MCP_PIG
ID MCP_PIG Reviewed; 363 AA.
AC O02839;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 25-MAY-2022, entry version 89.
DE RecName: Full=Membrane cofactor protein;
DE AltName: CD_antigen=CD46;
DE Flags: Precursor;
GN Name=CD46; Synonyms=MCP;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Aortic endothelium;
RX PubMed=9199970; DOI=10.1093/intimm/9.6.869;
RA Toyomura K., Fujimura T., Murakami H., Natsume T., Shigehisa T., Inoue N.,
RA Takeda J., Kinoshita T.;
RT "Molecular cloning of a pig homologue of membrane cofactor protein
RT (CD46).";
RL Int. Immunol. 9:869-876(1997).
RN [2]
RP PROTEIN SEQUENCE OF 45-72, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP FUNCTION, AND GLYCOSYLATION AT ASN-60.
RX PubMed=9029106;
RA van den Berg C.W., Perez de la Lastra J.M., Llanes D., Morgan B.P.;
RT "Purification and characterization of the pig analogue of human membrane
RT cofactor protein (CD46/MCP).";
RL J. Immunol. 158:1703-1709(1997).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=10469245; DOI=10.1046/j.1365-2567.1999.00830.x;
RA Perez de la Lastra J.M., Hanna S.M., Morgan B.P.;
RT "Distribution of membrane cofactor protein (MCP/CD46) on pig tissues.
RT Relevance To xenotransplantation.";
RL Immunology 98:144-151(1999).
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. {ECO:0000269|PubMed:9029106,
CC ECO:0000269|PubMed:9199970}.
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=2;
CC Name=1;
CC IsoId=O02839-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O02839-2; Sequence=VSP_019040;
CC -!- TISSUE SPECIFICITY: Broadly expressed. Expressed on erythrocytes,
CC leukocytes, granulocytes, platelets, vascular endothelial cells and
CC kidney epithelial cells. Not or weakly expressed in muscle cells and
CC skin (at protein level). {ECO:0000269|PubMed:10469245,
CC ECO:0000269|PubMed:9029106, ECO:0000269|PubMed:9199970}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9029106}.
CC -!- PTM: May be O-glycosylated. {ECO:0000269|PubMed:9029106}.
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DR EMBL; D70897; BAA20476.1; -; mRNA.
DR RefSeq; NP_999053.1; NM_213888.1. [O02839-1]
DR AlphaFoldDB; O02839; -.
DR SMR; O02839; -.
DR iPTMnet; O02839; -.
DR PeptideAtlas; O02839; -.
DR PRIDE; O02839; -.
DR GeneID; 396922; -.
DR KEGG; ssc:396922; -.
DR CTD; 4179; -.
DR InParanoid; O02839; -.
DR OrthoDB; 1239877at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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; IDA:AgBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; IDA:AgBase.
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:0045957; P:negative regulation of complement activation, alternative pathway; IDA:AgBase.
DR GO; GO:0045959; P:negative regulation of complement activation, classical pathway; IDA:AgBase.
DR GO; GO:0006508; P:proteolysis; IDA:AgBase.
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; Reference proteome; Repeat; Signal;
KW Sushi; Transmembrane; Transmembrane helix.
FT SIGNAL 1..44
FT /evidence="ECO:0000269|PubMed:9029106"
FT CHAIN 45..363
FT /note="Membrane cofactor protein"
FT /id="PRO_0000238972"
FT TOPO_DOM 45..329
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 330..350
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 351..363
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 45..105
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 106..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 REGION 290..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..319
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:9029106"
FT CARBOHYD 86
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT DISULFID 108..150
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 136..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 312..329
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9199970"
FT /id="VSP_019040"
FT CONFLICT 58
FT /note="F -> V (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 363 AA; 39692 MW; 8A5FF329B8E03153 CRC64;
MMAFCALRKA LPCRPENPFS SRCFVEILWV SLALVFLLPM PSDACDEPPK FESMRPQFLN
TTYRPGDRVE YECRPGFQPM VPALPTFSVC QDDNTWSPLQ EACRRKACSN LPDPLNGQVS
YPNGDMLFGS KAQFTCNTGF YIIGAETVYC QVSGNVMAWS EPSPLCEKIL CKPPGEIPNG
KYTNSHKDVF EYNEVVTYSC LSSTGPDEFS LVGESSLFCI GKDEWSSDPP ECKVVKCPYP
VVPNGEIVSG FGSKFYYKAE VVFKCNAGFT LHGRDTIVCG ANSTWEPEMP QCIKDSKPTD
PPATPGPSHP GPPSPSDASP PKDAESLDGG IIAAIVVGVL AAIAVIAGGV YFFHHKYNKK
RSK
