ROBO3

Protein identityUniProt · HPA

UniProt accession

Q96MS0

Gene

ROBO3

Ensembl

ENSG00000154134

Chromosome

11

Canonical length

1386 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Vesicles,Plasma membrane

OverviewNCBI Gene

This gene is a member of the Roundabout (ROBO) gene family that controls neurite outgrowth, growth cone guidance, and axon fasciculation. ROBO proteins are a subfamily of the immunoglobulin transmembrane receptor superfamily. SLIT proteins 1-3, a family of secreted chemorepellants, are ligands for ROBO proteins and SLIT/ROBO interactions regulate myogenesis, leukocyte migration, kidney morphogenesis, angiogenesis, and vasculogenesis in addition to neurogenesis. This gene, ROBO3, has a putative extracellular domain with five immunoglobulin (Ig)-like loops and three fibronectin (Fn) type III motifs, a transmembrane segment, and a cytoplasmic tail with three conserved signaling motifs: CC0, CC2, and CC3 (CC for conserved cytoplasmic). Unlike other ROBO family members, ROBO3 lacks motif CC1. The ROBO3 gene regulates axonal navigation at the ventral midline of the neural tube. In mouse, loss of Robo3 results in a complete failure of commissural axons to cross the midline throughout the spinal cord and the hindbrain. Mutations ROBO3 result in horizontal gaze palsy with progressive scoliosis (HGPPS); an autosomal recessive disorder characterized by congenital absence of horizontal gaze, progressive scoliosis, and failure of the corticospinal and somatosensory axon tracts to cross the midline in the medulla. [provided by RefSeq, May 2019]

Canonical amino-acid sequenceUniProt

1386 residues, UniProt reviewed canonical sequence.

>Q96MS0|ROBO3
     1  MLRYLLKTLL QMNLFADSLA GDISNSSELL LGFNSSLAAL NHTLLPPGDP SLNGSRVGPE
    61  DAMPRIVEQP PDLLVSRGEP ATLPCRAEGR PRPNIEWYKN GARVATVRED PRAHRLLLPS
   121  GALFFPRIVH GRRARPDEGV YTCVARNYLG AAASRNASLE VAVLRDDFRQ SPGNVVVAVG
   181  EPAVLECVPP RGHPEPSVSW RKDGARLKEE EGRITIRGGK LMMSHTLKSD AGMYVCVASN
   241  MAGERESAAA EVMVLERPSF LRRPVNQVVL ADAPVTFLCE VKGDPPPRLR WRKEDGELPT
   301  GRYEIRSDHS LWIGHVSAED EGTYTCVAEN SVGRAEASGS LSVHVPPQLV TQPQDQMAAP
   361  GESVAFQCET KGNPPPAIFW QKEGSQVLLF PSQSLQPTGR FSVSPRGQLN ITAVQRGDAG
   421  YYVCQAVSVA GSILAKALLE IKGASLDGLP PVILQGPANQ TLVLGSSVWL PCRVTGNPQP
   481  SVRWKKDGQW LQGDDLQFKT MANGTLYIAN VQEMDMGFYS CVAKSSTGEA TWSGWLKMRE
   541  DWGVSPDPPT EPSSPPGAPS QPVVTEITKN SITLTWKPNP QTGAAVTSYV IEAFSPAAGN
   601  TWRTVADGVQ LETHTVSGLQ PNTIYLFLVR AVGAWGLSEP SPVSEPVRTQ DSSPSRPVED
   661  PWRGQQGLAE VAVRLQEPIV LGPRTLQVSW TVDGPVQLVQ GFRVSWRVAG PEGGSWTMLD
   721  LQSPSQQSTV LRGLPPGTQI QIKVQAQGQE GLGAESLSVT RSIPEEAPSG PPQGVAVALG
   781  GDGNSSITVS WEPPLPSQQN GVITEYQIWC LGNESRFHLN RSAAGWARSA MLRGLVPGLL
   841  YRTLVAAATS AGVGVPSAPV LVQLPSPPDL EPGLEVGAGL AVRLARVLRE PAFLAGSGAA
   901  CGALLLGLCA ALYWRRKQRK ELSHYTASFA YTPAVSFPHS EGLSGASSRP PMGLGPAPYS
   961  WLADSWPHPS RSPSAQEPRG SCCPSNPDPD DRYYNEAGIS LYLAQTARGT AAPGEGPVYS
  1021  TIDPAGEELQ TFHGGFPQHP SGDLGPWSQY APPEWSQGDS GAKGGKVKLL GKPVQMPSLN
  1081  WPEALPPPPP SCELSCLEGP EEELEGSSEP EEWCPPMPER SHLTEPSSSG GCLVTPSRRE
  1141  TPSPTPSYGQ QSTATLTPSP PDPPQPPTDM PHLHQMPRRV PLGPSSPLSV SQPMLGIREA
  1201  RPAGLGAGPA ASPHLSPSPA PSTASSAPGR TWQGNGEMTP PLQGPRARFR KKPKALPYRR
  1261  ENSPGDLPPP PLPPPEEEAS WALELRAAGS MSSLERERSG ERKAVQAVPL AAQRVLHPDE
  1321  EAWLPYSRPS FLSRGQGTST CSTAGSNSSR GSSSSRGSRG PGRSRSRSQS RSQSQRPGQK
  1381  RREEPR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ROBO3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

8.7 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ROBO3.

Disease | AllUniProt

Conditions ROBO3 is implicated in, by any mechanism.

• Gaze palsy, familial horizontal, with progressive scoliosis, 1 (HGPPS1) MIM:607313

Disease | GeneticClinVar

42 pathogenic / likely-pathogenic of 442 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Gaze palsy, familial horizontal, with progressive scoliosis 1
• Inborn genetic diseases
• Conjugate gaze palsy
• ROBO3-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.71

gnomAD pLI

0

gnomAD missense Z

0.61

DepMap mean gene effect

0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon guidance
• axon midline choice point recognition
• brain development
• chemotaxis
• commissural neuron axon guidance
• dendrite self-avoidance
• homophilic cell adhesion via plasma membrane adhesion molecules
• negative regulation of negative chemotaxis
• neuron migration
• positive regulation of axon guidance
• positive regulation of axonogenesis
• tube development

Molecular functions

• cell-cell adhesion mediator activity

Cellular components

• axon
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Fibronectin type III
• Immunoglobulin-like domain
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Neural and epithelial cell adhesion domain-containing protein
• Fibronectin type III domain
• Immunoglobulin I-set domain
• Immunoglobulin domain

KeywordsUniProt

• Chemotaxis
• Developmental protein
• Differentiation
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Neurogenesis
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ROBO3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NELL1