Tumor Endothelial Marker Report: TEM8, PEM68 (Heyl)

	TEM domain structure

	TEM Sequence Analysis

name	from	to	source/E	description
unknown	1	39
bHLH	39	99	Aravind SDB, E=2e-11	The DNA-binding and protein dimerization domain of Heyl is predicted to bind to an E-box (prediction based on Gly 49).
orange	114	162	SMART, E= 1.5e-15	The orange domain has been shown to confer specificity of action to Hairy/E(SPL) proteins by an unknown mechanism. It has been determined as a more stringent determinant of specificity of HES family members than the bHLH domain.
unknown	162	315		A LCR (SEG25) is predicted to span from residue 184 to 312.
	162	217	SAPS	The region spans an uncharged run of L: 7(12.5%), A: 6(10.7%), S: 7(12.5%), P: 14(25.0%).
	217	269		LCR(R)
	269	320	SAPS	The region spans an uncharged run of A: 7(13.5%), S: 11(21.2%), P: 10(19.2%).
YHSW	315	319	by similarity	The modification of the conserved WRPW Hairy/E(SPL) motif required for groucho binding suggests a unique function in transcriptional control for TEM8/Heyl.
TEIGAF	323	328	by similarity	The motif is typical for Heyl proteins (and absent in other Hes).
328

	Remarks

• CLASSIFICATION: Hairy/Enhancer of split family of bHLH transcription factors.

• HOMOLOGUES: TEM8/Heyl shows a high degree of homology to other HES family members in the bHLH domain and in the extreme C-terminal segment, which has a function in corepressor binding. Similarity in the central region is lower.

• REGULATION: The Hey gene family members, Hey1, Hey2 and HeyL, possess RBP-Jkappa binding sites and are similarly responsive to Notch signaling. Jagged-Notch signaling has been shown to crucial in maintenance and development of vasculature.

• EXPRESSION: Mouse HeyL expression has been localized to the presomitic mesoderm, the somites, the peripheral nervous system and smooth muscle of all arteries.

• DOMAIN ARCHITECTURE: Shares several Hairy/Enhancer of split family traits : a bHLH domain, a characteristic domain adjacent to the HLH domain, the orange region carboxy-terminal of the bHLH sequence. Several characteristics differ from other Hairy/Enhancer of split family members: the bHLH domain and the conserved proline found to confer N-box binding specificity have diverged, the extreme carboxy-terminal YRPW-motif is changed to YHSW and an additional C-terminal TEIGAF-motif can be found. The C-terminal YRPW-motif is necessary for transcriptional repression of downstream targets and binds groucho corepressor.

• FUNCTION:
  By analysis of known conserved motifs in the bHLH region and the C-terminal corepressor binding region.
  
     Most bHLH proteins bind to the canonical E-box (CANNTG). Hairy proteins bind a variant called the N-box (CACNAG) due to a conserved proline in the basic region. TEM8/HEYL has a glycine at this position and is predicted to bind to an E-box.
     The Hairy/E(SPL) family members are thought to function through two separate repression mechanisms: repression via the bHLH & orange domains and repression WRPW domain. The orange domain has been shown to confer specificity of action to Hairy/ESP proteins by an unknown mechanism. WRPW is a conserved carboxyl-terminal tetrapeptide found in the Hairy family of basic helix-loop-helix transcription factors, including the Hairy, Deadpan, and Enhancer of split proteins. The WRPW motif is required for interaction with the corepressor groucho and for transcriptional repression. It is not known whether the 3-aa change in the tetrapeptide affects a putative interaction of Tem8/HEYL with Groucho or whether Tem8/HEYL mediates negative and/or positive regulation of transcription.
  Tem8/HEYL is likely acting by dimerizing with other bHLH proteins.
  By similarity to Hairy/E(SPL) genes Tem8/HEYL potentially functions in cell fate decisions.
     Notch has been implicated in angiogenesis, and Hairy/E(SPL) genes are known to act downstream of Notch. HESR1 (HEY-1), a human transcription factor of the same family, has been isolated as a EC gene upregulated during in vitro capillary-like network formation. It has been hypothesize that HESR1 is required to induce and maintain the mature vascular phenotype, in part by preventing EC proliferation and migration.
      TEM8/HEYL is likely to act by dimerizing with other bHLH proteins, thus, the observations made for HESR1 are of particular interest.

	Sequence Information

TEM	TEM8
Reliability of Gen2Tag mapping	Cid->tag (Hs.10225) frequency: TEM8 : CATG-CCTGGTTCAG= 7/7 (EST: oriented) Cid->tag (Hs.23823) frequency: Pem68: CATG-GGTTGTTGCG= 20/21 (EST: oriented) Tag occurrence in N-EC/T-EC: TEM8 : CATG-CCTGGTTCAG=0/15 Pem68: CATG-GGTTGTTGCG=6/21 REMARKS: Poly-T primed ESTs containing the SAGE-Tags for TEM8 (Tem8 ESTs) were alocated to a genomic sequence. Tem8 and Pem68 ESTs were found in close downstream proximity to Heyl(see genomic sequence). Thus Heyl is considered to encode Tem8 and Pem68. TEM8 AS A Pan-Endothelial Marker: A BlastN search against hEstDB was performed using the genomic sequence segment that includes parts of the HEYL cDNA and the proposed 3UTR with TEM8 and Pem68. The output contains EST hits defined by either the proposed Tem6 or Pem68 Tag in a relation as seen above in the Cid->tag frequency listing 7:21= Pem68-ESTs: Tem68ESTs. The Tag occurrence in N-EC&T-EC is higher for the Pem68-tag compared to the Tem8-tag but the difference is not correspondend to the relation derived above. Possible conclusions are either that Pem68 and Tem8 are alternative transcripts of Heyl not differentially expressed in an tumor versus normal endothelium (infering that Tem8 is misinterpreted as a Tem) or that Tem8 is a variant preferentially transcribed under angiogenic stimulation. As both the Tem8 and Pem8 are found downstream of the proposed Heyl CDS no indications can be found for a difference in the CDS for Tem8 with a possible implication for its expression in an angiogenic situation.
Analysis	BlastP against nr Output Created by a Suite of Single Sequence Analysis Techniques
Protein Description	SEQ.SOURCE: gi|7018334|emb|CAB75716.1| HEYL ANALYSIS: protein sequence derived from genomic sequence analysis
Protein Sequence	MKRPKEPSGSDGESDGPIDVGQEGQLSQMARPLSTPSSSQMQARKKRRGIIEKRRRDRINSSLSELRRLV PTAFEKQGSSKLEKAEVLQMTVDHLKMLHATGGTGFFDARALAVDFRSIGFRECLTEVIRYLGVLEGPSS RADPVRIRLLSHLNSYAAEMEPSPTPTGPLAFPAWPWSFFHSCPGLPALSNQLAILGRVPSPVLPGVSSP AYPIPALRTAPLRRATGIILPARRNVLPSRGASSTRRARPLERPATPVPVAPSSRAARSSHIAPLLQSSS PTPPGPTGSAAYVAVPTPNSSSPGPAGRPAGAMLYHSWVSEITEIGAF
SAGE-Tag	CATG-CCTGGTTCAGT
EST/cluster Description	UNIGEN CLUSTER: UniGene Cluster Hs.10225 SEQ.SOURCE: gi|7018333|emb|AJ272215.1|HSA272215 Homo sapiens mRNA for HEYL protein ANALYSIS: see genomic sequence analysis MARKINGS: TEM8 Tag in red first Poly-A-signal following the Tag in bold
EST/cluster Sequence	>ugc|Hs.10225.1|Hs.10225 invers complementaer CTCACTTCCAGCCTCATTTCTTGCCAGTCCCAGACTTGCTCCCTGAGCTTCTGCCACCTG CCCTTCCTTCATTTCCTCGACATTCCAGCCTTGTTCCCACCTCCAGCACTTTGCATATGC TGTTCCCTTTGCCAAGAATGCTCTTCCCCTACCCTGTGCATGGCTGAGTTCTGCAGACCC TCAGGCCTTGGCTTCAACGTTGCCTCGTCCAAGAGGCCTTCCTCGACTACTTTACTTGTG GAGTTCCTCTATCACAAGGCCTCTGTTCTTTCCCTTCATGGAGAATTTGCCACTGCATAT CCATTTGTGTAATTTACTTGTTGGTTGACTGTGCCTCCCACTCGAGTGTAAGCTCATGAG GCCAGGTGCCATGCCTGGTTCAGTCTCCACTCTGTACCCAGCATTGAGCACAGGGCCTGG TCCATAGTTGGCGTTCAATAAATACTTGTTGAAGAAGTGAAAAAAAAAAAAAAAA >gi|7018333|emb|AJ272215.1|HSA272215 Homo sapiens mRNA for HEYL protein TGCGTTCGCCATGAAGCGACCCAAGGAGCCGAGCGGCTCCGACGGGGAGTCCGACGGACCCATCGACGTG GGCCAAGAGGGCCAGCTGAGCCAGATGGCCAGGCCGCTGTCCACCCCCAGCTCTTCGCAGATGCAAGCCA GGAAGAAACGCAGAGGGATCATAGAGAAACGGCGTCGAGACCGCATCAACAGTAGCCTTTCTGAATTGCG ACGCTTGGTCCCCACTGCCTTTGAGAAACAGGGCTCTTCCAAGCTGGAGAAAGCCGAGGTCTTGCAGATG ACGGTGGATCACTTGAAAATGCTCCATGCCACTGGTGGGACAGGATTCTTTGATGCCCGAGCCCTGGCAG TTGACTTCCGGAGCATTGGTTTTCGGGAGTGCCTCACTGAGGTCATCAGGTACCTGGGGGTCCTTGAAGG GCCCAGCAGCCGTGCAGACCCCGTCCGGATTCGCCTTCTCTCCCACCTCAACAGCTACGCAGCCGAGATG GAGCCTTCGCCCACGCCCACTGGCCCTTTGGCCTTCCCTGCCTGGCCCTGGTCTTTCTTCCATAGCTGTC CAGGGCTGCCAGCCCTGAGCAACCAGCTCGCCATCCTGGGAAGAGTGCCCAGCCCTGTCCTCCCCGGTGT CTCCTCTCCTGCTTACCCCATCCCAGCCCTCCGAACCGCTCCCCTTCGCAGAGCCACAGGCATCATCCTG CCAGCCCGGAGGAATGTGCTGCCCAGTCGAGGGGCATCTTCCACCCGGAGGGCCCGCCCCCTAGAGAGGC CAGCGACCCCTGTGCCTGTCGCCCCCAGCAGCAGGGCTGCCAGGAGCAGCCACATCGCTCCCCTCCTGCA GTCTTCCTCCCCAACACCCCCTGGTCCTACAGGGTCGGCTGCTTACGTGGCTGTTCCCACCCCCAACTCA TCCTCCCCAGGGCCAGCTGGGAGGCCAGCGGGAGCCATGCTCTACCACTCCTGGGTCTCTGAAATCACTG AAATCGGGGCTTTCTGAGCTGCCCCTTCACCACCCCGCCCCAAGGAATAAGGAAGGTTCTTTTACCAGGA GCCC
Genomic Sequence Description	SEQ.SOURCE: gi|9801539|emb|AL033526.24|HS110F11 Human DNA chr 1p33-34.3 ANALYSIS: BlastN of the genomic DNA sequence against hESTDB. BlastN of the genomic DNA sequence 17345-2176 (including parts of the described HEYL cDNA and the two tags) against hESTDB. Promotoranalysis MARKINGS: TEM8 Tag in red Pem68 tag in mediumvioletred cDNA and first Poly-A-signal following the tag in bold
Genomic Sequence	1 TTTTCTCGGCTCCTGGTTGCCTTGGTCCCTGGTGCTCCATTCTCGCAGGATTCTCCTCCT 61 TCTTCCCAGAGAATCTTTGGCTATTGTTTCCCAGGGTCCTAGCCTAGGTTCTCCTCCCTT 121 CTGGATCTGCACTAGCTCCTTGGGACAGATATGTCATGTATCCCATGTCTTCAGCCACCA 181 AATCTCTCCTCCAGCCCAGACCTCTCCCTGGGTTCTCCTCCTGGGTGTGCGCTAGGTCTC 241 ACAAACAGCATGGCCATAGTGAGCTCCTTCCCTTCTCCAGTGTTTCCCCTTGGTGCTTGT 301 CACCTTCATCCATTCAGTCACCCAGACAGGAACCCAGTATCACTCGAATCCAGTCCTTAT 361 TGCCTGGCCTATTTTAAGAGTCTCCTGATTGGTCCACCCAGCTCTAATGCAGGTTGCAGT 421 GGTTACCAGCATGAATTCTGGCGCCAGACTGCTTGGTTAAAATCCTATTTCTACCACTTA 481 GTAGCTGTGTGATCTTGGGTAAGTTATTTAACCTCCCTGTATTTCAGGGTAACTTATGAA 541 GAAAAGAGGTTTAATTGGCTCACGGTTCTGCAGGCTGTACAGGAAGCACAGTAGCATCTG 601 CTTCTGGGGAGGCCTCAGGGAGCTTCCAGTCATGGTGGAAGGCAAAAGGGGAACAGGCAC 661 GTCACATGGCAAAAACAGGAACAAGAGAGGAAGCAGGGGAGGTGCCACACACCTTTAAAC 721 CACCAGATCCATGAAAACTCACTATCATGAGAACAGTACCAAGGGGATGGGACTAAACCA 781 TTCATGAAAAATCCACCGCCCTCACCTCCCACCAGGCTCCACCACCAACATTGGGGATTA 841 CAATTCAACATGAGATTTGGATGGGGACACAGATCCAAACCATATCACCATTCTATTGAT 901 ATTCCATGCTTGTTCCTACCTCAGGGCTTTCCACTTGCTGTTCCTTCTGCCTGGAATCCT 961 CTTCCCCAGATCTTCTTAGATTCCCTCTCTCCATTCGGGTCTCTGCATAAGTGATTCATC 1021 CTCAGAGACGATCTCCTGACCCCTAAGTAAAATAGCCACCAATCCCCCAGTCACCCTATG 1081 TCTCCACCTCACTTTATCTTATTTCACAGCATCTATTAATATCACTGACATTACATTATA 1141 TGTGTTGCTATATGTTTGTCATCCTAAGCTCTGGCCCCTGCAATGTGAGAATGGCCCAAT 1201 ACAAATGGCAAGAAGGCTGTCGTGGGTGAGTGGACAAGGCAGAAAGTGGTTGGGGATGAA 1261 GCTGGAGAGATGGGCAGGGGCCTGAGCTTAGGAGATGGTACCTCCAGTGTGCCCTGAACT 1321 GCCCTGGCATGATTATTAGTATTGCCTCCTTTCACTCTCAAAGGTGCCCAGGTTATTACA 1381 GTTGTTCTGTGTATAGGGCATGGTAAGCAGTTGGCATTTTATTTCAAATGGGATGTGAAG 1441 CGTGTGGATGGTTTTGAGCAGGAAGTGACATGATCTGACTGGCATTTTAAAAGGATCATG 1501 ACCAAGTCCTTGAAACACTCTTTTGGCTCCTGCCCACACCCCCCCACACACACCCCACTC 1561 TCCTCCACTGCCCTTTCAGTCTTCTCTGGCAGCTCTTTCTCTTCTACAACCTTTAAATCT 1621 TGGAGTTTCTCCAGACTAGCGGTTCCCAACTGGGGGCGATTTCTCCCCCAAGGGACATTT 1681 GGTATTTTATCTGGAGATATTTCTGATGGTCACAACTGGAGCGGGTATAACTGGCATCCA 1741 GTGGATAGAGGCCAGGGAGGCTGCTTACCATTCTACAATCCACAGAACAGCCCTACACAA 1801 TAAAGAATGACCTGACCCAAAATGCCAGTAGTCCTGAGGTTAAGAAACCCTGCACCAGAT 1861 TAGCACCATCCAATAGGAATATCATGGGAGCCAAATATGCAGTTTAACATTTTCTAGTAG 1921 TCACATTTTTAAAAACCTAAAAATAAAACAAGGGAAGTTAACTTTACTAATGTATTTTAT 1981 TTCATCCAATATTTATACAATATTATCATTGCAACATGTAATCATAACAAAAAATATCAA 2041 TGAGATAGTTCACACTTAAAAAAATTCTGGTGTGTATTTCATACTCACTGCACATACAGC 2101 AATTCAGACCAGCCACATTTCAAGTACTTAATAGCCATAGGGGGTTCGTGGCTATTATAT 2161 TGATGGCATAGCTCTAGGCTCAGTACTGGATAATATATCACAATGTTTAAGAGCTGTATA 2221 ATTGACGGGGTGTAGTGGCTTACTCCTGTAATCTTAACACTTTGGGAGGCCAAGGTGGGA 2281 AGATTGCTTGGCCCCAGGAGTTGAAGACCAGCCCGGGCAACATAGTGAGATCTCATCTCT 2341 ACCAAAAAAAATTTTTTTTTTTTTTTTTTTTTTTTTGAGACGGAGTCTTACTCTGTTGCC 2401 CAGGCTGGAGTGCAGTGGCGCCATCTTGGCTCACTGCAAGCTCCGCCTCCCGGGTTCACG 2461 CCATTCTCCTGACTCAGCCTCCCGAGTAGGTGGGACTACAGGTGCCTGCCACCACGCCTG 2521 GCTAATTTTTTGTATTTTTTAGTAGAGATGGGGTTTCACCGTGTTAGGCAGGATGGTCTC 2581 GATCTCCTGACCTTGTGATCCGCCTGCCTCAGCCTCCCAAAGTGCTGAGATTACAGGCGT 2641 GAGCCACCACACCTGGCAAAATGTTGTTTTTTTAATTAGCTGAGCATGGTGGTATGCCCC 2701 TGTAGTCTGAGCTATTCAGGAGGCTGAGGTGGGAGGATCACTTGAGCCAAGGAGTTCAAG 2761 GTTTCAGTGAGCTACGATGGCACCACTACACTCTAGCCTGGTGACAGAGTGAATCCTTGT 2821 CTTTATTTTTAAAAGAAGGGGGAGTACTGTATAAAGTAATAAAGCCTAATGTTTTGGCTC 2881 TGGAACTGAACTGCCTTGTTGAATTCCAGCCCTTCCATTTATTGCCTGTTGGCCTTAGGT 2941 GGAGTTAGTCTACCTCTCAGCCTTTGTTTCTCACTTGTAAAGTGGGGATTATAATATTAC 3001 TACTTTATAGGGTTGTCAAGGATTAAATGAGTTAATATTTACAAAAGACTTAGAATAGTT 3061 TCAGGTTTTATAATAAGGGCTCACCAAATGTTAAGTATTTAGCTAGGCCCCTGCTCTGTC 3121 TCCATCCACGTTTTCTGAATGATCCCATCTGCTCCCATAGCTTTAAATGCCATCAATTAC 3181 CTAATGACGTCCAAATTTAATATCCAGCTGAGACCTCTGTTCTGAACTCCATACCCTCTA 3241 TTTAACTGTGCACTGTATTTTGATGATCCAAGACATCTCACATGAAACGTCCATCACGGG 3301 GCCCTTGACCTTCCCCTGCAAATCTGCTCCTCTTCCAATCTTTGCTATCTCAGCCAATTA 3361 CACAGGGCAGCTATCTGGGAGGCTTCCTTGACTTCCGCCTTTCCAGGGAATGCATAACAC 3421 ATTGTGCAACTTCTCTGTTAGTTGAGGTTTCCACTGACTGGCATGTGCCCACAGAAGTGA 3481 TGTGAGTGCTGAGGGCATTTGGAATGAGAGTCCATAGTTGTGGCTGGGGCGACCACCAGG 3541 GCTTCCTGGTACTGATTGCTCACGACAGTTGCGCCTACCAGTATATATTTGTAAGTCTGT 3601 CCGTGTGTATGTGTTTGCATACCTGGCCAAATGGTTGTGTCTGTGGATGTGTGTGGACGG 3661 GGGCACAGGAACATTCTTTCCCATCAAGTAATCAAGTGTCCCCCAGCAAGCAGGCCTTGC 3721 TGTGGGGATGGAAGCACAGTTATTCTCAGATGACCAACCCGATTCTCCCACTTGAAGGGG 3781 TGGCTTCCCTCAGGTCCTGACCTGGTGGCGGGTAAAAAGGAAAAGACCTCTCATATCTAA 3841 CCCAGCACACCAAGACCTCCTCTATCTCCTCTTCCCTGCCCAAGAAGTCCAGCTCCAGGA 3901 TGCTCTCATGCAGCTTCCTTTGGAGCCTTAGGAGCTTCTCTGAGGTACTGGGCGCCTGAG 3961 GATGACCGGTGAATCTGAGAACTTCCCACAAGTCCCCCTAAGGACAGGGCAGCTAGAGCC 4021 CTCCCTGAGTGAACAGTTTGATGGGTTGCCAGAAGCAGAGGCCCCAGGAAGAGAGGCTGG 4081 AAGGTATCTTCCCTTTTCCTCTCCTTTTCCCACTTTGAGGCCCTGCCATAGCGTCTAGAA 4141 GGAGCCCTTTCCTGGCCTCCTGGCCGCCCAGGACAACTCGACCTCTGGTGAACTGGGAAC 4201 TGATTCCCAGGGACAACCCACCACTGCCACCACGCCAGGCCTTTAGGGACCTCGGCCAGA 4261 GCCCAGCTTTCTCAGATGCGGTGGCCACAACTTCAGCCGTCCCTTTTGGGGGTGACTGCC 4321 ACCTCTCAGAAGTGTAAGTGTCTTCCCCTTGCCCCCACCACACTATTCCACTTGCTTTGG 4381 GCCCCTATGGAGTTGCTGCTGGGGAATTCTTGCTGAGGATCAGGCCACAACCACCACGAC 4441 TAACTTCGACAAACTTGATGTGTCTGCTGCCTCCAGAACACCAGGAGGCAGGAGCGCGCA 4501 GGGTTGACCCTTGCGGAATCCCGGGCATCGAAGCGGCGCCTCTACAGGCCAGCAGCGCCC 4561 AGGCGACCCAGGGACAGACGGGGACTCCTGGCTTCCCCGCGGGGCCTCCCAGGGCACCTG 4621 CCCAAGGCCACCCAGCGCGCGGCAGCCGAGACAGCGGAGCAGAGCCGGACCTCCCAGCCG 4681 TCGATGAAGGCGGCGACCGCCTAGGGCCTTCCCACGGCTCGGCGGCGCGTCACCGCGGGG 4741 GCGAGGGGGCGCCTGGGCGCCCGGAGCTGCGGCGCAGGAAAGGGCCCTGGGAAAGGGCGG 4801 TGGCGGCGCCCCCGAGGCGGGGCCGGGGCGGGGCCGGGGCGGGGCCTGACTTCCCGACTG 4861 GGAGCCTTAGCCGCGGGGCTGAGACCAGGCAGCCTGCGTTCGCCATGAAGCGACCCAAGG 4921 AGCCGAGCGGCTCCGACGGGGAGTCCGACGGACCCATCGACGTGGGCCAAGAGGGCCAGC 4981 TGAGGTAAGGGCCGGGATGCGGGGACCGAGCAGGCGGAGGGCGAGCGGGGTGGGGGTCGG 5041 CCCGACGGGCTCGCCGAGCAGGCGGGCCAGCCCTCCAGCACCGCCTGGGCAGAGGCAGGT 5101 GAGCGCGGGGGCCACAGGTGTCGGCGTAGGGGGCGTGTGCGGGCCGTGCCGTTACACGCA 5161 CGAGTGCCTGGATCCTGCGCGCTCTCGGTCGTGCAGGGCTGGGGATGCTGGCAGGGAGGG 5221 AGAGTTCAGCTCGGGGGATCAGGTGGCTAGTGGGTTATCATCTATCTGTTGAAGTGGCCT 5281 AGGGGAGGCCATTGGCAGGTTTTCCCTGGAGATCTTAGAAAACTCTCATAGACTGATGGT 5341 ACTCTGGCCCCTGTCTGGAATCTGCTGACGATGCAGAGTAACCCCATTCTTTCCCAATTT 5401 TACCCTAGTTTGGATGCAGTTTTCATGTAGTCCACAAATTATTTCAGGAAGAAGAAAATT 5461 TGTCCTCCTTTGAGCAAATTGGAGTTTGGATTTAGGGACTTAGTATTGAAGAAAATAATA 5521 AGCGACTTGCAAGGGCCTAGACTCTAATTCCAATGTTCCTCCTATCGTGCCCCCATACTG 5581 CCAGTGTCTTTCAGCTCCTGGTAGATAGTCTGACCTGCTTCAAACCTGTCGAACAAACTG 5641 CGCTTGTATAGTTCTGCTACCTCGCAGTTCTGTAAACTGTCTAAGCTTCAGTTTCCTTAT 5701 CTGTTAAATGAGCATGAATAATAGAACCAACTTCATGGAAGTATTGGGAAAACCAAATGA 5761 GGCAAAGTATGTCAAGGGCTTAGCACAGCACATGCCTAGGTACACACCATGTGATTCCCA 5821 GCACCCTGAAAGAGCTGCAGGGCTGACTGGGAGTCTGCAGACCTGGGTCCCAGCCCCAAA 5881 TCTGCCACCAACTCACTATGTGGTCTTGGGCCATTGGTTTCCCTGACAGAGTCTGTCATC 5941 AGTTTCCCCATCAGTAAAACAAAGACAGCAGTGGAAAAGAAAGGGATATACTTCATCTCT 6001 CTTGGCTCATCTAGACTTGACTCTCTAGAACAGAATTGGAGGGGAATTCAGTTAATTCTT 6061 TCTTTCTTTCTTTTTGACATGGTCTCACTCTGTTGCCCATGCTGGAGTGCAGTGGCATGA 6121 TCATAGCTCATGGCAACCTTGATCTCCTGGGCTTAAGTGATCCTCCTGCCTTGGCCTCCC 6181 AAAGTGTTGGGATTACAGACATAAGCCAGTGAGCCAGGCCCAGTTAATTCTTAGGGATGT 6241 TTTTGAGGACATTTTGTAATTTTAGTGCTCTCCAGTTTTCTGAGATCCAAGGATCCTGCC 6301 TCAGTCTCAAATCCCAGGAAAATGCCATAATAGATATTCCTCTTGCAGCCTGTACATTTG 6361 TTTTTAGGGAGTATAACACAACTCGCTATGCAACGTATTAGCCTTTCTTAATTGTTTAGC 6421 AGAAACTGCTATTTAGAAAAGCAGTTATCTTAGCCTGTGCCTGTTAAGGGCCAGGAAAGG 6481 GCACAGCACCACGTGGTGGTGGTGGAGCGGGGTCTCAAATTCAATGGCATTGGGTCTTCA 6541 TAGATCAGAGGCACAAAATTGATGCCAGAGAACTAGGTTGATCAGAGCTGGCTTCTGTCC 6601 TCCACAAGTTTGCAGCCCAGTCAGTGACCTGCCAGGTCATAAAAACACCATGGACAGGAT 6661 GGAAAGGAGACAGACTGTGGGCTGTGAGGGCACTTAAGCAAAGAGAGGTCACTCTTAATC 6721 AAAGATGGCAAGGAGGGCTTCTTGAAGATAGTAGCATCTGGGCAACTGCTTACATGAGGC 6781 ATAAAGGATCAGTGGGCAGTTTTTTCCTATACATACAGCATTTCCTATATATACAGAGCC 6841 CATTTTTAGACACTGTTCTTAGAGGAGCAGACCCCTCTGAGGAGAGAAAGCAGCTGGACA 6901 TCTGGCAGAGGCTGACTTATAGATGCCCCTTTGTAGCACTCACCAAAGGGCCCTTCCCCC 6961 AGCAGACATCAATGCTTCAATTCAGGGAGCACTGAACGATGCCTGCTGTGGCCCAGACCC 7021 TGGGCTGGGCATAGGGGGCCCAGATGTATCCTGCTCAGCCTCTGCCCTCAGGGAACTCTC 7081 AGGGAAGAAGAGCTTCATGTACAAAGAAAGCAGATAAACACTGACAAAGGCCGCAGGACG 7141 GAGGCAGCCAGCCTCTCGGGGTCAGGGGCAGGGCGCAAAACCCCCACACTCAGAAACGTG 7201 AGAGTAAAGAGCAGGGTGTGTTCCACCATCACTGTGGCATCTGCCTGGTGGCAGTCCTGC 7261 CACATCTGTGAAACTCACCCACAGAGCTCTCATCTCAACCTGGCCCCATGACGCAGGATG 7321 AGTCCAAACTGAGAGTACAGCCTCTCCTCTCCCTCTGCAAACATCTAATGAGCACCTGCC 7381 ACATGTCAGACACTGGATCAGGGTCCTGTTCCTGCACAATATAAGGTGGTGGTCTTGGAG 7441 TCAGATAGACCTGAGTTTGAATTTTACCACCATTAACTTTGGCCAGTGACTTTTACCCCT 7501 TTCTGAACCTCAGTTTTCTCGCGTTCAAAATGGGAATACATTAGCACTCCTGCCTCGCAG 7561 GATAAGGTTTGATGAAGTAACATACATAAAGTTACATAGCTCCCTGCTTTGGCACAAAGT 7621 AACTTCCAATAAACGTTGCTGTCAAAGCGGTCACCATTCAGTTGGGGGGCAACATATTTA 7681 TGAGACAGCATGGTCTAATGAAAAGACCGGAAGTGTGAAGACTGGACTTACTGGAGTGAT 7741 TCTTAACTCCAGTGTCTCTGTCACTCCACCTGTAAAATGATTATTTTTCCTAAATGTGAA 7801 ATGGCCCAAAAAATACTTCACTTACAGTGCTATTGTGCAATAAATTAGACAAATGGATGT 7861 GGAAGTGCAGTATAGAACAAAAAGCACTGGCTCTGAGATCTACATGACGGGATGATGTAT 7921 ATATGGGGTGCACTGGCAAAAGCCCCAGATTAAAAGCCACTAGAGGCCGGGCACGGTGGC 7981 TCACGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGTGGGTGGATCACGAGGTCAAGAGA 8041 TCGAGACCATCCTGGCTAATATGGTGAAACCCCATCTCTACTAAAAATACAAAAAATTAG 8101 CTGGGCATGGTGACACGTGCCTGTAGTCCCAGTTACTTGGAAGGCTGAGACAGGAGAATC 8161 ACTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCTGAGATTGTGCCACTGCACTCCAGCCT 8221 GGGTGACAGAGTAAGACTCTGTCTCAAAAAAGAAAAGAAAAAAAAAAAAAAGCTACTAGA 8281 GTAGACCTGGCTGTAGTTCCGATTTTCCTCTAATTTGCTGTGTGGCCTGGGGAAGATCCC 8341 TTCCCCTCTGAGTTTCCTTATTTTACAAATGGACTCAGTTCTCTCTGAGATTCCTTCATT 8401 TGGGACATTGTGATTCTGCCTTTGGCTGACACAAAATGATTAGGGTCATCTGCAAGGGTT 8461 CCACGGGGGAGTTCCCAGGGGAAGTCAGCACTGAGGGTGGTCAGGACCACCTGGAAAGCT 8521 TCCCCCCATAAGAGACCGCCCCAGAATTCTGGCTAGGAGCCACTAGAGGCCTATGGAGCA 8581 GATCTTGATGGTCAACATATCTTCTCTGGGTCCATGAAAATCTGTGTCATTTTCAGATTC 8641 TCAGACAAGAGAATCCCACACCTCATCCCACTGTCAGGGCCAGATCGCAGGCTGGAAGGG 8701 AGCTCTGGCTGGGCTCTTGGGAACTTTAAAAATAAGGGGACCGGAGGGCTATTCAGACAG 8761 ACAGGAAGTAGGAATTAGAAGGGAAAAAATGCTGAAGCGGAGCCAGAAGATGCGGATTCC 8821 CTGCTGGCTTTGCTCCTTAGCAGCTGGGTAGGCTGGGCAACCTGCTTTAGCTCCCTGAAG 8881 CTCAGCAACCTCATCTGTAATATGGGCTTTTGTAAGGCTCAAAGGAGGGAAAGACATATA 8941 ATGTTGCCAAGAAAACTGTAATGTGAGGTTTGCCTCTGAGATATGGGAAGAGGAGAAGGG 9001 GGGAAATAATACGACAGGGACAAGCTGACCAGGAGATTGGAAAAAGGAATGGCAGCACTG 9061 CTTTGCCCTGAAATGGGTGCGTCAGCCTCCAACAGATGGTCCCAGCGGAGGGATCAGGCT 9121 GAGAGGCAGTGACGTGTGCAAGGCTAACCTAATACCCGGAAAGACGCTTTATCAAGCTGG 9181 GGGGAACAAAGGCCGTGTTTCTTAGTGTGTCTTGGCTCTTGGGGTTTGTCCCCAGTGAAC 9241 CAGTGAGGCTTTGTAAACAAGCTGCCCCATAGATCTCAAGATCTGGCCTCACAAGCCCTG 9301 GACCTAGCTTGCTGGGTCCTCCCTCCCAGGAGCTATTATAGACCTCTTACCAGGTCGGCT 9361 TGTCCAGATGTTTGGGTGGGAGATATCCTTTTCCAGATGTGTCTGGACAAAGCCAGAGAC 9421 ATAGCAGTAGGATTTGACAAATGCTATCTGGTCTCTTCTGCAACCTTCTCTGAGCAGTTG 9481 ATGAAAATGATCCAAATTCAAATGCCAAAAGGGTTGGGACCCTTGGGCTGGGACCCTTGT 9541 GTTAAGTCATATACGCCCCCATTCCACAAAGTCCTAGGCCATAGATTTTATGGTGCTTAC 9601 ATCTCTGTTCCCCAGTGATGCCAAAGACATGGGTGAGAGAAGAAAGCTCTACCATGAGTT 9661 CTGCTGTATTCCAAGCCCTTGCTGAGTACTGAAGCTGCAATAGTGAATGTAACAGACATG 9721 GTTCATGGCCTCATGGAGCTTATGGATTTGTTGGAGAGATAGACATCAATCAAATAACCA 9781 TATAAATATAAAACAATGAACTGGCATAAATGCTGTGAAAGCAGGGTGCTAGGAGAGTAT 9841 TGAGCAGGGGACACTAGTGGGAGGAGGAATGTTAGAAAAGGCTCCCCAGGGAGGTGCCAT 9901 CTGAGTTGAGATCTGATGGGTTGTAGAAGTTATGGGGCAAAGGGACTGGGGCTTGGGGTG 9961 ATGGGTGAACCAAAGATGGTGGACCTAGGCTAGGGGACAGTGCATGCAACTGAATGAAGG 10021 AGTTGGTGCATTCATAGGCTGGGGCATACAGAAGAAGACGGTTGAGTCTAGAGGGGTTGA 10081 CAGGGGCCAGTTGGACCACCTGAAATATGGTGGCCTTGATCTTAAAAAACATTGGGGCCA 10141 GCCATGGTGGCTCATGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGCGGGCAGATCACC 10201 TGAGGTCAGGAGTTCAAGACCATCCTGGCCAACATGGTGAAACCCCGTCTCTACTAAAAA 10261 TACAAAAATTAGCTGGACGTGGTGGTGGGTGCCTGTAATCCCAGCTATTTCGGAGGCTGA 10321 GGCAGGAGAATTACTTGAACCGGGTGGCGGAGGTTGTAGTGAGCCAAGATCATGCCAGTG 10381 CACTCCAGCCTGGGCAACAGAGTGAGACTACATCTAAAAAAAACCCAAAACAAACAAACA 10441 AAAGTTGGGGAGCCACTGAGGAGTTTTAAGTGAGTGATATGATCAGATTTCAATGATCAC 10501 TCTGCCTGCAGTGTGGAGATAGGCTTGTAGAGAGTAAAAGAGGGTGTAAAAGGACCCAAC 10561 AAGAAGCTCTTGCAGTCACCCAGATGAAAGATGATAAAGGCGTAGCATTGAGAGAAGTGG 10621 CGGAGAGGAAGAGGACAGACGTGAGATATATTTTAGACATAGCGTGGGCAGGTTTTGATG 10681 AGGTGGGGGTGAGGAGGAGGAGGAATCAAAGACAGCATCAGCTTTCCACCTTGCAGAACT 10741 GGGGTACCTTCACTGAGATGGGGAAACCCAGGGGCAGCAGGAGCAGGTGTGGGTGAAGGC 10801 CAGCTTGCAGATTCCTGTTCAGATGTGTGGCGTTGTGTCTTCTGAAACGGCAGGGGAGTC 10861 ACCTTGTTTGTTGTTTGTTGGTGCAGTGTCTGCCCACTGGAGCTGAGTTGAGGAAGGGAA 10921 GGGCTGGGGTCTGGCTGAGTGCACCAGCACCCACCCAGGCCTGAATAGGGCCTTAGAAGT 10981 GTTGGCCAAATGAATGATGCCTCAGTGGACCCAGCGAATCCTCACCATTCTAAGAGAGCT 11041 TCTGAAGCAGAAAACCTGAAGAAGGGTTAGCAGTTGGGCTGGAGATTATTTTGGTCAGAG 11101 TCTGGGCAGGAAAAGCCCCCCCAGGGCTGAGCCTCTTCTCTGTAATGGGAGCTCCTGGGG 11161 TGTGAGCAAACATCCATCATTCAACCGGGGCGCAGAGGGAAGGCCCGGAGTGGGAGGAGA 11221 GGCCGAGGTTGGAGGGACGGGGCCTTCTGGGAGGCCAGGGCAGTGTCCCAGAGCATCCGA 11281 GAGGGGCCTGTGACCCAGATGCCGCCTCCCCTTCGCCCCCGGCCGCACCGCGTGGGAGGA 11341 GGCGGCAGCTGCAGGCGGGGCGGAGGGCGGGCGGCCGGCGCGCCCGGCCCGTGGGAAGCA 11401 GCGGCATCTGCTCTTTCCACGCTCGTTCCCAGCGGCTCCCTCTGAAACCCAACCCGCCCG 11461 GCCCAGCCCCGCCGCCGCCGGCCAGTGCCCTCGCCCGCCCCGCCCCCGGGGATCGGGTTG 11521 CAGGAGCCGGAGCCACCGCGCCGCGGTACGCGGTTCCCCGACGGCCGCCGCGAGGGGCGA 11581 GGAGCGAGGAGCGAGGGGCGAAGGGCGAGGCCGAGCAGGTCCGGGCCAAGAGCCCAAAGT 11641 GGGCCCAGAGTGCATGAGAGGACTTGACCCGGGTTGAAATGAGCCCCCAGGAAGAAGGGG 11701 AGAGCAAGCTGCTCCTTCTAGGCCCAGCCTGTGGCTCCTCCTGGCCCGAGGTCGGCCCAG 11761 GCCGGGGAGACTGTCCCCCAGCCCTGAAAAATCAGCTTTTCTTTTCCTTTCCAGCCAGAT 11821 GGCCAGGCCGCTGTCCACCCCCAGCTCTTCGCAGATGCAAGCCAGGAAGAAACGCAGAGG 11881 GGTGAGTGTCCGTCTCAGCCTCTGAGTTGACCAACAAAGGGTTGCCATGAATCCCCTGCA 11941 GTCTGGCGGCGGGGAGAACCCTAGGCAGAAATTTCACCATGAAGCTAACTGCTTGGGTTC 12001 AAATCCCGGCTCTGTCACTAGCTATCAGGGTGATTCCAGGCAAGCCTGTTAACCTCTCTG 12061 AGCCTGATTTGCTCCTTTGTGTAACTGGAATAATGAGAGGGCCCACCTCAAAGGGCTGCT 12121 TTACAGATTAAGTGCATTAATGTAATGCTCTAAACAATAGCAGACACACAATAGGCCATT 12181 ATGATTGTTGTTCCTATCTTCTGTCTCCTCTCTGAGTCCAGAACTTTCATCCCCCTCAGT 12241 GTGCCGGGGTGGGGGAGGGGACAGAAGAAGGATCCCCACTTGCCGCTGTCATCTGTCCAT 12301 CATGTTCAGCCCCACTTTCCTCCCAGGATGCAGCTGTGTTTCTGCACTGGGAGTCCAGAC 12361 ACCTGGGGTCTGGCAGAGAGCAGCCTGACACTCACTGACTGTAAGCCCTTAGGCAAACCA 12421 CTTCCTTCCAGCCCTCATTTTCCTTATCTGTAAAATGGGGTCATATCTGTCCTGCTCCCG 12481 GTGTTCTGCTACCAGTATTGGAGGGAAGAATGAGAGTGTGTGGGTGGAAGGGCCCTGCAG 12541 CTAGAGAGAGCAACACGTGGGACTCCCCAAACCATCTCATGACCTCACAGATGACGGGGT 12601 CACCCTCCTGGCCCAGCACGGGCCTCCAGGGCCTGCTCCAGCACCGTGGCTGGTGTCCTC 12661 ATTGTGATTGGCTGTGCCCTGCTGTACCAGTGGTTAAACATCTTGAATATCACCCCTATA 12721 GACCGAGACAAGAGATCTGAGTTGTACTCCCAGCTCTGCGCTTTCTTGCTGTGTGACCTT 12781 AAGCAAATCACTGTCCTTCTCTGGGCCTTGGTTTTCTCCACCATAAAGTAAGACTAGATT 12841 GATCTCCCTCACAAAAATACTGTGTGGGTAAATATGAGTTGATGACCATCAAGGCACTTT 12901 GGAAACTGTGATGACACACCTGTGAGTAACTTCTTGTCATGATTGTTTAGATCATAGAGA 12961 AACGGCGTCGAGACCGCATCAACAGTAGCCTTTCTGAATTGCGACGCTTGGTCCCCACTG 13021 CCTTTGAGAAACAGGTATGTGACATTGCTGATTGTGCTAGAGGAAATACTGTGTGGGTGG 13081 CAGATAAGGTTCGTTTCTCATGGCATCTCTTGTTGATTGGTAGCAGCTGCCTGAGATGCT 13141 GTGATCATTTACCAATATCTGTCACTGGCCAGGGTAAAAGGAATGGAAATTTATACTTAG 13201 GTGTCTCAGGTGTCTTTATGTCTATCATCCCATTGAATTGACTCCTCAAAATGATCCCAA 13261 AGGTTAGGGATTATTATGCCCATGGCACAGGTAAAGAAACTGAAGCACAGAGAGGTGAAG 13321 TAACTTACACCAGATCACGCAGCTAGTAAATAGCAGGGCACAGGACTGTGTGATTCTCAA 13381 GCCCTCATCCCTCTGCACTACAGACATTTCTAGAGTGACTTGAAAGTGGAAAAGGCTGCT 13441 CAGGGAGTGAGCACTCTACCATTGAGCATGTTAGGTGGGGGAACTACAGCGGGGAATCAG 13501 ACAGTGGACTCAGCCTCAGAAATTCTCACCCTATGCACCAAGGCATAGGTCACGGGTCCT 13561 CTGCCTTCCTTTATGCTGGTGAGAACAAGTCAGTCATCCCACAGATGTTCACTAAAACCA 13621 TCACAGGACCAGCCATGAACTAGACCTAGTATCTGCCCTCAAGGGACTCCCATGGAGCCT 13681 CTGATCTTCAGGCTTCACCTGGAAAGCTTAGGAAGCATTTCCCAAGAGAGAAAAGAGGAA 13741 GAACAAGTGGTCTGGGGATAAGATGATGAGCTAGATCTTGGGCACATTGAGTCTGAAGTT 13801 GGATTCCCTGAAGAGCTGGTTTAAGAGGCATTCTGAGGATGGTGGCTAAAGCCATGGAGG 13861 TGACAAGCCTCTCTGCAGGGAGCAGCAGAATGCGAAGTGACACAGAAGGGACAGTACTGT 13921 GTTAAGAGACGGCAGATCAAGAGGCATGGTGAAAGGAGAGCCCAGAAACAGTGGTGTCGT 13981 GCAAGTCAAGGGAGGAGTGGTTTCAGGAAAGATGATCGGCAGCTGTACAGTGGACAGATG 14041 GTCTGAGAGGAGAACTGAAAAGAATGTTCTAGATTTGGAGAACTTGGCCAAAGCAGAAGC 14101 CCATTTGCAGGCAGCAGTGGAGTGGGAGGAAGGTGAGAAAATCGAGACGGTGAGTGCTGA 14161 TGACACCGCACAGCTACATGGTCAGCTGCAGGCTCCACCCTTCTGTCTTCTGTACCCGCA 14221 GGGCTCTTCCAAGCTGGAGAAAGCCGAGGTCTTGCAGATGACGGTGGATCACTTGAAAAT 14281 GCTCCATGCCACTGGTGGGACAGGTACCCATGCTCTTCTCTTTCAGGCGTCATTCATACA 14341 ACAAATATTTTGAGGCTGGGCCCTGGGGATATGCTGGTGAGCAAAGTCCACACGCTGCCC 14401 ACTCTGAGGAGCTCAGTCAATGGAGGGAACATTTGCAAAGCTTCTCTCTCTCCTTTCAGC 14461 ATCTCCCTCTCCACTTTCAGTGTCTCCATTTGTCGCAACCTTTTCCTCAGTTCAGCTCCC 14521 TCCAGTCTTAGACCTGGGAGGCGCTTTCTTCTGTAACAGACTGTTCCTATGGGTCCCACT 14581 CTTGTCCAACCCAGGACCTCATTAAGAATTCACCTGAATGAGCTAATTCTCACTGGGATC 14641 CCAATCTGACCCCCCTTAACCCAGGGAGGAGCCTGGTATCCTACCCACTGGTCTAGCCTT 14701 CTGGGCTACTGTGGGGTCCTTGGCAGAACTGGGGTGACATATCATGCTCACCACAGGTCT 14761 CAGGATTGTAGCAGGACACAAATTAACTCATTTTGTTATTTTAAGCCCATCAGTTACAAT 14821 AAAGTAAGGGAACAGTGGCTTTAAAGACACTTCCAGACAAATAGAAATTCTGTCTACTCA 14881 AAGTTTCTCTGTGTATTTGGTGATTTCAAAATTGGGAAACCTTGAAAGCTCCACAGGCCT 14941 TGGCCACAAAGACCTAAGTTCCAGAGACCTAACTTACTGCTACAGAAGAGGACAGTAGCA 15001 TTTTAAGTGGCCCATTCTGGTGCTTCTGAAGCCTCAGTGTATACCATTGTCACCTTGGGG 15061 CAGGCAGAATCAGGAGTCATCCCCCAGAGATTCTGAGGCAGTAGGTCTAGATTGAAGTTT 15121 AGGAGTTTGCAAGTTTAACAAGCCACCCAATTATCCTGGTGCAGGTGGTCCATTTGGGAA 15181 CTTCTGCCAAAAAAAATGCATTGCTAAGAGTGGAGACTTCCATCTCTAATGAACCAATGG 15241 GGGAGATTCAAATTACATTTATGGTTATCCAGTGAAAAGAAAAGTAGTGACTAATATGTG 15301 GATATCATTTGACAGTTTTAAAATGCTTTCACTTGTGTTGTTTCATTTGATTCTCACAAG 15361 AACCTGCAAGATGGGGGTTAGTGTTACCACCATTTTCTGACTGTGAACTAATGGGAAGAC 15421 AGAACTGTGGTTCACGGTATAGGCTTTAGATTTGAATCGGGCTCTACTGGTTACTAGCCG 15481 TATGACCTTAGACAAATGATTTAACCTCTCCCCTCCTCAGTTTCCTCATCTCTAAAATGG 15541 GAATAATTAGAGGGTTTTATGAGGATTAAATTAGATAACTTGATGAAATGCTTAGTAAGA 15601 ATTCAGCAAATGTTAGAAAAAAACAGCGGGCCGGGCGCGGTGGCTCACGCCTGTAGTCCC 15661 AGCACTTTAGGAGGCCGAAACAGGCGGATCACAAGGTCAGGAGATCGAGACCATCCTGGC 15721 TAACACGGTGAAACCCCATCTCTACTAAAAATACAAAAAAAGAAATCAGCCGGGTGTGGT 15781 GGTGGGCGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATGGCATGAACCCA 15841 GAAGGCGGAGCTTTCAGTGAGTCGAGATCGCACCACTGCACTCTAGCCTGGGCGACAGAG 15901 CGAGACTCCGTCTCAAAAATAAAAGAAAAAGAAAAAGAAAAGAACAGCAAAGGCCAGGCG 15961 CAGTGGCTCACACCTGTAATCCCAACACTTTGGGAGGCCGAGGTGGGCGGATCACCTGAG 16021 GTCAGGAGTTCGAGACCAACCTGGCCAACATGGTGAAACCCTGTCTCTACTAAAAATACA 16081 AAAATTAGTCGCTGTGATGGCTGTTGCCTGTAATCCCAGCTACTTTGGAGGCTAAGGCAG 16141 GAGAATCTCTTGAACCTGGGAGGCGGAGATTTCAGTGAGCCAAGATCGTGCCACTGCACT 16201 CCAGCCTGGGGGACAGAGCGAGACTCCATCTCAAAAAAAATAAAAAAAGAAAAAAAGAAC 16261 AGCAAACGCAGAAAGGTGAAGGGATTTGCTTGAACTTACATGGCTAAGTGTATAGCAGAT 16321 TTGGTTCTCACCCACAAGTTGACCTGACTCCAAACATAGTCTCCAGCTGAGCTGTTCCTC 16381 TGTGGGGGCCATGAACCAAGGACTAGATATTTGCTGCCATCGTCATGAGACCAGTGCTGG 16441 CTGGGGTTGTTGTGTCTTTGCCCAGAAGGTGGTCAAGAGAGGAACAGGTATGGAGAGGCA 16501 GTGAGGATGTGAATATTTGTACAGGAAGTTCACCTGGTTATCCATCAAAGAGAGGGTCCC 16561 TGGCCGATAACAGCAGCTGAGGATCACAGTGGGGTCTTGCTTTCCAGATTGCCTTTTGAG 16621 CCAAGGGACAAACTCAGATGCCAACAAGGCCAAGCCAGTAATATAAGTGATAGCTAACTT 16681 TTCATTTATTCAGCATTTTCTGTGCACTATTTTAATTTCACCCTCATAACTCTATACGGT 16741 AGGCACTGCTATATCCCCATTTTACAGCTAAGGAAATTGAGGCACAGAGAGATAAAGAGA 16801 CTTGTCCACAATCAGGCAGCTAGTTAAGTAGCAGAGCCAGGATTTGAACCCAGCTCTCCT 16861 GGCTTCCGACGACCTCACACTTCACTGCTACACTACGCTGCCTTCTCCAAGGGGCCTCCT 16921 CACTCTGATGGCTGCTGCCGCCACCTCCCTTCCTGGGCAACTGCCCCTCTCAGCAGGCAG 16981 AGTTGTTCTACACCTCCAAGTGCATAACCTTTCATATCTGTCAAGTATCTACTTCAATGA 17041 AGTTATCTTGGCCACAAAGTTTTTTCTTTGCATTAATCATGAATTGTGATGAAAGCAATA 17101 TTTTACATTTTATAATGCTTCATAGTTTAGTGAATTCATTGATCATTATAACCCATCATC 17161 CTCCACCCCAGGAAGGGATTTTTGTTCTCACTTTGCAGATGGGGAGACAGGCTCAGAGAG 17221 GCAGGATGACATGGCCACGGCTGCCCAGGGAGTGAGTGGAGGAGGCAGGTCCAGAACTCA 17281 GACAGTCAGACCCAGGCTCCATGCTTCTCCCCACACCTGGCATGACCTTCATCACGCCTC 17341 CCTTTGCAGGATTCTTTGATGCCCGAGCCCTGGCAGTTGACTTCCGGAGCATTGGTTTTC 17401 GGGAGTGCCTCACTGAGGTCATCAGGTACCTGGGGGTCCTTGAAGGGCCCAGCAGCCGTG 17461 CAGACCCCGTCCGGATTCGCCTTCTCTCCCACCTCAACAGCTACGCAGCCGAGATGGAGC 17521 CTTCGCCCACGCCCACTGGCCCTTTGGCCTTCCCTGCCTGGCCCTGGTCTCTCTTCCATA 17581 GCTGTCCAGGGCTGCCAGCCCTGAGCAACCAGCTCGCCATCCTGGGAAGAGTGCCCAGCC 17641 CTGTCCTCCCCGGTGTCTCCTCTCCTGCTTACCCCATCCCAGCCCTCCGAACCGCTCCCC 17701 TTCGCAGAGCCACAGGCATCATCCTGCCAGCCCGGAGGAATGTGCTGCCCAGTCGAGGGG 17761 CATCTTCCACCCGGAGGGCCCGCCCCCTAGAGAGGCCAGCGACCCCTGTGCCTGTCGCCC 17821 CCAGCAGCAGGGCTGCCAGGAGCAGCCACATCGCTCCCCTCCTGCAGTCTTCCTCCCCAA 17881 CACCCCCTGGTCCTACAGGGTCGGCTGCTTACGTGGCTGTTCCCACCCCCAACTCATCCT 17941 CCCCAGGGCCAGCTGGGAGGCCAGCGGGAGCCATGCTCTACCACTCCTGGGTCTCTGAAA 18001 TCACTGAAATCGGGGCTTTCTGAGCTGCCCCTTCACCACCCCGCCCCAAGGAATAAGGAA 18061 GGTTCTTTTACCAGGAGCCCAAAAAAGGGCACTGCCTTTTCTGCTTTGCTTCGTGGACTG 18121 GCTCATATGTGAAGGCACGTTCTCCAGCCATCAGAGGCCCCCTCCTCCTCCAACCCATCT 18181 CTCCTTCTCACTGTTATCCCAGCTTATCCACCCAGCTCTCCTGGAGCTGTTCTGGTCTCA 18241 GAGGCTTGGTTCCATTTCTCACCTGAACAGATGAGTCCTGGGAGAGACCCTCAGAGATCC 18301 GCCCAGACCCCTCTCCTGCCCTCTGCACACCAGCAGCAGGCATGAACCTTGGGTCTGGGA 18361 AAAAGCTTTAACCTGCAGGGCACCAGGACCCAAGGCAGGCTGTTCCTTGGGGCGGTCAGA 18421 CCCCAGTCAGGAGCAATGACTGACTGGCTGCAGCCTTCCCACGCCAAGAGGCTGGAACAT 18481 AGTGTCTGCCTCGCTTCCTGGAGATAGTAACTGAGCAGGGGCTACAAAGAGGTCTCCTGG 18541 GAACCCTGTCTGCCCCTTCCCACCTGTCCTTGGGCCACACCATCACACTGAACCACAGGA 18601 CAGACCCTTTCTCCACCACAGCCAAGGCCTGGAGACTGGGGGCCCAGCAGAGCCTGCTCC 18661 CACCCTCCTCCCAGCAGCAGACACCCACCCTCTCACTGACTAACAGGTCCCTGCACACAG 18721 CTGGCCTGGTAAACCCAGCTGGGAGGTTTCTAGGCAGCAGCAAAACTCTGTGACAGGGTG 18781 TCCTCACACCAGGCCTTGGACAGCTCTCCCAGACAGGAGCCAGGGTTGAGCAATGGAGAG 18841 CCCAGCCCCCACGTCTTACAGTCGCCATCCTCCAGGCGTGTGGTCCCTCCCCATTGGGTG 18901 CACAGTGCAGAGGGGCCGTGGCCCCATGTGATGGTGCGCAGAGAGGAACCTCTTGGGATT 18961 CAGCACCAGACGTCTGTGCTGCCTGGTTTGCATCCGGCTCACAGAGCCCAGACTGCTGGA 19021 ACAGCCAAGGACTGTCAGGCTGGACAAAAATAACTGCAAGGAGGGGCAAGAGAAAGGATG 19081 ATTCGAGGCACCTTGGCCCTTCAAGGTCATGCAGTGGGTCGAGCGCCTGAGATCCTGTTC 19141 ACCAGGACTCCACAGAGCTGGCTCTGCTCAGAAGCCATTTCATTCCCCGGCTCCACCCTA 19201 GGCCACTTTTTCTAACAGAGGAAACAAATGGTCCAGCAGTCGTTCCCAGCAGAACAGCGG 19261 AGCCTGGACTGACACCCAGTGGGACCAGTGTTGCCACACCAGTTGATAAAATGCAGAAAC 19321 CCTTCTGTACTCGTTGGTAAATATCTACTCCCCCAAGTGACTCCAGGTGCCCCCCACCGC 19381 CTGGCACTTCCCCCAGGACTCCTACGATCTGGTTACTGCCTGGCCGATCCAAGGCTGTGG 19441 AGTCCCAGAGCCAGCAGTTCACTGGTGCTCATTCCACACTGGTTAGATACTTCAGTTGTC 19501 ACCCCTGGGAAGATTCTCCCACCTCCTCCCTTTGATGGAACCACCCTCCCCAGAGGCTGC 19561 ATTGAGGAGACTCCACAGACTGAAAAGTGAGTTTGCAGAAACCTTGGGGAAAAGGGCCCT 19621 TTCAAAGAAGTGGATAAGAGGGAGGAGATCATTGAGTGACCCAGAAAGCTCTTTTGAAAA 19681 GACAGACTCCTCAAGGAGAGATAAAGAGGAAAGCACCTCTTTCATTTTTTAGTGTGAGCT 19741 AATTCCATCAGACTGCTGTCCTCCTGGACCCATCTGAGATGTGCAGTAGCAAGGAGAGGG 19801 GGGATCATTTTAGAGAGTGGGTCATTGGCAGGGAGTGCTCCGGAGGGAGGCAGAGGGGAG 19861 ACTGTGGTAGAAGGAAGACAGAACTCACACATGCTCCCAGGATTGGGGACAGGGACAGAG 19921 GAGGTAACAGAAGGCAAAGGCCAGTTTCCCCGTTATCATGAAGGGGCCCACTCAGGACAG 19981 GAACAAGGACAACTCCTCCTCCTCCTCCTCCTCTCCTGCTGCTCCTGGGATACCAGGTCA 20041 GTGATGTAGTCTTGCAGTTTGGCAACTTCCTAGCCTGAGAATCCCTAGTGGGGCTGTGGG 20101 AAACACATTTCCACGTTGCAAGCATGCAACTCCAAAGAATCTGTGATGCCACTGAAATGA 20161 GATGGGAATGATCCAGCTCTTTCAGCATCTTGGTTGAACTTGCTTTCATTGTCCCTGGGA 20221 TATTGTGGAAGGAAAGGTGACTGTGTGATCTGATTCTGTGGTCAAGGACTTGCATCTTGT 20281 GTTTCTATCCCCAAGCCTTCCTGGTGTCTCCAACTCCTACCCCATTGCATGGGTTGTTGC 20341 GGACATCCAATAAAGATTTTTTTAGTGCTTCTGGAAACTTCCAGTAGATTCTACTTCTAA 20401 ACTATCTCTGGAGTCCATCCACTTCTGTCTGCACCCACAGCCATCCTGGCCAGGCCACAT 20461 CACCTCCCCCAGATCACTGCCCTGGCCTCAGAAAGGTCTTCCCTCTTGCTTTGTCAATCA 20521 GTTCTCAGTAGCAGCAGAGAGAAATTGAAAGCTGCAGGTCATATCGTATCATCTTTAGTT 20581 TGAAAACCTCACTCTCTTACCCTATTGTTCTAAAGGTCTTCTTTTGGTCCCAACCTCACT 20641 TCCAGCCTCATTTCTTGCCAGTCCCAGACTTGCTCCCTGAGCTTCTGCCACCTGCCCTTC 20701 CTTCATTTCCTCGACATTCCAGCCTTGTTCCCACCTCCAGCACTTTGCATATGCTGTTCC 20761 CTTTGCCAAGAATGCTCTTCCCCTACCCTGTGCATGGCTGAGTTCTGCAGACCCTCAGGC 20821 CTTGGCTTCAACGTTGCCTCGTCCAAGAGGCCTTCCTCGACTACTTTACTTGTGGAGTTC 20881 CTCTATCACAAGGCCTCTGTTCTTTCCCTTCATGGAGAATTTGCCACTGCATATCCATTT 20941 GTGTAATTTACTTGTTGGTTGACTGTGCCTCCCACTCGAGTGTAAGCTCATGAGGCCAGG 21001 TGCCATGCCTGGTTCAGTCTCCACTCTGTACCCAGCATTGAGCACAGGGCCTGGTCCATA 21061 GTTGGCGTTCAATAAATACTTGTTGAAGAAGTGAACTGAGAAGGTGAGATATCTTCTGGA 21121 CTCATGCCGTGGATGGTCCAGGCCCCTTTAGGTGTGAACCCCCTGCTGGCCAACTTTGCG 21181 GGGAGGCTGCAGAGCAGAGGGAGAGCCAGGGCCAAGGGACTGGAAGTTCTGGCAAGTGGC 21241 CAGGAGGCCCTGGCCAAAGGCAAGTGCGAGTGTCCACTCCGAGTGCACACTGACAGCTGG 21301 GAGCAGGCAGGCTGTCCTGCCAGCAGGCATTGCTCTCCACCCTTGGCTTGGCTCTGTGAT 21361 GGATTTGGCTCGCAACAAATCCAACGAACACAGAGGTCTGCTCTGTGCCAGCCAGGCACA 21421 GTGGAGCCAGAGCTGGGAAGGACACAGTTGCTTTGAGTGGGGGGCACACCCTCCATCAGG 21481 ATGATAGTTTGGTGAGATGAGAGTAGGGAGGTTTGTTAGGAAGGCTGAAGGGAGCAGAGT 21541 TGGGGTATGTGGCCCTGCCCGGGGTGTCAAGCGGGTAGGGGGCTCTGGGAGGAAGCTTTC 21601 CAGGAGGAGAAGGAAGGGAACCATTCTATGTGCAAAGACCTGGAGACCTCATCAAGGAGA 21661 GCTGTAGACGTTGGCTCTGAGTTGAGCACGGGCCCTCAGTGACAGGGTGAGAGGTGGGCT 21721 AGCCTGGGCACTGAAGCCAGACTTCTTTATTAATGAGTTGTATGTAGTCT

	Literature

PubMed:11069914	The bHLH transcription factor HESR1 regulates endothelial cell tube formation. Henderson AM, Wang SJ, Taylor AC, Aitkenhead M, Hughes CC. J Biol Chem 2000 Nov 7
PubMed:8955070	An antisense oligonucleotide to the notch ligand jagged enhances fibroblast growth factor-induced angiogenesis in vitro. Zimrin AB, Pepper MS, McMahon GA, Nguyen F, Montesano R, Maciag T. J Biol Chem. 1996 Dec 20;271(51):32499-502.
PubMed:96069402	Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression. Dawson SR, Turner DL, Weintraub H, Parkhurst SM Mol Cell Biol 1995 Dec;15(12):6923-31
PubMed:10860664	Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family. Steidl C, Leimeister C, Klamt B, Maier M, Nanda I, Dixon M, Clarke R, Schmid M, Gessler M Genomics. 2000 Jun 1;66(2):195-203
PubMed:10415358	Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis. Leimeister C, Externbrink A, Klamt B, Gessler M Mech Dev 1999 Jul;85(1-2):173-7