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Roundabout homolog 3 (Roundabout-like protein 3)

 ROBO3_HUMAN             Reviewed;        1386 AA.
Q96MS0;
21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
21-JUN-2004, sequence version 2.
12-SEP-2018, entry version 147.
RecName: Full=Roundabout homolog 3;
AltName: Full=Roundabout-like protein 3;
Flags: Precursor;
Name=ROBO3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND VARIANTS HGPPS1
PRO-5; LEU-66; LYS-319; GLU-361; PRO-703 AND PRO-705.
PubMed=15105459; DOI=10.1126/science.1096437;
Jen J.C., Chan W.-M., Bosley T.M., Wan J.-J., Carr J.R., Rueb U.,
Shattuck D., Salamon G., Kudo L.C., Ou J., Lin D.D.M., Salih M.A.M.,
Kansu T., Al Dhalaan H., Al-Zayed Z., MacDonald D.B., Stigsby B.,
Plaitakis A., Dretakis E.K., Gottlob I., Pieh C., Traboulsi E.I.,
Wang Q., Wang L., Andrews C., Yamada K., Demer J.L., Karim S.,
Alger J.R., Geschwind D.H., Deller T., Sicotte N.L., Nelson S.F.,
Baloh R.W., Engle E.C.;
"Mutations in a human ROBO gene disrupt hindbrain axon pathway
crossing and morphogenesis.";
Science 304:1509-1513(2004).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS
MET-423 AND LEU-868.
PubMed=14702039; DOI=10.1038/ng1285;
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[3]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1263, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
-!- FUNCTION: Thought to be involved during neural development in
axonal navigation at the ventral midline of the neural tube. In
spinal chord development plays a role in guiding commissural axons
probably by preventing premature sensitivity to Slit proteins thus
inhibiting Slit signaling through ROBO1 (By similarity). Required
for hindbrain axon midline crossing. {ECO:0000250,
ECO:0000269|PubMed:15105459}.
-!- SUBUNIT: Probably interacts with SLIT2. {ECO:0000250}.
-!- INTERACTION:
Q99435-1:NELL2; NbExp=3; IntAct=EBI-1220465, EBI-16185191;
-!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
membrane protein {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q96MS0-1; Sequence=Displayed;
Name=2;
IsoId=Q96MS0-2; Sequence=VSP_010650, VSP_010651;
-!- DISEASE: Gaze palsy, familial horizontal, with progressive
scoliosis, 1 (HGPPS1) [MIM:607313]: An autosomal recessive
neurologic disorder characterized by eye movement abnormalities
apparent from birth, childhood-onset progressive scoliosis,
distinctive brainstem malformation and defective crossing of some
brainstem neuronal pathways. {ECO:0000269|PubMed:15105459}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- SIMILARITY: Belongs to the immunoglobulin superfamily. ROBO
family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AY509035; AAS91662.1; -; mRNA.
EMBL; AK056544; BAB71212.1; -; mRNA.
CCDS; CCDS44755.1; -. [Q96MS0-1]
RefSeq; NP_071765.2; NM_022370.3. [Q96MS0-1]
UniGene; Hs.435621; -.
ProteinModelPortal; Q96MS0; -.
SMR; Q96MS0; -.
BioGrid; 122111; 8.
DIP; DIP-38410N; -.
IntAct; Q96MS0; 2.
STRING; 9606.ENSP00000380903; -.
iPTMnet; Q96MS0; -.
PhosphoSitePlus; Q96MS0; -.
BioMuta; ROBO3; -.
DMDM; 49036492; -.
EPD; Q96MS0; -.
MaxQB; Q96MS0; -.
PaxDb; Q96MS0; -.
PeptideAtlas; Q96MS0; -.
PRIDE; Q96MS0; -.
ProteomicsDB; 77392; -.
ProteomicsDB; 77393; -. [Q96MS0-2]
DNASU; 64221; -.
Ensembl; ENST00000397801; ENSP00000380903; ENSG00000154134. [Q96MS0-1]
GeneID; 64221; -.
KEGG; hsa:64221; -.
UCSC; uc001qbc.4; human. [Q96MS0-1]
CTD; 64221; -.
DisGeNET; 64221; -.
EuPathDB; HostDB:ENSG00000154134.14; -.
GeneCards; ROBO3; -.
HGNC; HGNC:13433; ROBO3.
MalaCards; ROBO3; -.
MIM; 607313; phenotype.
MIM; 608630; gene.
neXtProt; NX_Q96MS0; -.
OpenTargets; ENSG00000154134; -.
Orphanet; 2744; Horizontal gaze palsy with progressive scoliosis.
PharmGKB; PA134896648; -.
eggNOG; KOG4222; Eukaryota.
eggNOG; ENOG410XPQS; LUCA.
GeneTree; ENSGT00910000144011; -.
HOGENOM; HOG000010267; -.
HOVERGEN; HBG073476; -.
InParanoid; Q96MS0; -.
KO; K06755; -.
OMA; YVCQAVS; -.
OrthoDB; EOG091G00CG; -.
PhylomeDB; Q96MS0; -.
TreeFam; TF351053; -.
Reactome; R-HSA-428542; Regulation of commissural axon pathfinding by SLIT and ROBO.
Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
Reactome; R-HSA-9010642; ROBO receptors bind AKAP5.
ChiTaRS; ROBO3; human.
GeneWiki; ROBO3; -.
GenomeRNAi; 64221; -.
PRO; PR:Q96MS0; -.
Proteomes; UP000005640; Chromosome 11.
Bgee; ENSG00000154134; Expressed in 198 organ(s), highest expression level in left ovary.
CleanEx; HS_ROBO3; -.
ExpressionAtlas; Q96MS0; baseline and differential.
Genevisible; Q96MS0; HS.
GO; GO:0030424; C:axon; IEA:InterPro.
GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0007411; P:axon guidance; NAS:UniProtKB.
GO; GO:0016199; P:axon midline choice point recognition; ISS:UniProtKB.
GO; GO:0035385; P:Roundabout signaling pathway; IEA:InterPro.
CDD; cd00063; FN3; 3.
Gene3D; 2.60.40.10; -; 8.
InterPro; IPR003961; FN3_dom.
InterPro; IPR036116; FN3_sf.
InterPro; IPR007110; Ig-like_dom.
InterPro; IPR036179; Ig-like_dom_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR013098; Ig_I-set.
InterPro; IPR003599; Ig_sub.
InterPro; IPR003598; Ig_sub2.
InterPro; IPR032987; Robo3.
PANTHER; PTHR44096:SF3; PTHR44096:SF3; 1.
Pfam; PF00041; fn3; 3.
Pfam; PF07679; I-set; 3.
SMART; SM00060; FN3; 3.
SMART; SM00409; IG; 5.
SMART; SM00408; IGc2; 5.
SUPFAM; SSF48726; SSF48726; 5.
SUPFAM; SSF49265; SSF49265; 2.
PROSITE; PS50853; FN3; 3.
PROSITE; PS50835; IG_LIKE; 5.
1: Evidence at protein level;
Alternative splicing; Chemotaxis; Complete proteome;
Developmental protein; Differentiation; Disease mutation;
Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
Neurogenesis; Phosphoprotein; Polymorphism; Receptor;
Reference proteome; Repeat; Signal; Transmembrane;
Transmembrane helix.
SIGNAL 1 20 {ECO:0000255}.
CHAIN 21 1386 Roundabout homolog 3.
/FTId=PRO_0000031038.
TOPO_DOM 21 891 Extracellular. {ECO:0000255}.
TRANSMEM 892 912 Helical. {ECO:0000255}.
TOPO_DOM 913 1386 Cytoplasmic. {ECO:0000255}.
DOMAIN 64 160 Ig-like C2-type 1.
DOMAIN 166 253 Ig-like C2-type 2.
DOMAIN 258 342 Ig-like C2-type 3.
DOMAIN 347 440 Ig-like C2-type 4.
DOMAIN 450 531 Ig-like C2-type 5.
DOMAIN 558 652 Fibronectin type-III 1.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
DOMAIN 671 766 Fibronectin type-III 2.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
DOMAIN 771 869 Fibronectin type-III 3.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
MOD_RES 1263 1263 Phosphoserine.
{ECO:0000244|PubMed:19690332}.
CARBOHYD 25 25 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 34 34 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 41 41 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 53 53 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 156 156 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 410 410 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 459 459 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 503 503 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 784 784 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 813 813 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 820 820 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 85 143 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 187 236 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 279 326 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 368 424 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 472 521 {ECO:0000255|PROSITE-ProRule:PRU00114}.
VAR_SEQ 1025 1034 AGEELQTFHG -> LTTPLLILTT (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_010650.
VAR_SEQ 1035 1386 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_010651.
VARIANT 5 5 L -> P (in HGPPS1; dbSNP:rs121918275).
{ECO:0000269|PubMed:15105459}.
/FTId=VAR_019119.
VARIANT 66 66 I -> L (in HGPPS1; dbSNP:rs121918276).
{ECO:0000269|PubMed:15105459}.
/FTId=VAR_019120.
VARIANT 319 319 E -> K (in HGPPS1; dbSNP:rs121918274).
{ECO:0000269|PubMed:15105459}.
/FTId=VAR_019073.
VARIANT 361 361 G -> E (in HGPPS1; dbSNP:rs121918270).
{ECO:0000269|PubMed:15105459}.
/FTId=VAR_019121.
VARIANT 416 416 R -> H (in dbSNP:rs3862618).
/FTId=VAR_053642.
VARIANT 423 423 V -> M (in dbSNP:rs4935898).
{ECO:0000269|PubMed:14702039}.
/FTId=VAR_034474.
VARIANT 703 703 R -> P (in HGPPS1; dbSNP:rs121918271).
{ECO:0000269|PubMed:15105459}.
/FTId=VAR_019074.
VARIANT 705 705 S -> P (in HGPPS1; dbSNP:rs121918272).
{ECO:0000269|PubMed:15105459}.
/FTId=VAR_019075.
VARIANT 868 868 P -> L (in dbSNP:rs55706177).
{ECO:0000269|PubMed:14702039}.
/FTId=VAR_062145.
VARIANT 1369 1369 Q -> R (in dbSNP:rs35723495).
/FTId=VAR_034475.
SEQUENCE 1386 AA; 148209 MW; 955A7300A2BDA27F CRC64;
MLRYLLKTLL QMNLFADSLA GDISNSSELL LGFNSSLAAL NHTLLPPGDP SLNGSRVGPE
DAMPRIVEQP PDLLVSRGEP ATLPCRAEGR PRPNIEWYKN GARVATVRED PRAHRLLLPS
GALFFPRIVH GRRARPDEGV YTCVARNYLG AAASRNASLE VAVLRDDFRQ SPGNVVVAVG
EPAVLECVPP RGHPEPSVSW RKDGARLKEE EGRITIRGGK LMMSHTLKSD AGMYVCVASN
MAGERESAAA EVMVLERPSF LRRPVNQVVL ADAPVTFLCE VKGDPPPRLR WRKEDGELPT
GRYEIRSDHS LWIGHVSAED EGTYTCVAEN SVGRAEASGS LSVHVPPQLV TQPQDQMAAP
GESVAFQCET KGNPPPAIFW QKEGSQVLLF PSQSLQPTGR FSVSPRGQLN ITAVQRGDAG
YYVCQAVSVA GSILAKALLE IKGASLDGLP PVILQGPANQ TLVLGSSVWL PCRVTGNPQP
SVRWKKDGQW LQGDDLQFKT MANGTLYIAN VQEMDMGFYS CVAKSSTGEA TWSGWLKMRE
DWGVSPDPPT EPSSPPGAPS QPVVTEITKN SITLTWKPNP QTGAAVTSYV IEAFSPAAGN
TWRTVADGVQ LETHTVSGLQ PNTIYLFLVR AVGAWGLSEP SPVSEPVRTQ DSSPSRPVED
PWRGQQGLAE VAVRLQEPIV LGPRTLQVSW TVDGPVQLVQ GFRVSWRVAG PEGGSWTMLD
LQSPSQQSTV LRGLPPGTQI QIKVQAQGQE GLGAESLSVT RSIPEEAPSG PPQGVAVALG
GDGNSSITVS WEPPLPSQQN GVITEYQIWC LGNESRFHLN RSAAGWARSA MLRGLVPGLL
YRTLVAAATS AGVGVPSAPV LVQLPSPPDL EPGLEVGAGL AVRLARVLRE PAFLAGSGAA
CGALLLGLCA ALYWRRKQRK ELSHYTASFA YTPAVSFPHS EGLSGASSRP PMGLGPAPYS
WLADSWPHPS RSPSAQEPRG SCCPSNPDPD DRYYNEAGIS LYLAQTARGT AAPGEGPVYS
TIDPAGEELQ TFHGGFPQHP SGDLGPWSQY APPEWSQGDS GAKGGKVKLL GKPVQMPSLN
WPEALPPPPP SCELSCLEGP EEELEGSSEP EEWCPPMPER SHLTEPSSSG GCLVTPSRRE
TPSPTPSYGQ QSTATLTPSP PDPPQPPTDM PHLHQMPRRV PLGPSSPLSV SQPMLGIREA
RPAGLGAGPA ASPHLSPSPA PSTASSAPGR TWQGNGEMTP PLQGPRARFR KKPKALPYRR
ENSPGDLPPP PLPPPEEEAS WALELRAAGS MSSLERERSG ERKAVQAVPL AAQRVLHPDE
EAWLPYSRPS FLSRGQGTST CSTAGSNSSR GSSSSRGSRG PGRSRSRSQS RSQSQRPGQK
RREEPR


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