000356037; ENSG00000123838.

GeneID

722.

KEGG

hsa:722.

UCSC

uc001hfo.3. human.

Organism-specific databases

CTD

722.

GeneCards

GC01P207277.

HGNC

HGNC:1325. C4BPA.

HPA

HPA000926.
HPA001578.

MIM

120830. gene.

neXtProt

NX_P04003.

PharmGKB

PA25905.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG150577.

HOGENOM

HOG000015324.

HOVERGEN

HBG004657.

InParanoid

P04003.

KO

K04002.

OMA

VENETIG.

OrthoDB

EOG4N04DG.

PhylomeDB

P04003.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P04003.

Bgee

P04003.

CleanEx

HS_C4BPA.

Genevestigator

P04003.

GermOnline

ENSG00000123838. Homo sapiens.

Family and domain databases

InterPro

IPR000436. Sushi_SCR_CCP.
[Graphical view]

Pfam

PF00084. Sushi. 8 hits.
[Graphical view]

SMART

SM00032. CCP. 8 hits.
[Graphical view]

SUPFAM

SSF57535. Complement_control_module. 8 hits.

PROSITE

PS50923. SUSHI. 8 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P04003.

GenomeRNAi

722.

NextBio

2938.

SOURCE

Search...

Entry information

Entry name

C4BPA_HUMAN

Accession

Primary (citable) accession number: P04003

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 1986
Last sequence update:	October 1, 1993
Last modified:	May 1, 2013
This is version 135 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.