NUANCE, a giant protein connecting the nucleus and actin cytoskeleton.
NUANCE (NUcleus and ActiN Connecting Element) was identified as a novel protein with an alpha-actinin-like actin-binding domain. A human 21.8 kb cDNA of NUANCE spreads over 373 kb on chromosome 14q22.1-q22.3. The cDNA sequence predicts a 796 kDa protein with an N-terminal actin-binding domain, a central coiled-coil rod domain and a predicted C-terminal transmembrane domain. High levels of NUANCE mRNA were detected in the kidney, liver, stomach, placenta, spleen, lymphatic nodes and peripheral blood lymphocytes. At the subcellular level NUANCE is present predominantly at the outer nuclear membrane and in the nucleoplasm. Domain analysis shows that the actin-binding domain binds to Factin in vitro and colocalizes with the actin cytoskeleton in vivo as a GFP-fusion protein. The C-terminal transmembrane domain is responsible for the targeting the nuclear envelope. Thus, NUANCE is the first alpha-actinin-related protein that has the potential to link the microfilament system with the nucleus.
Institute for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Yen-Yi
YY
Zhen
Thorsten
T
Libotte
Martina
M
Munck
Angelika A
AA
Noegel
Elena
E
Korenbaum
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002451:Cell Compartmentation / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure; D009687:Nuclear Proteins; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins
D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C485904:SYNE2 protein, human