P06684 (CO5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Complement C5

Alternative name(s):
Hemolytic complement

Cleaved into the following 4 chains:

1. Complement C5 beta chain
2. Complement C5 alpha chain
3. C5a anaphylatoxin
4. Complement C5 alpha' chain

Gene names

Name:	C5
Synonyms:	Hc

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1680 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	Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled. Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis).
Subunit structure	C5 precursor is first processed by the removal of 4 basic residues, forming two chains, beta and alpha, linked by a disulfide bond. C5 convertase activates C5 by cleaving the alpha chain, releasing C5a anaphylatoxin and generating C5b (beta chain + alpha' chain).
Subcellular location	Secreted.
Sequence similarities	Contains 1 anaphylatoxin-like domain. Contains 1 NTR domain.

Ontologies

Keywords
Biological process	Complement alternate pathway Complement pathway Cytolysis Immunity Inflammatory response Innate immunity
Cellular component	Membrane attack complex Secreted
Domain	Signal
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular calcium ion homeostasis Inferred from electronic annotation. Source: Compara chemotaxis Inferred from electronic annotation. Source: Compara complement activation, alternative pathway Inferred from electronic annotation. Source: UniProtKB-KW complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW cytolysis Inferred from electronic annotation. Source: UniProtKB-KW glucose homeostasis Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from genetic interaction PubMed 18947875. Source: MGI induction of apoptosis Inferred from electronic annotation. Source: Compara leukocyte migration involved in inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of dopamine secretion Inferred from electronic annotation. Source: Compara negative regulation of endopeptidase activity Inferred from electronic annotation. Source: GOC negative regulation of macrophage chemotaxis Inferred from electronic annotation. Source: Compara negative regulation of norepinephrine secretion Inferred from electronic annotation. Source: Compara positive regulation of angiogenesis Inferred from mutant phenotype PubMed 16452172. Source: BHF-UCL positive regulation of chemokine secretion Inferred from electronic annotation. Source: Compara positive regulation of chemotaxis Inferred from electronic annotation. Source: Compara positive regulation vascular endothelial growth factor production Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: InterPro membrane attack complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	endopeptidase inhibitor 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 – 18	18
	Chain	19 – 674	656	Complement C5 beta chain		PRO_0000005991
	Propeptide	675 – 678	4			PRO_0000005992
	Chain	679 – 1680	1002	Complement C5 alpha chain		PRO_0000005993
	Chain	679 – 755	77	C5a anaphylatoxin		PRO_0000005994
	Chain	756 – 1680	925	Complement C5 alpha' chain		PRO_0000005995
Regions
	Domain	702 – 736	35	Anaphylatoxin-like
	Domain	1536 – 1679	144	NTR
Amino acid modifications
	Glycosylation	427	1	N-linked (GlcNAc...) Ref.5 Ref.6
	Glycosylation	915	1	N-linked (GlcNAc...) Potential
	Glycosylation	1119	1	N-linked (GlcNAc...) Potential
	Glycosylation	1633	1	N-linked (GlcNAc...) Potential
	Disulfide bond	702 ↔ 728		By similarity
	Disulfide bond	703 ↔ 735		By similarity
	Disulfide bond	715 ↔ 736		By similarity
	Disulfide bond	1536 ↔ 1609		By similarity
	Disulfide bond	1557 ↔ 1679		By similarity
Natural variations
	Natural variant	216	1	Y → L in defective variant C5D.
	Natural variant	217 – 1680	1464	Missing in defective variant C5D.

Sequences

	Sequence		Length	Mass (Da)
	P06684 [UniParc]. Last modified November 1, 1990. Version 2. Checksum: 81EB5A16FAC7D95C	FASTA	1,680	188,878
	10 20 30 40 50 60 MGLWGILCLL IFLDKTWGQE QTYVISAPKI LRVGSSENVV IQVHGYTEAF DATLSLKSYP 70 80 90 100 110 120 DKKVTFSSGY VNLSPENKFQ NAALLTLQPN QVPREESPVS HVYLEVVSKH FSKSKKIPIT 130 140 150 160 170 180 YNNGILFIHT DKPVYTPDQS VKIRVYSLGD DLKPAKRETV LTFIDPEGSE VDIVEENDYT 190 200 210 220 230 240 GIISFPDFKI PSNPKYGVWT IKANYKKDFT TTGTAYFEIK EYVLPRFSVS IELERTFIGY 250 260 270 280 290 300 KNFKNFEITV KARYFYNKVV PDAEVYAFFG LREDIKDEEK QMMHKATQAA KLVDGVAQIS 310 320 330 340 350 360 FDSETAVKEL SYNSLEDLNN KYLYIAVTVT ESSGGFSEEA EIPGVKYVLS PYTLNLVATP 370 380 390 400 410 420 LFVKPGIPFS IKAQVKDSLE QAVGGVPVTL MAQTVDVNQE TSDLETKRSI THDTDGVAVF 430 440 450 460 470 480 VLNLPSNVTV LKFEIRTDDP ELPEENQASK EYEAVAYSSL SQSYIYIAWT ENYKPMLVGE 490 500 510 520 530 540 YLNIMVTPKS PYIDKITHYN YLILSKGKIV QYGTREKLFS STYQNINIPV TQNMVPSARL 550 560 570 580 590 600 LVYYIVTGEQ TAELVADAVW INIEEKCGNQ LQVHLSPDEY VYSPGQTVSL DMVTEADSWV 610 620 630 640 650 660 ALSAVDRAVY KVQGNAKRAM QRVFQALDEK SDLGCGAGGG HDNADVFHLA GLTFLTNANA 670 680 690 700 710 720 DDSHYRDDSC KEILRSKRNL HLLRQKIEEQ AAKYKHSVPK KCCYDGARVN FYETCEERVA 730 740 750 760 770 780 RVTIGPLCIR AFNECCTIAN KIRKESPHKP VQLGRIHIKT LLPVMKADIR SYFPESWLWE 790 800 810 820 830 840 IHRVPKRKQL QVTLPDSLTT WEIQGIGISD NGICVADTLK AKVFKEVFLE MNIPYSVVRG 850 860 870 880 890 900 EQIQLKGTVY NYMTSGTKFC VKMSAVEGIC TSGSSAASLH TSRPSRCVFQ RIEGSSSHLV 910 920 930 940 950 960 TFTLLPLEIG LHSINFSLET SFGKDILVKT LRVVPEGVKR ESYAGVILDP KGIRGIVNRR 970 980 990 1000 1010 1020 KEFPYRIPLD LVPKTKVERI LSVKGLLVGE FLSTVLSKEG INILTHLPKG SAEAELMSIA 1030 1040 1050 1060 1070 1080 PVFYVFHYLE AGNHWNIFYP DTLSKRQSLE KKIKQGVVSV MSYRNADYSY SMWKGASAST 1090 1100 1110 1120 1130 1140 WLTAFALRVL GQVAKYVKQD ENSICNSLLW LVEKCQLENG SFKENSQYLP IKLQGTLPAE 1150 1160 1170 1180 1190 1200 AQEKTLYLTA FSVIGIRKAV DICPTMKIHT ALDKADSFLL ENTLPSKSTF TLAIVAYALS 1210 1220 1230 1240 1250 1260 LGDRTHPRFR LIVSALRKEA FVKGDPPIYR YWRDTLKRPD SSVPSSGTAG MVETTAYALL 1270 1280 1290 1300 1310 1320 ASLKLKDMNY ANPIIKWLSE EQRYGGGFYS TQDTINAIEG LTEYSLLLKQ IHLDMDINVA 1330 1340 1350 1360 1370 1380 YKHEGDFHKY KVTEKHFLGR PVEVSLNDDL VVSTGYSSGL ATVYVKTVVH KISVSEEFCS 1390 1400 1410 1420 1430 1440 FYLKIDTQDI EASSHFRLSD SGFKRIIACA SYKPSKEEST SGSSHAVMDI SLPTGIGANE 1450 1460 1470 1480 1490 1500 EDLRALVEGV DQLLTDYQIK DGHVILQLNS IPSRDFLCVR FRIFELFQVG FLNPATFTVY 1510 1520 1530 1540 1550 1560 EYHRPDKQCT MIYSISDTRL QKVCEGAACT CVEADCAQLQ AEVDLAISAD SRKEKACKPE 1570 1580 1590 1600 1610 1620 TAYAYKVRIT SATEENVFVK YTATLLVTYK TGEAADENSE VTFIKKMSCT NANLVKGKQY 1630 1640 1650 1660 1670 1680 LIMGKEVLQI KHNFSFKYIY PLDSSTWIEY WPTDTTCPSC QAFVENLNNF AEDLFLNSCE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deficiency of the murine fifth complement component (C5). A 2-base pair gene deletion in a 5'-exon." Wetsel R.A., Fleischer D.T., Haviland D.L. J. Biol. Chem. 265:2435-2440(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Primary structure of the fifth component of murine complement." Wetsel R.A., Ogata R.T., Tack B.F. Biochemistry 26:737-743(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 41-1680.
[4]	"Structure of the murine fifth complement component (C5) gene. A large, highly interrupted gene with a variant donor splice site and organizational homology with the third and fourth complement component genes." Haviland D.L., Haviland J.C., Fleischer D.T., Wetsel R.A. J. Biol. Chem. 266:11818-11825(1991) [PubMed] [Europe PMC] [Abstract] Cited for: GENE STRUCTURE.
[5]	"Proteome-wide characterization of N-glycosylation events by diagonal chromatography." Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K. J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-427, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Plasma.
[6]	"Enhanced analysis of the mouse plasma proteome using cysteine-containing tryptic glycopeptides." Bernhard O.K., Kapp E.A., Simpson R.J. J. Proteome Res. 6:987-995(2007) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-427, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Plasma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M35525 mRNA. Translation: AAA37349.1. M35526 mRNA. Translation: AAA37348.1. AL845534 Genomic DNA. Translation: CAM17901.1.
IPI	IPI00330833.
PIR	C5MS. A35530.
RefSeq	NP_034536.1. NM_010406.2.
UniGene	Mm.2168.
3D structure databases
ProteinModelPortal	P06684.
SMR	P06684. Positions 22-673, 683-743.
ModBase	Search...
Protein family/group databases
MEROPS	I39.952.
PTM databases
PhosphoSite	P06684.
Proteomic databases
PaxDb	P06684.
PRIDE	P06684.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000028233; ENSMUSP00000028233; ENSMUSG00000026874.
GeneID	15139.
KEGG	mmu:15139.
UCSC	uc008jjn.2. mouse.
Organism-specific databases
CTD	15139.
MGI	MGI:96031. Hc.
Phylogenomic databases
eggNOG	NOG241555.
GeneTree	ENSGT00560000077078.
HOGENOM	HOG000231860.
HOVERGEN	HBG098067.
InParanoid	A2AS36.
KO	K03994.
OMA	VFYVFHY.
OrthoDB	EOG4S1T6B.
Gene expression databases
ArrayExpress	P06684.
Bgee	P06684.
CleanEx	MM_HC.
Genevestigator	P06684.
GermOnline	ENSMUSG00000026874. Mus musculus.
Family and domain databases
Gene3D	1.20.91.20. 1 hit. 2.60.40.690. 1 hit.
InterPro	IPR009048. A-macroglobulin_rcpt-bd. IPR011626. A2M_comp. IPR002890. A2M_N. IPR011625. A2M_N_2. IPR000020. Anaphylatoxin/fibulin. IPR018081. Anaphylatoxin_. IPR001599. Macroglobln_a2. IPR001134. Netrin_domain. IPR018933. Netrin_module_non-TIMP. IPR008930. Terpenoid_cyclase/PrenylTrfase. IPR008993. TIMP-like_OB-fold. [Graphical view]
Pfam	PF00207. A2M. 1 hit. PF07678. A2M_comp. 1 hit. PF01835. A2M_N. 1 hit. PF07703. A2M_N_2. 1 hit. PF07677. A2M_recep. 1 hit. PF01821. ANATO. 1 hit. PF01759. NTR. 1 hit. [Graphical view]
SMART	SM00104. ANATO. 1 hit. SM00643. C345C. 1 hit. [Graphical view]
SUPFAM	SSF49410. AM_receptor_bind. 1 hit. SSF47686. Anaphylatoxin. 1 hit. SSF48239. Terp_cyc_toroid. 1 hit. SSF50242. TIMP_like. 1 hit.
PROSITE	PS00477. ALPHA_2_MACROGLOBULIN. False negative. PS01177. ANAPHYLATOXIN_1. 1 hit. PS01178. ANAPHYLATOXIN_2. 1 hit. PS50189. NTR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	287602.
SOURCE	Search...

Entry information

Entry name

CO5_MOUSE

Accession

Primary (citable) accession number: P06684
Secondary accession number(s): A2AS36

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	November 1, 1990
Last modified:	May 1, 2013
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program