PD-L1

By Aditya, Sophia and Jeffrey

Function and Purpose

PD-L1 is a protein that has been found to suppress the immune system
during situations like pregnancy, tissue allografts, autoimmune disease and
others like hepatitis to build tolerance.

When PD-L1 binds with PD-1, a signal is sent out that greatly reduces the
amount of T-cells being produced at the lymph nodes in the area to stop it.

It is also upregulated in tumors to prevent the immune system (T-cells) from

killing the cells.

Characteristics

PD-L1, or Programmed Death-Ligand 1, binds almost exclusively with PD-1, a

cell surface receptor involved in the regulation of the immune system.

It is composed of a N-terminal Variable domain, and one C-domain joined by

a short linker, which provides it with enough flexibility to bind to its receptor.

It is a monomer when suspended in a solution.

Location

PD-L1 is a transmembrane protein, meaning that the protein is located on

both sides of the membrane.

It is expressed on immune cells, such as B-cells, T-cells, and dendritic cells,

in blood, bone marrow, the spleen, and lymph nodes.

It is also expressed in a variety of cancerous tumors.

GGCGCAACGCTGAGCAGCTGGCGCGTCCCGCGCGGCCCCAGTTCTGCGCAGCTTCCCGAGGCTCCGCACCAGCCGCGCTTCTGTCCGCCTGCAGGTAGGGAGCGTTGTTCCTCCGCGGGTGCCCACGGCCCAGTATCTCTGGCTAGCTCGCTGGGCACTTTAGGA
CGGAGGGTCTCTACACCCTTTCTTTGGGATGGAGAGAGGAGAAGGGAAAGGGAACGCGATGGTCTAGGGGGCAGTAGAGCCAATTACCTGTTGGGGTTAATAAGAACAGGCAATGCATCTGGCCTTCCTCCAGGCGCGATTCAGTTTTGCTCTAAAAATAATTTATAC
CTCTAAAAATAAATAAGATAGGTAGTATAGGATAGGTAGTCATTCTTATGCGACTGTGTGTTCAGAATATAGCTCTGATGCTAGGCTGGAGGTCTGGACACGGGTCCAAGTCCACCGCCAGCTGCTTGCTAGTAACATGACTTGTGTAAGTTATCCCAGCTGCAGCATCT
AAGTAAGTCTCTTCCTGCGCTAAGCAGGTCCAGGATCCCTGAACGGAATTTATTTGCTCTGTCCATTCTGAGAACCCAAAGGAGTCCTAAAAGAGGAATGGAGGAGCCTAAGAATAAAAATAGTATAATAAAACATTTCTTAGACACATTGACCTTGGCCTATGTCAAAGT
TCAGTCTGGGTTTGTCTTATAACACAAGGAGTAAAAGTACCATTGTTCTACCTCTTTTTTTAATACTTGAAAAAAATTTACTGTGGATGCTTTTCTATGAATTAAATAACCTTCTAAAAAATGTTTTCATTGCTGCATTCGATTAGATTGGGTAACTAAATGAAATTAATTCCTC
ACTGTTGGGTATAAAGGTTATTTACAGTGGTTCTGTCTTAGCCATTCACTGAACTCATTGCATATATATCTCTGGAATATTGCTGATTGTTTCCTTCAAGTAAACTTAGAAGTGTAACTACTTAGTCAAAGAGCCTGAATATTTTAAAGGCCTTTTGAAGAAAACTGAAAATGC
TTTCCAGAAAGGATGTATCAGTTGACAATGACAGTCGTCAACAGTATTTAAGGAGAACTATGATACTCTGAAGAAAAACTTAGCCTTTCTCAGTAAAAGTAGGTAGGCAGAGGCCACATGACAGCAGTTAGAGTGTGGTCTTCAAGGAAGTCACAGAAATACTGTGGGGA
ATTGAAACCCCATGTGGAAAATGTACAAGAGTGTCTCAGTGTGACTGAGAAGGAGGTTGGGCATGGGGTTTCATGGAGTTTAATAAAGTTTGGTCACTTAGTAGAGGTTTAATAAATCAACTGTCTTAATCTTTGATCCTACTTAAGAATTTTTTTTTTGTTTTTGTAGAGAT
GGGGCTCTTGTTATGTTGCCCAGGCTGTTCTCGAACTCCTAGCCTCAGGCGATCCTCCCTCCTCAGGCTCCAGAAGTCCTGGGATTACTGGCGGGAGCCACCATGCAGGCCTCTTGCTCCTACTTTTGAGAAAGGAAGTTTAACCGGTTTTTTTTGTCTTTTTTTTTTTTT
TTTTGAGACAGAGTCTCACTCTGTTGCCCATGCTGGAGTGCAGTGGTGCAATCTCAGCTCACTGCCTCCCGGGTTCAAGTGATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCACCTGCCACCACGCCCAGCTAATTTTTGTATTTTTAGTAGAAATGGG
GTTTCACCATATTGGCCAGGCTGATCTCGAACTCCTGACCTCAGGTGATCCGCCTGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCATGAGCCACTGCTCCTGGCTGCTTAACTTTTTCTCTATCTCATCCTCCTACCCATCCTACCCTTGGAAGATAGAGAAGTAGT
ATTAGTTCCATAGTGTTATACTGGGCTTCCCCCAGGGACAAACCCACTTCCCCAACCTGAATGAGCCATCACTTCTTCCCCAGTTTACATTTCATTGCTCTTTAAATGTCTCCATTCGGATATGGGAATTCACATATGGTCATAATTCTTACCTGAAGAAGATGTCAGTCTT
CTTCTCTTAGACCAACTGCCCTGATATGAGGTTTAGAGGTTAAAGAACATGTGTGTATTTACATGATCTTTGTATTCTGCCTTTTCGTCCCTCACTAATGACAGCTGCACCCCAAGGAAATGGAGCTGTGGAAGAGAGGGTTTGATAAGAAATTAAGTAAATATTGGATCTA
ATCCATCACCCTCCAGGAAGCCTTTATTACTCCTAAAAATTTCAACCAAATTCATTAAAGGACAAGAACTCCACCAGAGTAGGCCATAAACATTGGCAAAATTAGTTGTAATCCATGACTAGATTTAATGTCCCTTTGTTTTATTCCCATATGGTTATAATGCTTTGCTTGGC
ATTAGGGGTATTTTAAGTTTTCTTCTGCCTAGTAAGTGAATTTGTGTTTATAATACAATAATCATAAAATATCACATTAATATTTTATAACTGTACAGTTATAAAATATTTTATAAGTAATATTTATATTTTATAAGTAATATTTTATAACTGTACAGTTAACTCTGGCCCAAGGAA
AAGATAGTCTGATAGATGCTGCAGCCCCATTTTAGCAAATGTGACCTCACAGGCCTGAATGCCATCGCTATTCCACATCTACAGGATAGACGGAAAGGAAAGAAATAAAAAAATAGGTACCTAACACTGGCAAGAGGATGATGACTCATGTTATTTCACTTAACCTTTTTA
TCTTTTAACATGAAGGACTCATACAGGTTGATAAGAAACCAGTGACATAAACAGACCAAAAAATGATCAGATCTTTCAAATTAGCAAAAAAATAATATTTTTTAAACAATGGGTGAAAATACAGTGTAACAGTACCAATTATCAACATGTGTTGAGAACCAGAAAAATGTTCTT
TTTCTTTGATCAGCAACACTATTTGGGAAAATCTATCCTCAGGGCCTAGCCTGGGGCCCTGGCACACAGTAGGCACTCAACGAATATTTGCTGAACACACAAATACTTATGATATTTTAAAAAATTGGCAACAATCTGATACCTAACAATAGAGGGATTAAATATTATGGAA
CTGTTAAATAAGATGCTTATGAATACCATGCAGTAAGATGGGCAATATTTATGCCATAAGCTTTAATGAAACAAATGGGTATTAAATGTATGATAAGGTTATAAATTACTTTTTAAAAGATTACAGGGAAAAAAATTGAAAGATATACACTGAAATGTTTTTTGCTCACAGTGG
TGACAAGGTTTCTCAGCACTGGCACTGTTGACGTTTTAGGCTGTATGTCTTTGCTGTGGGAGGCTGGCCTGTGCACTGCAGGGTGTTTGGCAGCACTCTTGGCCTCTGCCCCTAGATAGCAATAGCAGTCCTCCCTCAACCAGCCCAATTTTGACAACCAAAAATGTTT
CCAGGCATCACCAGATGCTCCCTGGGTGAGAGTGATGAAATAGTAGGGGATTTTCCCCTTCTTTTCTTATTTTCTGTAATTCCATTATATTACTTTAATAATAAAGAAAAAAACATAAAAAATAAACGAATGTTATTATTCTACGTCAGTTTGGATGTTTGGACTCCATTTTGG
GGTTCTTTCCATTATATCACTTGGTCTGCTAAACATTCTACGGTTTGGTAAGGTGAAGTGATTCATGAAATTTTGGTTTTATTTTTTTCCTGATACTAAAAATAAAACATTCTTTCACTTGGAAATTTGGACACAGAACACCAAAAAAAATCCATAATCTCATCTCTCTTTTTCT
GTCTTTTCCTTCCTTTTTTCCCTTTAAAAACAATAAAGAGTGAAACCTACCTGTTCTCCCTCTAATTTAATTCCTAAATATAATCACTGTCAATATCTTGGACATTTCCTGTGTCTAAACACACACACACACTTTTTTTTTTCAGCAAAAGTGGATTTCTGCTACATGTAGTGTT
CTGCAACTTACTTTCTATGTGTTTACAAAATCAGTACATGTACATATGCTGAATTCAGTCCTTAATGGTATTATATTTTGTGAATATACCAAAATTTGTTTAACCACTTAGACAATCTAGGATATTCTCAGTTTGCTGTTATGAGCAATGCTCTTCCTTTACATATACAGACATA
TATATATATATGTGTGTGTGTGTGTTTTTGTTTTAGTAGGATAGATTTCTAGGAGAGGGTGAAAGGTCTTATGACATCCGCATTTACGATTGTAATAGGAAGTATCAAAGTGCCCCCTAAAGAAAAAAATCCTCCCATTAGTGGGTAAGAAAGCCTATTTGTTCATATCTTCA
CAAACACTAAATATTAGAAATATTTACAATTGTGGTCAAGCTCATAAGTGAAAATGGTATTTCATATCTTATATTTTTTATTGTGAGATTGAACATCTTTCATATGTTTACATGTCACCTGTATTTCTTATTCTCTGAACTATATGTTATGACCTTTCACTTTTTTTCCTCATGGGT
TATGTGTAGTTTGTATAGTTGTCTTATTGATTGTTAGGAGCTATTTATATATTAGGAACATTAATCTCCTGTCTTATATATACGTGGCATCGATTAGTTGATCATTTGTGAGTTCATGTCTGTATACAAAGATTGGAGAGGCACTAAGAGGGAAAACTTACCTCTTTCTTATCA
AAGTTTGTAAATATATGTATAACAGAAGAGGGAGAAAATATTAATAAATGCACAGATTGGCTGAAATAGAGTATAAATCTTTTACTCCCCTACTTCAACATAAACTGCAAAAGGAGAGTGACTTTTCTTTCACTCTGACTTCCGTATTCCTCATGCTTAAAATAGTGCCTAGC
ACAGAAGAGGTGCTCAATCAGTGTTTGCTAAACGAAATAATTAGTCACATTTCAAGCAGGATGACTAAATGAAGAATAGAATCTAGGCAGATACTCTGGAAGAGTGGCTGTGAGTCATTCATATCTTAGTATGAATTAGTCAAATCCAACTCTCTCCCCTTCCCACTCCCCA
CTGTTAGTAGAAGAATCTGTTTATTGAGAGAATAGATTTATAATTTAGAATAAGTGAGAGGGGCAGAAGAGGAGATTTTGAAGGATGGCACCTGAAGGAGGACTAGCATGGCTGAGACAGTGAAGTGGAAGCCTTGAATAGCTAAAGGGTAAGATGAAAGTATTTAGCTG
TAGGGGGAAAAAGCATTGACAGGTTGGAAAAGTAAAAGTCAGATTCTCCTTGCTCTGAAATTTTGTACAGGGCAGGTTCTACTAGGTATGTTACAATGCAGAAAAAACATGAAATAATTGAGAGGAATTTGGTGCAATATTATCTTCTTGGCTTCTTTTGAGTGGGCAGATT
TTTTTCACGGCCTGTAACTATAATAAATTTGAAACTTCTCATCTTTTAGTAACTTTTTTCACTTAAGTTTATGTGGCTGTGGGCAATGGAATGAAGATATTGAACTTCCAATTCCCTGTTGGGTTTCCACAATTACAAGTCAATCATGACTGGTTATTAGAAGACTATTTCAGTT
AGAACCACCAAGTCCCATATTGTCATATTGTATGTTTAATTATTAAGTGAAGCAGTCTTCTTTTCGTGTTTTCCATAATTAGGGCATTCCAGAAAGATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGGTAAGACACCAAATCCTTCCATTAG
GTTCTATATTTTAAATATTTTAACCATGAGTTTAAAACTAAAATGATCATTTAAAATGCATGCAATTTTCTTATAGAGAGAACATTCTATTCTTTCTTCTACTTTACACAATGGCAAAGTCTTCTTTCTACTTTACGCAATGATAAAGTTACCTGTGTCATTTTGTAAAAATATAGA
GAATATAGACAAATTGAAAGACACAAAATAATCTATTACCCATTTCCCAGGGTTAACTACTGAAAATATCTGGGGAAATGGCCTGTATGTATACATTTATTTGTTTGCTTTCAACAAGGCCAAGATCCTTTGATCTTTCAGTCTTGGTTGCTCTGTGACATGCCTTTCCTGAT
GAGGATACTTTAAGGAAGAATTGTAAGATACATGGAAAATGTCAGGCTAACACAGTACTGGCATCACCCTGTGCTCTTTCCTGAACTCCATACCAATGTACTTCTTGCCAGAAAACTGATCAAAAGTTTAGGGAAGTAAAAAGAGATGACTGTTAGAATCTACCATTCCCT
CTATGTAGGAAGCAAATAGGTGTCCTGTCAAAGGACATTCTGGGGATGTCTACATGAAACCAAGTCTCCCTGGTTGTAAGGACTCCATCTCCATATAATATTTATACAGTAATATATGTTTATAAATTGTGGGGGCAACTTGTTTAGCTAATTTTATTATTCTGCTATTGGGA
CACTGTGTCTCAGCATGAGATATAGTGTCCCAAAACATATTTCAAGCCCATTGGATAAAATATGTGTTTAGCAAGTTCTTAAATATAATGATAACATAACCGACCAGATAAAGTGATTTATAAACGCTGTGCCAATTTTGTAAATGTTTCGAGGAATTTTCCCTTTTCTGAAGA
TTGTCCTTCTTTCTTTTTAGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGC
ATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAG
CGAATTACTGTGAAAGTCAATGGTAAGAATTATTATAGATGAGAGGCCTGATCTTTATTGAAAACATATTCCAAGTGTTGAAGACTTTTCATTCTTGTAAGTCCATACTTATTTTCAAACAGAACAGCATAGTCTGTTCATTCATTCATTCAATTCATGAATTCATTCACATAAT
TATCCAATTTCTTGAGCACCTATTTGATAGTCACTGGAAATCCAGAGACAAACAACACAGAGCCATGTTCTACAGTATGTACAGTTTTCCAAAAAGAATTTCTAGTCTTTACTTTTTTATTACAAATGGAATACGTATACTTGCAAATAATTCAGATACTGTGGAAGAGATCAA
ATGAATTGCAAAAGTGTCCCTCCTCCCTTCACCACTATCTCCCATGGCATGCAGAGAGAGTAACCATTATTTGTGTGTCCCTCCAGAAATTTTTTTATTCAACTACTATTTTTTTATTTTATTAGGTCCGTCAGTTTTCCTTTTTTGAGCCTCTCTATATCAAATGCAAATAAAT
ATATTCAGAACAAACCCCACTGTAAGGTTCACATTAAAAAAGACTTGAAGTCACCCTATGAAGACAAAAAATAATCACATTAAGTGTGAAAGAACCTATTCTTCCAGTACAGGATAAGCCATACTTACTGGGCATATATTCATCTTGAAAATCTATACTGATGTTGTCTTGGG
GAATTGAAAAGGAACTAGGAGTGTTAGTTCCTCGGTATTGACCCACAGTTATGTTATCAGGTCACTTGAGTTCAAAGTTTTGTGTTGGCACTAGCTAAGTAAAGGAAAACACCTCTGCTTTCATTGTTGAGTTTCACAGAATTGAGAGCTGAAAGGATCCCAGGCAGGAGC
AGCTAATCCAAACTCCCACAAAGAACAAAAATCCCCCAGAGGATCTTCTGTTCTTATATTTCCTGCAATGGCGTCCCTGTCATATCCCACAATGGCCTCCCTGCCATTTGGATATCCCTTCCATATCCTGTTGAAATTACTCCCTAATAGTAAGCTGAAATCTGCCCCTCTA
GTTGTAGTCTTGGGATTATTTCATTTACATGATGACCTTTTAATATTTGACTAGAATTAAATCATCTCCCCTTGGTCTTTCCAT

TCCTGGGCTAACTACCATCAATCTGAGGGCTAACAATACAAGTAGAAAAAGTATACATTTGTCACTGATCACTGATCAATTATTAATCAATGATCACTGATAACTATAAACTCAAAAACAAAATCATGTGGGGATTAAGAGAAATGTATCAGTTTTATGTTGTATTTCTGGTC
CCTGATACTGGCTCAGGTAATGCCACTATTGTCAAGAAGATACCACTTGTAAAGTAGATTTAATTTTCATTATATTTTACCATATGCTTCTCCATTCATGACATCTCTTGAGATGTTGTGGTTTATACTTTCAGTTTTTCTCCAGTCCATCCGCAAATATCAGGCATCTACTGT
GTTC
ATGGGATGTAGAGCTGTGCTATATGGAAATAAAAATGATTTCTTTTTCTCAAGGGAGAATGATGGATGTGAAAAAATGTGGCATCCAAGATACAAACTCAAAGAAGCAAAGTGGTAAGAATATCAGAAGGAATTGGGAAGTAAAAGTCAAAGGAAACAAAAAGCTAAAGCA
ATAACCAGGGCAGAAAAACCTCATCCAGGTTATTGAACTAAGAAGAAAGTTATATTAAGGTTTCTAATTTTTTTAATGTAGTTAGAAACCAAACTTAACAATGAGCCCAAGTTTAAAGCAGTCTAATTAACCTGGACAAGCTCAGGCAAGTTTCATTCTGTGGCCCATAGCAT
CATCTGTGTTGTAAAGCTAAGTAGCAAATGTTGTTTGGGTCATGCTGGGGGACAAGCCATCCCAATTTGCTCAGGACTGAGGGGTTTTCCAGGATATCATGTAAGGATAATTGGGTACAAATATAACCTGCTGCTTTCTCTCATTTCAAATTTATCATTTATCATATCAGCA
ACTATGAGTTATGTTTTTTATTAGATTTCTTGTTACTTTTTCCCCAGACCACTTCCCATGAAATTAATATACTATTATCACTCTCCAGATACACATTTGGAGGAGACGTAATCCAGCATTGGAACTTCTGATCTTCAAGCAGGGATTCTCAACCTGTGGTTTAGGGGTTCATC
GGGGCTGAGCGTGACAAGAGGAAGGAATGGGCCCGTGGGATGCAGGCAATGTGGGACTTAAAAGGCCCAAGCACTGAAAATGGAACCTGGCGAAAGCAGAGGAGGAGAATGAAGAAAGATGGAGTCAAACAGGGAGCCTGGAGGGAGACCTTGATACTTTCAAATG
CCTGAGGGGCTCATCGACGCCTGTGACAGGGAGAAAGGATACTTCTGAACAAGGAGCCTCCAAGCAAATCATCCATTGCTCATCCTAGGAAGACGGGTTGAGAATCCCTAATTTGAGGGTCAGTTCCTGCAGAAGTGCCCTTTGCCTCCACTCAATGCCTCAATTTGTT
TTCTGCATGACTGAGAGTCTCAGTGTTGGAACGGGACAGTATTTATGTATGAGTTTTTCCTATTTATTTTGAGTCTGTGAGGTCTTCTTGTCATGTGAGTGTGGTTGTGAATGATTTCTTTTGAAGATATATTGTAGTAGATGTTACAATTTTGTCGCCAAACTAAACTTGCT
GCTTAATGATTTGCTCACATCTAGTAAAACATGGAGTATTTGTAAGGTGCTTGGTCTCCTCTATAACTACAAGTATACATTGGAAGCATAAAGATCAAACCGTTGGTTGCATAGGATGTCACCTTTATTTAACCCATTAATACTCTGGTTGACCTAATCTTATTCTCAGACCT
CAAGTGTCTGTGCAGTATCTGTTCCATTTAAATATCAGCTTTACAATTATGTGGTAGCCTACACACATAATCTCATTTCATCGCTGTAACCACCCTGTTGTGATAACCACTATTATTTTACCCATCGTACAGCTGAGGAAGCAAACAGATTAAGTAACTTGCCCAAACCAGTA
AATAGCAGACCTCAGACTGCCACCCACTGTCCTTTTATAATACAATTTACAGCTATATTTTACTTTAAGCAATTCTTTTATTCAAAAACCATTTATTAAGTGCCCTTGCAATATCAATCGCTGTGCCAGGCATTGAATCTACAGATGTGAGCAAGACAAAGTACCTGTCCTCA
AGGAGCTCATAGTATAATGAGGAGATTAACAAGAAAATGTATTATTACAATTTAGTCCAGTGTCATAGCATAAGGATGATGCGAGGGGAAAACCCGAGCAGTGTTGCCAAGAGGAGGAAATAGGCCAATGTGGTCTGGGACGGTTGGATATACTTAAACATCTTAATAAT
CAGAGTAATTTTCATTTACAAAGAGAGGTCGGTACTTAAAATAACCCTGAAAAATAACACTGGAATTCCTTTTCTAGCATTATATTTATTCCTGATTTGCCTTTGCCATATAATCTAATGCTTGTTTATATAGTGTCTGGTATTGTTTAACAGTTCTGTCTTTTCTATTTAAATGC
CACTAAATTTTAAATTCATACCTTTCCATGATTCAAAATTCAAAAGATCCCATGGGAGATGGTTGGAAAATCTCCACTTCATCCTCCAAGCCATTCAAGTTTCCTTTCCAGAAGCAACTGCTACTGCCTTTCATTCATATGTTCTTCTAAAGATAGTCTACATTTGGAAATGTA
TGTTAAAAGCACGTATTTTTAAAATTTTTTTCCTAAATAGTAACACATTGTATGTCTGCTGTGTACTTTGCTATTTTTATTTATTTTAGTGTTTCTTATATAGCAGATGGAATGAATTTGAAGTTCCCAGGGCTGAGGATCCATGCCTTCTTTGTTTCTAAGTTATCTTTCCCATA
GCTTTTCATTATCTTTCATATGATCCAGTATATGTTAAATATGTCCTACATATACATTTAGACAACCACCATTTGTTAAGTATTTGCTCTAGGACAGAGTTTGGATTTGTTTATGTTTGCTCAAAAGGAGACCCATGGGCTCTCCAGGGTGCACTGAGTCAATCTAGTCCTAA
AAAGCAATCTTATTATTAACTCTGTATGACAGAATCATGTCTGGAACTTTTGTTTTCTGCTTTCTGTCAAGTATAAACTTCACTTTGATGCTGTACTTGCAAAATCACATTTTCTTTCTGGAAATTCCGGCAGTGTACCTTGACTGCTAGCTACCCTGTGCCAGAAAAGCCTC
ATTCGTTGTGCTTGAACCCTTGAATGCCACCAGCTGTCATCACTACACAGCCCTCCTAAGAGGCTTCCTGGAGGTTTCGAGATTCAGATGCCCTGGGAGATCCCAGAGTTTCCTTTCCCTCTTGGCCATATTCTGGTGTCAATGACAAGGAGTACCTTGGCTTTGCCACA
TGTCAAGGCTGAAGAAACAGTGTCTCCAACAGAGCTCCTTGTGTTATCTGTTTGTACATGTGCATTTGTACAGTAATTGGTGTGACAGTGTTCTTTGTGTGAATTACAGGCAAGAATTGTGGCTGAGCAAGGCACATAGTCTACTCAGTCTATTCCTAAGTCCTAACTCCT
CCTTGTGGTGTTGGATTTGTAAGGCACTTTATCCCTTTTGTCTCATGTTTCATCGTAAATGGCATAGGCAGAGATGATACCTAATTCTGCATTTGATTGTCACTTTTTGTACCTGCATTAATTTAATAAAATATTCTTATTTATTTTGTTACTTGGTACACCAGCATGTCCATTT
TCTTGTTTATTTTGTGTTTAATAAAATGTTCAGTTTAACATCCCAGTGGAGAAAGTTACAAGATATTAAAGAAATCATCATGACTTAGCCTCATCAACAGCATTGCTAGATCTGGGATGGAAAGGAAGAGTATAATCCTGGCAGTCAGGAAGAAGGCAGCATAAAGTATAAG
TTTCTGCTTCCAAAAAAGGTCTCTCATCAGCCTGTAGGGAGTGTGTAGGGAAGGGACAGCTGTCCTTGTAGTAGGGAAGGGTTTTATTCAGGTCGTCTGGGCTCCATAATATCCCTTGTGTATCTGCAGTCTCCTTTGCCATGGATCAACACAATAGGAAATCTTCCGGC
ACTGATGGTTTTTCCAAGGGGGAGTTCTTCCTGGAGCAAAGCAAATGACCAACCAGGTTTGAGGACCTGATTTGTTTGACAATTCCATTTTGTATTGTAAATTACTTAATTGGCATTCTACTCCCAATCCATCTTGTCATTTGCATACAGTGGTTTTGGGATTGAGTTCAGC
TATACCAAAAGTCTGAACCTTCTGCACTTAGAACAAGGCAACCACCAAGCTTCACTTGCACTGAGGCCGTGTCTCCAATGGAAATGAGGCAGCTGGCTTGCAGGAGCTTCCCAACTCAGGGAAGTAGAACTCCTGAGTCACCTCCATATGCAAATGATTTCACAGTAATG
CTGTTGAACTTCACTTCCCATCACAGCAAATGTGTGGTAACATAGCTTCCCCACAGGAGTTTACTCACCATGGTATTTTAAAGGTGAAACATTTCAAAACTGAAATTTGAAAGAATTTAGTTTTGGATTCACTCAATTATCACTATCACTTCGGGTGTTATTGCACCTTTCTT
GTTTGTGAGTTTAAATGCCAGACTCTCAGGCCACTAACTTTCAATTAAAAGTGTTTTTCTTTAATCGCTGAACCTAACAGCAGGGAAAACGAAATGTTCATTCAGACTTTCAGAACCTTCAATGAGATTAGGCAGCTGAAAGATCAAAGTGTTGCATAGTTGTCCCGATAAA
GCTATTTGGATCATATGGACCAAATCGACTGCTGTCATTCCCCACCAACCCCATCTCTCCCCAAAATTCCCAGCCCTGTTTAAGTGTTCTCTGTAGCATTTATCTCTATCTAGTATATTGTGTAGCATATCATATCATACTTTTCTGTTTTGTTTATTGTCTCTCTCCTCCTAG
AATATAAACTCCACAAGCACAAAGATTTGGGCCTGTTTTATAATATTGTTGCATCCCCAGGGCCTGATATACAGCAGAGTGGTGGTACGAAAAGAGCACACAAAAAAATATTTGTTGAGTCAATGAATGAATGATTTCCTCAAATAGGATTAGCCTAAAATTTTGGAAACAT
GAACAGATTTGGATATGTGAAAATTTATTTCCAGACTGTTCATCAGGAACTGTTAGCAGCTTCTAAAGGGTACACTGGAGCAGCAGTAGTAAAAGGAGGAAGAGGAGCAGCTCTGCTACTGCTACTATCGAGTACTACTACAATTAGCACTTGCTTATTCTGTGTGTTAGG
CCCTGTACTGAACACTCTGTCTAAATTAGTTCATTTCCTCCTGGAAATGACTCTAGGGGGTAAGTGCTTCATCATGTAAGATGAGTATTTTTCACATTTTGTTGTGTCTGAAATCTGAGTGTGTCTTTCAATGATGGAATCTTTGATTCCATGATAAGTGGTATTATTCCCATT
TTAAGGATGAGGAAACTGAGGTCCAAAGAAATTAAGTAATTTGCCCAAATTCACCCAGCCTAGAAAATGATAAAGCTAGTTCTAAACCCAAGCAGATTAGCTCTGAAGTCTGGGCCCTTAATAACCACTTTTTATTGCCTATATTTGTACCTCTGGTGTACGTATCAAGTTA
TATGTTGACTTCAAAACTATCATGACCTTTTCTTGGTTTTGATTGTCCAACATTAGTATAGTGTTCTGGGTCTGCAAAAATTTTGATTACTCATCTCATCTGTAAAACATTTTGAACTCGTGTGTTTGTGCATGCACATTTGTGTGTAATTATAAAAATTTTACTTTCTGTTAATA
TATAAGTTGTATCATAAGAAACTGCCGTTTTTGAAGAGCAAAAAAAGGTTGAATGTTACCAGTTACATCTGGTTCAACCTAATAGACATTTGTACAAAAACAGACATTTTAAGAGGTTGAAATAAAAATTTAATAAACAATATTTTCAGTTTTTACTAATTGTGATGCTTCACTA
TCATTAGCTAATATGTCAAGGCATAATATACCTTAGGGTGAACTTTATCATTAACAAAGGTGGATGGTGTCAATAATCTTGAGGTTTGTGTTTTTTTATATAACACTGCGAGGTCTAATTAAGTACTTACTGTTTACCACCTCATACAGTGGCCGATAAAAAGTGTCACTTCT
GCTGTTTCCTCTGGGTTGTGCTTGAATTATTAGTATTATCTTCAGTCCTCAGTTTCTTTGTGGGAAACTTTTTAATTAGTTGTTTAATTTTGTAAGATGGTTAGTTTAGTCAAAATTAGATAAGAGAATTTGAAAATCCGTAGCTACCCCAAAGCAACCTACACATAAGAACTA
TTATTTTTGTGTTTTGAAATCATAATTTTATTGATTTCCAGTGTTTCCACTGGTAGTGGTTTCATTGATATAGGAGTATCAAAACATCACTCATTATTTATTTCAGTTTCATTTGATCCTAGCCGTTTTGTATTAACTCTCTGTGAAGAAATTACCTCACAAATCTATTGCTGTCC
TTGGTAAAGGAATGGAGAATTAAGGCTCTAGATCATTAGTGGTTACACTATAGTATTAGAAGTAAAAAAAAGATTATACCAACAAAATAAGAACATGTTAATGTACTTGTAATGAATAAACATGAATAAAGCTCTTATGCTATATAGGTGCACTAAACAATCTACTAGAATTGT
CAGCAAACTACGTATCTTAATCCTGAAAGGGTCCCAAACCAATGATCTAAAATTGAATCAAACTTTCTTCCTTGAGCATAATTACTTAAATGATTTATTAAAATAGCCAGCATTTAAAAGCTTAAAATGTAAATATCATAATGTGGTATCCTAGATAGCATCCCAGAACAGAAA
AAGGATATTAGGGAAAAACTGGAGGAATGGAATAAATTATGCAGTTTAGTTATTAATAATGTACTAACGTCCTTAGTTATGACGATTGTACCATGGTAATGTAAGATACTAACAATAGAGGAAACCGGGTAAGGAGTATACAGTAACTCTATACTATCTTTGCAACTTTTTTG
TAAATTTAAAACTTCTAAAATAAAGAACAAATTTAAACATTAAAAAGTATCACCAGGAACATATATCACTGTTTACAGATGAAATACTATGTATTTTCATATCTAATTTCTGATCATTGACTTCAAATCAGAAAAGTGAATGACACCTCAAAATCAGGTTTTCTGTTTACTGAAGT
CTAAGAAAAGAAAGCATACCAGCTGGAGAGATTCATGTTTATAAAGACAGATTTATAACAACAAAAATAAAATATCCAAGAATAAATTTAAGAAGAAGCACTTTACTGAGAAACATATGAAAACCTGAACAAATGGAGAGGGATATTTTGTATTTGAATAGAAAGACTTCTGG
TTTAAAGATAATTCTCTTTAAATTATTTTTTGTAGAAATTTAAGGGGTACAAGAGCAGTGTTGTCACATGGATATATTACATAGTGGTGAAGTCTGGGGTTTTAGTGTAAATTAATCTTTACATTTTGTTTGAGCCCAATAAATGTACCAACATGATTTTTATAGAAAGATAGTC
ATTCCTATTAATCCAAACTTGTCCCAACTTTGAATTGAATTGAGGCAGAGCTAGCAGGTGTTCCCCACGGCTGAGGCATCTGAACATTAAGCATATCCCTCTGAGAACCAGCCTGCATTGATACTCTTTCTAATGTGGACAGCATCAAGCTATGTACGTAGTTCTGTGCTC
AGCAAAAGCCCTGACTTCTTTTTGTTTATGTCCTAGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGT
GGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAAC

TAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGTAATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACCTAGCATGATGTCTGCCTATCATAGTCATTCAGTGATTGTTGAATAA
ATGAATGAATGAATAACACTATGTTTACAAAATATATCCTAATTCCTCACCTCCATTCATCCAAACCATATTGTTACTTAATAAACATTCAGCAGATATTTATGGAATATACCTTTTGTTCCATGCATTGTAGTACTCATTGGATACACATAGAATAATAAGACTCAGTTCACAC
TCTT
CAGGAAACAGATAAAAAACTAAGAAACAAACAAAAAACAGGCAATCCAACACCATGTGGGAAATGCTTTCATAGCCGGGAAACCTGGGGAATACCTGAGAGGAATACTCAATTCAGGCCTTGTTTCAGGAATCCAAATCCTGGCACATCAGAGCTGCTTCCCTCTTTCCA
GGGTGGCAGGAAATAAATGGAACATATTTTTCTATCTTATGCCAAACATGAGGGACCCTTTCTCCCCGGTGCCTCTCCCAAGGTAGTCTACAATATTTCAACTCTAGCAGTCTGCTTAGTGCATAGAACATGAGGCTGTGTGTCCCTGGGCAAATTACTAGACTTCTGTGT
GCTTCACTTTCCCTGTAGGATTATAATCTACTGAGCAAGCTTATTGTAAGGGTCAGATTAGCAACAGTGTATGAAAATGATTTGAGACCATTGCCTGCACAAATTCAACTATTTTTTTTTATCTCACTACTCTACAGAAGTAGGTAGGGTGGGAGACAGAGTCTGATGAGAG
GCTCAGAATGTGAAAGAAAGTGAGGCGAGTGAGCATGATATTTAATATAAACACAAAGATATTCTGAGAAGAGCTGCTCACTGCCCCCTCCCCCAATACATGTTGATAGGAAAATGCCACGTACTTCAGCAAAAACAACTGAAAAATTAGATAGAAAAGTCAATCAATAGG
AAAAGATAATCCAGGACGGTGTTGTGAACAGAAAGAGGGGGAAAAAACTTTAGAAAATGATGGGGATGCTCTTACTGGGGTACGAGTCCTCAGGTATTGAACTGGCTTTCAGTAAAAGCTAGATTAGTGGGTTCCTGCCATTTACAAGCTGTTTTATGACAACTTACTTGT
TGGGTGGCCTACAGTAACTCACCTAACTGCACTGAGTCTGTTTCCTCATCTGTAAATTGGGGATTTTTTTTTAAATACCTGGCATGCCTAACTCATAAAGTTGTTCTGAAACTGAAATAAAACATACGTGAACAGGCATTGTAAACTGTAAGTTACGGAAAAAGCTGGCTGT
TGTTGTGTCTTTAAAGTTTCACCTGGGTAGTCAAAGATGGATCATGGGTCTCAGTGGAGAGCTGAGCCAGGCAGGAGCTGACTAAGGGTGAGAGGTGGGAGTTAGCAGCCTCTGAACATCTGTGTACCATGGGACCCCCTTTCCTCCTGCATGGTACCCCAGACAAGG
AGCCTAGTAAGAGATACTAATGGCTTGTTGTCCAGAGATGTTCAAACTGCAGAGAAAGATAAGACAACAAGCATTGGCCTCCAATCATGATGACAGATAGGAGGAGGTGGGAGCTCCTTAGCAGTGCTGGTTGGCCTTCCATGTTCTACTGTGGGCCATCTCTGCCATG
TACTGTAGGCTACTAGCTTCTATATTAAAGAATGCAAGAGGGGCCAGGAGCGGAGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCAAGGTGGGCAGATCACTTGAGGTCAGGAGTTTGTGACCAGCCTGGCCAACATGGTGAAACTCTGCCTTTACTAAAAATAT
AAAAATTAGCTGGGTGTGGTGGTGTGCACCTGTAATCCCAGCTACTCGGGAGACTGAGGCACAAGAATTGCTTGAACCTGGGAGGCGGAAGTTGCAGTGAGCCCAGATTGCGCCACTGCACTCCACCCTGGGCAACAGAGAAAGACTCTGCCTCAAAAAAAAAAAAAA
AAAGCAAGAGGAAGTGAAATAATCAAGGCCGCCATTTAATAGTGAGCAGCCACTCCATGTGGTACTGTGCAAGCACATTATAAATATTAGCCTCACAAGAAATGTATTAGCATTTGTATTTTGTACACTGGTTAAGTATCTTGCCCAAGACCTCAAAACTGGTTAAGGGCA
GCAGAATTTAGCCCCAGCACCACCTTTTCAAAGCCTGGGCTTCTCACACTTCTCCATGCTGTTCCCATTTTAACACAGGTATCTCGCCATTCCAGCCACTCAAACTTTGGCATTTAAGAAAATTATCCTAAAGCTAAACTAAACTTCAAGGATGACCATTCTCCTGACCCCT
TCCCATCAAAATTTTATCTTTAGTCAGTTTGTTTTCGTTTTGTTTTGTTTTTCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGACTCACTTGGTAATTCTGGGAGCCATCTTATTATGCCTTGGTGTAGCACTGACATTCATCTTCCGTTTAAGAAAAGGTAGTATTTCC
TTAATTGCAGTGGTCTCCACTGGGGGTGAGGAAGGGGTGAGAATTGGATCATGGCTGCAAGGAAACCCGACTTAACCTCTGCAAGGTGGTGCAAAGGCATTCCACTGTTCAACAGCAATTATATTGAAGCTGAGTGGGATCACTGGGTGAAGATGAAGCGTAAGGGGT
GAGGGGCAGGAGAATGGGTATGGATGGAGGTAGAAGATGCAGTGTCATACAGTTTTTTTCTATCATGAAAATAACCACAGACTTACAGAAGAGAAAGAGCTAAAATGCCCGTCATTTTCAGTTGCATTTTAGTCTTGCATTAGTTGCAACCAGCTGGTTTCTGGGTACCCT
AAGTAATAAAAATAGTTCCTCTGTAGAACTGTAGTATGTTTACCATAGAGTATTTTGCAAAATTTTTGGTAGAGGATGTTACATAATTTGCATGTGTTCATTTCTCCATTTACCTGTGGGAACAATTAAAATCCAGGAAAATGAGTATATTCAAATAATTTCCTCCCATTTAAGA
TGAGTCAGAGTAAATAATTCCTCCAATACTTAGAGAAGTATACCAAGAGATCCAGTGATGGTATAGAGTTGTCTGATGTTAAATAGGGAAGTAGAATATGGAAGGGGATTCCAATAGTCGTTGAAAAATTCCCCATAACCCCTTACATGGGGGAAAGTAGTGTTAACTGAG
AGAGTAGAGATAAGCTGTTTCCAAAAATTATATTCTTAACAGGACTGAGATAGCCAGAATATAAGGATCAAGTTTCAATGACAGTAAGATCCTGAGATGGAGTTGATTTGCACAAAGAAATAATTGTTGCCAGCATGCATTTTGAATATTTCTCTGGAAAAAAAGATTAGTTG
GCAGTAGAAATGGATAGAAATCAATAGATATTAAAATACCTCAGAATTTGGTTCATCTCTGGGAAAAGATGAAAAATAAAAGTGTATACTCCTCAAGAACATCTAGGATCAAAAGCATGTGCCCTACACTATTGAATTAATTAACCTCATAAGTTGGGACCTGTGGAATAAG
GATGTCCACCAGACTTCCTAGGGATTACAAATGTTTCACAGAACTTGAAATTTAAACTTGGGTCACTGTAAAGAGAAATCCATCAGTCATAATCTCCTCTCCTTTTAAAGAATGCTGGTTCCCCTTTGCCTCACAGCTAACACAAGAACTCCTCCACCGTCTGAGGAGGTTT
AGGAGCAGGGAAGGGGAAGGAGTCAGCTTCATTTGCTAATCTTCTGTTGCCCTGCACCCTAGCAGCTCCTTGCAGCAGGGGACAAGGATGACTTAGGTGGATGGATAATTAATTGATTCTAAAATATTGTGTGTCAGTATTGTAATACTATGTTAATTGCACCATGCACG
GTATCTCATTTAATCCCCCACCCCTTGCCATTACCAAAGAGAGAGAGAGAGAGAGAGAGAGAAATACTAGAATTTATCCTCATTTTACAGTAGAGAAAACAGAGGGTCAAGAAGATAATGTAAAGTGCCCAAGAACACACAGCTGATCACAAAAATCAAGCTTGGGGGCC
ATTAGCCTAACCACAGACCCTTACTCTTAACCCATCTGCTTCAATCCATTTTGCTACAAATGTTTACATTTATAAGGAATGTGAAAGAAAGTGAGGCGAGTGAGCATGATATTTAATATAAACACAAAGATATTCTGAGAAGAGCTGCTCACTGCCCCCTCCCCCAATACAT
GTTGATAGGAAAATGCCACGTACTTCAGCAAAAACAACTGAAAAATTAGATAGAAAAGTCAATCAATAGGAAAAGATAATCCAGGACGGTGTTGTGAACAGAAAGAGGGGGAAAAAACTTTAGAAAATGATGGGGATGCTCTTACTGGGGTACGAGTCCTCAGGTATTGA
ACTGGCTTTCAGTAAAAGCTAGATTAGTGGGTTCCTGCCATTTACAAGCTGTTTTATGACAACTTACTTGTTGGGTGGCCTACAGTAACTCACCTAACTGCACTGAGTCTGTTTCCTCATCTGTAAATTGGGGATTTTTTTTTAAATACCTGGCATGCCTAACTCATAAAGTT
GTTCTGAAACTGAAATAAAACATACGTGAACAGGCATTGTAAACTGTAAGTTACGGAAAAAGCTGGCTGTTGTTGTGTCTTTAAAGTTTCACCTGGGTAGTCAAAGATGGATCATGGGTCTCAGTGGAGAGCTGAGCCAGGCAGGAGCTGACTAAGGGTGAGAGGTGGG
AGTTAGCAGCCTCTGAACATCTGTGTACCATGGGACCCCCTTTCCTCCTGCATGGTACCCCAGACAAGGAGCCTAGTAAGAGATACTAATGGCTTGTTGTCCAGAGATGTTCAAACTGCAGAGAAAGATAAGACAACAAGCATTGGCCTCCAATCATGATGACAGATAG
GAGGAGGTGGGAGCTCCTTAGCAGTGCTGGTTGGCCTTCCATGTTCTACTGTGGGCCATCTCTGCCATGTACTGTAGGCTACTAGCTTCTATATTAAAGAATGCAAGAGGGGCCAGGAGCGGAGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCAAGGTGGGCA
GATCACTTGAGGTCAGGAGTTTGTGACCAGCCTGGCCAACATGGTGAAACTCTGCCTTTACTAAAAATATAAAAATTAGCTGGGTGTGGTGGTGTGCACCTGTAATCCCAGCTACTCGGGAGACTGAGGCACAAGAATTGCTTGAACCTGGGAGGCGGAAGTTGCAGT
GAGCCCAGATTGCGCCACTGCACTCCACCCTGGGCAACAGAGAAAGACTCTGCCTCAAAAAAAAAAAAAAAAAGCAAGAGGAAGTGAAATAATCAAGGCCGCCATTTAATAGTGAGCAGCCACTCCATGTGGTACTGTGCAAGCACATTATAAATATTAGCCTCACAAG
AAATGTATTAGCATTTGTATTTTGTACACTGGTTAAGTATCTTGCCCAAGACCTCAAAACTGGTTAAGGGCAGCAGAATTTAGCCCCAGCACCACCTTTTCAAAGCCTGGGCTTCTCACACTTCTCCATGCTGTTCCCATTTTAACACAGGTATCTCGCCATTCCAGCCACT
CAAACTTTGGCATTTAAGAAAATTATCCTAAAGCTAAACTAAACTTCAAGGATGACCATTCTCCTGACCCCTTCCCATCAAAATTTTATCTTTAGTCAGTTTGTTTTCGTTTTGTTTTGTTTTTCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGACTCACTTGGTAATT
CTGGGAGCCATCTTATTATGCCTTGGTGTAGCACTGACATTCATCTTCCGTTTAAGAAAAGGTAGTATTTCCTTAATTGCAGTGGTCTCCACTGGGGGTGAGGAAGGGGTGAGAATTGGATCATGGCTGCAAGGAAACCCGACTTAACCTCTGCAAGGTGGTGCAAAGG
CATTCCACTGTTCAACAGCAATTATATTGAAGCTGAGTGGGATCACTGGGTGAAGATGAAGCGTAAGGGGTGAGGGGCAGGAGAATGGGTATGGATGGAGGTAGAAGATGCAGTGTCATACAGTTTTTTTCTATCATGAAAATAACCACAGACTTACAGAAGAGAAAGA
GCTAAAATGCCCGTCATTTTCAGTTGCATTTTAGTCTTGCATTAGTTGCAACCAGCTGGTTTCTGGGTACCCTAAGTAATAAAAATAGTTCCTCTGTAGAACTGTAGTATGTTTACCATAGAGTATTTTGCAAAATTTTTGGTAGAGGATGTTACATAATTTGCATGTGTTCAT
TTCTCCATTTACCTGTGGGAACAATTAAAATCCAGGAAAATGAGTATATTCAAATAATTTCCTCCCATTTAAGATGAGTCAGAGTAAATAATTCCTCCAATACTTAGAGAAGTATACCAAGAGATCCAGTGATGGTATAGAGTTGTCTGATGTTAAATAGGGAAGTAGAATAT
GGAAGGGGATTCCAATAGTCGTTGAAAAATTCCCCATAACCCCTTACATGGGGGAAAGTAGTGTTAACTGAGAGAGTAGAGATAAGCTGTTTCCAAAAATTATATTCTTAACAGGACTGAGATAGCCAGAATATAAGGATCAAGTTTCAATGACAGTAAGATCCTGAGATG
GAGTTGATTTGCACAAAGAAATAATTGTTGCCAGCATGCATTTTGAATATTTCTCTGGAAAAAAAGATTAGTTGGCAGTAGAAATGGATAGAAATCAATAGATATTAAAATACCTCAGAATTTGGTTCATCTCTGGGAAAAGATGAAAAATAAAAGTGTATACTCCTCAAGAA
CATCTAGGATCAAAAGCATGTGCCCTACACTATTGAATTAATTAACCTCATAAGTTGGGACCTGTGGAATAAGGATGTCCACCAGACTTCCTAGGGATTACAAATGTTTCACAGAACTTGAAATTTAAACTTGGGTCACTGTAAAGAGAAATCCATCAGTCATAATCTCCTC
TCCTTTTAAAGAATGCTGGTTCCCCTTTGCCTCACAGCTAACACAAGAACTCCTCCACCGTCTGAGGAGGTTTAGGAGCAGGGAAGGGGAAGGAGTCAGCTTCATTTGCTAATCTTCTGTTGCCCTGCACCCTAGCAGCTCCTTGCAGCAGGGGACAAGGATGACTTAG
GTGGATGGATAATTAATTGATTCTAAAATATTGTGTGTCAGTATTGTAATACTATGTTAATTGCACCATGCACGGTATCTCATTTAATCCCCCACCCCTTGCCATTACCAAAGAGAGAGAGAGAGAGAGAGAGAGAAATACTAGAATTTATCCTCATTTTACAGTAGAGAAAA
CAGAGGGTCAAGAAGATAATGTAAAGTGCCCAAGAACACACAGCTGATCACAAAAATCAAGCTTGGGGGCCATTAGCCTAACCACAGACCCTTACTCTTAACCCATCTGCTTCAATCCATTTTGCTACAAATGTTTACATTTATAAGCAGGGCAGAAAAACCTCATCCAGG
TTATTGAACTAAGAAGAAAGTTATATTAAGGTTTCTAATTTTTTTAATGTAGTTAGAAACCAAACTTAACAATGAGCCCAAGTTTAAAGCAGTCTAATTAACCTGGACAAGCTCAGGCAAGTTTCATTCTGTGGCCCATAGCATCATCTGTGTTGTAAAGCTAAGTAGCAAAT
GTTGTTTGGGTCATGCTGGGGGACAAGCCATCCCAATTTGCTCAGGACTGAGGGGTTTTCCAGGATATCATGTAAGGATAATTGGGTACAAATA

TAACCTGCTGCTTTCTCTCATTTCAAATTTATCATTTATCATATCAGCAACTATGAGTTATGTTTTTTATTAGATTTCTTGTTACTTTTTCCCCAGACCACTTCCCATGAAATTAATATACTATTATCACTCTCCAGATACACATTTGGAGGAGACGTAATCCAGCATTGGAACT
T
CTGATCTTCAAGCAGGGATTCTCAACCTGTGGTTTAGGGGTTCATCGGGGCTGAGCGTGACAAGAGGAAGGAATGGGCCCGTGGGATGCAGGCAATGTGGGACTTAAAAGGCCCAAGCACTGAAAATGGAACCTGGCGAAAGCAGAGGAGGAGAATGAAGAAAGAT
GGAGTCAAACAGGGAGCCTGGAGGGAGACCTTGATACTTTCAAATGCCTGAGGGGCTCATCGACGCCTGTGACAGGGAGAAAGGATACTTCTGAACAAGGAGCCTCCAAGCAAATCATCCATTGCTCATCCTAGGAAGACGGGTTGAGAATCCCTAATTTGAGGGTCA
GTTCCT
GCAGAAGTGCCCTTTGCCTCCACTCAATGCCTCAATTTGTTTTCTGCATGACTGAGAGTCTCAGTGTTGGAACGGGACAGTATTTATGTATGAGTTTTTCCTATTTATTTTGAGTCTGTGAGGTCTTCTTGTCATGTGAGTGTGGTTGTGAATGATTTCTTTTGAAGATATAT
TGTAGTAGATGTTACAATTTTGTCGCCAAACTAAACTTGCTGCTTAATGATTTGCTCACATCTAGTAAAACATGGAGTATTTGTAAGGTGCTTGGTCTCCTCTATAACTACAAGTATACATTGGAAGCATAAAGATCAAACCGTTGGTTGCATAGGATGTCACCTTTATTTAA
CCCATTAATACTCTGGTTGACCTAATCTTATTCTCAGACCTCAAGTGTCTGTGCAGTATCTGTTCCATTTAAATATCAGCTTTACAATTATGTGGTAGCCTACACACATAATCTCATTTCATCGCTGTAACCACCCTGTTGTGATAACCACTATTATTTTACCCATCGTACAGC
TGAGGAAGCAAACAGATTAAGTAACTTGCCCAAACCAGTAAATAGCAGACCTCAGACTGCCACCCACTGTCCTTTTATAATACAATTTACAGCTATATTTTACTTTAAGCAATTCTTTTATTCAAAAACCATTTATTAAGTGCCCTTGCAATATCAATCGCTGTGCCAGGCAT
TGAATCTACAGATGTGAGCAAGACAAAGTACCTGTCCTCAAGGAGCTCATAGTATAATGAGGAGATTAACAAGAAAATGTATTATTACAATTTAGTCCAGTGTCATAGCATAAGGATGATGCGAGGGGAAAACCCGAGCAGTGTTGCCAAGAGGAGGAAATAGGCCAATG
TGGTCTGGGACGGTTGGATATACTTAAACATCTTAATAATCAGAGTAATTTTCATTTACAAAGAGAGGTCGGTACTTAAAATAACCCTGAAAAATAACACTGGAATTCCTTTTCTAGCATTATATTTATTCCTGATTTGCCTTTGCCATATAATCTAATGCTTGTTTATATAGTG
TCTGGTATTGTTTAACAGTTCTGTCTTTTCTATTTAAATGCCACTAAATTTTAAATTCATACCTTTCCATGATTCAAAATTCAAAAGATCCCATGGGAGATGGTTGGAAAATCTCCACTTCATCCTCCAAGCCATTCAAGTTTCCTTTCCAGAAGCAACTGCTACTGCCTTTCA
TTCATATGTTCTTCTAAAGATAGTCTACATTTGGAAATGTATGTTAAAAGCACGTATTTTTAAAATTTTTTTCCTAAATAGTAACACATTGTATGTCTGCTGTGTACTTTGCTATTTTTATTTATTTTAGTGTTTCTTATATAGCAGATGGAATGAATTTGAAGTTCCCAGGGCTG
AGGATCCATGCCTTCTTTGTTTCTAAGTTATCTTTCCCATAGCTTTTCATTATCTTTCATATGATCCAGTATATGTTAAATATGTCCTACATATACATTTAGACAACCACCATTTGTTAAGTATTTGCTCTAGGACAGAGTTTGGATTTGTTTATGTTTGCTCAAAAGGAGACCC
ATGGGCTCTCCAGGGTGCACTGAGTCAATCTAGTCCTAAAAAGCAATCTTATTATTAACTCTGTATGACAGAATCATGTCTGGAACTTTTGTTTTCTGCTTTCTGTCAAGTATAAACTTCACTTTGATGCTGTACTTGCAAAATCACATTTTCTTTCTGGAAATTCCGGCAGT
GTACCTTGACTGCTAGCTACCCTGTGCCAGAAAAGCCTCATTCGTTGTGCTTGAACCCTTGAATGCCACCAGCTGTCATCACTACACAGCCCTCCTAAGAGGCTTCCTGGAGGTTTCGAGATTCAGATGCCCTGGGAGATCCCAGAGTTTCCTTTCCCTCTTGGCCATAT
TCTGGTGTCAATGACAAGGAGTACCTTGGCTTTGCCACATGTCAAGGCTGAAGAAACAGTGTCTCCAACAGAGCTCCTTGTGTTATCTGTTTGTACATGTGCATTTGTACAGTAATTGGTGTGACAGTGTTCTTTGTGTGAATTACAGGCAAGAATTGTGGCTGAGCAAGG
CACATAGTCTACTCAGTCTATTCCTAAGTCCTAACTCCTCCTTGTGGTGTTGGATTTGTAAGGCACTTTATCCCTTTTGTCTCATGTTTCATCGTAAATGGCATAGGCAGAGATGATACCTAATTCTGCATTTGATTGTCACTTTTTGTACCTGCATTAATTTAATAAAATATT
CTTATTTATTTTGTTACTTGGTACACCAGCATGTCCATTTTCTTGTTTATTTTGTGTTTAATAAAATGTTCAGTTTAACATCCCAGTGGAGAAAGTTA

Transcription (DNA->mRNA)

The process begins when helicase, a family of enzymes, unwinds a specific

portion of the DNA sequence, and a transcription bubble is made around the
antisense DNA strand.

In the next step, RNA polymerase synthesizes the complementary strand of

nucleotides for the RNA (formation of mRNA).

The process begins at the promoter of the gene, and ends at terminator
sequence.

Finally, the hydrogen bonds of the DNA and RNA nucleotides are broken, and
the mRNA strand goes to the ribosome, where it is translated.

ggcgcaacgcugagcagcuggcgcgucccgcgcggccccaguucugcgcagcuucccgaggcuccgcaccagccgcgcuucuguccgccugcagggcauuccagaaagaugaggauauuu
gcugucuuuauauucaugaccuacuggcauuugcugaacgcauuuacugucacgguucccaaggaccuauaugugguagaguaugguagcaauaugacaauugaaugcaaauuccca
guagaaaaacaauuagaccuggcugcacuaauugucuauugggaaauggaggauaagaacauuauucaauuugugcauggagaggaagaccugaagguucagcauaguagcuacaga
cagagggcccggcuguugaaggaccagcucucccugggaaaugcugcacuucagaucacagaugugaaauugcaggaugcagggguguaccgcugcaugaucagcuaugguggugccg
acuacaagcgaauuacugugaaagucaaugccccauacaacaaaaucaaccaaagaauuuugguuguggauccagucaccucugaacaugaacugacaugucaggcugagggcuacccc
aaggccgaagucaucuggacaagcagugaccaucaaguccugagugguaagaccaccaccaccaauuccaagagagaggagaagcuuuucaaugugaccagcacacugagaaucaacac
aacaacuaaugagauuuucuacugcacuuuuaggagauuagauccugaggaaaaccauacagcugaauuggucaucccagaacuaccucuggcacauccuccaaaugaaaggacucacu
ugguaauucugggagccaucuuauuaugccuugguguagcacugacauucaucuuccguuuaagaaaagggagaaugauggaugugaaaaaauguggcauccaagauacaaacucaa
agaagcaaagugauacacauuuggaggagacguaauccagcauuggaacuucugaucuucaagcagggauucucaaccugugguuuagggguucaucggggcugagcgugacaagag
gaaggaaugggcccgugggaugcaggcaaugugggacuuaaaaggcccaagcacugaaaauggaaccuggcgaaagcagaggaggagaaugaagaaagauggagucaaacagggagc
cuggagggagaccuugauacuuucaaaugccugaggggcucaucgacgccugugacagggagaaaggauacuucugaacaaggagccuccaagcaaaucauccauugcucauccuagga
agacggguugagaaucccuaauuugagggucaguuccugcagaagugcccuuugccuccacucaaugccucaauuuguuuucugcaugacugagagucucaguguuggaacgggacag
uauuuauguaugaguuuuuccuauuuauuuugagucugugaggucuucuugucaugugagugugguugugaaugauuucuuuugaagauauauuguaguagauguuacaauuuu
gucgccaaacuaaacuugcugcuuaaugauuugcucacaucuaguaaaacauggaguauuuguaaggugcuuggucuccucuauaacuacaaguauacauuggaagcauaaagauca
aaccguugguugcauaggaugucaccuuuauuuaacccauuaauacucugguugaccuaaucuuauucucagaccucaagugucugugcaguaucuguuccauuuaaauaucagcuuu
acaauuaugugguagccuacacacauaaucucauuucaucgcuguaaccacccuguugugauaaccacuauuauuuuacccaucguacagcugaggaagcaaacagauuaaguaacuu
gcccaaaccaguaaauagcagaccucagacugccacccacuguccuuuuauaauacaauuuacagcuauauuuuacuuuaagcaauucuuuuauucaaaaaccauuuauuaagugcccu
ugcaauaucaaucgcugugccaggcauugaaucuacagaugugagcaagacaaaguaccuguccucaaggagcucauaguauaaugaggagauuaacaagaaaauguauuauuacaa
uuuaguccagugucauagcauaaggaugaugcgaggggaaaacccgagcaguguugccaagaggaggaaauaggccaauguggucugggacgguuggauauacuuaaacaucuuaau
aaucagaguaauuuucauuuacaaagagaggucgguacuuaaaauaacccugaaaaauaacacuggaauuccuuuucuagcauuauauuuauuccugauuugccuuugccauauaau
cuaaugcuuguuuauauagugucugguauuguuuaacaguucugucuuuucuauuuaaaugccacuaaauuuuaaauucauaccuuuccaugauucaaaauucaaaagaucccaugg
gagaugguuggaaaaucuccacuucauccuccaagccauucaaguuuccuuuccagaagcaacugcuacugccuuucauucauauguucuucuaaagauagucuacauuuggaaaugu
auguuaaaagcacguauuuuuaaaauuuuuuuccuaaauaguaacacauuguaugucugcuguguacuuugcuauuuuuauuuauuuuaguguuucuuauauagcagauggaaug
aauuugaaguucccagggcugaggauccaugccuucuuuguuucuaaguuaucuuucccauagcuuuucauuaucuuucauaugauccaguauauguuaaauauguccuacauauac
auuuagacaaccaccauuuguuaaguauuugcucuaggacagaguuuggauuuguuuauguuugcucaaaaggagacccaugggcucuccagggugcacugagucaaucuaguccua
aaaagcaaucuuauuauuaacucuguaugacagaaucaugucuggaacuuuuguuuucugcuuucugucaaguauaaacuucacuuugaugcuguacuugcaaaaucacauuuucuu
ucuggaaauuccggcaguguaccuugacugcuagcuacccugugccagaaaagccucauucguugugcuugaacccuugaaugccaccagcugucaucacuacacagcccuccuaagagg
cuuccuggagguuucgagauucagaugcccugggagaucccagaguuuccuuucccucuuggccauauucuggugucaaugacaaggaguaccuuggcuuugccacaugucaaggcug
aagaaacagugucuccaacagagcuccuuguguuaucuguuuguacaugugcauuuguacaguaauuggugugacaguguucuuugugugaauuacaggcaagaauuguggcugag

Translation (mRNA->Protein)

The newly formed mRNA sequence moves to ribosomes, where the proteins
are formed in a linear polypeptide structure.

In the ribosome, various tRNA, transfer RNA, bind to codons on mRNA

through their anticodons on one end, and an amino acid on the other end.

Elongation of the peptide chain is facilitated by rRNA, ribosomal RNA, which

catalyzes the formation of peptide bonds.

The translation process always begins with the codon AUG, which codes for
methionine, and ends with a stop codon (UAA,UAG,UGA) that is recognized
by proteins known as release factors, which facilitates the separation of the
mRNA and protein.

Amino Acid Sequence

MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVY
WEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDA
GVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKA
EVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEE
NHTAELVIPELPLAHPPNERTHLVILGAILLCLGVALTFIFRLRKGRMMDVKKCGI
QDTNSKKQSDTHLEET

Protein Folding

After the mRNA is translated to a protein, it goes to the rough endoplasmic

reticulum to be folded into a specific three dimensional structure.

After being folded in the E.R., it is sent to the Golgi apparatus where it may be
further augmented with carbohydrates, which helps with receptor bonding.

A further change that may take place in the Golgi apparatus is

phosphorylation, which is the addition of a phosphate group that influences
protein activity

The physical folding of the polypeptide is facilitated by protein

disulfide-isomerase, which is an enzyme that catalyzes bonds between
cysteine amino acids.