`PROTEINS OF
`IMMUNOLOGICAL
`INTEREST
`FOURTH EDITION
`
`Tabulation and Analysis of
`
`Amino Acid and Nucleic Acid Sequences of
`
`
`
`Precursors, V-Regions, C-Regions, J-Chain,
`T-Cell Receptor for Antigen, T-Cell Surface Antigens,
`
`f32-Microglobulins, Major Histocompatibility Antigens,
`
`
`Thy-1, Complement, C-Reactive Protein, Thymopoietin,
`
`Post-gamma Globulin, and a2-Macroglobulin
`
`1987
`
`
`Elvin A. Kabat*, Tai Te Wu t, Margaret Reid-Miller :f:,
`Harold M. Perry :f:, and Kay S. Gottesman :f:
`
`• Depts. of Microbiology, Genetics and Development, and Neurology, Cancer Center/
`Institute of Cancer Research, College of Physicians and Surgeons, Columbia University, New
`York, NY 10032 and the National Institute of Allergy and Infectious Diseases, Bethesda, MD
`20892.
`tDepts. of Biochemistry, Molecular Biology, and Cell Biology, and Engineering Sciences and
`Applied Mathematics and Biomedical Engineering, Northwestern University, Evanston, IL 60201
`and the Cancer Center, Northwestern University Medical School, Chicago, IL 60611
`t Bolt Beranek and Newman Inc., Cambridge, MA 02238
`The collection and maintenance of this data ba�e is sponsored through Contract N01-RR-8-2158
`by the following components of the National Institutes of Health, Bethesda, MD 20892:
`
`Division of Research Resources
`National Cancer Institute
`National Institute of Allergy and Infectious Diseases
`National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases
`National Institute of General Medical Sciences
`
`U.S. DEPARTMENT OF HEALTH
`AND HUMAN SERVICES
`
`Public Health Service
`
`National Institutes of Health
`
`(1987)
`
`1 of 21
`
`BI Exhibit 1052
`
`
`
`Our listing of sequences will be kept up to date. Investigators are invited to send additional
`sequence data when accepted for publication. Send two copies of the manuscript together with a
`letter of acceptance from a journal to:
`
`Dr. E.A. Kabat
`National Institutes of Health
`Building 8, Room 126
`9000 Rockville Pike
`Bethesda, Maryland 20892
`It would be extremely helpful if you can send us your sequence data on magnetic tapes or floppy
`diskettes or a clean copy of the sequences. The file formats should be such that they can be read
`by a generic word processor.
`
`When published, three reprints should be provided.
`
`If any published sequences have been overlooked or if any errors are found, please bring them to
`our attention.
`
`2 of 21
`
`BI Exhibit 1052
`
`
`
`iii
`TABLE OF CONTENTS
`
`INTAOOVCTION
`
`REFERENCES TO INTRODUCTION
`
`SIGNAL SEQUENCES
`
`· · · · · · · · · . .
`
`. . . . . . . . ... . . • . . . . . . • . . • . . . . . . • . . • . . . . . . .. . • . . • • . . .. .. . ... , ....... xxb.
`
`. . . . . . .
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . • · · · · ·· · · · · · '
`
`SIGNAL PEPTIDES OF KAPPA LIGHT CHAINS .
`
`SIGNAL PEPTIDES OF LAMBDA LIGHT CHAINS . . •
`
`•
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .
`
`. • . • • • . . . .
`
`. . . . . . . . . . . . • •
`
`• • . • • •
`
`SIGNAL PEPTIDES OF HEAVY CHAINS.
`SIGNAL PEPTIDES OF BETA-2-MICROGLOBULINS.
`SIGNAL PEPTIDES OF MAJOR HISTOCOMl'A TIBILITY ANTIGENS C� I
`
`SIGNAL PEPTIOES OF I REGION ANTIGENS CLASS II
`
`.... .. . . . . . 1
`• . .. .
`• . .. . ... .
`... . .
`. . 8
`• .. . . .. . .. . .. . ... ... . . . . .. . . . . . . .. .. .. . . . . ... 11
`................................................ 19
`• .. . . . . ..
`. .. .. . . . . 21
`• . . . .... 24
`
`. . . . . . . . . . . . . . • • • •
`
`• •• • • • • • • • • •
`
`• • • . •
`
`•
`
`• . .. .. . ..... . . .. . . . 28
`.
`................ 30
`... ... . . . .. . .. . ... . .. . ... . . . 36
`. . . . . . . . .. .. .. ... .. . .. ... . . . .. . .. . . 38
`
`. . •
`SIGNAL PEPTIDES OF COMPLEMENT
`SIGNAL PEPTIDES OF T-LYMPHOCYTE RECEPTOR FOR ANTIGEN
`SIGNAL PEPTIDES OF T·CELL SURFACE ANTIGENS . . . . • • . • • .
`
`•
`
`. • • • • • • • • • • • • • • • • . •
`
`• • • • • • • • •• •
`
`. . . ... . .
`.. . .. . . .
`• .. . .. . . . .. .
`
`SIGNAL PEPTIDES O F OTHER PROTEINS • .
`VARIABLE REGION LIGHT CHAIN SEQUENCES
`
`. 50
`. . . . . . . . • . . . • .. • . . . . . . . . . • • . • • . .. . . . . .. 53
`. • . . • . . . . • . . . . . • . . . • . • • • • • . . • • . . . . .. 63
`• 66
`• .. • • • • • , • , ................................... 69
`
`• • • • • • . • . . . . • .
`
`• •
`
`• . • • • . . • . • . . • • • • • . . • • • • • • • . • . • • • • • • . . . • • . . • • • • • • • • .. • . . . . . . .. . . • • . • 41
`HUMAN KAPPA LIGHT CHAINS SUBGROUP I
`.. . . . • .. • . . • • • • . . • • • • • • • • . . • • • • • • • • . • . . • . . . • . . • . . . . . . . . . • . . . •
`HUMAN KAPPA LIGHT CHAINS SUBGROUP II
`• • • . . . . •
`HUMAN KAPPA LIGHT CHAINS SUBGROUP Ill. . • • • • . • . . • . . . . • • • • • •
`. . . . • • . • . • • • • • • . . • • • • • . . • • • • • • . • . . • • • . . • • • • • . • • . • • • • • • . . • . • • • • . . • . • 60
`HUMAN KAPPA LIGHT CHAINS SUBGROUP IV •
`.. • . . . . • . . .
`HUMAN LAMBDA LIGHT CHAINS SUBGROUP I
`.. . . • • . . • • . . . . . . • • .. .. . . . . • • . • . . • • . . . . • . . • . . . . . . . . . . . • . . . . •
`HUMAN LAMBDA LIGHT CHAINS SUBGROUP 11.
`• • • . . • • .. ..
`HUMAN LAMBDA LIGHT CHAINS SUBGROUP 111
`• . . • • . . • . . . . . . . , • . . . . • • • . . .. . . • . . • . . • . . • . . ..
`• . • . • . •
`. 72
`HUMAN LAMBDA LIGHT CHAINS SUBGROUP IV.
`. . . . . . . . . . . . . , • . • • . • . . • . • • . . . . • . . . . . . • . • • • . . • • • • • . . • • • • . • .
`. 74
`HUMAN LAMBDA LIGHT CHAINS SUBGROUP V .
`HUMAN LAMBDA LIGHT CHAINS SUBGROUP VI. . . • • • • . • . • • . • • • • • . • • . . • • . • . . • . • • • • • • . . . . • • • . • • . . • . • • • • • • . •
`• • . . 76
`• . .. . . . . . ... . . . . . . . . . . . , • . •
`
`MOUSE KAPPA LIGHT CHAINS I • • . • . .. . . . .. . . . • . . . . . . • • • . . • • • • .
`
`• •
`
`. 78
`
`MOUSE KAPPA LIGHT CHAINS 11.. • . . • • • . • . • • • • • . • • • • . • • • . . • . • • . • . • • . . . . • . . .. • • • • • • . • • • • • • . • . • . • . . • . • • . • . • • • • .. • . • • 85
`
`. • . . . . . . . . • , • . . • . • . . . . • . . . . • . . .. . . . . . . . .. • •
`MOUSE KAPPA LIGHT CHAINS Ill . . . . • . . . . . . . . . . . . . .. . . • .. .
`95
`MOUSE KAPPA LIGHT CHAINS IV... . • .. • • • . . . . • . • . . • . . • . • • . . • . . • • • . • • . •
`. . 102
`. . • . • • . . • •
`105
`MOUSE KAPPA LIGHT CHAINS V . . . . . . . • . • . . • • • • • • . • • . • • • . . • • . . . • . . . . • • • .. • •
`. .. . . . . • . . . . • • . • . . • . .. . • • .. • • • • • . • • . . • • . . • . • • • • . • .. • . . • • • . . . • •
`117
`MOUSE KAPPA LIGHT CHAINS VI
`•
`MOUSE KAPPA LIGHT CHAINS VII. • ..
`. . . • . .. . . . . . . . , .. .. • • . . • . . • . . • .. • . . , . . . . , .. • . . . . . . . . . . • ..
`124
`• • . • • . . . . . . . .. • • • . . • • • • • . . • • .. .. ... .. ....... 126
`MOUSE KAPPA LIGHT CHAINS MISCELLANEOUS
`MOUSE LAMBDA LIGHT CHAINS. • • • . . . . .. .. . .. . . . • • • .. • • .. • • .. • • . . . . • • . . • • • . • . . .. • • • .. • .. .. • . . • . • .. .. • . . . . • . . • . . • 129
`. . . . . • . .. • . . • . . . . . . . . . • . . .. . . . . . • . .• . . . . . . . . . . . . . � . . 134
`RAT KAPPA LIGHT �AINS
`RABBIT KAPPA LIGHT CHAINS . . . •
`... .. .................................. ................................... 136
`..
`................. ..... ................................................ 149
`RABBIT LAMBDA LIGHT �AINS
`
`•
`
`• • •
`
`
`
`• • • • • . • • • • • •
`
`. . •
`
`• •
`
`. ..
`
`. • • . . . . . . • . . ..
`
`OTHE.R KAPPA LIGHT CHAINS
`OTHER LAMBDA LIGHT CHAINS
`MISCELLANEOUS LIGHT CHAINS
`
`.. 151
`.. .. ..................................... .. .. .......................
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
`. . .. . . . .. .. . .. . . . . . . . . . . . . . .
`. .. .. .. . . . . . . . . . .. .. . . . .. . . . .. . . . .. . .. . . . . . . . . 157
`
`VARIABLE REGION HEAVY CHAIN SEQUENCES
`
`• • • . . • • . . . . • • . . • . . . . • • • • . .
`
`• • • •
`
`. .. .. .. • .. • .. .. . . • . . • . . . . • . . • . . .. • . . . • . . • .. • . . .. . . . . • .. . . • .. • .. .. . . • . . • • 160
`• • • • • • • • • • . . • .. .. .. . . • . . • . . . . • • •
`• • • .. • • .. • • . • • . • . . • • • .. . . • . • ... 164
`• • . . • • • • • • . . • . . . . . . . • .. 167
`.. ............................. 176
`• • . . . . . . . .. .. ... ....... 1 81
`• . . ....... . . .. . . . . . . . . . . 186
`• • .. • • .. . • • • • . . . • . . • . • • . • • . • • 192
`
`. . • . . • • • • • . .
`
`•
`
`• •
`
`•
`
`HUMAN HEAVY CHAINS SUBGROUP I
`HUMAN HEAVY CHAINS SUBGROUP II .
`HUMAN HEAVY CHAINS SUBGROUP 111
`MOUSE HEAVY CHAINS SUBGROUP I (A) • • .. . . .. . . • • • • . • • . • . • • • .. • .. . . • • . . . . •
`MOUSE HEAVY CHAINS SUBGROUP I (B) • • . . • • • . . . . • • • • . • • • •
`MOUSE HEAVY CHAINS SUBGROUP 11 (A). . . . . • • • • • • . . • • • . . • • • •
`MOUSE HEAVY CHAINS SUBGROUP 11 (B) . ..... ... , . .. . . . . • .. • . •
`MOUSE HEAVY CHAINS SUBGROUP 11 (C). . . . . . • . . . . • . • . . . . . • . . . • • • . • . . .. • • • • • . • . . . • , . • . . . . . . . • . . . . • .. .. . .. . . .. 200
`• • . • • . . . . . .. . .. . . . . . . . . . . . . .. . . . .. . 204
`MOUSE HEAVY CHAINS SUBGROUP Ill (A) . . • .. .. .. . • • • . . • . . . • .. • . . . . . .. . , . . • . .
`MOUSEHEAVYCHAINSSUBGROUP lll(B) ............................. ............................................ 214
`MOUSE HEAVY CHAINS SUBGROUP Ill (D) ....... . . . . . . . .. . . . . . . . . . , • . • .. . . • • . • • . • . • . • . • • . . . . • . . • • • . • • . . . • . . • • .. 222
`MOUSE HEAVY CHAINS SUBGROUP 111 (C) ... . . . . . . .. . . . . . . . . .. . . . . . . . . . .. . . . . . . . . . . . . . , • • • . . . . . . . .. .. . ... .. ... . . . . 219
`• • • . . . . • . . . . • • 232
`.. .......... 235
`
`MOUSE HEAVY CHAINS SUBGROUP V (A) ............................................................................ 226
`MOUSE HEAVY CHAINS SUBGROUP V(B) . .. . . ... ... .. . .. . . .. . .. . . . ... .... , • , • . • • • , • . . . . . • . . • • • • . • •
`. . • . . . . • . . . . . . . • • . . • • . • • . •
`MOUSE HEAVY CHAINS SUBGROUP MISCELLANEOUS • .. . .
`• . .
`........................................... 241
`
`RAT HEAVY CHAINS ..
`
`RABBIT HEAVY CHAINS
`• • • . • . • • • • . . . . • . • . • • 248
`• . . . . . , • . • . . • • • • . • . . • . • • • . • • . • . • • . .. • •
`GUINEA PIG HEAVY CHAINS.
`.. . • . . • . • . . • •
`CAT HEAVY CHAINS................. • . . .. • • . . . . . • .. • . . . . . . • . • . . . . . • . . • . • • • . . . • • • • • . • • . • • • . . • • • • . . . . • • • . • • . .
`250
`. . .. . . . .. • . • . . • . . • • , . . • . . . • • • . . • . • . . • . • • • • . • • . • . • • • . . • • • • . . . . • . • • . 252
`• . . . . . • • • • . .. .. • • • . • . . • • . • . • . . • • • • • •
`
`DOG HEAVY CHAINS • . . . . • .
`
`CHICKEN HEAVY CHAINS
`•
`SHARK HEAVY CHAINS
`MISCELLANEOUS HEAVY CHAINS
`
`•
`T ·LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (ALPHA CHAINS)
`T ·L YMPHOCVTE RECEPTOR FOR ANTIGEN VARIABLE REGION (BET A CHAINS SUBGROUP I)
`T ·LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (BETA CHAINS SUBGROUP II)
`T ·L YMPHOCVTE RECEPTOR FOR ANTIGEN VARIABLE REGION (GAMMA CHAINS)
`
`• . •
`
`. • • • • •
`
`• • • • • • • . • • • • • • • . • . . • . . . . • 274
`. • • • . • . • • • • • • •
`. • . • • . • • . . • • 279
`
`. . . • . • . • • • • . • . 254
`. • . . . ............................................. 256
`. . .. . . . . . .. .. . ... ... . . .. . . ... . 259
`• • • • • . • • • • • • . • • • · • · • • • · • • · • 262
`. • . • • • . •• • • • • · • • • • · 266
`
`CONSTANT REGION SEOUE.NCES
`
`KAPPA LIGHT CONSTANT CHAINS
`LAMBOA LIGHT CONSTANT CHAINS
`
`. .. • • . .. . . . . • . . • • . •
`. . . . . • • . . . . • . . • . . • • •
`
`• •
`
`. .
`
`• . .. . ... . ... . . . . . . .. . . . . . . .
`
`• • • . . .. . . , . . . .. . . . , •• , • .
`
`HEAVYCONSTANTCHAJNSCHI REGION.............................
`•• .'
`.. .. . . . •
`HEAVY CONSTANT CHAINS HINGE REGION
`HEAVYCONSTANTCHAJNSCH2REGION .
`. . .
`•
`HEAVY CONSTANT CHAINS CH3 REGION
`
`SEQUENCES OF RELATED PROTEINS
`
`•
`
`• •
`
`• • • • . • • • • • • • • • . . • .... .. . . . . . . . . .. .. . .. . . . . . .. . ... . .. 314
`• .. . .. . . . .. . . . .. .. .. ........... . ... 321
`
`• . . . • • • • . . .
`
`• • • • • • • • • • • • • . .. • . . . .. • . .. ................. 282
`• . . • • • • • • • • . . • . . • . . . . . . . . • • . . • • . . • • . . 287
`. .. .. ..... ... . . 293
`• . . .. .. .. ... . .. . . . . . . . . . . . . . . . 300
`• .... . . . . . . . . . . . .. .. . . . .. .. . . . .. ... .. . .. . . . . . .. .. . .... . 307
`HEAVY CONSTANT CHAINS EXTRA LONG CH3 REGION
`.. ................. ................ 323
`HEAVY CONSTANT CHA!NSCH4 REGION... .. . . . . . . • . • . . • .. .
`• • • • • • • • • . • • • . . • • • • • . .. • • • • • • • . • • • 325
`HEAVY CONSTANT CHAINS EXTRA LONG CH-4 AND MEMBRANE BOUNO REGIONS
`............... ... 332
`. ............. .... 334
`.. • • • • . • , • • . • . . • . • • . . . .. . ... ... . . .. . . . .. . .. . 345
`. . . . . . .. . ..... . . . . . . . .. . .. . . . . . . . . . . .. .. · • .. 353
`I REGION GENE PRODUCTS CLASS II A-CHAIN A2 F\EGION. . • • • . • • . • .. • . . . . . • . • • • . . ... .. . .. . ... . . . .. . · • • · • . . • • • · • .. • .. 362
`I REGION GENE PRODUCTS CLASS II A-CHAIN MEMBRANE BOUND REGION . . . . . .. . . . . . . . . .. . .. .. . . .. . . . .. . . • .. ... · · · · · • · 365
`I REGION GENE PRODUCTS CLASS II B-CHAIN B1 REGION
`
`................... ........... .
`JCHAIN
`BETA·2·MICROGL08ULINS........................ . ..... ..... . . . . . . . .
`MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS 1 N REGION • • . . . • . . • • • . • . . . • . • • . . • . • • • . . . . • •
`. • . . • . • . . • . . • • . . • • • • • •
`MAJOR HISTOCOMPATIB1LITY ANTIGENS CLASS I C1 REGION . . . . • . . •
`
`MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I C2 REGION .
`
`. • ..
`. ............... 337
`• . . .. . . . .. . . . . .. . ... 341
`
`. . .. . . . . .. . . . . . . . . . . . . . . .
`
`• .. . . . · 349
`
`MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I MEMEIRANE REGION . • . . . . . . • • . • . •
`MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I CVTOf'LASMIC REGION
`I REGION GENE PRODUCTS CLASS 11 A-CHAIN Al FIEGION . .
`• . • . • . •
`
`• .. .. . . .. .. . .. . . . ... . . ... .... . .. . • • . • • · • • • • · . 359
`
`................................................ 370
`
`3 of 21
`
`BI Exhibit 1052
`
`
`
`HUMAN KAPPA LIGHT CHAINS SUBGROUP I
`6
`5
`2
`3
`•
`REI HAU HKI01 sew AG WEA HK
`I
`7
`8'
`9
`INVARIANT
`137
`#
`ROY AU
`RESIDUES
`#
`I
`'CL
`I
`ASP ASP
`ASP ASP ASP
`!LE
`ILE
`ILE
`!LE
`ILE
`MET MET MET
`Gl.N Gl.N GLN
`Gl.N Gl.N
`MET MET
`THR THR THR
`THR THR
`GLN Gl.N
`GLN Gl.N GLN
`SER SER
`SER
`SER SER
`PRO PRO PRO
`PRO PRO
`SER SER
`SER
`SER SER
`SER SER
`SER SER
`SER
`LEU LEU
`LEU
`LEU LEU
`SER SER SER
`SER SER
`ALA ALA
`ALA ALA ALA
`SER SER
`SER
`SER SER
`VAL
`VAL VAL VAL
`VAL
`GLY GLY GLY GLY GLY
`ASP ASP ASP ASP ASP
`ARG ARG ARG ARG ARG
`VAL VAL VAL VAL
`VAL
`THR THR THR THR THR
`ILE ILE
`!LE
`ILE
`!LE
`THR THR THR THR
`THR
`CVS CVS CVS CtS CVS
`GLN Gl.N Gl.N ARG ARG
`ALA ALA ALA ALA ALA
`SER SEA SEA SER ARG
`GLN Gl.N Gl.N GLN GLN
`
`0 1
`
`2
`3
`4
`5
`
`THR{.98)
`
`SER{.96)
`
`19
`
`VAL(.97)
`
`CVS
`
`6 1 SER{.95)
`� PR0(.98)
`10
`11
`12
`13 14
`�� �t�.��
`17 18
`ri re.�:
`22 23
`24 � ALA(.95)
`27 27A
`278
`27C
`270
`27E
`27F
`29 30
`28
`
`F
`R 1
`
`c
`0
`R 1
`
`F
`A
`2
`
`c
`0
`R
`2
`
`F
`R
`3
`
`'Cl
`
`10
`H K 134
`'Cl I
`I
`ASP ASP ASP ASP
`ASP
`!LE
`!LE
`!LE
`ILE
`ILE
`GLN GU< Gl.N GLN
`Gl.N MET
`MET MET MET MET
`THR THR THR THR
`THR
`GLN Gl.N Gl.N GLN
`Gl.N
`SER SER SER SER
`SER
`PRO PRO PRO PRO
`PRO SER
`SER SER SER SER
`SER SER SER SER
`SER
`LEU LEU LEU LEU
`LEU
`SER SER SER SER
`SER
`ALA ALA ALA ALA
`ALA
`SER SER SER SER
`SER
`VAL VAL VAL VAL VAL
`GLV GLY GLV GLV GLY
`ASP ASP ASP ASP ASP
`ARG ARG ARG ARG ARG
`VAL VAL VAL VAL VAL
`T>!R THR THR THR THR
`ILE
`ILE
`ILE
`!LE
`ILE
`THR THR THR THR THR
`CVS CVS CVS CVS CVS
`GLN Gl.N ARG ARG ARG
`ALA ALA ALA ALA ALA
`SER SER SER SER SER
`GLN GLN GLN GLN GLN
`
`19 20
`
`18
`21
`RFZ PSM HOM ESM ESM W AT
`IGG
`IGM
`
`22
`
`23
`
`13
`
`t4
`
`16
`
`ASP
`!LE GLN
`MET
`THA
`GLN
`SER
`PRO
`SER
`SEA
`LEU
`SEA
`ALA
`SEA
`
`ASP !LE
`GLN
`MET
`THR GLN
`SER
`PRO
`SER
`SEA
`LEU
`SER
`ALA
`VAL VAL
`SER
`
`GLY
`ASP
`ARG
`VAL
`THR
`!LE
`THR
`CVS
`ARG
`ALA
`GL V
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`#
`
`PRO PAO PRO SER
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`
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`OLN GLN
`GL N GLN
`TYR TYA
`ASN ASP
`SER SER
`ASP PHE
`SER PRO
`
`5 of 21
`
`BI Exhibit 1052
`
`
`
`HUMAN KAPPA LIGHT CHAINS Su80JIOUP I (confd)
`
`SS
`St 52 53• S.
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`H8J FAA GR• PAUl MON HEI POT $-
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`VAL VAL VAL VAL
`VAL VAL V