Tumor Endothelial Marker Report: TEM2 (ras-like)

TEM domain structure

	TEM domain structure

TEM Sequence Analysis

name from to source/E description

unknown 1 33 An N-terminal extension of this size could carry an additional subdomain. Due to the similarity to rat Rhes the N-terminal extension is proposed to localize in general vicinity of the C-terminus, potentially being involved in direct physical interaction with the C-terminal domain.

RAS 33 198 PfamFrag, E=2e-37 The G1 to G5 motifs characteristic of GTPases are well conserved in TEM2.
Thus the GTP hydrolysis function is presumed to be conserved.

unknown 198 278 PROSITE: Y-Phosphorylation site (PS00007) at 232
PROSITE: Prenylation site (PS00294) at 275 The C-terminal region of TEM2 is helix-rich and shows 92% identity to rat Rhes and 46% identity to mouse Dexras1. The C-terminus of Dexras1 (235-280) is known to bind the PTB domain located at the N terminus of CAPON.

278

	TEM Sequence Analysis

name	from	to	source/E	description
unknown	1	33		An N-terminal extension of this size could carry an additional subdomain. Due to the similarity to rat Rhes the N-terminal extension is proposed to localize in general vicinity of the C-terminus, potentially being involved in direct physical interaction with the C-terminal domain.
RAS	33	198	PfamFrag, E=2e-37	The G1 to G5 motifs characteristic of GTPases are well conserved in TEM2. Thus the GTP hydrolysis function is presumed to be conserved.
unknown	198	278	PROSITE: Y-Phosphorylation site (PS00007) at 232 PROSITE: Prenylation site (PS00294) at 275	The C-terminal region of TEM2 is helix-rich and shows 92% identity to rat Rhes and 46% identity to mouse Dexras1. The C-terminus of Dexras1 (235-280) is known to bind the PTB domain located at the N terminus of CAPON.
278

Remarks

	Remarks

CLASSIFICATION: Ras superfamily member(subfamilies Ras, Rho, Rab, Ran, ARF, Rap, Rad/Gem/Kir), Rap subfamily. TEM2 (280 amino acids) is longer than most Ras subfamily members (180-220 amino acids), amino acid differences exist between Dexras1 and typical Ras subfamily members within some of the GTPase characteristic motifs (e.g. in regions G-2 and G-3).

HOMOLOGS: Orthologous in rat, mouse and Drosophila.

DOMAIN ARCHITECTURE: TEM2 shows the following motif characteristic of GTPases: G-1(38-45): Lysine 44 is proposed to form hydrogen bonds with the alpha and beta-phosphates of GTP or GDP, and the structure of the region is proposed not to change upon GDP-GTP exchange, G-2(60-68) with a conserved threonine involved in Mg ion coordination, G-3(81-90) with an aspartate involved in in Mg ion coordination, a glycine forming hydrogen bonds with the gamma of GTP, changes its conformation upon GDP-GTP exchange, G-4(148-55) with an asparagine forming the hydrogen bonds with goups of the guanine ring, asparagine and lysine stabilize the the structure by hydrogen bonding to the G-1 region, G-5(176-78) interacts indirectly with the guanine ring. The C-terminus has a typical CAAX (A aliphatic, X any) motif needed for the anchorage in the membrane following prenylation.cdc42 3D model
An extended C-terminus is also found in several transcriptionally regulated GTPases, e.g. the Rad/Gem/Kir/Rem subfamily. Yeast ras1, ras2 show a C-terminal domain as large as the guanine nucleotide binding domain.
FUNCTION BY SIMILARITY:
- DOWNSTREAM TARGETS: TEM2 is a small G-protein belonging to the Rap subfamily, which are known to signal through B-Rap preferentially to A-Rap. Tem2 has a effector loop (60-68) that is 78% identical to the Rap2a/b effector loop and thus could have similar effectors.
- Rhes protein[Rattus norvegicus],Ras homolog enriched in striatum. Identity =95%
  Rhes is not induced by dexamethasone, but its full expression is dependent upon thyroid hormone availability. Its accumulation is postnatal, consistent with the dependence upon thyroid hormone.
- Dexras1 Ras subfamily, induced by dexamethasone (Dex) Identity =61%
  Was the first Ras superfamily member identified that is induced in response to steroids. DexRas1 in dexamethasone-induced alterations in cell morphology, growth and cell-extracellular matrix interactions.
  TEM2, Rhes, Dexras1 have substantially longer C-termini than other members of the Ras-like small G-protein family. The extended C terminus of DexRas1 (235-280) mediates its interaction with the PTB domain of CAPON,and in this way provides the selectivity of nNOS-mediated activation of Dexras1/nNOS complexes. The PTB domain interacting with Dexras1 is related to the Numb-PTB domain that has a broad binding specificity and does not require tyrosine phosphorylation for peptide binding. The extended N-terminus is dispensable for the Dexras1/CAPON interaction. It is proposed that the CAPON/NOS/DexRas1 complex juxtapose nNOS with its targets. By analogy it could be proposed that the C-terminus of TEM2 could mediate its interaction with CAPON/PTB or related. Whether TEM2 is activated in a NO-dependent manner analogous to Dexras1 cannot be determined as a specific S-nitrosylation site for Dexras1 is not known (although proposed).
SEQUENCE CORRECTION: The extreme N-terminus of the used Tem-2 mRNA sequence appears to be predicted incorrectly. Reasons for this assumption have been:
1. In a BlastN against the human EST DB, the found ESTs show up to 100% alignment in the region 25-143 of the proposed TEM2-mRNA with a collective, sharp stop in the alignments at position 25. But the ESTs extend about 170 nt upstream of the aligned region; thus, they describe a protein with a N-terminus probably different from the putative TEM2. The EST hits were clustered and aligned against the mRNA to visualize the discrepancy between mRNA and ESTs that is restricted to the first 25 nt. The mRNA region, spanning over 25 nt, has been translated into the extreme, non-real N-terminus of the Tem-2 protein sequence.
2. The misprediction is potentially based on a prediction error that has included 25nt of the genomic DNA which are not part of the actual TEM2 RNA sequence. Take a look on the genomic sequence to see the actual TEM2 RNA= EST (in bold) and the potentially misinterpreted 25nt in the context of the genomic sequence.
3. The N-terminal region of the protein remains unclearly defined. The protein could extend further N-terminally as a prediction based on EST leads to a protein (ref|XP_001019.1) with a longer N-terminus (around 50aa), as can be viewed in the BlastP search. The longer protein has not been considered since the studied rat ortholog, Rhes, has a shorter sequence as can be seen in the BlastP search.

Sequence Information

TEM TEM2

Reliability of Gen2Tag mapping

Cid->tag (Hs.248222) frequency:
tem2: CATG-GATCTCCGTG=5/6 (ESTs, oriented)

Analysis
BlastP against nr

Output Created by a Suite of Single Sequence Analysis Techniques

Protein Description

SEQ.SOURCE: gi|9857402|gb|AAG00868.1|AF279143_1 tumor endothelial marker 2 [Homo sapiens]

ANALYSIS: TblastN against Unigen

Protein Sequence

MPASLALLQPRAMMKTLSSGNCTLSVPAKNSYRMVVLGASRVGKSSIVSRFLNGRFEDQYTPTIEDFHRK VYNIRGDMYQLDILDTSGNHPFPAMRRLSILTGDVFILVFSLDNRESFDEVKRLQKQILEVKSCLKNKTK EAAELPMVICGNKNDHGELCRQVPTTEAELLVSGDENCAYFEVSAKKNTNVDEMFYVLFSMAKLPHEMSP ALHRKISVQYGDAFHPRPFCMRRVKEMDAYGMVSPFARRPSVNSDLKYIKAKVLREGQARERDKCTIQ

SAGE-Tag CATG-GATCTCCGTGT

EST/cluster Description

UNIGEN CLUSTER: Hs.248222 : similar to mouse Ras, dexamethasone-induced 1

SEQ.SOURCE: ugc|Hs.248222.2|Hs.248222 GENE=RASD1
gi|9857401|gb|AF279143.1|AF279143 TEM2 mRNA

REMARKS:
BlastN against human ESTs
and alignment of mRNA with a contig created from the EST sequences
show that the annotation of the TEM2 mRNA start codon
cannot be supported by EST sequence consideration

MARKINGS: TEM2 Tag in red
first Poly-A-signal following the Tag in bold
wrongly annotated start codon of TEM2 mRNA in bold

EST/cluster Sequence

GGCCCTTCCGCCGTCTTGCCCGGCGGCGCCCAGCCCGGCGTCCGAGCAGCGCAGGGAAGGATCCCCGCGCAGTGACCCGG GAGCCACCACATGACTCTGGGAGGCTCGGCGGCTGGAGCAGCAGGCAGCTCCCCGCAGCTCCCGGCGCTTCCAGGCAGCT CTCTGAGCCGTGCCAGAGGCCCGGCCCGCCATTCCCAGCCCCGAGCCATGATGAAGACTTTGTCCAGCGGGAACTGCACG CTCAGTGTGCCCGCCAAAAACTCATACCGCATGGTGGTGCTGGGTGCCTCTCGGGTGGGGCAAGAGCTCCATCGTGTCTC GCTTCCTCAATGGCCGCTTTGAGGACCAGTACACACCCACCATCGAGGACTTCCACCGTAAGGTATACAACATCCGCGGC GACATGTACCAGCTCGACATCCTGGATACCTCTGGCAACCACCCCTTCCCCGCCATGCGCAGGCTGTCCATCCTCACAGG GGATGTCTTCATCCTGGTGTTCAGCCTGGATAACCGGGAGTCCTTCGATGAGGTCAAGCGCCTTCAGAAGCAGATCCTGG AGGTCAAGTCCTGCCTGAAGAACAAGACCAAGGAGGCGGCGGAGCTGCCCATGGTCATCTGTGGCAACAAGAACGACCAC GGCGAGCTGTGCCGCCAGGTGCCCACCACCGAGGCCGAGCTGCTGGTGTCGGGCGACGAGAACTGCGCCTACTTCGAGGT GTCGGCCAAGAAGAACACCAACGTGGACGAGATGTTCTACGTGCTCTTCAGCATGGCCAAGCTGCCACACGAGATGAGCC CCGCCCTGCATCGCAAGATCTCCGTGCAGTACGGTGACGCCTTCCACCCCAGGCCCTTCTGCATGCGCCGCGTCAAGGAG ATGGACGCCTATGGCATGGTCTCGCCCTTCGCCCGCCGCCCCAGCGTCAACAGTGACCTCAAGTACATCAAGGCCAAGGT CCTTCGGGAAGGCCAGGCCCGTGAGAGGGACAAGTGCACCATCCAGTGAGCGAGGGATGCTGGGGCGGGGCTTGGCCAGT GCCTTCAGGGAGGTGGCCCCAGATGCCCACTGTGCGCATCTCCCCACCGAGGCCCCGGCAGCAGTCTTGTTCACAGACCT TAGGCACCAGACTGGAGGCCCCCGGGCGCTGGCCTCCGCACATTCGTCTGCCTTCTCACAGCTTTCCTGAGTCCGCTTGT CCACAGCTCCTTGGTGGTTTCATCTCCTCTGTGGGAGGACACATCTCTGCAGCCTCAAGAGTTAGGCAGAGACTCAAGTT ACACCTTCCTCTCCTGGGGTTGGAAGAAATGTTGATGCCAGAGGGGTGAGGATTGCTGCGTCATATGGAGCCTCCTGGGA CAAGCCTCAGGATGAAAAGGACACAGAAGGCCAGATGAGAAAGGTCTCCTCTCTCCTGGCATAACACCCAGCTTGGTTTG GGTGGCAGCTGGGAGAACTTCTCTCCCAGCCCTGCAACTCTTACGCTCTGGTTCAGCTGCCTCTGCACCCCCTCCCACCC CCAGCACACACACAAGTTGGCCCCCAGCTGCGCCTGACATTGAGCCAGTGGACTCTGTGTCTGAAGGGGGCGTGGCCACA CCTCCTAGACCACGCCCACCACTTAGACCACGCCCACCTCCTGACCGCGTTCCTCAGCCTCCTCTCCTAGGTCCCTCCGC CCGACAGTTGTGCTTTGTTGTGGTTGCAGCTGTTTTCGTGTCATGTATAGTAGTAGAAATGGAAATCATTGTACTGTAAA AGCCTAGTGACTCCCTCCTTGGGCCAGGCCCTCACCCAGTTCAGATCCACGGCCTCCACCCGGGACGCCTTCCTCCTCTG CTCCCAAACAGGGTTTCCGTGGCCTGTTTGCAGCTAGACATTGACCTCCGCCATTGAGCTCCACGGTTTACAGACAATTG CACAAGCGTGGGGTGGGCAGGCCAGGACTGCTTTTTTTTAATGCTCCCATTTCACAGAGGATACCACCGAGACTCGGGAG GGGACACGATGAGCACCAGGCCCCACCTTTGTCCCCTAGCAAATTCAGGGTACAGCTCCACCTAGAACCAGGCTGCCCTC TACTGTGCTCGTTCCTCAAGCATTTATTAAGCACCTACTGGGTGCTGGGTTCACTGTGTCCTAGGAAACCAAGAGGGTCC CCAGTCCTGGCCTCTGCCCGCCCCTGCTGCCCCACCACCTTCTGCACACACAGCGGTGGGGAGGCGGGGAGGAGCAGCTG GGACCCAGAACTGAGCCTGGGAGGGATCCGACAGAAAAGCTCAGGGCGGGTCTTCTCCTTGTGCCCGGGATTGGGCTATG CTGGGTACCACCATGTACTCAGGCATGGTGGGTTTTGAACCCATAAACCAAAGGCCCTTGTCATCAGCTCTTAACAAGTA TATTTTGTATTTTAATCTCTCTAAACATATTGAAGTTTTAGGGCCCTAAGGAACCTTAGTGATCTTCTATTGGGTCTTTC TGAGGTTCAGAGAGGGTAAGTAACTTCCTCCAGGTCACACAGCAAGTCTGTGGGTGGCAGAAGCAAGCTAGCGCTGGGCA TTCAGTACATACCACGATGTGCTCCCTCTCTTGATGCTTGGCCCCTGGGGCCTTCAGGGCTTTGGGACATCTTGTCCTCA ACCCTCTCCCTAGATCAGTCTGTGAGGGTCCCTGTAGATATTGTGTACACCATGCCCATGTATATACAAGTACACACAGA TGTACACACAGATGTACACATGCTCCAGCCCCAGCTCTGCATACCTGCACCTGCACCCCAGCCTTGGCCCCTGCCTGCGT CTGTGCTCAAAGCAGCAGCTCCAACCCTGCCTCTGTCCCCTTCCCCACCCACTGCCTGAGCCTTCTGAGCAGACCAGGTA CCTTGGCTGCACCGGTGTGTGGCCCGCTCTCACCCAGGCACAGCCCCGCCACCATGGATCTCCGTGTACACTATCAATAA
AAGTGGGTTTGTTACAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAC

Genomic Sequence Description

SEQ.SOURCE: gi|8573266|ref|NT_001454.20|Hs22_1584| Homo sapiens 22q11.2-q13.2

MARKINGS: transcribed sequence (EST) in bold
first, potentially mispredicted nt of TEM2 mRNA in red

ANALYSIS: Promotoranalysis

Genomic Sequence

TGTTGTCAGCCTCAGTTTTCTCATCTACAAATGACTCTAATAATGCTTCTCCACGTAGGGTTGTGGTCTG GCTAAAATGGGTCCATGTAATTACAGGGATCCACCCAGTGCCTGCAAAGAGTGGGGGCTCCATAAATGGT CTTCATTGTGATTGCAAGCCTCTGGTCCACTCCAGCTCTTTCTCTCCTGGCTGCCCACTCAGCTTGGCCC AACCTGGTTGATCACAGTCATCATAGTTCCCTGCAAAAATATTCTGTGGTGCATTCTCAAGGACTAGATG AGGTCACAAAGGGCTGCCCTGTATGGTTGTGTAGGTTGCTTACTGTGCAAGGGCACTCAGCTGAGGAAAT AGCTTGTGCCTTTCCTTTCAAAACTGAGAGCTTTCCCTCAAAGCTGAGAGCTTTAAAGACGGCTGCCTCT GCCTGGGAAAGGAACCTTTCTTTTATTTGCATAAAAACAACACATGGGCTGGAAGGCACCTGAATCACCC GTGGTGGGATTAAACCAGCTTGGAAATGTAGACTCGGATGGGTCTCAGAGAGCACCCAACATTCTTGTTG GACAGAGGAAGAAACTGACCACTATTTATTCATTCATCCAACTTTTACTGCCCACTGATTGACAAGTACC ACCTCTCCTCTCAAGAGGGCGAGGACCCCATGACAGATTATTACATGCTTTTCAAACCTATTTGGATATT GATTCTGGACATCAAGAGTTTATATAGGAAGCTCTGGCCAGATGCAGTGGCTCACACCTGTAATTTCAAC ACATTGGGAGGCAGAGGCAGGAAGCTCGCTTGAGCCCAGGAGTTTGAGACCAGCCTGGGCAACATAGCAA GACCCTGTCTCTACAAAAAATTTAAAAATTAGCCGGGTGTGATGGTGCATGCCTGTAATCCTAGGTATTT AGGAGCCTGAGGTGGGAGGATCGCTTGAGCCCAGCAGGTTGAGGCTGTAGTGAGCCATGATCACAACACT GCACTCCAGTGTGAACTACAGAGCAAGACCCTGTCTCCAAAAAAAAAAGAAAAAAAAAAGAGTTTACATA GCAAGTTCAGAGAGTAAAAGATGATGCATTATCCAAATCTATTGGAACCCCAAGTTTCAGATATGAGTAG CAAGAGTTCAGACAGTGAGGGTTGAATCCAAAAGCAAAAGATTTCTGTAAGGCAGCTCCATGGAGCACAG AAGAGAGAGCAACCAAGACTTCCCAGAGGCAGTGATGCTTGATTCCAGAAGGAAAGCTAGGAGCCTGCTG GCAATCCAGAGATGAGCAGCCCCTCAGGCACAGGCTCCAGCATGTGCAAAGACCTAGGGTACAGAGAGCC TGGCAAGCTCAGGGAACTACAAGTCAGTGTCTTTGGCTGGAGCATAAAGGAGGGGAGGAAGAATGCCGGG CAATGAGGGTCAGAGACGTTAAGTGGCCCATTCAAGGGTCACACAGCAAACTTCTGTTTAGTTGGGATTA GAACCCAGGCTCCTGACTGAATTGGGGCTTGCTTGGATCATCGGGCTCAGTGGGTGGGGGGAGGGGCAGC AAGAGGCAGAAATGGTCAGATGCACCGGGGGCAGGGTGTGGCTGGTTCAGCTGTGCTCCTGTTGATCTTT GGCCTGGTGGGGCACCCCTCCTCCCATGTCATTGCCAGTCTGCCTTCAGGGATGTTTGGTGAGGCCTTGA ATGCCAGATGAGGTGCCAGCCTGTTCCGGCTATCTGCCCTCTGTACTGACTGGCACCTGACCCAGTGCCC CAGTCCAGCTGAGCTTATGCAGCTGGTGACCCATTGACCTCTGATGAAGTTCAAGGCTGGCACAGATGCC CAGGCCTGCCAAGGCAAGAGACTCAGTTAGAGGCTGTGTAGTCTGGGATGGTGCATTCAGCAGGAAAGAA TGAGCCTGTCATGAGCATGTGTTGAACTTGGTCAAGCCACAAACCGTCTCTTTTTTTTTTTTTTTTTGAG ACAGAGTCTCACTCTGTCGCCCAGGCTAGAGGGCAGTGGCGCAATCTTGGCTCACTGCAAGCTCCGCCTC CAGGGTTCATGCCATTCTGCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCGCCTGCCATTATGCCC AGCTAATTTTTTCTATTTTTAGTAGAGACAGGGTTTCACCCCGTTAGCCAGGGTGGTCTCGATCTCATGA CCTTGCGATCTGCCTGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCATGCCCAGCCCC ATCTCTTTGTCTACAAAACAGGAAGGCTGGGCCACATGACCTCTATGGTATCGCCAACTTCAATCTTCTG GCCAGTGCTTCTCAAACTTTGGCTTGCATCAGAATCACCAGGAGGGCTGGTTAAAACCAGGTGGCCTGGC CTCACTCCCAAAGCTTCAGGTTCACCGGCTTAGAGTGAGGCCTGAGATTCTGCATTTCCAAGTCCCAGAT GATGCTGATGCTGCTGGTCCAGGGACCACACTTTGAGAATTACTGCTCTAGCAACCCTGGGTGCACATTA GAATTACTTAGGGGAGCTTTAAACCGTATGGTGATGAAACCCAACTCCAGAGCAATTAAATCAGCATCTC TGAGTGGGGAGCCTGGGTTTTGGTATCTTTTAAAAGCTCCCCTAGGTGATTCTAATGCGCCGCCAGCATT AGGAACTGCTGTTCTAGAAAAGCAGCCTGACGTGTGCTTTTTTTCCTATTGGAATAATTTCTCTTGGACC CCAGCTCAGCCTCTCATTAGCTGCCTGGTTTTGAACAGTCTCCCTGAACCTCAGTTTCCCCTTCTGTAAG TGGGGCTGTTAGGAGGACTAAGTGAAACTCTGCTTCACTGTGTCTGTCCACCCTTCCCTGTGTCCAAGGA GAGCTTGTACGTTTCTTCTGCTCTGAGACTGTTTGGCTGAACACAATTCAATAAGCATTTATTAAAAACT TATAATGTGTGAGATGCTGCCCTTAATGATGTGAGAATAAAAGGATGAATCAGGCTCGGTCCCCACTCAA AAGAGCTCACATGCTAATGGGGGTGACGAGGCATGTGTCCAAAATATGAAGCAGGAAGTAACACCGGCTA CGGAGGAAGTAATCATGGTGAAGGCCATTATGTGTGAAGCACTTCGCAGTTTATTTTAATCCTCCCAACA ACTCCACGAGGCAGCTACTATTGTAACACCCACTTTTACAGGCCAAGAAACTGAGGCTTAAAGAGAGGAC CAGTTACCCACAGCACAAGAGCCAGGCTTTGGTGCTGTGGGAGCCCAGAGGAGGAGATTCACACCATTAG AAAGGCTGGGAGTAAGTTTTGTGGGGAGAAGTGTGGACACAGTGCTTTGAAGAATGTGTAGGAGTTTGAT GGGTAAATACAGAGAAAAGGGTATCCCTGATAAGAAACCAGCATACACAAGCTCAGAGGAGGGATAGCTT CTCTTCTTTAGAGACCCGGAAGTGATTTGATTTTGCTGGAATGGAGGTTGAGTGCAGGGCATGGTGGGAA TCACGTCCTGGTTGGAGGCCTTGTTCGCTAGGATAAGGAATTTAGATTTTTAGACTTTATATCTTTTTTT TTTTTTTGAGACAGAGTCTTGCTCCGTCGCCCAGGCTAGAGCACAGTGACACGATCTCGGCTCACTGCAA CCTCTGCCTCCTGGATACAAGCAATTCTCATGTCCCAGCCTCCCGAGTAGCTGGAATTATAGGCGCACAC CACCACGCCTGGGTAGTTTTTATATTTTTAGTATAAAATTATTATATTTTATATTTTTAGTAGTAGGGTT TTGCTATGTTGGCCAGGCTGGTCTCAAACTATTGGCCTCAAGTGATCCTCCCATCTTGGCCTCCCAAAGT GCTGGGATTATAGGCGTGAGCCACCACACCCAGCCCAAGATTTTATATCTTAAGCAATGGGGAGCCCTTG AAAACTCTTGAGCAGGAGGTGGCAGTTTTAGAACAGGGCTAAAATGGTCACAGGTTATATGGGAGAGAGA GGGTGACAGGGAGCCCAGGGACGAAGGGGGCAGCTATGACAAAGGGTCTGATGAGGGATGATAAAGCAAG TGGGTGGGGAGGGGGGAAGGGGAAAATAGGCACATGTGAGAAGTGTGCTGTTGCTACACAAAGCTTCCTT GGGCATCAGTTGATCCCTTATGTGTATTTGCTTATTGACTGAGCCCTACCATACCAGGAGTGGGGGAGGG CAGGAGCAGAAGACAGAGGCTGGGGCAAGTGGACCTCCCAGGGTTCTCACTCCACATGCAGCTCCCCTCG CGACTGGGATATGGTCAGTGGGACATGACCCATTCTGTTGAACAACTCTGCAGAAGCAGGGAGCAATTGG TTCTTGGGCCGTCTGCTACATTTCCGTGATGGAGGTGGCAGAGCTGGCCCAGCGACCTGAGTCTTCCTGA CCCCAGCCTTCCAGGTGAAGCGTGCCACCCTGCTCACCTCCCACTGCCAAGTTCACTGCCAGCTCAAGGC TCACAGCCTGTGTGTGTCATGCCCAGCACAAACCCTCCCGGGCTGAAGCCAGTTCCCAGAGGCAAAGTCT GGATGTGGAAAATGCACCAGGCTGCAATCCTGCCACTTGCCACCAGGTGACTTTGGGCACATCCCCTTAG CCCCTCTGTGGCCTAAATTGGGGCATTAAACACAATCAGGTAGTACAGGTACTGCACCCTCCACCCCCAC CTGCCCCATCCTCTCTGGTTAACTTTCCTGGAGAATCTCAAGATGTTACAGAGACAAGCAAAGCAAGTCA CTTTCCATATTCAAAGTCCCAGGCCATTTTAGTACTTCTGTCATTCTGTGGACCCATCAATATCATACCC ATTTTAGAGATGGCACAACCAGGACCCAGAGACTTTTCATGACGGCCCAGGGTCAGATATCTAGGTAGTT ACGGAGACAGGACTTGAACGCCAGTCTCTCAGCCAATGGAGCTGACCCCTCAGGTGCCCTCCCAGACCCC TGCGTCCTCTCATGAGGTAGGGAGGCCAGATCTGGGTTGGGGGTGAGGCTGGCAGACATCCCTGAGGTCC AGGGATCTGGAACTGAGGGACACAGACACAGCATCCCATCCCTTTGCTGTATCACACAACGAGAACATTC TCTTTTAAGCCTCCTGATATGTGAAGGAGAAAGTCTCTGTTAGGTGCTAATGGGTATTTAACACCTCTCC AAACCTTGCCAATCTCCCTTTTTCACTGAGGGCACACATCTCAAGCCTTGGCAGGCCACGGTTTCCAGCT GGAATTTAATAACCTTGCTTTGTTTTCACTGTGCTTATTTTAACTCTTACTTTCTATTTATGGCAAGTGA TACTGATTTCCCATTTAAGGCAGTGATATAATGATTCTCTAAAAAAACGTGTTTAAGGGGTGGGGAAAGT GGATCTGATATTTTAAAAAATATATTAAGTAATAAGTGGTGTGGAGATATGGCCCAGTGAGAAGGCCCGA TGTCTGGCCTAGGTCAAGCCCCTCATTTAAAGGTGGGGAGGGAGAATGCAGGCAGGAGACGCAATGCTCA AGGCACCTGGTGTGTCCCCGTCGGCCGTGGTCTCTGAGACTCGCATGCCTCGAAGACCTCTGGCTACTAA GCCTAGGTGACTCCCCGCCCCTCTGGGCGACACGTGCATGGCCCATGTGCCAGTCCGCAGGGTCCCGTGG GCACCGTGAGCTCGGGAGGGAGGCGGCGGCTGGGACAGGCAGGTTGGACACCTGGGAGGGCACCCGGGGA CTTCCGCGAAGGAGGAGGGCGCTGGAACCGTGGCGCGCTCGACCTGGCCGGGCGCAAGCCGCTGGAGACC CCGGCCGAGTGGGCAGGCGGCCGGACCCCATGCGGGTCACCTGCGGCCAGGCCGGGCGTGCGTGTGAGCG CGTGCGCAGACGTCAGCCTCCGAGGCCCGGGCCGCCTTCTGGGCAAGGTGCGCGCGCCCAGCGGCCCCGG CCCCACGCGCCCGGACACGCGGAACCGCAGACCGCGGCGCCCCGGAGGCCGCGAAAGGGATGGGCGGGGC CGGGCCGCGGGACCCGCCTCCCATTGGCCGGGCGCCGGGGCGAGGCGGGGCGCCGGGGTGGGGCGGGGCG AGCGGGCTCTGGGGGGCAGACGCTGGCGCTGGGCGGCGGGAGGCGCGGCTCGCGGGGGGCCGAAGGAGCA GGTGGGCGACGCTCGCAGGGGCGCGGGAGGGTGCCGCTGGGACCGTCATCAGGAGCCTGGGGTTCTGCCA CCTTTCGGAGGGATCAGCGACCTCTTCGCCCTGCGGGTGACAGTGGGGCATCTGCCTGCGAGAGGGGGAA GGAGGGAGAACCCAGGGCCACACACAAAGTTCTCCTCATCTGGGGACAGGAGGAGGTGAAGGAGGAGGAG CCGGGTTGATGCTAACTTGGAGCTGCGAAACCTTGGGGCGGCGTTCAAGGCCCCCTCCCACACGCGCGCA GAGCAGAGCGCCCTGCTCCTCCTTCAGCTGCTGGCGTCGCCGCGCGGGGAGAAAGAAGCCGTCCCTCCGG CGCTGGGAGAGCTGCAGAGCCGCGGGCAGAGAAGGAGGCCGCGGCCGAGCCCGGCAGCCCGATACCCCCC ATCCGAGCGACCCCCTTTGGGGCAGGCGGAGAAGGTGGCATAGGCGACCAGGAGGGTTCGCCCACCTGGG ACACGCACCCACAGTCACCTCCAAAGGACCCCCCCTCCCCAAGTCTCTAGGAGCTGCTCCTTCATCACTG GAGTCGCCCCTACCTCTCTGCCCCCAGCCCGAGAGCCCCAGGCGGGGACCCCCGGATCGGACGTCCCCAA GCCTCCGGGCACCTGGCTCAGCAGGAGGCCCCCGGCTCGGGGCAGGGCAGGGCCGGCGGCGGCGAGCCGG AGCCCGCCCCCTGCCCGGGCCCCGCCGAGCCCTCGGAGCCCACCCATGGGGCACCTGCCCCTTGCGCCTC CTTGCCCGGCCGCGCCCAGCCCGGCGTCCCGAGCAGCGCAGGGGAGGATCCCCGCGCAGTGACCCGGGAG CCACCACAGACTCTGGGAGGCTCGGCGGCTGGAGCAGCAGGCAGCTCCCCGCAGCTCCCGGCGCTTCCAG GCAGCTCTCTGAGCCGTGCCAGAGGCCCGGCCCGCCATTCCCAGGTAGGAGACGCCCCAACAGAGCTGGG CATCTGGGGGAAGTGGAGCAGCCGGGAAGAAAGGGTAGAGGCTTGGAGGAGGAAAGCTCAGTGATTCCTT AGATGACCAGAGAAAGTGAAATTGATTGAGCACCTACTATGTGCCGGGATCGTCTGGCAACTTTGCATAC CTAGAGAGAATTAAATTCGTTGAGCACCTACTGTATGTGTCAAACTGAGTGCTATACCCTTGACTTAATC CCAGGAAAGAAAGATTTATTGAGCTTCTACTATGTGCTAGTTTTGGTGCCACAGGCTTTGCATTTAAAGA GCTAGAGTAATAGCCCATTTAAATAGGAGGAAACGGGGGCTCAGGGAAGACGAGTCAACTACCACAAACA CTCCTGTCCCTCTTCTGGAGCTGGCTGCAGCCTGCATTACCTGGAGGTGGGGAAGGAAGATTAAGAAGCT CCTTCGTTATCCAGAGTTCTTGAGCTTTTTCTGGGTTGGTGCAGAGTGAGTTTCCTGGATGATTCCCTTC CCAGGAGGGGTTTCCTGTAACTTAGCTGTCTTGGAGGGCCCGGAAGGCAGCTCTGGAGGCCTCTCTGTGC CCTCCCCTCCCCTTGTCCCCAGCACCAGGAGGATGACAGGGGATGTTGTCCAAGACCTCATGGAAGGTGG GAAGCCAGGCTGGGAGGGAGCAGCCAGGTCAGGAGCCAGTGAATCAAGCCTCCTGTGGTGTCAGAGACAA GATGGGGTCCCTGCAAGACCTGCGCCTGCATTCCAGTCCAGCCTCACCAGGCTGCTCTAGGCAGCCCCAC GACTGCCAAGATAAAGTGCCACGAAGAAAAGAACCCAGCATGTGTTCAGGTTTGCTGCGGGTCAAGAGCT GGGTCAGCCTCCAGACTTATTGGAAACCCAGGGCCACACAGGGGGTTTATGTCTTACCATTAACAGAGGA ATAACCTGAGCCCCAGGAAGCCAAGTCATTTGCCCAGGGCTGCCGGGCTGGTGAGAGGCAGAGTTGGCCT GCCAGAAGTGGATGCCTGCCTACCTTCTACCACCTGAGCTGCCAAGGGTGGTGGGGTTGGCTTTGCCAAG CTCCCGGACTCTCAGAGTGGCAGCTGGAAGCCAGTGATGGCAATGTGCGTGTCCAAAGAGGCTGAGTGTG CACTGATGGAGGAGGCATGGGGGTGTGGAGGAGGGGCAGTGCAGTGAAACAGGCTCTGGGGCATACACCG GGAGGACACGTCCAGACTCTTGTCCTGCTGCCTGTGCCCGTGTGACCCCTTCATCTTTCAGGCAGGCCCT GGGAGAGAGGCTCAAGGGAGAAGTGGTGAATCCACAGGTGCACTTGCTCAGAGGTGGCTGGCAGGGTTAG GGGAGAATCCTGGGAGGTGCCTGCCCCCTTTCCGCTCCGCTGCCTGCAGGGAGAGAGGGAGTGAGAATAT AGTATGTCTCGGCGTCATCCCCCCGCCTGATGCCAGCTGAGGCTTCACTGAGACAGACAGTGTTTTGGAA AAGACCAGTTTTGGCTGGGGGTGGGTTTTCATAGAGTTAAGAGCCCAGACTTTGAAGCCAAACAGCCTGG TTCTGATCCCAGCCCAGCTAGTCATCTGCTGTGTGAACTGGGGCAAGTGACTTAACCTCTCTGAGCATCA GTGTCCCCATCAGTCAAGTGGGCTGATGGATGCCTTCCTGGCTGTGGTTACTGTGCCCCCAGGATGGCGT CCCCTCATCTCTGCTCTGGGAACTTTCTGGCTTCCACCTGTCCTCAGAATGGCCCTGTGATGGGGTCAGT AGTCACAGTATGTGCATTCAGATACCTGTGCCGCTAGGGGGTCTCCGTTGAATTTCCTGCCTCTCTGAGC CTCCTCTCTCTGATTCCTTACTTCCCCTCTCTGATTCCCTGCCTCCTCTCTCTGACTTCCTGAAATCCAT TCAGTCACTGATATTGGACTCTAAATTCCCAAAGGGCTCTTCAAACTCATCCCTGTCTGCTCCTCGCTGT ATGAGGTCAGCCTGGCTGAGGATGGAGAAGGGAGAACAGGCTGCAGAGGAGAGATGTGCCTACGAGGGTG CCCATGGTGCCACCTCTGGGGGAAGAGAGGGAAGAAAGATGTGGAGGCAGGAGGCGGAGCCCACAGAGGC ACTGTCCCCTGGCGTCCAGGTGTCCAGATGTCTCACACAGCCCCACGTGGCTCAGGCCATGTGAAGAATC AGTCTTCTCTCAGAGATAAAAACCACAGAGGATTTTTTTTCTCTTTTTCCCCACCCTGATTCCCTGTCTC TTATTTCTGACTCCTTGCCTCCTCTATCTGTCACCTTGCCTCCTCTCTCTGACTCTTTGCCTCCTCTCTG ACTCCCTGCCTCCTCTCTCTGTCTCCCTGCCTCCTCTGTCTGACTCCCTGCCTCCCCTCTCTGTCTCACT GCCTCCTCTCTCTGACTCTCTGCCTCCTCTCTCTGACTCCCTGCCTCCTCTCTCTGATTCCCTGCCTCTT TGACCCTCTGCCTCCTCTCTTTGACTCCCTGCCTCCTCTCTCCGATTCTCTGCGTCTTTGACTCCCTGCC TCCTCTCTCTGACTCCCTGAAGCTCATTCAGTCATTGCTATCAACTCGTCTGTACCAAGCTCTAGGCTGG AGGCTGGGCAGGGCAATGATGGAGACAAATACTGTCCCTGGGAGCTTCTGGCCCCTTTCCCATCCTGTTT AGACAGAAGTGACCGCCAGCAGAGTCAAGCTGTCTGCAGAAGGACTTGGGGAGGGGGCTGTCATGGGGTA GGGCTTCTTTCCCCCCATCTCTGCTGAAGGCCCAGGCTGGCTGAGACAGCCCCGGCAGAGACTGAGAAGG GCTCCCTGCTGTGGTCTGGCAGCCCCCTCTCCACCCTCCTCTCTCTCATTTCCTGCCTCCCACACGTATG CCCTGGGCACCTCATCAGGGCTGCCCTAGGGGAGGGCCCTCCTTGGCACAGCCCCTGGGCCAGTCAGGTG GTTGAGGCTGAGGAGAGAAGGTCCCAGAGTGGGGCTTCAGGCAAACCCAAAGACAGAGCCCTTTGCCATT TGATGAATGCACAGACCCTTTATTGAGCCCCTGCTCTGTTCATGGCATGGCAGTTTTGTGGGATAAATTC AAAGACAGCTTTAGGTGGGAGCTGGGTGGGGGATGTGGGGGTCTTAGGCTTGAACTACTACCCAGCCTCC TTTGTTAACCAAGTAGCTAGTCACGTAGCCTTCTGAGCTCGGGGCAGACCACCTGGGATCAAACCTCTCC TCTGCTGGTTACTGGCTGTGCAACTGTAAGCAAGTAATTTAACCTCTCTGTGCCTCAGTTTCCTCATCTG TAAATTGGAGAATAACACCACCTGCTTTCTGGGGTTATGAAGGGAGAAATAGGTTAACATGTGTGCAGCA CTTAGAACACTCTGGCATATTTTAGCTGCAAAATGAATGCCAGCTATGATTATTTCTATACTTAGTGCGG GGCTTGGCACACTGCATGGGCTCAAGTGGCAGCAGTTGTCGTCCTTGTGGCTCCAGGCCTGGGGTCCGCC GTGTGCTGAGCTGGCTTATTGTGCACGTCCCTTTGTGATTCATTCATCGAAGTCACATTAGTAGCTTAGA AGTGACCGTAGTGGGAGCATTTACGCCATGGAAATTGGCAATAGGGCTTTTAACAAAGGTATTTTTGAGA GCCGGTTTCCTGCACAGAGGCTGGTAGTTGGGCAGGGTGAGCAGATCCAGATGTGTGCCAGGGACTCGCA CGCAGGCAATCTCTCCACCTCCAGTGGCCATCTCAGACCTTAGCTTCATGATAGCCAGGAAGCGATGGTG TTGGAAAGCGCCTTGGGTCAATGGGCGAGGCACTCAAGGAAACCGACTTGGGGCATCCTGGGGTGGGGAC CGAGTTTGGGCACATACAGCCCTTTGTGTGAATTTAAAAACAGTGCCTTTTCCTCTACACAAGATGCCCT TTCGTCTGGGATACAGCCCCCACCTCTGGGATGCAGCCCCCACTTGCCCACCCAGCCATGCGCCTTGTGC AGTATCCAACCTGCACAACCTGTGGCAGCCTGTGGAAGACCTAGGGGATTGATATTTCAGCAGGCCTGTG CCCATTTGCAGTTCAGGGGCTGGAAAGCTCTCCTCTGGAGAGGGGAGGGATTCCTGCAAGGGTGAGGAGA TCAGAGAGGCCTTCAGAGAGCAGGTGGCACTTGAGCCAGACCCTGAAACATAAGGGGAAGAGGGTGTTCT GCAGAGGGGTGGCATGAGCAAAGGAGTGGAGGCTGATCTCAGCAGAGCTCAAACTGACGAGGGTGACTGG GGTCAGGGGTTCTGGGGCGGGGATTCTGGTGGGCGCTAAGGTAGGAAAGGAGGGAGGGCTGGGCTGTGAA GAGCCTTTGGGGTGAGCCTGGTGGAGCCTGCGGGTTTGCTTATACAAGAGCTTGGATCCATGTCGGCCTC TTTCATGAGGTCAAGAGGCTCCCATAGAAAGCTCTGGGTTTGCCCCAGAACCATAACCCTTGGAGTTGGG AGGGAAGCTTGAGCCAGCCATGGGTCGTTCCCCATTCCACATCCTCTACTCCGGGCCTCTGGGTCTCCTG GAGGCAAGTAAACACCTAGGGCCTGGGAGGCAAAAATATCCGGGCAGGTCATGGAGCGGAGGGAGCCCGC CAGATGCAGAGCACAGGTCTAAAGGTGGGTCCTCCTGAGGTGGCTGCAGGAGCAACCCCAGGCATTGGGC TTGGAGCATGCGGTGTGGACATAGCCTTCCCTTCTTCCCAGGAGGGCTGAATGGCCACAGAACCACCCCC TGCCCCAGGCTTAAGAAATGCATGCTAGTGCCTTCCCCATGTCTTATCCTAGAATCACAGGCTCCGGGAA AGCCAGATGGATGAACCAGGGAAAGAACGGATTCTCACCATAGATACCATTTTTGAGATTTCACCATGTG CTGAGCCCTTTGCAACAACTCTATGAATTGGGCTCATTTTGCAGATGAGAAAAGTGACTTCTAGAGAGGT TAAGCTACTAGCCCAAGATCAGTAGCTAGAGGCAAGGCAAGGATTCAAATCCCAGGAGTCCGGTGCTTGC ATAAATGAAAGGATGAATGAACGGATATTGAGTGAGTGAGTGGATGAAGGAAGGAGTAAAGGAGAGGGCA TGAATGAATGAGAGGGTAGAACTCCAAGACCCCTTAGAACCTCGTCTGATGTTCCCATTTTACAGACAGA AAACTGAGTCCTAGACAGAGGCCTAGAGGAGGCCAAGAGGTGGTGGGGCCAGGTCGGGGGGGCCCTGATG CCTGCTTCTCTCGCTTTGTTGCAGCCCCGAGCCATGATGAAGACTTTGTCCAGCGGGAACTGCACGCTCA GTGTGCCCGCCAAAAACTCATACCGCATGGTGGTGCTGGGTGCCTCTCGGGTGGGCAAGAGCTCCATCGT GTCTCGCTTCCTCAATGGCCGCTTTGAGGACCAGTACACACCCACCATCGAGGACTTCCACCGTAAGGTA TACAACATCCGCGGCGACATGTACCAGCTCGACATCCTGGATACCTCTGGCAACCACCCCTTCCCCGCCA TGCGCAGGCTGTCCATCCTCACAGGTGAGGCCCACTGGTGCCTGGGCTGGGGCGGCAGGGCCAGGGCATG GGTGCGGAGTGTGCTGGGCACTTGGCAGTTTGCATAGACTTGCATAGCCATCGTCTGAGACAGGCGTCAT CCCTGCACAATGAGGCTCAGAGAGGTTTTGCCATGTGCTGGAAATAGTGATGAAGTCGGGGGCCCCGATT CCATTCTGTTAGACTCCAGATCGATTACTCATGGCTGTCGGGGCCGCCTTCCAGATCAGGAGCTGATACC AGCATGCCCCAGGGATATTCCTTTCTAGGGAACAGAATGATGCCCTGGCTGCTGCTTTCCTTCTCCGGAA GATGACCCACCAGAGCTCCAGGGCCCAAGGTCAGTCCACGGGGCTCAGGTCTCCCACACCCCAGGCCTTT GCCACCTCCTAGAGAGGTAAGGGCAGGACCCAGGCAGTGATCACCAAAGGGAAGGGGGCTTGGTCATGGT CATAGTGATGGTGATGGCACTAGCTGACACTTATCAGAAGCTATGGGCCTGGCCCTGTTCTTAGAGCTTG GCATGTAGTTTTTTTTGAAACAGAGTCTCGCTCTGTCACCCAGGCTGGAGTGCAGTGGCGCGATCTCGGC TCACTGCAACCTCTGCCTCCCGGGTTCAAGCGATTCTCCTGCCTCAGTCCCCCAAGTAGCTGGGACTACA GGCATGTGCCACCATGCCCGGCTAATTTTTTGTATTTTTACTAGAGACGGGATTTCACCATGTTAGCCAG GATGGTCTCGATCTCCTGACCTCGTGATCTGCCTACCTCAGCCTCCCAAAGTGCTGAGATTACAGGCGTC AGCCACCGCGGCCAGCCAGCATGTAGTTATTTAACCCTCATAGTAAATAGTTATTCATTCCCTTTTTACA AGTGGGGAAACTGAAGCCCAGAGAGGTTAAGTAACTCACTCCAGTGGTAGCACAGCTCGTAAAGGCAGTC TGCTTTTGTGCTTTCAGACAAAGCCATACCACAGCCTCTCAGCCCTGCTGGGAAGGGTGAGGAGGGACAG GGAGGTTGGGGGGAAGAAGGGGTGAGTGGAGCTGAGGGGCTGTGCCCTTGTTTACACTGCATTAGCATGG TAGCTAAGAGGACAAGCCCGGGACCCAGCACCTGGGTGTGAGCCCTGGTTCCGCTGCTTCCTGGCTTTGT ACCTCGAGGCAAGGGATTTTATCTCCTTGTGTCTCAGCACTCTCATCTGTAAGACTGCACCACATCAACA CTCATCCTAAAGGGACTGTGAGACTTAAATGAATGAATATATGTAAGGCGCTTGGTGAGCAGATAGTAAA TGCACAATAAATCCCCAAGTCTTCTGTTGAGTCAGCATTTGCAAGTGGGCCTGCTACGGGTTACACGATC ATTTCCCAAGTCACGCCCCTGAAGTTGCTGAGCAGGGATAAGGGAAGGAGTGAGCAGGCAACTCTCTAGG CATCATTCAGATAACCCCCCAACTGAGGTACTTCTATACAGAGAAACCCATGCCACTCCCAGCCCTGCTG CCGCCTTGAGGCCAAGACTGAGGCTGCGGGGTGGCCCCTCCTTGAGTGCTTTCTCTTCCAGGCTGGCTTT TCCGAGCATCTGACCCAGACAGCAGTCAAGTTCTCCGCTCCACCCCGAGTTTTGGAGAAGGGGCATGTAG ATAGGAGAGCCCTGGGTCGACCTGTGTTCGAATCCTTGCTGGGCCTCTTGGCTTAAATGTGTGACCAGAG GCACATGCATCCTGTCTGAGTCTCAGCCTCCCCAGCCACACAGTGGGCTTAACCTCATACCCCGCAGGGA GGCTGTGAGGACTGCAAGAAGGCTTGTGGCGGGAGCTTCCAGCACGTGACGGGTATTGCATTGGTGTCAG CTCCCCCAGCCTTGGGGAGGGGACTGGGTACCCGCTGCAATGAATAAGGCTAATGACAGAGGGAAGGAGA GGGGAGATGTAGAGAGGAAGCACATGCATATTTTCAGCATTAATTTTCAGTGACACAAGTAATACCCAAA CACACCCTCCTGCAAACGCTACAGATAAAGCTAATGCCCCTTTGACCCATGTCCCCAATCCCAGGCTCCT GCCCCTGCCCCGGAGGTGGCCACCCTGGCAGTCTGGCATGGAGCCTTCCGGGCCTCCGTGACTACACCGG CATTCGTATTTGTATCCCCACAATGGAGAGTATTTTTGTCTGTCTCTTTTTTATGGCGCATATCATTCTG AGCACAGCTGTCTGATGCTTGTTTTTTTTTCACACACCAACCCGTGCCTCATTTTCCAACCTGGTGGAAC CTCATTTTTTCAACCTCATTTTCCTGCTGCTCAGGAAATTCTGAAAGCCATTAATTCCACTGCCAGCTCT TCTTCCAGCTGCCAGACGGGCCGATCTCTGATGCTTGGCATCGCAGTCTCGCATTTGAATATGTCAAGGC CACGAGTCCTCAGGGGCCCCGGATTAGCCTAACGGGATGGGGTTTGGCAGCCCAAGCAGGAAGAGTTGCC AAGCTGACGCTGCCTCGCAAGTGCCTTTCAGAAGAGCCCACACTGCAGTTCCCTCCATCACCTCCCATCC ATTCAGGCTTCCTTGGTTAACACTGACTGTGTGCCAGGCCCTGGGGAGACCAGGACGAGTGGGTGATGGA ACCCTTCTCTGTGCCCGAGCTGTTTGGAGCACACCTTTGATCTGGACACCATTCTGAATGTGCCATGTGC CATTAAATGGGGGTAAATGATGTGCTCTGGGGGTGCAGAGGAAGGTGGCAGCCATTCTGCCAGAAGCTGG AACTGGTTGCTTCTCTTCTCAAGAATTTGGGCCAATTGCTGATTCCTCTGGGCCTCAGTTTCCTCATCTG TGAGACAGGGATCTTGTCACACCACAAGGCTATCAAGAGTTTGAGCAAAAGTGGTTGGACGCAGTGGCTC ATGCCTGTAATCCCAGCTCTTTGGGAGGCCGAGGTGGGCAGATCTCTTGAGGTCAGGAGTTCAAGACCAG CCTGGCTAACACAGTGAAACACCGTCTCTACTAAAAAATACAAAAAATTAGCCAGGTGTGGTGATGGGCA CCTGTAATCCCAGTTACTCGGGAGGCTGAGGCAGGAGAATCTCTTGAACCCAGGAGGTGGAGGTTGCAGT GAGCTGAGATCTTGCCATTGCATTCCAGGCTGGGCAACAAGAGTGAAACTCTGTCTCAGAAAATAAATAA ATAAATAAATAAAAAATAGCTAGGCATGGTGACAGGCGCCTGTAATCCCAGCTGCTCCAGAGGCTGAGGC AGGAGAATCGCTTAAACCCAGGAGGTGGAAGTTGCAGTGAGCCAAGATCACACCACTGCACTCCAGCCTG GGCCACAGAGAAAGACTCCATCTCAAAAAAAAAAAAAAAAAAAAAAAAGTTTAAGCAAAAGTGAGGAAGG TGCTTATTAAAAGCTGGAAATCAGGATGGAGGTACCAGTCCAGACAGCCTCCCCACCACCCCACCGTCTC CACAGCAGCCCCTGTTTCAGATTCACAAGCCTGCCTTGAGTGATGCAGTGAGTTATCCTGGAGGCAGTGT GGGCCTTGGAGGCCAGCACTCACTTTTTCATCCTATGATTTATTTGAGAAGCAGAGAGCACCTACCGGGT GCCAGGCACGAGCTAGGTGAGAACAGAATCAGGTAGAAATCTCAGCCTAGCCACACGGAAGCTGTGTGAT CTTGGGCAGGCTGCATACCCTTTCTGAGCCTCAGTTTGCTCACCTGTAATGCAAAGGTAACAAAATCTTG ACAGAGGCATAGTGAGGAATCAAGAGAACAACGGGCCTGGAGCATACACCCAGTGCTTAGCCCCCAGTAG GCCCTCACTCTCATCATTACTGACACCTGAGGTCACTGAGCATGTGCCACTGTCCATTCATTATCTTGCA TAACTCCCAAAATCATCCTGCAAGGTAATATTTCATCTTCATGAAACAGACAGAGAAACTGAGGTTACAG AGGTTTCGTGATCTGCCCAAGTCTGCTGGCAGCTAAGCGGATGAGGCCAGATGCAAACTAGGCATTGAGC AAGACAGGCAGGACCCCTGCTCTCATAGAAATGATTTTTATTATTATCTGAACACAGTCCACACAAGTGA CCTACCCCTCTCCAGCCCTGCAAAGAAATGTGAAGTGAGTTAACTGTATTTGAACCAAGTGGTCCACGTG TTAGCTATGCGACTGTGAACAGGGGCTTCAACCCCCTCAGCCTCAGTTTCCTGTCCTGGAAAATAATCGC AGGGAGAATAATCGCAGCTACCCCGAAGAGTCGCTGTGTAGGTTAAAGCAGTTATGCCGCATAACTGCTT CAGGGCACCTGTGACTCCCAGCTCTTAGGGCTGATGTTCTGTGGCCAGAGGAGGGCAGGGGTTGCAGCTG GCCGGTGAACTCACTACCTGGGCTCTCTCCCTGCAGGGGATGTCTTCATCCTGGTGTTCAGCCTGGATAA CCGGGAGTCCTTCGATGAGGTCAAGCGCCTTCAGAAGCAGATCCTGGAGGTCAAGTCCTGCCTGAAGAAC AAGACCAAGGAGGCGGCGGAGCTGCCCATGGTCATCTGTGGCAACAAGAACGACCACGGCGAGCTGTGCC GCCAGGTGCCCACCACCGAGGCCGAGCTGCTGGTGTCGGGCGACGAGAACTGCGCCTACTTCGAGGTGTC GGCCAAGAAGAACACCAACGTGGACGAGATGTTCTACGTGCTCTTCAGCATGGCCAAGCTGCCACACGAG ATGAGCCCCGCCCTGCATCGCAAGATCTCCGTGCAGTACGGTGACGCCTTCCACCCCAGGCCCTTCTGCA TGCGCCGCGTCAAGGAGATGGACGCCTATGGCATGGTCTCGCCCTTCGCCCGCCGCCCCAGCGTCAACAG TGACCTCAAGTACATCAAGGCCAAGGTCCTTCGGGAAGGCCAGGCCCGTGAGAGGGACAAGTGCACCATC CAGTGAGCGAGGGATGCTGGGGCGGGGCTTGGCCAGTGCCTTCAGGGAGGTGGCCCCAGATGCCCACTGT GCGCATCTCCCCACCGAGGCCCCGGCAGCAGTCTTGTTCACAGACCTTAGGCACCAGACTGGAGGCCCCC GGGCGCTGGCCTCCGCACATTCGTCTGCCTTCTCACAGCTTTCCTGAGTCCGCTTGTCCACAGCTCCTTG GTGGTTTCATCTCCTCTGTGGGAGGACACATCTCTGCAGCCTCAAGAGTTAGGCAGAGACTCAAGTTACA CCTTCCTCTCCTGGGGTTGGAAGAAATGTTGATGCCAGAGGGGTGAGGATTGCTGCGTCATATGGAGCCT CCTGGGACAAGCCTCAGGATGAAAAGGACACAGAAGGCCAGATGAGAAAGGTCTCCTCTCTCCTGGCATA ACACCCAGCTTGGTTTGGGTGGCAGCTGGGAGAACTTCTCTCCCAGCCCTGCAACTCTTACGCTCTGGTT CAGCTGCCTCTGCACCCCCTCCCACCCCCAGCACACACACAAGTTGGCCCCCAGCTGCGCCTGACATTGA GCCAGTGGACTCTGTGTCTGAAGGGGGCGTGGCCACACCTCCTAGACCACGCCCACCACTTAGACCACGC CCACCTCCTGACCGCGTTCCTCAGCCTCCTCTCCTAGGTCCCTCCGCCCGACAGTTGTGCTTTGTTGTGG TTGCAGCTGTTTTCGTGTCATGTATAGTAGTAGAAATGGAAATCATTGTACTGTAAAAGCCTAGTGACTC CCTCCTTGGCCAGGCCCTCACCCAGTTCAGATCCACGGCCTCCACCCGGGACGCCTTCCTCCTCTGCTCC CAAACAGGGTTTCCGTGGCCTGTTTGCAGCTAGACATTGACCTCCGCCATTGAGCTCCACGGTTTACAGA CAATTGCACAAGCGTGGGGTGGGCAGGCCAGGACTGCTTTTTTTTAATGCTCCCATTTCACAGAGGATAC CACCGAGACTCGGAGGGGACACGATGAGCACCAGGCCCCACCTTTGTCCCCTAGCAAATTCAGGGTACAG CTCCACCTAGAACCAGGCTGCCCTCTACTGTGCTCGTTCCTCAAGCATTTATTAAGCACCTACTGGGTGC TGGGTTCACTGTGTCCTAGGAAACCAAGAGGGTCCCCAGTCCTGGCCTCTGCCCGCCCCTGCTGCCCCAC CACCTTCTGCACACACAGCGGTGGGGAGGCGGGGAGGAGCAGCTGGGACCCAGAACTGAGCCTGGGAGGG ATCCGACAGAAAAGCTCAGGGCGGGTCTTCTCCTTGTGCCCGGGATTGGGCTATGCTGGGTACCACCATG TACTCAGGCATGGTGGGTTTTGAACCCATAAACCAAAGGCCCTTGTCATCAGCTCTTAACAAGTATATTT TGTATTTTAATCTCTCTAAACATATTGAAGTTTTAGGGCCCTAAGGAACCTTAGTGATCTTCTATTGGGT CTTTCTGAGGTTCAGAGAGGGTAAGTAACTTCCTCCAGGTCACACAGCAAGTCTGTGGGTGGCAGAAGCA AGCTAGCGCTGGGCATTCAGTACATACCACGATGTGCTCCCTCTCTTGATGCTTGGCCCCTGGGGCCTTC AGGGCTTTGGGACATCTTGTCCTCAACCCTCTCCCTAGATCAGTCTGTGAGGGTCCCTGTAGATATTGTG TACACCATGCCCATGTATATACAAGTACACACAGATGTACACACAGATGTACACATGCTCCAGCCCCAGC TCTGCATACCTGCACCTGCACCCCAGCCTTGGCCCCTGCCTGCGTCTGTGCTCAAAGCAGCAGCTCCAAC CCTGCCTCTGTCCCCTTCCCCACCCACTGCCTGAGCCTTCTGAGCAGACCAGGTACCTTGGCTGCACCGG TGTGTGGCCCGCTCTCACCCAGGCACAGCCCCGCCACCATGGATCTCCGTGTACACTATCAATAAAAGTG GGTTTGTTACAAAGCCGTGTCCTTGCCCATGTGTATTTTTTGTATTTCCAAGAGGAGGTGTGCCCCTTTC CAGACCAAAGCTGGCCTTTCCCTCCCAAAATGCACCTGCCGTGTGCCCTGGCCCTGAGGGTCAGCACTGA GTCCACCTTCAAGTGTAAGTGTGGGGAGAGGGGGATAAGTCCCCCAGATGGAAGGTGATGCCCTCCTTCA GCCTGGCCCTCCTGGGTCCTCCGGGTGTGTGTACCGAGGTGTCTGTGTCCACAAAGAAGGGGCCCCCGTG GACCATTAGCTCCAGGAGGATCTCCGTGTCTGAGTTCTTTGTGATTCCTGTACAGCAGCAATTTCACCCG CAGGGGACAGTTGGCAATCTCTGGAAACCTTTTCCAAGCCTGGGGCTGGGGCTGCTACTCTCATCTGGTG GGTGGAGGCCAGGGACACCATTCAGTATCCTCCAACGCACAGGATGCCCCTCCACCCCCACCCCACTGAG AATTATCTGGCCTCAAATGCCAAGCGTGGGCAGCCTTACTTAGACTCACCCCAGGGGCTGGGACACGCCC CCACCTGCGTGTGATGGATTTGTTGGACCACATTCTGGACGGAACCCACAGCATGAGCACTCCTGTGAAG TGAGACAGGATGTGGGTGAGGATGGAAAGTGGAGGCTGAGGGAGAAGGTCTGGGCCCTGACCAACACGGA ATGTGCCCCCTGGGACTGAGAGGCTTCCCTGGGCAGAGGGAAAGGAGGAAGTCAGTGAGGTAAAATACTC CCTGTGTGTTTTACCCAGCGAGTCTCACGCCATCCTATCACCCAGCCCCGAGGGAAGCCCACTCATGTTC ACCCCATCTGAGCATTTAGGCTCAGAGAGCTCAATATCTTGTCCAAGATGGCACAGCTGGTGAAGTGGCA GATCAGAGATTCAACACCAGAGGCTGTCTGATTTCCGTCTGGCTGAAGAAAGATTTTGCATCAGGGAGGT GGAAACCATCTGTGCTTTTGATCAGCAAATGCCACCAGCAGGATCAGGGAGCTAGGCCATAAAGGAGGTC GAGAGACAGGCAGTGTAAGGTTCATTGGGAACCACATTGTCCATTGGGAAGCCACAACCTCTGCACAGAC ATTCACAAAACAGAGCCAGGCTGTGGTGGAGGCGAGACCACACAAGTCCATAGTGTGGGGAGCTGGAGAA CTCCCAGCCTCTACCTACCTGGGGGCCCCGCTCCCAGCCTGTGCATATCTGGGGGCCCGCTCCCAGCCTC TGCATATCTGGGGGCCCTGCTTTCAGCCTCTGCCTACCTGGGGGACCCTGCTTCTAGTCCCTGCCTACCT GGGGGCTCGGCTCCTAACCTCTGCCTACCTGGGGCCTGTCTCCCAGCTTCTGATAATCTAGCAGCCCAGC TCCCCTCCAATCCTTTGCCCACCCCAGCCACAGAAGGTCAGTGTGGGAGGCATGTCCCTCGGACACTTTC TAGATCCTGGTTTTCATACACACAAAGCATGGAGGCGAACACTCCCTTCTGCATCGCCATCAGCGCTGAA CCATAACAAGGGCGCTGGTGCACAGAGACAGGCCTCCACGGTGTCCCGCTGGAGCCCAGCCTGCTGCTGC CACTCCCTTTCTCTATGTGGGTCTGGAAATAAGTCTCGTCCCCTCGCAGGCCTCCTTTTCTTCATGAGTA AATGGGAGGCGGGAGGAAGGCATCCGGACCAGATACACACCAACAGCCTCTCGCAGCCCTGATGGTCTCT ACTAGAAGGAATTAATATTCCTATTGCATAACTCACAACATTCCAATCATCACCAAACAGAACACGCTCG CCCCAGCCCCAGCTCTAGCCCCACTCTTTGTTCCCTGCATCCCACAGTCCTTGCCCTGGAATGGGGTTGA CAGCAACAGGCTGCCACAGAGGAGAAAGACACATGTCTTCTTAGCCCTGGGACAGTGGGTAGGATAAGAT TGTAGGAAAATTCCCTTCATGGTGAGACCATTTAGAGCCAAGCCCAGGATAGCCGGCTAATCCCCCGACC CTAGGAAGGGAGCATTGGGAACATGATTTCAAAGAATTCTGCGCTGTGAACTCTAAGTACTTGTTCTGTT CCACCTCCCTGAACCTGTCACTTACTCGAAAGAAAAACTTCAGTCTGCATCACGGTTTGGTGGGGGCTGA TGGGAGGCCTGCCAGGGGCTCGGCAGTGAAGGCTGCCGGGAATGGGGGAAGGGAAAAGGAGCTGACCTTT GCGAAGACCTTACTCTGTGCCAAGCACTGTGCTGAGCCTTTTACCTGCGTCCTGTCATTGAATCCTCATG GCAGAGCTAGCTGGAATCCTTTTTTGGATAAGAGAGAATGGAGTTCAGAGAGGTAAAGTCACTTGTCCAA AGTTGCACAGCCAGGAAGGAGCAGAGCTGGATGAGAAACCATGTCTGATTCCAAAGCACATTTTTGTCTC CAGGGCTTTTATAACTGAGCCAGCTGAGAGGTTGCTCTCTAGTGGGAGAGTCCAGTGAGTTGGGGTGCAG TGTCTGGACGTGGTTCAGGGAACTCAGAAAATGGGGTGCTCTTCCGTTCACAATAAAAGGCTGAGCTGCT GTCACAAGAGAGGAACCCAACTTCTTTTTCATGGCAAAGTCACTCTGCTCCACCTGGTCACTCAGGCACC CAGGTTTCTTCCGTCTTCAGGTTCTTCCATCTCTAGGACCTTGTCACCATCTGCACGGTTGAAGCCACTG TAACATTCAGGTTCAGCCGAAGGGATAGGGGAAGAGAGTGTGGAAGAGGTACACCTGCTGTTTTCAGAGC CATGGACTCATCACTTCCACTTTCTAGCAATGGCAAGAGCCCAGCCATGTGACTGTACCTACCTATGAGA AGGCCTGAGAGATGCAGTCCTTTGCTAGGTGGCCCCATGCCCAGCGGTGACTCCACTGTGGAAAGGAGGA GGAGAGATCTGGTTGGCCAGCCTGTTGTCTCCAAACAGCCACCCTAATGCAGTGGGCCAGCCTCGGGACA CCACGGGCAGTCTGACTTCAAACAAGCTCCACTTAGCAGATGAAATCAGAAAGCAGCTCTAGGCTCCCAA GGCTGCTTTAAATTGGCTCTGAGCAGGCCGGGTGAGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAG GCTGAGGCGGGCGGATCACCTGAGGTCGGGAGTTCGAGCCCAGCCCGACCAACATGGAGAAACCTCGTCT CTACTAAAAATACAAAATTAACCAACCATGGTGGCGCATGCCTGTAATCCCAACTACTCGGGAGGCTGAG GCAGGAGAATAGCTTGAACCCGGGAGACGGAGGTTGCAGTGAGCCGAGATCACACCATTGCACTCCAGCC TGGGCAACAACAGCGAAACTCTGTCTCAAAAATAAATAAATAAATAAATAAAAATAATTGGCTCTGAGAA CTTATTCACATCCAACCCCCATCCCCAGATGAAAACTTAGACTATCCCATGATTTTTCTCATCTCTCTTG GAAAACAGAATATACCACAGACATTTTAAGTAGTAAGTAGAGTCTCAACTAAAATTCCTTGGCCAGTGTG ATCATCAGTTTCCAGTCTTCATTCAAAAGAGTTTCCCTCCCTCGCCCAGCGGTGGTCTATTGCACATAAA AAGCTGGAGACTTGGGAAGAGAAGGGTGGATACTTCACTTTTCTCACTTGCCTTCTCTCTCTTTAGCTAC TTCTGGTTCCTCTCTTCTCCATTCTTGGGAGGTGGGTTTGGGGGTGGAGGGAGAAGAGGCTGAGAAGGGG GTGGAGGGAGAAGAGCAGGGAGTTCTTCCTTGCCTAGTTACTACGGCACTTTGGGAAGATGGTGTCACGT TCCAAGCATGGCCAATGTTTAATGATACCATTAAAATCTCAGGGGTTATTTTGGAGATTGTTCCCTGCCA

	Sequence Information

Literature

	Literature

PubMed:9182795 (S)NO signals: translocation, regulation, and a consensus motif.
Stamler JS, Toone EJ, Lipton SA, Sucher NJ.
Neuron. 1997 May;18(5):691-6. Review.

PubMed:11086993 Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON.
Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH.
Neuron 2000 Oct;28(1):183-93

PubMed:10467249 Rhes: A striatal-specific Ras homolog related to Dexras1.
Falk JD, Vargiu P, Foye PE, Usui H, Perez J, Danielson PE, Lerner DL, Bernal J, Sutcliffe JG.
J Neurosci Res. 1999 Sep 15;57(6):782-8.

FAQ

PubMed:9182795	(S)NO signals: translocation, regulation, and a consensus motif. Stamler JS, Toone EJ, Lipton SA, Sucher NJ. Neuron. 1997 May;18(5):691-6. Review.
PubMed:11086993	Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH. Neuron 2000 Oct;28(1):183-93
PubMed:10467249	Rhes: A striatal-specific Ras homolog related to Dexras1. Falk JD, Vargiu P, Foye PE, Usui H, Perez J, Danielson PE, Lerner DL, Bernal J, Sutcliffe JG. J Neurosci Res. 1999 Sep 15;57(6):782-8.