MCP_CALJA
ID MCP_CALJA Reviewed; 392 AA.
AC Q8HYX8; O19123; Q8HYX7; Q8HYX9; Q8HYY0; Q8HYY1;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Membrane cofactor protein;
DE AltName: CD_antigen=CD46;
DE Flags: Precursor;
GN Name=CD46; Synonyms=MCP;
OS Callithrix jacchus (White-tufted-ear marmoset).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Callitrichinae; Callithrix; Callithrix.
OX NCBI_TaxID=9483;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-285 (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 31-160 (ISOFORMS 1/3), NUCLEOTIDE SEQUENCE
RP [MRNA] OF 286-392 (ISOFORMS 1/2 AND 3), TISSUE SPECIFICITY, GLYCOSYLATION,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Lung, and Testis;
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).
RN [3]
RP TISSUE SPECIFICITY.
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).
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:0000269|PubMed:12421914}; Single-pass type I
CC membrane protein {ECO:0000269|PubMed:12421914}. Note=Inner acrosomal
CC membrane of spermatozoa.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8HYX8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8HYX8-2; Sequence=VSP_019035, VSP_019036;
CC Name=3;
CC IsoId=Q8HYX8-3; Sequence=VSP_019037;
CC -!- TISSUE SPECIFICITY: Present in blood, liver, lung and testes. Isoform
CC 2, but not isoforms 1 or 3, is present at the erythrocyte membrane (at
CC protein level). Whereas isoforms 2/3 are ubiquitous, isoform 1 is
CC expressed only in testes, brain and heart.
CC {ECO:0000269|PubMed:12421914, ECO:0000269|PubMed:9223509,
CC ECO:0000269|PubMed:9525611}.
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; U87917; AAB66817.1; -; mRNA.
DR EMBL; AY157981; AAN64663.1; -; mRNA.
DR EMBL; AY157982; AAN64664.1; -; mRNA.
DR EMBL; AY157983; AAN64665.1; -; mRNA.
DR EMBL; AY157984; AAN64666.1; -; mRNA.
DR EMBL; AY157985; AAN64667.1; -; mRNA.
DR AlphaFoldDB; Q8HYX8; -.
DR SMR; Q8HYX8; -.
DR STRING; 9483.ENSCJAP00000006951; -.
DR eggNOG; ENOG502QPUC; Eukaryota.
DR InParanoid; Q8HYX8; -.
DR Proteomes; UP000008225; 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: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; Phosphoprotein; Reference proteome; Repeat; Signal; Sushi;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..392
FT /note="Membrane cofactor protein"
FT /id="PRO_0000238969"
FT TOPO_DOM 33..344
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 345..365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 366..392
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 33..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 REGION 281..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 307
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 313
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT DISULFID 35..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 64..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
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 VAR_SEQ 33
FT /note="D -> E (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9223509"
FT /id="VSP_019035"
FT VAR_SEQ 34..96
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9223509"
FT /id="VSP_019036"
FT VAR_SEQ 377..392
FT /note="TYLTDETHREVNFTSL -> KADGTAEYATYQSK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12421914"
FT /id="VSP_019037"
FT CONFLICT 131
FT /note="Y -> R (in Ref. 2; AAN64667)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="I -> R (in Ref. 2; AAN64666)"
FT /evidence="ECO:0000305"
FT MOD_RES Q8HYX8-3:384
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES Q8HYX8-3:387
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
SQ SEQUENCE 392 AA; 43601 MW; E089572B64CE7B80 CRC64;
MAPPSRRECP FPSRRFPGLL LAALVLLRSS CSDACGPPPT FEAMELTSKP KPYYKVGEQV
EYDCKKGYHH FAPFLTHSIC DRNHTWLPIS DEPCVKKVCH YIPNPLHGEA ILANGSYSFG
NQLHFICNDG YYLIGKEILY CELKGSDAVW SGRPPICQKI VCKPPPKINN GKHTFSDVEV
FEYLDAVTYS CDPAPGPDPF SLIGESTIYC RDNSLWSDDA PECKVVKCRF PVIENGKQIA
GFGKKFYYKA TVIFERDKGF HIIGSDTIVC NSNSTWDPPV PKCAKELPPS STKPPTLSHS
VSTSPTTVSP TSSVSGPRPT YKPPVSRYPG YPNPDEGMLN SLDEWAIALI VIAILVGVAI
ISFGLHRYLQ RRKKKGTYLT DETHREVNFT SL
