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Q9HCK4 (ROBO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Roundabout homolog 2
Gene names
Name:ROBO2
Synonyms:KIAA1568
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1378 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development.

Subunit structure

Interacts with SLIT2. Ref.7 Ref.8

Subcellular location

Membrane; Single-pass type I membrane protein Potential.

Involvement in disease

Vesicoureteral reflux 2 (VUR2) [MIM:610878]: A disease belonging to the group of congenital anomalies of the kidney and urinary tract. It is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys, and is a risk factor for urinary tract infections. Primary disease results from a developmental defect of the ureterovesical junction. In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy. Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, renal insufficiency and end-stage renal disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

A chromosomal aberration involving ROBO2 is a cause of multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. Translocation t(Y;3)(p11;p12) with PCDH11Y. This translocation disrupts ROBO2 and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro.

Sequence similarities

Belongs to the immunoglobulin superfamily. ROBO family.

Contains 3 fibronectin type-III domains.

Contains 5 Ig-like C2-type (immunoglobulin-like) domains.

Sequence caution

The sequence AAC39576.1 differs from that shown. Reason: Frameshift at position 601.

The sequence BAB13394.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processChemotaxis
Differentiation
Neurogenesis
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
   DiseaseDisease mutation
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process involved in luteolysis

Inferred from expression pattern PubMed 18566128. Source: UniProtKB

axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

axon midline choice point recognition

Inferred from sequence or structural similarity. Source: UniProtKB

brain development

Inferred from expression pattern PubMed 10197527. Source: UniProtKB

cellular response to hormone stimulus

Inferred from expression pattern PubMed 18566128. Source: UniProtKB

central nervous system development

Non-traceable author statement Ref.6. Source: UniProtKB

homophilic cell adhesion

Inferred from direct assay PubMed 12504588. Source: UniProtKB

metanephros development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of negative chemotaxis

Inferred from direct assay PubMed 11748139. Source: UniProtKB

negative regulation of synapse assembly

Inferred from sequence or structural similarity. Source: UniProtKB

olfactory bulb interneuron development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of axonogenesis

Inferred from direct assay PubMed 12504588. Source: UniProtKB

retinal ganglion cell axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

ureteric bud development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

   Cellular_componentaxolemma

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from direct assay PubMed 12504588. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionaxon guidance receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

identical protein binding

Inferred from direct assay PubMed 12504588. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12504588PubMed 15207848. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HCK4-1)

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.
Isoform 2 (identifier: Q9HCK4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1186-1378: Missing.
Isoform 3 (identifier: Q9HCK4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: MSLLMFTQLLLCGFLYVRVD → MARRHERVTRRMWTWAPGLLMMTVVFWGHQGNGQGQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 13781357Roundabout homolog 2
PRO_0000031036

Regions

Topological domain22 – 859838Extracellular Potential
Transmembrane860 – 88021Helical; Potential
Topological domain881 – 1378498Cytoplasmic Potential
Domain31 – 12797Ig-like C2-type 1
Domain133 – 22088Ig-like C2-type 2
Domain225 – 30985Ig-like C2-type 3
Domain314 – 40996Ig-like C2-type 4
Domain418 – 50487Ig-like C2-type 5
Domain524 – 61895Fibronectin type-III 1
Domain637 – 73599Fibronectin type-III 2
Domain739 – 83698Fibronectin type-III 3

Amino acid modifications

Glycosylation1231N-linked (GlcNAc...) Potential
Glycosylation4261N-linked (GlcNAc...) Potential
Glycosylation7521N-linked (GlcNAc...) Potential
Glycosylation7821N-linked (GlcNAc...) Potential
Glycosylation7891N-linked (GlcNAc...) Potential
Glycosylation8451N-linked (GlcNAc...) Potential
Disulfide bond52 ↔ 110 Potential
Disulfide bond154 ↔ 203 Potential
Disulfide bond246 ↔ 293 Potential
Disulfide bond335 ↔ 391 Potential
Disulfide bond439 ↔ 488 Potential

Natural variations

Alternative sequence1 – 2020MSLLM…YVRVD → MARRHERVTRRMWTWAPGLL MMTVVFWGHQGNGQGQ in isoform 3.
VSP_043394
Alternative sequence1186 – 1378193Missing in isoform 2.
VSP_010647
Natural variant9451I → T in VUR2. Ref.10
VAR_032960
Natural variant12361A → T in VUR2. Ref.10
VAR_032961

Experimental info

Sequence conflict4971T → A Ref.5

Secondary structure

.................................................. 1378
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 21, 2004. Version 2.
Checksum: 60F7CE3E53622B50

FASTA1,378151,200
        10         20         30         40         50         60 
MSLLMFTQLL LCGFLYVRVD GSRLRQEDFP PRIVEHPSDV IVSKGEPTTL NCKAEGRPTP 

        70         80         90        100        110        120 
TIEWYKDGER VETDKDDPRS HRMLLPSGSL FFLRIVHGRR SKPDEGSYVC VARNYLGEAV 

       130        140        150        160        170        180 
SRNASLEVAL LRDDFRQNPT DVVVAAGEPA ILECQPPRGH PEPTIYWKKD KVRIDDKEER 

       190        200        210        220        230        240 
ISIRGGKLMI SNTRKSDAGM YTCVGTNMVG ERDSDPAELT VFERPTFLRR PINQVVLEEE 

       250        260        270        280        290        300 
AVEFRCQVQG DPQPTVRWKK DDADLPRGRY DIKDDYTLRI KKTMSTDEGT YMCIAENRVG 

       310        320        330        340        350        360 
KMEASATLTV RAPPQFVVRP RDQIVAQGRT VTFPCETKGN PQPAVFWQKE GSQNLLFPNQ 

       370        380        390        400        410        420 
PQQPNSRCSV SPTGDLTITN IQRSDAGYYI CQALTVAGSI LAKAQLEVTD VLTDRPPPII 

       430        440        450        460        470        480 
LQGPANQTLA VDGTALLKCK ATGDPLPVIS WLKEGFTFPG RDPRATIQEQ GTLQIKNLRI 

       490        500        510        520        530        540 
SDTGTYTCVA TSSSGETSWS AVLDVTESGA TISKNYDLSD LPGPPSKPQV TDVTKNSVTL 

       550        560        570        580        590        600 
SWQPGTPGTL PASAYIIEAF SQSVSNSWQT VANHVKTTLY TVRGLRPNTI YLFMVRAINP 

       610        620        630        640        650        660 
QGLSDPSPMS DPVRTQDISP PAQGVDHRQV QKELGDVLVR LHNPVVLTPT TVQVTWTVDR 

       670        680        690        700        710        720 
QPQFIQGYRV MYRQTSGLQA TSSWQNLDAK VPTERSAVLV NLKKGVTYEI KVRPYFNEFQ 

       730        740        750        760        770        780 
GMDSESKTVR TTEEAPSAPP QSVTVLTVGS YNSTSISVSW DPPPPDHQNG IIQEYKIWCL 

       790        800        810        820        830        840 
GNETRFHINK TVDAAIRSVI IGGLFPGIQY RVEVAASTSA GVGVKSEPQP IIIGRRNEVV 

       850        860        870        880        890        900 
ITENNNSITE QITDVVKQPA FIAGIGGACW VILMGFSIWL YWRRKKRKGL SNYAVTFQRG 

       910        920        930        940        950        960 
DGGLMSNGSR PGLLNAGDPS YPWLADSWPA TSLPVNNSNS GPNEIGNFGR GDVLPPVPGQ 

       970        980        990       1000       1010       1020 
GDKTATMLSD GAIYSSIDFT TKTSYNSSSQ ITQATPYATT QILHSNSIHE LAVDLPDPQW 

      1030       1040       1050       1060       1070       1080 
KSSIQQKTDL MGFGYSLPDQ NKGNNGGKGG KKKKNKNSSK PQKNNGSTWA NVPLPPPPVQ 

      1090       1100       1110       1120       1130       1140 
PLPGTELEHY AVEQQENGYD SDSWCPPLPV QTYLHQGLED ELEEDDDRVP TPPVRGVASS 

      1150       1160       1170       1180       1190       1200 
PAISFGQQST ATLTPSPREE MQPMLQAHLD ELTRAYQFDI AKQTWHIQSN NQPPQPPVPP 

      1210       1220       1230       1240       1250       1260 
LGYVSGALIS DLETDVADDD ADDEEEALEI PRPLRALDQT PGSSMDNLDS SVTGKAFTSS 

      1270       1280       1290       1300       1310       1320 
QRPRPTSPFS TDSNTSAALS QSQRPRPTKK HKGGRMDQQP ALPHRREGMT DEEALVPYSK 

      1330       1340       1350       1360       1370 
PSFPSPGGHS SSGTASSKGS TGPRKTEVLR AGHQRNASDL LDIGYMGSNS QGQFTGEL 

« Hide

Isoform 2 [UniParc].

Checksum: 5A6ABDBD4A2111A3
Show »

FASTA1,185130,669
Isoform 3 [UniParc].

Checksum: 860FFDE4892D51B7
Show »

FASTA1,394153,120

References

« Hide 'large scale' references
[1]"Isolation and differential expression of two isoforms of the ROBO2/Robo2 axon guidance receptor gene in humans and mice."
Yue Y., Grossmann B., Galetzka D., Zechner U., Haaf T.
Genomics 88:772-778(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING.
[2]"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.
DNA Res. 7:273-281(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]Yue Y., Grossmann B., Galetzka D., Zechner U., Haaf T.
Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[4]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 845-1378 (ISOFORM 2).
Tissue: Ovary.
[6]"Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors."
Kidd T., Brose K., Mitchell K.J., Fetter R.D., Tessier-Lavigne M., Goodman C.S., Tear G.
Cell 92:205-215(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 323-607.
[7]"Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance."
Brose K., Bland K.S., Wang K.H., Arnott D., Henzel W., Goodman C.S., Tessier-Lavigne M., Kidd T.
Cell 96:795-806(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLIT2.
[8]"Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance."
Nguyen-Ba-Charvet K.T., Brose K., Ma L., Wang K.H., Marillat V., Sotelo C., Tessier-Lavigne M., Chedotal A.
J. Neurosci. 21:4281-4289(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLIT2.
[9]"Solution structure of the fifth Ig-like domain and of first and second fibronectin type III domain from human roundabout homolog 2."
RIKEN structural genomics initiative (RSGI)
Submitted (AUG-2007) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 417-734.
[10]"Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux."
Lu W., van Eerde A.M., Fan X., Quintero-Rivera F., Kulkarni S., Ferguson H., Kim H.-G., Fan Y., Xi Q., Li Q.-G., Sanlaville D., Andrews W., Sundaresan V., Bi W., Yan J., Giltay J.C., Wijmenga C., de Jong T.P.V.M. expand/collapse author list , Feather S.A., Woolf A.S., Rao Y., Lupski J.R., Eccles M.R., Quade B.J., Gusella J.F., Morton C.C., Maas R.L.
Am. J. Hum. Genet. 80:616-632(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VUR2 THR-945 AND THR-1236, CHROMOSOMAL TRANSLOCATION WITH PCDH11Y.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ533874 mRNA. Translation: ABF83431.1.
AB046788 mRNA. Translation: BAB13394.1. Different initiation.
DQ533873 mRNA. Translation: ABF83430.1.
AC016942 Genomic DNA. No translation available.
AC016952 Genomic DNA. No translation available.
AC024256 Genomic DNA. No translation available.
AC026877 Genomic DNA. No translation available.
AC067717 Genomic DNA. No translation available.
AC117514 Genomic DNA. No translation available.
AC117515 Genomic DNA. No translation available.
AC117516 Genomic DNA. No translation available.
AC126467 Genomic DNA. No translation available.
AC130004 Genomic DNA. No translation available.
AC131005 Genomic DNA. No translation available.
AC131154 Genomic DNA. No translation available.
AC133040 Genomic DNA. No translation available.
AC138974 Genomic DNA. No translation available.
BC064374 mRNA. Translation: AAH64374.1.
BC146772 mRNA. Translation: AAI46773.1.
AF040991 mRNA. Translation: AAC39576.1. Frameshift.
CCDSCCDS43109.1. [Q9HCK4-1]
CCDS54609.1. [Q9HCK4-3]
RefSeqNP_001122401.1. NM_001128929.3. [Q9HCK4-3]
NP_001276968.1. NM_001290039.1.
NP_001276969.1. NM_001290040.1.
NP_001276994.1. NM_001290065.1.
NP_002933.1. NM_002942.4. [Q9HCK4-1]
UniGeneHs.13305.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UEMNMR-A514-617[»]
1UJTNMR-A628-734[»]
2EDJNMR-A417-509[»]
ProteinModelPortalQ9HCK4.
SMRQ9HCK4. Positions 24-831.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112019. 13 interactions.
IntActQ9HCK4. 17 interactions.
MINTMINT-1418118.
STRING9606.ENSP00000417164.

PTM databases

PhosphoSiteQ9HCK4.

Polymorphism databases

DMDM49036496.

Proteomic databases

PaxDbQ9HCK4.
PRIDEQ9HCK4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000461745; ENSP00000417164; ENSG00000185008. [Q9HCK4-1]
ENST00000487694; ENSP00000417335; ENSG00000185008. [Q9HCK4-3]
GeneID6092.
KEGGhsa:6092.
UCSCuc003dpy.4. human. [Q9HCK4-1]
uc021xat.1. human. [Q9HCK4-3]

Organism-specific databases

CTD6092.
GeneCardsGC03P075955.
HGNCHGNC:10250. ROBO2.
HPAHPA013371.
MIM602431. gene.
610878. phenotype.
neXtProtNX_Q9HCK4.
Orphanet289365. Familial vesicoureteral reflux.
PharmGKBPA34621.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238978.
HOGENOMHOG000010267.
HOVERGENHBG073476.
KOK06754.
PhylomeDBQ9HCK4.
TreeFamTF351053.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressQ9HCK4.
BgeeQ9HCK4.
CleanExHS_ROBO2.
GenevestigatorQ9HCK4.

Family and domain databases

Gene3D2.60.40.10. 9 hits.
InterProIPR003961. Fibronectin_type3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
[Graphical view]
PfamPF00041. fn3. 3 hits.
PF07679. I-set. 5 hits.
[Graphical view]
SMARTSM00060. FN3. 3 hits.
SM00408. IGc2. 5 hits.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 3 hits.
PS50835. IG_LIKE. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSROBO2. human.
EvolutionaryTraceQ9HCK4.
GeneWikiROBO2.
GenomeRNAi6092.
NextBio23691.
PROQ9HCK4.
SOURCESearch...

Entry information

Entry nameROBO2_HUMAN
AccessionPrimary (citable) accession number: Q9HCK4
Secondary accession number(s): O43608, Q19AB4, Q19AB5
Entry history
Integrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: June 21, 2004
Last modified: July 9, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM