HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles
Abstract
:1. Introduction
2. Results
2.1. Extracellular Vesicles from Human Brain Microvascular Endothelial Cells (HBMEC-EVs) Are Enriched with the Major EV Markers
2.2. Cellular Component Enrichment of the Identified Surface and Total EV Proteins
2.3. HIV and Aβ Exposure Results in Unique HBMEC-EV Proteome Signatures
2.4. Functional Enrichment of the Unique HBMEC-EV Proteins
2.5. Analysis of Unique Protein Interactions
3. Discussion
4. Materials and Methods
4.1. Cell Cultures
4.2. HIV Infection and Aβ Treatment
4.3. EV Isolation
4.4. Proteomics
4.5. ExoCarta Database Search and Functional Enrichment Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
Aβ | amyloid beta |
AD | Alzheimer’s disease |
BBB | Blood–brain barrier |
ECGS | Endothelial cell growth supplement |
EV | Extracellular vesicle |
ELISA | Enzyme-linked immunosorbent assay |
HAND | HIV-associated neurocognitive disorders; |
HBMEC | Human brain microvascular endothelial cells |
HEK cells | Human embryonic kidney cells |
HIV | Human immunodeficiency virus type 1 |
PBS | Phosphate buffered saline |
PECAM | Platelet endothelial cell adhesion molecule |
RAGE | Receptor for advanced glycation end products |
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Gene Symbol | Detected in S | Detected in T | |
---|---|---|---|
1 | CD9 | − | + |
2 | HSPA8 | + | + |
3 | PDCD6IP | + | + |
4 | GAPDH | + | + |
5 | ACTB | + | + |
6 | ANXA2 | + | + |
7 | CD63 | − | + |
8 | SDCBP | + | + |
9 | ENO1 | + | + |
10 | HSP90AA1 | + | + |
11 | TSG101 | − | + |
12 | PKM | + | + |
13 | LDHA | + | + |
14 | EEF1A1 | + | + |
15 | YWHAZ | + | + |
16 | PGK1 | + | + |
17 | EEF2 | + | + |
18 | ALDOA | + | + |
19 | HSP90AB1 | + | + |
20 | ANXA5 | + | + |
21 | FASN | + | + |
22 | YWHAE | + | + |
23 | CLTC | + | + |
24 | CD81 | − | + |
25 | ALB | + | + |
26 | VCP | + | + |
27 | TPI1 | + | + |
28 | PPIA | + | + |
29 | MSN | + | + |
30 | CFL1 | + | + |
31 | PRDX1 | + | + |
32 | PFN1 | + | + |
33 | RAP1B | + | + |
34 | ITGB1 | + | + |
35 | HSPA5 | + | + |
36 | SLC3A2 | − | + |
37 | HIST1H4A | + | + |
38 | GNB2 | − | − |
39 | ATP1A1 | − | + |
40 | YWHAQ | + | + |
41 | FLOT1 | − | − |
42 | FLNA | + | + |
43 | CLIC1 | + | + |
44 | CDC42 | + | + |
45 | CCT2 | + | + |
46 | A2M | + | + |
47 | YWHAG | + | + |
48 | TUBA1B | + | + |
49 | RAC1 | − | + |
50 | LGALS3BP | + | + |
51 | HSPA1A | + | + |
52 | GNAI2 | + | + |
53 | ANXA1 | + | + |
54 | RHOA | − | − |
55 | MFGE8 | − | + |
56 | PRDX2 | + | − |
57 | GDI2 | + | + |
58 | EHD4 | − | + |
59 | ACTN4 | + | + |
60 | YWHAB | − | − |
61 | RAB7A | − | + |
62 | LDHB | + | + |
63 | GNAS | − | − |
64 | TFRC | − | − |
65 | RAB5C | − | + |
66 | ARF1 | − | − |
67 | ANXA6 | + | + |
68 | ANXA11 | − | + |
69 | ACTG1 | − | − |
70 | KPNB1 | + | + |
71 | EZR | − | + |
72 | ANXA4 | − | − |
73 | ACLY | + | + |
74 | TUBA1C | − | − |
75 | RAB14 | − | + |
76 | HIST2H4A | − | − |
77 | GNB1 | + | + |
78 | UBA1 | + | + |
79 | THBS1 | + | + |
80 | RAN | + | + |
81 | RAB5A | − | − |
82 | PTGFRN | + | + |
83 | CCT5 | + | + |
84 | CCT3 | − | + |
85 | BSG | − | + |
86 | AHCY | + | + |
87 | RAB5B | − | − |
88 | RAB1A | − | + |
89 | LAMP2 | − | + |
90 | ITGA6 | − | − |
91 | HIST1H4B | − | − |
92 | GSN | + | + |
93 | FN1 | + | + |
94 | YWHAH | − | + |
95 | TUBA1A | + | − |
96 | TKT | − | − |
97 | TCP1 | + | + |
98 | STOM | − | + |
99 | SLC16A1 | − | − |
100 | RAB8A | − | − |
Control vs. HIV | HIV vs. HIV+Aβ | ||||||
---|---|---|---|---|---|---|---|
Control Unique | HIV Unique | HIV Unique | HIV+Aβ Unique | ||||
1433E | GPC6 | TGM1 | TITIN DYH8 IGHG2 | TITIN NIN DYH8 CAP1 ARPC4 IGHG2 | 1433E | GPC1 | TCPA |
1433G | GSTP1 | TIG1 | 1433G | GPC6 | TCPB | ||
1433T | IGL1 | TIMP3 | 1A34 | GSTA5 | TCPE | ||
1A34 | ITA3 | TPM4 | 1B15 | GSTP1 | TCPH | ||
5NTD | ITAV | TRFE | 5NTD | HMCN1 | TCPZ | ||
6PGD | ITB1 | TSP4 | ACLY | IGL1 | TIG1 | ||
ACLY | K2C6B | UBB | ACTC | IMB1 | TPM4 | ||
ACTC | LAMA1 | UGPA | ADA10 | ITA3 | TRFE | ||
ALDOA | LCAT | URP2 | AL9A1 | ITA5 | TSP4 | ||
AMPN | LDHA | VINC | ALDOA | ITAV | UBA1 | ||
AMY1 | LDHB | WDR1 | AMY1 | ITB1 | UBB | ||
ANXA1 | LOXL2 | WNT5A | ANXA1 | LDHA | UGPA | ||
APOA4 | LRC17 | ARF3 | LDHB | URP2 | |||
ARF3 | LRP1 | ARP2 | LOXL2 | VINC | |||
ARGI1 | LTBP1 | ARP3 | LRC17 | WDR1 | |||
ARP2 | MIME | ASPM | LRP1 | WNT5A | |||
ARP3 | MMP2 | ATL1 | LTBP1 | ||||
ATS13 | MPRI | ATX2 | MIME | ||||
C1S | MYL6 | B4GA1 | MMP2 | ||||
CASPE | NID2 | C1S | NID2 | ||||
CCD80 | P3H1 | CAZA1 | P3H1 | ||||
CFAH | PAI1 | CCD80 | PAI1 | ||||
CHIA | PCOC1 | CDC42 | PDC6I | ||||
CLIC1 | PDC6I | CHIA | PDIA3 | ||||
CO4A2 | PDIA3 | CHSS2 | PGK1 | ||||
CO5A2 | PGK1 | CISY | PGM1 | ||||
CO7 | PLEC | CLIC1 | PLEC | ||||
CO7A1 | PLOD3 | CLUS | PLOD3 | ||||
COBA1 | PPIA | CO4A2 | PPIA | ||||
COF1 | PRDX4 | CO5A2 | PRDX2 | ||||
COFA1 | PYGB | CO7A1 | PRDX6 | ||||
COMP | RAB1B | COBA1 | PUR6 | ||||
EF1G | RACK1 | COF1 | PYGB | ||||
ENOB | RAP1B | COFA1 | PYGL | ||||
EXT1 | RLA0 | COMP | RACK1 | ||||
EXT2 | RS16 | EF1G | RAP1B | ||||
F13A | S10A9 | EXT1 | RGN | ||||
FA11 | SDCB1 | F13A | RIMB1 | ||||
FAS | SEPR | FA11 | RL12 | ||||
FBLN1 | SPB12 | FAS | S10A9 | ||||
FBN1 | SPR1B | FBLN1 | SDCB1 | ||||
FBN2 | SPR2E | FBN1 | SERA | ||||
FLNB | SRCRL | FBN2 | SERPH | ||||
FLNC | SRPX2 | FLNB | SPR2E | ||||
FPRP | SULF1 | FLNC | SRCRL | ||||
FRIH | SULF2 | FPRP | SRPX2 | ||||
FSCN1 | SYTC | FRIH | SULF1 | ||||
GAS6 | TAGL2 | FRIL | SULF2 | ||||
GNAI2 | TBA1A | FSCN1 | SYTC | ||||
GPC1 | TCPD | GDIB | TAGL2 |
Control vs. HIV | ||||||
---|---|---|---|---|---|---|
Control Unique | HIV Unique | |||||
ACTC MYH1 TAU | 1433T | CD81 | GDIB | MVP | S10AB | URP2 |
1433Z | CD82 | GELS | MYH9 | SAHH | VIME | |
1A24 | CLH1 | GGCT | MYL6 | SCRB2 | VINC | |
5NTD | CLIC1 | GNAI2 | MYOF | SDC4 | VPS35 | |
6PGD | CO1A2 | GPC6 | NID1 | SDCB1 | VTNC | |
A4 | CO3A1 | GRP78 | NID2 | SEPR | VWF | |
ACLY | CO4A1 | GSLG1 | NNMT | SERPH | WDR1 | |
ACTN1 | CO4A2 | GTR1 | OLFL3 | SND1 | WNT5A | |
ACTN4 | CO5 | H31 | PAI1 | SNED1 | ZA2G | |
ADA10 | CO5A1 | H4 | PDC6I | SPTB2 | ||
AEBP1 | CO5A2 | HEP2 | PDIA3 | SPTN1 | ||
AGRIN | CO6A2 | HS90A | PFKAP | SRCRL | ||
AHNK | CO7A1 | HS90B | PGK1 | SRGN | ||
ALDOA | CO9 | HSP7C | PGS1 | SRPX | ||
AMPN | COEA1 | HTRA1 | PGS2 | SRPX2 | ||
AMY1 | COFA1 | IF4A1 | PKP1 | SULF1 | ||
ANT3 | COIA1 | IGHA1 | PLEC | SULF2 | ||
ANX11 | COMP | ITA3 | PLMN | SYDC | ||
ANXA1 | CYTA | ITA4 | PLOD1 | SYTC | ||
ANXA5 | DPYL2 | ITA5 | PLOD3 | TAGL2 | ||
ANXA6 | DYHC1 | ITAV | PLS1 | TBA1B | ||
AP2A1 | EF1A1 | ITB1 | PLS3 | TBB4B | ||
AP2M1 | EF2 | ITIH1 | PPIB | TCPA | ||
APLP2 | EHD1 | ITIH3 | PRC2A | TCPB | ||
APOA4 | EHD2 | ITIH4 | PRDX1 | TCPD | ||
APOB | EMIL1 | KLK7 | PRDX6 | TCPH | ||
APOE | ENOA | KPYM | PROF1 | TCPQ | ||
ARF3 | ENPL | LAMA1 | PSB5 | TCPZ | ||
ARF4 | EXT1 | LAMA2 | PTX3 | TENA | ||
ARGI1 | EXT2 | LAMA4 | PXDN | TERA | ||
ARP2 | F13A | LAMA5 | RAB5C | TGM1 | ||
ARPC2 | FA5 | LAMP1 | RAB7A | TGM2 | ||
AT1A1 | FAS | LAMP2 | RAC1 | TGM3 | ||
ATL1 | FAT1 | LDHA | RACK1 | THBG | ||
ATS12 | FBLN1 | LDHB | RAN | THRB | ||
ATS13 | FBN1 | LEG1 | RAP1B | THY1 | ||
ATX2 | FBX50 | LORI | RB11A | TIG1 | ||
B4GA1 | FETA | LOXL2 | RHOC | TITIN | ||
BGH3 | FIBB | LRC17 | RIMB1 | TLN1 | ||
BMP1 | FILA | LRP1 | RL10A | TPIS | ||
C1QT3 | FLNA | LTBP1 | RL12 | TPM4 | ||
C1S | FLNB | LTBP2 | RL13A | TRFE | ||
CAP1 | FLNC | LYSC | RL27 | TRFL | ||
CASPE | FPRP | MAMC2 | RL6 | TSN14 | ||
CATA | FSCN1 | MARCS | RS16 | TSP 1 | ||
CCD80 | G3P | MFGM | RS3 | TSP 2 | ||
CD151 | GALK1 | MMP2 | RS4X | TSP 3 | ||
CD44 | GAS6 | MOES | RS8 | TTYH3 | ||
CD59 | GBB1 | MOT4 | RSSA | UBA1 | ||
CD63 | GBG12 | MRC2 | S10A9 | UBB | ||
HIV vs. HIV+Aβ | ||||||
HIV unique | HIV+Aβ unique | |||||
AHNK | 1433E | CO8B | MIME | RL3 | ||
ARGI1 | 1433F | COF1 | MOB1B | RL7 | ||
ATX2 | 1433G | COPB2 | MPRI | RL7A | ||
B4GA1 | 1B40 | COR1A | MRP | RLA0 | ||
CASPE | 2AAA | COR1C | MXRA5 | RS11 | ||
CATA | 4F2 | CTL1 | MYH16 | RS18 | ||
CYTA | ACTC | CTL2 | NDKA | RS2 | ||
FBX50 | AK1A1 | CTND1 | NEP | RS20 | ||
FILA | AL9A1 | CYFP1 | NIBL1 | RS25 | ||
GGCT | ALS | DHX9 | NOTC3 | RS3A | ||
HORN | ANGL2 | DSG4 | NRP1 | RS9 | ||
IGHA1 | ANGL4 | DX39B | OLM2B | RTN4 | ||
K1C13 | ANM1 | ECM1 | P3H1 | RUVB1 | ||
KLK7 | ANR31 | ECM2 | PAMR1 | SC23A | ||
LORI | AP1G1 | EEA1 | PARVB | SCUB3 | ||
LYSC | AP2B1 | EF1G | PCOC1 | SEM3C | ||
MYOF | APOM | EGLN | PDIA1 | SEP11 | ||
PLS1 | ARF6 | EHD4 | PDIA6 | SEPT2 | ||
PRC2A | ARP3 | EIF3A | PDLI5 | SERA | ||
RIMB1 | ARPC4 | EZRI | PGFRB | SLIT2 | ||
RL27 | ASSY | FA10 | PGM1 | STOM | ||
S10A9 | AT1B3 | FA11 | PIP | SVEP1 | ||
SNED1 | ATPA | FBN2 | PLOD2 | SYFB | ||
SPB12 | ATPB | FIBG | PP1B | SYHC | ||
TGM1 | ATS7 | FRIH | PPIA | SYK | ||
TGM3 | B4GT5 | G6PD | PRS23 | SYRC | ||
TITIN | BASI | G6PI | PRS8 | SYSC | ||
ZA2G | BASP1 | GANAB | PSA3 | TARSH | ||
BGAL | H13 | PSA6 | TBB2A | |||
C1R | H2A1 | PSD11 | TBB5 | |||
C1TC | H2B1K | PSD12 | TCPE | |||
CAD23 | HGFL | PSD13 | TCPG | |||
CALR | HHIP | PSMD1 | TGFB1 | |||
CAND1 | HMCN1 | PSMD2 | TICN1 | |||
CAPZB | HNRPK | PSMD3 | TIE1 | |||
CAV1 | IGSF8 | PUR6 | TIMP3 | |||
CAZA1 | ILK | PYGB | TS101 | |||
CBPN | IMB1 | PYGL | TSN6 | |||
CCBE1 | IPO5 | QSOX1 | TSN9 | |||
CD9 | IPO7 | RAB10 | TSP4 | |||
CDC42 | IQGA1 | RAB14 | UACA | |||
CEMIP | KCRM | RAB1A | UGDH | |||
CFAH | KR101 | RAB2A | VAT1 | |||
CHIA | KR111 | RALA | VDAC1 | |||
CHSS2 | KRA11 | RELN | VDAC2 | |||
CISY | LAMB2 | RGN | VGFR1 | |||
CLUS | LIS1 | RL14 | XPO1 | |||
CNTN1 | LMNA | RL18 | XPO2 | |||
CO7 | LRC15 | RL18A | XPP1 | |||
CO8A | LUM | RL22 | XRCC6 | |||
XYLT1 |
Gene Ontology (GO) Terms for Biological Processes 10 Most Significant Results per FDR (for all GO Terms, See Supplemental Table S1A) | |||||
Term description | Obs | Bgr | FDR | Matching proteins in the network | |
Extracellular structure organization | 16 | 339 | 2.01 × 10−10 | APOA4,COMP,FBLN1,FBN1,FBN2,GAS6,LAMA1,LCAT,LOXL2,MMP2,NID2,PLOD3,PRDX4,SERPINE1,SULF1,SULF2 | |
Extracellular matrix organization | 14 | 296 | 4.25 × 10−9 | COMP,FBLN1,FBN1,FBN2,GAS6,LAMA1,LOXL2,MMP2,NID2,PLOD3,PRDX4,SERPINE1,SULF1,SULF2 | |
Organonitrogen compound metabolic process | 42 | 5281 | 3.69 × 10 -6 | ACLY,AICDA,ALDOA,ANXA1,APOA4,C1S,CHIA,EEF1G,EXT1,EXT2,F13A1,FBLN1,FBN1,GAS6,GNB2L1,GPC1,GPC6,GSTP1,IGF2R,IGLL1,KRT1,LCAT,LDHA,LDHB,LEPRE1,LOXL2,LRP1,LTBP1,MMP2,MSRB1,PDIA3,PGD,PGK1,PLOD3,PPIA,PRDX4,RAB1B,SULF1,SULF2,TGM1,UBB,WNT5A | |
Immune response | 22 | 1560 | 6.48 × 10−6 | ACLY,ACTR3,AICDA,ALDOA,ANXA1,APOA4,C1S,CHIA,FAS,FLNB,GAS6,GSTP1,IGF2R,IGLL1,KRT1,LRP1,MSRB1,PPIA,PRDX4,PYGB,RAP1B,WNT5A | |
Vesicle-mediated transport | 23 | 1699 | 6.48 × 10−6 | ACLY,ACTR3,ALDOA,ANXA1,ARF3,F13A1,FERMT3,GAS6,GSTP1,IGF2R,IGLL1,KRT1,LOXL2,LRP1,PPIA,PRDX4,PYGB,RAB1B,RAP1B,SERPINE1,TIMP3,UBB,WDR1 | |
Regulated exocytosis | 15 | 691 | 6.48 × 10−6 | ACLY,ALDOA,F13A1,FERMT3,GAS6,GSTP1,IGF2R,KRT1,PPIA,PRDX4,PYGB,RAP1B,SERPINE1,TIMP3,WDR1 | |
Positive regulation of biological process | 42 | 5459 | 6.48 × 10−6 | ACLY,ACTC1,ACTR3,AICDA,ANXA1,APOA4,C1S,CHIA,CLIC1,FAS,FBLN1,FBN1,FBN2,FERMT3,FSCN1,GAS6,GNAI2,GNB2L1,GPC1,GSTP1,IGF2R,IGLL1,KRT1,LDHA,LEPRE1,LOXL2,LRP1,MMP2,PDIA3,PPIA,RAB1B,RAP1B,SERPINE1,SRPX2,SULF1,SULF2,TGM1,THBS4,TIMP3,UBB,WDR1,WNT5A | |
Anatomical structure development | 40 | 5085 | 6.48 × 10−6 | ACTC1,AICDA,ANXA1,APOA4,COMP,EXT1,EXT2,FAS,FBLN1,FBN1,FBN2,FERMT3,FLNB,FLNC,FSCN1,GAS6,GNB2L1,GPC1,GSTP1,IGF2R,KRT1,LDHA,LEPRE1,LOXL2,LRP1,LTBP1,MMP2,MYL6,PGK1,PLOD3,PRDX4,RAP1B,SERPINE1,SRPX2,SULF1,SULF2,TGM1,UBB,WDR1,WNT5A | |
Response to stimulus | 51 | 7824 | 6.48 × 10−6 | ACLY,ACTC1,ACTR3,AICDA,ALDOA,ANXA1,APOA4,C1S,CHIA,CLIC1,EEF1G,EXT1,EXT2,F13A1,FAS,FBLN1,FBN1,FERMT3,FLNB,FSCN1,GAS6,GNAI2,GNB2L1,GPC1,GPC6,GPRC5A,GSTP1,IGF2R,IGLL1,KRT1,LAMA1,LDHA,LOXL2,LRP1,LTBP1,MMP2,MSRB1,PDIA3,PGK1,PLOD3,PPIA,PRDX4,PYGB,RAP1B,SERPINE1,SULF1,SULF2,THBS4,TIMP3,UBB,WNT5A | |
Positive regulation of cellular process | 39 | 4898 | 7.40 × 10−6 | ACLY,ACTR3,AICDA,ANXA1,APOA4,CHIA,CLIC1,FAS,FBLN1,FBN1,FBN2,FERMT3,FSCN1,GAS6,GNAI2,GNB2L1,GPC1,GSTP1,IGF2R,IGLL1,LDHA,LEPRE1,LOXL2,LRP1,MMP2,PDIA3,PPIA,RAB1B,RAP1B,SERPINE1,SRPX2,SULF1,SULF2,TGM1,THBS4,TIMP3,UBB,WDR1,WNT5A | |
KEGG Pathways | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Proteoglycans in cancer | 7 | 195 | 0.00093 | FAS,FLNB,FLNC,GPC1,MMP2,TIMP3,WNT5A | |
Focal adhesion | 6 | 197 | 0.0053 | COMP,FLNB,FLNC,LAMA1,RAP1B,THBS4 | |
Glycolysis / Gluconeogenesis | 4 | 68 | 0.0054 | ALDOA,LDHA,LDHB,PGK1 | |
HIF-1 signaling pathway | 4 | 98 | 0.0155 | ALDOA,LDHA,PGK1,SERPINE1 | |
Cholesterol metabolism | 3 | 48 | 0.0195 | APOA4,LCAT,LRP1 | |
Malaria | 3 | 47 | 0.0195 | COMP,LRP1,THBS4 | |
10 Most Significant PMID Publications per FDR | |||||
Term ID | Term Description | Obs | Bgr | FDR | Matching Proteins in the Network |
PMID:21654676 | (2011) D-glucuronyl C5-epimerase suppresses small-cell lung cancer cell proliferation in vitro and tumour growth in vivo. | 8 | 62 | 1.79 × 10−5 | EXT1,EXT2,FAS,GPC1,GPC6,MMP2,SERPINE1,TIMP3 |
PMID:22393382 | (2012) In vitro phenotypic, genomic and proteomic characterization of a cytokine-resistant murine Beta-TC3 cell line. | 7 | 42 | 2.32 × 10−5 | ALDOA,FAS,GSTP1,LDHA,LDHB,PDIA3,PRDX4 |
PMID:25829250 | (2015) Insights into the key roles of proteoglycans in breast cancer biology and translational medicine. | 10 | 156 | 2.32 × 10−5 | EXT1,FBLN1,FBN1,GPC1,GPC6,MMP2,SULF1,SULF2,TIMP3,WNT5A |
PMID:26779482 | (2015) The Extracellular Matrix in Bronchopulmonary Dysplasia: Target and Source. | 7 | 41 | 2.32 × 10−5 | FBLN1,FBN1,FBN2,LOXL2,LTBP1,PLOD3,SULF2 |
PMID:23143224 | (2013) The biology of the extracellular matrix: Novel insights. | 6 | 28 | 5.53 × 10−5 | COMP,FBN1,FBN2,LTBP1,MMP2,TIMP3 |
PMID:24223867 | (2013) Lactate-modulated induction of THBS-1 activates transforming growth factor (TGF)-beta2 and migration of glioma cells in vitro. | 6 | 31 | 7.90 × 10−5 | COMP,LDHA,LDHB,MMP2,SERPINE1,THBS4 |
PMID:26076122 | (2015) Interactions of signaling proteins, growth factors and other proteins with heparan sulfate: Mechanisms and mysteries. | 6 | 31 | 7.90 × 10−5 | EXT1,EXT2,GPC1,GPC6,SULF1,SULF2 |
PMID:20236620 | (2010) Unraveling the mechanism of elastic fiber assembly: The roles of short fibulins. | 6 | 33 | 8.27 × 10−5 | FBLN1,FBN1,FBN2,LOXL2,LTBP1,TIMP3 |
PMID:20140087 | (2010) Comprehensive identification and modified-site mapping of S-nitrosylated targets in prostate epithelial cells. | 8 | 103 | 8.31 × 10−5 | ALDOA,ANXA1,CLIC1,FLNB,FLNC,PDIA3,PGK1,PLEC |
PMID:27513329 | (2016) Differential Expression Pattern of THBS1 and THBS2 in Lung Cancer: Clinical Outcome and a Systematic-Analysis of Microarray Databases. | 7 | 65 | 8.31 × 10−5 | COMP,FBLN1,FBN1,MMP2,NID2,SULF1,THBS4 |
Gene Ontology (GO) Terms for Biological Processes | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Cytoskeleton organization | 5 | 953 | 8.35 × 10−5 | ARPC4,CAP1,DNAH8,NIN,TTN | |
Supramolecular fiber organization | 4 | 383 | 0.00011 | ARPC4,CAP1,NIN,TTN | |
Actin filament organization | 3 | 200 | 0.0011 | ARPC4,CAP1,TTN | |
Cellular protein-containing complex assembly | 4 | 832 | 0.0012 | ARPC4,DNAH8,NIN,TTN | |
Actin polymerization or depolymerization | 2 | 43 | 0.0031 | ARPC4,CAP1 | |
Protein polymerization | 2 | 83 | 0.0058 | ARPC4,NIN | |
Localization | 5 | 5233 | 0.0296 | ARPC4,CAP1,DNAH8,NIN,TTN | |
PMID Publications | |||||
Term ID | Term Description | Obs | Bgr | FDR | Matching Proteins in the Network |
PMID:21050039 | (2010) Titin A-band-specific monoclonal antibody Tit1 5H1.1. Cellular Titin as a centriolar protein in non-muscle cells. | 2 | 2 | 0.0016 | NIN,TTN |
PMID:22985877 | (2012) Epitope of titin A-band-specific monoclonal antibody Tit1 5 H1.1 is highly conserved in several Fn3 domains of the titin molecule. Centriole staining in human, mouse and zebrafish cells. | 2 | 6 | 0.0037 | NIN,TTN |
PMID:26655833 | (2016) The centrosome is an actin-organizing centre. | 2 | 12 | 0.0081 | ARPC4,NIN |
PMID:27094867 | (2016) Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function. | 2 | 27 | 0.027 | NIN,TTN |
PMID:29255378 | (2017) The human, F-actin-based cytoskeleton as a mutagen sensor. | 2 | 35 | 0.0353 | DNAH8,TTN |
Gene ontology (GO) Terms for Biological Processes 10 Most Significant Results per FDR (for All GO Terms, See Supplementary Table S2A) | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Immune effector process | 18 | 927 | 9.47 × 10−6 | ACLY,ACTR3,AICDA,ALDOA,C1S,CDC42,GSTP,IGLL1,KPNB1,KRT1,LRP1,PGM1,PPIA,PRDX6,PYGB,PYGL,RAP1B,WDR1 | |
Leukocyte-mediated immunity | 15 | 632 | 9.47 × 10−6 | ACLY,AICDA,ALDOA,C1S,GSTP1,IGLL1,KPNB1,KRT1,PGM1,PPIA,PRDX6,PYGB,PYGL,RAP1B,WDR1 | |
Vesicle-mediated transport | 23 | 1699 | 9.70 × 10−6 | ACLY,ACTR3,ALDOA,ANXA1,ARF3,CDC42,F13A1,FERMT3,GSTP1,IGLL1,KPNB1,KRT1,LOXL2,LRP1,PGM1,PPIA,PRDX6,PYGB,PYGL,RAP1B,SERPINE1,UBB,WDR1 | |
Extracellular matrix organization | 11 | 296 | 9.70 × 10−6 | COMP,FBLN1,FBN1,FBN2,LOXL2,MMP2,NID2,PLOD3,SERPINE1,SULF1,SULF2 | |
Regulated exocytosis | 15 | 691 | 1.15 × 10−5 | ACLY,ALDOA,F13A1,FERMT3,GSTP1,KPNB1,KRT1,PGM1,PPIA,PRDX6,PYGB,PYGL,RAP1B,SERPINE1,WDR1 | |
Response to stimulus | 51 | 7824 | 1.20 × 10−5 | ACLY,ACTC1,ACTR3,AICDA,ALDOA,ANXA1,C1S,CDC42,CHIA,CLIC1,EEF1G,EXT1,F13A1,FAS,FBLN1,FBN1,FERMT3,FLNB,FSCN1,GNB2L1,GPC1,GPC6,GPRC5A,GSTP1,HMCN1,IGLL1,KPNB1,KRT1,LDHA,LOXL2,LRP1,LTBP1,MMP2,PDIA3,PGK1,PGM1,PHGDH,PLOD3,PPIA,PRDX2,PRDX6,PYGB,PYGL,RAP1B,SERPINE1,SULF1,SULF2,THBS4,UBA1,UBB,WNT5A | |
Negative regulation of cellular response to growth factor stimulus | 8 | 137 | 1.59 × 10−5 | FBN1,FBN2,GPC1,LTBP1,SULF1,SULF2,UBB,WNT5A | |
Immune system process | 26 | 2370 | 2.26 × 10−5 | ACLY,ACTR3,AICDA,ALDOA,ANXA1,C1S,CDC42,CHIA,FAS,FLNB,GPC1,GSTP1,IGLL1,KPNB1,KRT1,LRP1,PDIA3,PGM1,PPIA,PRDX6,PYGB,PYGL,RAP1B,UBB,WDR1,WNT5A | |
Carbohydrate metabolic process | 12 | 457 | 2.26 × 10−5 | ALDOA,AMY1B,CHIA,EXT1,FBN1,LDHA,LDHB,PGK1,PGM1,PYGB,PYGL,RGN | |
Immune response | 21 | 1560 | 2.26 × 10−5 | ACLY,ACTR3,AICDA,ALDOA,ANXA1,C1S,CHIA,FAS,FLNB,GSTP1,IGLL1,KPNB1,KRT1,LRP1,PGM1,PPIA,PRDX6,PYGB,PYGL,RAP1B,WNT5A | |
KEGG Pathways | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Glycolysis / Gluconeogenesis | 5 | 68 | 0.00077 | ALDOA,LDHA,LDHB,PGK1,PGM1 | |
Proteoglycans in cancer | 7 | 195 | 0.00077 | CDC42,FAS,FLNB,FLNC,GPC1,MMP2,WNT5A | |
Focal adhesion | 6 | 197 | 0.0035 | CDC42,COMP,FLNB,FLNC,RAP1B,THBS4 | |
Pentose phosphate pathway | 3 | 30 | 0.0068 | ALDOA,PGM1,RGN | |
Starch and sucrose metabolism | 3 | 33 | 0.0071 | PGM1,PYGB,PYGL | |
Metabolic pathways | 13 | 1250 | 0.0095 | ACLY,ALDOA,CHIA,EXT1,LDHA,LDHB,PGK1,PGM1,PHGDH,PRDX6,PYGB,PYGL,RGN | |
HIF-1 signaling pathway | 4 | 98 | 0.0095 | ALDOA,LDHA,PGK1,SERPINE1 | |
Glucagon signaling pathway | 4 | 100 | 0.0095 | LDHA,LDHB,PYGB,PYGL | |
Malaria | 3 | 47 | 0.0104 | COMP,LRP1,THBS4 | |
Carbon metabolism | 4 | 116 | 0.011 | ALDOA,PGK1,PHGDH,RGN | |
Fluid shear stress and atherosclerosis | 4 | 133 | 0.0164 | GPC1,GSTA5,GSTP1,MMP2 | |
Biosynthesis of amino acids | 3 | 72 | 0.0233 | ALDOA,PGK1,PHGDH | |
Platinum drug resistance | 3 | 70 | 0.0233 | FAS,GSTA5,GSTP1 | |
Necroptosis | 4 | 155 | 0.0233 | FAS,PPIA,PYGB,PYGL | |
Complement and coagulation cascades | 3 | 78 | 0.0251 | C1S,F13A1,SERPINE1 | |
Salmonella infection | 3 | 84 | 0.0288 | CDC42,FLNB,FLNC | |
MAPK signaling pathway | 5 | 293 | 0.0307 | CDC42,FAS,FLNB,FLNC,RAP1B | |
AGE-RAGE signaling pathway in diabetic complications | 3 | 98 | 0.0388 | CDC42,MMP2,SERPINE1 | |
Human papillomavirus infection | 5 | 317 | 0.0388 | CDC42,COMP,FAS,THBS4,WNT5A | |
Propanoate metabolism | 2 | 32 | 0.0405 | LDHA,LDHB | |
Leukocyte transendothelial migration | 3 | 112 | 0.0476 | CDC42,MMP2,RAP1B | |
Primary immunodeficiency | 2 | 37 | 0.0481 | AICDA,IGLL1 | |
10 Most Significant PMID Publications per FDR | |||||
Term ID | Term Description | Obs | Bgr | FDR | Matching Proteins in the Network |
PMID:23823696 | (2013) Isobaric Tagging-Based Quantification for Proteomic Analysis: A Comparative Study of Spared and Affected Muscles from mdx Mice at the Early Phase of Dystrophy. | 8 | 42 | 1.26 × 10−6 | ACLY,ALDOA,ANXA1,EEF1G,LDHB,PGM1,PPIA,PRDX2 |
PMID:29250190 | (2017) Role of exosomes in hepatocellular carcinoma cell mobility alteration. | 7 | 34 | 8.40 × 10−6 | ANXA1,CLIC1,FBLN1,LRP1,PPIA,PYGB,PYGL |
PMID:20140087 | (2010) Comprehensive identification and modified-site mapping of S-nitrosylated targets in prostate epithelial cells. | 9 | 103 | 9.47 × 10−6 | ALDOA,ANXA1,CLIC1,FLNB,FLNC,KPNB1,PDIA3,PGK1,PLEC |
PMID:29360750 | (2018) Proteomic Analysis of Secretomes of Oncolytic Herpes Simplex Virus-Infected Squamous Cell Carcinoma Cells. | 7 | 37 | 9.47 × 10−6 | ACLY,ANXA1,FBN1,FLNC,FSCN1,MMP2,PRDX2 |
PMID:26779482 | (2015) The Extracellular Matrix in Bronchopulmonary Dysplasia: Target and Source. | 7 | 41 | 1.08 × 10−5 | FBLN1,FBN1,FBN2,LOXL2,LTBP1,PLOD3,SULF2 |
PMID:24142637 | (2013) Gastric autoantigenic proteins in Helicobacter pylori infection. | 7 | 50 | 2.96 × 10−5 | ACTR3,GSTP1,LDHB,PDIA3,PRDX2,PRDX6,WDR1 |
PMID:26184160 | (2015) A Review: Proteomics in Nasopharyngeal Carcinoma. | 8 | 83 | 2.96 × 10−5 | ANXA1,CLIC1,KRT1,MMP2,PPIA,PRDX2,PRDX6,SERPINE1 |
PMID:26918450 | (2016) A nuclear-directed human pancreatic ribonuclease (PE5) targets the metabolic phenotype of cancer cells. | 8 | 89 | 3.71 × 10−5 | ACLY,CLIC1,GPC1,GPC6,LDHA,PGM1,PHGDH,WNT5A |
PMID:24223867 | (2013) Lactate-modulated induction of THBS-1 activates transforming growth factor (TGF)-beta2 and migration of glioma cells in vitro. | 6 | 31 | 5.98 × 10−5 | COMP,LDHA,LDHB,MMP2,SERPINE1,THBS4 |
PMID:20236620 | (2010) Unraveling the mechanism of elastic fiber assembly: The roles of short fibulins. | 6 | 33 | 7.46 × 10−5 | FBLN1,FBN1,FBN2,HMCN1,LOXL2,LTBP1 |
The 10 Most Significant PMID Publications According to FDR | |||||
Term ID | Term Description | Obs | Bgr | FDR | Matching Proteins in the Network |
PMID:19812696 | (2009) Cancer genomics identifies regulatory gene networks associated with the transition from dysplasia to advanced lung adenocarcinomas induced by c-Raf-1. | 3 | 154 | 0.0084 | ACTC1,MAPT,MYH1 |
PMID:20587776 | (2010) Mathematical modeling of endocytic actin patch kinetics in fission yeast: disassembly requires release of actin filament fragments. | 2 | 12 | 0.0086 | ACTC1,MYH1 |
PMID:25275480 | (2014) Urethral dysfunction in female mice with estrogen receptor Beta deficiency. | 2 | 10 | 0.0086 | ACTC1,MYH1 |
PMID:22406440 | (2012) Deferiprone reduces amyloid-Beta and tau phosphorylation levels but not reactive oxygen species generation in hippocampus of rabbits fed a cholesterol-enriched diet. | 2 | 15 | 0.0088 | ACTC1,MAPT |
PMID:10931867 | (2000) Distinct families of Z-line targeting modules in the COOH-terminal region of nebulin. | 2 | 25 | 0.0099 | ACTC1,MYH1 |
PMID:11994316 | (2002) The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo. | 2 | 26 | 0.0099 | ACTC1,MYH1 |
PMID:14557251 | (2003) Skeletal myosin heavy chain function in cultured lung myofibroblasts. | 2 | 26 | 0.0099 | ACTC1,MYH1 |
PMID:17908293 | (2007) Identification of genes differentially expressed during prenatal development of skeletal muscle in two pig breeds differing in muscularity. | 2 | 52 | 0.0099 | ACTC1,MYH1 |
PMID:19291799 | (2009) Fast-twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositis. | 2 | 36 | 0.0099 | MAPT,MYH1 |
PMID:19325835 | (2008) Myosin assembly, maintenance and degradation in muscle: Role of the chaperone UNC-45 in myosin thick filament dynamics. | 2 | 44 | 0.0099 | ACTC1,MYH1 |
Gene Ontology (GO) Terms for Biological Processes10 Most Significant Results per FDR (for All GO Terms, See Supplementary Table S4A) | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Vesicle-mediated transport | 57 | 1699 | 1.02 × 10−18 | ACLY,ACTN1,ACTN4,ALDOA,ANXA1,ANXA11,ANXA5,AP2A1,AP2M1,APLP2,APOB,APOE,ARF3,ARF4,ARPC2,CAP1,CD44,CD59,CD63,CD81,EEF2,EHD1,EHD2,F13A1,FERMT3,FLNA,GAS6,ITIH3,ITIH4,KRT1,LAMP1,LAMP2,LOXL2,LRP1,MFGE8,MRC2,MVP,MYH9,PKP1,PRDX6,PTX3,RAB5C,RAB7A,RAC1,RAP1B,SERPINE1,SPTBN1,SRGN,SRPX,TGM2,THBS1,TLN1,TTN,UBB,VPS35,VWF,WDR1 | |
Extracellular structure organization | 28 | 339 | 7.06 × 10−17 | AGRN,APOA4,APOB,APOE,BMP1,CD44,COMP,DCN,FBLN1,FBN1,GAS6,HTRA1,KLK7,LAMA1,LAMA2,LAMA4,LAMA5,LOXL2,MMP2,NID1,NID2,PLOD3,PXDN,SERPINE1,SULF1,SULF2,THBS1,VWF | |
Platelet degranulation | 20 | 129 | 2.26 × 10−16 | ACTN1,ACTN4,ALDOA,ANXA5,APLP2,CD63,F13A1,FERMT3,FLNA,GAS6,ITIH3,ITIH4,LAMP2,SERPINE1,SRGN,THBS1,TLN1,TTN,VWF,WDR1 | |
Regulated exocytosis | 35 | 691 | 1.19 × 10−15 | ACLY,ACTN1,ACTN4,ALDOA,ANXA5,APLP2,CAP1,CD44,CD59,CD63,EEF2,F13A1,FERMT3,FLNA,GAS6,ITIH3,ITIH4,KRT1,LAMP1,LAMP2,MVP,PKP1,PRDX6,PTX3,RAB5C,RAB7A,RAC1,RAP1B,SERPINE1,SRGN,THBS1,TLN1,TTN,VWF,WDR1 | |
Extracellular matrix organization | 25 | 296 | 2.14 × 10−15 | AGRN,BMP1,CD44,COMP,DCN,FBLN1,FBN1,GAS6,HTRA1,KLK7,LAMA1,LAMA2,LAMA4,LAMA5,LOXL2,MMP2,NID1,NID2,PLOD3,PXDN,SERPINE1,SULF1,SULF2,THBS1,VWF | |
Cellular component organization | 89 | 5163 | 2.93 × 10−14 | ACTN1,ACTN4,AGRN,ALDOA,ANXA1,ANXA6,AP2A1,AP2M1,APOA4,APOB,APOE,ARF4,ARPC2,ATL1,ATXN2,BMP1,CAP1,CD151,CD44,CD59,COMP,DCN,EHD1,EHD2,EXT1,FAS,FAT1,FBLN1,FBN1,FERMT3,FLNA,FLNB,FLNC,FSCN1,GAS6,GGCT,HIST1H4F,HTRA1,KLK7,KRT1,LAMA1,LAMA2,LAMA4,LAMA5,LAMP2,LOXL2,LTBP2,MFGE8,MMP2,MSRB1,MYH9,MYOF,NID1,NID2,PKP1,PLEC,PLOD3,PLS1,PLS3,PTGFRN,PXDN,RAB7A,RAC1,RAN,RHOC,SDC4,SEMG1,SERPINE1,SGCG,SLC25A6,SPAG1,SPTBN1,SRGN,SRPX,SULF1,SULF2,TGM1,TGM2,TGM3,THBS1,THY1,TLN1,TPM4,TTN,UBB,VPS35,VWF,WDR1,WNT5A | |
Secretion by cell | 37 | 959 | 2.43 × 10−13 | ACLY,ACTN1,ACTN4,ALDOA,ANXA1,ANXA5,APLP2,CAP1,CD44,CD59,CD63,EEF2,F13A1,FERMT3,FLNA,GAS6,ITIH3,ITIH4,KRT1,LAMP1,LAMP2,LTBP2,MVP,PKP1,PRDX6,PTX3,RAB5C,RAB7A,RAC1,RAP1B,SERPINE1,SRGN,THBS1,TLN1,TTN,VWF,WDR1 | |
Response to stimulus | 107 | 7824 | 6.96 × 10−12 | ACLY,ACTN4,AFP,AGRN,AHCY,AICDA,ALDOA,ANXA1,ANXA11,ANXA5,ANXA6,AP2A1,AP2M1,APLP2,APOA4,APOB,APOE,ARF4,ARPC2,AZGP1,C1S,CAP1,CD151,CD44,CD59,CD63,CD81,CD82,CLIC1,DCN,EEF2,EHD1,EHD2,EXT1,EXT2,F13A1,FAS,FBLN1,FBN1,FERMT3,FLNA,FLNB,FSCN1,GAS6,GGCT,GNAI2,GNB2L1,GPC6,GPRC5A,HIST1H4F,HSPA5,ITIH4,KRT1,LAMA1,LAMA2,LAMA5,LAMP1,LAMP2,LDHA,LOXL2,LRP1,LTBP1,LTBP2,MMP2,MRC2,MSRB1,MVP,MYH9,MYOF,NNMT,PDIA3,PGK1,PKP1,PLOD1,PLOD3,POLR3G,PRDX1,PRDX6,PTX3,PXDN,RAB5C,RAB7A,RAC1,RAN,RAP1B,RHOC,SDC4,SEMG1,SERPINE1,SLC25A6,SPTBN1,SRGN,SRPX,STK33,SULF1,SULF2,TGM2,THBS1,THRB,THY1,TLN1,TTN,UBA1,UBB,VPS35,VWF,WNT5A | |
Localization | 83 | 5233 | 9.26 × 10−11 | ACLY,ACTN1,ACTN4,AGRN,ALDOA,ANXA1,ANXA11,ANXA5,ANXA6,AP2A1,AP2M1,APLP2,APOA4,APOB,APOE,ARF3,ARF4,ARPC2,ATXN2,AZGP1,CAP1,CD151,CD44,CD59,CD63,CD81,CLIC1,EEF2,EHD1,EHD2,F13A1,FAT1,FBN1,FERMT3,FLNA,FLNB,FSCN1,GAS6,GPC6,HSPA5,ITIH3,ITIH4,KRT1,LAMA5,LAMP1,LAMP2,LOXL2,LRP1,LTBP1,LTBP2,MFGE8,MRC2,MVP,MYH9,PKP1,PLOD3,PLS1,PRDX6,PTX3,RAB5C,RAB7A,RAC1,RAN,RAP1B,RHOC,SDC4,SERPINE1,SLC25A6,SPTBN1,SRGN,SRPX,SRPX2,TGM2,THBS1,THY1,TLN1,TTN,TTYH3,UBB,VPS35,VWF,WDR1,WNT5A | |
Anatomical structure development | 80 | 5085 | 5.90 × 10−10 | ACTN1,AEBP1,AFP,AGRN,AICDA,ANXA1,AP2A1,APOA4,APOB,APOE,ARF4,ATL1,BMP1,C6orf58,CAP1,CD151,CD44,COMP,DCN,EEF2,EHD1,EXT1,EXT2,FAS,FAT1,FBLN1,FBN1,FERMT3,FLNA,FLNB,FLNC,FSCN1,GAS6,GNB2L1,HSPA5,HTRA1,KLK7,KRT1,LAMA2,LAMA5,LDHA,LOXL2,LRP1,LTBP1,MFGE8,MMP2,MYH9,MYL6,MYOF,NID1,NNMT,PGK1,PKP1,PLOD1,PLOD3,PLS3,PPIB,PRDX1,RAC1,RAP1B,RHOC,SDC4,SERPINE1,SGCG,SPTBN1,SRGN,SRPX2,SULF1,SULF2,TGM1,TGM2,TGM3,THBS1,THBS3,THRB,THY1,TTN,UBB,WDR1,WNT5A | |
KEGG Pathways | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Focal adhesion | 17 | 197 | 1.23 × 10−10 | ACTN1,ACTN4,COMP,FLNA,FLNB,FLNC,LAMA1,LAMA2,LAMA4,LAMA5,RAC1,RAP1B,THBS1,THBS2,THBS3,TLN1,VWF | |
ECM-receptor interaction | 12 | 81 | 5.47 × 10−10 | AGRN,CD44,COMP,LAMA1,LAMA2,LAMA4,LAMA5,SDC4,THBS1,THBS2,THBS3,VWF | |
Proteoglycans in cancer | 12 | 195 | 3.88 × 10−6 | CD44,CD63,DCN,FAS,FLNA,FLNB,FLNC,MMP2,RAC1,SDC4,THBS1,WNT5A | |
Phagosome | 10 | 145 | 1.40 × 10−5 | COMP,LAMP1,LAMP2,MRC2,RAB5C,RAB7A,RAC1,THBS1,THBS2,THBS3 | |
Amoebiasis | 8 | 94 | 4.01 × 10−5 | ACTN1,ACTN4,LAMA1,LAMA2,LAMA4,LAMA5,RAB5C,RAB7A | |
Malaria | 6 | 47 | 8.88 × 10−5 | CD81,COMP,LRP1,THBS1,THBS2,THBS3 | |
Salmonella infection | 7 | 84 | 0.00016 | ARPC2,FLNA,FLNB,FLNC,MYH9,RAB7A,RAC1 | |
Endocytosis | 10 | 242 | 0.00054 | AP2A1,AP2M1,ARF3,ARPC2,EHD1,EHD2,RAB5C,RAB7A,UBB,VPS35 | |
Leukocyte transendothelial migration | 7 | 112 | 0.0007 | ACTN1,ACTN4,GNAI2,MMP2,RAC1,RAP1B,THY1 | |
Human papillomavirus infection | 11 | 317 | 0.00079 | COMP,FAS,LAMA1,LAMA2,LAMA4,LAMA5,THBS1,THBS2,THBS3,VWF,WNT5A | |
PI3K-Akt signaling pathway | 10 | 348 | 0.0069 | COMP,LAMA1,LAMA2,LAMA4,LAMA5,RAC1,THBS1,THBS2,THBS3,VWF | |
Complement and coagulation cascades | 5 | 78 | 0.0069 | C1S,CD59,F13A1,SERPINE1,VWF | |
Cholesterol metabolism | 4 | 48 | 0.0088 | APOA4,APOB,APOE,LRP1 | |
Toxoplasmosis | 5 | 109 | 0.0226 | GNAI2,LAMA1,LAMA2,LAMA4,LAMA5 | |
Glycolysis / Gluconeogenesis | 4 | 68 | 0.0259 | ALDOA,LDHA,LDHB,PGK1 | |
p53 signaling pathway | 4 | 68 | 0.0259 | CD82,FAS,SERPINE1,THBS1 | |
Platelet activation | 5 | 123 | 0.0308 | FERMT3,GNAI2,RAP1B,TLN1,VWF | |
10 Most Significant PMID Publications per FDR | |||||
Term ID | Term Description | Obs | Bgr | FDR | Matching Proteins in the Network |
PMID:29250190 | (2017) Role of exosomes in hepatocellular carcinoma cell mobility alteration. | 17 | 34 | 1.84 × 10−18 | ACTN1,ANXA1,ANXA11,ANXA5,ANXA6,APOB,APOE,CAP1,CLIC1,FBLN1,FLNA,ITIH4,LRP1,MFGE8,NID1,RAN,TLN1 |
PMID:24009881 | (2012) Quantitative proteomics of extracellular vesicles derived from human primary and metastatic colorectal cancer cells. | 21 | 161 | 9.74 × 10−14 | AHCY,ANXA1,ANXA11,ANXA5,ANXA6,ARF3,ARPC2,CD44,CD63,CD81,FSCN1,KRT1,LAMP1,MFGE8,MYH9,MYL6,PGK1,PTGFRN,RAB5C,RAB7A,VPS35 |
PMID:19948009 | (2009) Proteomic analysis of blastema formation in regenerating axolotl limbs. | 22 | 221 | 1.76 × 10−12 | ANXA1,ANXA11,ANXA5,ANXA6,DCN,EEF2,FBN1,FLNB,GNB2L1,MVP,MYH9,MYL6,MYOF,PDIA3,PLS3,PRDX1,PXDN,RAN,SND1,TTN,UBA1,WNT5A |
PMID:24392111 | (2014) Proteomic analysis of C2C12 myoblast and myotube exosome-like vesicles: a new paradigm for myoblast-myotube cross talk? | 16 | 79 | 1.87 × 10−12 | ALDOA,ANXA5,CD44,CD63,CD81,CD82,EEF2,FLNC,LAMP1,LAMP2,LDHA,MYOF,PGK1,TLN1,TTN,VPS35 |
PMID:27605433 | (2016) Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo. | 17 | 107 | 5.36 × 10−12 | ACLY,ANXA1,ANXA6,CD44,CD63,CD81,CD82,FAT1,GNB2L1,LAMA1,LAMP1,MFGE8,MMP2,PLS3,SULF1,THBS1,VPS35 |
PMID:22897585 | (2012) Rat mammary extracellular matrix composition and response to ibuprofen treatment during postpartum involution by differential GeLC-MSMS analysis. | 13 | 42 | 1.24 × 10−11 | AGRN,ANXA1,ANXA11,ANXA5,ANXA6,CD44,DCN,FBN1,LAMA1,LAMA2,LAMA4,LAMA5,VWF |
PMID:27770278 | (2017) Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease. | 14 | 63 | 3.75 × 10−11 | ACTN4,ANXA1,CCT6A,CD44,EHD1,HSPA5,LAMA4,MMP2,MVP,MYH9,RAB5C,RAB7A,UBA1,VPS35 |
PMID:22159717 | (2012) The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. | 14 | 64 | 3.97 × 10−11 | AGRN,ANXA1,ANXA11,ANXA5,ANXA6,DCN,FBN1,LOXL2,LTBP2,NID1,NID2,SRPX,THBS1,VWF |
PMID:25201077 | (2015) Proteomics of apheresis platelet supernatants during routine storage: Gender-related differences. | 16 | 106 | 5.20 × 10−-11 | ACTN1,APOB,APOE,ARPC2,C1S,FERMT3,FLNA,ITIH4,LDHA,MMP2,MYL6,PRDX6,SRGN,THBS1,TLN1,VWF |
PMID:28071719 | (2017) Quantitative proteomic profiling of the extracellular matrix of pancreatic islets during the angiogenic switch and insulinoma progression. | 13 | 54 | 1.20 × 10−10 | ANXA1,ANXA11,ANXA5,ANXA6,DCN,FBN1,LAMA1,LAMA2,LAMA4,LAMA5,NID1,NID2,THBS2 |
Gene ontology (GO) Terms for Biological Processes | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Cell envelope organization | 2 | 3 | 0.0017 | TGM1,TGM3 | |
10 Most Significant PMID Publications per FDR | |||||
Term ID | Term Description | Obs | Bgr | FDR | Matching Proteins in the Network |
PMID:22329734 | (2012) Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair. | 3 | 14 | 0.0016 | KLK7,TGM1,TGM3 |
PMID:11093806 | (2000) Transglutaminase-3, an esophageal cancer-related gene. | 2 | 2 | 0.0136 | TGM1,TGM3 |
PMID:11562168 | (2001) Crystallization and preliminary X-ray analysis of human transglutaminase 3 from zymogen to active form. | 2 | 2 | 0.0136 | TGM1,TGM3 |
PMID:11980702 | (2002) Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation. | 2 | 2 | 0.0136 | TGM1,TGM3 |
PMID:12850301 | (2003) Analysis of epidermal-type transglutaminase (transglutaminase 3) in human stratified epithelia and cultured keratinocytes using monoclonal antibodies. | 2 | 3 | 0.0136 | TGM1,TGM3 |
PMID:14508061 | (2003) A model for the reaction mechanism of the transglutaminase 3 enzyme. | 2 | 2 | 0.0136 | TGM1,TGM3 |
PMID:14645372 | (2004) Structural basis for the coordinated regulation of transglutaminase 3 by guanine nucleotides and calciummagnesium. | 2 | 2 | 0.0136 | TGM1,TGM3 |
PMID:14987256 | (2004) Identification of calcium-inducible genes in primary keratinocytes using suppression-subtractive hybridization. | 2 | 8 | 0.0136 | KLK7,TGM1 |
PMID:15084592 | (2004) Crystal structure of transglutaminase 3 in complex with GMP: structural basis for nucleotide specificity. | 2 | 2 | 0.0136 | TGM1,TGM3 |
PMID:15172109 | (2004) Transglutaminase activity and transglutaminase mRNA transcripts in gerbil brain ischemia. | 2 | 3 | 0.0136 | TGM1,TGM3 |
Gene Ontology (GO) Terms for Biological Processes 10 Most Significant Results per FDR (for All GO Terms, See Supplementary Table S5A) | |||||
Term Description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Vesicle-mediated transport | 41 | 1699 | 2.01 × 10−13 | ACTR3,AP1G1,AP2B1,ARF6,ARPC4,CALR,CAND1,CAPZB,CAV1,CD9,CDC42,COPB2,ECM1,EEA1,EHD4,IGF2R,KPNB1,MME,NME1,PDIA6,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,RAB1A,RAB2A,RALA,SLC44A2,SOD1,STOM,SYK,TGFB1,TIMP3,VAT1,XRCC6 | |
Localization | 66 | 5233 | 4.37 × 10−11 | ACTR3,AP1G1,AP2B1,APOM,ARF6,ARPC4,CALR,CAND1,CAPZB,CAV1,CD9,CDC42,COPB2,CSE1L,DHX9,ECM1,EEA1,EHD4,FBN2,IGF2R,IGSF8,ILK,IPO5,IPO7,KPNB1,LMNA,MME,NME1,NRP1,PAFAH1B1,PDIA6,PGM1,PIP,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,RAB1A,RAB2A,RALA,RELN,RNF128,RPL14,RTN4,SLC3A2,SLC44A1,SLC44A2,SLIT2,SOD1,SPOCK1,STOM,SYK,TGFB1,THBS4,TIMP3,VAT1,VDAC1,VDAC2,WLS,XPO1,XRCC6 | |
Secretion | 30 | 1070 | 8.12 × 10−11 | CAND1,CAV1,CD9,ECM1,IGF2R,KPNB1,MME,NME1,PAFAH1B1,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,RAB1A,RALA,SLC44A2,SOD1,STOM,SYK,TGFB1,TIMP3,VAT1,WLS,XRCC6 | |
Transport | 57 | 4130 | 1.80 × 10−10 | ACTR3,AP1G1,AP2B1,APOM,ARF6,ARPC4,CALR,CAND1,CAPZB,CAV1,CD9,CDC42,COPB2,CSE1L,DHX9,ECM1,EEA1,EHD4,IGF2R,IPO5,IPO7,KPNB1,LMNA,MME,NME1,NRP1,PAFAH1B1,PDIA6,PGM1,PIP,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,RAB1A,RAB2A,RALA,RPL14,SLC3A2,SLC44A1,SLC44A2,SOD1,STOM,SYK,TGFB1,TIMP3,VAT1,VDAC1,VDAC2,WLS,XPO1,XRCC6 | |
Secretion by cell | 28 | 959 | 1.80 × 10−10 | CAND1,CD9,ECM1,IGF2R,KPNB1,MME,PAFAH1B1,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,RAB1A,RALA,SLC44A2,SOD1,STOM,SYK,TGFB1,TIMP3,VAT1,WLS,XRCC6 | |
Regulated exocytosis | 24 | 691 | 2.67 × 10−10 | CAND1,CD9,ECM1,IGF2R,KPNB1,MME,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,SLC44A2,SOD1,STOM,SYK,TGFB1,TIMP3,VAT1,XRCC6 | |
Exocytosis | 25 | 774 | 3.25 × 10−10 | CAND1,CD9,ECM1,IGF2R,KPNB1,MME,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,RALA,SLC44A2,SOD1,STOM,SYK,TGFB1,TIMP3,VAT1,XRCC6 | |
Neutrophil activation involved in immune response | 19 | 489 | 1.06 × 10−8 | CAND1,IGF2R,KPNB1,MME,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,SLC44A2,STOM,SYK,VAT1,XRCC6 | |
Myeloid leukocyte activation | 20 | 574 | 1.48 × 10−8 | CAND1,IGF2R,KPNB1,MME,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,SLC44A2,STOM,SYK,TGFB1,VAT1,XRCC6 | |
Neutrophil degranulation | 18 | 485 | 4.95 × 10−8 | CAND1,IGF2R,KPNB1,MME,PGM1,PPIA,PSMD1,PSMD2,PSMD3,PYGB,PYGL,QSOX1,RAB10,RAB14,SLC44A2,STOM,VAT1,XRCC6 | |
KEGG Pathways | |||||
Term description | Obs | Bgr | FDR | Matching Proteins in the Network | |
Endocytosis | 10 | 242 | 0.00016 | AP2B1,ARF6,ARPC4,CAPZB,CAV1,CDC42,EEA1,EHD4,IGF2R,RAB10 | |
Focal adhesion | 8 | 197 | 0.0012 | CAV1,CDC42,ILK,LAMB2,PARVB,PPP1CB,RELN,THBS4 | |
Bacterial invasion of epithelial cells | 5 | 72 | 0.003 | ARPC4,CAV1,CDC42,ILK,SEPT2 | |
Pentose phosphate pathway | 3 | 30 | 0.0278 | G6PD,PGM1,RGN | |
Starch and sucrose metabolism | 3 | 33 | 0.0278 | PGM1,PYGB,PYGL | |
Proteoglycans in cancer | 6 | 195 | 0.0278 | CAV1,CDC42,LUM,PPP1CB,TGFB1,TIMP3 | |
Proteasome | 3 | 43 | 0.0347 | PSMD1,PSMD2,PSMD3 | |
Necroptosis | 5 | 155 | 0.0347 | PPIA,PYGB,PYGL,VDAC1,VDAC2 | |
Fc gamma R-mediated phagocytosis | 4 | 89 | 0.0347 | ARF6,ARPC4,CDC42,SYK | |
Amino sugar and nucleotide sugar metabolism | 3 | 48 | 0.0396 | CHIA,PGM1,UGDH | |
HTLV-I infection | 6 | 250 | 0.0396 | CALR,NRP1,TGFB1,VDAC1,VDAC2,XPO1 | |
10 Most Significant PMID Publications per FDR | |||||
Term ID | Term Description | Obs | Bgr | FDR | Matching Proteins in the Network |
PMID:11149929 | (2001) The phagosome proteome: insight into phagosome functions. | 9 | 47 | 3.12 × 10−6 | ARF6,CALR,DFFA,P4HB,RAB10,RAB14,RAB2A,STOM,VDAC1 |
PMID:17892558 | (2007) Quantifying raft proteins in neonatal mouse brain by ‘tube-gel’ protein digestion label-free shotgun proteomics. | 10 | 83 | 6.99 × 10−6 | ACTC1,BASP1,CAV1,CNTN1,RAB10,RAB14,RAB1A,RAB2A,SLC3A2,VDAC1 |
PMID:22578496 | (2012) Harnessing the power of the endosome to regulate neural development. | 7 | 35 | 0.00014 | ARF6,EEA1,EHD4,NRP1,RAB14,RTN4,WLS |
PMID:24009881 | (2012) Quantitative proteomics of extracellular vesicles derived from human primary and metastatic colorectal cancer cells. | 11 | 161 | 0.00014 | ACTR3,CAPZB,CD9,EHD4,ILK,RAB10,RALA,SLC3A2,SLC44A1,SYK,UGDH |
PMID:27770278 | (2017) Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease. | 8 | 63 | 0.00016 | ACTR3,CALR,ECM1,IGF2R,IPO5,PSMD2,RAB10TGFB1 |
PMID:26205348 | (2015) Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex. | 6 | 22 | 0.00023 | AP1G1,CDC42,NME1,SOD1,VDAC1,VDAC2 |
PMID:20140087 | (2010) Comprehensive identification and modified-site mapping of S-nitrosylated targets in prostate epithelial cells. | 9 | 103 | 0.00024 | DHX9,HNRNPK,KPNB1,LMNA,P4HB,PDIA6,RTN4,VDAC1,VDAC2 |
PMID:27549615 | (2016) Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy. | 6 | 23 | 0.00024 | LMNA,PAMR1,PPIA,PSMD2,SLIT2,THBS4 |
PMID:23170974 | (2012) Integrated miRNA, mRNA and protein expression analysis reveals the role of post-transcriptional regulation in controlling CHO cell growth rate. | 6 | 27 | 0.00044 | HNRNPK,RAB10,RAB14,RAB1A,RAB2A,RPL14 |
PMID:24505448 | (2014) Characterisation of four LIM protein-encoding genes involved in infection-related development and pathogenicity by the rice blast fungus Magnaporthe oryzae. | 6 | 28 | 0.00047 | CDC42,ILK,LMNA,PHGDH,RAB2A,XRCC6 |
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András, I.E.; Sewell, B.B.; Toborek, M. HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles. Int. J. Mol. Sci. 2020, 21, 2741. https://doi.org/10.3390/ijms21082741
András IE, Sewell BB, Toborek M. HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles. International Journal of Molecular Sciences. 2020; 21(8):2741. https://doi.org/10.3390/ijms21082741
Chicago/Turabian StyleAndrás, Ibolya E., Brice B. Sewell, and Michal Toborek. 2020. "HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles" International Journal of Molecular Sciences 21, no. 8: 2741. https://doi.org/10.3390/ijms21082741