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Q8WZ75

- ROBO4_HUMAN

UniProt

Q8WZ75 - ROBO4_HUMAN

Protein

Roundabout homolog 4

Gene

ROBO4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (01 Mar 2002)
      Previous versions | rss
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    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

    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: 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: UniProt
    3. integral component of membrane Source: UniProtKB

    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

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    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

    ArrayExpressiQ8WZ75.
    BgeeiQ8WZ75.
    CleanExiHS_ROBO4.
    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 28-441.
    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.
    HOVERGENiHBG061836.
    InParanoidiQ8WZ75.
    KOiK06784.
    OMAiQILVHPQ.
    OrthoDBiEOG7FFMR3.
    PhylomeDBiQ8WZ75.
    TreeFamiTF351053.

    Family and domain databases

    Gene3Di2.60.40.10. 4 hits.
    InterProiIPR003961. Fibronectin_type3.
    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. Align

    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

    MGSGGDSLLG GRGSLPLLLL LIMGGMAQDS PPQILVHPQD QLFQGPGPAR     50
    MSCQASGQPP PTIRWLLNGQ PLSMVPPDPH HLLPDGTLLL LQPPARGHAH 100
    DGQALSTDLG VYTCEASNRL GTAVSRGARL SVAVLREDFQ IQPRDMVAVV 150
    GEQFTLECGP PWGHPEPTVS WWKDGKPLAL QPGRHTVSGG SLLMARAEKS 200
    DEGTYMCVAT NSAGHRESRA ARVSIQEPQD YTEPVELLAV RIQLENVTLL 250
    NPDPAEGPKP RPAVWLSWKV SGPAAPAQSY TALFRTQTAP GGQGAPWAEE 300
    LLAGWQSAEL GGLHWGQDYE FKVRPSSGRA RGPDSNVLLL RLPEKVPSAP 350
    PQEVTLKPGN GTVFVSWVPP PAENHNGIIR GYQVWSLGNT SLPPANWTVV 400
    GEQTQLEIAT HMPGSYCVQV AAVTGAGAGE PSRPVCLLLE QAMERATQEP 450
    SEHGPWTLEQ LRATLKRPEV IATCGVALWL LLLGTAVCIH RRRRARVHLG 500
    PGLYRYTSED AILKHRMDHS DSQWLADTWR STSGSRDLSS SSSLSSRLGA 550
    DARDPLDCRR SLLSWDSRSP GVPLLPDTST FYGSLIAELP SSTPARPSPQ 600
    VPAVRRLPPQ LAQLSSPCSS SDSLCSRRGL SSPRLSLAPA EAWKAKKKQE 650
    LQHANSSPLL RGSHSLELRA CELGNRGSKN LSQSPGAVPQ ALVAWRALGP 700
    KLLSSSNELV TRHLPPAPLF PHETPPTQSQ QTQPPVAPQA PSSILLPAAP 750
    IPILSPCSPP SPQASSLSGP SPASSRLSSS SLSSLGEDQD SVLTPEEVAL 800
    CLELSEGEET PRNSVSPMPR APSPPTTYGY ISVPTASEFT DMGRTGGGVG 850
    PKGGVLLCPP RPCLTPTPSE GSLANGWGSA SEDNAASARA SLVSSSDGSF 900
    LADAHFARAL AVAVDSFGFG LEPREADCVF IDASSPPSPR DEIFLTPNLS 950
    LPLWEWRPDW LEDMEVSHTQ RLGRGMPPWP PDSQISSQRS QLHCRMPKAG 1000
    ASPVDYS 1007
    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

    Sequence cautioni

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

    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:
    EMBL
    GenBank
    DDBJ
    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_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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS8455.1. [Q8WZ75-1 ]
    RefSeqi NP_061928.4. NM_019055.5. [Q8WZ75-1 ]
    UniGenei Hs.524121.

    3D structure databases

    ProteinModelPortali Q8WZ75.
    SMRi Q8WZ75. Positions 28-441.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120025. 4 interactions.
    IntActi Q8WZ75. 5 interactions.
    STRINGi 9606.ENSP00000304945.

    Protein family/group databases

    MEROPSi I43.001.

    PTM databases

    PhosphoSitei Q8WZ75.

    Polymorphism databases

    DMDMi 49036490.

    Proteomic databases

    PaxDbi Q8WZ75.
    PRIDEi Q8WZ75.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000306534 ; ENSP00000304945 ; ENSG00000154133 . [Q8WZ75-1 ]
    GeneIDi 54538.
    KEGGi hsa:54538.
    UCSCi uc001qbg.3. human. [Q8WZ75-1 ]
    uc001qbh.2. human. [Q8WZ75-3 ]
    uc001qbi.3. human. [Q8WZ75-2 ]

    Organism-specific databases

    CTDi 54538.
    GeneCardsi GC11M124753.
    HGNCi HGNC:17985. ROBO4.
    MIMi 607528. gene.
    neXtProti NX_Q8WZ75.
    PharmGKBi PA34622.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG325715.
    HOVERGENi HBG061836.
    InParanoidi Q8WZ75.
    KOi K06784.
    OMAi QILVHPQ.
    OrthoDBi EOG7FFMR3.
    PhylomeDBi Q8WZ75.
    TreeFami TF351053.

    Miscellaneous databases

    GeneWikii ROBO4.
    GenomeRNAii 54538.
    NextBioi 56970.
    PROi Q8WZ75.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8WZ75.
    Bgeei Q8WZ75.
    CleanExi HS_ROBO4.
    Genevestigatori Q8WZ75.

    Family and domain databases

    Gene3Di 2.60.40.10. 4 hits.
    InterProi IPR003961. Fibronectin_type3.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR013098. Ig_I-set.
    IPR003598. Ig_sub2.
    [Graphical view ]
    Pfami PF00041. fn3. 1 hit.
    PF07679. I-set. 2 hits.
    [Graphical view ]
    SMARTi SM00060. FN3. 2 hits.
    SM00408. IGc2. 2 hits.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 1 hit.
    PROSITEi PS50853. FN3. 2 hits.
    PS50835. IG_LIKE. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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(2002) [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(2004) [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(2004) [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(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-246.
      Tissue: Plasma.
    6. Cited for: GLYCOSYLATION AT ASN-246.

    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 21, 2004
    Last sequence update: March 1, 2002
    Last modified: October 1, 2014
    This is version 111 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