ELMO1

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Engulfment and cell motility 1
2VSZ.pdb1.png
Crystallographic structure of the dimeric human ELMO1 pleckstrin homology domain.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ELMO1 ; CED-12; CED12; ELMO-1
External IDs OMIM606420 MGI2153044 HomoloGene56685 GeneCards: ELMO1 Gene
RNA expression pattern
PBB GE ELMO1 204513 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 9844 140580
Ensembl ENSG00000155849 ENSMUSG00000041112
UniProt Q92556 Q8BPU7
RefSeq (mRNA) NM_001039459 NM_080288
RefSeq (protein) NP_001034548 NP_525027
Location (UCSC) Chr 7:
36.89 – 37.49 Mb
Chr 13:
20.09 – 20.61 Mb
PubMed search [1] [2]

Engulfment and cell motility protein 1 is a protein that in humans is encoded by the ELMO1 gene.[2][3] ELMO1 is located on chromosome number seven in humans and is located on chromosome number thirteen in mice.

Structure[edit]

The human engulfment and cell motility protein 1, ELMO1, is 720 residues in length. The protein contains the following three domains:

ELMO1 also has a pro-rich motif at the extreme C terminus. Secondary structure analysis has predicted that there are alpha-helical regions at both the N and C-terminus.[1]

The structure of the pleckstrin homology domain of ELMO1 has been determine by X-ray crystallography.[1]

Function[edit]

The protein encoded by this gene interacts with the dedicator of cyto-kinesis 1 protein to promote phagocytosis and effect cell shape changes. Similarity to a C. elegans protein suggests that this protein may function in apoptosis and in cell migration. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms.[3]

Interactions[edit]

ELMO1 has been shown to interact with Dock180[2][4] and HCK. ELMO1 directly interacts with the SH3 domain of HCK. The association between ELMO1 and HCK is dependent on polyproline interactions.[5]

When ELMO1 is complexed with DOCK180, Rac GTPase-dependent biological processes are activated. The pH domain of ELMO1 functions in trans to stabilize DOCK180 and make it resistant to degradation. When ELMO1 binds to DOCK180 it relieves the steric inhibition of DOCK180 which then activates the Rac GTPase. The pro-rich motif of the C terminus on ELMO1 is essential for the binding of ELMO1 to the SH3 domain at the N terminus of DOCK180.[1] The complex of ELMO1 and DOCK180 act as a regulator of Rac during development of a cell and cell migration. Mutation of both interaction sites for DOCK180 on ELMO1 will lead to the disruption of the ELMO1-DOCK180 complex. ELMO1 complexed with both DOCK180 and CrkII leads to maximal efficiency of phagocytosis in the cell. This complex of molecules happens upstream of Rac during phagocytosis. [2]

References[edit]

  1. ^ a b c d PDB 2VSZ; Komander D, Patel M, Laurin M, Fradet N, Pelletier A, Barford D, Côté JF (November 2008). "An alpha-helical extension of the ELMO1 pleckstrin homology domain mediates direct interaction to DOCK180 and is critical in Rac signaling". Mol. Biol. Cell 19 (11): 4837–51. doi:10.1091/mbc.E08-04-0345. PMC 2575150. PMID 18768751. 
  2. ^ a b c Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K, Walk SF, Nemergut ME, Macara IG, Francis R, Schedl T, Qin Y, Van Aelst L, Hengartner MO, Ravichandran KS (Oct 2001). "CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration". Cell 107 (1): 27–41. doi:10.1016/S0092-8674(01)00520-7. PMID 11595183. 
  3. ^ a b "Entrez Gene: ELMO1 engulfment and cell motility 1". 
  4. ^ Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, Macara IG, Madhani H, Fink GR, Ravichandran KS (August 2002). "Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex". Nat. Cell Biol. 4 (8): 574–82. doi:10.1038/ncb824. PMID 12134158. 
  5. ^ Scott MP, Zappacosta F, Kim EY, Annan RS, Miller WT (August 2002). "Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1". J. Biol. Chem. 277 (31): 28238–46. doi:10.1074/jbc.M202783200. PMID 12029088. 

Further reading[edit]