Signaling by ROBO receptors (Homo sapiens)

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712, 413, 5, 613, 6cytosolcytosolNck:Robo1:Slit2:GlypicanClasp:Abl:Robo1:Slit2:Glypican-1SLIT2Glypican-1:Slit2:Robo1:Ena/Vasp:ProfilinNCKRAC1-GTPOrthophosphateADPGlypican-1:Slit2:Robo1:Ena/Vasp proteinsCAP:Abl:Robo1:Slit2:Glypican-1GTPProfilinSOSRobo1/Robo2:Robo3A.1Robo1:Slit2:KIAA1688RAC1-GTPOrthophosphateRobo1/ Robo2SOS:PAK:Nck:Robo1:Slit2:GlypicanRAC1-GDPGDPEna/Vasp proteinsCDC42-GTPPak:Nck:Robo1:Slit2:GlypicanSlit2:Glypican-1Abl:pRobo1:slit2:Glypican-1Abl:Robo1:Slit2:Glypican-1ATPUnidentified proteaseSrGAPSlit2-NKIAA1688 proteinRobo1:Slit2:Glypican-1Abl tyrosine kinasesROBO1RAC1-GDPCLASPRobo1:Slit2:SrGAPGlypican-1:HSPGROBO3A.1Slit2-CCDC42-GDPPAKCAP


Description

The Roundabout (Robo) family encodes transmembrane receptors that regulate axonal guidance and cell migration. The major function of the Robo receptors is to mediate repulsion of the navigating growth cones. There are four human Robo homologues, Robo1, Robo2, Robo3 and Robo4. Most of the Robos have the similar ectodomain architecture as the cell adhesion molecules, five Ig domains followed by three FN3 repeats except for Robo4, it has 2Ig and 2FN3 repeats. The cytoplasmic domains of Robo receptors are in general poorly conserved. However, there are four short conserved cytoplasmic sequence motifs, named CC0-3, that serve as binding sites for adaptor proteins. The ligands for the human Robo receptors are the three Slit proteins Slit1, Slit2, and Slit3; all of the Slit proteins contain a tandem of four LRR (leucine rich repeat) domains at N terminus, termed D1 D4 followed by six EGF (epidermal growth factor)-like domains, a laminin G like domain (ALPS), three EGF-like domains, and a C-terminal cysteine knot domain. Most Slit proteins are cleaved within the EGF-like region by unknown proteases.

Slit protein binding modulates Robo interactions with the cytosolic adaptors. The cytoplasmic domain of Robo1 and Robo2 determines the repulsive responses of these receptors. Based on the studies from both invertebrate and vertebrate organisms its been inferred that Robo induces growth cone repulsion by controlling cytoskeletal dynamics via either Abelson kinase (Abl) and Enabled (Ena), or Rac activity.

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Bibliography

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History

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114743view16:23, 25 January 2021ReactomeTeamReactome version 75
113187view11:25, 2 November 2020ReactomeTeamReactome version 74
112415view15:35, 9 October 2020ReactomeTeamReactome version 73
101319view11:20, 1 November 2018ReactomeTeamreactome version 66
100856view20:53, 31 October 2018ReactomeTeamreactome version 65
100397view19:27, 31 October 2018ReactomeTeamreactome version 64
99945view16:11, 31 October 2018ReactomeTeamreactome version 63
99501view14:44, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94032view13:52, 16 August 2017ReactomeTeamreactome version 61
93654view11:30, 9 August 2017ReactomeTeamreactome version 61
86772view09:26, 11 July 2016ReactomeTeamreactome version 56
83078view09:53, 18 November 2015ReactomeTeamVersion54
81399view12:55, 21 August 2015ReactomeTeamVersion53
76868view08:14, 17 July 2014ReactomeTeamFixed remaining interactions
76573view11:55, 16 July 2014ReactomeTeamFixed remaining interactions
75906view09:56, 11 June 2014ReactomeTeamRe-fixing comment source
75606view10:45, 10 June 2014ReactomeTeamReactome 48 Update
74961view13:48, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74605view08:39, 30 April 2014ReactomeTeamReactome46
68889view17:27, 8 July 2013MaintBotUpdated to 2013 gpml schema
45209view17:22, 7 October 2011KhanspersOntology Term : 'signaling pathway' added !
42134view21:59, 4 March 2011MaintBotAutomatic update
39944view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Abl tyrosine kinases ProteinREACT_19619 (Reactome)
Abl:Robo1:Slit2:

Glypican-1

ComplexREACT_19950 (Reactome)
Abl:pRobo1:slit2:

Glypican-1

ComplexREACT_19439 (Reactome)
CAP ProteinREACT_20173 (Reactome)
CAP:Abl:Robo1:Slit2:

Glypican-1

ComplexREACT_20355 (Reactome)
CDC42-GDP ComplexREACT_20401 (Reactome)
CDC42-GTP ComplexREACT_12889 (Reactome)
CLASP ProteinREACT_20461 (Reactome)
Clasp:Abl:Robo1:

Slit2:Glypican-1

ComplexREACT_19830 (Reactome)
Ena/Vasp proteins ProteinREACT_20297 (Reactome)
GDP Metabolite17552 (ChEBI)
GTP Metabolite15996 (ChEBI)
Glypican-1:HSPG ComplexREACT_19843 (Reactome)
Glypican-1:Slit2:

Robo1:Ena/Vasp proteins

ComplexREACT_19985 (Reactome)
Glypican-1:Slit2:

Robo1:Ena/Vasp: Profilin

ComplexREACT_19848 (Reactome)
KIAA1688 protein ProteinQ9C0H5 (UniProt)
NCK ProteinREACT_17190 (Reactome)
Nck:Robo1:Slit2:

Glypican

ComplexREACT_20473 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
PAK ProteinREACT_19955 (Reactome)
Pak:Nck:Robo1:Slit2:

Glypican

ComplexREACT_19485 (Reactome)
Profilin ProteinREACT_20193 (Reactome)
RAC1-GDP ComplexREACT_22018 (Reactome)
RAC1-GTP ComplexREACT_21594 (Reactome)
ROBO1 ProteinQ9Y6N7 (UniProt)
ROBO3A.1 ProteinQ96MS0-1 (UniProt)
Robo1/ Robo2 ProteinREACT_19642 (Reactome)
Robo1/Robo2:

Robo3A.1

ComplexREACT_19631 (Reactome)
Robo1:Slit2:

Glypican-1

ComplexREACT_19858 (Reactome)
Robo1:Slit2:

KIAA1688

ComplexREACT_19688 (Reactome)
Robo1:Slit2:SrGAP ComplexREACT_19732 (Reactome)
SLIT2 ProteinO94813 (UniProt)
SOS ProteinREACT_20305 (Reactome)
SOS:PAK:Nck:Robo1:

Slit2:Glypican

ComplexREACT_20383 (Reactome)
Slit2-C ProteinO94813 (UniProt)
Slit2-N ProteinO94813 (UniProt)
Slit2:Glypican-1 ComplexREACT_19697 (Reactome)
SrGAP ProteinREACT_19581 (Reactome)
Unidentified

protease

REACT_19522 (Reactome)

Annotated Interactions

No annotated interactions

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