#  
# Data from Markiewicz, et al. Analysis of 4000 altered Escherichia coli 
# lac repressors reveals essential and non-essential residues, as well
# as "spacers" which do not require a specific sequence. J. Mol Biol.
# 240: 421-433.  Please reference this article if you publish using 
# this data.
#
# + means substitution does not alter phenotype
# - means substitution affects protein
# +- and -+ do not affect protein function as severely as "-"
# order of severity - > -+ > +-  > +
# 
# Questions about the format of this dataset? Email sift@fhcrc.org
#
K2S + 
K2Q +
K2Y +
K2L +
K2A +
K2C +
K2E +
K2G +
K2H +
K2F +
K2P -+  
K2R + 
P3S + 
P3Q +
P3Y - 
P3K +- 
P3L +  
P3A + 
P3C + 
P3E +
P3G +
P3H +
P3F -+  
P3R + 
V4S - 
V4Q +- 
V4Y -+ 
V4K +
V4L +-
V4A - 
V4C -+ 
V4E -+  
V4G +- 
V4H + 
V4F + 
V4P - 
V4R + 
T5S +-
T5Q - 
T5Y - 
T5K - 
T5L - 
T5A - 
T5C -+ 
T5E - 
T5G - 
T5H - 
T5F - 
T5P - 
T5R +-
L6S +-
L6Q +-
L6Y +-
L6K - 
L6A +
L6C + 
L6E - 
L6G +- 
L6H - 
L6F +
L6P - 
L6R - 
Y7S +-
Y7Q +-
Y7K +-
Y7L -+
Y7A +- 
Y7C +- 
Y7E +- 
Y7G -+  
Y7H +- 
Y7F +- 
Y7P - 
Y7R +- 
D8S +- 
D8Q +
D8Y - 
D8K -+  
D8L - 
D8A +- 
D8C - 
D8E -+  
D8G - 
D8H - 
D8F - 
D8P - 
D8R +- 
V9S - 
V9Q - 
V9Y - 
V9K - 
V9L +-
V9A - 
V9C -+  
V9E - 
V9G - 
V9H - 
V9F - 
V9P - 
V9R - 
A10S +- 
A10Q - 
A10Y - 
A10K - 
A10L - 
A10C - 
A10E - 
A10G + 
A10H - 
A10F - 
A10P - 
A10R - 
E11S +
E11Q + 
E11Y + 
E11K + 
E11L + 
E11A + 
E11C + 
E11G + 
E11H + 
E11F + 
E11P -  
E11R + 
Y12S + 
Y12Q + 
Y12K +
Y12L +
Y12A + 
Y12C + 
Y12E + 
Y12G + 
Y12H + 
Y12F + 
Y12P - 
Y12R + 
A13L +-
A13F  -
A13C + 
A13G +-
A13S + 
A13Y  -
A13P  -
A13H  -
A13E  -
A13Q  -
A13K  -
A13R  -
G14S + 
G14Q + 
G14Y - 
G14K +- 
G14L +- 
G14A + 
G14C + 
G14E + 
G14H + 
G14F -+  
G14P - 
G14R + 
V15S - 
V15Q - 
V15Y + 
V15K - 
V15L +- 
V15A -+  
V15C + 
V15E - 
V15G - 
V15H - 
V15F + 
V15P - 
V15R - 
S16Q - 
S16Y - 
S16K - 
S16L - 
S16A -+  
S16C -+  
S16E - 
S16G - 
S16H - 
S16F - 
S16P - 
S16R - 
Y17S -+  
Y17Q -+  
Y17K -+  
Y17L -+  
Y17A -+  
Y17C -+  
Y17E - 
Y17G -+  
Y17H -+  
Y17F -+  
Y17P -+  
Y17R -+  
Q18S - 
Q18Y - 
Q18K - 
Q18L - 
Q18A -+
Q18C - 
Q18E -+  
Q18G +- 
Q18H -
Q18F - 
Q18P - 
Q18R - 
T19S +- 
T19Q - 
T19Y - 
T19K - 
T19L - 
T19A - 
T19C - 
T19E - 
T19G - 
T19H - 
T19F - 
T19P - 
T19R - 
V20S - 
V20Q - 
V20Y - 
V20K - 
V20L - 
V20A +- 
V20C +- 
V20E - 
V20G - 
V20H - 
V20F - 
V20P - 
V20R - 
S21Q - 
S21Y - 
S21K - 
S21L - 
S21A -+  
S21C - 
S21E - 
S21G - 
S21H - 
S21F - 
S21P - 
S21R - 
R22S - 
R22Q - 
R22Y - 
R22K - 
R22L - 
R22A - 
R22C - 
R22E - 
R22G - 
R22H - 
R22F - 
R22P - 
V23S - 
V23Q - 
V23Y - 
V23K - 
V23L - 
V23A -+  
V23C -+  
V23E - 
V23G - 
V23H - 
V23F - 
V23P - 
V23R - 
V24S + 
V24Q + 
V24Y + 
V24K -+  
V24L -+ 
V24A +
V24C + 
V24E - 
V24G +- 
V24H + 
V24F -+ 
V24P - 
V24R + 
N25S +- 
N25Q +- 
N25Y - 
N25K -+ 
N25L -+  
N25A +- 
N25C -+  
N25E - 
N25G + 
N25H -+  
N25F - 
N25P - 
N25R +- 
Q26S + 
Q26Y + 
Q26K + 
Q26L + 
Q26A + 
Q26C + 
Q26E + 
Q26G + 
Q26H + 
Q26F + 
Q26P - 
Q26R + 
A27L + 
A27F +-
A27C + 
A27G + 
A27S +
A27Y + 
A27P + 
A27H + 
A27E + 
A27Q +
A27K + 
A27R + 
S28Q + 
S28Y + 
S28K + 
S28L -+ 
S28A + 
S28C + 
S28E + 
S28G + 
S28H + 
S28F + 
S28P -+ 
S28R + 
H29S + 
H29Q + 
H29Y - 
H29K - 
H29L + 
H29A + 
H29C -+  
H29E +- 
H29G + 
H29F - 
H29P -+  
H29R +- 
V30L -
V30F -
V30C -+
V30A + 
V30G -
V30S -+ 
V30Y - 
V30P -
V30H -
V30E -
V30Q -
V30K -
V30R - 
S31L  - 
S31F  - 
S31C  - 
S31A +  
S31G +  
S31Y  - 
S31P  - 
S31H +  
S31E  - 
S31Q  +- 
S31K +  
S31R +  
A32L +  
A32F +  
A32C +  
A32G +  
A32S +  
A32Y +  
A32P +  
A32H +  
A32E +  
A32Q +  
A32K +  
A32R +  
K33L  +- 
K33F  -+ 
K33C  - 
K33A  +- 
K33G +  
K33S  +- 
K33Y  +- 
K33P +  
K33H  -+ 
K33E  +- 
K33Q  +- 
K33R +  
T34L  +- 
T34F  - 
T34C  -+ 
T34A +  
T34G  - 
T34S  +- 
T34Y  - 
T34P  - 
T34H  - 
T34E  - 
T34Q  - 
T34K  - 
T34R  +- 
R35L +  
R35F  +- 
R35C  -+ 
R35A +  
R35G  - 
R35S  +- 
R35Y  +- 
R35P  - 
R35H  +- 
R35E  -+ 
R35Q +  
R35K +  
E36L +  
E36F +  
E36C +  
E36A +  
E36G +  
E36S +  
E36Y +  
E36P +- 
E36H +- 
E36Q +  
E36K +  
E36R +  
K37L +  
K37F +- 
K37C +  
K37A +  
K37G +  
K37S +- 
K37Y +- 
K37P  - 
K37H +  
K37E +  
K37Q +  
K37R +  
V38L  - 
V38F  - 
V38C  - 
V38A  - 
V38G  - 
V38S  - 
V38Y  - 
V38P  - 
V38H  - 
V38E  - 
V38Q  - 
V38K  - 
V38R  - 
E39L +  
E39F +  
E39C +  
E39A +  
E39G +  
E39S +  
E39Y +  
E39P  - 
E39H +  
E39Q +  
E39K +  
E39R +  
A40L +  
A40F +  
A40C +  
A40G +  
A40S +  
A40Y +  
A40P - 
A40H +  
A40E +  
A40Q +  
A40K +  
A40R +  
A41L  -+ 
A41F  - 
A41C  +- 
A41G  +- 
A41S +- 
A41Y  - 
A41P  - 
A41H  - 
A41E  - 
A41Q  - 
A41K  - 
A41R  -+ 
M42L +  
M42F +  
M42C +  
M42A +  
M42G  - 
M42S  - 
M42Y  - 
M42P  - 
M42H  - 
M42E  - 
M42Q  -+ 
M42K  - 
M42R  +- 
A43L +  
A43F +  
A43C +  
A43G +  
A43S +  
A43Y +  
A43P  - 
A43H + 
A43E + 
A43Q + 
A43K + 
A43R +  
E44L +  
E44F +  
E44C +  
E44A +  
E44G +  
E44S +  
E44Y +  
E44P  - 
E44H +  
E44Q +  
E44K +  
E44R +  
L45F  -+ 
L45C +  
L45A  - 
L45G  - 
L45S  - 
L45Y  -+ 
L45P  - 
L45H  +- 
L45E  - 
L45Q  - 
L45K  - 
L45R  -+ 
N46L +  
N46F +  
N46C +  
N46A +  
N46G +  
N46S +  
N46Y +  
N46P  - 
N46H +  
N46E +  
N46Q +  
N46K +  
N46R +  
Y47L  - 
Y47F  +- 
Y47C  - 
Y47A  - 
Y47G  - 
Y47S  - 
Y47P  - 
Y47H  - 
Y47E  - 
Y47Q  - 
Y47K  - 
Y47R  - 
I48L  -+ 
I48F  +- 
I48C  - 
I48A  - 
I48G  - 
I48S  - 
I48Y  - 
I48P  - 
I48H  -+ 
I48E  - 
I48Q  - 
I48K  - 
I48R  -+ 
P49L  - 
P49F  - 
P49C  - 
P49A  -+ 
P49G  - 
P49S  - 
P49Y  - 
P49H  - 
P49E +  
P49Q  -+ 
P49K  - 
P49R  - 
N50L  - 
N50F  -+ 
N50C +  
N50A  - 
N50G  - 
N50S +  
N50Y  -+ 
N50P  - 
N50H  -+ 
N50E  - 
N50Q  - 
N50K  - 
N50R  - 
R51L  +- 
R51F +  
R51C  -+ 
R51A  +- 
R51G  -+ 
R51S  -+ 
R51Y  +- 
R51P  -+ 
R51H  -+ 
R51E  - 
R51Q  -+ 
R51K +  
V52L -  
V52F +  
V52C -  
V52A -  
V52G +- 
V52S -  
V52Y +  
V52P +  
V52H -  
V52E  -+ 
V52Q +  
V52K  -+ 
V52R  -+ 
A53L  - 
A53F  - 
A53C  - 
A53G  - 
A53S  - 
A53Y  - 
A53P  - 
A53H  - 
A53E  - 
A53Q  - 
A53K  - 
A53R  - 
Q54L  - 
Q54F  - 
Q54C  - 
Q54A  +- 
Q54G  - 
Q54S  - 
Q54Y  - 
Q54P  - 
Q54H  - 
Q54E  - 
Q54K  - 
Q54R  - 
Q55L +- 
Q55F  +- 
Q55C  +- 
Q55A +  
Q55G  - 
Q55S  -+ 
Q55Y  +- 
Q55P  - 
Q55H +  
Q55E  -+ 
Q55K +  
Q55R +  
L56F  - 
L56C  - 
L56A  - 
L56G  - 
L56S  - 
L56Y  - 
L56P  - 
L56H  - 
L56E  - 
L56Q  - 
L56K  - 
L56R  - 
A57L  - 
A57F  - 
A57C  -+ 
A57G  +- 
A57S  -+ 
A57Y  - 
A57P  - 
A57H  - 
A57E  - 
A57Q  - 
A57K  - 
A57R  - 
G58L  - 
G58F  - 
G58C +- 
G58A  -+ 
G58S  -+ 
G58Y  - 
G58P  - 
G58H  - 
G58E  - 
G58Q  -+ 
G58K +- 
G58R +  
K59L +- 
K59F +- 
K59C +- 
K59A +- 
K59G +- 
K59S  -+ 
K59Y +- 
K59P  -+ 
K59H +- 
K59E  - 
K59Q  -+ 
K59R +  
Q60L +  
Q60F +  
Q60C +  
Q60A +- 
Q60G +  
Q60S +  
Q60Y +  
Q60P +- 
Q60H +  
Q60E +  
Q60K  -+ 
Q60R +  
S61L -  
S61F -  
S61C +  
S61A +  
S61G +  
S61Y -  
S61P +- 
S61H -+  
S61E +  
S61Q +  
S61K +  
S61R +  
L62F +  
L62C +  
L62A +  
L62G +  
L62S +  
L62Y +  
L62P +  
L62H +  
L62E +  
L62Q +  
L62K +  
L62R +  
L63F +  
L63C +  
L63A +  
L63G +  
L63S +  
L63Y +  
L63P +  
L63H +  
L63E +  
L63Q  -+ 
L63K +  
L63R  -+ 
I64L +  
I64F +  
I64C +  
I64A +  
I64G  - 
I64S  - 
I64Y +  
I64P  - 
I64H -  
I64E  - 
I64Q  - 
I64K  - 
I64R  - 
G65L  - 
G65F  - 
G65C  - 
G65A  - 
G65S  - 
G65Y  - 
G65P  - 
G65H  - 
G65E  - 
G65Q  - 
G65K  - 
G65R  - 
V66L  -+ 
V66F  - 
V66C +  
V66A +  
V66G  - 
V66S  - 
V66Y  - 
V66P  - 
V66H +  
V66E  - 
V66Q  - 
V66K  - 
V66R  - 
A67L +  
A67F  -+ 
A67C +  
A67G +  
A67S +  
A67Y  -+ 
A67P  -+ 
A67H  -+ 
A67E  -+ 
A67Q +  
A67K  - 
A67R  - 
T68L  -+ 
T68F  -+ 
T68C +  
T68A +  
T68G +  
T68S +  
T68Y  -+ 
T68P +- 
T68H +- 
T68E  - 
T68Q  -+ 
T68K  - 
T68R  - 
S69L  -+ 
S69F +  
S69C +  
S69A +  
S69G +  
S69Y +  
S69P +- 
S69H +- 
S69E  -+ 
S69Q  -+ 
S69K  -+ 
S69R  -+ 
S70L +  
S70F +  
S70C +  
S70A +- 
S70G +- 
S70Y +  
S70P  -+ 
S70H +  
S70E +- 
S70Q +  
S70K +  
S70R +  
L71F +  
L71C  - 
L71A  - 
L71G  - 
L71S  - 
L71Y  -+ 
L71P  -+ 
L71H  -+ 
L71E  -+ 
L71Q  -+ 
L71K  - 
L71R  - 
A72L +- 
A72F  - 
A72C +  
A72G +  
A72S +  
A72Y  -+ 
A72P  -+ 
A72H +  
A72E +  
A72Q +  
A72K +  
A72R +  
L73F +  
L73C +  
L73A  - 
L73G  - 
L73S  - 
L73Y +  
L73P  -+ 
L73H +  
L73E  - 
L73Q  - 
L73K  - 
L73R  - 
H74L +  
H74F  - 
H74C +  
H74A +  
H74G +  
H74S +  
H74Y  - 
H74P  - 
H74E +  
H74Q +  
H74K +  
H74R  -+ 
A75L  - 
A75F  - 
A75C  - 
A75G  - 
A75S  - 
A75Y  - 
A75P  - 
A75H  - 
A75E  - 
A75Q  - 
A75K  - 
A75R  - 
P76L +- 
P76F  -+ 
P76C +  
P76A +  
P76G  -+ 
P76S  -+ 
P76Y  - 
P76H  -+ 
P76E  -+ 
P76Q  -+ 
P76K  - 
P76R  -+ 
S77L  -+ 
S77F  -+ 
S77C  -+ 
S77A +  
S77G +  
S77Y  - 
S77P  -+ 
S77H  -+ 
S77E  -+ 
S77Q  -+ 
S77K  - 
S77R  -+ 
Q78L +- 
Q78F +  
Q78C  - 
Q78A  -+ 
Q78G  -+ 
Q78S +  
Q78Y +- 
Q78P  - 
Q78H  -+ 
Q78E  -+ 
Q78K  - 
Q78R  - 
I79L  -+ 
I79F  -+ 
I79C +  
I79A +  
I79G +- 
I79S +  
I79Y  -+ 
I79P  -+ 
I79H  - 
I79E +- 
I79Q +- 
I79K  -+ 
I79R  -+ 
V80L  -+
V80F  - 
V80C + 
V80A +  
V80G +  
V80S +  
V80Y  - 
V80P +- 
V80H  - 
V80E  - 
V80Q +  
V80K +- 
V80R  -+ 
A81L  -+ 
A81F +  
A81C +- 
A81G +- 
A81S +  
A81Y  -+ 
A81P +  
A81H +  
A81E  - 
A81Q +- 
A81K  -+ 
A81R +- 
A82L +- 
A82F +  
A82C +- 
A82G  -+ 
A82S  -+ 
A82Y +  
A82P  -+ 
A82H +  
A82E +- 
A82Q  - 
A82K +- 
A82R +  
I83L +  
I83F +  
I83C +  
I83A +  
I83G  - 
I83S  -+ 
I83Y  - 
I83P  - 
I83H  - 
I83E  +- 
I83Q  -+ 
I83K  - 
I83R  - 
K84L - 
K84F  - 
K84C  - 
K84A  - 
K84G  - 
K84S  - 
K84Y  - 
K84P -+ 
K84H  -+ 
K84E  -+ 
K84Q  -+ 
K84R +  
S85L +- 
S85F +  
S85C +  
S85A +  
S85G +  
S85Y +- 
S85P +- 
S85H +  
S85E +  
S85Q +  
S85K +- 
S85R +  
R86L  -+ 
R86F +  
R86C +  
R86A +  
R86G +  
R86S +  
R86Y +  
R86P +- 
R86H +  
R86E +  
R86Q +  
R86K +  
A87L  -+ 
A87F +- 
A87C +  
A87G +  
A87S +  
A87Y  - 
A87P  - 
A87H  - 
A87E  -+ 
A87Q  -+ 
A87K  - 
A87R  - 
D88L  - 
D88F  - 
D88C  - 
D88A  - 
D88G  - 
D88S  -  
D88Y  - 
D88P  - 
D88H  - 
D88E  - 
D88Q  - 
D88K  - 
D88R  - 
Q89L +  
Q89F  -+ 
Q89C +  
Q89A +  
Q89G +  
Q89S +  
Q89Y +  
Q89P  -+ 
Q89H +  
Q89E  -+ 
Q89K +  
Q89R +  
L90F +  
L90C +  
L90A +  
L90G +  
L90S +  
L90Y +  
L90P +- 
L90H +  
L90E +  
L90Q +  
L90K +  
L90R +  
G91L +  
G91F +  
G91C +  
G91A +  
G91S +  
G91Y +  
G91P +  
G91H +  
G91E +  
G91Q +  
G91K +  
G91R +  
A92L  -+ 
A92F  - 
A92C +  
A92G  -+ 
A92S +  
A92Y  - 
A92P +  
A92H +- 
A92E +- 
A92Q  -+ 
A92K  - 
A92R  - 
S93L  -+ 
S93F +  
S93C +  
S93A +  
S93G +  
S93Y +  
S93P +  
S93H +  
S93E +  
S93Q +  
S93K +  
S93R +  
V94L  -+ 
V94F  -+ 
V94C +  
V94A +  
V94G  -+ 
V94S  -+ 
V94Y  -+ 
V94P  -+ 
V94H +  
V94E +- 
V94Q +  
V94K  - 
V94R  -+ 
V95L +- 
V95F  - 
V95C  -+ 
V95A  - 
V95G  - 
V95S  -+ 
V95Y  - 
V95P  - 
V95H  - 
V95E  - 
V95Q  - 
V95K - 
V95R  - 
V96L  - 
V96F  - 
V96C  - 
V96A  -+ 
V96G  - 
V96S  -+ 
V96Y  -+ 
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S190A +  
S190G +  
S190Y +  
S190P +  
S190H +  
S190E +  
S190Q +  
S190K +  
S190R +  
S191L - 
S191F - 
S191C  - 
S191A  - 
S191G  - 
S191Y  - 
S191P  - 
S191H  - 
S191E  - 
S191Q - 
S191K  - 
S191R  - 
V192L  -+ 
V192F  - 
V192C +- 
V192A  - 
V192G +  
V192S  - 
V192Y  - 
V192P  -+ 
V192H  - 
V192E -+ 
V192Q  -+ 
V192K  -+ 
V192R  -+ 
S193L  - 
S193F  - 
S193C  - 
S193A  - 
S193G  - 
S193Y  - 
S193P  - 
S193H  - 
S193E  - 
S193Q  - 
S193K  - 
S193R  - 
A194L +  
A194F  - 
A194C  -+ 
A194G +  
A194S +  
A194Y  - 
A194P  - 
A194H +- 
A194E  - 
A194Q  - 
A194K  - 
A194R  - 
R195L  -+ 
R195F  -+ 
R195C +  
R195A +  
R195G  -+ 
R195S +  
R195Y  -+ 
R195P  - 
R195H  -+ 
R195E  -+ 
R195Q  -+ 
R195K +  
L196F +  
L196C +  
L196A +  
L196G +  
L196S +  
L196Y +  
L196P  -+ 
L196H +  
L196E +  
L196Q +  
L196K +  
L196R  - 
R197L  - 
R197F  - 
R197C  - 
R197A  - 
R197G  -+ 
R197S  - 
R197Y  - 
R197P  -+ 
R197H  - 
R197E  - 
R197Q  - 
R197K  - 
L198F +  
L198C +  
L198A +  
L198G +  
L198S +  
L198Y +  
L198P  -+ 
L198H +  
L198E +  
L198Q +  
L198K +  
L198R +  
A199L +  
A199F +  
A199C +  
A199G +  
A199S +  
A199Y +  
A199P +  
A199H +  
A199E +  
A199Q +  
A199K +  
A199R +  
G200L  - 
G200F  - 
G200C +  
G200A +  
G200S +  
G200Y -+ 
G200P  - 
G200H  -+ 
G200E  +- 
G200Q  +- 
G200K  +- 
G200R  - 
W201L  - 
W201F +  
W201C  - 
W201A  - 
W201G  - 
W201S  - 
W201Y +  
W201P  - 
W201H +  
W201E  - 
W201Q  - 
W201K  - 
W201R  - 
H202L +  
H202F +  
H202C +  
H202A +  
H202G +  
H202S +  
H202Y +  
H202P +- 
H202E +  
H202Q +  
H202K +  
H202R +  
K203L +  
K203F +  
K203C +  
K203A +  
K203G +  
K203S +  
K203Y +  
K203P  -+ 
K203H +  
K203E +  
K203Q +  
K203R +  
Y204L +  
Y204F +  
Y204C +  
Y204A +  
Y204G +  
Y204S +  
Y204P +  
Y204H +  
Y204E +  
Y204Q +  
Y204K +  
Y204R +  
L205F +  
L205C +  
L205A +  
L205G +  
L205S +  
L205Y  - 
L205P  - 
L205H +  
L205E -  
L205Q -  
L205K -  
L205R -  
T206L +  
T206F +  
T206C +  
T206A +  
T206G +  
T206S +  
T206Y +  
T206P +  
T206H +  
T206E +  
T206Q +  
T206K +  
T206R +  
R207L +  
R207F +  
R207C +  
R207A +  
R207G +  
R207S +  
R207Y +  
R207P +  
R207H +  
R207E +  
R207Q +  
R207K +  
N208L +  
N208F +  
N208C +  
N208A +  
N208G +  
N208S +  
N208Y +  
N208P +  
N208H +  
N208E +  
N208Q +  
N208K +  
N208R +  
Q209L +  
Q209F +  
Q209C +  
Q209A +  
Q209G +  
Q209S +  
Q209Y +  
Q209P +  
Q209H +  
Q209E +  
Q209K +  
Q209R +  
I210L +  
I210F +  
I210C +  
I210A +  
I210G +  
I210S +  
I210Y +  
I210P +- 
I210H +  
I210E +  
I210Q +  
I210K +  
I210R +  
Q211L +  
Q211F +  
Q211C +  
Q211A +  
Q211G +  
Q211S +  
Q211Y +  
Q211P +  
Q211H +  
Q211E +  
Q211K +  
Q211R +  
P212L +  
P212F + 
P212C + 
P212A + 
P212G +  
P212S +  
P212Y +  
P212H +  
P212E +  
P212Q +  
P212K +  
P212R +  
I213L +  
I213F +  
I213C +  
I213A +  
I213G +  
I213S +  
I213Y +  
I213P - 
I213H +  
I213E +  
I213Q +  
I213K  - 
I213R  - 
A214L +  
A214F +  
A214C +  
A214G +  
A214S +  
A214Y +  
A214P +  
A214H +  
A214E +  
A214Q +  
A214K +  
A214R +  
E215L +  
E215F +  
E215C +  
E215A +  
E215G +  
E215S +  
E215Y +  
E215P +  
E215H +  
E215Q +  
E215K +  
E215R + 
R216L +  
R216F +  
R216C +  
R216A +  
R216G +  
R216S +  
R216Y +  
R216P +  
R216H +  
R216E +  
R216Q +  
R216K +  
E217L +  
E217F +  
E217C +  
E217A +  
E217G +  
E217S +  
E217Y +  
E217P +  
E217H +  
E217Q +  
E217K +  
E217R +  
G218L +- 
G218F  - 
G218C +  
G218A +  
G218S +  
G218Y  - 
G218P  - 
G218H  - 
G218E  - 
G218Q  - 
G218K  - 
G218R  - 
D219L +  
D219F +  
D219C +  
D219A +  
D219G +  
D219S +  
D219Y +  
D219P -+ 
D219H +  
D219E +  
D219Q +  
D219K +  
D219R +  
W220L  - 
W220F  - 
W220C  - 
W220A  - 
W220G  - 
W220S  - 
W220Y  -+ 
W220P  -+ 
W220H  - 
W220E  - 
W220Q  - 
W220K  - 
W220R  - 
S221L +  
S221F +- 
S221C +  
S221A +  
S221G +  
S221Y  -+ 
S221P +- 
S221H +  
S221E +  
S221Q +  
S221K +  
S221R +  
A222L  - 
A222F  - 
A222C +  
A222G +  
A222S +  
A222Y  - 
A222P  -+ 
A222H  -+ 
A222E  - 
A222Q  - 
A222K  - 
A222R  - 
M223L +  
M223F +  
M223C +  
M223A +  
M223G +  
M223S +  
M223Y +  
M223P +- 
M223H +  
M223E +  
M223Q +  
M223K +  
M223R +  
S224L +  
S224F +  
S224C +  
S224A +  
S224G +  
S224Y +  
S224P +- 
S224H +  
S224E +  
S224Q +  
S224K +  
S224R +  
G225L  - 
G225F  - 
G225C  - 
G225A +  
G225S  +- 
G225Y  - 
G225P  - 
G225H  - 
G225E  - 
G225Q  - 
G225K  - 
G225R  - 
F226L +  
F226C +  
F226A +  
F226G  - 
F226S  - 
F226Y +  
F226P  - 
F226H +  
F226E +- 
F226Q +  
F226K -+ 
F226R +  
Q227L +  
Q227F +  
Q227C +  
Q227A +  
Q227G +  
Q227S +  
Q227Y +  
Q227P -+ 
Q227H + 
Q227E + 
Q227K +  
Q227R +  
Q228L +  
Q228F +  
Q228C +  
Q228A +  
Q228G +  
Q228S +  
Q228Y +  
Q228P +- 
Q228H +  
Q228E +  
Q228K +  
Q228R +  
T229L +  
T229F +  
T229C +  
T229A + 
T229G +  
T229S +  
T229Y  - 
T229P  - 
T229H  - 
T229E  +- 
T229Q +  
T229K  - 
T229R  - 
M230L +  
M230F +  
M230C +  
M230A +  
M230G +  
M230S +  
M230Y +  
M230P  - 
M230H +  
M230E +  
M230Q +  
M230K +  
M230R +  
Q231L +  
Q231F +  
Q231C +  
Q231A +  
Q231G +  
Q231S +  
Q231Y +  
Q231P +- 
Q231H +  
Q231E +  
Q231K +  
Q231R +  
M232L +  
M232F +  
M232C +  
M232A +  
M232G +
M232S -  
M232Y +  
M232P  - 
M232H +  
M232E +  
M232Q +  
M232K  - 
M232R  - 
L233F +  
L233C +  
L233A +  
L233G  - 
L233S  - 
L233Y +  
L233P  - 
L233H +  
L233E  - 
L233Q  +- 
L233K  - 
L233R  +- 
N234L +  
N234F +  
N234C +  
N234A +  
N234G +  
N234S +  
N234Y +  
N234P +  
N234H +  
N234E +  
N234Q +  
N234K +  
N234R +  
E235L +  
E235F +  
E235C +  
E235A +  
E235G +  
E235S +  
E235Y +  
E235P +-  
E235H +  
E235Q +  
E235K +  
E235R +  
G236L +  
G236F +  
G236C +  
G236A +  
G236S +  
G236Y +  
G236P +  
G236H +  
G236E +  
G236Q +  
G236K +  
G236R +  
I237L +  
I237F +  
I237C +  
I237A +  
I237G +  
I237S +  
I237Y +  
I237P +  
I237H +  
I237E +  
I237Q +  
I237K +  
I237R +  
V238L +  
V238F +  
V238C +  
V238A +  
V238G +  
V238S +  
V238Y + 
V238P + 
V238H +  
V238E +  
V238Q +  
V238K +  
V238R +  
P239L +  
P239F +  
P239C +  
P239A +  
P239G +  
P239S +  
P239Y +  
P239H +  
P239E +-  
P239Q +  
P239K  - 
P239R  - 
T240L +  
T240F +  
T240C +  
T240A +  
T240G +  
T240S +  
T240Y +  
T240P +  
T240H +  
T240E +  
T240Q +  
T240K +  
T240R +  
A241L  - 
A241F  - 
A241C +  
A241G +  
A241S +  
A241Y  - 
A241P  - 
A241H  - 
A241E  - 
A241Q  - 
A241K  - 
A241R  - 
M242L +  
M242F +  
M242C +  
M242A +  
M242G  - 
M242S  - 
M242Y +  
M242P  - 
M242H  - 
M242E  - 
M242Q +  
M242K  - 
M242R  - 
L243F +- 
L243C +  
L243A +- 
L243G  - 
L243S  - 
L243Y  - 
L243P  - 
L243H  - 
L243E  - 
L243Q  - 
L243K  - 
L243R  - 
V244L +  
V244F +  
V244C +  
V244A +  
V244G +  
V244S +  
V244Y  - 
V244P  - 
V244H +- 
V244E  - 
V244Q  - 
V244K  - 
V244R  - 
A245L  - 
A245F  - 
A245C +  
A245G +  
A245S +  
A245Y  - 
A245P  - 
A245H  - 
A245E  - 
A245Q  - 
A245K  - 
A245R  - 
N246L  -+ 
N246F  - 
N246C +  
N246A  -+ 
N246G  - 
N246S  -+ 
N246Y  -+ 
N246P  - 
N246H  - 
N246E  - 
N246Q  - 
N246K  -+ 
N246R  - 
D247L  - 
D247F  - 
D247C  - 
D247A  - 
D247G  - 
D247S  - 
D247Y  - 
D247P  - 
D247H  - 
D247E  - 
D247Q  - 
D247K  - 
D247R  - 
Q248L  - 
Q248F  - 
Q248C  - 
Q248A  - 
Q248G  - 
Q248S  - 
Q248Y  - 
Q248P  - 
Q248H  - 
Q248E +  
Q248K  - 
Q248R  - 
M249L +  
M249F  - 
M249C  - 
M249A  +- 
M249G  - 
M249S +  
M249Y  - 
M249P  - 
M249H  - 
M249E +  
M249Q  -+ 
M249K  - 
M249R  - 
A250L  - 
A250F  - 
A250C +  
A250G +  
A250S +  
A250Y  - 
A250P  - 
A250H  - 
A250E  - 
A250Q  - 
A250K  - 
A250R  - 
L251F  - 
L251C +  
L251A +  
L251G +- 
L251S +- 
L251Y  - 
L251P  - 
L251H  - 
L251E  - 
L251Q  +- 
L251K  - 
L251R  - 
G252L  - 
G252F  - 
G252C  - 
G252A  - 
G252S +  
G252Y  - 
G252P  - 
G252H  - 
G252E  - 
G252Q  - 
G252K  - 
G252R  - 
A253L +  
A253F  - 
A253C +  
A253G +  
A253S +  
A253Y  - 
A253P  - 
A253H  - 
A253E  - 
A253Q  - 
A253K  - 
A253R  - 
M254L +  
M254F +  
M254C +  
M254A +  
M254G +  
M254S +  
M254Y +- 
M254P - 
M254H +  
M254E  - 
M254Q +  
M254K  - 
M254R  - 
R255L +  
R255F +- 
R255C +- 
R255A +- 
R255G +  
R255S +- 
R255Y + 
R255P  - 
R255H +  
R255E +- 
R255Q +  
R255K +- 
A256L +  
A256F +  
A256C +  
A256G +  
A256S +  
A256Y +  
A256P - 
A256H +  
A256E -  
A256Q +- 
A256K  - 
A256R  - 
I257L +  
I257F +  
I257C +  
I257A +  
I257G  -+ 
I257S +- 
I257Y +  
I257P  - 
I257H  - 
I257E  - 
I257Q  - 
I257K  - 
I257R  - 
T258L +  
T258F +  
T258C +  
T258A +  
T258G +  
T258S +  
T258Y +  
T258P +  
T258H +  
T258E +  
T258Q +  
T258K +  
T258R +  
E259L +  
E259F  - 
E259C  -+ 
E259A +- 
E259G +  
E259S +- 
E259Y +- 
E259P  - 
E259H + 
E259Q +  
E259K  - 
E259R  - 
S260L +  
S260F +  
S260C +  
S260A +  
S260G +  
S260Y +  
S260P +  
S260H +  
S260E +  
S260Q +  
S260K +  
S260R +  
G261L +  
G261F +  
G261C +  
G261A +  
G261S +  
G261Y +  
G261P +  
G261H +  
G261E +  
G261Q +  
G261K +  
G261R +  
L262F +  
L262C +  
L262A +  
L262G +  
L262S +  
L262Y +  
L262P +- 
L262H + 
L262E +  
L262Q +  
L262K +  
L262R +  
R263L -  
R263F -  
R263C  - 
R263A +  
R263G +  
R263S +  
R263Y  - 
R263P - 
R263H +  
R263E +  
R263Q +  
R263K  - 
V264L +  
V264F  - 
V264C +  
V264A +  
V264G +  
V264S +  
V264Y  - 
V264P +  
V264H  - 
V264E  - 
V264Q  -+ 
V264K  - 
V264R  - 
G265L +- 
G265F - 
G265C +  
G265A +  
G265S +  
G265Y  -+ 
G265P +  
G265H  -+ 
G265E +  
G265Q +  
G265K  - 
G265R +  
A266L +  
A266F +  
A266C +  
A266G +  
A266S +  
A266Y +  
A266P +  
A266H +  
A266E +  
A266Q +  
A266K +  
A266R +  
D267L  - 
D267F  -+ 
D267C +  
D267A +  
D267G +  
D267S +  
D267Y  -+ 
D267P  -+ 
D267H +  
D267E +  
D267Q +  
D267K - 
D267R +  
I268L  - 
I268F  - 
I268C  - 
I268A  - 
I268G  - 
I268S  - 
I268Y  - 
I268P  - 
I268H  - 
I268E  - 
I268Q  - 
I268K  - 
I268R  - 
S269L  - 
S269F  - 
S269C +  
S269A +  
S269G +  
S269Y  - 
S269P  - 
S269H +  
S269E +- 
S269Q +  
S269K  - 
S269R  - 
V270L +  
V270F +  
V270C +  
V270A +  
V270G  - 
V270S  - 
V270Y  - 
V270P  - 
V270H  - 
V270E  - 
V270Q  - 
V270K  - 
V270R  - 
V271L +  
V271F +  
V271C +  
V271A +  
V271G  - 
V271S +- 
V271Y  - 
V271P  - 
V271H -  
V271E  - 
V271Q +  
V271K  - 
V271R  - 
G272L  - 
G272F  - 
G272C  - 
G272A +  
G272S  - 
G272Y  - 
G272P  - 
G272H  - 
G272E  - 
G272Q  - 
G272K  - 
G272R  - 
Y273L + 
Y273F  - 
Y273C  - 
Y273A  - 
Y273G  - 
Y273S  - 
Y273P  - 
Y273H  -+ 
Y273E  - 
Y273Q  - 
Y273K  - 
Y273R  - 
D274L  - 
D274F  - 
D274C  - 
D274A  - 
D274G  - 
D274S  - 
D274Y  - 
D274P  - 
D274H  - 
D274E +  
D274Q  - 
D274K  - 
D274R  - 
D275L  - 
D275F  - 
D275C  - 
D275A  - 
D275G  - 
D275S  - 
D275Y  - 
D275P  - 
D275H  - 
D275E  - 
D275Q  - 
D275K  -+ 
D275R  - 
T276L  -+ 
T276F  - 
T276C  - 
T276A  - 
T276G  - 
T276S  - 
T276Y  - 
T276P  - 
T276H  - 
T276E  - 
T276Q  - 
T276K  - 
T276R  - 
E277L +  
E277F +  
E277C +  
E277A +  
E277G +  
E277S +  
E277Y +  
E277P +  
E277H +  
E277Q +  
E277K +  
E277R +  
D278L  - 
D278F  -+ 
D278C  -+ 
D278A  - 
D278G +  
D278S +  
D278Y +  
D278P +  
D278H +  
D278E  - 
D278Q +  
D278K  - 
D278R  - 
S279L  - 
S279F  - 
S279C  -+ 
S279A  -+ 
S279G  - 
S279Y  - 
S279P  - 
S279H  - 
S279E  - 
S279Q  - 
S279K  - 
S279R  - 
S280L +  
S280F +  
S280C +  
S280A +  
S280G +  
S280Y + 
S280P +-  
S280H +  
S280E +  
S280Q +  
S280K +  
S280R +  
C281L +  
C281F +  
C281A +  
C281G  -+ 
C281S +  
C281Y +  
C281P  - 
C281H +  
C281E +  
C281Q +  
C281K  - 
C281R +  
Y282L +  
Y282F +  
Y282C  - 
Y282A  - 
Y282G  - 
Y282S  - 
Y282P  - 
Y282H  - 
Y282E  - 
Y282Q  - 
Y282K  - 
Y282R  - 
I283L +  
I283F +  
I283C +  
I283A +  
I283G +  
I283S +  
I283Y +  
I283P  -+ 
I283H +  
I283E +- 
I283Q +  
I283K  - 
I283R +  
P284L +  
P284F +  
P284C  - 
P284A  -+ 
P284G  - 
P284S  - 
P284Y +  
P284H +  
P284E +- 
P284Q +  
P284K  - 
P284R +- 
P285L  - 
P285F  - 
P285C +- 
P285A +  
P285G +  
P285S +  
P285Y  - 
P285H  - 
P285E +  
P285Q +  
P285K  - 
P285R +- 
L286F  - 
L286C +- 
L286A +- 
L286G  - 
L286S  - 
L286Y  - 
L286P  - 
L286H  - 
L286E  - 
L286Q  - 
L286K  - 
L286R  - 
T287L  - 
T287F  - 
T287C +  
T287A +  
T287G  - 
T287S +  
T287Y  - 
T287P  - 
T287H  - 
T287E  - 
T287Q  - 
T287K  - 
T287R  - 
T288L  - 
T288F  - 
T288C +  
T288A +  
T288G +  
T288S +  
T288Y  - 
T288P  - 
T288H  - 
T288E  - 
T288Q  - 
T288K  - 
T288R  - 
I289L +  
I289F  -+ 
I289C +  
I289A  - 
I289G  - 
I289S  - 
I289Y  - 
I289P  - 
I289H  - 
I289E  - 
I289Q  - 
I289K  - 
I289R  - 
K290L +  
K290F +  
K290C +  
K290A +  
K290G +  
K290S +  
K290Y +  
K290P  -+ 
K290H +  
K290E +  
K290Q +  
K290R +  
Q291L +  
Q291F +  
Q291C +  
Q291A +  
Q291G +- 
Q291S +  
Q291Y +- 
Q291P +- 
Q291H +  
Q291E -+  
Q291K +- 
Q291R -+  
D292L  - 
D292F  - 
D292C +  
D292A +  
D292G +- 
D292S + 
D292Y  - 
D292P +  
D292H +  
D292E  -+ 
D292Q  -+ 
D292K  -+ 
D292R +- 
F293L  -+
F293C  -
F293A  -+
F293G  -
F293S + 
F293Y  -
F293P  -
F293H  -
F293E  -
F293Q  -
F293K  -
F293R  -
R294L + 
R294F +
R294C +
R294A +
R294G + 
R294S + 
R294Y + 
R294P + 
R294H + 
R294E + 
R294Q + 
R294K + 
L295F +
L295C + 
L295A + 
L295G  -+
L295S + 
L295Y +-
L295P + 
L295H +
L295E + 
L295Q + 
L295K + 
L295R + 
L296F - 
L296C +
L296A + 
L296G + 
L296S + 
L296Y - 
L296P -+
L296H -+ 
L296E + 
L296Q + 
L296K -
L296R  -
G297L  -
G297F  -
G297C  -
G297A +-
G297S +-
G297Y  -
G297P  -
G297H  -
G297E  -
G297Q  -
G297K  -
G297R  -
Q298L + 
Q298F  -+
Q298C + 
Q298A + 
Q298G + 
Q298S + 
Q298Y  -+
Q298P + 
Q298H +
Q298E +
Q298K + 
Q298R + 
T299L + 
T299F +
T299C + 
T299A + 
T299G + 
T299S + 
T299Y + 
T299P  -+
T299H + 
T299E + 
T299Q + 
T299K + 
T299R + 
S300L + 
S300F  -+
S300C + 
S300A + 
S300G + 
S300Y  -
S300P  -
S300H  -
S300E  -
S300Q  -
S300K  -
S300R  -
V301L + 
V301F +-
V301C + 
V301A + 
V301G -+
V301S -
V301Y +-
V301P  -
V301H + 
V301E  -
V301Q  -
V301K  -
V301R  -
D302L + 
D302F +
D302C + 
D302A + 
D302G + 
D302S + 
D302Y + 
D302P + 
D302H + 
D302E + 
D302Q + 
D302K + 
D302R + 
R303L + 
R303F +
R303C + 
R303A + 
R303G + 
R303S + 
R303Y + 
R303P +-
R303H + 
R303E + 
R303Q + 
R303K + 
L304F + 
L304C + 
L304A  -+
L304G +-
L304S  -+
L304Y + 
L304P  -
L304H  -+
L304E + 
L304Q  -+
L304K  -
L304R  -
L305F +
L305C + 
L305A + 
L305G +-
L305S +-
L305Y + 
L305P + 
L305H + 
L305E + 
L305Q + 
L305K + 
L305R + 
Q306L + 
Q306F + 
Q306C + 
Q306A + 
Q306G + 
Q306S + 
Q306Y + 
Q306P + 
Q306H + 
Q306E + 
Q306K + 
Q306R + 
L307F + 
L307C + 
L307A + 
L307G + 
L307S +
L307Y + 
L307P + 
L307H + 
L307E +
L307Q + 
L307K + 
L307R +
S308L + 
S308F + 
S308C +
S308A + 
S308G + 
S308Y +
S308P + 
S308H + 
S308E + 
S308Q + 
S308K + 
S308R + 
Q309L + 
Q309F +
Q309C + 
Q309A + 
Q309G +
Q309S + 
Q309Y + 
Q309P +
Q309H +
Q309E + 
Q309K + 
Q309R + 
G310L + 
G310F + 
G310C + 
G310A + 
G310S + 
G310Y + 
G310P + 
G310H + 
G310E + 
G310Q + 
G310K + 
G310R +
Q311L + 
Q311F + 
Q311C + 
Q311A +
Q311G +
Q311S + 
Q311Y + 
Q311P + 
Q311H + 
Q311E + 
Q311K + 
Q311R +
A312L + 
A312F +
A312C + 
A312G + 
A312S + 
A312Y + 
A312P + 
A312H +
A312E +
A312Q + 
A312K + 
A312R + 
V313L + 
V313F + 
V313C + 
V313A + 
V313G + 
V313S + 
V313Y + 
V313P +
V313H + 
V313E + 
V313Q + 
V313K + 
V313R +
K314L + 
K314F + 
K314C + 
K314A +
K314G + 
K314S + 
K314Y + 
K314P + 
K314H + 
K314E + 
K314Q + 
K314R + 
G315L + 
G315F + 
G315C + 
G315A +
G315S + 
G315Y + 
G315P + 
G315H + 
G315E + 
G315Q +
G315K + 
G315R + 
N316L + 
N316F +
N316C + 
N316A + 
N316G + 
N316S + 
N316Y +
N316P +
N316H + 
N316E + 
N316Q + 
N316K + 
N316R + 
Q317L + 
Q317F +
Q317C + 
Q317A + 
Q317G +
Q317S + 
Q317Y + 
Q317P + 
Q317H + 
Q317E + 
Q317K + 
Q317R + 
L318F + 
L318C + 
L318A + 
L318G +
L318S +
L318Y + 
L318P + 
L318H + 
L318E + 
L318Q +
L318K + 
L318R + 
L319F  - 
L319C +  
L319A +- 
L319G  -+ 
L319S  -+ 
L319Y  -+ 
L319P  - 
L319H  -+ 
L319E  -+ 
L319Q  -+ 
L319K  -+ 
L319R  -+ 
P320L +  
P320F +  
P320C +  
P320A +  
P320G +  
P320S +  
P320Y +  
P320H +  
P320E +  
P320Q +  
P320K +  
P320R +  
V321L +  
V321F -+ 
V321C +  
V321A +  
V321G +  
V321S +  
V321Y  - 
V321P +  
V321H  -+ 
V321E  -+ 
V321Q +  
V321K  - 
V321R  - 
S322L +  
S322F +  
S322C +  
S322A +  
S322G +  
S322Y +  
S322P +  
S322H +  
S322E +  
S322Q +  
S322K +  
S322R +  
L323F +  
L323C +  
L323A +  
L323G  - 
L323S  - 
L323Y +  
L323P +- 
L323H +- 
L323E  -+ 
L323Q  - 
L323K  - 
L323R +- 
V324L +  
V324F +  
V324C +  
V324A +  
V324G +  
V324S +  
V324Y +  
V324P +- 
V324H +  
V324E +  
V324Q +  
V324K +  
V324R +  
K325L +  
K325F +  
K325C +  
K325A +  
K325G +  
K325S +  
K325Y +  
K325P +  
K325H +  
K325E +  
K325Q +  
K325R +  
R326L  - 
R326F  - 
R326C  - 
R326A  - 
R326G  - 
R326S  - 
R326Y  - 
R326P  - 
R326H  - 
R326E  - 
R326Q  - 
R326K +- 
K327L +  
K327F +  
K327C +  
K327A +  
K327G +  
K327S +  
K327Y +  
K327P +  
K327H +  
K327E +  
K327Q +  
K327R +  
T328L  - 
T328F  - 
T328C  - 
T328A +- 
T328G +  
T328S +  
T328Y  - 
T328P  - 
T328H  - 
T328E  - 
T328Q  - 
T328K  - 
T328R  - 
T329L +- 
T329F +  
T329C +  
T329A  - 
T329G +  
T329S +  
T329Y +  
T329P +  
T329H  -+ 
T329E  - 
T329Q  -+ 
T329K  - 
T329R +