Group:MUZIC:ALP

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ALP subfamily: PDZ/LIM domain proteins of the cytoskeleton

On the basis of structural similarities, the ALP (α-Actinin-associated LIM domain Proteins) subfamily are related to the Enigma subfamily [4], containing PDZ/LIM-domains, as well as internal motifs viz ALP-like motif (AM) and ZASP-like motif (ZM). However, the ALP subfamily differs from the Enigma subfamily as each member of the ALP subfamily possess an N-terminal PDZ domain and only one C-terminal LIM domain. Four proteins: ALP (PDLIM3)[1], CLP36(hCLIM1(human)[2], Elfin (mouse)[3], PDLIM1), RIL(PDLIM4) and Mystique[4],[5] (SLIM, PDLIM2) have been classified into the ALP subfamily.

CLP36 (C-terminal LIM Protein 36 kDa)[6] and RIL (Reversion-Induced LIM)[7] protein were the first to be characterized. α-Actinin-associated LIM protein (ALP) was later identified as a 39 kDa protein in rat skeletal muscle with a slightly shorter isoform in heart [8], which shares a high degree of homology with previously characterized CLP36 and RIL proteins[9].

Sequence annotation and domain organization

Domain map of the PDZ- and LIM-domains in the first isoforms of human Enigma subfamily members: ZASP [1]ENH [2]Enigma [3]
Domain map of the PDZ- and LIM-domains in the first isoforms of human Enigma subfamily members: ZASP [1]ENH [2]Enigma [3]



ZASP (Z-disk Alternatively Spliced PDZ domain protein), also referred to as LIM domain-binding protein 3 (LDB-3), is the 78 kDa, 727-amino-acid human ortholog of cypher, independently identified in heart and skeletal muscle[10]. Five alternatively spliced isoforms of ZASP have been identified (UniProtKB: O75112)[5]. Apart from the PDZ domain, ZASP possess an internal motif (ZASP-like motif) which confers the ability to interact with the spectrin repeats of α-actinin-2 [11].

Enigma Homologue (ENH) protein, also referred to as PDLIM5, is ~67 kDa, 596-amino-acid human ortholog of rat ENH protein [12] with four alternatively spliced isoforms (UniProtKB ID: Q96HC4)[6].

Enigma protein alternatively referred to as PDLIM7 (PDZ and LIM domain protein 7) is the first and representative member of the Enigma subfamily. Initially characterized in human as ~49.85 kDa, 457 amino-acid protein with an N-terminal PDZ domain and three C-terminal LIM domains [13] [14]. Five alternatively spliced isoforms are presently identified (UniProtKB ID: Q9NR12)[7].

Structure

Function and Interactions

Pathology

References

  1. ↑ Xia H, Winokur ST, Kuo WL, Altherr MR, Bredt DS. Actinin-associated LIM protein: identification of a domain interaction between PDZ and spectrin-like repeat motifs. J Cell Biol. 1997 Oct 20;139(2):507-15. PMID:9334352
  2. ↑ Kotaka M, Ngai SM, Garcia-Barcelo M, Tsui SK, Fung KP, Lee CY, Waye MM. Characterization of the human 36-kDa carboxyl terminal LIM domain protein (hCLIM1). J Cell Biochem. 1999 Feb 1;72(2):279-85. PMID:10022510
  3. ↑ Kotaka M, Lau YM, Cheung KK, Lee SM, Li HY, Chan WY, Fung KP, Lee CY, Waye MM, Tsui SK. Elfin is expressed during early heart development. J Cell Biochem. 2001 Aug 21-Sep 5;83(3):463-72. PMID:11596114
  4. ↑ Torrado M, Senatorov VV, Trivedi R, Fariss RN, Tomarev SI. Pdlim2, a novel PDZ-LIM domain protein, interacts with alpha-actinins and filamin A. Invest Ophthalmol Vis Sci. 2004 Nov;45(11):3955-63. PMID:15505042 doi:10.1167/iovs.04-0721
  5. ↑ Loughran G, Healy NC, Kiely PA, Huigsloot M, Kedersha NL, O'Connor R. Mystique is a new insulin-like growth factor-I-regulated PDZ-LIM domain protein that promotes cell attachment and migration and suppresses Anchorage-independent growth. Mol Biol Cell. 2005 Apr;16(4):1811-22. Epub 2005 Jan 19. PMID:15659642 doi:10.1091/mbc.E04-12-1052
  6. ↑ Wang H, Harrison-Shostak DC, Lemasters JJ, Herman B. Cloning of a rat cDNA encoding a novel LIM domain protein with high homology to rat RIL. Gene. 1995 Nov 20;165(2):267-71. PMID:8522188
  7. ↑ Kiess M, Scharm B, Aguzzi A, Hajnal A, Klemenz R, Schwarte-Waldhoff I, Schafer R. Expression of ril, a novel LIM domain gene, is down-regulated in Hras-transformed cells and restored in phenotypic revertants. Oncogene. 1995 Jan 5;10(1):61-8. PMID:7824279
  8. ↑ Xia H, Winokur ST, Kuo WL, Altherr MR, Bredt DS. Actinin-associated LIM protein: identification of a domain interaction between PDZ and spectrin-like repeat motifs. J Cell Biol. 1997 Oct 20;139(2):507-15. PMID:9334352
  9. ↑ Zheng M, Cheng H, Banerjee I, Chen J. ALP/Enigma PDZ-LIM domain proteins in the heart. J Mol Cell Biol. 2010 Apr;2(2):96-102. Epub 2009 Dec 30. PMID:20042479 doi:10.1093/jmcb/mjp038
  10. ↑ Faulkner G, Pallavicini A, Formentin E, Comelli A, Ievolella C, Trevisan S, Bortoletto G, Scannapieco P, Salamon M, Mouly V, Valle G, Lanfranchi G. ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol. 1999 Jul 26;146(2):465-75. PMID:10427098
  11. ↑ Klaavuniemi T, Ylanne J. Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with alpha-actinin--analysis of patient mutations. Exp Cell Res. 2006 May 1;312(8):1299-311. Epub 2006 Feb 14. PMID:16476425 doi:10.1016/j.yexcr.2005.12.036
  12. ↑ Ueki N, Seki N, Yano K, Masuho Y, Saito T, Muramatsu M. Isolation, tissue expression, and chromosomal assignment of a human LIM protein gene, showing homology to rat enigma homologue (ENH). J Hum Genet. 1999;44(4):256-60. PMID:10429367 doi:10.1007/s100380050155
  13. ↑ Wu RY, Gill GN. LIM domain recognition of a tyrosine-containing tight turn. J Biol Chem. 1994 Oct 7;269(40):25085-90. PMID:7929196
  14. ↑ Guy PM, Kenny DA, Gill GN. The PDZ domain of the LIM protein enigma binds to beta-tropomyosin. Mol Biol Cell. 1999 Jun;10(6):1973-84. PMID:10359609
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