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Protein

Complement C4-A

Gene

C4A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens.
Derived from proteolytic degradation of complement C4, C4a 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1125Responsible for effective binding to form amide bonds with immune aggregates or protein antigens1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionBlood group antigen
Biological processComplement pathway, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-166663 Initial triggering of complement
R-HSA-174577 Activation of C3 and C5
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-977606 Regulation of Complement cascade
SABIO-RKiP0C0L4

Names & Taxonomyi

Protein namesi
Recommended name:
Complement C4-A
Alternative name(s):
Acidic complement C4
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2
Cleaved into the following 6 chains:
Gene namesi
Name:C4A
Synonyms:CO4, CPAMD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000244731.7
HGNCiHGNC:1323 C4A
MIMi120810 gene
neXtProtiNX_P0C0L4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell projection, Secreted, Synapse

Pathology & Biotechi

Involvement in diseasei

Complement component 4A deficiency (C4AD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.
See also OMIM:614380
Systemic lupus erythematosus (SLE)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Interindividual copy-number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.
Disease descriptionA chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
See also OMIM:152700

Keywords - Diseasei

Disease mutation, Systemic lupus erythematosus

Organism-specific databases

DisGeNETi100293534
720
721
MalaCardsiC4A
MIMi120790 phenotype
152700 phenotype
614374 phenotype
614380 phenotype
OpenTargetsiENSG00000244731
Orphaneti117 Behcet disease
169147 Immunodeficiency due to an early component of complement deficiency
536 Systemic lupus erythematosus
PharmGKBiPA25903
PA25904

Chemistry databases

DrugBankiDB00028 Immune Globulin Human

Polymorphism and mutation databases

BioMutaiC4A
DMDMi476007827

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Add BLAST19
ChainiPRO_000000596620 – 675Complement C4 beta chainAdd BLAST656
PropeptideiPRO_0000005967676 – 6791 Publication4
ChainiPRO_0000005968680 – 1446Complement C4-A alpha chainAdd BLAST767
ChainiPRO_0000005969680 – 756C4a anaphylatoxinAdd BLAST77
ChainiPRO_0000005970757 – 1446C4b-AAdd BLAST690
ChainiPRO_0000042698957 – 1336C4d-AAdd BLAST380
PropeptideiPRO_00000059711447 – 14537
ChainiPRO_00000059721454 – 1744Complement C4 gamma chainAdd BLAST291

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi226N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi702 ↔ 728By similarity
Disulfide bondi703 ↔ 735By similarity
Disulfide bondi716 ↔ 736By similarity
Glycosylationi862N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei918Phosphoserine; by FAM20C1 Publication1
Cross-linki1010 ↔ 1013Isoglutamyl cysteine thioester (Cys-Gln)
Glycosylationi1244O-linked (GalNAc...) threonine1 Publication1
Glycosylationi1328N-linked (GlcNAc...) (complex) asparagine4 Publications1
Glycosylationi1391N-linked (GlcNAc...) asparagine3 Publications1
Modified residuei1417Sulfotyrosine1 Publication1
Modified residuei1420Sulfotyrosine1 Publication1
Modified residuei1422Sulfotyrosine1 Publication1
Disulfide bondi1595 ↔ 1673By similarity
Disulfide bondi1618 ↔ 1742By similarity

Post-translational modificationi

Prior to secretion, the single-chain precursor is enzymatically cleaved to yield non-identical chains alpha, beta and gamma. During activation, the alpha chain is cleaved by C1 into C4a and C4b, and C4b stays linked to the beta and gamma chains. Further degradation of C4b by C1 into the inactive fragments C4c and C4d blocks the generation of C3 convertase. The proteolytic cleavages often are incomplete so that many structural forms can be found in plasma.
N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan.8 Publications

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation, Thioester bond

Proteomic databases

EPDiP0C0L4
MaxQBiP0C0L4
PaxDbiP0C0L4
PeptideAtlasiP0C0L4
PRIDEiP0C0L4
ProteomicsDBi52292

PTM databases

CarbonylDBiP0C0L4
GlyConnecti651
iPTMnetiP0C0L4
PhosphoSitePlusiP0C0L4
UniCarbKBiP0C0L4

Miscellaneous databases

PMAP-CutDBiP0C0L4

Expressioni

Tissue specificityi

Complement component C4 is expressed at highest levels in the liver, at moderate levels in the adrenal cortex, adrenal medulla, thyroid gland,and the kidney, and at lowest levels in the heart, ovary, small intestine, thymus, pancreas and spleen. The extra-hepatic sites of expression may be important for the local protection and inflammatory response.1 Publication

Gene expression databases

BgeeiENSG00000244731 Expressed in 88 organ(s), highest expression level in right lobe of liver
GenevisibleiP0C0L4 HS

Organism-specific databases

HPAiCAB009811
CAB032603
HPA046356
HPA048287
HPA050103

Interactioni

Subunit structurei

Circulates in blood as a disulfide-linked trimer of an alpha, beta and gamma chain.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107181, 25 interactors
107182, 2 interactors
IntActiP0C0L4, 19 interactors
STRINGi9606.ENSP00000396688

Structurei

Secondary structure

11744
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP0C0L4
SMRiP0C0L4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0C0L4

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini702 – 736Anaphylatoxin-likePROSITE-ProRule annotationAdd BLAST35
Domaini1595 – 1742NTRPROSITE-ProRule annotationAdd BLAST148

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOGENOMiHOG000290712
HOVERGENiHBG107123
InParanoidiP0C0L4
KOiK03989
OMAiDFACYSP
OrthoDBiEOG091G00FL
PhylomeDBiP0C0L4
TreeFamiTF313285

Family and domain databases

CDDicd00017 ANATO, 1 hit
Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR000020 Anaphylatoxin/fibulin
IPR018081 Anaphylatoxin_comp_syst
IPR001840 Anaphylatoxn_comp_syst_dom
IPR037569 Complement_C4A
IPR013783 Ig-like_fold
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR001134 Netrin_domain
IPR018933 Netrin_module_non-TIMP
IPR008930 Terpenoid_cyclase/PrenylTrfase
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11412:SF134 PTHR11412:SF134, 1 hit
PfamiView protein in 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
PF10569 Thiol-ester_cl, 1 hit
PRINTSiPR00004 ANAPHYLATOXN
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SM00104 ANATO, 1 hit
SM00643 C345C, 1 hit
SUPFAMiSSF47686 SSF47686, 1 hit
SSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit
PS01177 ANAPHYLATOXIN_1, 1 hit
PS01178 ANAPHYLATOXIN_2, 1 hit
PS50189 NTR, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P0C0L4-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MRLLWGLIWA SSFFTLSLQK PRLLLFSPSV VHLGVPLSVG VQLQDVPRGQ
60 70 80 90 100
VVKGSVFLRN PSRNNVPCSP KVDFTLSSER DFALLSLQVP LKDAKSCGLH
110 120 130 140 150
QLLRGPEVQL VAHSPWLKDS LSRTTNIQGI NLLFSSRRGH LFLQTDQPIY
160 170 180 190 200
NPGQRVRYRV FALDQKMRPS TDTITVMVEN SHGLRVRKKE VYMPSSIFQD
210 220 230 240 250
DFVIPDISEP GTWKISARFS DGLESNSSTQ FEVKKYVLPN FEVKITPGKP
260 270 280 290 300
YILTVPGHLD EMQLDIQARY IYGKPVQGVA YVRFGLLDED GKKTFFRGLE
310 320 330 340 350
SQTKLVNGQS HISLSKAEFQ DALEKLNMGI TDLQGLRLYV AAAIIESPGG
360 370 380 390 400
EMEEAELTSW YFVSSPFSLD LSKTKRHLVP GAPFLLQALV REMSGSPASG
410 420 430 440 450
IPVKVSATVS SPGSVPEVQD IQQNTDGSGQ VSIPIIIPQT ISELQLSVSA
460 470 480 490 500
GSPHPAIARL TVAAPPSGGP GFLSIERPDS RPPRVGDTLN LNLRAVGSGA
510 520 530 540 550
TFSHYYYMIL SRGQIVFMNR EPKRTLTSVS VFVDHHLAPS FYFVAFYYHG
560 570 580 590 600
DHPVANSLRV DVQAGACEGK LELSVDGAKQ YRNGESVKLH LETDSLALVA
610 620 630 640 650
LGALDTALYA AGSKSHKPLN MGKVFEAMNS YDLGCGPGGG DSALQVFQAA
660 670 680 690 700
GLAFSDGDQW TLSRKRLSCP KEKTTRKKRN VNFQKAINEK LGQYASPTAK
710 720 730 740 750
RCCQDGVTRL PMMRSCEQRA ARVQQPDCRE PFLSCCQFAE SLRKKSRDKG
760 770 780 790 800
QAGLQRALEI LQEEDLIDED DIPVRSFFPE NWLWRVETVD RFQILTLWLP
810 820 830 840 850
DSLTTWEIHG LSLSKTKGLC VATPVQLRVF REFHLHLRLP MSVRRFEQLE
860 870 880 890 900
LRPVLYNYLD KNLTVSVHVS PVEGLCLAGG GGLAQQVLVP AGSARPVAFS
910 920 930 940 950
VVPTAAAAVS LKVVARGSFE FPVGDAVSKV LQIEKEGAIH REELVYELNP
960 970 980 990 1000
LDHRGRTLEI PGNSDPNMIP DGDFNSYVRV TASDPLDTLG SEGALSPGGV
1010 1020 1030 1040 1050
ASLLRLPRGC GEQTMIYLAP TLAASRYLDK TEQWSTLPPE TKDHAVDLIQ
1060 1070 1080 1090 1100
KGYMRIQQFR KADGSYAAWL SRDSSTWLTA FVLKVLSLAQ EQVGGSPEKL
1110 1120 1130 1140 1150
QETSNWLLSQ QQADGSFQDP CPVLDRSMQG GLVGNDETVA LTAFVTIALH
1160 1170 1180 1190 1200
HGLAVFQDEG AEPLKQRVEA SISKANSFLG EKASAGLLGA HAAAITAYAL
1210 1220 1230 1240 1250
TLTKAPVDLL GVAHNNLMAM AQETGDNLYW GSVTGSQSNA VSPTPAPRNP
1260 1270 1280 1290 1300
SDPMPQAPAL WIETTAYALL HLLLHEGKAE MADQASAWLT RQGSFQGGFR
1310 1320 1330 1340 1350
STQDTVIALD ALSAYWIASH TTEERGLNVT LSSTGRNGFK SHALQLNNRQ
1360 1370 1380 1390 1400
IRGLEEELQF SLGSKINVKV GGNSKGTLKV LRTYNVLDMK NTTCQDLQIE
1410 1420 1430 1440 1450
VTVKGHVEYT MEANEDYEDY EYDELPAKDD PDAPLQPVTP LQLFEGRRNR
1460 1470 1480 1490 1500
RRREAPKVVE EQESRVHYTV CIWRNGKVGL SGMAIADVTL LSGFHALRAD
1510 1520 1530 1540 1550
LEKLTSLSDR YVSHFETEGP HVLLYFDSVP TSRECVGFEA VQEVPVGLVQ
1560 1570 1580 1590 1600
PASATLYDYY NPERRCSVFY GAPSKSRLLA TLCSAEVCQC AEGKCPRQRR
1610 1620 1630 1640 1650
ALERGLQDED GYRMKFACYY PRVEYGFQVK VLREDSRAAF RLFETKITQV
1660 1670 1680 1690 1700
LHFTKDVKAA ANQMRNFLVR ASCRLRLEPG KEYLIMGLDG ATYDLEGHPQ
1710 1720 1730 1740
YLLDSNSWIE EMPSERLCRS TRQRAACAQL NDFLQEYGTQ GCQV
Length:1,744
Mass (Da):192,785
Last modified:April 3, 2013 - v2
Checksum:i9396A4CC4DA3602C
GO
Isoform 2 (identifier: P0C0L4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1458-1503: Missing.

Note: No experimental confirmation available.
Show »
Length:1,698
Mass (Da):187,704
Checksum:i6169C0C84E28C512
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2JPR0A0A0G2JPR0_HUMAN
Complement C4-A
C4A
1,744Annotation score:
A0A140TA32A0A140TA32_HUMAN
Complement C4-A
C4A
1,698Annotation score:
A0A140TA49A0A140TA49_HUMAN
Complement C4-A
C4A
1,698Annotation score:
A0A140TA44A0A140TA44_HUMAN
Complement C4-A
C4A
1,698Annotation score:

Sequence cautioni

The sequence AAB59537 differs from that shown. During cDNA synthesis, the 5' end has been inverted (PubMed:3838531).1 Publication
The sequence BAE06071 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti217A → V in AAI71786 (PubMed:15489334).Curated1
Sequence conflicti643A → S in AAH63289 (PubMed:15489334).Curated1
Sequence conflicti729R → W in AAH63289 (PubMed:15489334).Curated1
Sequence conflicti1013Q → E AA sequence (PubMed:6978711).Curated1
Sequence conflicti1013Q → E AA sequence (PubMed:3696167).Curated1
Sequence conflicti1013Q → E AA sequence (PubMed:6950384).Curated1
Sequence conflicti1109 – 1110SQ → IA AA sequence (PubMed:3696167).Curated2
Sequence conflicti1182K → I in AAH63289 (PubMed:15489334).Curated1
Sequence conflicti1245P → Q in AAH63289 (PubMed:15489334).Curated1
Sequence conflicti1271H → V AA sequence (PubMed:3696167).Curated1
Sequence conflicti1271H → V AA sequence (PubMed:6832377).Curated1
Sequence conflicti1300R → V AA sequence (PubMed:3696167).Curated1
Sequence conflicti1300R → V AA sequence (PubMed:6832377).Curated1
Sequence conflicti1419 – 1421Missing in AAB59537 (PubMed:6546707).Curated3
Sequence conflicti1635D → G in AAH12372 (PubMed:15489334).Curated1
Sequence conflicti1637R → S in AAI44547 (PubMed:15489334).Curated1
Sequence conflicti1637R → S in AAI46850 (PubMed:15489334).Curated1
Sequence conflicti1678E → G in AAI71786 (PubMed:15489334).Curated1
Sequence conflicti1704D → E in AAH12372 (PubMed:15489334).Curated1

Polymorphismi

The complement component C4 is the most polymorphic protein of the complement system. It is the product of 2 closely linked and highly homologous genes, C4A and C4B. Once polymorphic variation is discounted, the 2 isotypes differ by only 4 amino acids at positions 1120-1125: PCPVLD for C4A and LSPVIH for C4B. The 2 isotypes bear several antigenic determinants defining Chido/Rodgers blood group system [MIMi:614374]. Rodgers determinants are generally associated with C4A allotypes, and Chido with C4B. Variations at these loci involve not only nucleotide polymorphisms, but also gene number and gene size. Some individuals may lack either C4A, or C4B gene. Partial deficiency of C4A or C4B is the most commonly inherited immune deficiency known in humans with a combined frequency over 31% in the normal Caucasian population (PubMed:11367523). C4A6 allotype is deficient in hemolytic activity. Allotype C4A13 is infrequent. Common copy-number variants of C4A and C4B affecting expression of complement component C4 in the brain have been associated with schizophrenia risk (PubMed:26814963).2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069154141L → V. Corresponds to variant dbSNP:rs9296005Ensembl.1
Natural variantiVAR_019778347S → Y in allotype C4A3a, allotype C4A6. 3 PublicationsCorresponds to variant dbSNP:rs392610Ensembl.1
Natural variantiVAR_069155418V → A in allotype C4A4. 1 Publication1
Natural variantiVAR_001987477R → W in allotype C4A6. 1 Publication1
Natural variantiVAR_069156549H → P1 PublicationCorresponds to variant dbSNP:rs2229405Ensembl.1
Natural variantiVAR_001988726P → L in allotype C4A3a. 1 Publication1
Natural variantiVAR_019779727D → N1 Publication1
Natural variantiVAR_019780907A → T1 PublicationCorresponds to variant dbSNP:rs429329Ensembl.1
Natural variantiVAR_0691581073D → G in allotype C4A1, allotype C4A2. 3 PublicationsCorresponds to variant dbSNP:rs147162052Ensembl.1
Natural variantiVAR_0691591176N → S in allotype C4A1. 4 PublicationsCorresponds to variant dbSNP:rs17874654Ensembl.1
Natural variantiVAR_0019921201T → S in allotype C4A4. 1 Publication1
Natural variantiVAR_0019931207V → A in allotype C4A1, allotype C4A13. 3 PublicationsCorresponds to variant dbSNP:rs28357075Ensembl.1
Natural variantiVAR_0019941210L → R in allotype C4A1, allotype C4A13. 3 PublicationsCorresponds to variant dbSNP:rs28357076Ensembl.1
Natural variantiVAR_0019951286S → A in allotype C4A1, allotype C4A3a, allotype C4A6. 6 PublicationsCorresponds to variant dbSNP:rs201016130Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0462521458 – 1503Missing in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02403 mRNA Translation: AAB59537.1 Sequence problems.
M59815, M59816 Genomic DNA Translation: AAA51855.1
L26261 Genomic DNA Translation: AAA20121.2
AB209989 mRNA Translation: BAE06071.1 Different initiation.
AL645922 Genomic DNA No translation available.
AL844853 Genomic DNA No translation available.
AL929593 Genomic DNA No translation available.
CR936924 Genomic DNA No translation available.
BC012372 mRNA Translation: AAH12372.2
BC063289 mRNA Translation: AAH63289.1
BC144546 mRNA Translation: AAI44547.1
BC146673 mRNA Translation: AAI46674.1
BC146849 mRNA Translation: AAI46850.1
BC151204 mRNA Translation: AAI51205.1
BC171786 mRNA Translation: AAI71786.1
M14824 Genomic DNA Translation: AAA52292.1
X77491 Genomic DNA Translation: CAA54627.1
AY379925 Genomic DNA Translation: AAR89152.1
AY379926 Genomic DNA Translation: AAR89153.1
AY379927 Genomic DNA Translation: AAR89154.1
AY379928 Genomic DNA Translation: AAR89155.1
AY379929 Genomic DNA Translation: AAR89156.1
AY379930 Genomic DNA Translation: AAR89157.1
AY379931 Genomic DNA Translation: AAR89158.1
AY379932 Genomic DNA Translation: AAR89159.1
AY379933 Genomic DNA Translation: AAR89160.1
AY379934 Genomic DNA Translation: AAR89161.1
AY379935 Genomic DNA Translation: AAR89162.1
AY379960 Genomic DNA Translation: AAR89164.1
AY379962 Genomic DNA Translation: AAR89166.1
AY379963 Genomic DNA Translation: AAR89167.1
AY379964 Genomic DNA Translation: AAR89168.1
AY379965 Genomic DNA Translation: AAR89169.1
AY379966 Genomic DNA Translation: AAR89170.1
U77886 Genomic DNA Translation: AAK49810.1
V00502 mRNA Translation: CAA23760.1
K00830 mRNA Translation: AAA36229.1
CCDSiCCDS47404.1 [P0C0L4-1]
CCDS59005.1 [P0C0L4-2]
PIRiB20807
I56095 C4HU
RefSeqiNP_001002029.3, NM_001002029.3
NP_001239133.1, NM_001252204.1 [P0C0L4-2]
NP_009224.2, NM_007293.2 [P0C0L4-1]
UniGeneiHs.534847
Hs.720022

Genome annotation databases

EnsembliENST00000383325; ENSP00000372815; ENSG00000206340
ENST00000421274; ENSP00000388662; ENSG00000227746
ENST00000428956; ENSP00000396688; ENSG00000244731 [P0C0L4-1]
ENST00000498271; ENSP00000420212; ENSG00000244731 [P0C0L4-2]
GeneIDi720
721
KEGGihsa:720
hsa:721
UCSCiuc011doy.3 human [P0C0L4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

dbRBC/BGMUT

Blood group antigen gene mutation database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02403 mRNA Translation: AAB59537.1 Sequence problems.
M59815, M59816 Genomic DNA Translation: AAA51855.1
L26261 Genomic DNA Translation: AAA20121.2
AB209989 mRNA Translation: BAE06071.1 Different initiation.
AL645922 Genomic DNA No translation available.
AL844853 Genomic DNA No translation available.
AL929593 Genomic DNA No translation available.
CR936924 Genomic DNA No translation available.
BC012372 mRNA Translation: AAH12372.2
BC063289 mRNA Translation: AAH63289.1
BC144546 mRNA Translation: AAI44547.1
BC146673 mRNA Translation: AAI46674.1
BC146849 mRNA Translation: AAI46850.1
BC151204 mRNA Translation: AAI51205.1
BC171786 mRNA Translation: AAI71786.1
M14824 Genomic DNA Translation: AAA52292.1
X77491 Genomic DNA Translation: CAA54627.1
AY379925 Genomic DNA Translation: AAR89152.1
AY379926 Genomic DNA Translation: AAR89153.1
AY379927 Genomic DNA Translation: AAR89154.1
AY379928 Genomic DNA Translation: AAR89155.1
AY379929 Genomic DNA Translation: AAR89156.1
AY379930 Genomic DNA Translation: AAR89157.1
AY379931 Genomic DNA Translation: AAR89158.1
AY379932 Genomic DNA Translation: AAR89159.1
AY379933 Genomic DNA Translation: AAR89160.1
AY379934 Genomic DNA Translation: AAR89161.1
AY379935 Genomic DNA Translation: AAR89162.1
AY379960 Genomic DNA Translation: AAR89164.1
AY379962 Genomic DNA Translation: AAR89166.1
AY379963 Genomic DNA Translation: AAR89167.1
AY379964 Genomic DNA Translation: AAR89168.1
AY379965 Genomic DNA Translation: AAR89169.1
AY379966 Genomic DNA Translation: AAR89170.1
U77886 Genomic DNA Translation: AAK49810.1
V00502 mRNA Translation: CAA23760.1
K00830 mRNA Translation: AAA36229.1
CCDSiCCDS47404.1 [P0C0L4-1]
CCDS59005.1 [P0C0L4-2]
PIRiB20807
I56095 C4HU
RefSeqiNP_001002029.3, NM_001002029.3
NP_001239133.1, NM_001252204.1 [P0C0L4-2]
NP_009224.2, NM_007293.2 [P0C0L4-1]
UniGeneiHs.534847
Hs.720022

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HZFX-ray2.30A957-1323[»]
4FXGX-ray3.75A/D20-675[»]
B/E680-1446[»]
C/F1454-1744[»]
4FXKX-ray3.60A20-675[»]
B680-1446[»]
C1454-1744[»]
4XAMX-ray4.20C/E757-1446[»]
D/F1454-1744[»]
5JPMX-ray3.75A/D20-675[»]
B/E680-1446[»]
C/F1454-1744[»]
5JPNX-ray3.60A20-675[»]
B680-1446[»]
C1455-1744[»]
5JTWX-ray3.50A/D20-675[»]
B/E757-1446[»]
C/F1454-1744[»]
ProteinModelPortaliP0C0L4
SMRiP0C0L4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107181, 25 interactors
107182, 2 interactors
IntActiP0C0L4, 19 interactors
STRINGi9606.ENSP00000396688

Chemistry databases

DrugBankiDB00028 Immune Globulin Human

PTM databases

CarbonylDBiP0C0L4
GlyConnecti651
iPTMnetiP0C0L4
PhosphoSitePlusiP0C0L4
UniCarbKBiP0C0L4

Polymorphism and mutation databases

BioMutaiC4A
DMDMi476007827

Proteomic databases

EPDiP0C0L4
MaxQBiP0C0L4
PaxDbiP0C0L4
PeptideAtlasiP0C0L4
PRIDEiP0C0L4
ProteomicsDBi52292

Protocols and materials databases

DNASUi721
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000383325; ENSP00000372815; ENSG00000206340
ENST00000421274; ENSP00000388662; ENSG00000227746
ENST00000428956; ENSP00000396688; ENSG00000244731 [P0C0L4-1]
ENST00000498271; ENSP00000420212; ENSG00000244731 [P0C0L4-2]
GeneIDi720
721
KEGGihsa:720
hsa:721
UCSCiuc011doy.3 human [P0C0L4-1]

Organism-specific databases

CTDi720
721
DisGeNETi100293534
720
721
EuPathDBiHostDB:ENSG00000244731.7
GeneCardsiC4A
HGNCiHGNC:1323 C4A
HPAiCAB009811
CAB032603
HPA046356
HPA048287
HPA050103
MalaCardsiC4A
MIMi120790 phenotype
120810 gene
152700 phenotype
614374 phenotype
614380 phenotype
neXtProtiNX_P0C0L4
OpenTargetsiENSG00000244731
Orphaneti117 Behcet disease
169147 Immunodeficiency due to an early component of complement deficiency
536 Systemic lupus erythematosus
PharmGKBiPA25903
PA25904
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOGENOMiHOG000290712
HOVERGENiHBG107123
InParanoidiP0C0L4
KOiK03989
OMAiDFACYSP
OrthoDBiEOG091G00FL
PhylomeDBiP0C0L4
TreeFamiTF313285

Enzyme and pathway databases

ReactomeiR-HSA-166663 Initial triggering of complement
R-HSA-174577 Activation of C3 and C5
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-977606 Regulation of Complement cascade
SABIO-RKiP0C0L4

Miscellaneous databases

ChiTaRSiC4A human
EvolutionaryTraceiP0C0L4
GeneWikiiC4A
PMAP-CutDBiP0C0L4
PROiPR:P0C0L4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000244731 Expressed in 88 organ(s), highest expression level in right lobe of liver
GenevisibleiP0C0L4 HS

Family and domain databases

CDDicd00017 ANATO, 1 hit
Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR000020 Anaphylatoxin/fibulin
IPR018081 Anaphylatoxin_comp_syst
IPR001840 Anaphylatoxn_comp_syst_dom
IPR037569 Complement_C4A
IPR013783 Ig-like_fold
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR001134 Netrin_domain
IPR018933 Netrin_module_non-TIMP
IPR008930 Terpenoid_cyclase/PrenylTrfase
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11412:SF134 PTHR11412:SF134, 1 hit
PfamiView protein in 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
PF10569 Thiol-ester_cl, 1 hit
PRINTSiPR00004 ANAPHYLATOXN
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SM00104 ANATO, 1 hit
SM00643 C345C, 1 hit
SUPFAMiSSF47686 SSF47686, 1 hit
SSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit
PS01177 ANAPHYLATOXIN_1, 1 hit
PS01178 ANAPHYLATOXIN_2, 1 hit
PS50189 NTR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCO4A_HUMAN
AccessioniPrimary (citable) accession number: P0C0L4
Secondary accession number(s): A6H8M8
, A6NHJ5, A7E2V2, B0QZR6, B0V2C8, B2RUT6, B7ZVZ6, P01028, P78445, Q13160, Q13906, Q14033, Q14835, Q4LE82, Q5JNX2, Q5JQM8, Q6P4R1, Q6U2E5, Q6U2E8, Q6U2F0, Q6U2F3, Q6U2F4, Q6U2F6, Q6U2F8, Q6U2G0, Q96EG2, Q96SA8, Q9NPK5, Q9UIP5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 3, 2013
Last modified: October 10, 2018
This is version 143 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Blood group antigen proteins
    Nomenclature of blood group antigens and list of entries
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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