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{{Infobox_gene}}
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'''Engulfment and cell motility protein 1''' is a [[protein]] that in humans is encoded by the ''ELMO1'' [[gene]].<ref name="pmid11595183">{{cite journal |vauthors=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 | title = CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration | journal = Cell | volume = 107 | issue = 1 | pages = 27–41 |date=Oct 2001 | pmid = 11595183 | pmc =  | doi =10.1016/S0092-8674(01)00520-7  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ELMO1 engulfment and cell motility 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9844| accessdate = }}</ref> ELMO1 is located on chromosome number seven in humans and is located on chromosome number thirteen in mice.
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Engulfment and cell motility 1
| HGNCid = 16286
| Symbol = ELMO1
| AltSymbols =; CED-12; CED12; ELMO-1; KIAA0281; MGC126406
| OMIM = 606420
| ECnumber = 
| Homologene = 56685
| MGIid = 2153044
| GeneAtlas_image1 = PBB_GE_ELMO1_204513_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0017124 |text = SH3 domain binding}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005856 |text = cytoskeleton}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}}
| Process = {{GNF_GO|id=GO:0006909 |text = phagocytosis}} {{GNF_GO|id=GO:0006911 |text = phagocytosis, engulfment}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0006928 |text = cell motility}} {{GNF_GO|id=GO:0016601 |text = Rac protein signal transduction}} {{GNF_GO|id=GO:0030036 |text = actin cytoskeleton organization and biogenesis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 9844
    | Hs_Ensembl = ENSG00000155849
    | Hs_RefseqProtein = NP_001034548
    | Hs_RefseqmRNA = NM_001039459
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 7
    | Hs_GenLoc_start = 36860492
    | Hs_GenLoc_end = 37454981
    | Hs_Uniprot = Q92556
    | Mm_EntrezGene = 140580
    | Mm_Ensembl = ENSMUSG00000041112
    | Mm_RefseqmRNA = NM_080288
    | Mm_RefseqProtein = NP_525027
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 13
    | Mm_GenLoc_start = 20098084
    | Mm_GenLoc_end = 20613993
    | Mm_Uniprot = Q571D6
  }}
}}
'''Engulfment and cell motility 1''', also known as '''ELMO1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: ELMO1 engulfment and cell motility 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9844| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The human engulfment and cell motility protein 1, ELMO1, is 720 residues in length.  The protein contains the following three domains:
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: ELMO1 engulfment and cell motility 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9844| accessdate = }}</ref>
}}


==References==
* [[N-terminus|N-terminal]] [[Armadillo repeats|Armadillo]] domain (residues 82-262)
{{reflist|2}}
* central [[ELMO (protein)|ELMO]] (<u>E</u>ngulfment and Cel<u>l</u> <u>Mo</u>tility) domain (301-492)
==Further reading==
* [[C-terminus|C-terminal]] [[pleckstrin homology domain]] (residues 527-674)
 
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.<ref name="pmid18768751">{{PDB|2VSZ}}; {{cite journal | vauthors = Komander D, Patel M, Laurin M, Fradet N, Pelletier A, Barford D, Côté JF | title = An alpha-helical extension of the ELMO1 pleckstrin homology domain mediates direct interaction to DOCK180 and is critical in Rac signaling | journal = Mol. Biol. Cell | volume = 19 | issue = 11 | pages = 4837–51 | date =November 2008 | pmid = 18768751 | pmc = 2575150 | doi = 10.1091/mbc.E08-04-0345 | url = | issn = }}</ref>
 
The structure of the pleckstrin homology domain of ELMO1 has been determine by X-ray crystallography.<ref name="pmid18768751"/>
 
== 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.<ref name="entrez"/>
 
== Interactions ==
 
ELMO1 has been shown to [[Protein-protein interaction|interact]] with [[Dock180]]<ref name="pmid11595183" /><ref name="pmid12134158">{{cite journal |vauthors=Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, Macara IG, Madhani H, Fink GR, Ravichandran KS | title = Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex | journal = Nat. Cell Biol. | volume = 4 | issue = 8 | pages = 574–82 |date=August 2002 | pmid = 12134158 | doi = 10.1038/ncb824 | url = | issn = }}</ref> and [[HCK]].  ELMO1 directly interacts with the SH3 domain of HCK.  The association between ELMO1 and HCK is dependent on polyproline interactions.<ref name="pmid12029088">{{cite journal |vauthors=Scott MP, Zappacosta F, Kim EY, Annan RS, Miller WT | title = Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1 | journal = J. Biol. Chem. | volume = 277 | issue = 31 | pages = 28238–46 |date=August 2002 | pmid = 12029088 | doi = 10.1074/jbc.M202783200 | url = | issn = }}</ref>
 
When ELMO1 is complexed with DOCK180, [[Rac (GTPase)|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.<ref name="pmid18768751"/>  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.<ref name="pmid11595183"/>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  |vauthors=Ohara O, Nagase T, Ishikawa K |title=Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins. |journal=DNA Res. |volume=4 |issue= 1 |pages= 53–9 |year= 1997 |pmid= 9179496 |doi=10.1093/dnares/4.1.53 |display-authors=etal}}
| citations =
*{{cite journal  |vauthors=Wiemann S, Weil B, Wellenreuther R |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422–35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.GR1547R  | pmc=311072 |display-authors=etal}}
*{{cite journal  | author=Ohara O, Nagase T, Ishikawa K, ''et al.'' |title=Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins. |journal=DNA Res. |volume=4 |issue= 1 |pages= 53-9 |year= 1997 |pmid= 9179496 |doi=  }}
*{{cite journal  |vauthors=Scott MP, Zappacosta F, Kim EY |title=Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1. |journal=J. Biol. Chem. |volume=277 |issue= 31 |pages= 28238–46 |year= 2002 |pmid= 12029088 |doi= 10.1074/jbc.M202783200 |display-authors=etal}}
*{{cite journal  | author=Wiemann S, Weil B, Wellenreuther R, ''et al.'' |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422-35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.154701 }}
*{{cite journal  |vauthors=Brugnera E, Haney L, Grimsley C |title=Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. |journal=Nat. Cell Biol. |volume=4 |issue= 8 |pages= 574–82 |year= 2002 |pmid= 12134158 |doi= 10.1038/ncb824 |display-authors=etal}}
*{{cite journal  | author=Gumienny TL, Brugnera E, Tosello-Trampont AC, ''et al.'' |title=CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. |journal=Cell |volume=107 |issue= 1 |pages= 27-41 |year= 2001 |pmid= 11595183 |doi= }}
*{{cite journal  |vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
*{{cite journal  | author=Scott MP, Zappacosta F, Kim EY, ''et al.'' |title=Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1. |journal=J. Biol. Chem. |volume=277 |issue= 31 |pages= 28238-46 |year= 2002 |pmid= 12029088 |doi= 10.1074/jbc.M202783200 }}
*{{cite journal  |vauthors=Scherer SW, Cheung J, MacDonald JR |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767–72 |year= 2003 |pmid= 12690205  | pmc=2882961 |doi= 10.1126/science.1083423 |display-authors=etal}}
*{{cite journal  | author=Brugnera E, Haney L, Grimsley C, ''et al.'' |title=Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. |journal=Nat. Cell Biol. |volume=4 |issue= 8 |pages= 574-82 |year= 2002 |pmid= 12134158 |doi= 10.1038/ncb824 }}
*{{cite journal  |vauthors=Sanui T, Inayoshi A, Noda M |title=DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. |journal=Blood |volume=102 |issue= 8 |pages= 2948–50 |year= 2003 |pmid= 12829596 |doi= 10.1182/blood-2003-01-0173 |display-authors=etal}}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  |vauthors=Katoh H, Negishi M |title=RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. |journal=Nature |volume=424 |issue= 6947 |pages= 461–4 |year= 2003 |pmid= 12879077 |doi= 10.1038/nature01817 }}
*{{cite journal  | author=Scherer SW, Cheung J, MacDonald JR, ''et al.'' |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767-72 |year= 2003 |pmid= 12690205 |doi= 10.1126/science.1083423 }}
*{{cite journal  |vauthors=Grimsley CM, Kinchen JM, Tosello-Trampont AC |title=Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. |journal=J. Biol. Chem. |volume=279 |issue= 7 |pages= 6087–97 |year= 2004 |pmid= 14638695 |doi= 10.1074/jbc.M307087200 |display-authors=etal}}
*{{cite journal  | author=Sanui T, Inayoshi A, Noda M, ''et al.'' |title=DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. |journal=Blood |volume=102 |issue= 8 |pages= 2948-50 |year= 2003 |pmid= 12829596 |doi= 10.1182/blood-2003-01-0173 }}
*{{cite journal  |vauthors=Wang X, Wu YC, Fadok VA |title=Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. |journal=Science |volume=302 |issue= 5650 |pages= 1563–6 |year= 2003 |pmid= 14645848 |doi= 10.1126/science.1087641 |display-authors=etal}}
*{{cite journal  | author=Katoh H, Negishi M |title=RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. |journal=Nature |volume=424 |issue= 6947 |pages= 461-4 |year= 2003 |pmid= 12879077 |doi= 10.1038/nature01817 }}
*{{cite journal  |vauthors=Ota T, Suzuki Y, Nishikawa T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |display-authors=etal}}
*{{cite journal  | author=Grimsley CM, Kinchen JM, Tosello-Trampont AC, ''et al.'' |title=Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. |journal=J. Biol. Chem. |volume=279 |issue= 7 |pages= 6087-97 |year= 2004 |pmid= 14638695 |doi= 10.1074/jbc.M307087200 }}
*{{cite journal  |vauthors=Janardhan A, Swigut T, Hill B |title=HIV-1 Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis. |journal=PLoS Biol. |volume=2 |issue= 1 |pages= E6 |year= 2006 |pmid= 14737186 |doi= 10.1371/journal.pbio.0020006  | pmc=314466 |display-authors=etal}}
*{{cite journal  | author=Wang X, Wu YC, Fadok VA, ''et al.'' |title=Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. |journal=Science |volume=302 |issue= 5650 |pages= 1563-6 |year= 2003 |pmid= 14645848 |doi= 10.1126/science.1087641 }}
*{{cite journal  |vauthors=Lu M, Kinchen JM, Rossman KL |title=PH domain of ELMO functions in trans to regulate Rac activation via Dock180. |journal=Nat. Struct. Mol. Biol. |volume=11 |issue= 8 |pages= 756–62 |year= 2004 |pmid= 15247908 |doi= 10.1038/nsmb800 |display-authors=etal}}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  |vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 |display-authors=etal}}
*{{cite journal  | author=Janardhan A, Swigut T, Hill B, ''et al.'' |title=HIV-1 Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis. |journal=PLoS Biol. |volume=2 |issue= 1 |pages= E6 |year= 2006 |pmid= 14737186 |doi= 10.1371/journal.pbio.0020006 }}
*{{cite journal  |vauthors=deBakker CD, Haney LB, Kinchen JM |title=Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. |journal=Curr. Biol. |volume=14 |issue= 24 |pages= 2208–16 |year= 2005 |pmid= 15620647 |doi= 10.1016/j.cub.2004.12.029 |display-authors=etal}}
*{{cite journal  | author=Lu M, Kinchen JM, Rossman KL, ''et al.'' |title=PH domain of ELMO functions in trans to regulate Rac activation via Dock180. |journal=Nat. Struct. Mol. Biol. |volume=11 |issue= 8 |pages= 756-62 |year= 2004 |pmid= 15247908 |doi= 10.1038/nsmb800 }}
*{{cite journal  |vauthors=Akakura S, Kar B, Singh S |title=C-terminal SH3 domain of CrkII regulates the assembly and function of the DOCK180/ELMO Rac-GEF. |journal=J. Cell. Physiol. |volume=204 |issue= 1 |pages= 344–51 |year= 2005 |pmid= 15700267 |doi= 10.1002/jcp.20288 |display-authors=etal}}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  |vauthors=Lu M, Kinchen JM, Rossman KL |title=A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs. |journal=Curr. Biol. |volume=15 |issue= 4 |pages= 371–7 |year= 2005 |pmid= 15723800 |doi= 10.1016/j.cub.2005.01.050 |display-authors=etal}}
*{{cite journal  | author=deBakker CD, Haney LB, Kinchen JM, ''et al.'' |title=Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. |journal=Curr. Biol. |volume=14 |issue= 24 |pages= 2208-16 |year= 2005 |pmid= 15620647 |doi= 10.1016/j.cub.2004.12.029 }}
*{{cite journal  |vauthors=Shimazaki A, Kawamura Y, Kanazawa A |title=Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. |journal=Diabetes |volume=54 |issue= 4 |pages= 1171–8 |year= 2005 |pmid= 15793258 |doi=10.2337/diabetes.54.4.1171  |display-authors=etal}}
*{{cite journal  | author=Akakura S, Kar B, Singh S, ''et al.'' |title=C-terminal SH3 domain of CrkII regulates the assembly and function of the DOCK180/ELMO Rac-GEF. |journal=J. Cell. Physiol. |volume=204 |issue= 1 |pages= 344-51 |year= 2005 |pmid= 15700267 |doi= 10.1002/jcp.20288 }}
*{{cite journal  |vauthors=Yokoyama N, deBakker CD, Zappacosta F |title=Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src-family kinase Hck. |journal=Biochemistry |volume=44 |issue= 24 |pages= 8841–9 |year= 2005 |pmid= 15952790 |doi= 10.1021/bi0500832 | pmc=2441568 |display-authors=etal}}
*{{cite journal  | author=Lu M, Kinchen JM, Rossman KL, ''et al.'' |title=A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs. |journal=Curr. Biol. |volume=15 |issue= 4 |pages= 371-7 |year= 2005 |pmid= 15723800 |doi= 10.1016/j.cub.2005.01.050 }}
*{{cite journal  | author=Shimazaki A, Kawamura Y, Kanazawa A, ''et al.'' |title=Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. |journal=Diabetes |volume=54 |issue= 4 |pages= 1171-8 |year= 2005 |pmid= 15793258 |doi=  }}
*{{cite journal  | author=Yokoyama N, deBakker CD, Zappacosta F, ''et al.'' |title=Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src-family kinase Hck. |journal=Biochemistry |volume=44 |issue= 24 |pages= 8841-9 |year= 2005 |pmid= 15952790 |doi= 10.1021/bi0500832 }}
}}
{{refend}}
{{refend}}


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Latest revision as of 00:27, 31 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Engulfment and cell motility protein 1 is a protein that in humans is encoded by the ELMO1 gene.[1][2] 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.[3]

The structure of the pleckstrin homology domain of ELMO1 has been determine by X-ray crystallography.[3]

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.[2]

Interactions

ELMO1 has been shown to interact with Dock180[1][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.[3] 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.[1]

References

  1. ↑ 1.0 1.1 1.2 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.
  2. ↑ 2.0 2.1 "Entrez Gene: ELMO1 engulfment and cell motility 1".
  3. ↑ 3.0 3.1 3.2 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.
  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


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