MCP_MOUSE
ID MCP_MOUSE Reviewed; 365 AA.
AC O88174; Q9R0R9;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Membrane cofactor protein;
DE AltName: CD_antigen=CD46;
DE Flags: Precursor;
GN Name=Cd46; Synonyms=Mcp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=9461505; DOI=10.1042/bj3300163;
RA Tsujimura A., Shida K., Kitamura M., Nomura M., Takeda J., Tanaka H.,
RA Matsumoto M., Matsumiya K., Okuyama A., Nishimune Y., Okabe M., Seya T.;
RT "Molecular cloning of a murine homologue of membrane cofactor protein
RT (CD46): preferential expression in testicular germ cells.";
RL Biochem. J. 330:163-168(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=9799332; DOI=10.1007/s002510050447;
RA Miwa T., Nonaka M., Okada N., Wakana S., Shiroishi T., Okada H.;
RT "Molecular cloning of rat and mouse membrane cofactor protein (MCP, CD46):
RT preferential expression in testis and close linkage between the mouse Mcp
RT and Cr2 genes on distal chromosome 1.";
RL Immunogenetics 48:363-371(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=10630288; DOI=10.1007/s002510050600;
RA Nomura M., Tsujimura A., Shida K., Matsumoto M., Matsuda Y., Toyoshima K.,
RA Seya T.;
RT "Membrane and secretory forms of mouse membrane cofactor protein (CD46)
RT generated from a single gene through alternative splicing.";
RL Immunogenetics 50:245-254(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP GLYCOSYLATION, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=12640142; DOI=10.1128/mcb.23.7.2614-2622.2003;
RA Inoue N., Ikawa M., Nakanishi T., Matsumoto M., Nomura M., Seya T.,
RA Okabe M.;
RT "Disruption of mouse CD46 causes an accelerated spontaneous acrosome
RT reaction in sperm.";
RL Mol. Cell. Biol. 23:2614-2622(2003).
CC -!- FUNCTION: May be involved in the fusion of the spermatozoa with the
CC oocyte during fertilization. {ECO:0000269|PubMed:12640142}.
CC -!- SUBUNIT: Interacts with C3b. Interacts with C4b. Interacts with
CC moesin/MSN. {ECO:0000250|UniProtKB:P15529}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasmic vesicle, secretory
CC vesicle, acrosome inner membrane; Single-pass type I membrane protein.
CC Note=Inner acrosomal membrane of spermatozoa.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=O88174-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O88174-2; Sequence=VSP_019038, VSP_019039;
CC -!- TISSUE SPECIFICITY: Present only in testis (at protein level).
CC {ECO:0000269|PubMed:12640142, ECO:0000269|PubMed:9461505,
CC ECO:0000269|PubMed:9799332}.
CC -!- DEVELOPMENTAL STAGE: Not expressed until 29 dpc. Expressed in parallel
CC with synthesis of spermatids. {ECO:0000269|PubMed:9461505}.
CC -!- PTM: May be O-glycosylated. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12640142}.
CC -!- DISRUPTION PHENOTYPE: Mice have normal testis and fertile sperm.
CC {ECO:0000269|PubMed:12640142}.
CC -!- MISCELLANEOUS: [Isoform 2]: Lacks transmembrane domain, probably
CC secreted. {ECO:0000305}.
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DR EMBL; AB001566; BAA31859.1; -; mRNA.
DR EMBL; AB010919; BAA34810.1; -; mRNA.
DR EMBL; AB022600; BAA86056.1; -; mRNA.
DR EMBL; AK006632; BAB24682.1; -; mRNA.
DR CCDS; CCDS35828.1; -. [O88174-1]
DR RefSeq; NP_034908.1; NM_010778.4. [O88174-1]
DR AlphaFoldDB; O88174; -.
DR SMR; O88174; -.
DR STRING; 10090.ENSMUSP00000123931; -.
DR GlyGen; O88174; 6 sites.
DR PhosphoSitePlus; O88174; -.
DR PaxDb; O88174; -.
DR PRIDE; O88174; -.
DR ProteomicsDB; 295714; -. [O88174-1]
DR ProteomicsDB; 295715; -. [O88174-2]
DR Antibodypedia; 2378; 1246 antibodies from 45 providers.
DR DNASU; 17221; -.
DR Ensembl; ENSMUST00000162650; ENSMUSP00000123931; ENSMUSG00000016493. [O88174-1]
DR GeneID; 17221; -.
DR KEGG; mmu:17221; -.
DR UCSC; uc007eet.1; mouse. [O88174-1]
DR CTD; 4179; -.
DR MGI; MGI:1203290; Cd46.
DR VEuPathDB; HostDB:ENSMUSG00000016493; -.
DR eggNOG; ENOG502QPUC; Eukaryota.
DR GeneTree; ENSGT00940000161381; -.
DR HOGENOM; CLU_020107_1_2_1; -.
DR InParanoid; O88174; -.
DR OMA; PPPFEAM; -.
DR OrthoDB; 1239877at2759; -.
DR PhylomeDB; O88174; -.
DR TreeFam; TF334137; -.
DR Reactome; R-MMU-977606; Regulation of Complement cascade.
DR BioGRID-ORCS; 17221; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Cd46; mouse.
DR PRO; PR:O88174; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; O88174; protein.
DR Bgee; ENSMUSG00000016493; Expressed in seminiferous tubule of testis and 139 other tissues.
DR ExpressionAtlas; O88174; baseline and differential.
DR Genevisible; O88174; MM.
DR GO; GO:0001669; C:acrosomal vesicle; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0002079; C:inner acrosomal membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0045296; F:cadherin binding; ISO:MGI.
DR GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR GO; GO:0045959; P:negative regulation of complement activation, classical pathway; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0043382; P:positive regulation of memory T cell differentiation; ISO:MGI.
DR GO; GO:0045862; P:positive regulation of proteolysis; ISO:MGI.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR GO; GO:0071636; P:positive regulation of transforming growth factor beta production; ISO:MGI.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISO:MGI.
DR GO; GO:0035581; P:sequestering of extracellular ligand from receptor; ISO:MGI.
DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW.
DR GO; GO:0002456; P:T cell mediated immunity; ISO:MGI.
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; Cytoplasmic vesicle; Disulfide bond; Fertilization;
KW Glycoprotein; Membrane; Reference proteome; Repeat; Secreted; Signal;
KW Sushi; Transmembrane; Transmembrane helix.
FT SIGNAL 1..44
FT /evidence="ECO:0000255"
FT CHAIN 45..365
FT /note="Membrane cofactor protein"
FT /id="PRO_0000238971"
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..365
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 45..106
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 107..170
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 171..236
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 237..296
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
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 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT DISULFID 109..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 137..168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 173..221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 202..234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 239..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 267..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 297..310
FT /note="GPRPTHPTKPPVYN -> VTF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10630288"
FT /id="VSP_019038"
FT VAR_SEQ 311..365
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10630288"
FT /id="VSP_019039"
SQ SEQUENCE 365 AA; 40881 MW; 84A4CA8EE165C629 CRC64;
MTAAPLMPDS THPCRRRKSY TFFWCSLGVY AEALLFLLSH LSDACELPRP FEAMELKGTP
KLFYAVGEKI EYKCKKGYLY LSPYLMIATC EPNHTWVPIS DAGCIKVQCT MLQDPSFGKV
YYIDGSFSWG ARAKFTCMEG YYVVGMSVLH CVLKGDDEAY WNGYPPHCEK IYCLPPPKIK
NGTHTLTDIN VFKYHEAVSY SCDPTPGPDK FSLVGTSMIF CAGHNTWSNS PPECKVVKCP
NPVLQNGRLI SGAGEIFSYQ STVMFECLQG FYMEGSSMVI CSANNSWEPS IPKCLKGPRP
THPTKPPVYN YTGYPSPREG IFSQELDAWI IALIVITSIV GVFILCLIVL RCFEHRKKTN
VSAAR
