ELMO1

Last updated
ELMO1
2VSZ.pdb1.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ELMO1 , CED-12, CED12, ELMO-1, engulfment and cell motility 1
External IDs OMIM: 606420 MGI: 2153044 HomoloGene: 56685 GeneCards: ELMO1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001039459
NM_001206480
NM_001206482
NM_014800
NM_130442

Contents

NM_080288
NM_198093

RefSeq (protein)

NP_001034548
NP_001193409
NP_001193411
NP_055615
NP_569709

NP_525027
NP_932761

Location (UCSC) Chr 7: 36.85 – 37.45 Mb Chr 13: 20.27 – 20.79 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Engulfment and cell motility protein 1 is a protein that in humans is encoded by the ELMO1 gene. [5] [6] ELMO1 is located on chromosome number seven in humans and is located on chromosome number thirteen in mice.

Structure

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. [7]

The structure of the pleckstrin homology domain of ELMO1 has been determine by X-ray crystallography. [7]

Function

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. [6]

Interactions

ELMO1 has been shown to interact with Dock180 [5] [8] and HCK. ELMO1 directly interacts with the SH3 domain of HCK. The association between ELMO1 and HCK is dependent on polyproline interactions. [9]

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. [7] 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. [5]

Related Research Articles

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<span class="mw-page-title-main">ELMO2</span> Protein-coding gene in the species Homo sapiens

Engulfment and cell motility protein 2 is a protein that in humans is encoded by the ELMO2 gene.

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<span class="mw-page-title-main">Dedicator of cytokinesis protein 4</span> Protein found in humans

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<span class="mw-page-title-main">Dedicator of cytokinesis protein 3</span> Protein found in humans

Dedicator of cytokinesis protein 3 (Dock3), also known as MOCA and PBP, is a large protein encoded in the human by the DOCK3 gene, involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins. Dock3 specifically activates the small G protein Rac.

<span class="mw-page-title-main">Dedicator of cytokinesis protein 9</span> Protein found in humans

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DHR1, also known as CZH1 or Docker1, is a protein domain of approximately 200–250 amino acids that is present in the DOCK family of signalling proteins. This domain binds phospholipids and so may assist in recruitment to cellular membranes. There is evidence that this domain may also mediate protein–protein interactions.

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<span class="mw-page-title-main">Dedicator of cytokinesis protein 5</span> Protein found in humans

Dedicator of cytokinesis protein 5 (Dock5) is a large protein encoded in the human by the DOCK5 gene, involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins. Dock5 is predicted to activate the small G protein Rac.

<span class="mw-page-title-main">Dedicator of cytokinesis protein 6</span> Protein found in humans

Dedicator of cytokinesis protein 6 (Dock6), also known as Zir1 is a large protein encoded in the human by the DOCK6 gene, involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G-proteins.

Engulfment and cell motility 3, also known as ELMO3, is a human gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000155849 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041112 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 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" (PDF). Cell. 107 (1): 27–41. doi:10.1016/S0092-8674(01)00520-7. PMID   11595183. S2CID   15232864. Archived from the original (PDF) on 2021-09-22. Retrieved 2020-09-28.
  6. 1 2 "Entrez Gene: ELMO1 engulfment and cell motility 1".
  7. 1 2 3 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.
  8. 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. S2CID   36363774.
  9. 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