supplementary figure 1 reported (nonredundant) protein … · 2017-07-26 · supplementary figure 3...

46
Supplementary Figure 1 Reported (nonredundant) protein interactions in PSD scaffold complexes Comparison of Dlg4, Dlgap1 and Shank3 protein interactions isolated by HPLC-MS/MS compared to interactions reported in the BioGRID 15 and Mentha 16 protein-protein interaction databases. Heatmap shows comparison to e14/p7/p14/adult redundant interactions without discrimination between developmental stage Nature Neuroscience: doi:10.1038/nn.4594

Upload: others

Post on 05-Jul-2020

9 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

Supplementary Figure 1

Reported (nonredundant) protein interactions in PSD scaffold complexes

Comparison of Dlg4, Dlgap1 and Shank3 protein interactions isolated by HPLC-MS/MS compared to interactions reported in the BioGRID

15 and Mentha

16 protein-protein interaction databases. Heatmap shows comparison to e14/p7/p14/adult redundant interactions

without discrimination between developmental stage

Nature Neuroscience: doi:10.1038/nn.4594

Page 2: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

Supplementary Figure 2

Assay classification of reported protein–protein interactions.

Figure illustrates the distribution of the methods used to characterize previously reported protein-protein interactions that are also reported in the current study. The methods include those that show direct protein-protein interactions (yeast two-hybrid and co-crystallization) and indirect protein-protein interactions (co-fractionation, affinity capture followed by mass spectrometry, affinity capture followed by western blot, reconstituted complex, co-localization, co-purification, and far-western blotting). Each previously reported interaction listed in supplementary table 2 was annotated as being shown by direct methods, indirect methods, or both where applicable. Detection methods are separated by the corresponding species in which the protein-protein interaction was shown as in A) All species combined, B) Homo sapiens, C) Mus musculus, and D) Rattus Norvegicus.

Nature Neuroscience: doi:10.1038/nn.4594

Page 3: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

Supplementary Figure 3

Reported (nonredundant) protein interactions in PSD scaffold interactors complexes Comparison of scaffold interactomes isolated by HPLC-MS/MS compared to interactions reported in the BioGRID15 and Mentha16 protein-protein interaction databases for interactions at different developmental stages and spatial localization (top, redundant) and interactions without any discrimination between developmental stage or cellular localization (bottom, non-redundant).

Nature Neuroscience: doi:10.1038/nn.4594

Page 4: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

Supplementary Figure 4

Protein content analysis Protein content in Tnik-/- and Shank3ΔC-/+ mice. Quantitation of total protein content for protein interactions determined by MS (Figure 7) in mouse PFC. Representative cropped images of WB from four independent experiments which were analyzed using the unpaired t-test. All data represented as mean ± s.e.m.

Nature Neuroscience: doi:10.1038/nn.4594

Page 5: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

Supplementary Dataset 1 Hierarchical clustering of protein domains in scaffold complexes Jaccard clustering of protein domain architectures in Dlg4, Dlgap1, and Shank3, developmental protein complexes. Supplementary Dataset 2 Hierarchical clustering of protein domains in scaffold-interactors complexes Jaccard clustering of protein domain architectures in scaffold interactomes, developmental/localization protein complexes.

Nature Neuroscience: doi:10.1038/nn.4594

Page 6: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZNF_R

BZZN

F_C2H

2W

WW

H2

WH

1VITVW

ATYR

KCSO

RB

RAS

RAB

PX RH

OG

APPU

RPP2ACM

IROLR

RC

TLR

RN

TLR

R_TYP

LRR

1LR

R4

LRR

LIMVH

PL27KISCPH IQ SEC

7SEC

14IG

C2

RH

OG

EFH

DC

GU

KCPD

ZSH

3TSP1G

PSH

OR

MR

GKAP

GELSO

LINFN

3EN

THEFHDYN

CG

EDFH

2D

RF_FH

3D

RF_G

BDD

NAJ

RASG

EFNR

ASGEF

CN

MP

DEP

CH

SPECC

AP_GLY

C2

RASG

APC

NH

C1

S_TKCBTBBEAC

HW

D40

B41FA FER

MC

ARM

ARFG

APG

ITAR

FAN

KSAMAD

FAC

RD

ISIN14−3−3FA58CFBGEG

F4.1MLAM

G

YWHAZYWHAQYWHAHYWHAGYWHABYWHAEWASF1SNAP91RAPGEF4RAP1ARAB1PURAPPP3CBPPP1CCPPP3CAPDE4BLRRTM1LGI1LRRC15KIF5AKIF5CITIH4IQGAP2SYNE1SPTBN1SPTBN2HOMER1GSNNBEAGNB1GNB2FBXO41LRRC7ERBB2IPMPDZPTK2EPB4.1L1EPB41L3DSTNDNAJC6DLGAP4DLGAP3DLGAP1DLGAP2DIAPH1DDNCYLDFARP1KALRNTRIODNM1SYNGAP1DAB2IPRASAL2CYTH3IQSEC3IQSEC1IQSEC2CNKSR2MPRIPMAPK3MAPK1CDK5CAMK2GCAMK2DCAMK2ACAMK2BMINK1TNIKCITPRKCBPRKCGBTBD11KCNA4KCNA1KCNA2SPNA2SHANK2CASKIN1SHANK1SHANK3DLG4DLG3DLG1DLG2BAIAP2SH3KBP1SORBS1SORBS2BAI2BAI3CTNND2CTNND1ARVCFCTNNB1ARHGAP32ARHGAP39ARF3ARF5DZANK1AGAP2GIT1ABLIM1ADAM22CNTNAP1NRXN1

0

0.2

0.4

0.6

0.8

1

A

Supplementary Dataset 1

Adult Dlgap1

Domain architectures in scaffold protein complexes

Nature Neuroscience: doi:10.1038/nn.4594

Page 7: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

Adult_Shank3: Jaccard

ZNF_C

2H2

WH

2W

H1

WD

40VITVW

AU

BA_E1_CR

HO

GEF

RASG

APPP2ACPLPPLC

XCPLC

YCPEPTIDYLPRO

LINE_ISO

MER

ASEM

YOSIN

LRR

CAP

LRR

1LR

R4

KISCIQ SEC

7ILW

EQIR

SIG

C1

L27G

UKC

PDZ

SH3

GKAP

IG FN3

IGC

2FBGFA58CLAM

GEN

THEFHG

AS2PLECDYN

CG

EDD

EATHZU

5D

CX

CU

LLINCULLIN

−NED

D8

CO

RTBP2D

EPC

NM

PR

ASGEF

RASG

EFNC

NH

PH CH

SPECEG

FLIN

KC

CP

CLEC

TC

AP_GLY

S_TKCC

1C

2B41FA FER

MC

ARFG

APM

IROAR

FPTBAN

KSAM14−3−3AAA

YWHAZYWHAGYWHABYWHAEWASF1UBA1SNAP91PPP1R7PPP1CCPPP3CAPPIAPLCB1NCANSIRPAMACF1SPNA2LRRC7KIF5CITIH1MYO5AIQSEC1IQSEC2HOMER3HOMER1HOMER2HCN1HCN2RAPGEF2RAPGEF4GPM6AGNB1FBXO41EPB41L3TLN2DYNC1H1SYNGAP1DNM1SPTBN2SPNB4SPTBN1DLGAP4DLGAP3DLGAP1DLGAP2CYLDDCTN1CUL3CNTNAP1TNRKALRNCNTN1NFASCPRKCGPRKCEPRKCAPRKCBCITROCK2TNIKDCLK1TAOK2SLKRPS6KA2MAP3K5GSK3BCAMK2GCAMK2ACAMK2DARF3PPP1R9ASHANK2ANKS1BCASKIN1SHANK1SHANK3ABI1BAIAP2MPP2DLG4DLG1DLG2AGAP2CTTNBP2ANK2ANK3

0

0.2

0.4

0.6

0.8

1

Adult Shank3

Nature Neuroscience: doi:10.1038/nn.4594

Page 8: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

e14_Dlg4: Jaccard

S_TKCR

HO

GEF

PILTLR

RC

TLR

R_TYP

LIMVH

PKH PH IQ SEC

7L27SH

3G

UKC

PDZ

GKAP

FN3

IG IGC

2D

CX

CR

IC_R

AS_SIGSAMKISCC

AP_GLY

FHA

WW

C1

HEC

TCBEAC

HW

D40

ARM

ADF

ACR

DISIN

EGF

LAMG

FBG4.1MFA58C

TJAP1NEDD4LKIF13BKIF2AKIF3AFMR1DLGAP5DLGAP3DLGAP4DCXDCAF7NBEADBN1CTNNB1CNTN1LRFN1CNKSR3MPP2DLG4DLG3DLG1DLG2PRKACBCAMK2DMAPK1ARHGEF26IQSEC1ABLIM1ADAM22CNTNAP1

0

0.2

0.4

0.6

0.8

1

e14-Dlg4

Nature Neuroscience: doi:10.1038/nn.4594

Page 9: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

p7_Dlg4: Jaccard

TPRSO

RB

SAMR

ASGAP

RAS

PRO_ISO

MER

ASEPP2ACM

IROLR

R_TYP

LRR

CT

LRR

NT

LIMVH

PKISCKASHIQ SEC

7IPPCG

UKC

PDZ

SH3

GTP_BIN

DIN

GTSP1G

PSH

OR

MR

GKAP

FN3

IG IGC

2D

CX

CN

MP

CN

HPH PLECEFHG

AS2C

HSPECS_TKCC

1C

2BEAC

HW

D40

B41TYR

KCAR

MAR

FGAP

GIT

ARF

ANK

DEATH

ZU5

AMP_BIN

DIN

GAD

FAC

RD

ISINAAAC

DC

48_214−3−3FA58CFBGEG

F4.1MLAM

G

YWHABYWHAESYNJ1RAP2BRAC1PTK2PRKAR2BPPP3CBPPP3CAPPP1CAPPP1CBPPIBNSFMACF1SYNE1SYNE2LGI1KIF2AKIF5ASYNGAP1IQGAP2IQSEC1GNB1NBEADLGAP3DLGAP4PPP1R9BDLG4DLG3DLG1DLG2SHANK1SHANK2DIP2BDCXDBN1DSTNCTNNB1CYFIP2CNTN1NCAM1PRKACBMAPK1CAMK2DCAMK2ACAMK2BCITPRKCGPRKCBPRKCEBAIAP2SORBS1SORBS2BAI3ARF3ARF5AGAP2GIT1ARHGAP32ANK2ANK3ABLIM1ADAM22CNTNAP1NRXN1

0

0.2

0.4

0.6

0.8

1

p7-Dlg4

Nature Neuroscience: doi:10.1038/nn.4594

Page 10: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

p14_Dlg4: Jaccard

UQ

_CO

NU

BA_E1_CTU

BULIN

TUBU

LIN_C

SOR

BR

HO

GEF

RAS

PRO_ISO

MER

ASEPPRPP2ACPG

AMPEPTIDYLPRO

LINE_ISO

MER

ASEM

TCM

IROM

ATHLR

R_TYP

LRR

CT

LRR

NT

LIMVH

PPH IQ SEC

7IPPCG

_ALPHA

GU

KCPD

ZSH

3G

TP_BIND

ING

GKAP

GAF

HD

CIG FN

3IG

C2

ENO

LASE_CEN

OLASE_N

EGF−C

ALY D

EATHZU

5C

UB

LDLA

CN

PASEC

NM

PC

NH

CLH

CLA

CLB

CH

SPECEFHG

AS2PLECS_TKCC

1C

2BTKR

ASGAP

BTB_2BTBBEAC

HW

D40

BAND

_7PH

BB41TYR

KCAR

FGAP

GIT

ARF

PTBAN

KSAMAM

P_BIND

ING

ADF

ACR

DISIN

ACID

PPCAAAC

DC

48_214−3−3FA58CFBGEG

F4.1MLAM

GYWHABYWHAEUBE2V1UBE2V2UBA1TUBB2BTUBB6TRAF3SYNJ1SFXN3RAP2BPTK2PRKAR2BPPP3CBPPP3CAPPP1CAPPP1CBPPIBPPIAPLPP3PHB2PGAM5PDE2ANSFMACF1SYNE1LRPPRCLRP1NETO1LGI1KCNA3IQSEC1IQSEC2RASAL1SYNGAP1GNB1NBEAGNAI1ENO1DSTNDLGAP4DLGAP1DLGAP3PPP1R9BDLG4DLG3DLG1DLG2SHANK2SHANK1SHANK3DIP2BKALRNCNTN1NCAM1CNPCLUCLTCPRKACBMAPK1CDK5CAMK2DCAMK2ACAMK2BPRKCGPRKCBPRKCECITROCK2BTBD11KCNA1SPNB2BAIAP2SORBS2ARF3ARF5AGAP2GIT1ANK3ANKS1ANKS1BADAM22CNTNAP1NRXN1ABLIM1RAC12−SEPEEF1A1

0

0.2

0.4

0.6

0.8

1

p14-Dlg4

Nature Neuroscience: doi:10.1038/nn.4594

Page 11: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

Adult_Dlg4: Jaccard

UQ

_CO

NU

BA_E1_CTU

BULIN

TUBU

LIN_C

SDF

RH

OG

APR

HO

GEF

RAS

RAB

PRO_ISO

MER

ASEPPRPP2ACPLPPG

AMPEPTIDYLPRO

LINE_ISO

MER

ASEM

TCM

ATHLR

R_TYP

LRR

CT

LRR

NT

LIMVH

PIQ SEC

7IPPCG

_ALPHA

GU

KCPD

ZSH

3G

TP_BIND

ING

GKAP

GAF

HD

CIG FN

3IG

C2

ENO

LASE_CEN

OLASE_N

EGF−C

ALY C

UB

LDLA

CN

PASEC

LHC

LAC

LBPLECC

HG

AS2EFHSPECC

D225

S_TKCC

1C

NH

BTKR

ASGAP

C2

PH BTB_2BTBBEAC

HW

D40

BAND

_7PH

BB41FER

MAR

MAR

FPTBAN

KSAMAM

P_BIND

ING

ADF

ACR

DISIN

ACID

PPCAAAC

DC

48_27TM

_2FA58CFBGEG

F4.1MLAM

G14−3−31−C

YSPRX_C

AHPC

−TSA

YWHABYWHAEUBE2V1UBE2V2UBA1TUBB2BTUBB6TRAF3SYNJ1SLC1A2SFXN3RAP2BRAB3CRAB10RAB14PRRT1PRDX1PRDX2PPP3CBPPP3CAPPP2CBPPP1CAPPP1CBPPIBPPIAPLPP3PHB2PGAM5PDE2ANSFMACF1LRPPRCLRP1NETO1LGI1KCNA3GPM6AGNB1NBEAGNAI1FRMPD3ENO1DLGAP4DLGAP1DLGAP3DIP2BKALRNCNTN1NCAM1CNPCLUCLTCCFL1DSTNCAND1PRKACBMAPK1CDK5CAMK2DCAMK2ACAMK2BPRKCBCITROCK2BTBD11KCNA1KCNA2DLG4DLG3DLG1DLG2SHANK2SHANK1SHANK3BAIAP2SPNB2ARF3ANKS1ANKS1BADGRA1ADAM22CNTNAP1NRXN1IQSEC1IQSEC2ABRRASAL1SYNGAP1ABLIM1RAC1EEF1A111−SEP5−SEP

0

0.2

0.4

0.6

0.8

1

Adult Dlg4

Nature Neuroscience: doi:10.1038/nn.4594

Page 12: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

e14_Dlgap1: Jaccard

WD

40U

CH

UBA

WW

EKH SEC

7IQ PH SH

3G

UKC

PDZ

GKAP

CN

HS_TKCAR

MH

ECTC

C1

WW

USP9XMAP4K4TNIKIQSEC1HUWE1NEDD4LFMR1FXR1DLGAP5DLGAP3DLGAP4DLG4DLG3DLG1DLG2CAPRIN1CTNNB1

0

0.2

0.4

0.6

0.8

1

e14-Dlgap1

Nature Neuroscience: doi:10.1038/nn.4594

Page 13: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

p7_Dlgap1: Jaccard

WH

2W

H1

TYRKC

TPRSO

RB

RASG

APR

ASR

ABPU

RPP2ACM

IROLR

R_TYP

LRR

CT

LRR

NT

LRR

1LR

R4

LIMVH

PKISCIQ SEC

7SEC

14IG

C2

RH

OG

EFL27SH

3G

UKC

PDZ

GTP_BIN

DIN

GTSP1G

PSH

OR

MR

GKAP

GELSO

LINEN

THEFHDYN

CG

EDD

CX

CR

IC_R

AS_SIGR

ASGEFN

RASG

EFC

NM

PD

EPC

NH

S_TKCPH C

HSPECLIN

KIG C

CP

CLEC

TC

1C

2BEAC

HW

D40

B41FA FER

MC

ARM

CLASP

ARFG

APG

ITAR

FAN

KSAMAD

FAC

RD

ISIN14−3−3EG

FLAM

GFBG4.1MFA58C

YWHAQYWHAHYWHABYWHAEWASF1SNAP91RAPGEF4RAP1ARAC1RAB1PURAPPP6CPPP1CAPPP3CALGI1KIF5CKIF2AKIF5AIQGAP2SYNE1SPTBN1SPTBN2HOMER1HOMER3GSNGNB1NBEAPTK2EPB4.1L1EPB41L3SYNGAP1DNM1IQSEC1DLGAP3DLGAP4DCXDBN1DSTNLRRC7CNKSR3SHANK2SHANK1SHANK3PRKCBPRKCGMAPK1CAMK2GCAMK2DCAMK2ACAMK2BMAP4K4TNIKTRIOCASKDLG4DLG3DLG1DLG2SPNA2BAIAP2SH3KBP1SORBS1SORBS2BAI3GNB2ARVCFCTNNB1ARF3ARF5ARHGAP32AGAP2GIT1ABLIM1NCDNADAM22CNTNAP1

0

0.2

0.4

0.6

0.8

1

p7-Dlgap1

Nature Neuroscience: doi:10.1038/nn.4594

Page 14: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

p14_Dlgap1: Jaccard

WH

2W

H1

TYRKC

TPRSO

RB

RAS

RAB

PUR

PP2ACM

IROLR

R_TYP

LRR

CT

LRR

NT

LRR

1LR

R4

LIMVH

PKISCPH IQ SEC

7SEC

14IG

C2

RH

OG

EFG

UKC

PDZ

SH3

GTP_BIN

DIN

GTSP1G

PSH

OR

MR

GKAP

GELSO

LINEN

THEFHDYN

CG

EDFH

2D

RF_FH

3D

RF_G

BDD

NAJ

CR

IC_R

AS_SIGR

ASGEFN

RASG

EFC

NM

PD

EPC

HSPECLIN

KIG C

CP

CLEC

TC

AP_GLY

C2

RASG

APC

1C

NH

S_TKCBEAC

HW

D40

B41FA FER

MC

ARM

CLASP

ARFG

APG

ITAR

FAN

KSAMAD

FAC

RD

ISIN14−3−3EG

FLAM

GFBG4.1MFA58C

YWHAQYWHAHYWHABYWHAEWASF1SNAP91RAPGEF4RAP1ARAC1RAB1PURAPPP6CPPP1CAPPP3CALGI1KIF5AKIF5CIQGAP2SYNE1SPTBN1SPTBN2HOMER1HOMER3GSNGNB1NBEAPTK2EPB4.1L1EPB41L3DSTNDNAJC6DLGAP3DLGAP4DIAPH1IQSEC3IQSEC1IQSEC2DNM1SYNGAP1DAB2IPRASAL2CYLDLRRC7CNKSR3SHANK2SHANK1SHANK3MAPK1CAMK2GCAMK2DCAMK2ACAMK2BTNIKMAP4K4MINK1CITPRKCBPRKCGDLG4DLG3DLG1DLG2BAIAP2SH3KBP1SORBS1SORBS2SPNA2TRIOBAI3GNB2CTNND2CTNND1ARVCFCTNNB1ARF3ARF5ARHGAP32AGAP2GIT1ABLIM1NCDNADAM22CNTNAP1

0

0.2

0.4

0.6

0.8

1

p14-Dlgap1

Nature Neuroscience: doi:10.1038/nn.4594

Page 15: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

e14_Shank3: Jaccard

ZNF_U

1W

H2

WH

1TYR

KCTH

IOR

EDO

X_DSBH

SAPSR

ASGAP

SEC14

PX PTNPRO

FPP2ACPIPKCPH R

HO

GEF

LRR

1LR

R4

ZNF_C

2H2

KRAB

SCAN

KISCKH IF FN

2D

UF3166

DU

F1220D

CX

CN

HS_TKCW

WC

2H

ECTC

RIN

GBBCBRO

MO

SABFER

MC

B41FA AN

KSH

3PD

ZSAMAA_PER

MEASE_2

ADF

ZNF318ZFP263WASF1WASF2TRIM28SPATA20SOGA3SLC7A3PPP6R2PPP6CPIP4K2CPFN2PDE4DIPNF1NESMDKLRRC7PPP1R9ASHANK1SHANK2LMTK3KIF7KIF15KIF3BIGF2RHOMER3HOMER1HOMER2HECW1FXR1EPB41L1DBN1MAP4K4TNIKDCLK1CAMK2BGSK3BANKRD28SPATA13SH3PXD2BABI2BAIAP2

0

0.2

0.4

0.6

0.8

1

e14-Shank3

Nature Neuroscience: doi:10.1038/nn.4594

Page 16: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

p7_Shank3: Jaccard

ZNF_U

1W

H2

WH

1TYR

KCSAMR

HO

GEF

RAS

PX PP2ACPLC

XCPLC

YCPIPKCPEPTIDYLPRO

LINE_ISO

MER

ASELR

R1

LRR

4ZN

F_C2H

2KR

ABSC

ANKISCW

D40

IQ SEC7

ILWEQ

IRS

L27G

UKC

PDZ

SH3

GTP_BIN

DIN

GG

KAPIG FN

3IG

C2

DYNC

GED

DC

XC

NH

PBDPH S_TKCC

HSPECPLECEFHG

AS2H

ECTC

WW

C1

C2

B41SABFA FER

MC

ARFG

APM

IROAN

KD

EATHZU

5AD

FAA_PER

MEASE_2

14−3−3AAA

ZNF318ZFP263YWHABYWHAEWASF1SLC7A3RAP1ARAC1PPP1CCPPP3CAPPIAPLCB1PIP4K2CMACF1SPTBN1SPTBN2LRRC7PPP1R9ASHANK1SHANK2LMTK3KIF15KIF7KALRNNFASCNRCAMHOMER3HOMER1HOMER2NEDD4LHECW1NEDD4GNB1KIF21AEPB41L1TLN2DYNC1H1DNM1IQSEC1DLGAP3DLGAP4DBN1MAP4K4TNIKCDC42BPBCITPRKCEPRKCGDCLK1TAOK2MAPK1MAP3K5MAP2K4GSK3BCSNK2A1CAMK2GCAMK2ACAMK2BMPP2DLG4DLG1DLG2SH3PXD2BABI1BAIAP2AGAP2ANK2ANK3

0

0.2

0.4

0.6

0.8

1

p7-Shank3

Nature Neuroscience: doi:10.1038/nn.4594

Page 17: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

p14_Shank3: Jaccard

WH

2W

H1

SH2

TYRKC

RH

OG

EFR

ASGAP

RAS

RA

PP2ACPLC

XCPLC

YCPEPTIDYLPRO

LINE_ISO

MER

ASEM

YOSIN

LRR

1LR

R4

KISCW

D40

IQ SEC7

ILWEQ

IRS

IGC

1L27SH

3G

UKC

PDZ

GTP_BIN

DIN

GG

KAPIG FN

3IG

C2

ENTH

EFHG

AS2PLECDYN

CG

EDD

EATHZU

5D

CX

CO

RTBP2D

EPC

NM

PR

ASGEF

RASG

EFNC

NH

PH CH

SPECS_TKCC

1C

2SABB41FA FER

MC

ARFG

APM

IROAR

FPTBAN

KSAMAAA14−3−3FBGLAM

GFA58C4.1MEG

F

YWHABYWHAEWASF1SNAP91SIRPARAP1APPP3CBPPP1CCPPP3CAPPIAPLCB1PRKCAPRKCGPRKCBPRKCEMACF1SPTBN2SPNB4SPTBN1LRRC7KIF5CMYO5AIQSEC1IQSEC2HOMER3HOMER1HOMER2HCN1HCN2RAPGEF2RAPGEF4GNB1KIF21ATLN2EPB41L1EPB41L3DYNC1H1DNM1SYNGAP1DLGAP4DLGAP1DLGAP3CNTNAP1TNRKALRNNRCAMCNTN1NFASCCITROCK2TNIKDCLK1TAOK2SLKRPS6KA2MAPK3MAPK1MAP3K5MAP2K4GSK3BCSNK2A1CAMK2GCAMK2DCAMK2ACAMK2BARF3PPP1R9ASHANK2ANKS1BCASKIN1SHANK1AGAP2CTTNBP2ANK2ANK3RAC13−SEP7−SEPMPP2DLG4DLG1DLG2SRCSPNA2ABI1BAIAP2

0

0.2

0.4

0.6

0.8

1

p14-Shank3

Nature Neuroscience: doi:10.1038/nn.4594

Page 18: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZNF_U

1ZN

F_RBZ

ZNF_G

ATAZN

F_C3H

1W

WW

H1

USP

TUD

OR

UBA

TRASH

TPRSEC

7SEC

14SAMPPIPP2ACPH

RR

CC

1PBDN

TF2R

RM

NO

SICN

EUZ

MYB_D

NA−BIN

DLTDLISHW

D40

LEU_ZIP

KISCKH IQ M

YOSIN

IF HPC

2H

OX

ZNF_C

2H2

HLH

TBOX

HEAT

GU

KCL27PD

ZSH

3G

NAT

GELSO

LINIG

C2

FN3

PTPCFH

AFH FC

HR

HO

GAP

FBOX

ELMSAN

TSEALAM

GKAZALFO

LNEG

FEG

F_LAMEFGD

UF3402

N1221

DU

F3166D

UF1220

DH

RD

EACETYLASE

DC

XD

BC1

S1_LIKEH

ECTC

ZNFZZ

CYT−B5

TECPR

CTLH

SPRYC

PSASEM

GS

CN

MP

RASG

EFND

EPR

ASGEF

CN

HS_TKCSPECC

HKASHC

ADH

ERIN

PH C1

RH

OG

EFBTBD

EXDC

HELIC

CBR

KC

HRO

MO

BRC

TR

ING

BROM

OBBCBBO

XBARAR

FGAP

GIT

ARM

SAMP

APCEB1PR

E−SETAN

KSETAM

INO

_OXIDASE

SWIR

MAAAAC

TIN

ZMYM2ZC3H4USP10UBN2TP53BP1TDRD3SYNE2STRIP1SOGA3SRGAP3SH3GL2SH3KBP1SEC23ASEC24CPTPRSRAPGEF4PRKAR2APRKAR2BPPP3CBPDE4DIPNOP56NEURL4NESNAT10MYCBP2TRIM28MSANTD2MGALMNB1LMNB2KIF7KIF5CKIF2AKIF5AKDM1AKCTD9IQSEC1MYO5AHOMER3HERC2NEDD4HDAC2GATAD2BFXR2FMR1FXR1FKBP15FBXO45RANBP9EWSR1G3BP1GIT1EHMT1EHMT2EFTUD2STRN4STRN3EDC4HIRATAF5TBL1XR1DYNC1H1DOCK11DOCK7DCXCHD8DDX3XCEP170CENPFPCDH8CDH2DCHS1SMARCC2CDC5LNCOR2RCOR1RCOR2CCAR2PAK7TLK2CAMK2DGSK3BMAP4K4TNIKCADCABIN1TANC2ARHGEF2TRIOARHGAP21SHANK2CASKDLG1APCCTNNB1PPP2R1AAGRNACTR1AMATR3FOXP2ADNPZEB2ZIC2ZFP462ZFP219BCL11BWIZ

0

0.2

0.4

0.6

0.8

1

Protein domain architectures in scaffold interactors

e14-Tnik

Supplementary Dataset 2

Nature Neuroscience: doi:10.1038/nn.4594

Page 19: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZNF_FYVE

WH

2W

D40

UC

HSC

ANZN

F_C2H

2SAN

TSAMR

HO

GAP

WW

PUR

PPIPP2ACPH R

HO

GEF

PBDM

IROLR

R1

LRR

4KISCIQ SEC

7IM

DIG

_FLMN

WW

EH

ECTC

UBA

SH3

PDZ

GU

KCL27G

ELSOLIN

FN3

IGC

2PTPCFH

AFBGFAD

_BIND

ING

EFHDYN

CG

EDD

UF3166

DU

F1220D

CX

DAGKA

DAGKC

SPRYC

TLHLISHC

ORTBP2

CN

PASEC

NM

PR

ASGEFN

DEP

RASG

EFC

NH

CH

SPECC

ARP

CAD

HER

INS_TKCC

1C

2BR

CT

BROM

OBBCBBO

XR

ING

BARAR

MH

EATAR

FGAP

GIT

ANK

TPRAD

FAAAC

DC

48_2

ZSCAN18WASF1USP9XTRIM46TRIM28TRIM3TP53BP1STRN4STRNSTRN3SOGA3RANBP9PURATNRPTPRDPTPRSPPP2CBPDE4DIPNSFMTSS1LKIF2AKIF2CHUWE1RAPGEF4HCN1PRKAR2BGELSOLINFKBP15DSTNPPP2R1ACTNND2CTNNB1CTNND1CNPRIMS1LRRC7CNKSR2NOS1CEP170CEP170BPCDH8CDH10CDH2CDC5LCAP2PRKCBPRKCGTNIKPAK7DCLK1TAOK2PRKACBPRKACAMAPK1CAMKVCAMK2GCAMK2DCAMK2ACAMK2BARHGEF2BCRSPTBN1SPTBN2DNM1IQSEC1ARHGAP39PEX5LARHGAP32TANC2DLG3CASKDLG1SPTAN1RIMBP2BIN1SH3KBP1ABI1ABI2DGKICTTNBP2AGAP2GIT1

0

0.2

0.4

0.6

0.8

1

non-PSD-Tnik

Nature Neuroscience: doi:10.1038/nn.4594

Page 20: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZNF_R

BZZN

F_FYVEW

H1

VWA

TPRSO

RB

SAMR

ASGAP

RAPG

APPP2ACPLPR

ING

PHR

RC

C1

LRR

1LR

R4

LIMVH

PKH PH IQ SEC

7H

ECTC

WW

L27PD

ZG

UKC

SH3

GKAP

RH

OG

EFFN

3IG

C2

ENTH

DAGKA

DAGKC

CN

MP

RASG

EFND

EPR

ASGEF

CN

HS_TKCC

LAC

LBC

HSPECPLECEFHG

AS2C

1C

2BEAC

HW

D40

B2_ADAPT_APP_CAR

MH

EATALPH

A_ADAPTINC

2AN

KD

EATHZU

5

SNAP91SYNGAP1UNC13APRKCBPRKCGRAPGEF4PRKAR1BPRKAR2BPPP1CAPPP1CCNEDD4NEDD4LNBEAMYCBP2KALRNNGEFHOMER1GPM6AFMR1DSTMACF1SPTBN1SYNE1DLGAP1CLUCLASP1CTNNB1MAGI2CASKMPP5TJP1DLG4DLG1DLG2CNKSR2SHANK2SHANK1SHANK3RIMS1LRRC7SIPA1L1CITTNIKCAMK2ACAMK2BCACNA2D1CACNA1EIQSEC2IQSEC3SORBS2BAIAP2CACNB1CACNB4AP2B1AP2A1AP2A2ABLIM1DGKIANK2ANK3DZANK1TANC2

0

0.2

0.4

0.6

0.8

1

Adult PSD-Tnik

Nature Neuroscience: doi:10.1038/nn.4594

Page 21: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZF_UBR

VASPW

H1

UBA_E1_C

UBA

TCP10

SPRYSH

3SO

RB

SEC14

RR

MZN

F_RBZ

RH

OG

APR

ABAPATINPTNPP2ACPH

DPH

BPH R

HO

GEF

PGAM

LTDLR

R_TYP

PDZ

KU78

SAPKH KBPKASHH

OX

ZNF_C

2H2

HO

OK

HEAT

FYVEG

OLD

FN3

SEALAM

GKAZALFO

LNEG

FEG

F_LAMEFGD

UF3166

DU

F1220D

DH

DSAMW

D40

CTLH

LISHC

PSASEM

GS

CN

MP

CN

HS_TKCC

KKEFHC

HSPECG

AS2PLECKISCC

AP_GLY

FHA

C2

RASG

APC

1PB1BR

CT

RIN

GBRO

MO

BBCBBO

XBTBBAC

KKELC

HB41FER

MC

ARM

DN

AJAN

KAM

P_DEAM

INASE

AAAAM

P_BIND

ING

XRCC6UBR4UBAP2LUBA1TP53BP1STOML2SORBS2SOGA3SEC23IPRANBP9WDR26WDR47RAI1RACGAP1RABEP1RABEP2PRKAR2APRKAR2BPPP6CPGAM5PDE4DIPPARD3SCRIBMDKMAP4K4TNIKPRKCIROCK1MACF1SYNE2LMNB1LMNB2LETM1KLHL7KBPFYCO1FXR2RDXEZRMSNENAHHOMER3EFTUD2DZIP3TRIM28DYNC1H1NAV1DIP2BDAB2IPNF1ZEB1ZBTB22CLIP1ZNF516CEP170KIF13BCENPJKIF21BKIF7KIF4AKIF2AKIF23CENPEKIF15CCDC88ACCDC88CCAMSAP1CAMSAP3CADATF7IPDNAJC13CLASP1ARMCX4CTNNB1ARHGEF12PHLDB2TRIOBPANKRD28TP53BP2AMPD2AGRNALYREFEWSR1

0

0.2

0.4

0.6

0.8

1

e14-Pde4dip

Nature Neuroscience: doi:10.1038/nn.4594

Page 22: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZF_UBR

WH

2VPS9ZN

F_A20VASPW

H1

UBA

SOR

BR

RM

RASG

APR

ABAPATINPX PU

RPTPCPH

BM

IROLTDKR

ABSC

ANKH IQ SEC

7IG

_FLMN

IGC

2SEC

14PH R

HO

GEF

GR

IPFYVEG

OLD

FBGFN

3EFHZN

F_C2H

2D

ZFZN

F_U1

DU

F3166D

UF1220

DN

AJR

GS

DEP

GG

LD

DH

DC

RIC

_RAS_SIG

PDZ

CR

ASPRYC

TLHLISHC

NPASE

CN

HS_TKCC

LASPC

LAC

LBC

HSPECFH

AC

AP_GLY

KISCC

ADH

ERIN

C1

C2

BEACH

WD

40BRO

MO

RIN

GBBCBBO

XBARR

HO

GAP

B41FER

MC

ARM

HEAT

ARFG

APG

ITSH

3AN

KSAMAM

P_DEAM

INASE

AMP_BIN

DIN

GAC

TINAAAC

DC

48_2

WASF1TRIM28TRIM3TNRSTOML2SORBS2UBASH3BSOGA3RGS6WDR26RANBP10RANBP9RABGEF1RABEP1RABEP2PURAPURBPTPRN2PDE4DIPNSFNF1UBR4NBEASTRNLMNB1LMNB2LETM1SPNA2KSR2KIF2AGOLGA1FYCO1FXR2RDXEZRMSNZKSCAN14TAX1BP1ERC2MATR3ENAHHOMER1ELAVL4ELAVL3ELAVL1ELAVL2DIP2BCNPCLUCLIP1CLIP2KIF13BCEP170CEP170BCDH2CDH10CDH11CASKIN1SHANK1CNKSR3PPFIA3SEC23IPSRPK2PRKACBMAPK1CAMK2ACAMK2BMINK1TNIKCITPRKCBPRKCGDNAJC13CLASP2PRKAR2APKP4ARMC8CTNNB1CLASP1PPP2R1AKALRNARHGEF12BCRSPTBN1IQSEC1DAB2IPOSBPL3ARHGAP32ARHGAP44SH3BP1AMPD2ACTBANKRD28AGAP2GIT1

0

0.2

0.4

0.6

0.8

1

Adult non-PSD-Pde4dip

Nature Neuroscience: doi:10.1038/nn.4594

Page 23: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZNF_U

1ZF_U

BRW

WW

H1

USP

UIM

UC

HTYR

KCTU

DO

RU

BATO

PRIM

TOP1AC

TOP1BC

SCAN

RR

MSAPR

ANG

APR

ANBD

ZNF_R

BZPX PR

MT

PP2ACPIN

CR

ING

PHR

RC

C1

PH RH

OG

APPBDPAZPIW

IM

RG

MBD

LRR

_TYPKISCKH IBN

_NPACH

LHPASH

EATH

DAC_IN

TERAC

TPAHG

YFPD

ZG

UKC

SH3

ZU5

GR

IPFH

AM

IF4GEIF5CM

A3LY LD

LAEG

FEG

F−CA

DH

RD

EACETYLASE

DBC

1S1_LIKEDAXD

EPH

ECTC

ZNFZZ

CYT−B5

TECPR

CU

ESM

RLISHC

TLHSPRYC

NH

S_TKCC

HSH

CH

ROM

OSAN

TC

HSPECPLECEFHG

AS2BTZBTBZN

F_C2H

2H

SAQ

LQBR

KD

EXDC

HELIC

CPH

DJM

JNBR

IGH

TJM

JCBR

CT

BETA−CASP

LACTAM

ASE_BBEAC

HW

D40

BROM

OBBCBBO

XBAHH

MG

ARM

SAMP

APCEB1AN

KSETAM

INO

_OXIDASE

SWIR

MAAAAC

TIN

USP9XUSP28USP10TP53BP1TOP3BTDRD3UBAP2UBAP2LSMG6SIN3BRANGAP1RANBP9RANBP2PRMT1PPP1CANISCHNCOA2NCOA3N4BP2MYCBP2TRIM28MORF4L1MBD3LRP1LMTK3KPNB1KIF2AKIF5CKDM5ATCF20KDM1AHOMER3HERC2NEDD4HDAC2HDAC3GOLGA4GIGYF2PCBP1FXR2FMR1FXR1ZNFX1EWSR1TRA2BG3BP2NCLEIF4GEHMT2UBR4TBL1XTBL1XR1NBEAEDC4KIF21BDYNC1H1DOCK7DNMT1PBRM1MACF1DIXDC1LRCH2PAK7MAP4K4SRPK2GSK3BDAPK3CSNK2A1CSNK2A2CPSF2SMARCA4DDX3XCHD4CHD7CEP170SMARCC2NCOR2CDC5LNCOR1CCAR2CBX3CASC3MAGI1TJP1DVL2ARHGAP21PARD3SCRIBAPCCLASP1APC2CTNNB1MATR3ZSCAN12ZBTB1CBLL1ZFP219BCL11BAKAP8BCL11AACTR1AAGO1AGO2

0

0.2

0.4

0.6

0.8

1

e14-Fmr1

Nature Neuroscience: doi:10.1038/nn.4594

Page 24: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZN_H

OO

KZN

F_U1

ZNF_R

BZU

SPU

CH

TUD

OR

UBA

TOPR

IMTO

P1ACTO

P1BCSTI1TPRSAN

TR

RM

SAPR

HO

GEF

PUR

PTPCPTBSH

2PH R

HO

GAP

PAZPIW

ILIMZN

F_C2H

2KR

ABSC

ANKISCKH IQ SEC

7IG

_FLMN

IG IGC

2H

LHPASH

ECTC

WW

HEAT

GYF

ZU5

GU

KCSH

3G

RIP

GAF

HD

CFH

AFBGFN

3FA58CLAM

GM

IF4GEIF5CM

A3EG

FLY EG

F−CA

LDLA

EFHDYN

CG

EDD

UF3166

DEAC

ETYLASEFH

2D

RF_G

BDDADD

RF_FH

3SPRYC

TLHLISHPD

ZR

ASGEFN

RASG

EFC

NM

PR

AC

KKC

HSPECC

ARD

S_TKCC

1C

2PH

DJM

JNBR

IGH

TJM

JCW

D40

BEACH

FYVEBRO

MO

RIN

GBBCBBO

XBARAR

MSAM

PAPCEB1AN

KSAMAM

P_BIND

ING

AAAC

DC

48_2

USP9XUSP10TRIM28TRIM3TOP3BTNRSOGA3TDRD3SIK3UBAP2UBAP2LRANBP9RAD50PURAPURBPTPRN2PDE2ANUMBLTNS1NCOR1NCOR2NCOA3MCCRAPGEF2SOGA2MATR3ZC2HC1ALMO3WTIPKLC1STIP1KIF5CKIF2AKIF5AKDM5AITCHHDAC3GOLGA4GIGYF2WDFY3EML1MIOSTBL1XWDR47ZNFX1ELAVL4ELAVL3ELAVL1ELAVL2EIF4G1EHD3DZANK1DYNC1H1NSFDIP2BDIAPH2CNTNAP5ALRP1CNTN1ICAM5CEP170CEP170BCAMSAP2RIPK2SRPK2MAPK1DAPK3CAMK2GCAMK2DCAMK2BBRSK1CAMK2APRKD1PRKCBPRKCGTJP1CACNB4CACNB1CACNB2BIN1CASKIN1SPTBN1IQSEC1DNM1ARHGAP21ARHGAP24ARHGEF2LPPR4APCPPP2R1ACTNNB1PKP4AGO1AGO2ANKRD17KHSRPFXR2FMR1FXR1

0

0.2

0.4

0.6

0.8

1

Adult non-PSD Fmr1

Nature Neuroscience: doi:10.1038/nn.4594

Page 25: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

TYRKC

TPRSAN

TR

RM

SAPR

HO

GAP

RASG

APKH PH IQ SEC

7IG IG

C2

HEC

TCG

YFZU

5G

UKC

PDZ

SH3

GR

IPG

KAPG

AFH

DC

LAMG

EGF

FA58CC

NH

CH

SPECS_TKCC

1C

2AR

FGAP

GIT

ARF

AAAC

DC

48_2AN

KSAM

PDE2ANSFNCOR1KLC1ICAM5HERC4GOLGA4GIT1GIGYF2KHSRPFMR1FXR2DLGAP3CNTNAP5APRKCBPRKCGTNIKCAMK2ANEK9TNK2SHANK1SHANK3CACNB1TJP1DLG4DLG1DLG2SYNGAP1SPTBN1ARHGAP21IQSEC1IQSEC2ARF3ALYREFZNFX1

0

0.2

0.4

0.6

0.8

1

Adult PSD-Fmr1

Nature Neuroscience: doi:10.1038/nn.4594

Page 26: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZNF_U

1ZF_U

BRU

SPU

BAW

WE

TCP1

TBCSKP1SH

3SO

RB

SCAN

ZNF_C

2H2

SAMR

RM

ZNF_R

BZR

HO

GAP

RG

SPP2ACPH

RR

CC

1PD

ZR

APGAP

NTF2

LTDLR

R_TYP

LIMVH

PKISCW

D40

KH KASHW

WIQ R

ASGAP

IPTIF H

DC

H4

H2A

GU

KCZU

5G

ELSOLIN

FBOX

SPRYEFG

_CEFG

_IVD

SPCD

HR

DEXD

CH

ELICC

DEAC

ETYLASED

CX

SAPD

BC1

S1_LIKEH

ECTC

ZNFZZ

CYT−B5

TECPR

CPSASE

MG

SC

NH

CLASP

CH

ROM

OSAN

TC

HG

AS2PLECEFHSPECC

AP_GLY

S_TKCC

2H

R1

PH C1

RH

OG

EFBR

CT

WG

RR

ING

BROM

OBBCBBO

XAR

MH

EATSAM

PAPCEB1AN

KD

EATHAD

F14−3−3AAAVW

A

ZNF618ZSCAN18YWHAZUSP10TBC1D5SSH1SSH2SORBS1SORBS2SMARCC1SMARCC2SKP1TJP1SIPA1SIPA1L3SCRIBPPP1R9APPP1R9BPPP1CAPPP1CBPDE1BPARP1NFATC3NESMYCBP2TRIM28LMNB1HIST1H4AHIST1H2AHHERC2HUWE1HDAC2SVILGSNSEC23AFMR1FXR1FBXO45MATR3G3BP1MYEF2ELAVL1G3BP2TAF15EWSR1FUSEEF2DYNC1H1MDN1DSTMACF1SPTBN1SYNE2IQGAP1LRCH2LIMCH1SPECC1LTAGLN3DOCK7DDX3XEIF4A1DCXDCTN1DBN1TWF1PKN1MAP4K4CSNK1A1DCLK1UBR4KIF21BWDR18WDR1SEC31ACORO1BCORO1CCCT3CCT4CCAR1SPTAN1CALM1EFHD2CADARHGAP21ARHGEF11ARHGEF2MPRIPAPCCLASP2KPNA1CLASP1PPP2R1ALIMA1ABLIM1ABLIM3UACAANK2DAPK1

0

0.2

0.4

0.6

0.8

1

e14-Mycbp2

Nature Neuroscience: doi:10.1038/nn.4594

Page 27: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WD

40U

CH

TUD

OR

UBA

TPRTC

P1TBCSPECSM

C_H

ING

ER

RM

ZNF_C

2H2

ZNF_U

1PX R

HO

GAP

SH3

PP2ACPBDS_TKCLR

R_TYP

PDZ

KISCKH IG

C2

PTPCH

ECTC

WW

HATPASE_C

GO

LDFN

2FH FBGFN

3EPH

_LBDTYR

KCEFG

_CEFG

_IVD

UF3166

DN

AJD

HR

DEXD

CH

ELICC

DC

XC

PSASEM

GS

LINK

IG CC

PC

LECT

EGF

TNFR

LAMG

HO

RM

RC

ADH

ERIN

GPS

BRC

TR

ING

BROM

OBBCBBO

XAR

MH

EATAN

KSAMAM

P_DEAM

INASE

14−3−3AM

INO

_OXIDASE

SWIR

M

YWHAQYWHAZUSP9XTRIM28TTC3TP53BP1TMED10TMED9TDRD3TBC1D7SOGA3SMC2SESTD1SCRIBRPTORPTPRSTNRPPP2CBNEDD4MATR3SFPQKIF5CKDM1AIGF2RHSP90AA1HSP90AB1FOXG1FXR2FMR1FXR1EPHA4TNKSEIF4A2EEF2PAK7WNK3DYRK1AWNK2DOCK7DNAJA1DNAJA2DCXCLASP1CTNNB1CELSR2NCANTENM2CCT3CCT8CADAMPD2ARHGAP32NISCH

0

0.2

0.4

0.6

0.8

1

e14-Tsc1

Nature Neuroscience: doi:10.1038/nn.4594

Page 28: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

RIN

GTPRKU

78SAPIF W

WE

HEC

TCU

BAEFG

_CEFG

_IVC

NH

S_TKCAN

KBR

CT

XRCC6TTC3TP53BP1TNIKNESKANK2EEF2HUWE1

0

0.2

0.4

0.6

0.8

1

e14-Huwe1

Nature Neuroscience: doi:10.1038/nn.4594

Page 29: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

UBQ

TPRSAPSPRYPU

RPKDPH R

HO

GEF

KU78

VWA

KISCIG IG

C2

WW

EH

ECTC

UBA

HD

CFBGFN

3FAD

_BIND

ING

PDZ

DU

F3166C

NPASE

CN

HC

HSPECC

ATION

_ATPASE_NS_TKCC

1C

2BR

CT

BEACH

WD

40R

ING

IG_FLM

NBBCBBO

XBARSH

3FER

MC

B41FA AAAC

DC

48_2AN

KAR

FGAP

GIT

XRCC5XRCC6TRIM3TP53BP1SOGA3RPS27APURAPDE4AOGTNSFNPTNNOS1WDR81KIF21AWDR91KIAA0319TNRHUWE1HNRNPUL2GIT1KANK2EPB41L3CNPPRKCGCAMK2ATNIKBIN1ATP2B4SPTBN1APPL1ARHGEF12ARHGEF18

0

0.2

0.4

0.6

0.8

1

Adult non-PSD Huwe1

Nature Neuroscience: doi:10.1038/nn.4594

Page 30: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WD

40ZF_U

BRSO

RB

RR

MZN

F_U1

PP2ACPH PD

ZR

APGAP

NEU

ZKISCKH KASHIQ M

YSCG

ELSOLIN

FHA

SH3

FCH

RH

OG

APD

HR

DEXD

CH

ELICC

DEAC

ETYLASED

DH

DSAMH

ECTC

ZNFZZ

CYT−B5

TECPR

CN

HS_TKCC

HSPECPLECEFHG

AS2BR

CT

FN3

BBCBBO

XPH

DSETR

ING

PWW

PAW

SPO

STSETZN

F_C2H

2AT_H

OO

KBTBZU

5AN

KD

EATHAD

F14−3−3AAAM

CM

YWHAZTP53BP1TNIKSORBS1SRGAP2SIPA1PPP1CAPPFIA1SEC23IPNSD1RAI1NEURL4MYH10MCM3TRIM67PATZ1MATR3TRERF1KIF5CKIF11KIF15HDAC2HERC2GM15800UBE3AFXR1FLIISEC23ADSTMACF1SPTBN1SYNE2DOCK7DDX3XDBN1CORO1CUBR4ANK2CEP170

0

0.2

0.4

0.6

0.8

1

e14-Herc2

Nature Neuroscience: doi:10.1038/nn.4594

Page 31: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WH

2U

BA_E1_CTC

P1SEC

7R

RM

RPEL

RH

OG

EFR

HO

RASG

APR

ASPTBPP2ACPLPPI3KAPI3KCM

HD

LRR

_TYPKO

WKISCKH IQ M

YOSIN

IGC

2TYR

KCLR

RC

TLR

RN

TIBN

_NH

DC

GU

KCPD

ZSH

3EN

THD

ZFZN

F_C2H

2ZN

F_U1

PH DYNC

GED

DN

AJD

EATHZU

5U

DEN

NG

RAM

DD

ENN

DEN

ND

CX

CU

LLINCULLIN

−NED

D8

SEC14

CR

AL_TRIO

_NPTPCR

ASGEFN

RASG

EFC

NM

PR

AC

HSPECEFHG

AS2PLECLIN

KIG C

CP

CLEC

TC

BSC

AP_GLY

S_TKCC

1C

2BRO

1R

ING

IG_FLM

NBBCBBO

XB41FA FER

MC

ARFG

APM

IROAR

FAN

KSAMALPH

A_ADAPTINC

2B2_ADAPT_APP_CAD

FAC

TINEG

FLAM

GFBG4.1MFA58CAAACDC48_2

WASF1UBA6TRIM3SGIP1RPL27RHEBRAPGEF2RAC1RHOCPTPN9PPP1CCSNAP91PICALMSNAP1PI4KAPHACTR1PDE4APDCD6IPNUMBLMACF1SPTBN1SPTBN2LRRC24NTRK2KIF2AIQSEC1MYO5AIPO4IMPDH2GPM6AETF1ERC2MATR3EPB4.1L1EPB41L3DYNC1H1NSFGLULOPA1DNM1LDNM3DNM1DNM2DNAJC6DCTN1DBN1DSTNCUL3CNTNAP1NCANCCT3SBF1SYNGAP1ARHGEF2FARP1FERMT3ARF3AP2B1AP1B1AP2A1AGAP2ANK2ANKRD17TRPC4ACTBPRKCGPRKCBPRKCEDCLK1RPS6KB1PAK1GSK3BCAMKVAAK1CAMK2ADLG2DLG4SHANK1SHANK3SPNA2ABI1BAIAP2

0

0.2

0.4

0.6

0.8

1

Adult PSD-Cyfip1

Nature Neuroscience: doi:10.1038/nn.4594

Page 32: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WH

1W

D40

RASG

APR

ABPU

RPR

A1PLPPLC

XCPLC

YCLR

R1

LRR

4LIMIQ SEC

7IPPCH

YDRO

LASEH

ECTC

GU

KCPD

ZSH

3TSP1G

PSH

OR

MR

GKAP

RH

OG

EFFN

3IG

C2

FERM

FBOX

DEATH

ZU5

DAGKA

DAGKC

CU

LLINCULLIN

−NED

D8

PH CH

SPECS_TKCC

1C

2BTBEG

FLAM

GFBGB41FA58CAR

FGAP

MIRO

ARF

PTBAN

KSAMAAAEG

F_LIKEAC

RD

ISIN

UBR5SYNJ1SPTBN1SPTBN2RAB3CRAB3ARAB10RAB2APURAPRAF2PLCL1SYNGAP1LRRC7MYO5AIQSEC1IQSEC2HOMER1GPM6AFBXO2EPB41L2DYNC1H1DPYSL2GDADMXL2DLGAP4DLGAP1DLGAP3CUL3CNTNAP1KALRNCAMK2ACAMK2BPRKCEPRKCGBTBD9SHANK2SHANK1SHANK3BAIAP2CACNB2DLG4DLG3DLG1DLG2BAI2ARF3ARF5DGKZAGAP2ANK2ANKS1BABLIM1ADAM22ADAM9

0

0.2

0.4

0.6

0.8

1

Adult PSD-Syngap1

Nature Neuroscience: doi:10.1038/nn.4594

Page 33: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

SAMR

HO

GEF

RH

OG

APW

WR

ASPG

KIQ PH SEC

7LR

R_TYP

LRR

CT

IG IGC

2G

UKC

PDZ

FBGFN

3EFHSH

3C

NH

S_TKCC

HSPECAN

KG

ITC

1C

2

TNRRHEBPGK1LRIG2GIT1DLG3SPNA2PRKCGPRKACBCSNK2A1CAMK2ACAMK2BMINK1TNIKARHGAP39ARHGEF7SPTBN1SPTBN2CNKSR2IQSEC1CYTH3CYTH1CYTH2

0

0.2

0.4

0.6

0.8

1

Adult non-PSD Cnksr2

Nature Neuroscience: doi:10.1038/nn.4594

Page 34: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

SAMIQ PH SEC

7ZU

5SH

3G

UKC

PDZ

GKAP

ENTH

EFHSPECC

NH

S_TKCC

1C

214−3−3AN

KAR

FGAP

MIRO

YWHAZSNAP91DLGAP1CNKSR2SHANK3PRKCGCAMK2ACAMK2BMINK1TNIKAGAP2IQSEC1CYTH1CYTH3TJP1DLG4DLG1DLG2BAIAP2SPNA2

0

0.2

0.4

0.6

0.8

1

Adult-PSD Cnksr2

Nature Neuroscience: doi:10.1038/nn.4594

Page 35: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

SAMIQ M

YOSIN

SH3

GU

KCPD

ZG

ELSOLIN

FYVEG

OLD

FCH

RH

OG

APEFHDYN

CG

EDC

NH

S_TKCSPECC

HPH C

ADH

ERIN

ARM

ANK

CO

RTBP2ALPH

A_ADAPTINC

2LAM

GFBGFA58C4.1MEG

F

NCKAP1MYO5AFYCO1DNM1SPTBN1SPTBN2CTTNBP2CTNNB1CNTNAP1CDH10CDH2TNIKCAMK2AMAP3K5AP2A1SHANK1DLG4SHANK3SRGAP3SPTAN1ABI1ABI2

0

0.2

0.4

0.6

0.8

1

Adult-PSD Cyfip2

Nature Neuroscience: doi:10.1038/nn.4594

Page 36: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

UIM

UC

HTYR

KCTU

DO

RU

BATO

PRIM

TOP1AC

TOP1BC

RR

MR

ING

TPRR

ANG

APR

ANBD

ZNF_R

BZPTNPH

RR

CC

1N

OSIC

MH

DSH

DLR

R_TYP

PDZ

LEU_ZIP

KISCKH IBN

_NH

OO

KH

LHIPTH

ECTC

WW

GO

LDG

NAT

GELSO

LINFH

AR

AELMD

UF1220

DSR

MD

ZFD

NAJ

DH

RU

DEN

NG

RAM

DD

ENN

DEN

NSAPD

BC1

S1_LIKEC

UE

SMR

WD

40C

TLHLISHC

PSASEM

GS

CN

HS_TKCC

HRO

MO

SANT

CH

SH3

PH RH

OG

EFC

AP_GLY

ZNF_C

2H2

CAD

HER

INC

2EFHEH C

1BTBFYVEQ

LQH

SAH

ELICC

BRK

DEXD

CBR

CT

BBCBRO

MO

B41FER

MC

B3−4B5 B2_ADAPT_APP_CAR

MALPH

A_ADAPTINC

2AR

FGAP

ANK

GIT

USP9XTRIM28TTC3TP53BP1TOP3BTDRD3UBAP2UBAP2LSTON2SMARCA4SEC24CSCRIBRDXRANGAP1RANBP2PDE4DIPNOP56NEDD4NAT10N4BP2MYCBP2MDKLMTK3KPNB1KIF2AKIF7ILF2ILF3GIT1GIT2FXR2FMR1FXR1FARSBEPS15EPS15L1WDR47KIF21AEDC4STRNEBF3DOCK7DNAJA1DNAJC9CTNNB1MLLT4CEP170CEP170BCENPFCDH2SMARCC2RCOR2NCOR2CDC5LNCOR1CCDC88ACCAR1CCAR2CADBAIAP2MIA3SBF1ARHGEF2ITSN1ARHGEF7SPATA13AP2B1AP2A1AP2A2ANKFY1FYCO1SRSF1ALYREFMYEF2MAP4K4TBK1SRPK2PAK3PAK2PAK1AAK1GSK3BCLIP1ZFP295AKAP8ZFP219

0

0.2

0.4

0.6

0.8

1

e14-Fxr1

Nature Neuroscience: doi:10.1038/nn.4594

Page 37: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

TUD

OR

UBA

S_TKCSAPSPRYSAMR

RM

RL11

PUR

PP2C_SIG

PAZPIW

IKH FBGFN

3EN

DO

NU

CLEASE

NU

CSH

3R

HO

GEF

CH

PH CAD

HER

INBTBFYVEBR

CT

FERM

CB41FA B3−4B5 AR

MALPH

A_ADAPTINC

2AN

KAR

FGAP

GIT

TP53BP1TNRTDRD3RPL12PURAPPM1HPPFIA3HNRNPUHNRNPUL2HNRNPKFXR2FMR1FXR1FARSBEXOGEPB41L3PABPC1HNRNPMGM10110ELAVL4ELAVL1ELAVL2EIF2C1EIF2C2CTNNB1CDH2PAK3PAK2PAK1CAMK2ACAMK2BARHGEF7BAIAP2AP2A1AP2A2ANKFY1GIT1

0

0.2

0.4

0.6

0.8

1

Adult-non-PSD Fxr1

Nature Neuroscience: doi:10.1038/nn.4594

Page 38: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WD

40TPRS_TKCSAMR

HO

GEF

PDZ

PAZPIW

IM

YSCIQ M

YOSIN

IGC

2FBGFN

3EFHSH

3D

EATHZU

5C

NM

PSPECC

HPH IG LIN

KEG

FC

CP

CLEC

TC

ADH

ERIN

C1

C2

BTBB2_ADAPT_APP_CAR

MAN

KAR

FGAP

GIT

ALPHA_ADAPTIN

C2

ADF

ALDO

LASE_II

WDR7TNRSPTAN1SPTBN1TANC2PEX5PEX5LPARD3MYH9MYO5AKCTD16ICAM5NCANHCN4HCN3HCN1HCN2DBN1CTNNB1CTNND2CDH11CDH2CAMK2AARHGEF2UNC13AAP2B1AP2A1AP2A2GIT1ANK2CASKIN1ADD1AGO3AGO1AGO2

0

0.2

0.4

0.6

0.8

1

Adult non-PSD Pex5l

Nature Neuroscience: doi:10.1038/nn.4594

Page 39: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

TPRSPECSAMPTBSH

2MOPTER

IN−BD

_DOM

MOEA_LIN

KER/N

MOCF_BIO

SYNTH

_CS

MOEA_C

_DOMAIN

_IVL27GUKC

SH3

IGC

2FN

3IG C

NPASE

CN

MP

RH

OG

EFC

HPH C

2FYVES_TKCC

1C

NH

BTBAN

KAR

FGAP

GIT

PDZ

ASD1

ASD2

TNS1RPH3APEX5LMPDZSHROOM3KCTD12KCTD16PRKAR1BPRKAR1AHCN4HCN1HCN2GIT1DSCAMMAPK8IP1MAPK8IP2SH3D19SH3KBP1DLG1SHANK3CNPCITSPTBN1PAK3PAK1GSK3BCSNK2A1CAMK2ACAMK2BBSNARHGEF7SPTBN2

0

0.2

0.4

0.6

0.8

1

Adult-non-PSD Hcn1

Nature Neuroscience: doi:10.1038/nn.4594

Page 40: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WH

2M

HD

KH EFHSH

3DYN

CG

EDC

NH

S_TKCSPECC

HPH ALPH

A_ADAPTINC

2FER

MC

B41FA

WASF1SPTBN1SPTBN2SGIP1FMR1EPB4.1L1EPB41L3DNM1LTNIKCAMK2AGSK3BAP2A1SPTAN1BAIAP2ABI1ABI2

0

0.2

0.4

0.6

0.8

1

Adult-PSD Nckap1

Nature Neuroscience: doi:10.1038/nn.4594

Page 41: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WH

2W

H1

SEC7

PP2ACPEPTIDYLPRO

LINE_ISO

MER

ASESH

3PD

ZSAMIG IG

C1

GKAP

FN3

IGC

2FBGEFHDYN

CG

EDD

HR

PH CH

SPECS_TKCC

1C

2SPRYR

ING

BBOX

PRYBAR14−3−3AN

KAR

FGAP

MIRO

YWHAZYWHABYWHAEWASF1TRIM21SIRPAPPP3CAPPIAHOMER1GIPC1SHANK2SHANK1SHANK3DOCK7DNM1LDLGAP1TNRCNTN4NCAM1PRKCACAMK2AMAP3K5SPTAN1CALM1EFHD2BIN1AGAP2CYTH3SPTBN1SPTBN2

0

0.2

0.4

0.6

0.8

1

Adult-PSD Homer1

Nature Neuroscience: doi:10.1038/nn.4594

Page 42: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WH

2TPRSAMR

ING

PHR

RC

C1

PEPTIDASE_S8KH IQ M

YOSIN

FYVEG

OLD

FCH

RH

OG

APSH

3EFHSPECDYN

CG

EDC

NH

S_TKCC

HPH C

ADH

ERIN

ARM

LAMG

FBGFA58C4.1MEG

FAN

KC

ORTBP2

WASF1TPP2PEX5LMYO5AMYCBP2FYCO1FMR1CTTNBP2CTNNB1CNTNAP1CDH10CDH2TNIKNEK9MAP3K5CAMK2ACAMK2BSRGAP3SPTAN1SPTBN1ABI2CASKIN1SPTBN2APPL1DNM1

0

0.2

0.4

0.6

0.8

1

Adult-non-PSD Cyfip2

Nature Neuroscience: doi:10.1038/nn.4594

Page 43: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

WD

40R

ASGAP

C2

PH CN

HS_TKC

TNIKCAMK2AIQSEC3MYCBP2

0

0.2

0.4

0.6

0.8

1

Adult-PSD Mycbp2

Nature Neuroscience: doi:10.1038/nn.4594

Page 44: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

RR

MZN

F_C2H

2ZN

F_U1

PI3KCR

ING

PHR

RC

C1

PH IQ SEC7

HD

CSH

3G

UKC

PDZ

FBOX

SPRYC

HSPECS_TKCC

2H

R1

TNIKSPTBN2SYT3PKN1WDR45MTORMYCBP2MATR3PDE1BIQSEC3G3BP2UNC79CYFIP2CAMK2ACAMK2B

0

0.2

0.4

0.6

0.8

1

Adult-non-PSD Mycbp2

Nature Neuroscience: doi:10.1038/nn.4594

Page 45: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

PP2ACPH R

ASGAP

GU

KCC

ULLIN

CULLIN

−NED

D8

CN

HS_TKCC

1C

2AR

MAN

KSAMPD

ZSH

3

SYNGAP1PPP3CADLG4SHANK3CUL3CTNNB1PRKCBPRKCGCAMK2GCDK5MINK1TNIK

0

0.2

0.4

0.6

0.8

1

Adult-PSD Tsc1

Nature Neuroscience: doi:10.1038/nn.4594

Page 46: Supplementary Figure 1 Reported (nonredundant) protein … · 2017-07-26 · Supplementary Figure 3 Reported (nonredundant) protein interactions in PSD scaffold interactors complexes

ZNF_C

2H2

WH

2TBCR

ASR

ABPU

RLR

R_TYP

LRR

CT

LRR

NT

GTP_BIN

DIN

GG

ELSOLIN

FBGFN

3D

NAJ

CU

LLINCULLIN

−NED

D8

CN

HS_TKCC

1C

2R

ASGAP

BTKPH R

ING

IG_FLM

NBBCBBO

X14−3−3AR

M

YWHAZWASF1TRIM3TNRTBC1D7SEC23ARASAL1RAC1RAB14RAB7APURALGI1RAP2BHRAS1KRASFBXO41DNAJA4DNAJA1DNAJA2CUL3CTNNB1PRKCBPRKCGTNIKCAMK2ACDK5

0

0.2

0.4

0.6

0.8

1

Adult-non-PSD Tsc1

Nature Neuroscience: doi:10.1038/nn.4594