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Protein

Roundabout homolog 4

Gene

ROBO4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins (By similarity).By similarity

GO - Molecular functioni

  • cell-cell adhesion mediator activity Source: GO_Central
  • signaling receptor activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • axon guidance Source: GO_Central
  • dendrite self-avoidance Source: GO_Central
  • homophilic cell adhesion via plasma membrane adhesion molecules Source: GO_Central
  • regulation of cell migration Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processAngiogenesis, Differentiation

Enzyme and pathway databases

SIGNORiQ8WZ75

Names & Taxonomyi

Protein namesi
Recommended name:
Roundabout homolog 4
Alternative name(s):
Magic roundabout
Gene namesi
Name:ROBO4
ORF Names:UNQ421/PRO3674
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000154133.14
HGNCiHGNC:17985 ROBO4
MIMi607528 gene
neXtProtiNX_Q8WZ75

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi54538
OpenTargetsiENSG00000154133
PharmGKBiPA34622

Polymorphism and mutation databases

BioMutaiROBO4
DMDMi49036490

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000003104028 – 1007Roundabout homolog 4Add BLAST980

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi53 ↔ 114PROSITE-ProRule annotation
Disulfide bondi158 ↔ 207PROSITE-ProRule annotation
Glycosylationi246N-linked (GlcNAc...) (complex) asparagine2 Publications1
Glycosylationi360N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi389N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi396N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi680N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei805PhosphoserineCombined sources1
Modified residuei938PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8WZ75
PeptideAtlasiQ8WZ75
PRIDEiQ8WZ75
ProteomicsDBi75232
75233 [Q8WZ75-2]
75234 [Q8WZ75-3]

PTM databases

iPTMnetiQ8WZ75
PhosphoSitePlusiQ8WZ75

Expressioni

Tissue specificityi

Specifically expressed in endothelial cells. Expressed at sites of angiogenesis in different tumor types.1 Publication

Gene expression databases

BgeeiENSG00000154133 Expressed in 196 organ(s), highest expression level in visceral pleura
CleanExiHS_ROBO4
ExpressionAtlasiQ8WZ75 baseline and differential
GenevisibleiQ8WZ75 HS

Organism-specific databases

HPAiHPA065212

Interactioni

Subunit structurei

Interacts with SLIT2 and ENAH.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120025, 5 interactors
IntActiQ8WZ75, 6 interactors
STRINGi9606.ENSP00000304945

Structurei

3D structure databases

ProteinModelPortaliQ8WZ75
SMRiQ8WZ75
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 131Ig-like C2-type 1Add BLAST100
Domaini137 – 224Ig-like C2-type 2Add BLAST88
Domaini248 – 345Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST98
Domaini347 – 442Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST96

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi715 – 784Pro/Ser-richAdd BLAST70

Sequence similaritiesi

Belongs to the immunoglobulin superfamily. ROBO family.Curated

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410INZ5 Eukaryota
ENOG410YX7X LUCA
GeneTreeiENSGT00930000150875
HOVERGENiHBG061836
InParanoidiQ8WZ75
KOiK06784
OMAiPDWLEDM
OrthoDBiEOG091G01DJ
PhylomeDBiQ8WZ75
TreeFamiTF351053

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF07679 I-set, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SM00409 IG, 2 hits
SM00408 IGc2, 2 hits
SUPFAMiSSF48726 SSF48726, 2 hits
SSF49265 SSF49265, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 2 hits
PS50835 IG_LIKE, 2 hits

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8WZ75-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGSGGDSLLG GRGSLPLLLL LIMGGMAQDS PPQILVHPQD QLFQGPGPAR
60 70 80 90 100
MSCQASGQPP PTIRWLLNGQ PLSMVPPDPH HLLPDGTLLL LQPPARGHAH
110 120 130 140 150
DGQALSTDLG VYTCEASNRL GTAVSRGARL SVAVLREDFQ IQPRDMVAVV
160 170 180 190 200
GEQFTLECGP PWGHPEPTVS WWKDGKPLAL QPGRHTVSGG SLLMARAEKS
210 220 230 240 250
DEGTYMCVAT NSAGHRESRA ARVSIQEPQD YTEPVELLAV RIQLENVTLL
260 270 280 290 300
NPDPAEGPKP RPAVWLSWKV SGPAAPAQSY TALFRTQTAP GGQGAPWAEE
310 320 330 340 350
LLAGWQSAEL GGLHWGQDYE FKVRPSSGRA RGPDSNVLLL RLPEKVPSAP
360 370 380 390 400
PQEVTLKPGN GTVFVSWVPP PAENHNGIIR GYQVWSLGNT SLPPANWTVV
410 420 430 440 450
GEQTQLEIAT HMPGSYCVQV AAVTGAGAGE PSRPVCLLLE QAMERATQEP
460 470 480 490 500
SEHGPWTLEQ LRATLKRPEV IATCGVALWL LLLGTAVCIH RRRRARVHLG
510 520 530 540 550
PGLYRYTSED AILKHRMDHS DSQWLADTWR STSGSRDLSS SSSLSSRLGA
560 570 580 590 600
DARDPLDCRR SLLSWDSRSP GVPLLPDTST FYGSLIAELP SSTPARPSPQ
610 620 630 640 650
VPAVRRLPPQ LAQLSSPCSS SDSLCSRRGL SSPRLSLAPA EAWKAKKKQE
660 670 680 690 700
LQHANSSPLL RGSHSLELRA CELGNRGSKN LSQSPGAVPQ ALVAWRALGP
710 720 730 740 750
KLLSSSNELV TRHLPPAPLF PHETPPTQSQ QTQPPVAPQA PSSILLPAAP
760 770 780 790 800
IPILSPCSPP SPQASSLSGP SPASSRLSSS SLSSLGEDQD SVLTPEEVAL
810 820 830 840 850
CLELSEGEET PRNSVSPMPR APSPPTTYGY ISVPTASEFT DMGRTGGGVG
860 870 880 890 900
PKGGVLLCPP RPCLTPTPSE GSLANGWGSA SEDNAASARA SLVSSSDGSF
910 920 930 940 950
LADAHFARAL AVAVDSFGFG LEPREADCVF IDASSPPSPR DEIFLTPNLS
960 970 980 990 1000
LPLWEWRPDW LEDMEVSHTQ RLGRGMPPWP PDSQISSQRS QLHCRMPKAG

ASPVDYS
Length:1,007
Mass (Da):107,457
Last modified:March 1, 2002 - v1
Checksum:iE43F246C59BE1415
GO
Isoform 2 (identifier: Q8WZ75-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     932-933: DA → GM
     934-1007: Missing.

Show »
Length:933
Mass (Da):98,994
Checksum:i1939F45D34AB81FA
GO
Isoform 3 (identifier: Q8WZ75-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-133: Missing.
     813-1007: Missing.

Show »
Length:702
Mass (Da):75,282
Checksum:i3988CDE4BF9FEE9B
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DYV8B4DYV8_HUMAN
cDNA FLJ54518, highly similar to Ro...
ROBO4
862Annotation score:

Sequence cautioni

The sequence AAH64643 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA91382 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB15082 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB55411 differs from that shown. Reason: Frameshift at position 706.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti175G → E in BAB55411 (PubMed:14702039).Curated1
Sequence conflicti498H → L in BAA91382 (PubMed:14702039).Curated1
Sequence conflicti652Q → P in BAB55411 (PubMed:14702039).Curated1
Sequence conflicti662G → D in BAB84989 (PubMed:14702039).Curated1
Sequence conflicti860P → L in BAB15082 (PubMed:14702039).Curated1
Sequence conflicti864L → F in BAB15082 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06214654Q → R. Corresponds to variant dbSNP:rs59648931Ensembl.1
Natural variantiVAR_053644669R → Q. Corresponds to variant dbSNP:rs4408324Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01065424 – 133Missing in isoform 3. 1 PublicationAdd BLAST110
Alternative sequenceiVSP_010657813 – 1007Missing in isoform 3. 1 PublicationAdd BLAST195
Alternative sequenceiVSP_010658932 – 933DA → GM in isoform 2. 1 Publication2
Alternative sequenceiVSP_010659934 – 1007Missing in isoform 2. 1 PublicationAdd BLAST74

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF361473 mRNA Translation: AAL31867.1
AY358083 mRNA Translation: AAQ88450.1
AK000805 mRNA Translation: BAA91382.1 Different initiation.
AK025195 mRNA Translation: BAB15082.1 Different initiation.
AK027852 mRNA Translation: BAB55411.1 Frameshift.
AK074163 mRNA Translation: BAB84989.1
AK289769 mRNA Translation: BAF82458.1
BC039602 mRNA Translation: AAH39602.1
BC064643 mRNA Translation: AAH64643.1 Different initiation.
BC111562 mRNA Translation: AAI11563.1
BC111748 mRNA Translation: AAI11749.1
CCDSiCCDS8455.1 [Q8WZ75-1]
RefSeqiNP_001288017.1, NM_001301088.1
NP_061928.4, NM_019055.5 [Q8WZ75-1]
UniGeneiHs.524121

Genome annotation databases

EnsembliENST00000306534; ENSP00000304945; ENSG00000154133 [Q8WZ75-1]
GeneIDi54538
KEGGihsa:54538
UCSCiuc001qbg.4 human [Q8WZ75-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF361473 mRNA Translation: AAL31867.1
AY358083 mRNA Translation: AAQ88450.1
AK000805 mRNA Translation: BAA91382.1 Different initiation.
AK025195 mRNA Translation: BAB15082.1 Different initiation.
AK027852 mRNA Translation: BAB55411.1 Frameshift.
AK074163 mRNA Translation: BAB84989.1
AK289769 mRNA Translation: BAF82458.1
BC039602 mRNA Translation: AAH39602.1
BC064643 mRNA Translation: AAH64643.1 Different initiation.
BC111562 mRNA Translation: AAI11563.1
BC111748 mRNA Translation: AAI11749.1
CCDSiCCDS8455.1 [Q8WZ75-1]
RefSeqiNP_001288017.1, NM_001301088.1
NP_061928.4, NM_019055.5 [Q8WZ75-1]
UniGeneiHs.524121

3D structure databases

ProteinModelPortaliQ8WZ75
SMRiQ8WZ75
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120025, 5 interactors
IntActiQ8WZ75, 6 interactors
STRINGi9606.ENSP00000304945

PTM databases

iPTMnetiQ8WZ75
PhosphoSitePlusiQ8WZ75

Polymorphism and mutation databases

BioMutaiROBO4
DMDMi49036490

Proteomic databases

PaxDbiQ8WZ75
PeptideAtlasiQ8WZ75
PRIDEiQ8WZ75
ProteomicsDBi75232
75233 [Q8WZ75-2]
75234 [Q8WZ75-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306534; ENSP00000304945; ENSG00000154133 [Q8WZ75-1]
GeneIDi54538
KEGGihsa:54538
UCSCiuc001qbg.4 human [Q8WZ75-1]

Organism-specific databases

CTDi54538
DisGeNETi54538
EuPathDBiHostDB:ENSG00000154133.14
GeneCardsiROBO4
HGNCiHGNC:17985 ROBO4
HPAiHPA065212
MIMi607528 gene
neXtProtiNX_Q8WZ75
OpenTargetsiENSG00000154133
PharmGKBiPA34622
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INZ5 Eukaryota
ENOG410YX7X LUCA
GeneTreeiENSGT00930000150875
HOVERGENiHBG061836
InParanoidiQ8WZ75
KOiK06784
OMAiPDWLEDM
OrthoDBiEOG091G01DJ
PhylomeDBiQ8WZ75
TreeFamiTF351053

Enzyme and pathway databases

SIGNORiQ8WZ75

Miscellaneous databases

GeneWikiiROBO4
GenomeRNAii54538
PROiPR:Q8WZ75
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000154133 Expressed in 196 organ(s), highest expression level in visceral pleura
CleanExiHS_ROBO4
ExpressionAtlasiQ8WZ75 baseline and differential
GenevisibleiQ8WZ75 HS

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF07679 I-set, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SM00409 IG, 2 hits
SM00408 IGc2, 2 hits
SUPFAMiSSF48726 SSF48726, 2 hits
SSF49265 SSF49265, 1 hit
PROSITEiView protein in PROSITE
PS50853 FN3, 2 hits
PS50835 IG_LIKE, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiROBO4_HUMAN
AccessioniPrimary (citable) accession number: Q8WZ75
Secondary accession number(s): A8K154
, Q14DU7, Q8TEG1, Q96JV6, Q9H718, Q9NWJ8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: March 1, 2002
Last modified: November 7, 2018
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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