| Playing with Fingers
 
 Canonical forms for DNA binding zinc finger:
 Form 1: (F/Y)XCX2-5CX3(F/Y)X5ψX2HX3-5H
 Form 2: X2CX2,4CX12H-X3-5H
 
 ZF1 (542-563)	SMART E=55.4 	zps=2.2	Not in UniProt HMER, non-canonical
QYCX2CX3FX5ψXHX3H
           1
     ■■■■■■■■■■■■■■■■■■■■■■
              -1123456789
h.s. QYCVLCDKEFLGHRIVRHAQKH
100% QYClLCDKEFLGHRIVRHAQKH
 90% QYCVLCDKEFLGHRIVRHAQKH
 80% QYCVLCDKEFLGHRIVRHAQKH
 70% QYCVLCDKEFLGHRIVRHAQKH
     ph0hh0-+-hh0++hh++hp++
 
     QYCLLCDKEFLGHRIVRHAQKH (Mouse)
     ***:******************
     QYCVLCDKEFLGHRIVRHAQKH (Xenopus Laevis)
     ********************** 
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD 
p.Asp548Asn   1  1        23       1      5.73  22.4
α=0 β=1
PWM calculated using zf.princeton.edu with Expanded Linear SVM
 
| base       1       2       3       4 
   a   0.000   0.005   0.005   0.000 
   c   0.000   0.973   0.005   0.000 
   g   1.000   0.000   0.000   1.000 
   t   0.000   0.022   0.989   0.000 
Ent=   0.000   0.200   0.098   0.000 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.000   0.018   0.106   0.005 
   c   0.000   0.503   0.088   0.980 
   g   0.999   0.168   0.001   0.014 
   t   0.001   0.311   0.805   0.001 
Ent=   0.014   1.558   0.915   0.161 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 1-2 (564-568, 5aa)
     ■■■■■
h.s. YKDGI
100% aKDGl
 90% YKDGl
 80% YKDGI
 70% YKDGI
ZF2 (569-591)	SMART E=0.101 	zps=18.5 Canonical
YXCX2CX3FX5ψX2HX3H
         1       *1
     ■■■■■■■■■■■■■■■■■■■■■■■
               -1123456789
h.s. YSCPICAKNFNSKETFVPHVTLH
100% YSCPICAppasSK-sFVPHVThH
 90% YSCPICApNFNSKEsFVPHVTLH
 80% YSCPICAKNFNSKEoFVPHVTLH
 70% YSCPICAKNFNSKETFVPHVTLH
     hp00h0h+phpp+-phh0+hph+
     
     YSCPICAKNFNSKDSFVPHVTLH (Mouse)
     *************::********
     YSCPICAQQYSSKENFVPHVTFH (Xenopus Laevis)
     *******:::.***.******:*
               
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD 
p.Ile573Val   1  0.999    21       1      5.49  13.47
p.Lys581Arg   22 0.906    26       1      5.49  14.54
p.Glu582Asp    1 0.067    45       1      3     10.53
α=2 β=1
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.009   0.017   0.013 
   c   0.001   0.052   0.038 
   g   0.978   0.659   0.018 
   t   0.012   0.272   0.931 
Ent=   0.175   1.230   0.461 |   |  
| base       1       2       3       4 
   a   0.024   0.000   0.009   0.000 
   c   0.438   0.929   0.001   0.001 
   g   0.432   0.000   0.568   0.998 
   t   0.107   0.071   0.422   0.000 
Ent=   1.518   0.372   1.062   0.019 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.018   0.015   0.116   0.009 
   c   0.308   0.447   0.012   0.017 
   g   0.500   0.034   0.024   0.968 
   t   0.175   0.504   0.847   0.006 
Ent=   1.567   1.272   0.770   0.252 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 2-3 (592-671, 80aa)
     ■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■
h.s. VKQSSKERLAAMKPLRRLGRPPKITTTNENQKTNTVAKQEQRPIKKNSLYSTDFIVFNDNDGSDDENDDKDKSYEPEVIP
100% VKpSsKERLtsMKPLR+lG+PPKhsss..sp+.ss.sppppR.IKKNshY.sDFIVFNDNDtS-D-p.-...........
 90% VKpSSKERLAAMKPLRRLGRPPKlssspcNQKssslsKQEQRPIKKNSLYSsDFIVFNDNDGSDDEsDDKDKsY.P-lh.
 80% VKQSSKERLAAMKPLRRLGRPPKIosspENQKTNsVsKQEQRPIKKNSLYSTDFIVFNDNDGSDDENDDKDKSYEPEllP
 70% VKQSSKERLAAMKPLRRLGRPPKITTTNENQKTNsVuKQEQRPIKKNSLYSTDFIVFNDNDGSDDENDDKDKSYEPEVIP
     ■■■■■■■■■■■
h.s. VQKPVPVNEFN
100% .........hs
 90% lQKPhPVNEFs
 80% VQKPlPVNEFN
 70% VQKPVPVNEFN
ZF3 (681-705) SMART E=0.352	zps=23.5 Canonical
FXCX4CX3FX5ψX2HX3H
     
      1    1 1     1        2
     ■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. FNCPVTFCKKGFKYFKNLIAHVKGH
100% hsCPVthCKKGFKYFKNLIAHs+GH
 90% FsCPVohCKKGFKYFKNLIAHsKGH
 80% FNCPVTFCKKGFKYFKNLIAHVKGH
 70% FNCPVTFCKKGFKYFKNLIAHVKGH
     hp00hph0++0h+hh+phhh+h+0+
     FNCPVTFCKKGFKYFKNLIAHVKGH (Mouse)
     *************************
     FACPVHLCKKGFKYFKNLIAHVRGH (Xenopus Laevis)
     * *** :***************:**
      
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD 
p.Asn682Ser   1  0.109     46      1      4.86   6.168
p.Phe687Leu   1  0.001     22      1      5.96   2.918
p.Lys689Arg   1  0.33      26      1      5.96   8.586
p.Phe695Ser   1  1        155      1      5.96  18
p.Gly704Ala   2  0.034     60      1      5.07   0.932
α=2 β=3
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.293   0.077   0.189 
   c   0.104   0.756   0.475 
   g   0.452   0.106   0.217 
   t   0.151   0.061   0.119 
Ent=   1.788   1.181   1.808 |   |  
| base       1       2       3       4 
   a   0.223   1.000   0.000   0.007 
   c   0.002   0.000   0.266   0.054 
   g   0.722   0.000   0.705   0.937 
   t   0.053   0.000   0.029   0.002 
Ent=   1.066   0.002   1.013   0.383 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.184   0.997   0.009   0.012 
   c   0.056   0.001   0.009   0.880 
   g   0.527   0.001   0.972   0.096 
   t   0.233   0.001   0.009   0.011 
Ent=   1.658   0.037   0.228   0.639 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 3-4 (706-721)
     ■■■■■■■■■■■■■■■
h.s. DNEDAKRFLEMQSKK
100% ss--ApRFLEhQSKK
 90% DsE-AKRFLEMQSKK
 80% DNEDAKRFLEMQSKK
 70% DNEDAKRFLEMQSKK
ZF4 (722-744)	SMART E=0.153	zps=17.5 Non-canonical (but V is smaller hydrophobic aa)
VXCX2CX3FX5ψX2HX3H
     
        1   1    1   5   1
     ■■■■■■■■■■■■■■■■■■■■■■■
               -1123456789
h.s. VICQYCRRHFVSVTHLNDHLQMH
100% VlCQYCRRpFVSlsHLNDHLQMH
 90% VICQYCRRHFVSVTHLNDHLQMH
 80% VICQYCRRHFVSVTHLNDHLQMH
 70% VICQYCRRHFVSVTHLNDHLQMH
     hh0ph0+++hhphp+hp-+hph+
     
     VICQYCRRHFVSVTHLNDHLQMH (Mouse)
     ***********************
     VVCQYCRRQFVSLAHLNDHLQMH (Xenopus Laevis)
     *:******:***::*********
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD 
p.Gln725Arg   1  0.996    43       1      5.97  18.21
p.Arg729Gln   1  1        43       0.99   5.97  22.9
p.Val734Ile   1  0.959    21       1      5.97  17.7
p.Asn738Ser   5  1        46       0.999  4.82  15.7
p.Gln742Arg   1  0.852    43       1      5.97  15.02
α=3 β=2
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.237   0.733   0.005 
   c   0.639   0.019   0.054 
   g   0.084   0.103   0.323 
   t   0.040   0.145   0.618 
Ent=   1.391   1.179   1.219 |   |  
| base       1       2       3       4 
   a   0.215   0.000   0.701   0.000 
   c   0.214   0.000   0.000   0.000 
   g   0.006   1.000   0.267   1.000 
   t   0.565   0.000   0.032   0.000 
Ent=   1.464   0.002   1.031   0.001 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.217   0.244   0.008   0.018 
   c   0.316   0.047   0.029   0.168 
   g   0.008   0.707   0.015   0.777 
   t   0.460   0.002   0.947   0.037 
Ent=   1.573   1.074   0.373   0.995 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 4-5 (745-749)
     ■■■■■
h.s. CGSKP
100% CGspP
 90% CGSKP
 80% CGSKP
 70% CGSKP
ZF5 (750-774)	SMART E=1.23	zps=8.9 Canonical
YXCX4CX3FX5ψX2HX3H
     
        1    1          1
     ■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. YICIQMKCKAGFNSYAELLTHRKEH
100% YICIQhKCKAuFpoYA-LLsHR+EH
 90% YICIQMKCKAGFNSYAELLsHRKEH
 80% YICIQMKCKAGFNSYAELLTHRKEH
 70% YICIQMKCKAGFNSYAELLTHRKEH
     hh0hph+0+h0hpphh-hhp+++-+
     
     YICIQMKCKAGFNSYAELLAHRKEH (Mouse)
     *******************:*****
     YICIQMKCKASFETYADLLSHRKEH (Xenopus Laevis)
     **********.*::**:**:*****
   
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD 
p.Ile753Thr   1  1        89       1      5.76  16.77
p.Lys758Gln   1  1        53       1      5.76  17.19
p.Thr769Ser   1  0.007    58       1      5.76   4.553 
α=1 β=2
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.078   0.116   0.129 
   c   0.586   0.039   0.224 
   g   0.094   0.798   0.091 
   t   0.242   0.047   0.556 
Ent=   1.555   1.011   1.649 |   |  
| base       1       2       3       4 
   a   0.034   0.001   0.278   0.000 
   c   0.000   0.136   0.001   0.000 
   g   0.043   0.003   0.001   0.993 
   t   0.924   0.860   0.719   0.007 
Ent=   0.466   0.608   0.879   0.059 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.079   0.124   0.021   0.484 
   c   0.014   0.455   0.031   0.435 
   g   0.017   0.026   0.028   0.011 
   t   0.891   0.394   0.920   0.070 
Ent=   0.621   1.559   0.529   1.367 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 5-6 (775-778)
     ■■■■
h.s. QVFR
100% .VFR
 90% QVFR
 80% QVFR
 70% QVFR
ZF6 (779-803)	SMART E=10.8	zps=15.9 Non-canonical (but A is smaller hydrophobic aa)
AXCX4CX3FX5ψX2HX3H
     
                      1 1
     ■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. AKCMFPKCGRIFSEAYLLYDHEAQH
100% A+ChFPKCGRlFStAYhLaDHEAQH
 90% AKChFPKCGRIFSpAYLLYDHEAQH
 80% AKCMFPKCGRIFSEAYLLYDHEAQH
 70% AKCMFPKCGRIFSEAYLLYDHEAQH
     h+0hh0+00+hhp-hhhhh-+-hp+
     AKCLFPKCGRIFSQAYLLYDHEAQH (Mouse)
     ***:*********:***********
     ARCMFPKCGRIFSAAYMLFDHEAQH (Xenopus Laevis)
     *:*********** **:*:******
     
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Ala801Val   1  1        64       1      5.76 17.96
p.His803Arg   1  1        29       1      5.76 16.51
α=2 β=0
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.564   0.440   0.111 
   c   0.071   0.206   0.119 
   g   0.138   0.197   0.636 
   t   0.227   0.157   0.134 
Ent=   1.615   1.872   1.521 |   |  
| base       1       2       3       4 
   a   0.215   0.001   0.003   0.000 
   c   0.214   0.947   0.005   0.985 
   g   0.006   0.051   0.991   0.015 
   t   0.565   0.001   0.002   0.000 
Ent=   1.464   0.316   0.090   0.110 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.230   0.001   0.045   0.005 
   c   0.230   0.971   0.031   0.027 
   g   0.008   0.024   0.785   0.963 
   t   0.532   0.004   0.138   0.005 
Ent=   1.517   0.213   1.026   0.273 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 6-7 (804-806)
     ■■■
h.s. YNT
100% YNT
 90% YNT
 80% YNT
 70% YNT
ZF7 (807-831)	SMART E=0.000369	zps=29.8 HMMER=3.8e-07 Canonical
YXCX4CX3YX5ψX2HX3H
     
           2     *1  1     3
     ■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. YTCKFTGCGKVYRSQGELEKHLDDH
100% aTC+hssCGKlY+SQ.ph-KH.ptH
 90% YTCKFTGCGKVYRSQsEhEKHl--H
 80% YTCKFTGCGKVYRSQuELEKHL-DH
 70% YTCKFTGCGKVYRSQuELEKHLDDH
     hp0+hp000+hh+pp0-h-++h--+
     
     YTCKFTGCGKVYRSQSEMEKHQDGH (Mouse)
     ***************.*:*** *.*
     FTCKYVGCGKIYHSQLQLEKHLSEH (Xenopus Laevis)
     :***:.****:*:** :*****.:*
      
gnomAD v2.1 Controls 
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Gly813Asp   2  0.001     94      1      3.99   5.806
p.Arg819Cys   4  1        180      1      5.76   15.96
p.Arg819His   6  0.477     29      1      5.76   10.78
p.Ser820Pro   1  1         74      1      5.76  17.67
p.Glu823Gly   1  0.999     98      1      5.76  16
p.Asp829His   1  0.808     88      1      5.67  14.17
p.Asp829Asn   2  0.196     23      1      5.62  13.09
α=4 β=1
PWMs calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.061   0.234   0.096 
   c   0.541   0.078   0.088 
   g   0.187   0.231   0.552 
   t   0.211   0.457   0.264 
Ent=   1.652   1.781   1.614 |   |  
| base       1       2       3       4 
   a   0.250   0.002   0.122   0.000 
   c   0.002   0.993   0.000   0.000 
   g   0.374   0.002   0.002   1.000 
   t   0.374   0.002   0.876   0.000 
Ent=   1.581   0.072   0.558   0.000 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.413   0.193   0.002   0.000 
   c   0.004   0.324   0.002   0.999 
   g   0.289   0.060   0.001   0.001 
   t   0.293   0.423   0.995   0.000 
Ent=   1.599   1.753   0.057   0.009 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
ZF8 (1098-1123)	SMART E=0.0767	zps=21 Canonical
FXCX4CX3YX5ψX2HX4H
           1         14
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. FSCQVEGCTRTYNSSQSIGKHMKTAH
100% FpCpVEGCTR.YNSsQSIGKHMKsAH
 90% FsCQVEGCTRoYNSSQSIGKHMKTAH
 80% FSCQVEGCTRTYNSSQSIGKHMKTAH
 70% FSCQVEGCTRTYNSSQSIGKHMKTAH
     hp0ph-00p+phppppph0++h+ph+
     FSCQVEGCTRTYNSSQSIGKHMKTAH (Mouse)
     **************************
     FKCSVEGCTRIYNSVQSIGKHMKTAH (Xenopus Laevis)
     *.*.****** *** ***********
          
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Gly1104Glu  1  1         98      1      5.55  18.29
p.Ser1114Gly  1  0.997     56      1      5.55  22.2
p.Ile1115Ser  4  0.999    142      1      5.55  21
α=2 β=1
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.296   0.596   0.229 
   c   0.182   0.142   0.454 
   g   0.094   0.186   0.269 
   t   0.428   0.075   0.049 
Ent=   1.812   1.578   1.726 |   |  
| base       1       2       3       4 
   a   0.250   0.000   0.001   0.007 
   c   0.002   0.811   0.000   0.036 
   g   0.374   0.000   0.000   0.893 
   t   0.374   0.188   0.998   0.064 
Ent=   1.581   0.707   0.018   0.622 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.352   0.001   0.019   0.297 
   c   0.002   0.248   0.018   0.479 
   g   0.509   0.000   0.021   0.144 
   t   0.137   0.751   0.942   0.080 
Ent=   1.435   0.824   0.412   1.722 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
ZF9 (1375-1397)	SMART E=193	zps=11.7 (degenerate in UniProt) Non-canonical (longer α-helix with terminal C)
Fits Interpro ZF_C2HC_RNF
FXCX3CX3FX5ψX2HX6C
                 2
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
               -1123456789
h.s. FICSRCYRAFTNPRSLGGHLSKRSYC
100% FICSRCaRsFoNPRSLGGHLSKRuhC
 90% FICSRCaRsFTNPRSLGGHLSKRSaC
 80% FICSRCYRAFTNPRSLGGHLSKRSYC
 70% FICSRCYRAFTNPRSLGGHLSKRSYC
     hh0p+0h+hhpp0+ph00+hp++ph0
     
     FICSRCYRAFTNPRSLGGHLSKRSYC (Mouse)
     **************************
     FICSRCFRAFTNPRSLGGHLSKRAVC
     ******:****************: *
            
gnomAD v2.1 Controls 
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Pro1387His  2  1        77       1      5.32  16.89
α=1 β=0
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.207   0.406   0.184 
   c   0.336   0.352   0.448 
   g   0.103   0.198   0.208 
   t   0.354   0.045   0.160 
Ent=   1.868   1.722   1.862 |   |  
| base       1       2       3       4 
   a   0.124   0.000   0.013   0.000 
   c   0.255   0.069   0.001   0.453 
   g   0.124   0.000   0.815   0.547 
   t   0.497   0.931   0.171   0.000 
Ent=   1.750   0.363   0.765   0.994 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.206   0.001   0.308   0.002 
   c   0.216   0.078   0.127   0.801 
   g   0.206   0.000   0.269   0.193 
   t   0.373   0.921   0.296   0.005 
Ent=   1.947   0.409   1.930   0.765 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 9-10
coiled-coil (1830-1850)
     ■■■■■■■■■■■■■■■■■■■■■
h.s. VSHKEDQIQEILEGLQKLKLE
100% ...c..ph.-Ih-hlppLpL.
 90% h..K-sQl.EILEGLppLKLE
 80% h.pK-DQlQEILEGLQKLKLE
 70% l.HKEDQIQEILEGLQKLKLE
Suspected Z-Box binding (10-12)
ZF10 (1904-1927)	SMART E=0.0767	zps=10.9 Non-canonical
FXCX4CX1YX7ψX2HX4H
 
                       1
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. FVCQNQGCNYSAMTKDALFKHYGKIH
100% FhCQt.sCsYsAMTKDALFKHYuKlH
 90% FVCQspGCsYSAMTKDALFKHYuKIH
 80% FVCQNQGCNYSAMTKDALFKHYGKIH
 70% FVCQNQGCNYSAMTKDALFKHYGKIH
     hh0ppp00phphhp+-hhh++h0+h+
    
     FVCQNQGCNYSAMTKDALFKHYGKIH (Mouse)
     **************************
     FICQETDCTYCAMTKDALFKHYAKVH (Xenopus Laevis)
     *:**: .*.*.***********.*:*
        
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Phe1920Ile  1  0.976    21       0.933  6.17  16.61
α=1 β=0
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.131   0.150   0.081 
   c   0.194   0.075   0.846 
   g   0.027   0.577   0.038 
   t   0.649   0.198   0.035 
Ent=   1.387   1.612   0.846 |   |  
| base       1       2       3       4 
   a   0.250   0.011   0.000   0.000 
   c   0.002   0.002   0.000   0.000 
   g   0.374   0.017   0.035   1.000 
   t   0.374   0.969   0.965   0.000 
Ent=   1.581   0.236   0.218   0.003 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.263   0.017   0.003   0.000 
   c   0.001   0.007   0.000   1.000 
   g   0.466   0.004   0.003   0.000 
   t   0.270   0.973   0.994   0.000 
Ent=   1.540   0.217   0.063   0.004 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 10-11 (1928-1946, 19aa)
     ■■■■■■■■■■■■■■■■■■■
h.s. QYTPEMILEIKKNQLKFAP
100% .YT.EhIh-IKKpQLKaAP
 90% QYTsEMILEIKKpQLKaAP
 80% QYTPEMILEIKKNQLKFAP
 70% QYTPEMILEIKKNQLKFAP
ZF11 (1947-1972)	SMART E=193	zps=27.9 HMMER=2.1e-06 Canonical
FXCX4CX3FX5ψX2HX4H
         1             1    1
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. FKCVVPTCTKTFTRNSNLRAHCQLVH
100% FKCVVsoCsKTFTRNSNLRAHCQ.hH
 90% FKCVVsoCsKTFTRNSNLRAHCQLVH
 80% FKCVVPTCTKTFTRNSNLRAHCQLVH
 70% FKCVVPTCTKTFTRNSNLRAHCQLVH
     h+0hh0p0p+php+ppph+h+0phh+
     
     FKCVVPSCTKTFTRNSNLRAHCQLVH (Mouse)
     ******:*******************
     FKCVVPSCTKTFTRNSNLRAHCQSMH (Xenopus Laevis)
     ******:**************** :*
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Val1951Ile  1  0.997     29      1      6.11  13.62
p.Arg1965Gly  1  1        125      0.998  6.11  15.18
p.Leu1970Phe  1  0.267     22      1      4.35  11.09
α=2 β=1
PWMs calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.055   0.262   0.159 
   c   0.064   0.235   0.289 
   g   0.393   0.309   0.248 
   t   0.488   0.195   0.305 
Ent=   1.519   1.980   1.960 |   |  
| base       1       2       3       4 
   a   0.223   1.000   0.000   0.000 
   c   0.002   0.000   0.000   0.168 
   g   0.722   0.000   0.999   0.813 
   t   0.053   0.000   0.001   0.018 
Ent=   1.066   0.002   0.010   0.782 |  |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.137   1.000   0.000   0.152 
   c   0.040   0.000   0.000   0.846 
   g   0.517   0.000   1.000   0.001 
   t   0.305   0.000   0.000   0.000 
Ent=   1.593   0.004   0.005   0.632 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 11-12 (1973-2113, 141 aa)
     ■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■
h.s. HFTTEEMVKLKIKRPYGRKSQSENVPASRSTQVKKQLAMTEENKKESQPALELRAETQNTHSNVAVIPEKQLVEKKSPDK
100% pFT.EpMlKLKlKRsYG++sp.p........p...........p..................p...h.tp...E....p.
 90% HFTsEEMVKLKIKRPYGR+oQsEs.sssp..plpp...hh.-scpp...shph....p.sh.p.shl.-p.h.EppsP-p
 80% HFTTEEMVKLKIKRPYGRKSQsEs.sssp.sQVK+Q.shsEEsKpE.psshclts.ppsshsslullPEKQlhEKKSP-+
 70% HFTTEEMVKLKIKRPYGRKSQsENlousp.sQVK+Q.shTEENK+E.QPslELts.pcsshsNlAVIPEKQLhEKKSP-K
     ■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■
h.s. TESSLQVITVTSEQCNTNALTNTQTKGRKIRRHKKEKEEKKRKKPVSQSLEFPTRYSPYRP
100% .t.s................tp...KhpK.++.pKEhp-h.thp..pp....stpassY+P
 90% .Eps.p.hshs.-p.s.ts.sphp.KsRK.+R++KEKEE++c+pPsspu.EhPs+YSsYRP
 80% hEsS.QslslssEQhs.sshoshpsKGRKhRRH+KEKEE++cKKPVopShEhPTRYSPYRP
 70% sESS.QVloVoSEQpNssuLTNhQTKGRKlRRH+KEKEEKKRKKPVSQSlEFPTRYSPYRP
ZF12 (2114-2139)	SMART E=0.44	zps=16.3 Canonical
YXCX4CX3FX5ψX2HX4H
            1   1      1
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. YRCVHQGCFAAFTIQQNLILHYQAVH
100% YpCVHQGChAAFTIQQNLILHYQAVH
 90% YpCVHQGCFAAFTIQQNLILHYQAVH
 80% YRCVHQGCFAAFTIQQNLILHYQAVH
 70% YRCVHQGCFAAFTIQQNLILHYQAVH
     h+0h+p00hhhhphppphhh+hphh+
     
     YCCVHQGCFAAFTIQQNLILHYQAVH (Mouse)
     * ************************
     YQCVHQGCTAAFTIQQNLILHYQAVH (Xenopus)
     *:****** *****************
 
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Tyr2114del  1                           5.77
p.Arg2115del  1                           5.77
p.Cys2121Phe  1  0.999    206      1      5.54  21.7
p.Phe2122Ser  1  0.958    155      1      5.54   7.947
p.Ile2132Val  1  0.66      29      1      5.54 16.83
α=1 β=4
PWMs calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.288   0.884   0.003 
   c   0.519   0.008   0.026 
   g   0.023   0.043   0.856 
   t   0.170   0.065   0.115 
Ent=   1.567   0.665   0.711 |   |  
| base       1       2       3       4 
   a   0.309   1.000   0.010   0.222 
   c   0.313   0.000   0.001   0.157 
   g   0.309   0.000   0.086   0.000 
   t   0.069   0.000   0.903   0.620 
Ent=   1.838   0.000   0.515   1.333 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.161   0.993   0.005   0.278 
   c   0.599   0.006   0.005   0.138 
   g   0.160   0.001   0.985   0.507 
   t   0.081   0.001   0.005   0.077 
Ent=   1.582   0.070   0.138   1.689 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 12-13 (2140-2171, 32aa)
     ■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■
h.s. KSDLPAFSAEVEEESEAGKESEETETKQTLKE
100% KSs...Fs.E.tE.........p.Est...+E
 90% KSsLPsFSsElEEEsE.sK-p-EhEsK.shKE
 80% KSDLPuFSAEVEEEsEssKEsEEhETKpohKE
 70% KSDLPAFSAEVEEESEsGKESEEhETKQThKE
ZF13 (2172-2197)	SMART E=.0472	zps=15 Canonical
FXCX4CX3FX5ψX2HX4H
      1   13 1    12   11  1
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. FRCQVSDCSRIFQAITGLIQHYMKLH
100% FRC...sCSRIFQtlsuLlQHYMKhH
 90% FRCphSDCSRIFQtlTuLIQHYMKLH
 80% FRCQVSDCSRIFQAITGLIQHYMKLH
 70% FRCQVSDCSRIFQAITGLIQHYMKLH
     h+0php-0p+hhphhp0hhp+hh+h+
     
     FRCQVSDCSRIFQAITGLIQHYMKLH  (Mouse)
     **************************
     FRCMEIDCSRIFQEVGSLVQHYMKLH  (Xenopus)
     ***   ******* : .*:*****:*
    
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP  CADD
p.Arg2173Gln  1  1         43      1      5.54  32
p.Ser2177Ile  1  0.974    142      1      5.54  18.61
p.Asp2178Asn  3  0.289     23      1      5.54  15.4
p.Ser2180Cys  1  1        112      1      5.54  22.9
p.Ala2185Ser  1  0.435     99      1      4.66  12.79
p.Ile2186Val  2  0.002     29      1      5.54   1.247
p.Ile2190Met  1  0.961     10      1      4.24  15.83
p.Gln2191Lys  1  0.993     53      1      5.42  17.59
p.Met2194Val  1  0.15      21      1      5.42  11.3
α=5 β=4
PWMs calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.078   0.721   0.482 
   c   0.204   0.145   0.085 
   g   0.035   0.100   0.196 
   t   0.683   0.034   0.237 
Ent=   1.299   1.241   1.763 |   |  
| base       1       2       3       4 
   a   0.251   0.000   0.963   0.001 
   c   0.251   0.000   0.028   0.016 
   g   0.250   0.000   0.004   0.980 
   t   0.247   1.000   0.005   0.002 
Ent=   2.000   0.001   0.268   0.154 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.540   0.026   0.401   0.014 
   c   0.400   0.066   0.550   0.132 
   g   0.024   0.053   0.006   0.616 
   t   0.035   0.854   0.044   0.238 
Ent=   1.310   0.816   1.246   1.396 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 13-14 (2198-2215, 18aa)
     ■■■■■■■■■■■■■■■■■■
h.s. EMTPEEIESMTASVDVGK
100% pM.sEpItsh.s..phup
 90% EMoPEEItSMpsulslG+
 80% EMTPEEIESMTuuVDVGK
 70% EMTPEEIESMTASVDVGK
ZF14 (2216-2241)	SMART E=0.498	zps=10.2 Canonical
FXCX4CX3FX5ψX2HX4H
     
             9    11  1 1    2
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. FPCDQLECKSSFTTYLNYVVHLEADH
100% F.CDQ.pCt..FTshhsYl.HLE..H
 90% FsCDQ.pCKSSFTsYLsYllHLEsDH
 80% FPCDQ.ECKSSFTTYLNYVVHLEsDH
 70% FPCDQLECKSSFTTYLNYVVHLEsDH
     h00-ph-0+pphpphhphhh+h-h-+
     FPCDQLECKLSFTTYLSYVVHLEVDH (Mouse)
     ********* ******.******.**
     FKCDQLNCALLFTSCTSYIEHLEEVH (Xenopus)
     * ****:*   **:  .*: ***  *
        
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP   CADD
p.Lys2224Asn  9  0.999     94      0.998  -0.083 15.9
p.Thr2229Ala  1  0.002     58      0.984   3.75   8.2
p.Tyr2230His  1  0.989     83      0.978   4     18.4
p.Tyr2233Cys  1  1        194      1       5     17.78
p.Val2235Ile  1  0.002     29      0.989  -2.21  10.67
p.Asp2240Asn  1  0.115     23      1       5.63  15.2
p.Asp2240Glu  1  0         45      1       2.93   9.146
α=5 β=1
PWMs calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.599   0.438   0.083 
   c   0.261   0.073   0.114 
   g   0.024   0.101   0.155 
   t   0.116   0.388   0.648 
Ent=   1.436   1.662   1.479 |   |  
| base       1       2       3       4 
   a   0.444   0.997   0.000   0.000 
   c   0.442   0.000   0.000   0.010 
   g   0.098   0.003   0.001   0.990 
   t   0.016   0.000   0.999   0.000 
Ent=   1.465   0.031   0.008   0.082 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.739   1.000   0.003   0.001 
   c   0.222   0.000   0.000   0.993 
   g   0.037   0.000   0.001   0.006 
   t   0.002   0.000   0.997   0.000 
Ent=   0.999   0.006   0.034   0.066 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 14-15 (2242-2255, 14aa)
     ■■■■■■■■■■■■■■
h.s. GIGLRASKTEEDGV
100% tht.+..+..t-th
 90% ulth+ssKsE-DGh
 80% GIGhRssKsE-DGl
 70% GIGhRsSKTEEDGl
ZF15 (2256-2281)	SMART E=0.164	zps=23	HMMER=2.2e-06 Canonical
YXCX4CX3YX5ψX2HX4H
   
      1      11    2        1
     ■■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. YKCDCEGCDRIYATRSNLLRHIFNKH
100% aKCDCEGCDRlYATRSNLLRHIFNKH
 90% aKCDCEGCDRIYATRSNLLRHIFNKH
 80% YKCDCEGCDRIYATRSNLLRHIFNKH
 70% YKCDCEGCDRIYATRSNLLRHIFNKH
     h+0-0-00-+hhhp+pphh++hhp++
      
     YKCDCEGCDRIYATRSNLLRHIFNKH (Mouse)
     **************************
     YKCDCEGCDRVYATRSNLLRHIFNKH (Xenopus)
     **********:***************
 
gnomAD v2.1 Controls
Mutation      N  PolyPhen Grantham Phast  GERP   CADD
p.Lys2257Arg  1  0.997     26      1      5.65   15.51
p.Asp2264Gly  1  1         94      1      5.63   14.41
p.Arg2265Cys  1  1        181      1      4.68   15.89
p.Arg2270Trp  2  1        101      0.959  4.68   15.99
p.Asn2279Ser  1  0.997     46      1      5.62   14.92
α=2 β=3
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.440   0.728   0.089 
   c   0.450   0.005   0.202 
   g   0.025   0.011   0.520 
   t   0.086   0.256   0.189 
Ent=   1.476   0.947   1.721 |   |  
| base       1       2       3       4 
   a   0.000   1.000   0.000   0.000 
   c   0.000   0.000   0.000   0.333 
   g   1.000   0.000   0.000   0.333 
   t   0.000   0.000   1.000   0.333 
Ent=   0.000   0.000   0.000   1.587 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.000   1.000   0.000   0.664 
   c   0.000   0.000   0.000   0.332 
   g   1.000   0.000   0.000   0.004 
   t   0.000   0.000   1.000   0.000 
Ent=   0.000   0.000   0.001   0.954 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
Linker 15-16 (2282-2385, 104)
     ■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■
h.s. NDKHKAHLIRPRRLTPGQENMSSKANQEKSKSKHRGTKHSRCGKEGIKMPKTKRKKKNNLENKNAKIVQIEENKPYSLKR
100% N-+HKtHLIRPR+.h.sQ-shspKs.p-+sh.+.......+.tpcu.c..+.+Rp................ppp.hoLKh
 90% ND+HKsHLIRPR+LT.GQENhSSKANQEKshtK.Rsh...RsG+-G.+h.KsKRKKp.sh-sKs.Kh.php-sKsYSLKR
 80% NDKHKAHLIRPR+LTsGQENhSSKANQEKsKsKaRGTKa.RsGKEGhKhsKTKRKKKsNLEsKsuKllQIEENKPYSLKR
 70% NDKHKAHLIRPRRLTPGQENhSSKANQEKoKSKaRGTKH.RsGKEGhKhPKTKRKKKsNLENKsAKIVQIEENKPYSLKR
     ■■■■■■■■■■■■■■■■■■■■■■■■
h.s. GKHVYSIKARNDALSECTSRFVTQ
100% G+asa.lKs+ptAhsECssphhhQ
 90% GKHVYSIKARN-ALSECTS+FVTQ
 80% GKHVYSIKARNDALSECTS+FVTQ
 70% GKHVYSIKARNDALSECTSRFVTQ
coiled-coil 2334-2354 (21)
ZF16 (2386-2410)	SMART E=0.286	zps=7.6 Non-canonical (but V a smaller hyrophic aa replaces F at postion C2+3)
YXCX4CX9ψX2HX3H   
     
          1     2    2
     ■■■■■■■■■■■■■■■■■■■■■■■■■
                 -1123456789
h.s. YPCMIKGCTSVVTSESNIIRHYKCH
100% YPCMlpGCoSVVTSEpsIIRHYKCH
 90% YPCMIKGCoSVVTSEsNIIRHYKCH
 80% YPCMIKGCTSVVTSESNIIRHYKCH
 70% YPCMIKGCTSVVTSESNIIRHYKCH
     h00hh+00pphhpp-pphh++h+0+
     
     YPCMIKGCTSVVTSESNIIRHYKCH  (Mouse)
     *************************
     YPCMVRGCTSVVTSERSIIRHYKCH  (Xenopus)
     ****::********* .********
     
gnomAD v2.1 Control
Mutation      N  PolyPhen Grantham Phast  GERP   CADD
p.Lys2391Met  1  1         95      1      5.63   13.75
p.Val2397Phe  2  0.999      5      1      5.43   15.36
p.Asn2402Ser  2  0.816     46      1      5.43    4.25
α=1 β=2
PWM calculated using zf.princeton.edu with Expanded Linear SVM
| base       1       2       3 
   a   0.260   0.576   0.221 
   c   0.281   0.116   0.245 
   g   0.385   0.154   0.250 
   t   0.074   0.154   0.284 
Ent=   1.827   1.650   1.994 |   |  
| base       1       2       3       4 
   a   0.000   1.000   0.000   0.000 
   c   0.000   0.000   0.000   0.000 
   g   1.000   0.000   0.002   0.998 
   t   0.000   0.000   0.998   0.002 
Ent=   0.000   0.000   0.022   0.023 |   |  PWM calculated using zf.princeton.edu with Polynomial SVM
 
| base       1       2       3       4 
   a   0.000   1.000   0.002   0.888 
   c   0.000   0.000   0.002   0.112 
   g   1.000   0.000   0.003   0.001 
   t   0.000   0.000   0.993   0.000 
Ent=   0.000   0.000   0.070   0.513 |   |  PWM calculated using zf.princeton.edu with B1H RFR
 
coiled-coil 2530-2550
LKRVNKEKNVSQNKKRKVEK
| base       1       2       3 
   a   0.016   0.953   0.007 
   c   0.001   0.008   0.166 
   g   0.981   0.019   0.018 
   t   0.002   0.020   0.809 
Ent=   0.149   0.341   0.833 |   |  |