MCP_SAISC
ID MCP_SAISC Reviewed; 285 AA.
AC O62685; O19125;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 25-MAY-2022, entry version 67.
DE RecName: Full=Membrane cofactor protein;
DE AltName: CD_antigen=CD46;
DE Flags: Precursor; Fragment;
GN Name=CD46; Synonyms=MCP;
OS Saimiri sciureus (Common squirrel monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Saimiriinae; Saimiri.
OX NCBI_TaxID=9521;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Lymphocyte;
RX PubMed=9223509; DOI=10.1128/jvi.71.8.6144-6154.1997;
RA Hsu E.C., Doerig R.E., Sarangi F., Marcil A., Iorio C., Richardson C.D.;
RT "Artificial mutations and natural variations in the CD46 molecules from
RT human and monkey cells define regions important for measles virus
RT binding.";
RL J. Virol. 71:6144-6154(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-185 (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=9525611; DOI=10.1128/jvi.72.4.2905-2916.1998;
RA Hsu E.C., Sarangi F., Iorio C., Sidhu M.S., Udem S.A., Dillehay D.L.,
RA Xu W., Rota P.A., Bellini W.J., Richardson C.D.;
RT "A single amino acid change in the hemagglutinin protein of measles virus
RT determines its ability to bind CD46 and reveals another receptor on
RT marmoset B cells.";
RL J. Virol. 72:2905-2916(1998).
RN [3]
RP TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=12421914; DOI=10.4049/jimmunol.169.10.5405;
RA Riley R.C., Tannenbaum P.L., Abbott D.H., Atkinson J.P.;
RT "Inhibiting measles virus infection but promoting reproduction: an
RT explanation for splicing and tissue-specific expression of CD46.";
RL J. Immunol. 169:5405-5409(2002).
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. Also
CC acts as a costimulatory factor for T-cells which induces the
CC differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells
CC suppress immune responses by secreting interleukin-10, and therefore
CC are thought to prevent autoimmunity (By similarity). {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=2;
CC Name=1;
CC IsoId=O62685-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O62685-2; Sequence=VSP_019048, VSP_019049;
CC -!- TISSUE SPECIFICITY: Present in blood and sperm. Isoform 2, but not
CC isoform 1, is present at the erythrocyte membrane (at protein level).
CC {ECO:0000269|PubMed:12421914, ECO:0000269|PubMed:9223509}.
CC -!- DOMAIN: Sushi domains 3 and 4 are the most important for interaction
CC with C3b and C4b. {ECO:0000250}.
CC -!- PTM: N-glycosylated. Probably less N-glycosylated in testis.
CC {ECO:0000269|PubMed:12421914}.
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DR EMBL; U87919; AAB66819.1; -; mRNA.
DR EMBL; AF025483; AAC39671.1; -; mRNA.
DR AlphaFoldDB; O62685; -.
DR SMR; O62685; -.
DR GO; GO:0009986; C:cell surface; IEA:InterPro.
DR GO; GO:0002079; C:inner acrosomal membrane; IEA:UniProtKB-SubCell.
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:0007338; P:single fertilization; IEA:UniProtKB-KW.
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 Disulfide bond; Fertilization; Glycoprotein; Immunity; Innate immunity;
KW Membrane; Repeat; Signal; Sushi.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..285
FT /note="Membrane cofactor protein"
FT /id="PRO_0000238977"
FT DOMAIN 35..96
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 97..159
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 160..225
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 226..285
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT DISULFID 99..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 127..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 162..210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 191..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 228..270
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 256..283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 33
FT /note="D -> E (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9223509"
FT /id="VSP_019048"
FT VAR_SEQ 34..96
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9223509"
FT /id="VSP_019049"
FT NON_TER 285
SQ SEQUENCE 285 AA; 31664 MW; C7D465C62DB9755A CRC64;
MAPPSRRECP FPSRRFPGLF LAALALLLSS RSDACGPPPT FVAMELTSRP KPYYKVGEQV
EYDCKKGYHH FAPFLTHTVC DRNHTWLPIS DAPCVKKVCH YIPNPAHGQA ILANGTYSFG
NQLHFICNDG YYLIGKAILY CELKGSDAVW SGRPPICQKI LCKPPPTIKN GKHTFSEVDV
FEYLDAVTYS CDPAPGPDPF SLVGESTIYC RDSLGWSGDP PECKVVKCRF PVIENGRQTA
GFGIKFYYNA AVMFECYEGF HIIGSDTIVC NSNSTWDPPV PKCVK
