dbPTM

CLUS_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CLUS_HUMAN
UniProt AC	P10909
Protein Name	Clusterin
Gene Name	CLU
Organism	Homo sapiens (Human).
Sequence Length	449
Subcellular Localization	Isoform 1: Secreted. Can retrotranslocate from the secretory compartments to the cytosol upon cellular stress. Nucleus. Cytoplasm. Mitochondrion membrane Peripheral membrane protein Cytoplasmic side. Cytoplasm, cytosol. Microsome. Endoplasmic reti
Protein Description	Isoform 1 functions as extracellular chaperone that prevents aggregation of nonnative proteins. Prevents stress-induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. Secreted isoform 1 protects cells against apoptosis and against cytolysis by complement. Intracellular isoforms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity. Nuclear isoforms promote apoptosis. Mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation..
Protein Sequence	MMKTLLLFVGLLLTWESGQVLGDQTVSDNELQEMSNQGSKYVNKEIQNAVNGVKQIKTLIEKTNEERKTLLSNLEEAKKKKEDALNETRESETKLKELPGVCNETMMALWEECKPCLKQTCMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLENDRQQTHMLDVMQDHFSRASSIIDELFQDRFFTREPQDTYHYLPFSLPHRRPHFFFPKSRIVRSLMPFSPYEPLNFHAMFQPFLEMIHEAQQAMDIHFHSPAFQHPPTEFIREGDDDRTVCREIRHNSTGCLRMKDQCDKCREILSVDCSTNNPSQAKLRRELDESLQVAERLTRKYNELLKSYQWKMLNTSSLLEQLNEQFNWVSRLANLTQGEDQYYLRVTTVASHTSDSDVPSGVTEVVVKLFDSDPITVTVPVEVSRKNPKFMETVAEKALQEYRKKHREE

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
25	Phosphorylation	GQVLGDQTVSDNELQ CCCCCCCCCCHHHHH	27.07	24505115
27	Phosphorylation	VLGDQTVSDNELQEM CCCCCCCCHHHHHHH	37.80	24505115
54	Ubiquitination	QNAVNGVKQIKTLIE HHHHHHHHHHHHHHH	47.94	29967540
57	Ubiquitination	VNGVKQIKTLIEKTN HHHHHHHHHHHHHCH	34.48	29967540
57	Sumoylation	VNGVKQIKTLIEKTN HHHHHHHHHHHHHCH	34.48	-
57	Sumoylation	VNGVKQIKTLIEKTN HHHHHHHHHHHHHCH	34.48	-
58	Phosphorylation	NGVKQIKTLIEKTNE HHHHHHHHHHHHCHH	34.30	28060719
68	Ubiquitination	EKTNEERKTLLSNLE HHCHHHHHHHHHHHH	46.97	29967540
69	Phosphorylation	KTNEERKTLLSNLEE HCHHHHHHHHHHHHH	38.87	23911959
72	Phosphorylation	EERKTLLSNLEEAKK HHHHHHHHHHHHHHH	42.34	21712546
78	Acetylation	LSNLEEAKKKKEDAL HHHHHHHHHHHHHHH	69.29	30587723
78	Ubiquitination	LSNLEEAKKKKEDAL HHHHHHHHHHHHHHH	69.29	29967540
78	2-Hydroxyisobutyrylation	LSNLEEAKKKKEDAL HHHHHHHHHHHHHHH	69.29	-
86	N-linked_Glycosylation	KKKEDALNETRESET HHHHHHHHHHHHHHH	50.76	9336835
86	N-linked_Glycosylation	KKKEDALNETRESET HHHHHHHHHHHHHHH	50.76	9336835
88	Phosphorylation	KEDALNETRESETKL HHHHHHHHHHHHHHH	38.37	30622161
91	Phosphorylation	ALNETRESETKLKEL HHHHHHHHHHHHHHC	47.47	30622161
93	Phosphorylation	NETRESETKLKELPG HHHHHHHHHHHHCCC	51.46	30622161
103	N-linked_Glycosylation	KELPGVCNETMMALW HHCCCCCCHHHHHHH	45.42	2721499
103	N-linked_Glycosylation	KELPGVCNETMMALW HHCCCCCCHHHHHHH	45.42	9336835
131	Phosphorylation	FYARVCRSGSGLVGR HHHHHHHCCCCHHHH	31.98	24719451
133	Phosphorylation	ARVCRSGSGLVGRQL HHHHHCCCCHHHHHH	30.15	28258704
145	N-linked_Glycosylation	RQLEEFLNQSSPFYF HHHHHHHHCCCCEEE	45.04	9336835
145	N-linked_Glycosylation	RQLEEFLNQSSPFYF HHHHHHHHCCCCEEE	45.04	2721499
151	Phosphorylation	LNQSSPFYFWMNGDR HHCCCCEEEEECCHH	10.34	24173317
155	N-linked_Glycosylation	SPFYFWMNGDRIDSL CCEEEEECCHHHHHH	39.55	-
170	Phosphorylation	LENDRQQTHMLDVMQ HHCHHHHHHHHHHHH	10.83	24505115
184	Phosphorylation	QDHFSRASSIIDELF HHHHHHHHHHHHHHH	22.44	28857561
185	Phosphorylation	DHFSRASSIIDELFQ HHHHHHHHHHHHHHH	23.68	26657352
197	O-linked_Glycosylation	LFQDRFFTREPQDTY HHHHCCCCCCCCCCC	31.26	OGP
210	O-linked_Glycosylation	TYHYLPFSLPHRRPH CCCCCCCCCCCCCCC	38.77	55835455
222	Ubiquitination	RPHFFFPKSRIVRSL CCCCCCCHHHHHHHC	47.40	-
291	N-linked_Glycosylation	VCREIRHNSTGCLRM HHHHHHCCCCCCCCC	31.27	2721499
291	N-linked_Glycosylation	VCREIRHNSTGCLRM HHHHHHCCCCCCCCC	31.27	9336835
310	Phosphorylation	DKCREILSVDCSTNN HHHHHHEEEECCCCC	22.90	23911959
314	Phosphorylation	EILSVDCSTNNPSQA HHEEEECCCCCHHHH	29.70	23911959
315	Phosphorylation	ILSVDCSTNNPSQAK HEEEECCCCCHHHHH	45.40	21712546
317	N-linked_Glycosylation	SVDCSTNNPSQAKLR EEECCCCCHHHHHHH	37.37	18780401
319	Phosphorylation	DCSTNNPSQAKLRRE ECCCCCHHHHHHHHH	44.91	21712546
322	Ubiquitination	TNNPSQAKLRRELDE CCCHHHHHHHHHHHH	34.58	29967540
340	Ubiquitination	VAERLTRKYNELLKS HHHHHHHHHHHHHHH	47.39	29967540
346	Ubiquitination	RKYNELLKSYQWKML HHHHHHHHHHCHHHC	60.79	29967540
347	Phosphorylation	KYNELLKSYQWKMLN HHHHHHHHHCHHHCC	23.64	29083192
348	Phosphorylation	YNELLKSYQWKMLNT HHHHHHHHCHHHCCH	19.46	29083192
354	N-linked_Glycosylation	SYQWKMLNTSSLLEQ HHCHHHCCHHHHHHH	34.12	9336835
354	N-linked_Glycosylation	SYQWKMLNTSSLLEQ HHCHHHCCHHHHHHH	34.12	9336835
356	Phosphorylation	QWKMLNTSSLLEQLN CHHHCCHHHHHHHHH	20.22	24505115
357	Phosphorylation	WKMLNTSSLLEQLNE HHHCCHHHHHHHHHH	34.63	24505115
374	N-linked_Glycosylation	NWVSRLANLTQGEDQ CHHHHHHCCCCCCCE	48.49	9336835
374	N-linked_Glycosylation	NWVSRLANLTQGEDQ CHHHHHHCCCCCCCE	48.49	9336835
387	Phosphorylation	DQYYLRVTTVASHTS CEEEEEEEEEEECCC	14.77	27130503
388	O-linked_Glycosylation	QYYLRVTTVASHTSD EEEEEEEEEEECCCC	15.95	OGP
388	Phosphorylation	QYYLRVTTVASHTSD EEEEEEEEEEECCCC	15.95	27130503
391	Phosphorylation	LRVTTVASHTSDSDV EEEEEEEECCCCCCC	23.98	28857561
393	Phosphorylation	VTTVASHTSDSDVPS EEEEEECCCCCCCCC	31.56	19824718
394	Phosphorylation	TTVASHTSDSDVPSG EEEEECCCCCCCCCC	29.68	27130503
396	Phosphorylation	VASHTSDSDVPSGVT EEECCCCCCCCCCCE	40.03	16263699
396	O-linked_Glycosylation	VASHTSDSDVPSGVT EEECCCCCCCCCCCE	40.03	OGP
400	Phosphorylation	TSDSDVPSGVTEVVV CCCCCCCCCCEEEEE	45.82	28060719
403	Phosphorylation	SDVPSGVTEVVVKLF CCCCCCCEEEEEECC	26.96	28060719
412	Phosphorylation	VVVKLFDSDPITVTV EEEECCCCCCEEEEE	37.64	21712546
429	Ubiquitination	EVSRKNPKFMETVAE ECCCCCHHHHHHHHH	67.73	30230243

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
-	K	Ubiquitination	E3 ubiquitin ligase	VHL	P40337	PMID:22532874
-	K	Ubiquitination	E3 ubiquitin ligase	SYVN1	Q86TM6	PMID:16611981

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of CLUS_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of CLUS_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CLUS_HUMAN	CLU	physical	12551933
TGFR2_HUMAN	TGFBR2	physical	8555189
XRCC6_HUMAN	XRCC6	physical	10219089
CO8B_HUMAN	C8B	physical	8345200
CO7_HUMAN	C7	physical	8345200
CO9_HUMAN	C9	physical	8345200
LRP2_HUMAN	LRP2	physical	7768901
TGFR1_HUMAN	TGFBR1	physical	8555189
XRCC6_HUMAN	XRCC6	physical	12551933
COMD1_HUMAN	COMMD1	physical	20068069
VHL_HUMAN	VHL	physical	22532874
IKKA_HUMAN	CHUK	physical	20028970
BAX_HUMAN	BAX	physical	19177010
XRCC6_HUMAN	XRCC6	physical	19177010
BAX_HUMAN	BAX	physical	19118032
XRCC6_HUMAN	XRCC6	physical	19118032
CD209_HUMAN	CD209	physical	22013110
ACTN1_HUMAN	ACTN1	physical	17974975
ZWINT_HUMAN	ZWINT	physical	17974975
KTNA1_HUMAN	KATNA1	physical	17974975
SKAP_HUMAN	KNSTRN	physical	17974975
B3AT_HUMAN	SLC4A1	physical	22016805
HBA_HUMAN	HBA1	physical	22016805
BAX_HUMAN	BAX	physical	16113678
CLUS_HUMAN	CLU	physical	17872975
LRP2_HUMAN	LRP2	physical	9228033
LYSC_HUMAN	LYZ	physical	17407782
XRCC6_HUMAN	XRCC6	physical	21042904
COMD1_HUMAN	COMMD1	physical	22130675
CLUA1_HUMAN	CLUAP1	physical	15480429
IL24_HUMAN	IL24	physical	21732348
CH60_HUMAN	HSPD1	physical	22012253
APRIO_HUMAN	PRNP	physical	18786636
PRIO_HUMAN	PRNP	physical	18786636
PON1_HUMAN	PON1	physical	8292612
B2CL1_HUMAN	BCL2L1	physical	21567405
BAX_HUMAN	BAX	physical	21567405
RPAC1_HUMAN	POLR1C	physical	21988832
CP2E1_HUMAN	CYP2E1	physical	21988832
MK09_HUMAN	MAPK9	physical	21988832
CTIP_HUMAN	RBBP8	physical	21988832
KLF11_HUMAN	KLF11	physical	21988832
RL23_HUMAN	RPL23	physical	21988832
KEAP1_HUMAN	KEAP1	physical	21988832
T22D4_HUMAN	TSC22D4	physical	21988832
HS71L_HUMAN	HSPA1L	physical	22863883
NUCB2_HUMAN	NUCB2	physical	22863883
TBB6_HUMAN	TUBB6	physical	22863883
EFTU_HUMAN	TUFM	physical	22863883
GRP78_HUMAN	HSPA5	physical	23457489
GRP78_HUMAN	HSPA5	physical	22689054
ENPL_HUMAN	HSP90B1	physical	22689054
HYOU1_HUMAN	HYOU1	physical	22689054
BAX_HUMAN	BAX	physical	23538443
TRFL_HUMAN	LTF	physical	17567961
EPPI_HUMAN	EPPIN	physical	17567961
SEMG1_HUMAN	SEMG1	physical	17567961
PACR_HUMAN	ADCYAP1R1	physical	25451228
CALX_HUMAN	CANX	physical	26496610
PDIA3_HUMAN	PDIA3	physical	26496610
FXR1_HUMAN	FXR1	physical	26496610
SETX_HUMAN	SETX	physical	26496610
DOCK6_HUMAN	DOCK6	physical	26496610
GPAT1_HUMAN	GPAM	physical	26496610
ATG3_HUMAN	ATG3	physical	25503391
MLP3A_HUMAN	MAP1LC3A	physical	25503391
MMP9_HUMAN	MMP9	physical	26716898
VEGFA_HUMAN	VEGFA	physical	26716898
SDK2_HUMAN	SDK2	physical	28514442
PTPRS_HUMAN	PTPRS	physical	28514442
TEN3_HUMAN	TENM3	physical	28514442
FAT4_HUMAN	FAT4	physical	28514442
FBX27_HUMAN	FBXO27	physical	28514442
ITA8_HUMAN	ITGA8	physical	28514442
EDEM2_HUMAN	EDEM2	physical	28514442
MANEA_HUMAN	MANEA	physical	28514442
EXTL2_HUMAN	EXTL2	physical	28514442
TOR1A_HUMAN	TOR1A	physical	28514442
MA1A1_HUMAN	MAN1A1	physical	28514442
TNFL9_HUMAN	TNFSF9	physical	28514442
PCYXL_HUMAN	PCYOX1L	physical	28514442
PTPRF_HUMAN	PTPRF	physical	28514442
GBB2_HUMAN	GNB2	physical	28514442
MA1A2_HUMAN	MAN1A2	physical	28514442
CELR1_HUMAN	CELSR1	physical	28514442
NLGN2_HUMAN	NLGN2	physical	28514442
TXD11_HUMAN	TXNDC11	physical	28514442
INT5_HUMAN	INTS5	physical	28514442
PCYOX_HUMAN	PCYOX1	physical	28514442
OCAD1_HUMAN	OCIAD1	physical	28514442
LMA2L_HUMAN	LMAN2L	physical	28514442
EIF3F_HUMAN	EIF3F	physical	26988917

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D09403	Custirsen sodium (USAN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of CLUS_HUMAN

Related Literatures of Post-Translational Modification

N-linked Glycosylation
Reference	PubMed
"Enrichment of glycopeptides for glycan structure and attachment siteidentification."; Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E.,Brinkmalm G., Larson G.; Nat. Methods 6:809-811(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374, STRUCTURE OFCARBOHYDRATES, AND MASS SPECTROMETRY.	19838169 [Abstract]
"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry."; Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; J. Proteome Res. 8:651-661(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-103; ASN-145;ASN-354 AND ASN-374, AND MASS SPECTROMETRY.	19159218 [Abstract]
"Identification of N-linked glycoproteins in human milk by hydrophilicinteraction liquid chromatography and mass spectrometry."; Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.; Proteomics 8:3833-3847(2008). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-291; ASN-317 AND ASN-374,AND MASS SPECTROMETRY.	18780401 [Abstract]
"Elucidation of N-glycosylation sites on human platelet proteins: aglycoproteomic approach."; Lewandrowski U., Moebius J., Walter U., Sickmann A.; Mol. Cell. Proteomics 5:226-233(2006). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374, AND MASSSPECTROMETRY.	16263699 [Abstract]
"Identification of N-linked glycoproteins in human saliva byglycoprotein 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). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374, AND MASSSPECTROMETRY.	16740002 [Abstract]
"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). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-103; ASN-145;ASN-291; ASN-354 AND ASN-374, AND MASS SPECTROMETRY.	16335952 [Abstract]
"Screening for N-glycosylated proteins by liquid chromatography massspectrometry."; Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; Proteomics 4:454-465(2004). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-354 AND ASN-374, AND MASSSPECTROMETRY.	14760718 [Abstract]
"Identification and quantification of N-linked glycoproteins usinghydrazide chemistry, stable isotope labeling and mass spectrometry."; Zhang H., Li X.-J., Martin D.B., Aebersold R.; Nat. Biotechnol. 21:660-666(2003). Cited for: GLYCOSYLATION AT ASN-354.	12754519 [Abstract]
"Identification and characterization of glycosylation sites in humanserum 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). Cited for: GLYCOSYLATION AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 ANDASN-374.	9336835 [Abstract]
"SP-40,40, a protein involved in the control of the complementpathway, possesses a unique array of disulphide bridges."; Kirszbaum L., Bozas S.E., Walker I.D.; FEBS Lett. 297:70-76(1992). Cited for: PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS, AND GLYCOSYLATION ATASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374.	1551440 [Abstract]
"Molecular cloning and characterization of the novel, humancomplement-associated protein, SP-40,40: a link between the complementand 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). Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEINSEQUENCE.	2721499 [Abstract]
Phosphorylation
Reference	PubMed
"An initial characterization of the serum phosphoproteome."; Zhou W., Ross M.M., Tessitore A., Ornstein D., Vanmeter A.,Liotta L.A., Petricoin E.F. III; J. Proteome Res. 8:5523-5531(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-393; SER-394 ANDSER-396, TISSUE SPECIFICITY, AND MASS SPECTROMETRY.	19824718 [Abstract]