Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit

Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3′untranslated region of 112 n...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1985-12, Vol.82 (23), p.8085-8089
Hauptverfasser: Rajavashisth, T.B, Kaptein, J.S, Reue, K.L, Lusis, A.J
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container_issue 23
container_start_page 8085
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 82
creator Rajavashisth, T.B
Kaptein, J.S
Reue, K.L
Lusis, A.J
description Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3′untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an 11-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The 11-nucleotide unit -TCGGACGAGGC- is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-(Glu/Asp)-(Glu/Asp)-Xaa-Arg-Xaa-Arg-Leu-Gly-Xaa-Xaa. We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related 11-nucleotide ancestral sequence.
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Psychology</topic><topic>Generally accepted auditing standards</topic><topic>Genes</topic><topic>Genes. Genome</topic><topic>Gin</topic><topic>Humans</topic><topic>LIPOPROTEINAS</topic><topic>LIPOPROTEINE</topic><topic>LIPOPROTEINS</topic><topic>Messenger RNA</topic><topic>METABOLISM</topic><topic>METABOLISME</topic><topic>METABOLISMO</topic><topic>MICE</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>NUCLEOTIDE</topic><topic>Nucleotide sequences</topic><topic>NUCLEOTIDES</topic><topic>NUCLEOTIDOS</topic><topic>Protein Conformation</topic><topic>RATON</topic><topic>Rats</topic><topic>Reading frames</topic><topic>Repetitive Sequences, Nucleic Acid</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>SOURIS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rajavashisth, T.B</creatorcontrib><creatorcontrib>Kaptein, J.S</creatorcontrib><creatorcontrib>Reue, K.L</creatorcontrib><creatorcontrib>Lusis, A.J</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rajavashisth, T.B</au><au>Kaptein, J.S</au><au>Reue, K.L</au><au>Lusis, A.J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1985-12-01</date><risdate>1985</risdate><volume>82</volume><issue>23</issue><spage>8085</spage><epage>8089</epage><pages>8085-8089</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3′untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an 11-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The 11-nucleotide unit -TCGGACGAGGC- is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-(Glu/Asp)-(Glu/Asp)-Xaa-Arg-Xaa-Arg-Leu-Gly-Xaa-Xaa. We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related 11-nucleotide ancestral sequence.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>3865219</pmid><doi>10.1073/pnas.82.23.8085</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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ispartof Proceedings of the National Academy of Sciences - PNAS, 1985-12, Vol.82 (23), p.8085-8089
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subjects Amino Acid Sequence
Amino acids
Animals
Apolipoproteins E - genetics
Base Sequence
Biological and medical sciences
Biological Evolution
Complementary DNA
EVOLUCION
EVOLUTION
Fundamental and applied biological sciences. Psychology
Generally accepted auditing standards
Genes
Genes. Genome
Gin
Humans
LIPOPROTEINAS
LIPOPROTEINE
LIPOPROTEINS
Messenger RNA
METABOLISM
METABOLISME
METABOLISMO
MICE
Molecular and cellular biology
Molecular genetics
NUCLEOTIDE
Nucleotide sequences
NUCLEOTIDES
NUCLEOTIDOS
Protein Conformation
RATON
Rats
Reading frames
Repetitive Sequences, Nucleic Acid
Sequence Homology, Nucleic Acid
SOURIS
title Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit
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