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Protein

Roundabout homolog 4

Gene

ROBO4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  1. receptor activity Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: UniProtKB
  2. cell differentiation Source: UniProtKB-KW
  3. negative regulation of cell migration Source: Ensembl
  4. regulation of cell migration Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Angiogenesis, Differentiation

Protein family/group databases

MEROPSiI43.001.

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
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:17985. ROBO4.

Subcellular locationi

GO - Cellular componenti

  1. external side of plasma membrane Source: Ensembl
  2. extracellular vesicular exosome Source: UniProtKB
  3. integral component of membrane Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA34622.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 1007980Roundabout homolog 4PRO_0000031040Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi53 ↔ 114PROSITE-ProRule annotation
Disulfide bondi158 ↔ 207PROSITE-ProRule annotation
Glycosylationi246 – 2461N-linked (GlcNAc...) (complex)2 Publications
Glycosylationi360 – 3601N-linked (GlcNAc...)Sequence Analysis
Glycosylationi389 – 3891N-linked (GlcNAc...)Sequence Analysis
Glycosylationi396 – 3961N-linked (GlcNAc...)Sequence Analysis
Glycosylationi680 – 6801N-linked (GlcNAc...)Sequence Analysis
Modified residuei805 – 8051Phosphoserine1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8WZ75.
PRIDEiQ8WZ75.

PTM databases

PhosphoSiteiQ8WZ75.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ8WZ75.
CleanExiHS_ROBO4.
ExpressionAtlasiQ8WZ75. baseline and differential.
GenevestigatoriQ8WZ75.

Interactioni

Subunit structurei

Interacts with SLIT2 and ENAH.By similarity

Protein-protein interaction databases

BioGridi120025. 4 interactions.
IntActiQ8WZ75. 5 interactions.
STRINGi9606.ENSP00000304945.

Structurei

3D structure databases

ProteinModelPortaliQ8WZ75.
SMRiQ8WZ75. Positions 28-440.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 131100Ig-like C2-type 1Add
BLAST
Domaini137 – 22488Ig-like C2-type 2Add
BLAST
Domaini248 – 34598Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini347 – 44296Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi715 – 78470Pro/Ser-richAdd
BLAST

Sequence similaritiesi

Belongs to the immunoglobulin superfamily. ROBO family.Curated
Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal

Phylogenomic databases

eggNOGiNOG325715.
GeneTreeiENSGT00780000121850.
HOVERGENiHBG061836.
InParanoidiQ8WZ75.
KOiK06784.
OMAiQILVHPQ.
OrthoDBiEOG7FFMR3.
PhylomeDBiQ8WZ75.
TreeFamiTF351053.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF07679. I-set. 2 hits.
[Graphical view]
SMARTiSM00060. FN3. 2 hits.
SM00408. IGc2. 2 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 1 hit.
PROSITEiPS50853. FN3. 2 hits.
PS50835. IG_LIKE. 2 hits.
[Graphical view]

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

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:February 28, 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

Sequence cautioni

The sequence AAH64643.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAA91382.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAB15082.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAB55411.1 differs from that shown. Reason: Frameshift at position 706. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti175 – 1751G → E in BAB55411 (PubMed:14702039).Curated
Sequence conflicti498 – 4981H → L in BAA91382 (PubMed:14702039).Curated
Sequence conflicti652 – 6521Q → P in BAB55411 (PubMed:14702039).Curated
Sequence conflicti662 – 6621G → D in BAB84989 (PubMed:14702039).Curated
Sequence conflicti860 – 8601P → L in BAB15082 (PubMed:14702039).Curated
Sequence conflicti864 – 8641L → F in BAB15082 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti54 – 541Q → R.
Corresponds to variant rs59648931 [ dbSNP | Ensembl ].
VAR_062146
Natural varianti103 – 1031Q → P.
Corresponds to variant rs4995424 [ dbSNP | Ensembl ].
VAR_053643
Natural varianti669 – 6691R → Q.
Corresponds to variant rs4408324 [ dbSNP | Ensembl ].
VAR_053644

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei24 – 133110Missing in isoform 3. 1 PublicationVSP_010654Add
BLAST
Alternative sequencei813 – 1007195Missing in isoform 3. 1 PublicationVSP_010657Add
BLAST
Alternative sequencei932 – 9332DA → GM in isoform 2. 1 PublicationVSP_010658
Alternative sequencei934 – 100774Missing in isoform 2. 1 PublicationVSP_010659Add
BLAST

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.3. human. [Q8WZ75-1]
uc001qbh.2. human. [Q8WZ75-3]
uc001qbi.3. human. [Q8WZ75-2]

Polymorphism databases

DMDMi49036490.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. Positions 28-440.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120025. 4 interactions.
IntActiQ8WZ75. 5 interactions.
STRINGi9606.ENSP00000304945.

Protein family/group databases

MEROPSiI43.001.

PTM databases

PhosphoSiteiQ8WZ75.

Polymorphism databases

DMDMi49036490.

Proteomic databases

PaxDbiQ8WZ75.
PRIDEiQ8WZ75.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306534; ENSP00000304945; ENSG00000154133. [Q8WZ75-1]
GeneIDi54538.
KEGGihsa:54538.
UCSCiuc001qbg.3. human. [Q8WZ75-1]
uc001qbh.2. human. [Q8WZ75-3]
uc001qbi.3. human. [Q8WZ75-2]

Organism-specific databases

CTDi54538.
GeneCardsiGC11M124753.
HGNCiHGNC:17985. ROBO4.
MIMi607528. gene.
neXtProtiNX_Q8WZ75.
PharmGKBiPA34622.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG325715.
GeneTreeiENSGT00780000121850.
HOVERGENiHBG061836.
InParanoidiQ8WZ75.
KOiK06784.
OMAiQILVHPQ.
OrthoDBiEOG7FFMR3.
PhylomeDBiQ8WZ75.
TreeFamiTF351053.

Miscellaneous databases

GeneWikiiROBO4.
GenomeRNAii54538.
NextBioi56970.
PROiQ8WZ75.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WZ75.
CleanExiHS_ROBO4.
ExpressionAtlasiQ8WZ75. baseline and differential.
GenevestigatoriQ8WZ75.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF07679. I-set. 2 hits.
[Graphical view]
SMARTiSM00060. FN3. 2 hits.
SM00408. IGc2. 2 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 1 hit.
PROSITEiPS50853. FN3. 2 hits.
PS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis."
    Huminiecki L., Gorn M., Suchting S., Poulsom R., Bicknell R.
    Genomics 79:547-552(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-1007 (ISOFORM 1).
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
    Tissue: Adipose tissue, Brain and Colon.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain and Ovary.
  5. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
    Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
    J. Proteome Res. 4:2070-2080(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-246.
    Tissue: Plasma.
  6. Cited for: GLYCOSYLATION AT ASN-246.
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-805, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiROBO4_HUMAN
AccessioniPrimary (citable) accession number: Q8WZ75
Secondary accession number(s): A8K154
, Q14DU7, Q8TEG1, Q96JV6, Q9H718, Q9NWJ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2004
Last sequence update: February 28, 2002
Last modified: March 3, 2015
This is version 116 of the entry and version 1 of the sequence. [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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.