ID MCP_HUMAN Reviewed; 392 AA. AC P15529; A0T1T0; A0T1T1; A0T1T2; Q15429; Q53GV9; Q5HY94; Q5VWS6; Q5VWS7; AC Q5VWS8; Q5VWS9; Q5VWT0; Q5VWT1; Q5VWT2; Q6N0A1; Q7Z3R5; Q9NNW2; Q9NNW3; AC Q9NNW4; Q9UCJ4; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 16-JAN-2004, sequence version 3. DT 27-MAR-2024, entry version 242. DE RecName: Full=Membrane cofactor protein; DE AltName: Full=TLX; DE AltName: Full=Trophoblast leukocyte common antigen; DE AltName: CD_antigen=CD46; DE Flags: Precursor; GN Name=CD46; Synonyms=MCP, MIC10; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), PROTEIN SEQUENCE OF 35-58, AND RP INTERACTION WITH C3B. RX PubMed=3260937; DOI=10.1084/jem.168.1.181; RA Lublin D.M., Liszewski M.K., Post T.W., Arce M.A., le Beau M.M., RA Rebentisch M.B., Lemons R.S., Seya T., Atkinson J.P.; RT "Molecular cloning and chromosomal localization of human membrane cofactor RT protein (MCP). Evidence for inclusion in the multigene family of RT complement-regulatory proteins."; RL J. Exp. Med. 168:181-194(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), AND ALTERNATIVE SPLICING. RX PubMed=2050389; DOI=10.1007/bf00216692; RA Purcell D.F., Russell S.M., Deacon N.J., Brown M.A., Hooker D.J., RA McKenzie I.F.; RT "Alternatively spliced RNAs encode several isoforms of CD46 (MCP), a RT regulator of complement activation."; RL Immunogenetics 33:335-344(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C; D; E AND F). RX PubMed=1711570; DOI=10.1084/jem.174.1.93; RA Post T.W., Liszewski M.K., Adams E.M., Tedja I., Miller E.A., RA Atkinson J.P.; RT "Membrane cofactor protein of the complement system: alternative splicing RT of serine/threonine/proline-rich exons and cytoplasmic tails produces RT multiple isoforms that correlate with protein phenotype."; RL J. Exp. Med. 174:93-102(1991). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM F). RC TISSUE=Testis; RX PubMed=8418811; DOI=10.1002/mrd.1080340117; RA Cervoni F., Fenichel P., Akhoundi C., Hsi B.L., Rossi B.; RT "Characterization of a cDNA clone coding for human testis membrane cofactor RT protein (MCP, CD46)."; RL Mol. Reprod. Dev. 34:107-113(1993). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM N). RC TISSUE=Testis; RX PubMed=9659228; DOI=10.1046/j.1365-2567.1998.00455.x; RA Hara T., Suzuki Y., Nakazawa T., Nishimura H., Nagasawa S., Nishiguchi M., RA Matsumoto M., Hatanaka M., Kitamura M., Seya T.; RT "Post-translational modification and intracellular localization of a splice RT product of CD46 cloned from human testis: role of the intracellular domains RT in O-glycosylation."; RL Immunology 93:546-555(1998). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS D; F AND L). RA Xue Z.T., Widegren B., Salford L.; RT "Molecular cloning of human CD46 (membrane cofactor protein) CDS from RT cancer cell lines in a retroviral vector system."; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). RC TISSUE=Teratocarcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS D AND E). RC TISSUE=Fetal kidney, Liver, and Salivary gland; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B), AND VARIANT PHE-13. RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-266; LEU-324; VAL-353 RP AND GLY-355. RG SeattleSNPs variation discovery resource; RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-158, AND VARIANTS PHE-13 AND GLN-59. RX PubMed=10751138; DOI=10.1086/315386; RA Kusuhara K., Sasaki Y., Nakao F., Ihara K., Hattori H., Yamashita S., RA Nihei K., Koide N., Aiba H., Takeshita K., Hara T.; RT "Analysis of measles virus binding sites of the CD46 gene in patients with RT subacute sclerosing panencephalitis."; RL J. Infect. Dis. 181:1447-1449(2000). RN [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-34. RX PubMed=7691939; RA Cui W., Hourcade D., Post T.W., Greenlund A.C., Atkinson J.P., Kumar V.; RT "Characterization of the promoter region of the membrane cofactor protein RT (CD46) gene of the human complement system and comparison to a membrane RT cofactor protein-like genetic element."; RL J. Immunol. 151:4137-4146(1993). RN [16] RP PROTEIN SEQUENCE OF 35-60. RC TISSUE=Sperm; RX PubMed=1479546; DOI=10.1248/bpb1978.15.455; RA Okabe M., Ying X., Nagira M., Ikawa M., Kohama Y., Mimura T., Tanaka K.; RT "Homology of an acrosome-reacted sperm-specific antigen to CD46."; RL J. Pharmacobio-Dyn. 15:455-459(1992). RN [17] RP PROTEIN SEQUENCE OF 35-58. RX PubMed=2298462; DOI=10.1007/bf00702485; RA Purcell D.F., Deacon N.J., Andrew S.M., McKenzie I.F.; RT "Human non-lineage antigen, CD46 (HuLy-m5): purification and partial RT sequencing demonstrates structural homology with complement-regulating RT glycoproteins."; RL Immunogenetics 31:21-28(1990). RN [18] RP PROTEIN SEQUENCE OF 35-49, AND BINDING TO MEASLES VIRUS. RX PubMed=8371352; DOI=10.1128/jvi.67.10.6025-6032.1993; RA Naniche D., Varior-Krishnan G., Cervoni F., Wild T.F., Rossi B., RA Rabourdin-Combe C., Gerlier D.; RT "Human membrane cofactor protein (CD46) acts as a cellular receptor for RT measles virus."; RL J. Virol. 67:6025-6032(1993). RN [19] RP INTERACTION WITH C3B AND C4B. RX PubMed=1717583; RA Adams E.M., Brown M.C., Nunge M., Krych M., Atkinson J.P.; RT "Contribution of the repeating domains of membrane cofactor protein (CD46) RT of the complement system to ligand binding and cofactor activity."; RL J. Immunol. 147:3005-3011(1991). RN [20] RP ALTERNATIVE SPLICING. RX PubMed=1601037; DOI=10.1002/eji.1830220625; RA Russell S.M., Sparrow R.L., McKenzie I.F.C., Purcell D.F.J.; RT "Tissue-specific and allelic expression of the complement regulator CD46 is RT controlled by alternative splicing."; RL Eur. J. Immunol. 22:1513-1518(1992). RN [21] RP BINDING TO MEASLES VIRUS. RX PubMed=8402913; DOI=10.1016/0092-8674(93)80071-l; RA Doerig R.E., Marcil A., Chopra A., Richardson C.D.; RT "The human CD46 molecule is a receptor for measles virus (Edmonston RT strain)."; RL Cell 75:295-305(1993). RN [22] RP BINDING TO MEASLES VIRUS. RX PubMed=7534417; DOI=10.1073/pnas.92.6.2303; RA Manchester M., Valsamakis A., Kaufman R., Liszewski M.K., Alvarez J., RA Atkinson J.P., Lublin D.M., Oldstone M.B.; RT "Measles virus and C3 binding sites are distinct on membrane cofactor RT protein (CD46)."; RL Proc. Natl. Acad. Sci. U.S.A. 92:2303-2307(1995). RN [23] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH STREPTOCOCCUS PYOGENES RP M PROTEIN. RX PubMed=7708671; DOI=10.1073/pnas.92.7.2489; RA Okada N., Liszewski M.K., Atkinson J.P., Caparon M.; RT "Membrane cofactor protein (CD46) is a keratinocyte receptor for the M RT protein of the group A streptococcus."; RL Proc. Natl. Acad. Sci. U.S.A. 92:2489-2493(1995). RN [24] RP INTERACTION WITH MSN. RX PubMed=7884872; DOI=10.1128/jvi.69.4.2248-2256.1995; RA Schneider-Schaulies J., Dunster L.M., Schwartz-Albiez R., Krohne G., RA ter Meulen V.; RT "Physical association of moesin and CD46 as a receptor complex for measles RT virus."; RL J. Virol. 69:2248-2256(1995). RN [25] RP MUTAGENESIS OF ASN-83; ASN-114 AND ASN-273. RX PubMed=8764003; DOI=10.1128/jvi.70.8.4973-4977.1996; RA Maisner A., Alvarez J., Liszewski M.K., Atkinson D.J., Atkinson J.P., RA Herrler G.; RT "The N-glycan of the SCR 2 region is essential for membrane cofactor RT protein (CD46) to function as a measles virus receptor."; RL J. Virol. 70:4973-4977(1996). RN [26] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH NEISSERIA TYPE IV RP PILI. RX PubMed=9379894; DOI=10.1046/j.1365-2958.1997.4841857.x; RA Kaellstroem H., Liszewski M.K., Atkinson J.P., Jonsson A.-B.; RT "Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for RT pathogenic Neisseria."; RL Mol. Microbiol. 25:639-647(1997). RN [27] RP MUTAGENESIS OF ASN-83; ASN-114 AND ASN-273. RX PubMed=9759896; RA Liszewski M.K., Leung M.K., Atkinson J.P.; RT "Membrane cofactor protein: importance of N- and O-glycosylation for RT complement regulatory function."; RL J. Immunol. 161:3711-3718(1998). RN [28] RP BINDING OF HUMAN HERPESVIRUS 6. RX PubMed=10619434; DOI=10.1016/s0092-8674(00)81678-5; RA Santoro F., Kennedy P.E., Locatelli G., Malnati M.S., Berger E.A., RA Lusso P.; RT "CD46 is a cellular receptor for human herpesvirus 6."; RL Cell 99:817-827(1999). RN [29] RP PHOSPHORYLATION AT TYR-384 (ISOFORM B), PHOSPHORYLATION AT TYR-369 (ISOFORM RP D), PHOSPHORYLATION AT TYR-354 (ISOFORM F), PHOSPHORYLATION AT TYR-370 RP (ISOFORM H), PHOSPHORYLATION AT TYR-355 (ISOFORM J), PHOSPHORYLATION AT RP TYR-340 (ISOFORM L), AND PHOSPHORYLATION AT TYR-321 (ISOFORM 3). RX PubMed=10657632; DOI=10.4049/jimmunol.164.4.1839; RA Wang G., Liszewski M.K., Chan A.C., Atkinson J.P.; RT "Membrane cofactor protein (MCP; CD46): isoform-specific tyrosine RT phosphorylation."; RL J. Immunol. 164:1839-1846(2000). RN [30] RP FUNCTION. RX PubMed=10843656; DOI=10.4049/jimmunol.164.12.6091; RA Astier A., Trescol-Biemont M.-C., Azocar O., Lamouille B., RA Rabourdin-Combe C.; RT "CD46, a new costimulatory molecule for T cells, that induces p120CBL and RT LAT phosphorylation."; RL J. Immunol. 164:6091-6095(2000). RN [31] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH MEASLES VIRUS H RP PROTEIN. RX PubMed=10972291; DOI=10.1038/35022579; RA Tatsuo H., Ono N., Tanaka K., Yanagi Y.; RT "SLAM (CDw150) is a cellular receptor for measles virus."; RL Nature 406:893-897(2000). RN [32] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH NEISSERIA TYPE IV PILI, RP AND MUTAGENESIS OF ASN-83; ASN-114 AND ASN-273. RX PubMed=11260136; DOI=10.1046/j.1462-5822.2001.00095.x; RA Kaellstroem H., Blackmer Gill D., Albiger B., Liszewski M.K., RA Atkinson J.P., Jonsson A.-B.; RT "Attachment of Neisseria gonorrhoeae to the cellular pilus receptor CD46: RT identification of domains important for bacterial adherence."; RL Cell. Microbiol. 3:133-143(2001). RN [33] RP BINDING OF HUMAN HERPESVIRUS 6. RX PubMed=12171934; DOI=10.1074/jbc.m206488200; RA Greenstone H.L., Santoro F., Lusso P., Berger E.A.; RT "Human Herpesvirus 6 and Measles Virus employ distinct CD46 domains for RT receptor function."; RL J. Biol. Chem. 277:39112-39118(2002). RN [34] RP PHOSPHORYLATION (ISOFORMS B/D/F/H/J/L/3). RX PubMed=11901164; DOI=10.1083/jcb.200109005; RA Lee S.W., Bonnah R.A., Higashi D.L., Atkinson J.P., Milgram S.L., So M.; RT "CD46 is phosphorylated at tyrosine 354 upon infection of epithelial cells RT by Neisseria gonorrhoeae."; RL J. Cell Biol. 156:951-957(2002). RN [35] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH STREPTOCOCCUS PYOGENES RP M PROTEIN. RX PubMed=11971006; DOI=10.4049/jimmunol.168.9.4585; RA Giannakis E., Jokiranta T.S., Ormsby R.J., Duthy T.G., Male D.A., RA Christiansen D., Fischetti V.A., Bagley C., Loveland B.E., Gordon D.L.; RT "Identification of the streptococcal M protein binding site on membrane RT cofactor protein (CD46)."; RL J. Immunol. 168:4585-4592(2002). RN [36] RP SUBCELLULAR LOCATION, AND GLYCOSYLATION. RX PubMed=12112588; DOI=10.1002/mrd.10144; RA Riley R.C., Kemper C., Leung M., Atkinson J.P.; RT "Characterization of human membrane cofactor protein (MCP; CD46) on RT spermatozoa."; RL Mol. Reprod. Dev. 62:534-546(2002). RN [37] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN HERPESVIRUS 6 GH RP PROTEIN. RX PubMed=12724329; DOI=10.1074/jbc.m302373200; RA Santoro F., Greenstone H.L., Insinga A., Liszewski M.K., Atkinson J.P., RA Lusso P., Berger E.A.; RT "Interaction of glycoprotein H of human herpesvirus 6 with the cellular RT receptor CD46."; RL J. Biol. Chem. 278:25964-25969(2003). RN [38] RP SUBCELLULAR LOCATION. RX PubMed=14597734; DOI=10.1084/jem.20031159; RA Gill D.B., Koomey M., Cannon J.G., Atkinson J.P.; RT "Down-regulation of CD46 by piliated Neisseria gonorrhoeae."; RL J. Exp. Med. 198:1313-1322(2003). RN [39] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN HERPESVIRUS 6 GH RP PROTEIN. RX PubMed=12663806; DOI=10.1128/jvi.77.8.4992-4999.2003; RA Mori Y., Yang X., Akkapaiboon P., Okuno T., Yamanishi K.; RT "Human herpesvirus 6 variant A glycoprotein H-glycoprotein L-glycoprotein Q RT complex associates with human CD46."; RL J. Virol. 77:4992-4999(2003). RN [40] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN ADENOVIRUS B RP FIBER PROTEIN. RX PubMed=12915534; DOI=10.1128/jvi.77.17.9183-9191.2003; RA Segerman A., Atkinson J.P., Marttila M., Dennerquist V., Wadell G., RA Arnberg N.; RT "Adenovirus type 11 uses CD46 as a cellular receptor."; RL J. Virol. 77:9183-9191(2003). RN [41] RP DISEASE. RX PubMed=14615110; DOI=10.1016/s0140-6736(03)14742-3; RA Noris M., Brioschi S., Caprioli J., Todeschini M., Bresin E., Porrati F., RA Gamba S., Remuzzi G.; RT "Familial haemolytic uraemic syndrome and an MCP mutation."; RL Lancet 362:1542-1547(2003). RN [42] RP FUNCTION. RX PubMed=12540904; DOI=10.1038/nature01315; RA Kemper C., Chan A.C., Green J.M., Brett K.A., Murphy K.M., Atkinson J.P.; RT "Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory RT cell 1 phenotype."; RL Nature 421:388-392(2003). RN [43] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HUMAN ADENOVIRUS B FIBER RP PROTEIN, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=14566335; DOI=10.1038/nm952; RA Gaggar A., Shayakhmetov D.M., Lieber A.; RT "CD46 is a cellular receptor for group B adenoviruses."; RL Nat. Med. 9:1408-1412(2003). RN [44] RP GLYCOSYLATION, AND SUBCELLULAR LOCATION. RX PubMed=15307194; DOI=10.1002/eji.200424969; RA Hakulinen J., Junnikkala S., Sorsa T., Meri S.; RT "Complement inhibitor membrane cofactor protein (MCP; CD46) is RT constitutively shed from cancer cell membranes in vesicles and converted by RT a metalloproteinase to a functionally active soluble form."; RL Eur. J. Immunol. 34:2620-2629(2004). RN [45] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HUMAN ADENOVIRUS D TYPE 37 RP PIV/FIBER PROTEIN, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15047806; DOI=10.1128/jvi.78.8.3897-3905.2004; RA Wu E., Trauger S.A., Pache L., Mullen T.-M., von Seggern D.J., Siuzdak G., RA Nemerow G.R.; RT "Membrane cofactor protein is a receptor for adenoviruses associated with RT epidemic keratoconjunctivitis."; RL J. Virol. 78:3897-3905(2004). RN [46] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN ADENOVIRUS B RP TYPE 3 FIBER PROTEIN. RX PubMed=15078926; DOI=10.1128/jvi.78.9.4454-4462.2004; RA Sirena D., Lilienfeld B., Eisenhut M., Kaelin S., Boucke K., Beerli R.R., RA Vogt L., Ruedl C., Bachmann M.F., Greber U.F., Hemmi S.; RT "The human membrane cofactor CD46 is a receptor for species B adenovirus RT serotype 3."; RL J. Virol. 78:4454-4462(2004). RN [47] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN ADENOVIRUS B RP TYPE 35 FIBER PROTEIN. RX PubMed=15919905; DOI=10.1128/jvi.79.12.7503-7513.2005; RA Gaggar A., Shayakhmetov D.M., Liszewski M.K., Atkinson J.P., Lieber A.; RT "Localization of regions in CD46 that interact with adenovirus."; RL J. Virol. 79:7503-7513(2005). RN [48] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN ADENOVIRUS B RP FIBER PROTEIN. RX PubMed=16254377; DOI=10.1128/jvi.79.22.14429-14436.2005; RA Marttila M., Persson D., Gustafsson D., Liszewski M.K., Atkinson J.P., RA Wadell G., Arnberg N.; RT "CD46 is a cellular receptor for all species B adenoviruses except types 3 RT and 7."; RL J. Virol. 79:14429-14436(2005). RN [49] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [50] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 35-160. RX PubMed=10357804; DOI=10.1093/emboj/18.11.2911; RA Casasnovas J.M., Larvie M., Stehle T.; RT "Crystal structure of two CD46 domains reveals an extended measles virus- RT binding surface."; RL EMBO J. 18:2911-2922(1999). RN [51] RP CHARACTERIZATION OF VARIANTS AHUS2 PRO-240 AND 271-ASP-SER-272 DEL. RX PubMed=14566051; DOI=10.1073/pnas.2135497100; RA Richards A., Kemp E.J., Liszewski M.K., Goodship J.A., Lampe A.K., RA Decorte R., Muesluemanoglu M.H., Kavukcu S., Filler G., Pirson Y., RA Wen L.S., Atkinson J.P., Goodship T.H.J.; RT "Mutations in human complement regulator, membrane cofactor protein (CD46), RT predispose to development of familial hemolytic uremic syndrome."; RL Proc. Natl. Acad. Sci. U.S.A. 100:12966-12971(2003). RN [52] RP VARIANT AHUS2 TYR-35. RX PubMed=16621965; DOI=10.1182/blood-2005-10-007252; RG The international registry of recurrent and familial HUS/TTP; RA Caprioli J., Noris M., Brioschi S., Pianetti G., Castelletti F., RA Bettinaglio P., Mele C., Bresin E., Cassis L., Gamba S., Porrati F., RA Bucchioni S., Monteferrante G., Fang C.J., Liszewski M.K., Kavanagh D., RA Atkinson J.P., Remuzzi G.; RT "Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical RT presentation, response to treatment, and outcome."; RL Blood 108:1267-1279(2006). RN [53] RP VARIANT AHUS2 SER-165. RX PubMed=16386793; DOI=10.1016/j.molimm.2005.11.008; RA Esparza-Gordillo J., Jorge E.G., Garrido C.A., Carreras L., RA Lopez-Trascasa M., Sanchez-Corral P., de Cordoba S.R.; RT "Insights into hemolytic uremic syndrome: segregation of three independent RT predisposition factors in a large, multiple affected pedigree."; RL Mol. Immunol. 43:1769-1775(2006). RN [54] RP VARIANTS [LARGE SCALE ANALYSIS] TYR-228 AND VAL-353. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [55] RP VARIANTS AHUS2 CYS-216 AND ARG-231. RX PubMed=20513133; DOI=10.1002/humu.21256; RA Maga T.K., Nishimura C.J., Weaver A.E., Frees K.L., Smith R.J.H.; RT "Mutations in alternative pathway complement proteins in American patients RT with atypical hemolytic uremic syndrome."; RL Hum. Mutat. 31:E1445-E1460(2010). 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. {ECO:0000269|PubMed:10843656, CC ECO:0000269|PubMed:12540904}. CC -!- FUNCTION: (Microbial infection) A number of viral and bacterial CC pathogens seem to bind MCP in order to exploit its immune regulation CC property and directly induce an immunosuppressive phenotype in T-cells. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Adenovirus CC subgroup B2 and Ad3. {ECO:0000269|PubMed:12915534, CC ECO:0000269|PubMed:14566335, ECO:0000269|PubMed:15047806, CC ECO:0000269|PubMed:15078926, ECO:0000269|PubMed:15919905, CC ECO:0000269|PubMed:16254377}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for cultured Measles CC virus. {ECO:0000269|PubMed:10972291}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Herpesvirus CC 6/HHV-6. {ECO:0000269|PubMed:12663806, ECO:0000269|PubMed:12724329}. CC -!- FUNCTION: (Microbial infection) May act as a receptor for pathogenic CC bacteria Neisseria and Streptococcus pyogenes (PubMed:7708671, CC PubMed:9379894, PubMed:11260136, PubMed:11971006). CC -!- SUBUNIT: Interacts with C3b (PubMed:3260937, PubMed:1717583). Interacts CC with C4b (PubMed:1717583). Interacts with moesin/MSN (PubMed:7884872). CC {ECO:0000269|PubMed:1717583, ECO:0000269|PubMed:3260937, CC ECO:0000269|PubMed:7884872}. CC -!- SUBUNIT: (Microbial infection) Interacts with measles virus H protein. CC {ECO:0000269|PubMed:10972291}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpesvirus 6 GH CC protein (PubMed:12663806, PubMed:12724329). CC {ECO:0000269|PubMed:12663806, ECO:0000269|PubMed:12724329}. CC -!- SUBUNIT: (Microbial infection) Interacts with human adenovirus B/D CC fiber protein (PubMed:12915534, PubMed:14566335, PubMed:15047806, CC PubMed:15078926, PubMed:15919905, PubMed:16254377). CC {ECO:0000269|PubMed:12915534, ECO:0000269|PubMed:14566335, CC ECO:0000269|PubMed:15047806, ECO:0000269|PubMed:15078926, CC ECO:0000269|PubMed:15919905, ECO:0000269|PubMed:16254377}. CC -!- SUBUNIT: (Microbial infection) Binds to Streptococcus pyogenes M CC protein and to type IV pili from Neisseria (PubMed:7708671, CC PubMed:9379894, PubMed:11260136, PubMed:11971006). CC {ECO:0000269|PubMed:11260136, ECO:0000269|PubMed:11971006, CC ECO:0000269|PubMed:7708671, ECO:0000269|PubMed:9379894}. CC -!- INTERACTION: CC P15529; P01024: C3; NbExp=2; IntAct=EBI-2623451, EBI-905851; CC P15529; P78504: JAG1; NbExp=5; IntAct=EBI-2623451, EBI-2847071; CC P15529-3; Q8TD06: AGR3; NbExp=3; IntAct=EBI-13046140, EBI-3925742; CC P15529-3; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-13046140, EBI-12109402; CC P15529-3; O60883: GPR37L1; NbExp=3; IntAct=EBI-13046140, EBI-2927498; CC P15529-3; Q12837: POU4F2; NbExp=3; IntAct=EBI-13046140, EBI-17236143; CC P15529-3; Q9UEU0: VTI1B; NbExp=3; IntAct=EBI-13046140, EBI-723716; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome CC inner membrane {ECO:0000269|PubMed:12112588, CC ECO:0000269|PubMed:14597734, ECO:0000269|PubMed:15307194}; Single-pass CC type I membrane protein {ECO:0000269|PubMed:12112588, CC ECO:0000269|PubMed:14597734, ECO:0000269|PubMed:15307194}. Note=Inner CC acrosomal membrane of spermatozoa. Internalized upon binding of Measles CC virus, Herpesvirus 6 or Neisseria gonorrhoeae, which results in an CC increased susceptibility of infected cells to complement-mediated CC injury. In cancer cells or cells infected by Neisseria, shedding leads CC to a soluble peptide. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=16; CC Comment=Additional isoforms seem to exist. The complete sequences of CC the isoforms are not known. Isoforms are classified as alpha (isoform CC C and isoform D), beta (isoform E and isoform F), gamma (isoform A CC and isoform B) and delta (isoform N). Isoforms gamma are CC preferentially expressed in EBV-B cells and leukemic cells. Isoforms CC alpha (66 kDa) and isoforms beta (56 kDa) are found in all tissues CC except sperm. Isoform delta is expressed in spermatozoa. The exon 9 CC is specifically deleted in some placentae isoforms. All tissues CC differentially splice exon 13.; CC Name=A; Synonyms=no del, ABC1; CC IsoId=P15529-1; Sequence=Displayed; CC Name=B; Synonyms=del 13, ABC2; CC IsoId=P15529-2; Sequence=VSP_001204; CC Name=C; Synonyms=del 7, BC1; CC IsoId=P15529-11; Sequence=VSP_009174; CC Name=D; Synonyms=del 7-13, BC2; CC IsoId=P15529-3; Sequence=VSP_009174, VSP_001204; CC Name=E; Synonyms=del 7-8, C1; CC IsoId=P15529-12; Sequence=VSP_009175; CC Name=F; Synonyms=del 7-8-13, C2; CC IsoId=P15529-4; Sequence=VSP_009175, VSP_001204; CC Name=G; Synonyms=del 9; CC IsoId=P15529-13; Sequence=VSP_009177; CC Name=H; Synonyms=del 9-13; CC IsoId=P15529-5; Sequence=VSP_009177, VSP_001204; CC Name=I; Synonyms=del 7-9; CC IsoId=P15529-14; Sequence=VSP_009174, VSP_009177; CC Name=J; Synonyms=del 7-9-13; CC IsoId=P15529-6; Sequence=VSP_009174, VSP_009177, VSP_001204; CC Name=K; Synonyms=del 7-8-9; CC IsoId=P15529-15; Sequence=VSP_009176; CC Name=L; Synonyms=del 7-8-9-13; CC IsoId=P15529-7; Sequence=VSP_009176, VSP_001204; CC Name=M; Synonyms=del 7-12a-13; CC IsoId=P15529-8; Sequence=VSP_009174, VSP_001202, VSP_001203; CC Name=N; Synonyms=del 7-8-12-13; CC IsoId=P15529-9; Sequence=VSP_009175, VSP_009178; CC Name=2; CC IsoId=P15529-10; Sequence=VSP_001201; CC Name=3; CC IsoId=P15529-16; Sequence=VSP_019005, VSP_019006, VSP_001204; CC -!- TISSUE SPECIFICITY: Expressed by all cells except erythrocytes. CC -!- DOMAIN: Sushi domains 1 and 2 are required for interaction with human CC adenovirus B PIV/FIBER protein and with Measles virus H protein. Sushi CC domains 2 and 3 are required for Herpesvirus 6 binding. Sushi domain 3 CC is required for Neisseria binding. Sushi domains 3 and 4 are required CC for interaction with Streptococcus pyogenes M protein and are the most CC important for interaction with C3b and C4b. CC -!- PTM: N-glycosylated on Asn-83; Asn-114 and Asn-273 in most tissues, but CC probably less N-glycosylated in testis. N-glycosylation on Asn-114 and CC Asn-273 is required for cytoprotective function. N-glycosylation on CC Asn-114 is required for Measles virus binding. N-glycosylation on Asn- CC 273 is required for Neisseria binding. N-glycosylation is not required CC for human adenovirus binding. CC -!- PTM: Extensively O-glycosylated in the Ser/Thr-rich domain. O- CC glycosylation is required for Neisseria binding but not for Measles CC virus or human adenovirus binding. CC -!- PTM: In epithelial cells, isoforms B/D/F/H/J/L/3 are phosphorylated by CC YES1 in response to infection by Neisseria gonorrhoeae; which promotes CC infectivity. In T-cells, these isoforms may be phosphorylated by LCK. CC -!- DISEASE: Hemolytic uremic syndrome, atypical, 2 (AHUS2) [MIM:612922]: CC An atypical form of hemolytic uremic syndrome. It is a complex genetic CC disease characterized by microangiopathic hemolytic anemia, CC thrombocytopenia, renal failure and absence of episodes of CC enterocolitis and diarrhea. In contrast to typical hemolytic uremic CC syndrome, atypical forms have a poorer prognosis, with higher death CC rates and frequent progression to end-stage renal disease. CC {ECO:0000269|PubMed:14566051, ECO:0000269|PubMed:16386793, CC ECO:0000269|PubMed:16621965, ECO:0000269|PubMed:20513133}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. Other genes may play a role in modifying the CC phenotype. Patients with CD46 mutations seem to have an overall better CC prognosis compared to patients carrying CFH mutations. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/mcp/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y00651; CAA68675.1; -; mRNA. DR EMBL; M58050; AAA62833.1; -; mRNA. DR EMBL; X59405; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; X59406; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; X59407; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; X59408; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; X59409; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; X59410; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; S51940; AAB24802.1; -; mRNA. DR EMBL; D84105; BAA12224.1; -; mRNA. DR EMBL; EF076055; ABK81635.1; -; mRNA. DR EMBL; EF076056; ABK81636.1; -; mRNA. DR EMBL; EF076057; ABK81637.1; -; mRNA. DR EMBL; EF076058; ABK81638.1; -; mRNA. DR EMBL; AK291227; BAF83916.1; -; mRNA. DR EMBL; BX537451; CAD97694.1; -; mRNA. DR EMBL; BX640613; CAE45719.1; -; mRNA. DR EMBL; BX649050; CAI45983.1; -; mRNA. DR EMBL; AK222822; BAD96542.1; -; mRNA. DR EMBL; AY916779; AAW82433.1; -; Genomic_DNA. DR EMBL; AL035209; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL365178; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471100; EAW93465.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93470.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93476.1; -; Genomic_DNA. DR EMBL; BC030594; AAH30594.1; -; mRNA. DR EMBL; AF209712; AAF73844.1; -; mRNA. DR EMBL; AF209713; AAF73845.1; -; mRNA. DR EMBL; AF209714; AAF73846.1; -; mRNA. DR EMBL; S65879; AAD13968.1; -; Genomic_DNA. DR CCDS; CCDS1479.1; -. [P15529-9] DR CCDS; CCDS1480.1; -. [P15529-3] DR CCDS; CCDS1481.1; -. [P15529-4] DR CCDS; CCDS1482.1; -. [P15529-2] DR CCDS; CCDS1484.1; -. [P15529-7] DR CCDS; CCDS1485.1; -. [P15529-1] DR CCDS; CCDS31008.1; -. [P15529-11] DR CCDS; CCDS31009.1; -. [P15529-12] DR CCDS; CCDS86048.1; -. [P15529-6] DR PIR; G02913; G02913. DR PIR; I54479; I54479. DR PIR; I57998; I57998. DR PIR; S01896; S01896. DR RefSeq; NP_002380.3; NM_002389.4. [P15529-1] DR RefSeq; NP_722548.1; NM_153826.3. [P15529-3] DR RefSeq; NP_758860.1; NM_172350.2. [P15529-9] DR RefSeq; NP_758861.1; NM_172351.2. [P15529-11] DR RefSeq; NP_758862.1; NM_172352.2. [P15529-12] DR RefSeq; NP_758863.1; NM_172353.2. [P15529-4] DR RefSeq; NP_758869.1; NM_172359.2. [P15529-2] DR RefSeq; NP_758871.1; NM_172361.2. [P15529-7] DR RefSeq; XP_011507865.1; XM_011509563.1. [P15529-5] DR RefSeq; XP_011507866.1; XM_011509564.1. DR RefSeq; XP_016856797.1; XM_017001308.1. DR RefSeq; XP_016856798.1; XM_017001309.1. DR RefSeq; XP_016856799.1; XM_017001310.1. DR PDB; 1CKL; X-ray; 3.10 A; A/B/C/D/E/F=35-160. DR PDB; 2O39; X-ray; 2.85 A; C/D=35-160. DR PDB; 3INB; X-ray; 3.10 A; C/D=35-160. DR PDB; 3L89; X-ray; 3.50 A; M/N/O/P/Q/R/S/T/U/V/W/X=35-160. DR PDB; 3O8E; X-ray; 2.84 A; B/D=35-286. DR PDB; 5FO8; X-ray; 2.40 A; C=35-286. DR PDB; 8QK3; EM; 3.20 A; E=1-392. DR PDBsum; 1CKL; -. DR PDBsum; 2O39; -. DR PDBsum; 3INB; -. DR PDBsum; 3L89; -. DR PDBsum; 3O8E; -. DR PDBsum; 5FO8; -. DR PDBsum; 8QK3; -. DR AlphaFoldDB; P15529; -. DR EMDB; EMD-18455; -. DR SMR; P15529; -. DR BioGRID; 110346; 41. DR DIP; DIP-41232N; -. DR IntAct; P15529; 21. DR MINT; P15529; -. DR STRING; 9606.ENSP00000313875; -. DR GlyConnect; 1501; 8 N-Linked glycans (2 sites). DR GlyCosmos; P15529; 21 sites, 7 glycans. DR GlyGen; P15529; 22 sites, 7 N-linked glycans (2 sites), 2 O-linked glycans (2 sites). DR iPTMnet; P15529; -. DR PhosphoSitePlus; P15529; -. DR SwissPalm; P15529; -. DR BioMuta; CD46; -. DR DMDM; 41019474; -. DR EPD; P15529; -. DR jPOST; P15529; -. DR MassIVE; P15529; -. DR MaxQB; P15529; -. DR PaxDb; 9606-ENSP00000313875; -. DR PeptideAtlas; P15529; -. DR ProteomicsDB; 53167; -. [P15529-1] DR ProteomicsDB; 53168; -. [P15529-10] DR ProteomicsDB; 53169; -. [P15529-11] DR ProteomicsDB; 53170; -. [P15529-12] DR ProteomicsDB; 53171; -. [P15529-13] DR ProteomicsDB; 53172; -. [P15529-14] DR ProteomicsDB; 53173; -. [P15529-15] DR ProteomicsDB; 53174; -. [P15529-16] DR ProteomicsDB; 53175; -. [P15529-2] DR ProteomicsDB; 53176; -. [P15529-3] DR ProteomicsDB; 53177; -. [P15529-4] DR ProteomicsDB; 53178; -. [P15529-5] DR ProteomicsDB; 53179; -. [P15529-6] DR ProteomicsDB; 53180; -. [P15529-7] DR ProteomicsDB; 53181; -. [P15529-8] DR ProteomicsDB; 53182; -. [P15529-9] DR Pumba; P15529; -. DR TopDownProteomics; P15529-4; -. [P15529-4] DR ABCD; P15529; 10 sequenced antibodies. DR Antibodypedia; 2378; 1410 antibodies from 46 providers. DR DNASU; 4179; -. DR Ensembl; ENST00000322875.8; ENSP00000313875.4; ENSG00000117335.21. [P15529-2] DR Ensembl; ENST00000322918.9; ENSP00000314664.5; ENSG00000117335.21. [P15529-9] DR Ensembl; ENST00000354848.5; ENSP00000346912.1; ENSG00000117335.21. [P15529-3] DR Ensembl; ENST00000357714.5; ENSP00000350346.1; ENSG00000117335.21. [P15529-4] DR Ensembl; ENST00000358170.6; ENSP00000350893.2; ENSG00000117335.21. [P15529-1] DR Ensembl; ENST00000360212.6; ENSP00000353342.2; ENSG00000117335.21. [P15529-7] DR Ensembl; ENST00000367041.5; ENSP00000356008.1; ENSG00000117335.21. [P15529-12] DR Ensembl; ENST00000367042.6; ENSP00000356009.1; ENSG00000117335.21. [P15529-11] DR Ensembl; ENST00000367047.5; ENSP00000356014.1; ENSG00000117335.21. [P15529-16] DR Ensembl; ENST00000480003.5; ENSP00000418471.1; ENSG00000117335.21. [P15529-6] DR GeneID; 4179; -. DR KEGG; hsa:4179; -. DR MANE-Select; ENST00000367042.6; ENSP00000356009.1; NM_172351.3; NP_758861.1. [P15529-11] DR UCSC; uc001hgc.4; human. [P15529-1] DR AGR; HGNC:6953; -. DR CTD; 4179; -. DR DisGeNET; 4179; -. DR GeneCards; CD46; -. DR GeneReviews; CD46; -. DR HGNC; HGNC:6953; CD46. DR HPA; ENSG00000117335; Low tissue specificity. DR MalaCards; CD46; -. DR MIM; 120920; gene+phenotype. DR MIM; 612922; phenotype. DR neXtProt; NX_P15529; -. DR OpenTargets; ENSG00000117335; -. DR Orphanet; 544472; Atypical hemolytic uremic syndrome with complement gene abnormality. DR Orphanet; 244242; HELLP syndrome. DR PharmGKB; PA30700; -. DR VEuPathDB; HostDB:ENSG00000117335; -. DR eggNOG; ENOG502QPUC; Eukaryota. DR GeneTree; ENSGT00940000161381; -. DR HOGENOM; CLU_020107_1_2_1; -. DR InParanoid; P15529; -. DR OMA; KVECEDP; -. DR OrthoDB; 5400619at2759; -. DR PhylomeDB; P15529; -. DR TreeFam; TF334137; -. DR PathwayCommons; P15529; -. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P15529; -. DR SIGNOR; P15529; -. DR BioGRID-ORCS; 4179; 32 hits in 1167 CRISPR screens. DR ChiTaRS; CD46; human. DR EvolutionaryTrace; P15529; -. DR GeneWiki; CD46; -. DR GenomeRNAi; 4179; -. DR Pharos; P15529; Tbio. DR PRO; PR:P15529; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P15529; Protein. DR Bgee; ENSG00000117335; Expressed in palpebral conjunctiva and 213 other cell types or tissues. DR ExpressionAtlas; P15529; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0002079; C:inner acrosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:AgBase. DR GO; GO:0045296; F:cadherin binding; IPI:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW. DR GO; GO:0002250; P:adaptive immune response; IC:UniProtKB. 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:0010629; P:negative regulation of gene expression; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:UniProtKB. DR GO; GO:0043382; P:positive regulation of memory T cell differentiation; IDA:UniProtKB. DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IDA:UniProtKB. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:UniProtKB. DR GO; GO:0071636; P:positive regulation of transforming growth factor beta production; IDA:UniProtKB. DR GO; GO:0008593; P:regulation of Notch signaling pathway; IDA:UniProtKB. DR GO; GO:0035581; P:sequestering of extracellular ligand from receptor; IDA:UniProtKB. DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW. DR GO; GO:0002456; P:T cell mediated immunity; IMP:UniProtKB. DR CDD; cd00033; CCP; 4. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 4. DR InterPro; IPR017341; CD46. DR InterPro; IPR035976; Sushi/SCR/CCP_sf. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR PANTHER; PTHR19325; COMPLEMENT COMPONENT-RELATED SUSHI DOMAIN-CONTAINING; 1. DR PANTHER; PTHR19325:SF571; MEMBRANE COFACTOR PROTEIN; 1. DR Pfam; PF00084; Sushi; 4. DR PIRSF; PIRSF037971; TLX_CD46; 1. DR SMART; SM00032; CCP; 4. DR SUPFAM; SSF57535; Complement control module/SCR domain; 4. DR PROSITE; PS50923; SUSHI; 4. DR Genevisible; P15529; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complement pathway; KW Cytoplasmic vesicle; Direct protein sequencing; Disease variant; KW Disulfide bond; Fertilization; Glycoprotein; Hemolytic uremic syndrome; KW Host cell receptor for virus entry; Host-virus interaction; Immunity; KW Innate immunity; Membrane; Phosphoprotein; Receptor; Reference proteome; KW Repeat; Signal; Sushi; Transmembrane; Transmembrane helix. FT SIGNAL 1..34 FT /evidence="ECO:0000269|PubMed:1479546, FT ECO:0000269|PubMed:2298462, ECO:0000269|PubMed:3260937, FT ECO:0000269|PubMed:8371352" FT CHAIN 35..392 FT /note="Membrane cofactor protein" FT /id="PRO_0000006008" FT TOPO_DOM 35..343 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 344..366 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 367..392 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" 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 REGION 291..328 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 293..320 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 83 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 114 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 163 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 273 FT /note="N-linked (GlcNAc...) asparagine" 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 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 305 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 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 CARBOHYD 326 FT /note="O-linked (GalNAc...) serine" 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 DISULFID 256..283 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT VAR_SEQ 33 FT /note="D -> G (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_019005" FT VAR_SEQ 34..96 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_019006" FT VAR_SEQ 286..329 FT /note="Missing (in isoform K and isoform L)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_009176" FT VAR_SEQ 286..315 FT /note="Missing (in isoform E, isoform F and isoform N)" FT /evidence="ECO:0000303|PubMed:1711570, FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:8418811, FT ECO:0000303|PubMed:9659228, ECO:0000303|Ref.6" FT /id="VSP_009175" FT VAR_SEQ 286..300 FT /note="Missing (in isoform C, isoform D, isoform I, isoform FT J and isoform M)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1711570, FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:2050389, FT ECO:0000303|PubMed:3260937, ECO:0000303|Ref.6" FT /id="VSP_009174" FT VAR_SEQ 301..305 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001201" FT VAR_SEQ 316..329 FT /note="Missing (in isoform G, isoform H, isoform I and FT isoform J)" FT /evidence="ECO:0000305" FT /id="VSP_009177" FT VAR_SEQ 355..392 FT /note="VVGVAVICVVPYRYLQRRKKKGTYLTDETHREVKFTSL -> GKQMVELNMP FT LTRLNQPLQQSREAE (in isoform N)" FT /evidence="ECO:0000303|PubMed:9659228" FT /id="VSP_009178" FT VAR_SEQ 355..367 FT /note="Missing (in isoform M)" FT /evidence="ECO:0000305" FT /id="VSP_001202" FT VAR_SEQ 368..392 FT /note="YLQRRKKKGTYLTDETHREVKFTSL -> GKQMVELNMPLTRLNQPLQQSRE FT AE (in isoform M)" FT /evidence="ECO:0000305" FT /id="VSP_001203" FT VAR_SEQ 377..392 FT /note="TYLTDETHREVKFTSL -> KADGGAEYATYQTKSTTPAEQRG (in FT isoform B, isoform D, isoform F, isoform H, isoform J, FT isoform L and isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1711570, FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:3260937, FT ECO:0000303|PubMed:8418811, ECO:0000303|Ref.6, FT ECO:0000303|Ref.9" FT /id="VSP_001204" FT VARIANT 13 FT /note="S -> F (in dbSNP:rs138843816)" FT /evidence="ECO:0000269|PubMed:10751138, ECO:0000269|Ref.9" FT /id="VAR_026567" FT VARIANT 35 FT /note="C -> Y (in AHUS2; dbSNP:rs121909591)" FT /evidence="ECO:0000269|PubMed:16621965" FT /id="VAR_063656" FT VARIANT 59 FT /note="R -> Q (in dbSNP:rs780693519)" FT /evidence="ECO:0000269|PubMed:10751138" FT /id="VAR_026568" FT VARIANT 165 FT /note="P -> S (in AHUS2; reduced cell surface expression; FT dbSNP:rs759136081)" FT /evidence="ECO:0000269|PubMed:16386793" FT /id="VAR_026569" FT VARIANT 216 FT /note="W -> C (in AHUS2)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063657" FT VARIANT 228 FT /note="C -> Y (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035828" FT VARIANT 231 FT /note="P -> R (in AHUS2; dbSNP:rs1271761432)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063658" FT VARIANT 240 FT /note="S -> P (in AHUS2; no change in cell surface FT expression but reduced activity; dbSNP:rs121909589)" FT /evidence="ECO:0000269|PubMed:14566051" FT /id="VAR_026570" FT VARIANT 266 FT /note="D -> N (in dbSNP:rs17006830)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_022262" FT VARIANT 271..272 FT /note="Missing (in AHUS2; no cell surface expression)" FT /evidence="ECO:0000269|PubMed:14566051" FT /id="VAR_026571" FT VARIANT 324 FT /note="P -> L (in dbSNP:rs41317833)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_022263" FT VARIANT 353 FT /note="A -> V (in dbSNP:rs35366573)" FT /evidence="ECO:0000269|PubMed:16959974, ECO:0000269|Ref.10" FT /id="VAR_022264" FT VARIANT 355 FT /note="V -> G" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_022265" FT MUTAGEN 83 FT /note="N->Q: No effect on cytoprotective function. No FT effect on Neisseria binding. No effect on Measles virus FT binding." FT /evidence="ECO:0000269|PubMed:11260136, FT ECO:0000269|PubMed:8764003, ECO:0000269|PubMed:9759896" FT MUTAGEN 114 FT /note="N->Q: Strongly decreases cytoprotective function. FT Decreases Neisseria binding. Abolishes Measles virus FT binding." FT /evidence="ECO:0000269|PubMed:11260136, FT ECO:0000269|PubMed:8764003, ECO:0000269|PubMed:9759896" FT MUTAGEN 273 FT /note="N->Q: Strongly decreases cytoprotective function. FT Abolishes Neisseria binding. No effect on Measles virus FT binding." FT /evidence="ECO:0000269|PubMed:11260136, FT ECO:0000269|PubMed:8764003, ECO:0000269|PubMed:9759896" FT CONFLICT 25 FT /note="V -> A (in Ref. 8; CAE45719)" FT /evidence="ECO:0000305" FT CONFLICT 108 FT /note="G -> S (in Ref. 8; CAD97694)" FT /evidence="ECO:0000305" FT CONFLICT 159 FT /note="K -> S (in Ref. 8; CAD97694)" FT /evidence="ECO:0000305" FT CONFLICT 162 FT /note="C -> R (in Ref. 8; CAI45983)" FT /evidence="ECO:0000305" FT STRAND 42..48 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 59..64 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 68..70 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 77..80 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 84..86 FT /evidence="ECO:0007829|PDB:3O8E" FT HELIX 91..93 FT /evidence="ECO:0007829|PDB:3L89" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 108..112 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 115..118 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 122..127 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 131..135 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 137..146 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 148..152 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 156..159 FT /evidence="ECO:0007829|PDB:3O8E" FT STRAND 171..174 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 183..191 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 201..204 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 206..210 FT /evidence="ECO:0007829|PDB:5FO8" FT HELIX 212..214 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 215..218 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 222..224 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 236..240 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 251..256 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 260..264 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 266..270 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 276..278 FT /evidence="ECO:0007829|PDB:5FO8" FT STRAND 282..285 FT /evidence="ECO:0007829|PDB:5FO8" FT MOD_RES P15529-2:384 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10657632" FT MOD_RES P15529-3:369 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10657632" FT MOD_RES P15529-4:354 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10657632" FT MOD_RES P15529-5:370 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10657632" FT MOD_RES P15529-6:355 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10657632" FT MOD_RES P15529-7:340 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10657632" FT MOD_RES P15529-16:321 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10657632" SQ SEQUENCE 392 AA; 43747 MW; 85FE0CF100EA703E CRC64; MEPPGRRECP FPSWRFPGLL LAAMVLLLYS FSDACEEPPT FEAMELIGKP KPYYEIGERV DYKCKKGYFY IPPLATHTIC DRNHTWLPVS DDACYRETCP YIRDPLNGQA VPANGTYEFG YQMHFICNEG YYLIGEEILY CELKGSVAIW SGKPPICEKV LCTPPPKIKN GKHTFSEVEV FEYLDAVTYS CDPAPGPDPF SLIGESTIYC GDNSVWSRAA PECKVVKCRF PVVENGKQIS GFGKKFYYKA TVMFECDKGF YLDGSDTIVC DSNSTWDPPV PKCLKVLPPS STKPPALSHS VSTSSTTKSP ASSASGPRPT YKPPVSNYPG YPKPEEGILD SLDVWVIAVI VIAIVVGVAV ICVVPYRYLQ RRKKKGTYLT DETHREVKFT SL //