CLUS_HUMAN
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 03-AUG-2022, entry version 239.
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};
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;
DE AltName: Full=Complement cytolysis inhibitor a chain;
DE Contains:
DE RecName: Full=Clusterin alpha chain;
DE AltName: Full=ApoJbeta;
DE AltName: Full=Complement cytolysis inhibitor b chain;
DE Flags: Precursor;
GN Name=CLU {ECO:0000312|HGNC:HGNC:2095};
GN Synonyms=APOJ {ECO:0000303|PubMed:2387851},
GN CLI {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), PARTIAL PROTEIN
RP SEQUENCE, SUBUNIT, AND TISSUE SPECIFICITY.
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, PubMed:1974459). Self-
CC associates and forms higher oligomers (PubMed:1903064). Interacts with
CC a broad range of misfolded proteins, including APP, APOC2 and LYZ
CC (PubMed:17407782, PubMed:8328966, PubMed:17412999). Slightly acidic pH
CC promotes interaction with misfolded proteins (PubMed:12176985). Forms
CC high-molecular weight oligomers upon interaction with misfolded
CC proteins (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 envoronment (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="http://atlasgeneticsoncology.org/Genes/CLUID40107ch8p21.html";
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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 AlphaFoldDB; P10909; -.
DR SMR; P10909; -.
DR BioGRID; 107603; 257.
DR DIP; DIP-37546N; -.
DR IntAct; P10909; 159.
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 GlyGen; P10909; 9 sites, 149 N-linked glycans (6 sites), 1 O-linked glycan (1 site).
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 SWISS-2DPAGE; P10909; -.
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; P10909; -.
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 ABCD; P10909; 1 sequenced antibody.
DR Antibodypedia; 631; 1266 antibodies from 51 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 CTD; 1191; -.
DR DisGeNET; 1191; -.
DR GeneCards; CLU; -.
DR HGNC; HGNC:2095; CLU.
DR HPA; ENSG00000120885; Tissue enhanced (brain, 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; 973835at2759; -.
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 1077 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 207 other tissues.
DR ExpressionAtlas; P10909; baseline and differential.
DR Genevisible; P10909; HS.
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:UniProtKB.
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:0051087; F:chaperone binding; ISS:ParkinsonsUK-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:0046982; F:protein heterodimerization activity; TAS:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-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:0060548; P:negative regulation of cell death; IMP:ARUK-UCL.
DR GO; GO:1905892; P:negative regulation of cellular response to thapsigargin; IMP:ARUK-UCL.
DR GO; GO:1905895; P:negative regulation of cellular response to tunicamycin; IMP:ARUK-UCL.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:BHF-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:1901216; P:positive regulation of neuron death; IDA: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:1902949; P:positive regulation of tau-protein kinase activity; IMP:Alzheimers_University_of_Toronto.
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:1901214; P:regulation of neuron death; IDA:Alzheimers_University_of_Toronto.
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; PTHR10970; 1.
DR PANTHER; PTHR10970:SF1; PTHR10970:SF1; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Chaperone; Complement pathway; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Immunity; Innate immunity; Membrane;
KW Microsome; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome;
KW Secreted; 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:1974459"
FT /id="PRO_0000005530"
FT CHAIN 228..449
FT /note="Clusterin alpha chain"
FT /evidence="ECO:0000269|PubMed:1974459"
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
