MCP_BOVIN
ID MCP_BOVIN Reviewed; 361 AA.
AC Q6VE48; Q7YRJ3;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 25-MAY-2022, entry version 99.
DE RecName: Full=Membrane cofactor protein;
DE AltName: CD_antigen=CD46;
DE Flags: Precursor;
GN Name=CD46; Synonyms=MCP;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain endothelium;
RX PubMed=12125738; DOI=10.1093/jnen/61.7.597;
RA Shusta E.V., Zhu C., Boado R.J., Pardridge W.M.;
RT "Subtractive expression cloning reveals high expression of CD46 at the
RT blood-brain barrier.";
RL J. Neuropathol. Exp. Neurol. 61:597-604(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), PROTEIN SEQUENCE OF 49-69
RP AND 237-254, GLYCOSYLATION, TISSUE SPECIFICITY, AND INTERACTION WITH BOVINE
RP VIRAL DIARRHEA VIRUS.
RC TISSUE=Lymph node;
RX PubMed=14747544; DOI=10.1128/jvi.78.4.1792-1799.2004;
RA Maurer K., Krey T., Moennig V., Thiel H.-J., Ruemenapf T.;
RT "CD46 is a cellular receptor for bovine viral diarrhea virus.";
RL J. Virol. 78:1792-1799(2004).
CC -!- FUNCTION: Acts as a cofactor for complement factor I, a serine protease
CC which protects autologous cells against complement-mediated injury by
CC cleaving C3b and C4b deposited on host tissue. May be involved in the
CC fusion of the spermatozoa with the oocyte during fertilization. May act
CC as a costimulatory factor for T-cells which induces the differentiation
CC of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune
CC responses by secreting interleukin-10, and therefore are thought to
CC prevent autoimmunity (By similarity). In case of bovine viral diarrhea
CC virus (BVDV) infection, involved in virus attachment to cells.
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with C3b. Interacts with C4b. Interacts with
CC moesin/MSN. {ECO:0000250|UniProtKB:P15529}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome
CC inner membrane {ECO:0000250}; Single-pass type I membrane protein
CC {ECO:0000250}. Note=Inner acrosomal membrane of spermatozoa.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6VE48-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6VE48-2; Sequence=VSP_019033;
CC Name=3;
CC IsoId=Q6VE48-3; Sequence=VSP_019034;
CC -!- TISSUE SPECIFICITY: Highly expressed at the blood-brain barrier.
CC Broadly expressed, with highest levels in thymus and spleen (at protein
CC level). {ECO:0000269|PubMed:12125738, ECO:0000269|PubMed:14747544}.
CC -!- DOMAIN: Sushi domains 3 and 4 are the most important for interaction
CC with C3b and C4b. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:14747544}.
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DR EMBL; AY333119; AAP92712.1; -; mRNA.
DR EMBL; AY342429; AAR04015.1; -; mRNA.
DR RefSeq; NP_001229493.1; NM_001242564.1.
DR RefSeq; NP_898903.2; NM_183080.2.
DR AlphaFoldDB; Q6VE48; -.
DR SMR; Q6VE48; -.
DR IntAct; Q6VE48; 1.
DR STRING; 9913.ENSBTAP00000007107; -.
DR PaxDb; Q6VE48; -.
DR PeptideAtlas; Q6VE48; -.
DR PRIDE; Q6VE48; -.
DR GeneID; 280851; -.
DR KEGG; bta:280851; -.
DR CTD; 4179; -.
DR eggNOG; ENOG502QPUC; Eukaryota.
DR InParanoid; Q6VE48; -.
DR OrthoDB; 1239877at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0009986; C:cell surface; IEA:InterPro.
DR GO; GO:0002079; C:inner acrosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045959; P:negative regulation of complement activation, classical pathway; IBA:GO_Central.
DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW.
DR GO; GO:0002456; P:T cell mediated immunity; IBA:GO_Central.
DR CDD; cd00033; CCP; 4.
DR InterPro; IPR017341; CD46.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00084; Sushi; 4.
DR PIRSF; PIRSF037971; TLX_CD46; 1.
DR SMART; SM00032; CCP; 4.
DR SUPFAM; SSF57535; SSF57535; 4.
DR PROSITE; PS50923; SUSHI; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Complement pathway; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Fertilization; Glycoprotein;
KW Immunity; Innate immunity; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Signal; Sushi; Transmembrane; Transmembrane helix.
FT SIGNAL 1..42
FT /evidence="ECO:0000255"
FT CHAIN 43..361
FT /note="Membrane cofactor protein"
FT /id="PRO_0000238968"
FT TOPO_DOM 43..311
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 43..104
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 105..168
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 169..234
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 235..294
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT DISULFID 107..149
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 135..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 171..219
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 200..232
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 237..279
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 265..292
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 324..361
FT /note="VLIGVGLLLCLYCCFCRQRKKGIYVTGESHRQDILFSL -> LLALDYCSAC
FT TAVFADRGRKGKQNVALRTPLIRIKQPLQQNR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12125738,
FT ECO:0000303|PubMed:14747544"
FT /id="VSP_019033"
FT VAR_SEQ 346..361
FT /note="IYVTGESHRQDILFSL -> KAECSATYTTYQDKATTATEQMN (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14747544"
FT /id="VSP_019034"
FT CONFLICT 23
FT /note="R -> L (in Ref. 1; AAP92712)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="S -> C (in Ref. 1; AAP92712)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="H -> R (in Ref. 1; AAP92712)"
FT /evidence="ECO:0000305"
FT CONFLICT 104..109
FT /note="KRRCPT -> RRQCPN (in Ref. 1; AAP92712)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="S -> N (in Ref. 2; AAR04015)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="S -> N (in Ref. 2; AAR04015)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="Q -> K (in Ref. 1; AAP92712)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="H -> Y (in Ref. 1; AAP92712)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="Y -> Q (in Ref. 1; AAP92712)"
FT /evidence="ECO:0000305"
FT MOD_RES Q6VE48-3:353
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES Q6VE48-3:356
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
SQ SEQUENCE 361 AA; 39391 MW; D8D877437E4DE772 CRC64;
MRASCTPLKA PLRRPERLAS SGRFAWVLLL APLLLLPTSS DACDDPPRFV SMKPQGTLKP
SYSPGEQIVY ECHLGFQPVT PGQVLALVCQ DNNTWSSLQE GCKKRRCPTL ADPTNGQVIL
VNGSTEFGSE VHYVCNNGYY LLGTNISYCE VSSGTGVNWS DNPPTCEKIL CQPPPEIQNG
KYTNSHKDVF EYNEVVTYSC DPSNGPDEYS LVGESKLTCI GNGEWSSQPP QCKVVKCVYP
AIEHGTIVSG FGPKYYYKAT VVLKCNEGFN LYGNSVVVCG ENSTWEPELP KCIKGHPPRP
TDASPPNGAE GLGAGYIVLV IVAVLIGVGL LLCLYCCFCR QRKKGIYVTG ESHRQDILFS
L
