ID CLUS_HUMAN Reviewed; 449 AA. AC P10909; B2R9Q1; B3KSE6; P11380; P11381; Q2TU75; Q5HYC1; Q7Z5B9; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 248. DE RecName: Full=Clusterin; DE AltName: Full=Aging-associated gene 4 protein {ECO:0000303|Ref.20}; DE AltName: Full=Apolipoprotein J {ECO:0000303|PubMed:2387851}; DE Short=Apo-J; DE AltName: Full=Complement cytolysis inhibitor {ECO:0000303|PubMed:2780565}; DE Short=CLI {ECO:0000303|PubMed:2780565}; DE AltName: Full=Complement-associated protein SP-40,40 {ECO:0000303|PubMed:1903064, ECO:0000303|PubMed:2721499}; DE AltName: Full=Ku70-binding protein 1; DE AltName: Full=NA1/NA2 {ECO:0000303|PubMed:1903064}; DE AltName: Full=Sulfated glycoprotein 2 {ECO:0000303|PubMed:1924317}; DE Short=SGP-2 {ECO:0000303|PubMed:1924317}; DE AltName: Full=Testosterone-repressed prostate message 2 {ECO:0000250|UniProtKB:P05371}; DE Short=TRPM-2 {ECO:0000303|PubMed:8181474}; DE Contains: DE RecName: Full=Clusterin beta chain; DE AltName: Full=ApoJalpha {ECO:0000303|PubMed:1974459, ECO:0000303|PubMed:2387851}; DE AltName: Full=Complement cytolysis inhibitor a chain {ECO:0000303|PubMed:2780565}; DE AltName: Full=SP-40,40 beta-chain {ECO:0000303|PubMed:2721499}; DE Contains: DE RecName: Full=Clusterin alpha chain; DE AltName: Full=ApoJbeta {ECO:0000303|PubMed:1974459, ECO:0000303|PubMed:2387851}; DE AltName: Full=Complement cytolysis inhibitor b chain {ECO:0000303|PubMed:2780565}; DE AltName: Full=SP-40,40 alpha-chain {ECO:0000303|PubMed:2721499}; DE Flags: Precursor; GN Name=CLU {ECO:0000312|HGNC:HGNC:2095}; GN Synonyms=APOJ {ECO:0000303|PubMed:2387851}, CLI GN {ECO:0000303|PubMed:2780565}, KUB1; ORFNames=AAG4; 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 1), PROTEIN SEQUENCE OF N-TERMINUS, RP SUBUNIT, DISULFIDE BONDS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP FUNCTION. RC TISSUE=Liver; RX PubMed=2780565; DOI=10.1073/pnas.86.18.7123; RA Jenne D.E., Tschopp J.; RT "Molecular structure and functional characterization of a human complement RT cytolysis inhibitor found in blood and seminal plasma: identity to sulfated RT glycoprotein 2, a constituent of rat testis fluid."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7123-7127(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL NUCLEOTIDE SEQUENCE [MRNA] RP (ISOFORM 2), AND TISSUE SPECIFICITY. RX PubMed=8181474; DOI=10.1111/j.1432-1033.1994.tb18807.x; RA Wong P., Taillefer D., Lakins J., Pineault J., Chader G., Tenniswood M.; RT "Molecular characterization of human TRPM-2/clusterin, a gene associated RT with sperm maturation, apoptosis and neurodegeneration."; RL Eur. J. Biochem. 221:917-925(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 6), SUBCELLULAR LOCATION, AND RP GLYCOSYLATION (ISOFORM 1). RX PubMed=24073260; DOI=10.1371/journal.pone.0075303; RA Prochnow H., Gollan R., Rohne P., Hassemer M., Koch-Brandt C., RA Baiersdoerfer M.; RT "Non-secreted clusterin isoforms are translated in rare amounts from RT distinct human mRNA variants and do not affect Bax-mediated apoptosis or RT the NF-kappaB signaling pathway."; RL PLoS ONE 8:E75303-E75303(2013). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND PARTIAL NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Stomach, and Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Small intestine; 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-317; ASN-328 AND RP LEU-396. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND PARTIAL NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain, and Spinal ganglion; 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 [10] RP PROTEIN SEQUENCE OF 23-33; 229-242; 303-317 AND 397-403, SUBUNIT, AND RP INTERACTION WITH APOA1. RX PubMed=1903064; DOI=10.1161/01.atv.11.3.645; RA James R.W., Hochstrasser A.-C., Borghini I., Martin B.M., Pometta D., RA Hochstrasser D.F.; RT "Characterization of a human high density lipoprotein-associated protein, RT NA1/NA2. Identity with SP-40,40, an inhibitor of complement-mediated RT cytolysis."; RL Arterioscler. Thromb. 11:645-652(1991). RN [11] RP PROTEIN SEQUENCE OF 23-52 AND 228-257, SUBUNIT, DISULFIDE BOND, PROTEOLYTIC RP PROCESSING, GLYCOSYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=2387851; DOI=10.1016/s0021-9258(18)77299-2; RA de Silva H., Stuart W.D., Park Y.B., Mao S.J.T., Gil C.M., Wetterau J.R., RA Busch S.J., Harmony J.A.K.; RT "Purification and characterization of apolipoprotein J."; RL J. Biol. Chem. 265:14292-14297(1990). RN [12] RP PROTEIN SEQUENCE OF 23-41 AND 228-246, INTERACTION WITH APP, SUBCELLULAR RP LOCATION, DISULFIDE BOND, AND TISSUE SPECIFICITY. RX PubMed=8328966; DOI=10.1042/bj2930027; RA Ghiso J., Matsubara E., Koudinov A., Choi-Miura N.-H., Tomita M., RA Wisniewski T., Frangione B.; RT "The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is RT complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement RT membrane-attack complex."; RL Biochem. J. 293:27-30(1993). RN [13] RP PROTEIN SEQUENCE OF 23-37 AND 228-242, AND INTERACTION WITH COMPLEMENT RP COMPLEX. RX PubMed=2601725; DOI=10.1016/0161-5890(89)90139-9; RA Choi N.H., Mazda T., Tomita M.; RT "A serum protein SP40,40 modulates the formation of membrane attack complex RT of complement on erythrocytes."; RL Mol. Immunol. 26:835-840(1989). RN [14] RP PROTEIN SEQUENCE OF 23-33 AND 228-240, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=3154963; RA Hochstrasser A.-C., James R.W., Martin B.M., Harrington M., RA Hochstrasser D.F., Pometta D., Merril C.R.; RT "HDL particle associated proteins in plasma and cerebrospinal fluid: RT identification and partial sequencing."; RL Appl. Theor. Electrophor. 1:73-76(1988). RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-449 (ISOFORMS 1/2/4/5/6), PROTEIN SEQUENCE RP OF 124-127; 195-221; 254-268; 336-353 AND 442-449, AND TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=1974459; DOI=10.1021/bi00474a025; RA de Silva H.V., Harmony J.A.K., Stuart W.D., Gil C.M., Robbins J.; RT "Apolipoprotein J: structure and tissue distribution."; RL Biochemistry 29:5380-5389(1990). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 61-449. RC TISSUE=Astrocytoma; RX PubMed=1924317; DOI=10.1073/pnas.88.19.8577; RA Danik M., Chabot J.G., Mercier C., Benabid A.L., Chauvin C., Quirion R., RA Suh M.; RT "Human gliomas and epileptic foci express high levels of a mRNA related to RT rat testicular sulfated glycoprotein 2, a purported marker of cell death."; RL Proc. Natl. Acad. Sci. U.S.A. 88:8577-8581(1991). RN [17] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 140-449. RC TISSUE=Fetal liver; RA Glew M.D., Kirszbaum L., Bozas S.E., Walker I.D.; RL Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases. RN [18] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN RP SEQUENCE. RC TISSUE=Liver; RX PubMed=2721499; DOI=10.1002/j.1460-2075.1989.tb03430.x; RA Kirszbaum L., Sharpe J.A., Murphy B., D'Apice J.F.A., Classon B., RA Hudson P., Walker I.D.; RT "Molecular cloning and characterization of the novel, human complement- RT associated protein, SP-40,40: a link between the complement and RT reproductive systems."; RL EMBO J. 8:711-718(1989). RN [19] RP PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-86; RP ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374. RX PubMed=1551440; DOI=10.1016/0014-5793(92)80330-j; RA Kirszbaum L., Bozas S.E., Walker I.D.; RT "SP-40,40, a protein involved in the control of the complement pathway, RT possesses a unique array of disulphide bridges."; RL FEBS Lett. 297:70-76(1992). RN [20] RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kim J.W.; RT "Identification of human aging-associated gene."; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [21] RP INTERACTION WITH APOA1. RX PubMed=1742316; DOI=10.1016/0005-2760(91)90167-g; RA Ehnholm C., Bozas S.E., Tenkanen H., Kirszbaum L., Metso J., Murphy B., RA Walker I.D.; RT "The apolipoprotein A-I binding protein of placenta and the SP-40,40 RT protein of human blood are different proteins which both bind to RT apolipoprotein A-I."; RL Biochim. Biophys. Acta 1086:255-260(1991). RN [22] RP DISULFIDE BONDS. RX PubMed=1491011; DOI=10.1093/oxfordjournals.jbchem.a123938; RA Choi-Miura N.H., Takahashi Y., Nakano Y., Tobe T., Tomita M.; RT "Identification of the disulfide bonds in human plasma protein SP-40,40 RT (apolipoprotein-J)."; RL J. Biochem. 112:557-561(1992). RN [23] RP INTERACTION WITH PON1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=8292612; DOI=10.1021/bi00169a026; RA Kelso G.J., Stuart W.D., Richter R.J., Furlong C.E., Jordan-Starck T.C., RA Harmony J.A.K.; RT "Apolipoprotein J is associated with paraoxonase in human plasma."; RL Biochemistry 33:832-839(1994). RN [24] RP INTERACTION WITH TGFBR2 AND ACVR1. RX PubMed=8555189; DOI=10.1021/bi951880a; RA Reddy K.B., Karode M.C., Harmony A.K., Howe P.H.; RT "Interaction of transforming growth factor beta receptors with RT apolipoprotein J/clusterin."; RL Biochemistry 35:309-314(1996). RN [25] RP GLYCOSYLATION AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374. RC TISSUE=Serum; RX PubMed=9336835; DOI=10.1002/pro.5560061007; RA Kapron J.T., Hilliard G.M., Lakins J.N., Tenniswood M.P., West K.A., RA Carr S.A., Crabb J.W.; RT "Identification and characterization of glycosylation sites in human serum RT clusterin."; RL Protein Sci. 6:2120-2133(1997). RN [26] RP FUNCTION, SUBCELLULAR LOCATION, ABSENCE OF ATPASE ACTIVITY, AND TISSUE RP SPECIFICITY. RX PubMed=11123922; DOI=10.1021/bi002189x; RA Poon S., Easterbrook-Smith S.B., Rybchyn M.S., Carver J.A., Wilson M.R.; RT "Clusterin is an ATP-independent chaperone with very broad substrate RT specificity that stabilizes stressed proteins in a folding-competent RT state."; RL Biochemistry 39:15953-15960(2000). RN [27] RP FUNCTION, AND SUBUNIT. RX PubMed=12047389; DOI=10.1046/j.1432-1033.2002.02957.x; RA Hatters D.M., Wilson M.R., Easterbrook-Smith S.B., Howlett G.J.; RT "Suppression of apolipoprotein C-II amyloid formation by the extracellular RT chaperone, clusterin."; RL Eur. J. Biochem. 269:2789-2794(2002). RN [28] RP FUNCTION, SUBUNIT, AND CIRCULAR DICHROISM. RX PubMed=12176985; DOI=10.1074/jbc.m204855200; RA Poon S., Rybchyn M.S., Easterbrook-Smith S.B., Carver J.A., Pankhurst G.J., RA Wilson M.R.; RT "Mildly acidic pH activates the extracellular molecular chaperone RT clusterin."; RL J. Biol. Chem. 277:39532-39540(2002). RN [29] RP ALTERNATIVE SPLICING, IDENTIFICATION OF ISOFORM 4, AND SUBCELLULAR RP LOCATION. RX PubMed=12551933; DOI=10.1074/jbc.m209233200; RA Leskov K.S., Klokov D.Y., Li J., Kinsella T.J., Boothman D.A.; RT "Synthesis and functional analyses of nuclear clusterin, a cell death RT protein."; RL J. Biol. Chem. 278:11590-11600(2003). RN [30] RP FUNCTION. RX PubMed=12882985; DOI=10.1074/jbc.c300252200; RA Santilli G., Aronow B.J., Sala A.; RT "Essential requirement of apolipoprotein J (clusterin) signaling for RT IkappaB expression and regulation of NF-kappaB activity."; RL J. Biol. Chem. 278:38214-38219(2003). RN [31] RP GLYCOSYLATION AT ASN-354. RC TISSUE=Serum; RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [32] RP INTERACTION WITH CLUAP1. RX PubMed=15480429; DOI=10.1038/sj.onc.1208100; RA Takahashi M., Lin Y.-M., Nakamura Y., Furukawa Y.; RT "Isolation and characterization of a novel gene CLUAP1 whose expression is RT frequently upregulated in colon cancer."; RL Oncogene 23:9289-9294(2004). RN [33] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-354 AND ASN-374. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [34] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-103; ASN-145; ASN-291; RP ASN-354 AND ASN-374. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [35] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BAX. RX PubMed=16113678; DOI=10.1038/ncb1291; RA Zhang H., Kim J.K., Edwards C.A., Xu Z., Taichman R., Wang C.Y.; RT "Clusterin inhibits apoptosis by interacting with activated Bax."; RL Nat. Cell Biol. 7:909-915(2005). RN [36] RP INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16548883; DOI=10.1111/j.1462-5822.2005.00644.x; RA Leong W.F., Chow V.T.; RT "Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal RT differential cellular gene expression in response to enterovirus 71 RT infection."; RL Cell. Microbiol. 8:565-580(2006). RN [37] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374. RC TISSUE=Saliva; RX PubMed=16740002; DOI=10.1021/pr050492k; RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.; RT "Identification of N-linked glycoproteins in human saliva by glycoprotein RT capture and mass spectrometry."; RL J. Proteome Res. 5:1493-1503(2006). RN [38] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [39] RP FUNCTION, SUBUNIT, INTERACTION WITH LRP2, GLYCOSYLATION, SUBCELLULAR RP LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, CIRCULAR DICHROISM, AND RP TISSUE SPECIFICITY. RX PubMed=17260971; DOI=10.1021/bi062082v; RA Stewart E.M., Aquilina J.A., Easterbrook-Smith S.B., Murphy-Durland D., RA Jacobsen C., Moestrup S., Wilson M.R.; RT "Effects of glycosylation on the structure and function of the RT extracellular chaperone clusterin."; RL Biochemistry 46:1412-1422(2007). RN [40] RP FUNCTION, INDUCTION, PROTEASOMAL DEGRADATION, AND SUBCELLULAR LOCATION. RX PubMed=17689225; DOI=10.1016/j.bbadis.2007.06.004; RA Ranney M.K., Ahmed I.S., Potts K.R., Craven R.J.; RT "Multiple pathways regulating the anti-apoptotic protein clusterin in RT breast cancer."; RL Biochim. Biophys. Acta 1772:1103-1111(2007). RN [41] RP IDENTIFICATION IN A COMPLEX WITH LTF; SEMG1 AND EPPIN. RX PubMed=17567961; DOI=10.1095/biolreprod.107.060194; RA Wang Z., Widgren E.E., Richardson R.T., O'Rand M.G.; RT "Characterization of an eppin protein complex from human semen and RT spermatozoa."; RL Biol. Reprod. 77:476-484(2007). RN [42] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17412999; DOI=10.1096/fj.06-7986com; RA Yerbury J.J., Poon S., Meehan S., Thompson B., Kumita J.R., Dobson C.M., RA Wilson M.R.; RT "The extracellular chaperone clusterin influences amyloid formation and RT toxicity by interacting with prefibrillar structures."; RL FASEB J. 21:2312-2322(2007). RN [43] RP ALTERNATIVE SPLICING, IDENTIFICATION OF ISOFORMS 1 AND 2, AND INDUCTION BY RP ANDROGEN. RX PubMed=17148459; DOI=10.1074/jbc.m608162200; RA Cochrane D.R., Wang Z., Muramaki M., Gleave M.E., Nelson C.C.; RT "Differential regulation of clusterin and its isoforms by androgens in RT prostate cells."; RL J. Biol. Chem. 282:2278-2287(2007). RN [44] RP FUNCTION, AND SUBUNIT. RX PubMed=17407782; DOI=10.1016/j.jmb.2007.02.095; RA Kumita J.R., Poon S., Caddy G.L., Hagan C.L., Dumoulin M., Yerbury J.J., RA Stewart E.M., Robinson C.V., Wilson M.R., Dobson C.M.; RT "The extracellular chaperone clusterin potently inhibits human lysozyme RT amyloid formation by interacting with prefibrillar species."; RL J. Mol. Biol. 369:157-167(2007). RN [45] RP ALTERNATIVE SPLICING, IDENTIFICATION OF ISOFORMS 1; 2 AND 5, AND TISSUE RP SPECIFICITY. RX PubMed=17322305; DOI=10.1074/mcp.m600261-mcp200; RA Andersen C.L., Schepeler T., Thorsen K., Birkenkamp-Demtroder K., RA Mansilla F., Aaltonen L.A., Laurberg S., Orntoft T.F.; RT "Clusterin expression in normal mucosa and colorectal cancer."; RL Mol. Cell. Proteomics 6:1039-1048(2007). RN [46] RP SUBCELLULAR LOCATION, INTERACTION WITH SYVN1, AND UBIQUITINATION. RX PubMed=17451556; DOI=10.1111/j.1600-0854.2007.00549.x; RA Nizard P., Tetley S., Le Drean Y., Watrin T., Le Goff P., Wilson M.R., RA Michel D.; RT "Stress-induced retrotranslocation of clusterin/ApoJ into the cytosol."; RL Traffic 8:554-565(2007). RN [47] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-291 AND ASN-374. RC TISSUE=Milk; RX PubMed=18780401; DOI=10.1002/pmic.200701057; RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.; RT "Identification of N-linked glycoproteins in human milk by hydrophilic RT interaction liquid chromatography and mass spectrometry."; RL Proteomics 8:3833-3847(2008). RN [48] RP FUNCTION, AND SUBUNIT. RX PubMed=19535339; DOI=10.1074/jbc.m109.033688; RA Wyatt A.R., Yerbury J.J., Wilson M.R.; RT "Structural characterization of clusterin-chaperone client protein RT complexes."; RL J. Biol. Chem. 284:21920-21927(2009). RN [49] RP FUNCTION, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=19137541; DOI=10.1002/jcp.21671; RA Rizzi F., Caccamo A.E., Belloni L., Bettuzzi S.; RT "Clusterin is a short half-life, poly-ubiquitinated protein, which controls RT the fate of prostate cancer cells."; RL J. Cell. Physiol. 219:314-323(2009). RN [50] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-103; ASN-145; ASN-354 RP AND ASN-374. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [51] RP GLYCOSYLATION AT ASN-86 AND ASN-374. RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [52] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374, AND STRUCTURE OF RP CARBOHYDRATES. RC TISSUE=Cerebrospinal fluid; RX PubMed=19838169; DOI=10.1038/nmeth.1392; RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., RA Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [53] RP FUNCTION. RX PubMed=19996109; DOI=10.1074/jbc.m109.079566; RA Wyatt A.R., Wilson M.R.; RT "Identification of human plasma proteins as major clients for the RT extracellular chaperone clusterin."; RL J. Biol. Chem. 285:3532-3539(2010). RN [54] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH COMMD1; UBIQUITIN; CUL1 RP AND BTRC, AND IDENTIFICATION IN A E3 UBIQUITIN-PROTEIN LIGASE COMPLEX. RX PubMed=20068069; DOI=10.1158/1541-7786.mcr-09-0277; RA Zoubeidi A., Ettinger S., Beraldi E., Hadaschik B., Zardan A., Klomp L.W., RA Nelson C.C., Rennie P.S., Gleave M.E.; RT "Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF-kappaB RT activity in prostate cancer cells."; RL Mol. Cancer Res. 8:119-130(2010). RN [55] RP FUNCTION. RX PubMed=21505792; DOI=10.1007/s00018-011-0684-8; RA Wyatt A.R., Yerbury J.J., Berghofer P., Greguric I., Katsifis A., RA Dobson C.M., Wilson M.R.; RT "Clusterin facilitates in vivo clearance of extracellular misfolded RT proteins."; RL Cell. Mol. Life Sci. 68:3919-3931(2011). RN [56] RP INTERACTION WITH BCL2L1, AND FUNCTION. RX PubMed=21567405; DOI=10.1002/jcp.22836; RA Kim N., Yoo J.C., Han J.Y., Hwang E.M., Kim Y.S., Jeong E.Y., Sun C.H., RA Yi G.S., Roh G.S., Kim H.J., Kang S.S., Cho G.J., Park J.Y., Choi W.S.; RT "Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL RT through C-terminal coiled coil domain."; RL J. Cell. Physiol. 227:1157-1167(2012). RN [57] RP INTERACTION WITH HSPA5, SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-86; RP ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374, GLYCOSYLATION, AND RP FUNCTION. RX PubMed=22689054; DOI=10.1038/onc.2012.212; RA Li N., Zoubeidi A., Beraldi E., Gleave M.E.; RT "GRP78 regulates clusterin stability, retrotranslocation and mitochondrial RT localization under ER stress in prostate cancer."; RL Oncogene 32:1933-1942(2013). RN [58] RP GLYCOSYLATION, PROTEOLYTIC CLEAVAGE, MUTAGENESIS OF VAL-226 AND ARG-227, RP AND SITE. RX PubMed=25402950; DOI=10.1159/000366365; RA Rohne P., Prochnow H., Wolf S., Renner B., Koch-Brandt C.; RT "The chaperone activity of clusterin is dependent on glycosylation and RT redox environment."; RL Cell. Physiol. Biochem. 34:1626-1639(2014). RN [59] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133 AND SER-396, AND 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 [60] RP INTERACTION WITH VLDLR AND LRP8. RX PubMed=24381170; DOI=10.1074/jbc.m113.529271; RA Leeb C., Eresheim C., Nimpf J.; RT "Clusterin is a ligand for apolipoprotein E receptor 2 (ApoER2) and very RT low density lipoprotein receptor (VLDLR) and signals via the Reelin- RT signaling pathway."; RL J. Biol. Chem. 289:4161-4172(2014). CC -!- FUNCTION: [Isoform 1]: Functions as extracellular chaperone that CC prevents aggregation of non native proteins (PubMed:11123922, CC PubMed:19535339). Prevents stress-induced aggregation of blood plasma CC proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, CC PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, CC B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) CC (PubMed:12047389, PubMed:17412999, PubMed:17407782). Does not require CC ATP (PubMed:11123922). Maintains partially unfolded proteins in a state CC appropriate for subsequent refolding by other chaperones, such as CC HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself CC (PubMed:11123922). Binding to cell surface receptors triggers CC internalization of the chaperone-client complex and subsequent CC lysosomal or proteasomal degradation (PubMed:21505792). Protects cells CC against apoptosis and against cytolysis by complement (PubMed:2780565). CC Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box CC protein) E3 ubiquitin-protein ligase complexes and promote the CC ubiquitination and subsequent proteasomal degradation of target CC proteins (PubMed:20068069). Promotes proteasomal degradation of COMMD1 CC and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional CC activity (PubMed:12882985). A mitochondrial form suppresses BAX- CC dependent release of cytochrome c into the cytoplasm and inhibit CC apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the CC regulation of cell proliferation (PubMed:19137541). An intracellular CC form suppresses stress-induced apoptosis by stabilizing mitochondrial CC membrane integrity through interaction with HSPA5 (PubMed:22689054). CC Secreted form does not affect caspase or BAX-mediated intrinsic CC apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). CC Secreted form act as an important modulator during neuronal CC differentiation through interaction with STMN3 (By similarity). Plays a CC role in the clearance of immune complexes that arise during cell injury CC (By similarity). {ECO:0000250|UniProtKB:P05371, CC ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:11123922, CC ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, CC ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:16113678, CC ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, CC ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, CC ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, CC ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, CC ECO:0000269|PubMed:21505792, ECO:0000269|PubMed:22689054, CC ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:2780565}. CC -!- FUNCTION: [Isoform 6]: Does not affect caspase or BAX-mediated CC intrinsic apoptosis and TNF-induced NF-kappa-B-activity. CC {ECO:0000269|PubMed:24073260}. CC -!- FUNCTION: [Isoform 4]: Does not affect caspase or BAX-mediated CC intrinsic apoptosis and TNF-induced NF-kappa-B-activity CC (PubMed:24073260). Promotes cell death through interaction with BCL2L1 CC that releases and activates BAX (PubMed:21567405). CC {ECO:0000269|PubMed:21567405, ECO:0000269|PubMed:24073260}. CC -!- SUBUNIT: Antiparallel disulfide-linked heterodimer of an alpha chain CC and a beta chain (PubMed:12047389, PubMed:1491011, PubMed:1551440, CC PubMed:2780565, PubMed:2387851, PubMed:8328966). Self-associates and CC forms higher oligomers (PubMed:1903064). Interacts with a broad range CC of misfolded proteins, including APP, APOC2 and LYZ (PubMed:17407782, CC PubMed:8328966, PubMed:17412999). Slightly acidic pH promotes CC interaction with misfolded proteins (PubMed:12176985). Forms high- CC molecular weight oligomers upon interaction with misfolded proteins CC (PubMed:19535339). Interacts with APOA1, LRP2, CLUAP1 and PON1 CC (PubMed:15480429, PubMed:17260971, PubMed:1742316, PubMed:8292612, CC PubMed:1903064). Interacts with the complement complex CC (PubMed:2601725). Interacts (via alpha chain) with XRCC6 (By CC similarity). Interacts with SYVN1, COMMD1, BTRC, CUL1 and with CC ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase CC complexes (PubMed:17451556, PubMed:20068069). Interacts (via alpha CC chain) with BAX in stressed cells, where BAX undergoes a conformation CC change leading to association with the mitochondrial membrane CC (PubMed:16113678). Does not interact with BAX in unstressed cells CC (PubMed:16113678). Found in a complex with LTF, CLU, EPPIN and SEMG1 CC (PubMed:17567961). Interacts (immaturely glycosylated pre-secreted CC form) with HSPA5; this interaction promotes CLU stability and CC facilitates stress-induced CLU retrotranslocation from the secretory CC pathway to the mitochondria, thereby reducing stress-induced apoptosis CC by stabilizing mitochondrial membrane integrity (PubMed:22689054). CC Interacts (isoform 4) with BCL2L1; this interaction releases and CC activates BAX and promotes cell death (PubMed:21567405). Interacts with CC TGFBR2 and ACVR1 (PubMed:8555189). Interacts (secreted form) with CC STMN3; this interaction may act as an important modulator during CC neuronal differentiation (By similarity). Interacts with VLDLR and LRP8 CC (PubMed:24381170). {ECO:0000250|UniProtKB:P05371, CC ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:12047389, CC ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:1491011, CC ECO:0000269|PubMed:15480429, ECO:0000269|PubMed:1551440, CC ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, CC ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, CC ECO:0000269|PubMed:1742316, ECO:0000269|PubMed:17451556, CC ECO:0000269|PubMed:17567961, ECO:0000269|PubMed:1903064, CC ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:1974459, CC ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21567405, CC ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:2387851, CC ECO:0000269|PubMed:24381170, ECO:0000269|PubMed:2601725, CC ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:8292612, CC ECO:0000269|PubMed:8328966, ECO:0000269|PubMed:8555189}. CC -!- INTERACTION: CC P10909; P18509: ADCYAP1; NbExp=4; IntAct=EBI-1104674, EBI-8588930; CC P10909; P05067: APP; NbExp=3; IntAct=EBI-1104674, EBI-77613; CC P10909; PRO_0000000093 [P05067]: APP; NbExp=4; IntAct=EBI-1104674, EBI-2431589; CC P10909; Q9NRI5: DISC1; NbExp=4; IntAct=EBI-1104674, EBI-529989; CC P10909; P01100: FOS; NbExp=2; IntAct=EBI-1104674, EBI-852851; CC P10909; P30101: PDIA3; NbExp=2; IntAct=EBI-1104674, EBI-979862; CC P10909; P37231: PPARG; NbExp=3; IntAct=EBI-1104674, EBI-781384; CC P10909; P37840: SNCA; NbExp=4; IntAct=EBI-1104674, EBI-985879; CC P10909-4; Q07817-1: BCL2L1; NbExp=6; IntAct=EBI-4322678, EBI-287195; CC P10909-5; PRO_0000000092 [P05067]: APP; NbExp=2; IntAct=EBI-10961636, EBI-821758; CC P10909-5; Q9NZV6: MSRB1; NbExp=10; IntAct=EBI-10961636, EBI-12330065; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted CC {ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:17260971, CC ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17451556, CC ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:24073260, CC ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:3154963, CC ECO:0000269|PubMed:8292612, ECO:0000269|PubMed:8328966}. Note=Can CC retrotranslocate from the secretory compartments to the cytosol upon CC cellular stress. {ECO:0000269|PubMed:17451556}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm CC {ECO:0000269|PubMed:24073260}. Note=Keeps cytoplasmic localization in CC stressed and unstressed cell. {ECO:0000269|PubMed:24073260}. CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Cytoplasm CC {ECO:0000269|PubMed:24073260}. Note=Keeps cytoplasmic localization in CC stressed and unstressed cell. {ECO:0000269|PubMed:24073260}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12551933, CC ECO:0000269|PubMed:19137541}. Cytoplasm {ECO:0000269|PubMed:12551933, CC ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:19137541, CC ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:22689054, CC ECO:0000269|PubMed:24073260}. Mitochondrion membrane; Peripheral CC membrane protein; Cytoplasmic side {ECO:0000269|PubMed:17689225}. CC Cytoplasm, cytosol {ECO:0000269|PubMed:17451556, CC ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260}. Microsome CC {ECO:0000269|PubMed:22689054}. Endoplasmic reticulum CC {ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:22689054}. CC Mitochondrion {ECO:0000269|PubMed:16113678, CC ECO:0000269|PubMed:22689054}. Mitochondrion membrane CC {ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17689225}. Cytoplasm, CC perinuclear region {ECO:0000250|UniProtKB:P05371}. Cytoplasmic vesicle, CC secretory vesicle, chromaffin granule {ECO:0000250}. Note=Secreted CC isoforms can retrotranslocate from the secretory compartments to the CC cytosol upon cellular stress (PubMed:17451556). Detected in perinuclear CC foci that may be aggresomes containing misfolded, ubiquitinated CC proteins (PubMed:20068069). Detected at the mitochondrion membrane upon CC induction of apoptosis (PubMed:17689225). Under ER stress, a immaturely CC glycosylated pre-secreted form retrotranslocates from the endoplasmic CC reticulum (ER)-Golgi network to the cytoplasm to localize in the CC mitochondria through HSPA5 interaction (PubMed:22689054). ER stress CC reduces secretion (PubMed:22689054). Under the stress, minor amounts of CC non-secreted forms accumulate in cytoplasm (PubMed:24073260, CC PubMed:22689054, PubMed:17451556). Non-secreted forms emerge mainly CC from failed translocation, alternative splicing or non-canonical CC initiation start codon (PubMed:24073260, PubMed:12551933). CC {ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:17451556, CC ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:20068069, CC ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=2, CLU35, sCLU; CC IsoId=P10909-1; Sequence=Displayed; CC Name=2; Synonyms=1, CLU34; CC IsoId=P10909-2; Sequence=VSP_037661; CC Name=3; CC IsoId=P10909-3; Sequence=VSP_041475; CC Name=4; Synonyms=nCLU {ECO:0000303|PubMed:12551933}; CC IsoId=P10909-4; Sequence=VSP_041476; CC Name=5; Synonyms=CLU36; CC IsoId=P10909-5; Sequence=VSP_041477; CC Name=6; CC IsoId=P10909-6; Sequence=VSP_060188, VSP_060192; CC -!- TISSUE SPECIFICITY: Detected in blood plasma, cerebrospinal fluid, CC milk, seminal plasma and colon mucosa. Detected in the germinal center CC of colon lymphoid nodules and in colon parasympathetic ganglia of the CC Auerbach plexus (at protein level). Ubiquitous. Detected in brain, CC testis, ovary, liver and pancreas, and at lower levels in kidney, CC heart, spleen and lung. {ECO:0000269|PubMed:11123922, CC ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17322305, CC ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:1974459, CC ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:2780565, CC ECO:0000269|PubMed:3154963, ECO:0000269|PubMed:8181474, CC ECO:0000269|PubMed:8292612, ECO:0000269|PubMed:8328966}. CC -!- INDUCTION: Up-regulated in response to enterovirus 71 (EV71) infection CC (at protein level) (PubMed:16548883). Up-regulated by agents that CC induce apoptosis, both at mRNA and protein level (PubMed:17689225). CC Isoform 1 is up-regulated by androgen (PubMed:17148459). Isoform 2 is CC down-regulated by androgen (PubMed:17148459). CC {ECO:0000269|PubMed:16548883, ECO:0000269|PubMed:17148459, CC ECO:0000269|PubMed:17689225}. CC -!- PTM: Proteolytically cleaved on its way through the secretory system, CC probably within the Golgi lumen (PubMed:2387851). Proteolytic cleavage CC is not necessary for its chaperone activity (PubMed:25402950). All non- CC secreted forms are not proteolytically cleaved (PubMed:24073260). CC Chaperone activity of uncleaved forms is dependent on a non-reducing CC environment (PubMed:25402950). {ECO:0000269|PubMed:2387851, CC ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:25402950}. CC -!- PTM: Polyubiquitinated, leading to proteasomal degradation CC (PubMed:17451556, PubMed:19137541). Under cellular stress, the CC intracellular level of cleaved form is reduced due to proteasomal CC degradation (PubMed:17451556). {ECO:0000269|PubMed:17451556, CC ECO:0000269|PubMed:19137541}. CC -!- PTM: Extensively glycosylated with sulfated N-linked carbohydrates CC (PubMed:17260971, PubMed:2387851). About 30% of the protein mass is CC comprised of complex N-linked carbohydrate (PubMed:2387851). CC Endoplasmic reticulum (ER) stress induces changes in glycosylation CC status and increases level of hypoglycosylated forms (PubMed:22689054). CC Core carbohydrates are essential for chaperone activity CC (PubMed:25402950). Non-secreted forms are hypoglycosylated or CC unglycosylated (PubMed:24073260). {ECO:0000269|PubMed:17260971, CC ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:2387851, CC ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:25402950}. CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform. Major isoform. Detectable at CC protein level in stressed and unstressed cells (PubMed:24073260). CC {ECO:0000269|PubMed:24073260}. CC -!- MISCELLANEOUS: [Isoform 4]: Minor isoform that has been detected in a CC breast cancer cell line, but not in any other tissues or cell lines CC (PubMed:12551933). Not glycosylated. Not detected in unstressed cells. CC Detectable at low level in stressed cells (PubMed:24073260). CC {ECO:0000269|PubMed:24073260, ECO:0000303|PubMed:12551933}. CC -!- MISCELLANEOUS: [Isoform 6]: Translated from an unconventional CC translation initiation site CTG (PubMed:24073260). Not glycosylated CC (PubMed:24073260). Not detected in unstressed cells. Detectable at low CC level in stressed cells (PubMed:24073260). CC {ECO:0000269|PubMed:24073260}. CC -!- SIMILARITY: Belongs to the clusterin family. {ECO:0000305}. CC -!- CAUTION: Isoform 4 has been previously detected in cytosol and in the CC nuclei of apoptotic cells and promoted apoptosis following irradiation CC (PubMed:12551933). However the nuclear localization and apoptosis CC promotion has not been confirmed in other cell types (PubMed:24073260). CC {ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:24073260}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35692.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAB06508.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAB06508.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence={ECO:0000305}; CC Sequence=AAH10514.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH19588.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAP88927.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=AAP88927.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAT08041.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG36598.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA32847.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/clu/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40107/CLU"; 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; M25915; AAA35692.1; ALT_INIT; mRNA. DR EMBL; M63379; AAB06507.1; -; Genomic_DNA. DR EMBL; M63376; AAB06507.1; JOINED; Genomic_DNA. DR EMBL; M63377; AAB06507.1; JOINED; Genomic_DNA. DR EMBL; M63378; AAB06507.1; JOINED; Genomic_DNA. DR EMBL; M64722; AAB06508.1; ALT_SEQ; mRNA. DR EMBL; AK093399; BAG52708.1; -; mRNA. DR EMBL; AK313870; BAG36598.1; ALT_INIT; mRNA. DR EMBL; CR599675; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BX648414; CAI45990.1; -; mRNA. DR EMBL; AY341244; AAP88927.1; ALT_INIT; Genomic_DNA. DR EMBL; AF311103; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC010514; AAH10514.1; ALT_INIT; mRNA. DR EMBL; BC019588; AAH19588.1; ALT_INIT; mRNA. DR EMBL; BU150467; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; J02908; AAA51765.1; -; mRNA. DR EMBL; M74816; AAA60321.1; -; mRNA. DR EMBL; L00974; AAA60567.1; -; Genomic_DNA. DR EMBL; X14723; CAA32847.1; ALT_INIT; mRNA. DR EMBL; AY513288; AAT08041.1; ALT_INIT; mRNA. DR CCDS; CCDS47832.1; -. [P10909-1] DR PIR; S43646; A41386. DR RefSeq; NP_001822.3; NM_001831.3. [P10909-1] DR PDB; 7ZET; X-ray; 2.80 A; A=23-449. DR PDB; 7ZEU; X-ray; 3.50 A; A/D=23-449. DR PDBsum; 7ZET; -. DR PDBsum; 7ZEU; -. DR AlphaFoldDB; P10909; -. DR SMR; P10909; -. DR BioGRID; 107603; 274. DR DIP; DIP-37546N; -. DR IntAct; P10909; 177. DR MINT; P10909; -. DR STRING; 9606.ENSP00000315130; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR GuidetoPHARMACOLOGY; 3195; -. DR CarbonylDB; P10909; -. DR GlyConnect; 759; 142 N-Linked glycans (6 sites). DR GlyCosmos; P10909; 7 sites, 157 glycans. DR GlyGen; P10909; 12 sites, 158 N-linked glycans (6 sites), 3 O-linked glycans (4 sites). DR iPTMnet; P10909; -. DR PhosphoSitePlus; P10909; -. DR BioMuta; CLU; -. DR DMDM; 116533; -. DR DOSAC-COBS-2DPAGE; P10909; -. DR OGP; P10909; -. DR REPRODUCTION-2DPAGE; IPI00291262; -. DR CPTAC; CPTAC-478; -. DR CPTAC; CPTAC-479; -. DR CPTAC; CPTAC-661; -. DR CPTAC; CPTAC-662; -. DR CPTAC; CPTAC-728; -. DR CPTAC; non-CPTAC-1096; -. DR CPTAC; non-CPTAC-1097; -. DR CPTAC; non-CPTAC-1098; -. DR EPD; P10909; -. DR jPOST; P10909; -. DR MassIVE; P10909; -. DR MaxQB; P10909; -. DR PaxDb; 9606-ENSP00000315130; -. DR PeptideAtlas; P10909; -. DR PRIDE; P10909; -. DR ProteomicsDB; 52663; -. [P10909-1] DR ProteomicsDB; 52664; -. [P10909-2] DR ProteomicsDB; 52665; -. [P10909-3] DR ProteomicsDB; 52666; -. [P10909-4] DR ProteomicsDB; 52667; -. [P10909-5] DR Pumba; P10909; -. DR ABCD; P10909; 1 sequenced antibody. DR Antibodypedia; 631; 1388 antibodies from 52 providers. DR CPTC; P10909; 1 antibody. DR DNASU; 1191; -. DR Ensembl; ENST00000316403.15; ENSP00000315130.10; ENSG00000120885.22. [P10909-1] DR Ensembl; ENST00000405140.7; ENSP00000385419.3; ENSG00000120885.22. [P10909-1] DR Ensembl; ENST00000523500.5; ENSP00000429620.1; ENSG00000120885.22. [P10909-1] DR GeneID; 1191; -. DR KEGG; hsa:1191; -. DR MANE-Select; ENST00000316403.15; ENSP00000315130.10; NM_001831.4; NP_001822.3. DR UCSC; uc003xfw.3; human. [P10909-1] DR AGR; HGNC:2095; -. DR CTD; 1191; -. DR DisGeNET; 1191; -. DR GeneCards; CLU; -. DR HGNC; HGNC:2095; CLU. DR HPA; ENSG00000120885; Tissue enhanced (liver). DR MIM; 185430; gene. DR neXtProt; NX_P10909; -. DR NIAGADS; ENSG00000120885; -. DR OpenTargets; ENSG00000120885; -. DR PharmGKB; PA26620; -. DR VEuPathDB; HostDB:ENSG00000120885; -. DR eggNOG; ENOG502RBQP; Eukaryota. DR GeneTree; ENSGT00530000063668; -. DR HOGENOM; CLU_042162_2_0_1; -. DR InParanoid; P10909; -. DR OMA; QGSKYIN; -. DR OrthoDB; 4321242at2759; -. DR PhylomeDB; P10909; -. DR TreeFam; TF333030; -. DR PathwayCommons; P10909; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-166665; Terminal pathway of complement. DR Reactome; R-HSA-6803157; Antimicrobial peptides. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P10909; -. DR SIGNOR; P10909; -. DR BioGRID-ORCS; 1191; 13 hits in 1159 CRISPR screens. DR ChiTaRS; CLU; human. DR GeneWiki; Clusterin; -. DR GenomeRNAi; 1191; -. DR Pharos; P10909; Tbio. DR PRO; PR:P10909; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; P10909; Protein. DR Bgee; ENSG00000120885; Expressed in lateral globus pallidus and 209 other cell types or tissues. DR ExpressionAtlas; P10909; baseline and differential. DR GO; GO:0097440; C:apical dendrite; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0042583; C:chromaffin granule; IEA:UniProtKB-SubCell. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:ParkinsonsUK-UCL. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0097418; C:neurofibrillary tangle; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0099020; C:perinuclear endoplasmic reticulum lumen; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0045202; C:synapse; IEA:Ensembl. DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL. DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:ARUK-UCL. DR GO; GO:0051787; F:misfolded protein binding; IDA:UniProtKB. DR GO; GO:0140597; F:protein carrier chaperone; IDA:ARUK-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL. DR GO; GO:0051087; F:protein-folding chaperone binding; ISS:ParkinsonsUK-UCL. DR GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL. DR GO; GO:0048156; F:tau protein binding; IPI:ARUK-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; IMP:UniProtKB. DR GO; GO:0000902; P:cell morphogenesis; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0032286; P:central nervous system myelin maintenance; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB. DR GO; GO:0006956; P:complement activation; TAS:ProtInc. DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW. DR GO; GO:0002434; P:immune complex clearance; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc. DR GO; GO:0001774; P:microglial cell activation; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0061518; P:microglial cell proliferation; IDA:Alzheimers_University_of_Toronto. DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; IDA:ARUK-UCL. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IDA:Alzheimers_University_of_Toronto. DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:BHF-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:ARUK-UCL. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:ARUK-UCL. DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; TAS:ARUK-UCL. DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; IMP:ARUK-UCL. DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; TAS:ARUK-UCL. DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:1902998; P:positive regulation of neurofibrillary tangle assembly; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:ARUK-UCL. DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IGI:ARUK-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:Alzheimers_University_of_Toronto. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0017038; P:protein import; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB. DR GO; GO:0061740; P:protein targeting to lysosome involved in chaperone-mediated autophagy; IDA:ARUK-UCL. DR GO; GO:1900221; P:regulation of amyloid-beta clearance; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:1902847; P:regulation of neuronal signal transduction; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IC:BHF-UCL. DR GO; GO:0051788; P:response to misfolded protein; IDA:BHF-UCL. DR GO; GO:0009615; P:response to virus; IEP:UniProtKB. DR GO; GO:0043691; P:reverse cholesterol transport; TAS:BHF-UCL. DR InterPro; IPR016016; Clusterin. DR InterPro; IPR000753; Clusterin-like. DR InterPro; IPR016015; Clusterin_C. DR InterPro; IPR033986; Clusterin_CS. DR InterPro; IPR016014; Clusterin_N. DR PANTHER; PTHR10970; CLUSTERIN; 1. DR PANTHER; PTHR10970:SF1; CLUSTERIN; 1. DR Pfam; PF01093; Clusterin; 1. DR PIRSF; PIRSF002368; Clusterin; 1. DR SMART; SM00035; CLa; 1. DR SMART; SM00030; CLb; 1. DR PROSITE; PS00492; CLUSTERIN_1; 1. DR PROSITE; PS00493; CLUSTERIN_2; 1. DR SWISS-2DPAGE; P10909; -. DR Genevisible; P10909; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Chaperone; KW Complement pathway; Cytoplasm; Cytoplasmic vesicle; KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; KW Glycoprotein; Immunity; Innate immunity; Membrane; Microsome; KW Mitochondrion; Nucleus; Phosphoprotein; Reference proteome; Secreted; KW Signal; Ubl conjugation. FT SIGNAL 1..22 FT /evidence="ECO:0000269|PubMed:1903064, FT ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:2601725, FT ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:3154963, FT ECO:0000269|PubMed:8328966" FT CHAIN 23..449 FT /note="Clusterin" FT /id="PRO_0000005529" FT CHAIN 23..227 FT /note="Clusterin beta chain" FT /evidence="ECO:0000269|PubMed:2387851, FT ECO:0000269|PubMed:2721499" FT /id="PRO_0000005530" FT CHAIN 228..449 FT /note="Clusterin alpha chain" FT /evidence="ECO:0000269|PubMed:2387851, FT ECO:0000269|PubMed:2721499" FT /id="PRO_0000005531" FT MOTIF 78..81 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:Q06890" FT MOTIF 443..447 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:Q06890" FT SITE 227..228 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:25402950" FT MOD_RES 133 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 396 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:1551440, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:9336835" FT CARBOHYD 103 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:1551440, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:2721499, ECO:0000269|PubMed:9336835" FT CARBOHYD 145 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:1551440, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:2721499, ECO:0000269|PubMed:9336835" FT CARBOHYD 291 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:1551440, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:18780401, FT ECO:0000269|PubMed:2721499, ECO:0000269|PubMed:9336835" FT CARBOHYD 354 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:1551440, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:9336835" FT CARBOHYD 374 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:1551440, ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002, FT ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, FT ECO:0000269|PubMed:9336835" FT DISULFID 102..313 FT /note="Interchain (between beta and alpha chains)" FT DISULFID 113..305 FT /note="Interchain (between beta and alpha chains)" FT DISULFID 116..302 FT /note="Interchain (between beta and alpha chains)" FT DISULFID 121..295 FT /note="Interchain (between beta and alpha chains)" FT DISULFID 129..285 FT /note="Interchain (between beta and alpha chains)" FT VAR_SEQ 1..175 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041475" FT VAR_SEQ 1..33 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_041476" FT VAR_SEQ 1..20 FT /note="Missing (in isoform 6)" FT /id="VSP_060188" FT VAR_SEQ 1 FT /note="M -> MQVCSQPQRGCVREQSAINTAPPSAHNAASPGGARGHRVPLTEACKD FT SRIGGM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:2780565, ECO:0000303|Ref.5" FT /id="VSP_037661" FT VAR_SEQ 1 FT /note="M -> MEACKDSRIGGM (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_041477" FT VAR_SEQ 21 FT /note="L -> M (in isoform 6)" FT /id="VSP_060192" FT VARIANT 317 FT /note="N -> H (in dbSNP:rs9331936)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019366" FT VARIANT 328 FT /note="D -> N (in dbSNP:rs9331938)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019367" FT VARIANT 396 FT /note="S -> L (in dbSNP:rs13494)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_019368" FT MUTAGEN 86 FT /note="N->Q: Decreases molecular mass of beta chain; when FT associated with Q-103 and Q-145." FT /evidence="ECO:0000269|PubMed:22689054" FT MUTAGEN 103 FT /note="N->Q: Decreases molecular mass of beta chain; when FT associated with Q-86 and Q-145." FT /evidence="ECO:0000269|PubMed:22689054" FT MUTAGEN 145 FT /note="N->Q: Decreases molecular mass of beta chain; when FT associated with Q-86 and Q-103." FT /evidence="ECO:0000269|PubMed:22689054" FT MUTAGEN 226 FT /note="V->T: Does not affect proteolytic cleavage." FT /evidence="ECO:0000269|PubMed:25402950" FT MUTAGEN 227 FT /note="R->Q: Affects proteolytic cleavage." FT /evidence="ECO:0000269|PubMed:25402950" FT MUTAGEN 291 FT /note="N->Q: Decreases molecular mass of alpha chain; when FT associated with Q-354 and Q-374. Decreases secretion; when FT associated with Q-354 and Q-374." FT /evidence="ECO:0000269|PubMed:22689054" FT MUTAGEN 354 FT /note="N->Q: Decreases molecular mass of alpha chain; when FT associated with Q-291 and Q-374. Decreases secretion; when FT associated with Q-291 and Q-374." FT /evidence="ECO:0000269|PubMed:22689054" FT MUTAGEN 374 FT /note="N->Q: Decreases molecular mass of alpha chain; when FT associated with Q-291 and Q-354. Decreases secretion; when FT associated with Q-291 and Q-354." FT /evidence="ECO:0000269|PubMed:22689054" FT CONFLICT 28 FT /note="D -> S (in Ref. 10; AA sequence and 14; AA FT sequence)" FT /evidence="ECO:0000305" FT CONFLICT 47 FT /note="Q -> H (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 52 FT /note="G -> Q (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 172 FT /note="M -> V (in Ref. 6; CAI45990)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="R -> L (in Ref. 4; BAG36598)" FT /evidence="ECO:0000305" FT CONFLICT 305 FT /note="C -> M (in Ref. 10; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 388 FT /note="T -> M (in Ref. 6; CAI45990)" FT /evidence="ECO:0000305" FT CONFLICT 411 FT /note="D -> G (in Ref. 4; BAG36598)" FT /evidence="ECO:0000305" SQ SEQUENCE 449 AA; 52495 MW; 9583DE4CCECC169F CRC64; MMKTLLLFVG LLLTWESGQV LGDQTVSDNE LQEMSNQGSK YVNKEIQNAV NGVKQIKTLI EKTNEERKTL LSNLEEAKKK KEDALNETRE SETKLKELPG VCNETMMALW EECKPCLKQT CMKFYARVCR SGSGLVGRQL EEFLNQSSPF YFWMNGDRID SLLENDRQQT HMLDVMQDHF SRASSIIDEL FQDRFFTREP QDTYHYLPFS LPHRRPHFFF PKSRIVRSLM PFSPYEPLNF HAMFQPFLEM IHEAQQAMDI HFHSPAFQHP PTEFIREGDD DRTVCREIRH NSTGCLRMKD QCDKCREILS VDCSTNNPSQ AKLRRELDES LQVAERLTRK YNELLKSYQW KMLNTSSLLE QLNEQFNWVS RLANLTQGED QYYLRVTTVA SHTSDSDVPS GVTEVVVKLF DSDPITVTVP VEVSRKNPKF METVAEKALQ EYRKKHREE //