Reviewed, UniProtKB/Swiss-Prot P10909 (CLUS_HUMAN)

Names and origin

Protein names

Recommended name:
    Clusterin
Alternative name(s):
    Complement-associated protein SP-40,40
    Complement cytolysis inhibitor
      Short name=CLI
    NA1/NA2
    Apolipoprotein J
      Short name=Apo-J
    Testosterone-repressed prostate message 2
      Short name=TRPM-2
    Ku70-binding protein 1
Cleaved into the following 2 chains:
    1- Recommended name:
            Clusterin beta chain
        Alternative name(s):
            ApoJalpha
            Complement cytolysis inhibitor a chain
    2- Recommended name:
            Clusterin alpha chain
        Alternative name(s):
            ApoJbeta
            Complement cytolysis inhibitor b chain

Gene names

Name:	CLU
Synonyms:	APOJ, CLI, KUB1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	449 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Not yet clear. It is known to be expressed in a variety of tissues and it seems to be able to bind to cells, membranes and hydrophobic proteins. It has been associated with programmed cell death (apoptosis).
Subunit structure	Antiparallel disulfide-linked heterodimer. Interacts with CLUAP1 AND PON1.
Subcellular location	Secreted.
Sequence similarities	Belongs to the clusterin family.

Ontologies

Keywords
Biological process	Apoptosis Complement pathway Immune response Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
PTM	Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW lipid metabolic process Ref.10 Non-traceable author statement. Source: ProtInc
Cellular component	extracellular space Non-traceable author statement. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DISC1	Q9NRI5	2	EBI-1104674,EBI-529989

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22
	Chain	23 – 449	427	Clusterin		PRO_0000005529
	Chain	23 – 227	205	Clusterin beta chain		PRO_0000005530
	Chain	228 – 449	222	Clusterin alpha chain		PRO_0000005531
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...)
	Glycosylation	103	1	N-linked (GlcNAc...)
	Glycosylation	145	1	N-linked (GlcNAc...)
	Glycosylation	291	1	N-linked (GlcNAc...)
	Glycosylation	354	1	N-linked (GlcNAc...)
	Glycosylation	374	1	N-linked (GlcNAc...)
	Disulfide bond	102 ↔ 313		Interchain (between beta and alpha chains)
	Disulfide bond	113 ↔ 305		Interchain (between beta and alpha chains)
	Disulfide bond	116 ↔ 302		Interchain (between beta and alpha chains)
	Disulfide bond	121 ↔ 295		Interchain (between beta and alpha chains)
	Disulfide bond	129 ↔ 285		Interchain (between beta and alpha chains)
Natural variations
	Natural variant	317	1	N → H: dbSNP rs9331936.		VAR_019366
	Natural variant	328	1	D → N: dbSNP rs9331938.		VAR_019367
	Natural variant	396	1	S → L: dbSNP rs9331940.		VAR_019368
Experimental info
	Sequence conflict	28	1	D → S AA sequence Ref.9
	Sequence conflict	28	1	D → S AA sequence Ref.13
	Sequence conflict	47	1	Q → H AA sequence Ref.10
	Sequence conflict	52	1	G → Q AA sequence Ref.10
	Sequence conflict	172	1	M → V in CAI45990. Ref.7
	Sequence conflict	305	1	C → M AA sequence Ref.9
	Sequence conflict	388	1	T → M in CAI45990. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P10909-1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 9583DE4CCECC169F	FASTA	449	52,495
	10 20 30 40 50 60 MMKTLLLFVG LLLTWESGQV LGDQTVSDNE LQEMSNQGSK YVNKEIQNAV NGVKQIKTLI 70 80 90 100 110 120 EKTNEERKTL LSNLEEAKKK KEDALNETRE SETKLKELPG VCNETMMALW EECKPCLKQT 130 140 150 160 170 180 CMKFYARVCR SGSGLVGRQL EEFLNQSSPF YFWMNGDRID SLLENDRQQT HMLDVMQDHF 190 200 210 220 230 240 SRASSIIDEL FQDRFFTREP QDTYHYLPFS LPHRRPHFFF PKSRIVRSLM PFSPYEPLNF 250 260 270 280 290 300 HAMFQPFLEM IHEAQQAMDI HFHSPAFQHP PTEFIREGDD DRTVCREIRH NSTGCLRMKD 310 320 330 340 350 360 QCDKCREILS VDCSTNNPSQ AKLRRELDES LQVAERLTRK YNELLKSYQW KMLNTSSLLE 370 380 390 400 410 420 QLNEQFNWVS RLANLTQGED QYYLRVTTVA SHTSDSDVPS GVTEVVVKLF DSDPITVTVP 430 440 VEVSRKNPKF METVAEKALQ EYRKKHREE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40: a link between the complement and reproductive systems." Kirszbaum L., Sharpe J.A., Murphy B., D'Apice J.F.A., Classon B., Hudson P., Walker I.D. EMBO J. 8:711-718(1989) [PubMed: 2721499] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"Apolipoprotein J: structure and tissue distribution." de Silva H.V., Harmony J.A.K., Stuart W.D., Gil C.M., Robbins J. Biochemistry 29:5380-5389(1990) [PubMed: 1974459] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration." Wong P., Taillefer D., Lakins J., Pineault J., Chader G., Tenniswood M. Eur. J. Biochem. 221:917-925(1994) [PubMed: 8181474] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	The German cDNA consortium Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Small intestine.
[5]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-317; ASN-328 AND LEU-396.
[6]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[8]	"Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma: identity to sulfated glycoprotein 2, a constituent of rat testis fluid." Jenne D.E., Tschopp J. Proc. Natl. Acad. Sci. U.S.A. 86:7123-7127(1989) [PubMed: 2780565] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-449.
[9]	"Characterization of a human high density lipoprotein-associated protein, NA1/NA2. Identity with SP-40,40, an inhibitor of complement-mediated cytolysis." James R.W., Hochstrasser A.-C., Borghini I., Martin B.M., Pometta D., Hochstrasser D.F. Arterioscler. Thromb. 11:645-652(1991) [PubMed: 1903064] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-33; 229-242; 303-317 AND 397-403.
[10]	"Purification and characterization of apolipoprotein J." de Silva H., Stuart W.D., Park Y.B., Mao S.J.T., Gil C.M., Wetterau J.R., Busch S.J., Harmony J.A.K. J. Biol. Chem. 265:14292-14297(1990) [PubMed: 2387851] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-52 AND 228-257.
[11]	"The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex." Ghiso J., Matsubara E., Koudinov A., Choi-Miura N.-H., Tomita M., Wisniewski T., Frangione B. Biochem. J. 293:27-30(1993) [PubMed: 8328966] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-41 AND 228-246.
[12]	"A serum protein SP40,40 modulates the formation of membrane attack complex of complement on erythrocytes." Choi N.H., Mazda T., Tomita M. Mol. Immunol. 26:835-840(1989) [PubMed: 2601725] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-37 AND 228-242.
[13]	"HDL particle associated proteins in plasma and cerebrospinal fluid: identification and partial sequencing." Hochstrasser A.-C., James R.W., Martin B.M., Harrington M., Hochstrasser D.F., Pometta D., Merril C.R. Appl. Theor. Electrophor. 1:73-76(1988) [PubMed: 3154963] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-33 AND 228-240.
[14]	"Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death." Danik M., Chabot J.G., Mercier C., Benabid A.L., Chauvin C., Quirion R., Suh M. Proc. Natl. Acad. Sci. U.S.A. 88:8577-8581(1991) [PubMed: 1924317] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-449. Tissue: Astrocytoma.
[15]	Glew M.D., Kirszbaum L., Bozas S.E., Walker I.D. Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 140-449. Tissue: Fetal liver.
[16]	"SP-40,40, a protein involved in the control of the complement pathway, possesses a unique array of disulphide bridges." Kirszbaum L., Bozas S.E., Walker I.D. FEBS Lett. 297:70-76(1992) [PubMed: 1551440] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374.
[17]	"Identification of the disulfide bonds in human plasma protein SP-40,40 (apolipoprotein-J)." Choi-Miura N.H., Takahashi Y., Nakano Y., Tobe T., Tomita M. J. Biochem. 112:557-561(1992) [PubMed: 1491011] [Abstract] Cited for: DISULFIDE BONDS.
[18]	"Apolipoprotein J is associated with paraoxonase in human plasma." Kelso G.J., Stuart W.D., Richter R.J., Furlong C.E., Jordan-Starck T.C., Harmony J.A.K. Biochemistry 33:832-839(1994) [PubMed: 8292612] [Abstract] Cited for: INTERACTION WITH PON1.
[19]	"Identification and characterization of glycosylation sites in human serum clusterin." Kapron J.T., Hilliard G.M., Lakins J.N., Tenniswood M.P., West K.A., Carr S.A., Crabb J.W. Protein Sci. 6:2120-2133(1997) [PubMed: 9336835] [Abstract] Cited for: GLYCOSYLATION AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374.
[20]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-354.
[21]	"Isolation and characterization of a novel gene CLUAP1 whose expression is frequently upregulated in colon cancer." Takahashi M., Lin Y.-M., Nakamura Y., Furukawa Y. Oncogene 23:9289-9294(2004) [PubMed: 15480429] [Abstract] Cited for: INTERACTION WITH CLUAP1.
[22]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed: 14760718] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-354 AND ASN-374, MASS SPECTROMETRY. Tissue: Plasma.
[23]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374, MASS SPECTROMETRY. Tissue: Plasma.
[24]	"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry." Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A. J. Proteome Res. 5:1493-1503(2006) [PubMed: 16740002] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374, MASS SPECTROMETRY. Tissue: Saliva.
[25]	"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach." Lewandrowski U., Moebius J., Walter U., Sickmann A. Mol. Cell. Proteomics 5:226-233(2006) [PubMed: 16263699] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374, MASS SPECTROMETRY. Tissue: Platelet.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X14723 mRNA. Translation: CAA32847.1. J02908 mRNA. Translation: AAA51765.1. Different initiation. M63379 , M63376, M63377, M63378 Genomic DNA. Translation: AAB06507.1. M64722 mRNA. Translation: AAB06508.1. BX648414 mRNA. Translation: CAI45990.1. AY341244 Genomic DNA. Translation: AAP88927.1. Sequence problems. AF311103 Genomic DNA. No translation available. BC010514 mRNA. Translation: AAH10514.1. BC019588 mRNA. Translation: AAH19588.1. M25915 mRNA. Translation: AAA35692.1. Different initiation. M74816 mRNA. Translation: AAA60321.1. L00974 Genomic DNA. Translation: AAA60567.1.
PIR	A41386. S43646.
RefSeq	NP_001822.2. NP_976084.1.
UniGene	Hs.436657
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P10909.
Polymorphism databases
NIEHS-SNPs	Search...
2-D gel databases
SWISS-2DPAGE	P10909.
Cornea-2DPAGE	P10909.
DOSAC-COBS-2DPAGE	P10909.
OGP	P10909.
REPRODUCTION-2DPAGE	IPI00291262.
Genome annotation databases
Ensembl	ENSG00000120885. Homo sapiens. [Contig view]
GeneID	1191.
KEGG	hsa:1191.
Organism-specific databases
H-InvDB	HIX0007408.
HGNC	HGNC:2095. CLU.
HPA	CAB000476. CAB016253. HPA000572.
MIM	185430. gene.
PharmGKB	PA26620.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P10909.
HOVERGEN	P10909.
Gene expression databases
ArrayExpress	P10909.
CleanEx	HS_CLU.
GermOnline	ENSG00000120885. Homo sapiens.
Family and domain databases
InterPro	IPR016016. Clusterin. IPR000753. Clusterin-like. IPR016015. Clusterin_C. IPR016014. Clusterin_N. [Graphical view]
PANTHER	PTHR10970:SF1. Clusterin. 1 hit.
Pfam	PF01093. Clusterin. 1 hit. [Graphical view]
PIRSF	PIRSF002368. Clusterin. 1 hit.
SMART	SM00035. CLa. 1 hit. SM00030. CLb. 1 hit. [Graphical view]
PROSITE	PS00492. CLUSTERIN_1. 1 hit. PS00493. CLUSTERIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	4922.
SOURCE	Search...

Entry information

Entry name

CLUS_HUMAN

Accession

Primary (citable) accession number: P10909
Secondary accession number(s): P11380 , P11381, Q5HYC1, Q7Z5B9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	November 25, 2008
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)