CO4_RAT
ID CO4_RAT Reviewed; 1737 AA.
AC P08649; Q62895; Q8R403;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 25-MAR-2003, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Complement C4;
DE Contains:
DE RecName: Full=Complement C4 beta chain;
DE Contains:
DE RecName: Full=Complement C4 alpha chain;
DE Contains:
DE RecName: Full=C4a anaphylatoxin;
DE Contains:
DE RecName: Full=Complement C4 gamma chain;
DE Flags: Precursor;
GN Name=C4; Synonyms=C4a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Chen C.-B., Wallis R.;
RT "Substrate recognition by zymogen and activated forms of mannose-binding
RT protein-associated serine proteases.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-266.
RC STRAIN=Brown Norway;
RX PubMed=12136338; DOI=10.1007/s00251-002-0460-x;
RA Walter L., Hurt P., Himmelbauer H., Sudbrak R., Guenther E.;
RT "Physical mapping of the major histocompatibility complex class II and
RT class III regions of the rat.";
RL Immunogenetics 54:268-275(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1656-1737, AND INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Hepatic stellate cell;
RX PubMed=8805663;
RA Fimmel C.J., Brown K.E., O'Neill R., Kladney R.D.;
RT "Complement C4 protein expression by rat hepatic stellate cells.";
RL J. Immunol. 157:2601-2609(1996).
RN [4]
RP PROTEIN SEQUENCE OF 678-753.
RX PubMed=3262196; DOI=10.1016/0161-5890(88)90101-0;
RA Cui L.-X., Ferreri K., Hugli T.E.;
RT "Structural characterization of the C4a anaphylatoxin from rat.";
RL Mol. Immunol. 25:663-671(1988).
RN [5]
RP PROTEIN SEQUENCE OF 678-753.
RA Cui L.-X., Ferreri K., Hugli T.E.;
RT "Characterization of rat anaphylatoxins C4a and C5a.";
RL Fed. Proc. 44:991-991(1985).
CC -!- FUNCTION: Non-enzymatic component of C3 and C5 convertases and thus
CC essential for the propagation of the classical complement pathway.
CC Covalently binds to immunoglobulins and immune complexes and enhances
CC the solubilization of immune aggregates and the clearance of IC through
CC CR1 on erythrocytes (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Derived from proteolytic degradation of complement C4, C4a
CC anaphylatoxin is a mediator of local inflammatory processes. It induces
CC the contraction of smooth muscle, increases vascular permeability and
CC causes histamine release from mast cells and basophilic leukocytes.
CC -!- SUBUNIT: This protein is synthesized as a single-chain precursor and,
CC prior to secretion, is enzymatically cleaved to form a trimer of non-
CC identical chains alpha, beta and gamma.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0C0L4}. Synapse
CC {ECO:0000250|UniProtKB:P0C0L4}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P0C0L4}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P0C0L4}.
CC -!- INDUCTION: Induced in hepatic stellate cells by iron overload and by
CC gamma-interferon. {ECO:0000269|PubMed:8805663}.
CC -!- MISCELLANEOUS: C4 is a major histocompatibility complex class-III
CC protein.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA91231.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY149995; AAN72415.1; -; mRNA.
DR EMBL; AY091787; AAM14719.1; -; Genomic_DNA.
DR EMBL; U42719; AAA91231.1; ALT_FRAME; mRNA.
DR PIR; JL0036; JL0036.
DR RefSeq; NP_113692.2; NM_031504.3.
DR AlphaFoldDB; P08649; -.
DR SMR; P08649; -.
DR BioGRID; 246420; 1.
DR IntAct; P08649; 2.
DR MINT; P08649; -.
DR STRING; 10116.ENSRNOP00000037902; -.
DR MEROPS; I39.951; -.
DR GlyGen; P08649; 5 sites.
DR iPTMnet; P08649; -.
DR PhosphoSitePlus; P08649; -.
DR jPOST; P08649; -.
DR PaxDb; P08649; -.
DR PRIDE; P08649; -.
DR GeneID; 24233; -.
DR KEGG; rno:24233; -.
DR UCSC; RGD:620005; rat.
DR CTD; 720; -.
DR RGD; 620005; C4a.
DR eggNOG; KOG1366; Eukaryota.
DR InParanoid; P08649; -.
DR OrthoDB; 28894at2759; -.
DR PhylomeDB; P08649; -.
DR Reactome; R-RNO-166663; Initial triggering of complement.
DR Reactome; R-RNO-174577; Activation of C3 and C5.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR Reactome; R-RNO-977606; Regulation of Complement cascade.
DR SABIO-RK; P08649; -.
DR PRO; PR:P08649; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0005601; C:classical-complement-pathway C3/C5 convertase complex; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0001849; F:complement component C1q complex binding; ISO:RGD.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:0006956; P:complement activation; ISO:RGD.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:2000427; P:positive regulation of apoptotic cell clearance; ISO:RGD.
DR CDD; cd00017; ANATO; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 2.60.40.690; -; 1.
DR InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR InterPro; IPR011625; A2M_N_BRD.
DR InterPro; IPR011626; Alpha-macroglobulin_TED.
DR InterPro; IPR000020; Anaphylatoxin/fibulin.
DR InterPro; IPR018081; Anaphylatoxin_comp_syst.
DR InterPro; IPR001840; Anaphylatoxn_comp_syst_dom.
DR InterPro; IPR037569; Complement_C4A.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR001599; Macroglobln_a2.
DR InterPro; IPR019742; MacrogloblnA2_CS.
DR InterPro; IPR002890; MG2.
DR InterPro; IPR041555; MG3.
DR InterPro; IPR040839; MG4.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11412:SF86; PTHR11412:SF86; 1.
DR Pfam; PF00207; A2M; 1.
DR Pfam; PF07703; A2M_BRD; 1.
DR Pfam; PF07677; A2M_recep; 1.
DR Pfam; PF01821; ANATO; 1.
DR Pfam; PF01835; MG2; 1.
DR Pfam; PF17791; MG3; 1.
DR Pfam; PF17789; MG4; 1.
DR Pfam; PF01759; NTR; 1.
DR Pfam; PF07678; TED_complement; 1.
DR PRINTS; PR00004; ANAPHYLATOXN.
DR SMART; SM01360; A2M; 1.
DR SMART; SM01359; A2M_N_2; 1.
DR SMART; SM01361; A2M_recep; 1.
DR SMART; SM00104; ANATO; 1.
DR SMART; SM00643; C345C; 1.
DR SUPFAM; SSF47686; SSF47686; 1.
DR SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
DR PROSITE; PS01177; ANAPHYLATOXIN_1; 1.
DR PROSITE; PS01178; ANAPHYLATOXIN_2; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cleavage on pair of basic residues; Complement pathway;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Inflammatory response; Innate immunity; Reference proteome; Secreted;
KW Signal; Sulfation; Synapse; Thioester bond.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..673
FT /note="Complement C4 beta chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005979"
FT PROPEP 674..677
FT /evidence="ECO:0000250"
FT /id="PRO_0000005980"
FT CHAIN 678..1442
FT /note="Complement C4 alpha chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005981"
FT CHAIN 678..753
FT /note="C4a anaphylatoxin"
FT /id="PRO_0000005982"
FT PROPEP 1443..1446
FT /evidence="ECO:0000250"
FT /id="PRO_0000005983"
FT CHAIN 1447..1737
FT /note="Complement C4 gamma chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005984"
FT DOMAIN 700..734
FT /note="Anaphylatoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022"
FT DOMAIN 1588..1735
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT MOD_RES 1412
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 1414
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 1416
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 1676
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 664
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 743
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 1323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 700..726
FT /evidence="ECO:0000250"
FT DISULFID 701..733
FT /evidence="ECO:0000250"
FT DISULFID 714..734
FT /evidence="ECO:0000250"
FT DISULFID 1588..1666
FT /evidence="ECO:0000250"
FT DISULFID 1611..1735
FT /evidence="ECO:0000250"
FT CROSSLNK 1005..1008
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250"
FT CONFLICT 706
FT /note="T -> A (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1700
FT /note="T -> S (in Ref. 3; AAA91231)"
FT /evidence="ECO:0000305"
FT CONFLICT 1709
FT /note="R -> H (in Ref. 3; AAA91231)"
FT /evidence="ECO:0000305"
FT CONFLICT 1731
FT /note="S -> R (in Ref. 3; AAA91231)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1737 AA; 192163 MW; 67FA7BFA27A3DDFA CRC64;
MRLLWGLAWA FSFFASSLQK PRLLLFSPSV VNLGTPLSVG VQLLDAPAGQ EVKGSVYLRN
PTSGPCSPKK DFKLSSGNDF VLLRLEVPLK DVRSCGLFGL RRAPHIQLVA HSPWLKNTAS
KATETQGVNL LFSSRRGHIF VQTDQPIYNP GQRVRYRVFA LDQKMRPSTD TLTVTVENSH
GLRVRKKEVF APTSIFQDDF IIPDISEPGT WKISARFSDG LESNRSTHFE VKKYVLPNFE
VKLTPWKPYI LTVPSYREEI QLDVQARYVY GKPVQGVAYT RFALMDEQGK KSFLRGLETQ
TKLVEGQTHI SISRDQFQAA LGKVNTEIGD LEGLRLYAAV AVIESPGGEM EEAELTSWPF
VSSAFSLDLS HTKQHLVPGA PFLLQALVRE MSGSEASDVP VKVSATLLSG SDSKVLDFQQ
NTNGIGQVSF SIHVPPTITE LRLLVSAGSL YPAVAKLTVQ APPSRGPGFL SIEPLDLRSP
RVGDTFVLSL RTVGIPMPTF SHYYYMIISR GQIMAMSREP RRALTSISVL VDHHLAPSFY
FVAYFYHQGL PVANSLLINV QPGDCEGKLE LKVDGAKEYR NGDSMKLQLQ TDSEALVALG
AVDTALYAVG GRSHKPLDMS KVFEVMNSYN LGCGPGGGDD ALQVFQTAGL AFSDGDRLTQ
TKENLSCPKE KKSRQKRNVN FQKAISEKLG QYSSPDTKRC CQDGMTKLPM ARTCEQRAAR
VPQPACREPF LSCCKFAEDL RRNQTRSQAG LARAQDMLQE EDLIDEDDIL VRSFFPENWL
WRVEPVDRSK LLTVWLPDSL TTWEIHGVSL SKSKGLCVAK PTRVRVFREF HLHLRLPISV
RRFEQLELRP VLYNYLSEDV TVSVHVSPVE GLCLAGGGLL AQQVSVPAGS ARPVAFSVVP
TAAASIPLKV VARGSFTIGD AVSKILQIEK EGAIHREEIV YNLDPLNNLG RSLEIPGSSD
PNVIPDGDFS SFVRVTASEP LETLGSEGAL SPGGVASLLR LPRGCAEQTM IYLAPTLTAS
HYLDRTEQWS KLPPETKDHA VDLIQKGHMR IQQFRKKDGS FGAWLHRDSS TWLTAFVLKI
LSLAQEQIGD SPEKLQETAG WLLGQQLDDG SFHDPCPVIH RGMQGGLVGT DETVALTAFV
VIALHHGLAV FQDENSQQLK KRVEASITKA NSFLGQKASA GLLGAHASAI TAYALTLTKA
SEDLQNVAHN SLMAMAEETG ENLYWGSAIG SQDNVVSSTP APRNPSEPVP QAPALWIETT
AYGLLHLLLR EGKGEMADKV ATWLTHQGSF QGGFRSTQDT VVTLDALSAY WIASHTTEEK
ALNVTLSSMG RNGYKSHLLQ LNNHQVKGLE EELKFSLGST INVKVGGNSK GTLKILRTYN
VLDMKNTTCQ DLRIEVTVTG YVEYTREANE DYEYDYDMPA ADDPSVHSQP VTPLQLFEGR
RSRRRREAPK AADEQESRVQ YTVCIWRNGN LGLSGMAIAD ITLLSGFQAL RADLEKLTSL
SDRYVSHFET DGPHVLLYFD SVPTTRECVG FGALQEVAVG LVQPASAVLY DYYSPDHKCS
VFYAAPTKSK LLSTLCSADV CQCAEGKCPR QRRSLERGVE DKDGYRMKFA CYYPRVEYGF
QVKVLREDSR AAFRLFETKI TQVLHFTKDA KASIGQTRNF LVRASCRLRL EPSKEYLIMG
MDGVTSDLKG DPQYLLDSNT WIEEMPSERL CRSTRQRAAC GQLNDFLQEY SSQGCQV
