ID ROBO2_HUMAN Reviewed; 1378 AA.
AC Q9HCK4; O43608; Q19AB4; Q19AB5;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2004, sequence version 2.
DT 01-MAY-2013, entry version 115.
DE RecName: Full=Roundabout homolog 2;
DE Flags: Precursor;
GN Name=ROBO2; Synonyms=KIAA1568;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING.
RX PubMed=16829019; DOI=10.1016/j.ygeno.2006.05.011;
RA Yue Y., Grossmann B., Galetzka D., Zechner U., Haaf T.;
RT "Isolation and differential expression of two isoforms of the
RT ROBO2/Robo2 axon guidance receptor gene in humans and mice.";
RL Genomics 88:772-778(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes.
RT XVIII. The complete sequences of 100 new cDNA clones from brain which
RT code for large proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Yue Y., Grossmann B., Galetzka D., Zechner U., Haaf T.;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 845-1378 (ISOFORM 2).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 323-607.
RX PubMed=9458045; DOI=10.1016/S0092-8674(00)80915-0;
RA Kidd T., Brose K., Mitchell K.J., Fetter R.D., Tessier-Lavigne M.,
RA Goodman C.S., Tear G.;
RT "Roundabout controls axon crossing of the CNS midline and defines a
RT novel subfamily of evolutionarily conserved guidance receptors.";
RL Cell 92:205-215(1998).
RN [7]
RP INTERACTION WITH SLIT2.
RX PubMed=10102268; DOI=10.1016/S0092-8674(00)80590-5;
RA Brose K., Bland K.S., Wang K.H., Arnott D., Henzel W., Goodman C.S.,
RA Tessier-Lavigne M., Kidd T.;
RT "Slit proteins bind Robo receptors and have an evolutionarily
RT conserved role in repulsive axon guidance.";
RL Cell 96:795-806(1999).
RN [8]
RP INTERACTION WITH SLIT2.
RX PubMed=11404413;
RA Nguyen-Ba-Charvet K.T., Brose K., Ma L., Wang K.H., Marillat V.,
RA Sotelo C., Tessier-Lavigne M., Chedotal A.;
RT "Diversity and specificity of actions of Slit2 proteolytic fragments
RT in axon guidance.";
RL J. Neurosci. 21:4281-4289(2001).
RN [9]
RP STRUCTURE BY NMR OF 417-734.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the fifth Ig-like domain and of first and
RT second fibronectin type III domain from human roundabout homolog 2.";
RL Submitted (AUG-2007) to the PDB data bank.
RN [10]
RP VARIANTS VUR2 THR-945 AND THR-1236, AND CHROMOSOMAL TRANSLOCATION WITH
RP PCDH11Y.
RX PubMed=17357069; DOI=10.1086/512735;
RA Lu W., van Eerde A.M., Fan X., Quintero-Rivera F., Kulkarni S.,
RA Ferguson H., Kim H.-G., Fan Y., Xi Q., Li Q.-G., Sanlaville D.,
RA Andrews W., Sundaresan V., Bi W., Yan J., Giltay J.C., Wijmenga C.,
RA de Jong T.P.V.M., Feather S.A., Woolf A.S., Rao Y., Lupski J.R.,
RA Eccles M.R., Quade B.J., Gusella J.F., Morton C.C., Maas R.L.;
RT "Disruption of ROBO2 is associated with urinary tract anomalies and
RT confers risk of vesicoureteral reflux.";
RL Am. J. Hum. Genet. 80:616-632(2007).
CC -!- FUNCTION: Receptor for SLIT2, and probably SLIT1, which are
CC thought to act as molecular guidance cue in cellular migration,
CC including axonal navigation at the ventral midline of the neural
CC tube and projection of axons to different regions during neuronal
CC development.
CC -!- SUBUNIT: Interacts with SLIT2.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9HCK4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HCK4-2; Sequence=VSP_010647;
CC Name=3;
CC IsoId=Q9HCK4-3; Sequence=VSP_043394;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Vesicoureteral reflux 2 (VUR2) [MIM:610878]: A disease
CC belonging to the group of congenital anomalies of the kidney and
CC urinary tract. It is characterized by the reflux of urine from the
CC bladder into the ureters and sometimes into the kidneys, and is a
CC risk factor for urinary tract infections. Primary disease results
CC from a developmental defect of the ureterovesical junction. In
CC combination with intrarenal reflux, the resulting inflammatory
CC reaction may result in renal injury or scarring, also called
CC reflux nephropathy. Extensive renal scarring impairs renal
CC function and may predispose patients to hypertension, proteinuria,
CC renal insufficiency and end-stage renal disease. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=A chromosomal aberration involving ROBO2 is a cause
CC of multiple congenital abnormalities, including severe bilateral
CC VUR with ureterovesical junction defects. Translocation
CC t(Y;3)(p11;p12) with PCDH11Y. This translocation disrupts ROBO2
CC and produces dominant-negative ROBO2 proteins that abrogate SLIT-
CC ROBO signaling in vitro.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. ROBO
CC family.
CC -!- SIMILARITY: Contains 3 fibronectin type-III domains.
CC -!- SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC39576.1; Type=Frameshift; Positions=601;
CC Sequence=BAB13394.1; Type=Erroneous initiation;
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DR EMBL; DQ533874; ABF83431.1; -; mRNA.
DR EMBL; AB046788; BAB13394.1; ALT_INIT; mRNA.
DR EMBL; DQ533873; ABF83430.1; -; mRNA.
DR EMBL; AC016942; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC016952; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC024256; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC067717; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117514; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117515; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC126467; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC130004; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC131005; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC131154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133040; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138974; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064374; AAH64374.1; -; mRNA.
DR EMBL; BC146772; AAI46773.1; -; mRNA.
DR EMBL; AF040991; AAC39576.1; ALT_FRAME; mRNA.
DR IPI; IPI00385980; -.
DR IPI; IPI00420043; -.
DR IPI; IPI00900311; -.
DR RefSeq; NP_001122401.1; NM_001128929.2.
DR RefSeq; NP_002933.1; NM_002942.4.
DR UniGene; Hs.13305; -.
DR PDB; 1UEM; NMR; -; A=516-617.
DR PDB; 1UJT; NMR; -; A=630-734.
DR PDB; 2EDJ; NMR; -; A=417-509.
DR PDBsum; 1UEM; -.
DR PDBsum; 1UJT; -.
DR PDBsum; 2EDJ; -.
DR ProteinModelPortal; Q9HCK4; -.
DR IntAct; Q9HCK4; 8.
DR MINT; MINT-1418118; -.
DR STRING; 9606.ENSP00000417164; -.
DR PhosphoSite; Q9HCK4; -.
DR DMDM; 49036496; -.
DR PaxDb; Q9HCK4; -.
DR PRIDE; Q9HCK4; -.
DR Ensembl; ENST00000461745; ENSP00000417164; ENSG00000185008.
DR Ensembl; ENST00000487694; ENSP00000417335; ENSG00000185008.
DR GeneID; 6092; -.
DR KEGG; hsa:6092; -.
DR UCSC; uc003dpy.4; human.
DR CTD; 6092; -.
DR GeneCards; GC03P075955; -.
DR HGNC; HGNC:10250; ROBO2.
DR HPA; HPA013371; -.
DR MIM; 602431; gene.
DR MIM; 610878; phenotype.
DR neXtProt; NX_Q9HCK4; -.
DR Orphanet; 289365; Familial vesicoureteral reflux.
DR PharmGKB; PA34621; -.
DR eggNOG; NOG238978; -.
DR HOGENOM; HOG000010267; -.
DR HOVERGEN; HBG073476; -.
DR KO; K06754; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; ROBO2; human.
DR EvolutionaryTrace; Q9HCK4; -.
DR GenomeRNAi; 6092; -.
DR NextBio; 23691; -.
DR ArrayExpress; Q9HCK4; -.
DR Bgee; Q9HCK4; -.
DR CleanEx; HS_ROBO2; -.
DR Genevestigator; Q9HCK4; -.
DR GO; GO:0030673; C:axolemma; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0008046; F:axon guidance receptor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0061364; P:apoptotic process involved in luteolysis; IEP:UniProtKB.
DR GO; GO:0016199; P:axon midline choice point recognition; ISS:UniProtKB.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:UniProtKB.
DR GO; GO:0007156; P:homophilic cell adhesion; IDA:UniProtKB.
DR GO; GO:0001656; P:metanephros development; ISS:UniProtKB.
DR GO; GO:0050925; P:negative regulation of negative chemotaxis; IDA:UniProtKB.
DR GO; GO:0051964; P:negative regulation of synapse assembly; ISS:UniProtKB.
DR GO; GO:0021891; P:olfactory bulb interneuron development; ISS:UniProtKB.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IDA:UniProtKB.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; ISS:UniProtKB.
DR GO; GO:0001657; P:ureteric bud development; IMP:UniProtKB.
DR Gene3D; 2.60.40.10; -; 9.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003598; Ig_sub2.
DR Pfam; PF00041; fn3; 3.
DR Pfam; PF07679; I-set; 5.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00408; IGc2; 5.
DR SUPFAM; SSF49265; FN_III-like; 3.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS50835; IG_LIKE; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chemotaxis;
KW Chromosomal rearrangement; Complete proteome; Developmental protein;
KW Differentiation; Disease mutation; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Neurogenesis; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 21 Potential.
FT CHAIN 22 1378 Roundabout homolog 2.
FT /FTId=PRO_0000031036.
FT TOPO_DOM 22 859 Extracellular (Potential).
FT TRANSMEM 860 880 Helical; (Potential).
FT TOPO_DOM 881 1378 Cytoplasmic (Potential).
FT DOMAIN 31 127 Ig-like C2-type 1.
FT DOMAIN 133 220 Ig-like C2-type 2.
FT DOMAIN 225 309 Ig-like C2-type 3.
FT DOMAIN 314 409 Ig-like C2-type 4.
FT DOMAIN 418 504 Ig-like C2-type 5.
FT DOMAIN 522 607 Fibronectin type-III 1.
FT DOMAIN 634 724 Fibronectin type-III 2.
FT DOMAIN 736 826 Fibronectin type-III 3.
FT CARBOHYD 123 123 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 426 426 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 752 752 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 782 782 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 789 789 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 845 845 N-linked (GlcNAc...) (Potential).
FT DISULFID 52 110 Potential.
FT DISULFID 154 203 Potential.
FT DISULFID 246 293 Potential.
FT DISULFID 335 391 Potential.
FT DISULFID 439 488 Potential.
FT VAR_SEQ 1 20 MSLLMFTQLLLCGFLYVRVD -> MARRHERVTRRMWTWAP
FT GLLMMTVVFWGHQGNGQGQ (in isoform 3).
FT /FTId=VSP_043394.
FT VAR_SEQ 1186 1378 Missing (in isoform 2).
FT /FTId=VSP_010647.
FT VARIANT 945 945 I -> T (in VUR2).
FT /FTId=VAR_032960.
FT VARIANT 1236 1236 A -> T (in VUR2).
FT /FTId=VAR_032961.
FT CONFLICT 497 497 T -> A (in Ref. 5).
FT STRAND 419 422
FT STRAND 427 437
FT STRAND 440 442
FT STRAND 448 461
FT STRAND 473 477
FT TURN 480 482
FT STRAND 485 491
FT STRAND 501 507
FT STRAND 529 533
FT STRAND 538 541
FT STRAND 548 550
FT STRAND 554 561
FT TURN 562 564
FT STRAND 565 575
FT STRAND 577 582
FT STRAND 590 599
FT STRAND 602 606
FT HELIX 630 636
FT STRAND 639 641
FT STRAND 651 660
FT STRAND 667 679
FT TURN 680 682
FT STRAND 685 688
FT STRAND 696 701
FT STRAND 704 718
FT STRAND 727 731
SQ SEQUENCE 1378 AA; 151200 MW; 60F7CE3E53622B50 CRC64;
MSLLMFTQLL LCGFLYVRVD GSRLRQEDFP PRIVEHPSDV IVSKGEPTTL NCKAEGRPTP
TIEWYKDGER VETDKDDPRS HRMLLPSGSL FFLRIVHGRR SKPDEGSYVC VARNYLGEAV
SRNASLEVAL LRDDFRQNPT DVVVAAGEPA ILECQPPRGH PEPTIYWKKD KVRIDDKEER
ISIRGGKLMI SNTRKSDAGM YTCVGTNMVG ERDSDPAELT VFERPTFLRR PINQVVLEEE
AVEFRCQVQG DPQPTVRWKK DDADLPRGRY DIKDDYTLRI KKTMSTDEGT YMCIAENRVG
KMEASATLTV RAPPQFVVRP RDQIVAQGRT VTFPCETKGN PQPAVFWQKE GSQNLLFPNQ
PQQPNSRCSV SPTGDLTITN IQRSDAGYYI CQALTVAGSI LAKAQLEVTD VLTDRPPPII
LQGPANQTLA VDGTALLKCK ATGDPLPVIS WLKEGFTFPG RDPRATIQEQ GTLQIKNLRI
SDTGTYTCVA TSSSGETSWS AVLDVTESGA TISKNYDLSD LPGPPSKPQV TDVTKNSVTL
SWQPGTPGTL PASAYIIEAF SQSVSNSWQT VANHVKTTLY TVRGLRPNTI YLFMVRAINP
QGLSDPSPMS DPVRTQDISP PAQGVDHRQV QKELGDVLVR LHNPVVLTPT TVQVTWTVDR
QPQFIQGYRV MYRQTSGLQA TSSWQNLDAK VPTERSAVLV NLKKGVTYEI KVRPYFNEFQ
GMDSESKTVR TTEEAPSAPP QSVTVLTVGS YNSTSISVSW DPPPPDHQNG IIQEYKIWCL
GNETRFHINK TVDAAIRSVI IGGLFPGIQY RVEVAASTSA GVGVKSEPQP IIIGRRNEVV
ITENNNSITE QITDVVKQPA FIAGIGGACW VILMGFSIWL YWRRKKRKGL SNYAVTFQRG
DGGLMSNGSR PGLLNAGDPS YPWLADSWPA TSLPVNNSNS GPNEIGNFGR GDVLPPVPGQ
GDKTATMLSD GAIYSSIDFT TKTSYNSSSQ ITQATPYATT QILHSNSIHE LAVDLPDPQW
KSSIQQKTDL MGFGYSLPDQ NKGNNGGKGG KKKKNKNSSK PQKNNGSTWA NVPLPPPPVQ
PLPGTELEHY AVEQQENGYD SDSWCPPLPV QTYLHQGLED ELEEDDDRVP TPPVRGVASS
PAISFGQQST ATLTPSPREE MQPMLQAHLD ELTRAYQFDI AKQTWHIQSN NQPPQPPVPP
LGYVSGALIS DLETDVADDD ADDEEEALEI PRPLRALDQT PGSSMDNLDS SVTGKAFTSS
QRPRPTSPFS TDSNTSAALS QSQRPRPTKK HKGGRMDQQP ALPHRREGMT DEEALVPYSK
PSFPSPGGHS SSGTASSKGS TGPRKTEVLR AGHQRNASDL LDIGYMGSNS QGQFTGEL
//
