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UniProtKB/Swiss-Prot entry Q8NEZ4


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name MLL3_HUMAN
Primary accession number Q8NEZ4
Secondary accession numbers Q8NC02 Q8NDF6 Q9H9P4 Q9NR13 Q9P222 Q9UDR7
Integrated into Swiss-Prot on October 10, 2003
Sequence was last modified on October 10, 2003 (Sequence version 2)
Annotations were last modified on    November 25, 2008 (Entry version 68)
Name and origin of the protein
Protein name Histone-lysine N-methyltransferase MLL3
Synonyms EC 2.1.1.43
Myeloid/lymphoid or mixed-lineage leukemia protein 3
Homologous to ALR protein
Lysine N-methyltransferase 2C
Gene name
Name: MLL3
Synonyms: HALR, KIAA1506, KMT2C
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Fetal thymus;
DOI=10.1016/S0378-1119(02)00392-X; PubMed=11891048 [NCBI, ExPASy, EBI, Israel, Japan]
Ruault M., Brun M.-E., Ventura M., Roizes G., De Sario A.;
"MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia.";
Gene 284:73-81(2002).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Cervix carcinoma;
PubMed=11718452 [NCBI, ExPASy, EBI, Israel, Japan]
Tan Y.C., Chow V.T.;
"Novel human HALR (MLL3) gene encodes a protein homologous to ALR and to ALL-1 involved in leukemia, and maps to chromosome 7q36 associated with leukemia and developmental defects.";
Cancer Detect. Prev. 25:454-469(2001).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature01782; PubMed=12853948 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 556-3865 (ISOFORM 1).
TISSUE=Brain;
DOI=10.1093/dnares/7.2.143; PubMed=10819331 [NCBI, ExPASy, EBI, Israel, Japan]
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.";
DNA Res. 7:143-150(2000).
[5]
SEQUENCE REVISION.
DOI=10.1093/dnares/9.3.99; PubMed=12168954 [NCBI, ExPASy, EBI, Israel, Japan]
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.";
DNA Res. 9:99-106(2002).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3193-3865 AND 4460-4911.
TISSUE=Placenta;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3879-4911.
TISSUE=Testis;
The German cDNA consortium;
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
[8]
INTERACTION WITH MLL2/MLL3 COMPLEX (ISOFORM 2).
TISSUE=Cervix carcinoma;
DOI=10.1128/MCB.23.1.140-149.2003; PubMed=12482968 [NCBI, ExPASy, EBI, Israel, Japan]
Goo Y.-H., Sohn Y.C., Kim D.-H., Kim S.-W., Kang M.-J., Jung D.-J., Kwak E., Barlev N.A., Berger S.L., Chow V.T., Roeder R.G., Azorsa D.O., Meltzer P.S., Suh P.-G., Song E.J., Lee K.-J., Lee Y.C., Lee J.W.;
"Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins.";
Mol. Cell. Biol. 23:140-149(2003).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-4018 AND SER-4022, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[10]
ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-2809, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.molcel.2006.06.026; PubMed=16916647 [NCBI, ExPASy, EBI, Israel, Japan]
Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.";
Mol. Cell 23:607-618(2006).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4034 AND SER-4050, AND MASS SPECTROMETRY.
DOI=10.2116/analsci.24.161; PubMed=18187866 [NCBI, ExPASy, EBI, Israel, Japan]
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Anal. Sci. 24:161-166(2008).
[12]
VARIANTS [LARGE SCALE ANALYSIS] GLY-347; ASN-400; TRP-478 AND SER-3698.
DOI=10.1126/science.1133427; PubMed=16959974 [NCBI, ExPASy, EBI, Israel, Japan]
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal cancers.";
Science 314:268-274(2006).
[13]
FUNCTION, ENZYME ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MLL3/MLL4 COMPLEX.
DOI=10.1074/jbc.M701574200; PubMed=17500065 [NCBI, ExPASy, EBI, Israel, Japan]
Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T., Dressler G.R., Copeland T.D., Kalkum M., Ge K.;
"PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex.";
J. Biol. Chem. 282:20395-20406(2007).
Comments
  • FUNCTION: Histone methyltransferase. Methylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Central component of the MLL2/MLL3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. MLL3 may be a catalytic subunit of this complex. May be involved in leukemogenesis and developmental disorder.
  • CATALYTIC ACTIVITY: S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine.
  • SUBUNIT: Component of the MLL2/MLL3 complex (also named ASCOM complex), at least composed of MLL2, MLL3, ASH2L, RBBP5, DPY30, NCOA6, WDR5, MEN1, UTX and PAXIP1/PTIP. Component of the MLL3/MLL4 complex at least composed of MLL3, MLL4, ASH2L, RBBP5, DPY30, WDR5, NCOA6, UTX, PAXIP1/PTIP and C16orf53/PA1. Interacts with histone H3.
  • INTERACTION:
    P00568:AK1; NbExp=1; IntAct=EBI-1042997, EBI-1044943;
  • SUBCELLULAR LOCATION: Nucleus (Probable).
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDQ8NEZ4-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDQ8NEZ4-2
    Features which should be applied to build the isoform sequence: VSP_008561, VSP_008562.
  • TISSUE SPECIFICITY: Highly expressed in testis and ovary, followed by brain and liver. Also expressed in placenta, peripherical blood, fetal thymus, heart, lung and kidney. Within brain, expression was highest in hippocampus, caudate nucleus, and substantia nigra. Not detected in skeletal muscle and fetal liver.
  • DOMAIN: The SET domain interacts with histone H3 but not H2A, H2B and H4, and may have a H3 lysine specific methylation activity.
  • MISCELLANEOUS: Found in a critical region of chromosome 7, which is commonly deleted in malignant myeloid disorders. Partial duplication of the MLL3 gene are found in the juxtacentromeric region of chromosomes 1, 2, 13 and 21. Juxtacentromeric reshuffling of the MLL3 gene has generated the BAGE genes.
  • SIMILARITY: Belongs to the histone-lysine methyltransferase family. TRX/MLL subfamily.
  • SIMILARITY: Contains 1 A.T hook DNA-binding domain.
  • SIMILARITY: Contains 1 DHHC-type zinc finger.
  • SIMILARITY: Contains 6 PHD-type zinc fingers.
  • SIMILARITY: Contains 1 post-SET domain.
  • SIMILARITY: Contains 1 RING-type zinc finger.
  • SIMILARITY: Contains 1 SET domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AY024361; AAK00583.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF264750; AAF74766.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC006017; AAD45822.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC104692; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
AC005631; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
AB040939; BAA96030.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK022687; BAB14179.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK075113; BAC11409.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL833924; CAD38780.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_733751.2; -.
UniGene Hs.647120
3D structure databases
PDB
2YSM; NMR; -; A=342-439.[ExPASy / RCSB / EBI]
2YUK; NMR; -; A=1624-1713.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 2YSM; -.
2YUK; -.
ModBase Q8NEZ4.
Protein-protein interaction databases
IntAct Q8NEZ4; -.
PTM databases
PhosphoSite Q8NEZ4; -.
Organism-specific databases
H-InvDB HIX0033996; -.
HGNC HGNC:13726; MLL3.
GenAtlas MLL3.
MIM 606833; gene. [NCBI / EBI]
PharmGKB PA30847; -.
GeneCards Q8NEZ4.
HUGE KIAA1506.
Gene expression databases
ArrayExpress Q8NEZ4; -.
CleanEx HS_MLL3; -.
GermOnline ENSG00000055609; Homo sapiens.
Ontologies
GO
GO:0005634; Cellular component: nucleus (inferred from electronic annotation from InterPro).
GO:0018024; Molecular function: histone-lysine N-methyltransferase activity (inferred from electronic annotation from EC).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0003700; Molecular function: transcription factor activity (inferred from electronic annotation from InterPro).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from InterPro).
GO:0016568; Biological process: chromatin modification (inferred from electronic annotation from UniProtKB-KW).
GO:0007242; Biological process: intracellular signaling cascade (inferred from electronic annotation from InterPro).
GO:0006355; Biological process: regulation of transcription, DNA-dependent (inferred from electronic annotation from InterPro).
QuickGo view.
Family and domain databases
InterPro IPR000637; AT_hook_DNA_bd.
IPR002219; DAG_PE_bd.
IPR003889; FYrich_C.
IPR003888; FYrich_N.
IPR000910; HMG_1/2_box.
IPR003616; Post-SET_Zn_bd.
IPR001214; SET.
IPR001594; Znf_DHHC.
IPR001965; Znf_PHD.
IPR001841; Znf_RING.
IPR013083; Znf_RING/FYVE/PHD.
Graphical view of domain structure.
Gene3D G3DSA:3.30.40.10; Znf_RING/FYVE/PHD; 4.
Pfam PF02178; AT_hook; 1.
PF05965; FYRC; 1.
PF05964; FYRN; 1.
PF00505; HMG_box; 1.
PF00628; PHD; 6.
PF00856; SET; 1.
Pfam graphical view of domain structure.
SMART SM00384; AT_hook; 2.
SM00109; C1; 2.
SM00542; FYRC; 1.
SM00541; FYRN; 1.
SM00398; HMG; 1.
SM00249; PHD; 8.
SM00508; PostSET; 1.
SM00184; RING; 4.
SM00317; SET; 1.
SMART graphical view of domain structure.
PROSITE PS00354; HMGI_Y; 1.
PS50868; POST_SET; 1.
PS50280; SET; 1.
PS50216; ZF_DHHC; 1.
PS01359; ZF_PHD_1; 5.
PS50016; ZF_PHD_2; 6.
PS50089; ZF_RING_2; 1.
PROSITE graphical view of domain structure (profiles).
ProtoNet Q8NEZ4.
Genome annotation databases
Ensembl ENSG00000055609; Homo sapiens. [Contig view]
GeneID 58508; -.
KEGG hsa:58508; -.
Phylogenomic databases
HOVERGEN Q8NEZ4; -.
Other
LinkHub Q8NEZ4; -.
NextBio 65023; -.
SOURCE MLL3; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Activator; Alternative splicing; Chromatin regulator; Coiled coil; DNA-binding; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Polymorphism; Repeat; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Zinc; Zinc-finger.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
CHAIN   1   4911  4911     Histone-lysine N-methyltransferase MLL3. PRO_0000124879
DOMAIN   4770   4891  122     SET. 
DOMAIN   4895   4911  17     Post-SET. 
DNA_BIND   34     46  13     A.T hook. 
ZN_FING   341    391  51     PHD-type 1. 
ZN_FING   344    389  46     RING-type. 
ZN_FING   388    438  51     PHD-type 2. 
ZN_FING   436    489  54     DHHC-type. 
ZN_FING   464    520  57     PHD-type 3. 
ZN_FING   957   1010  54     PHD-type 4. 
ZN_FING   1007   1057  51     PHD-type 5. 
ZN_FING   1084   1139  56     PHD-type 6. 
COILED   92    112  21     Potential. 
COILED   644    672  29     Potential. 
COILED   1338   1366  29     Potential. 
COILED   1754   1787  34     Potential. 
COILED   3054   3081  28     Potential. 
COILED   3173   3272  100     Potential. 
COILED   3391   3433  43     Potential. 
COMPBIAS   1719   1796  78     Gln-rich. 
COMPBIAS   1834   2281  448     Pro-rich. 
COMPBIAS   2412   2630  219     Pro-rich. 
COMPBIAS   2690   2786  97     Asp-rich. 
COMPBIAS   3012   3509  498     Gln-rich. 
COMPBIAS   3277   3381  105     Pro-rich. 
MOD_RES   2809   2809        N6-acetyllysine. 
MOD_RES   4018   4018        Phosphotyrosine. 
MOD_RES   4022   4022        Phosphoserine. 
MOD_RES   4034   4034        Phosphoserine. 
MOD_RES   4050   4050        Phosphoserine. 
VAR_SEQ   1    939        Missing (in isoform 2). VSP_008561
VAR_SEQ   3890   3890        Q -> QVRQLSLLPLMEPIIGVNFAHFLPYGSGQFNSGNRLLGTF GSATLEGVSDYYSQLIYK (in isoform 2). VSP_008562
VARIANT   347    347  1     C -> G (in a colorectal cancer sample; somatic mutation). VAR_036311 
VARIANT   400    400  1     D -> N (in a colorectal cancer sample; somatic mutation). VAR_036312 
VARIANT   478    478  1     L -> W (in a colorectal cancer sample; somatic mutation). VAR_036313 
VARIANT   526    526  1     P -> T (in dbSNP:rs3735156 [NCBI]). VAR_017116 
VARIANT   823    823  1     I -> N (in dbSNP:rs2838171 [NCBI]). VAR_017118 
VARIANT   823    823  1     I -> T (in dbSNP:rs2838171 [NCBI]). VAR_017117 
VARIANT   3698   3698  1     T -> S (in a colorectal cancer sample; somatic mutation). VAR_036314 
CONFLICT   526    526        P -> R (in Ref. 3). 
CONFLICT   579    579        A -> T (in Ref. 1). 
CONFLICT   1286   1286        V -> M (in Ref. 2 and 4). 
CONFLICT   2360   2360        P -> S (in Ref. 1). 
CONFLICT   2797   2797        R -> K (in Ref. 2 and 4). 
CONFLICT   2882   2882        T -> A (in Ref. 1). 
CONFLICT   3289   3289        P -> S (in Ref. 6; BAC11409). 
CONFLICT   3428   3428        R -> W (in Ref. 6; BAC11409). 
CONFLICT   3879   3890        YSSTDTFTHLKQ -> GVSDYYSQLIYK (in Ref. 7). 
CONFLICT   4613   4613        I -> V (in Ref. 6; BAB14179). 
CONFLICT   4721   4724        Missing (in Ref. 2). 
CONFLICT   4866   4866        H -> P (in Ref. 6; BAB14179). 
TURN   345    347  3      
TURN   353    355  3      
STRAND   356    358  3      
STRAND   360    362  3      
TURN   368    372  5      
TURN   377    379  3      
TURN   386    388  3      
TURN   392    394  3      
STRAND<