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