shanmuganathan r, et al. proteomic signature of ... · shanmuganathan r, et al. proteomic signature...

5
Proteomic Signature of Intervertebral Discs Shanmuganathan R, et al. https://doi.org/10.14245/ns.2040056.028 www.e-neurospine.org Supplementary Table 2. Detailed list of 105 enriched pathways from STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database No. Enriched pathways Total number of proteins involved p-value Gene symbols 1 Extracellular matrix organization 37 8.90E-24 A2M, ACAN, ASPN, BGN, CD47, COL10A1, COL11A2, COL14A1, COL15A1, COL1A1, COL1A2, COL2A1, CO- L6A1, COL6A2, COL6A3, COMP, DCN, FGA, FGB, FGG, FMOD, GDF5, HAPLN1, HSPG2, HTRA1, LOX, LUM, MMP10, PCOLCE, PCOLCE2, PPIB, THBS1, TIMP1, TNC, TTR, VCAN, VTN 2 ECM proteoglycans 18 9.26E-16 ACAN, ASPN, BGN, COL1A1, COL1A2, COL2A1, COL6A1, COL6A2, COL6A3, COMP, DCN, FMOD, HAPLN1, HSPG2, LUM, TNC, VCAN, VTN 3 Integrin cell surface interactions 17 6.49E-14 CD47, COL10A1, COL1A1, COL1A2, COL2A1, COL6A1, COL6A2, COL6A3, COMP, FGA, FGB, FGG, HSPG2, LUM, THBS1, TNC, VTN 4 Collagen biosynthesis and modify- ing enzymes 13 1.63E-10 COL10A1, COL11A2, COL14A1, COL15A1, COL1A1, COL1A2, COL2A1, COL6A1, COL6A2, COL6A3, PCOLCE, PCOLCE2, PPIB 5 Collagen formation 14 2.61E-10 COL10A1, COL11A2, COL14A1, COL15A1, COL1A1, COL1A2, COL2A1, COL6A1, COL6A2, COL6A3, LOX, PCOLCE, PCOLCE2, PPIB 6 Glycosaminoglycan metabolism 12 4.88E-07 ACAN, B3GNT7, BGN, DCN, FMOD, HSPG2, LUM, OGN, OMD, PRELP, VCAN, XYLT1 7 Keratan sulfate degradation 6 5.80E-07 ACAN, FMOD, LUM, OGN, OMD, PRELP 8 Gluconeogenesis 5 0.00054 ENO1, GAPDH, PGAM2, PGK1, TPI1 9 Formation of the cornified envelope 29 1.66E-24 CDSN, DSG1, DSP, JUP, KRT1, KRT10, KRT14, KRT15, KRT16, KRT17, KRT19, KRT2, KRT33A, KRT4, KRT5, KRT6A, KRT6B, KRT6C, KRT72, KRT73, KRT76, KRT77, KRT78, KRT79, KRT8, KRT80, KRT84, KRT9, TGM5 10 Platelet degranulation 22 1.04E-16 A1BG, A2M, ALB, ANXA5, APOA1, CD109, CLEC3B, CLU, F13A1, FGA, FGB, FGG, HRG, ITIH4, QSOX1, SER- PINA1, SERPING1, TF, THBS1, TIMP1, TIMP3, TTN 11 Platelet activation, signalling and aggregation 25 6.50E-14 A1BG, A2M, ALB, ANXA5, APOA1, CD109, CLEC3B, CLU, COL1A1, COL1A2, F13A1, FGA, FGB, FGG, HRG, ITIH4, QSOX1, RASGRP2, SERPINA1, SERPING1, TF, THBS1, TIMP1, TIMP3, TTN 12 Innate immune system 45 2.71E-13 A1BG, ACTG1, ANXA2, ARG1, C1S, C3, C9, CALML5, CASP8, CD47, CFB, CFI, CHI3L1, CLU, DCD, DSG1, DSP, FABP5, FGA, FGB, FGG, FLG2, FTL, GSN, HBB, HP, HRNR, JUP, KRT1, LTF, LYZ, MIF, PKM, PLA2G2A, QSOX1, RASGRP2, S100A1, S100A8, S100A9, SERPINA1, SERPINB1, SERPING1, TNFAIP6, TTR, VTN 13 Hemostasis 34 1.31E-12 A1BG, A2M, ALB, ANXA2, ANXA5, APOA1, CD109, CD47, CLEC3B, CLU, COL1A1, COL1A2, F13A1, FGA, FGB, FGG, HBB, HBD, HRG, ITIH4, KIF1B, MIF, QSOX1, RASGRP2, SERPINA1, SERPINA5, SERPINC1, SER- PINE2, SERPING1, TF, THBS1, TIMP1, TIMP3, TTN 14 Neutrophil degranulation 29 1.53E-11 A1BG, ANXA2, ARG1, C3, CALML5, CD47, CHI3L1, DSG1, DSP, FABP5, FLG2, FTL, GSN, HBB, HP, HRNR, JUP, KRT1, LTF, LYZ, MIF, PKM, QSOX1, S100A8, S100A9, SERPINA1, SERPINB1, TNFAIP6, TTR 15 Degradation of the extracellular ma- trix 17 7.17E-11 A2M, ACAN, COL10A1, COL11A2, COL14A1, COL15A1, COL1A1, COL1A2, COL2A1, COL6A1, COL6A2, CO- L6A3, DCN, HSPG2, HTRA1, MMP10, TIMP1 16 Post-translational protein phos- phorylation 15 1.94E-10 ALB, APOA1, C3, CP, FGA, FGG, MFGE8, MFI2, QSOX1, SERPINA1, SERPINC1, TF, TIMP1, TNC, VCAN 17 Immune system 57 3.58E-10 A1BG, ACTG1, ANXA1, ANXA2, ARG1, BLMH, C1S, C3, C9, CA1, CALML5, CASP8, CD47, CFB, CFI, CHI3L1, CLU, COL1A1, COL1A2, COL2A1, CSF3R, DCD, DSG1, DSP, F13A1, FABP5, FGA, FGB, FGG, FLG2, FTL, GSN, HBB, HP, HRNR, JUP, KRT1, LTF, LYZ, MIF, MSN, PKM, PLA2G2A, QSOX1, RASGRP2, S100A1, S100A8, S100A9, SERPINA1, SERPINB1, SERPING1, TIMP1, TNFAIP6, TNFRSF11B, TTR, VIM, VTN (Continued to the next page)

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Page 1: Shanmuganathan R, et al. Proteomic Signature of ... · Shanmuganathan R, et al. Proteomic Signature of Intervertebral Discs   No. Enriched pathways Total number

Proteomic Signature of Intervertebral DiscsShanmuganathan R, et al.

https://doi.org/10.14245/ns.2040056.028www.e-neurospine.org

Supp

lem

enta

ry T

able

2. D

etai

led

list o

f 105

enric

hed

path

way

s fro

m S

TRIN

G (S

earc

h To

ol fo

r the

Ret

rieva

l of I

nter

actin

g G

enes

/Pro

tein

s) d

atab

ase

No.

Enric

hed

path

way

sTo

tal n

umbe

r of

pro

tein

s in

volv

edp-

valu

eG

ene s

ymbo

ls

1Ex

trac

ellu

lar m

atrix

org

aniz

atio

n37

8.90

E-24

A2M

, ACA

N, A

SPN

, BG

N, C

D47

, CO

L10A

1, C

OL1

1A2,

CO

L14A

1, C

OL1

5A1,

CO

L1A

1, C

OL1

A2,

CO

L2A

1, C

O-

L6A

1, C

OL6

A2,

CO

L6A

3, C

OM

P, D

CN, F

GA

, FG

B, F

GG

, FM

OD

, GD

F5, H

APL

N1,

HSP

G2,

HTR

A1,

LO

X, L

UM

, M

MP1

0, P

COLC

E, P

COLC

E2, P

PIB,

TH

BS1,

TIM

P1, T

NC,

TTR

, VCA

N, V

TN 2

ECM

pro

teog

lyca

ns18

9.26

E-16

ACA

N, A

SPN

, BG

N, C

OL1

A1,

CO

L1A

2, C

OL2

A1,

CO

L6A

1, C

OL6

A2,

CO

L6A

3, C

OM

P, D

CN, F

MO

D, H

APL

N1,

H

SPG

2, L

UM

, TN

C, V

CAN

, VTN

3In

tegr

in ce

ll su

rfac

e int

erac

tions

176.

49E-

14CD

47, C

OL1

0A1,

CO

L1A

1, C

OL1

A2,

CO

L2A

1, C

OL6

A1,

CO

L6A

2, C

OL6

A3,

CO

MP,

FGA

, FG

B, F

GG

, HSP

G2,

LU

M, T

HBS

1, T

NC,

VTN

4C

olla

gen

bios

ynth

esis

and

mod

ify-

ing

enzy

mes

131.

63E-

10CO

L10A

1, C

OL1

1A2,

CO

L14A

1, C

OL1

5A1,

CO

L1A

1, C

OL1

A2,

CO

L2A

1, C

OL6

A1,

CO

L6A

2, C

OL6

A3,

PCO

LCE,

PC

OLC

E2, P

PIB

5C

olla

gen

form

atio

n14

2.61

E-10

COL1

0A1,

CO

L11A

2, C

OL1

4A1,

CO

L15A

1, C

OL1

A1,

CO

L1A

2, C

OL2

A1,

CO

L6A

1, C

OL6

A2,

CO

L6A

3, L

OX,

PC

OLC

E, P

COLC

E2, P

PIB

6G

lyco

sam

inog

lyca

n m

etab

olism

124.

88E-

07AC

AN

, B3G

NT7

, BG

N, D

CN, F

MO

D, H

SPG

2, L

UM

, OG

N, O

MD

, PRE

LP, V

CAN

, XYL

T1 7

Kera

tan

sulfa

te d

egra

datio

n6

5.80

E-07

ACA

N, F

MO

D, L

UM

, OG

N, O

MD

, PRE

LP 8

Glu

cone

ogen

esis

50.

0005

4EN

O1,

GA

PDH

, PG

AM

2, P

GK1

, TPI

1 9

Form

atio

n of

the c

orni

fied

enve

lope

291.

66E-

24CD

SN, D

SG1,

DSP

, JU

P, KR

T1, K

RT10

, KRT

14, K

RT15

, KRT

16, K

RT17

, KRT

19, K

RT2,

KRT

33A

, KRT

4, K

RT5,

KR

T6A

, KRT

6B, K

RT6C

, KRT

72, K

RT73

, KRT

76, K

RT77

, KRT

78, K

RT79

, KRT

8, K

RT80

, KRT

84, K

RT9,

TG

M5

10Pl

atel

et d

egra

nula

tion

221.

04E-

16A

1BG

, A2M

, ALB

, AN

XA5,

APO

A1,

CD

109,

CLE

C3B,

CLU

, F13

A1,

FG

A, F

GB,

FG

G, H

RG, I

TIH

4, Q

SOX1

, SER

-PI

NA

1, S

ERPI

NG

1, T

F, TH

BS1,

TIM

P1, T

IMP3

, TTN

11Pl

atel

et ac

tivat

ion,

sign

allin

g an

d ag

greg

atio

n25

6.50

E-14

A1B

G, A

2M, A

LB, A

NXA

5, A

POA

1, C

D10

9, C

LEC3

B, C

LU, C

OL1

A1,

CO

L1A

2, F

13A

1, F

GA

, FG

B, F

GG

, HRG

, IT

IH4,

QSO

X1, R

ASG

RP2,

SER

PIN

A1,

SER

PIN

G1,

TF,

THBS

1, T

IMP1

, TIM

P3, T

TN12

Inna

te im

mun

e sys

tem

452.

71E-

13A

1BG

, ACT

G1,

AN

XA2,

ARG

1, C

1S, C

3, C

9, C

ALM

L5, C

ASP8

, CD

47, C

FB, C

FI, C

HI3

L1, C

LU, D

CD, D

SG1,

DSP

, FA

BP5,

FG

A, F

GB,

FG

G, F

LG2,

FTL

, GSN

, HBB

, HP,

HRN

R, JU

P, KR

T1, L

TF, L

YZ, M

IF, P

KM, P

LA2G

2A,

QSO

X1, R

ASG

RP2,

S10

0A1,

S10

0A8,

S10

0A9,

SER

PIN

A1,

SER

PIN

B1, S

ERPI

NG

1, T

NFA

IP6,

TTR

, VTN

13H

emos

tasis

341.

31E-

12A

1BG

, A2M

, ALB

, AN

XA2,

AN

XA5,

APO

A1,

CD

109,

CD

47, C

LEC3

B, C

LU, C

OL1

A1,

CO

L1A

2, F

13A

1, F

GA

, FG

B, F

GG

, HBB

, HBD

, HRG

, ITI

H4,

KIF

1B, M

IF, Q

SOX1

, RAS

GRP

2, S

ERPI

NA

1, S

ERPI

NA

5, S

ERPI

NC1

, SER

-PI

NE2

, SER

PIN

G1,

TF,

THBS

1, T

IMP1

, TIM

P3, T

TN14

Neu

troph

il de

gran

ulat

ion

291.

53E-

11A

1BG

, AN

XA2,

ARG

1, C

3, C

ALM

L5, C

D47

, CH

I3L1

, DSG

1, D

SP, F

ABP

5, F

LG2,

FTL

, GSN

, HBB

, HP,

HRN

R, JU

P, KR

T1, L

TF, L

YZ, M

IF, P

KM, Q

SOX1

, S10

0A8,

S10

0A9,

SER

PIN

A1,

SER

PIN

B1, T

NFA

IP6,

TTR

15D

egra

datio

n of

the e

xtra

cellu

lar m

a-tr

ix17

7.17

E-11

A2M

, ACA

N, C

OL1

0A1,

CO

L11A

2, C

OL1

4A1,

CO

L15A

1, C

OL1

A1,

CO

L1A

2, C

OL2

A1,

CO

L6A

1, C

OL6

A2,

CO

-L6

A3,

DCN

, HSP

G2,

HTR

A1,

MM

P10,

TIM

P116

Post-

tran

slatio

nal p

rote

in p

hos-

phor

ylat

ion

151.

94E-

10A

LB, A

POA

1, C

3, C

P, FG

A, F

GG

, MFG

E8, M

FI2,

QSO

X1, S

ERPI

NA

1, S

ERPI

NC1

, TF,

TIM

P1, T

NC,

VCA

N

17Im

mun

e sys

tem

573.

58E-

10A

1BG

, ACT

G1,

AN

XA1,

AN

XA2,

ARG

1, B

LMH

, C1S

, C3,

C9,

CA

1, C

ALM

L5, C

ASP8

, CD

47, C

FB, C

FI, C

HI3

L1,

CLU,

CO

L1A

1, C

OL1

A2,

CO

L2A

1, C

SF3R

, DCD

, DSG

1, D

SP, F

13A

1, F

ABP

5, F

GA

, FG

B, F

GG

, FLG

2, F

TL, G

SN,

HBB

, HP,

HRN

R, JU

P, KR

T1, L

TF, L

YZ, M

IF, M

SN, P

KM, P

LA2G

2A, Q

SOX1

, RAS

GRP

2, S

100A

1, S

100A

8,

S100

A9,

SER

PIN

A1,

SER

PIN

B1, S

ERPI

NG

1, T

IMP1

, TN

FAIP

6, T

NFR

SF11

B, T

TR, V

IM, V

TN

(Con

tinue

d to

the n

ext p

age)

Page 2: Shanmuganathan R, et al. Proteomic Signature of ... · Shanmuganathan R, et al. Proteomic Signature of Intervertebral Discs   No. Enriched pathways Total number

Proteomic Signature of Intervertebral DiscsShanmuganathan R, et al.

https://doi.org/10.14245/ns.2040056.028 www.e-neurospine.org

No.

Enric

hed

path

way

sTo

tal n

umbe

r of

pro

tein

s in

volv

edp-

valu

eG

ene s

ymbo

ls

18A

ssem

bly

of co

llage

n fib

rils a

nd

othe

r mul

timer

ic st

ruct

ures

126.

15E-

10CO

L10A

1, C

OL1

1A2,

CO

L14A

1, C

OL1

5A1,

CO

L1A

1, C

OL1

A2,

CO

L2A

1, C

OL6

A1,

CO

L6A

2, C

OL6

A3,

LO

X,

PCO

LCE

19re

gula

tion

of in

sulin

-like

gro

wth

fa

ctor

tran

spor

t and

upt

ake b

y in

-su

lin-li

ke g

row

th fa

ctor

bin

ding

pr

otei

ns

151.

03E-

09A

LB, A

POA

1, C

3, C

P, FG

A, F

GG

, MFG

E8, M

FI2,

QSO

X1, S

ERPI

NA

1, S

ERPI

NC1

, TF,

TIM

P1, T

NC,

VCA

N

20D

iseas

es as

soci

ated

with

gly

cosa

mi-

nogl

ycan

met

abol

ism10

3.96

E-09

ACA

N, B

GN

, DCN

, FM

OD

, HSP

G2,

LU

M, O

GN

, OM

D, P

RELP

, VCA

N

21C

olla

gen

chai

n tr

imer

izat

ion

108.

43E-

09CO

L10A

1, C

OL1

1A2,

CO

L14A

1, C

OL1

5A1,

CO

L1A

1, C

OL1

A2,

CO

L2A

1, C

OL6

A1,

CO

L6A

2, C

OL6

A3

22D

evel

opm

enta

l bio

logy

371.

28E-

08AC

TG1,

AN

K2, C

DSN

, CO

L2A

1, C

OL6

A1,

CO

L6A

2, C

OL6

A3,

DSG

1, D

SP, H

2AFV

, JU

P, KR

T1, K

RT10

, KRT

14,

KRT1

5, K

RT16

, KRT

17, K

RT19

, KRT

2, K

RT33

A, K

RT4,

KRT

5, K

RT6A

, KRT

6B, K

RT6C

, KRT

72, K

RT73

, KRT

76,

KRT7

7, K

RT78

, KRT

79, K

RT8,

KRT

80, K

RT84

, KRT

9, M

SN, T

GM

523

Col

lage

n de

grad

atio

n11

1.37

E-08

COL1

0A1,

CO

L11A

2, C

OL1

4A1,

CO

L15A

1, C

OL1

A1,

CO

L1A

2, C

OL2

A1,

CO

L6A

1, C

OL6

A2,

CO

L6A

3, M

MP1

024

Form

atio

n of

fibr

in cl

ot (c

lotti

ng

casc

ade)

95.

04E-

08A

2M, F

13A

1, F

GA

, FG

B, F

GG

, SER

PIN

A5,

SER

PIN

C1, S

ERPI

NE2

, SER

PIN

G1

25D

efec

tive S

T3G

AL3

caus

es M

CT1

2 an

d EI

EE15

65.

33E-

08AC

AN

, FM

OD

, LU

M, O

GN

, OM

D, P

RELP

26Bi

ndin

g an

d up

take

of l

igan

ds b

y sc

aven

ger r

ecep

tors

95.

63E-

08A

LB, A

POA

1, C

OL1

A1,

CO

L1A

2, F

TL, H

BA1,

HBB

, HP,

HPX

27N

onin

tegr

in m

embr

ane-

ECM

inte

r-ac

tions

106.

87E-

08CO

L10A

1, C

OL1

1A2,

CO

L1A

1, C

OL1

A2,

CO

L2A

1, H

SPG

2, T

HBS

1, T

NC,

TTR

, VTN

28A

myl

oid

fiber

form

atio

n11

7.28

E-08

APC

S, A

POA

1, A

POA

4, F

GA

, GSN

, HSP

G2,

LTF

, LYZ

, MFG

E8, T

GFB

I, TT

R29

Def

ectiv

e CH

ST6

caus

es M

CD

C1

67.

93E-

08AC

AN

, FM

OD

, LU

M, O

GN

, OM

D, P

RELP

30D

efec

tive B

4GA

LT1

caus

es

B4G

ALT

1-C

DG

(CD

G-2

d)6

7.93

E-08

ACA

N, F

MO

D, L

UM

, OG

N, O

MD

, PRE

LP

31M

etab

olism

of c

arbo

hydr

ates

173.

11E-

07AC

AN

, B3G

NT7

, BG

N, D

CN, E

NO

1, F

MO

D, G

APD

H, H

SPG

2, L

UM

, OG

N, O

MD

, PG

AM

2, P

GK1

, PRE

LP, T

PI1,

VC

AN

, XYL

T132

Com

mon

pat

hway

of f

ibrin

clot

for-

mat

ion

73.

54E-

07F1

3A1,

FG

A, F

GB,

FG

G, S

ERPI

NA

5, S

ERPI

NC1

, SER

PIN

E2

33Sc

aven

ging

of h

eme f

rom

pla

sma

65.

80E-

07A

LB, A

POA

1, H

BA1,

HBB

, HP,

HPX

34Ke

rata

n su

lfate

bio

synt

hesis

71.

03E-

06AC

AN

, B3G

NT7

, FM

OD

, LU

M, O

GN

, OM

D, P

RELP

35Re

gula

tion

of co

mpl

emen

t cas

cade

82.

02E-

06C1

S, C

3, C

9, C

FB, C

FI, C

LU, S

ERPI

NG

1, V

TN36

Regu

latio

n of

TLR

by

endo

geno

us

ligan

d6

3.19

E-06

FGA

, FG

B, F

GG

, S10

0A1,

S10

0A8,

S10

0A9

37D

iseas

es o

f gly

cosy

latio

n11

9.04

E-06

ACA

N, B

GN

, DCN

, FM

OD

, HSP

G2,

LU

M, O

GN

, OM

D, P

RELP

, TH

BS1,

VCA

N

Supp

lem

enta

ry T

able

2. C

ontin

ued

(Con

tinue

d to

the n

ext p

age)

Page 3: Shanmuganathan R, et al. Proteomic Signature of ... · Shanmuganathan R, et al. Proteomic Signature of Intervertebral Discs   No. Enriched pathways Total number

Proteomic Signature of Intervertebral DiscsShanmuganathan R, et al.

https://doi.org/10.14245/ns.2040056.028www.e-neurospine.org

No.

Enric

hed

path

way

sTo

tal n

umbe

r of

pro

tein

s in

volv

edp-

valu

eG

ene s

ymbo

ls

38Er

ythr

ocyt

es ta

ke u

p ox

ygen

and

re-

leas

e car

bon

diox

ide

47.

48E-

05CA

1, C

A2,

HBA

1, H

BB

39Pl

atel

et ag

greg

atio

n (p

lug

form

a-tio

n)6

8.18

E-05

COL1

A1,

CO

L1A

2, F

GA

, FG

B, F

GG

, RAS

GRP

2

40In

trin

sic p

athw

ay o

f fib

rin cl

ot fo

r-m

atio

n5

0.00

011

A2M

, SER

PIN

A5,

SER

PIN

C1, S

ERPI

NE2

, SER

PIN

G1

41A

tetr

asac

char

ide l

inke

r seq

uenc

e is

requ

ired

for G

AG

synt

hesis

50.

0002

2BG

N, D

CN, H

SPG

2, V

CAN

, XYL

T1

42Sy

ndec

an in

tera

ctio

ns5

0.00

022

COL1

A1,

CO

L1A

2, T

HBS

1, T

NC,

VTN

43Er

ythr

ocyt

es ta

ke u

p ca

rbon

dio

xide

an

d re

leas

e oxy

gen

40.

0002

4CA

1, C

A2,

HBA

1, H

BB

44Ap

opto

tic ex

ecut

ion

phas

e6

0.00

037

CASP

8, D

SG1,

DSP

, GSN

, HIS

T1H

1C, V

IM45

Sign

alin

g by

PD

GF

60.

0005

4CO

L2A

1, C

OL6

A1,

CO

L6A

2, C

OL6

A3,

TH

BS1,

TH

BS3

46A

ntim

icro

bial

pep

tides

70.

0007

6CL

U, D

CD, L

TF, L

YZ, P

LA2G

2A, S

100A

8, S

100A

947

Cro

sslin

king

of c

olla

gen

fibril

s4

0.00

08CO

L1A

1, C

OL1

A2,

LO

X, P

COLC

E48

Scav

engi

ng b

y cl

ass A

rece

ptor

s4

0.00

08A

POA

1, C

OL1

A1,

CO

L1A

2, F

TL49

Apop

totic

clea

vage

of c

ellu

lar p

ro-

tein

s5

0.00

082

CASP

8, D

SG1,

DSP

, GSN

, VIM

50M

etal

sequ

estr

atio

n by

antim

icro

bial

pr

otei

ns3

0.00

088

LTF,

S100

A8,

S10

0A9

51D

efec

tive B

4GA

LT7

caus

es E

DS,

pr

oger

oid

type

40.

0011

BGN

, DCN

, HSP

G2,

VCA

N

52D

efec

tive B

3GAT

3 ca

uses

JDSS

D-

HD

40.

0011

BGN

, DCN

, HSP

G2,

VCA

N

53D

efec

tive B

3GA

LT6

caus

es E

DSP

2 an

d SE

MD

JL1

40.

0011

BGN

, DCN

, HSP

G2,

VCA

N

54Si

gnal

ing

by re

cept

or ty

rosin

e ki-

nase

s15

0.00

13AC

TG1,

CIL

P, CO

L11A

2, C

OL1

A1,

CO

L1A

2, C

OL2

A1,

CO

L6A

1, C

OL6

A2,

CO

L6A

3, F

GFB

P2, H

SPB1

, JU

P, M

ST1,

TH

BS1,

TH

BS3

55D

efec

tive C

HST

3 ca

uses

SED

CJD

30.

0016

BGN

, DCN

, VCA

N56

Def

ectiv

e CH

ST14

caus

es E

DS,

m

uscu

loco

ntra

ctur

al ty

pe3

0.00

16BG

N, D

CN, V

CAN

57D

efec

tive C

HSY

1 ca

uses

TPB

S3

0.00

16BG

N, D

CN, V

CAN

58Re

tinoi

d m

etab

olism

and

tran

spor

t5

0.00

16A

POA

1, A

POA

4, H

SPG

2, R

BP4,

TTR

59In

tegr

in al

phaI

Ib b

eta3

sign

alin

g4

0.00

2FG

A, F

GB,

FG

G, R

ASG

RP2

Supp

lem

enta

ry T

able

2. C

ontin

ued

(Con

tinue

d to

the n

ext p

age)

Page 4: Shanmuganathan R, et al. Proteomic Signature of ... · Shanmuganathan R, et al. Proteomic Signature of Intervertebral Discs   No. Enriched pathways Total number

Proteomic Signature of Intervertebral DiscsShanmuganathan R, et al.

https://doi.org/10.14245/ns.2040056.028 www.e-neurospine.org

No.

Enric

hed

path

way

sTo

tal n

umbe

r of

pro

tein

s in

volv

edp-

valu

eG

ene s

ymbo

ls

60D

erm

atan

sulfa

te b

iosy

nthe

sis3

0.00

29BG

N, D

CN, V

CAN

61M

ET ac

tivat

es P

TK2

signa

ling

40.

0031

COL1

1A2,

CO

L1A

1, C

OL1

A2,

CO

L2A

162

Cas

pase

-med

iate

d cle

avag

e of c

yto-

skel

etal

pro

tein

s3

0.00

35CA

SP8,

GSN

, VIM

63D

iseas

e24

0.00

39AC

AN

, ACT

G1,

ALB

, BG

N, C

P, D

CN, F

GA

, FG

B, F

GG

, FM

OD

, HSP

G2,

IPO

5, L

TF, L

UM

, OG

N, O

MD

, PRD

X1,

PRD

X2, P

RELP

, RBP

4, T

HBS

1, T

TR, V

CAN

, YW

HA

E64

GRB

2:SO

S pr

ovid

es li

nkag

e to

MA

PK si

gnal

ing

for I

nteg

rins

30.

0042

FGA

, FG

B, F

GG

65D

issol

utio

n of

fibr

in cl

ot3

0.00

42A

NXA

2, H

RG, S

ERPI

NE2

66C

ell-C

ell c

omm

unic

atio

n7

0.00

45AC

TG1,

AN

G, C

D47

, FLN

C, JU

P, KR

T14,

KRT

567

Cel

l jun

ctio

n or

gani

zatio

n6

0.00

45AC

TG1,

AN

G, F

LNC,

JUP,

KRT1

4, K

RT5

68C

S/D

S de

grad

atio

n3

0.00

47BG

N, D

CN, V

CAN

69p1

30C

as li

nkag

e to

MA

PK si

gnal

ing

for i

nteg

rins

30.

0047

FGA

, FG

B, F

GG

70Si

gnal

ing

by h

igh-

kina

se ac

tivity

BR

AF

mut

ants

40.

0051

ACTG

1, F

GA

, FG

B, F

GG

71Vi

sual

pho

totr

ansd

uctio

n6

0.00

55A

POA

1, A

POA

4, H

SPG

2, R

BP4,

RD

H8,

TTR

72G

lyco

lysis

50.

0064

ENO

1, G

APD

H, P

GA

M2,

PG

K1, T

PI1

73G

ene a

nd p

rote

in ex

pres

sion

by

JAK

-STA

T sig

nalin

g af

ter I

nter

leu-

kin-

12 st

imul

atio

n

40.

0065

AN

XA2,

CA

1, M

IF, M

SN

74M

AP2

K an

d M

APK

activ

atio

n4

0.00

7AC

TG1,

FG

A, F

GB,

FG

G75

Sign

alin

g by

mod

erat

e kin

ase a

ctiv

i-ty

BRA

F m

utan

ts4

0.00

7AC

TG1,

FG

A, F

GB,

FG

G

76Pa

rado

xica

l act

ivat

ion

of R

AF

sig-

nalin

g by

kin

ase i

nact

ive B

RAF

40.

007

ACTG

1, F

GA

, FG

B, F

GG

77Pl

asm

a lip

opro

tein

asse

mbl

y3

0.00

8A

2M, A

POA

1, A

POA

478

NC

AM

1 in

tera

ctio

ns4

0.00

85CO

L2A

1, C

OL6

A1,

CO

L6A

2, C

OL6

A3

79C

hond

roiti

n su

lfate

bio

synt

hesis

30.

0089

BGN

, DCN

, VCA

N80

TLR

casc

ades

70.

0099

CASP

8, F

GA

, FG

B, F

GG

, S10

0A1,

S10

0A8,

S10

0A9

81In

itial

trig

gerin

g of

com

plem

ent

30.

0113

C1S,

C3,

CFB

82A

ltern

ativ

e com

plem

ent a

ctiv

atio

n2

0.01

2C3

, CFB

Supp

lem

enta

ry T

able

2. C

ontin

ued

(Con

tinue

d to

the n

ext p

age)

Page 5: Shanmuganathan R, et al. Proteomic Signature of ... · Shanmuganathan R, et al. Proteomic Signature of Intervertebral Discs   No. Enriched pathways Total number

Proteomic Signature of Intervertebral DiscsShanmuganathan R, et al.

https://doi.org/10.14245/ns.2040056.028www.e-neurospine.org

No.

Enric

hed

path

way

sTo

tal n

umbe

r of

pro

tein

s in

volv

edp-

valu

eG

ene s

ymbo

ls

83D

ereg

ulat

ed C

DK

5 tr

igge

rs m

ultip

le

neur

odeg

ener

ativ

e pat

hway

s in

Alz

heim

er d

iseas

e mod

els

30.

0123

PRD

X1, P

RDX2

, YW

HA

E

84Ap

opto

sis7

0.01

35CA

SP8,

DSG

1, D

SP, G

SN, H

IST1

H1C

, VIM

, YW

HA

E85

The c

anon

ical

retin

oid

cycle

in ro

ds

(twili

ght v

ision

)3

0.01

35RB

P4, R

DH

8, T

TR

86Si

gnal

ing

by R

AS

mut

ants

40.

0155

ACTG

1, F

GA

, FG

B, F

GG

87A

ctiv

atio

n of

C3

and

C5

20.

0185

C3, C

FB88

HD

L as

sem

bly

20.

0185

A2M

, APO

A1

89Te

rmin

al p

athw

ay o

f com

plem

ent

20.

0222

C9, C

LU90

Sign

alin

g by

BRA

F an

d RA

F fu

sions

40.

0225

ACTG

1, F

GA

, FG

B, F

GG

91Pl

asm

a lip

opro

tein

rem

odel

ing

30.

024

ALB

, APO

A1,

APO

A4

92H

DL

rem

odel

ing

20.

026

ALB

, APO

A1

93A

dher

ens j

unct

ions

inte

ract

ions

30.

0278

ACTG

1, A

NG

, JU

P94

Chy

lom

icro

n as

sem

bly

20.

0304

APO

A1,

APO

A4

95C

hylo

mic

ron

rem

odel

ing

20.

0304

APO

A1,

APO

A4

96Ve

sicle

-med

iate

d tr

ansp

ort

150.

0308

ACTG

1, A

LB, A

NK2

, APO

A1,

CO

L1A

1, C

OL1

A2,

FTL

, HBA

1, H

BB, H

P, H

PX, K

IF1B

, SER

PIN

A1,

TF,

YWH

AE

97Pl

asm

a lip

opro

tein

asse

mbl

y, re

-m

odel

ing,

and

clear

ance

40.

0318

A2M

, ALB

, APO

A1,

APO

A4

98In

terle

ukin

-4 an

d In

terle

ukin

-13

signa

ling

50.

0318

AN

XA1,

CO

L1A

2, F

13A

1, T

IMP1

, VIM

99D

etox

ifica

tion

of re

activ

e oxy

gen

spec

ies

30.

0332

PRD

X1, P

RDX2

, SO

D3

100

Apop

totic

clea

vage

of c

ell a

dhes

ion

prot

eins

20.

0338

DSG

1, D

SP

101

GP1

b-IX

-V ac

tivat

ion

signa

lling

20.

0338

COL1

A1,

CO

L1A

210

2Ty

pe I

hem

ides

mos

ome a

ssem

bly

20.

0338

KRT1

4, K

RT5

103

Reve

rsib

le h

ydra

tion

of ca

rbon

di-

oxid

e2

0.03

82CA

1, C

A2

104

Retin

oid

cycle

dise

ase e

vent

s2

0.03

82RB

P4, T

TR10

5G

alph

a (i)

signa

lling

even

ts10

0.04

99AG

T, A

NXA

1, A

POA

1, A

POA

4, C

3, H

SPG

2, IN

SL5,

RBP

4, R

DH

8, T

TR

ECM

, ext

race

llula

r mat

rix; T

LR, T

oll-l

ike r

ecep

tor;

GA

G, g

lyco

sam

inog

lyca

ns; P

DG

F, pl

atel

et-d

eriv

ed g

row

th fa

ctor

; ED

S, E

hler

s–D

anlo

s syn

drom

e; TP

BS, t

emta

my

prea

xial

bra

chyd

ac-

tyly

synd

rom

e; PT

K2,

pro

tein

tyro

sine k

inas

e 2; M

APK

, mito

gen-

activ

ated

pro

tein

kin

ase;

HD

L, h

igh-

dens

ity li

popr

otei

n.

Supp

lem

enta

ry T

able

2. C

ontin

ued