Q96MS0 (ROBO3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Roundabout homolog 3

Alternative name(s):
Roundabout-like protein 3

Gene names

Name:

ROBO3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1386 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.1
Subunit structure	Probably interacts with SLIT2 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Potential.
Involvement in disease	Familial horizontal gaze palsy with progressive scoliosis (HGPPS) [MIM:607313]: Patients show a medulla where motor and sensory projections appear uncrossed. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1
Sequence similarities	Belongs to the immunoglobulin superfamily. ROBO family. Contains 3 fibronectin type-III domains. Contains 5 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Chemotaxis Differentiation Neurogenesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon midline choice point recognition Inferred from sequence or structural similarity. Source: UniProtKB neuron migration Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from electronic annotation. Source: Compara integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96MS0-1)

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: Q96MS0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1025-1034: AGEELQTFHG → LTTPLLILTT
     1035-1386: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 1386	1366	Roundabout homolog 3		PRO_0000031038
Regions
	Topological domain	21 – 891	871	Extracellular Potential
	Transmembrane	892 – 912	21	Helical; Potential
	Topological domain	913 – 1386	474	Cytoplasmic Potential
	Domain	64 – 160	97	Ig-like C2-type 1
	Domain	166 – 253	88	Ig-like C2-type 2
	Domain	258 – 342	85	Ig-like C2-type 3
	Domain	347 – 440	94	Ig-like C2-type 4
	Domain	450 – 531	82	Ig-like C2-type 5
	Domain	555 – 647	93	Fibronectin type-III 1
	Domain	669 – 762	94	Fibronectin type-III 2
	Domain	768 – 863	96	Fibronectin type-III 3
Amino acid modifications
	Modified residue	1263	1	Phosphoserine Ref.3
	Glycosylation	25	1	N-linked (GlcNAc...) Potential
	Glycosylation	34	1	N-linked (GlcNAc...) Potential
	Glycosylation	41	1	N-linked (GlcNAc...) Potential
	Glycosylation	53	1	N-linked (GlcNAc...) Potential
	Glycosylation	156	1	N-linked (GlcNAc...) Potential
	Glycosylation	410	1	N-linked (GlcNAc...) Potential
	Glycosylation	459	1	N-linked (GlcNAc...) Potential
	Glycosylation	503	1	N-linked (GlcNAc...) Potential
	Glycosylation	784	1	N-linked (GlcNAc...) Potential
	Glycosylation	813	1	N-linked (GlcNAc...) Potential
	Glycosylation	820	1	N-linked (GlcNAc...) Potential
	Disulfide bond	85 ↔ 143		Potential
	Disulfide bond	187 ↔ 236		Potential
	Disulfide bond	279 ↔ 326		Potential
	Disulfide bond	368 ↔ 424		Potential
	Disulfide bond	472 ↔ 521		Potential
Natural variations
	Alternative sequence	1025 – 1034	10	AGEELQTFHG → LTTPLLILTT in isoform 2.		VSP_010650
	Alternative sequence	1035 – 1386	352	Missing in isoform 2.		VSP_010651
	Natural variant	5	1	L → P in HGPPS. Ref.1		VAR_019119
	Natural variant	66	1	I → L in HGPPS. Ref.1		VAR_019120
	Natural variant	319	1	E → K in HGPPS. Ref.1		VAR_019073
	Natural variant	361	1	G → E in HGPPS. Ref.1		VAR_019121
	Natural variant	416	1	R → H. Corresponds to variant rs3862618 [ dbSNP | Ensembl ].		VAR_053642
	Natural variant	423	1	V → M. Ref.2 Corresponds to variant rs4935898 [ dbSNP | Ensembl ].		VAR_034474
	Natural variant	703	1	R → P in HGPPS. Ref.1		VAR_019074
	Natural variant	705	1	S → P in HGPPS. Ref.1		VAR_019075
	Natural variant	868	1	P → L. Ref.2 Corresponds to variant rs55706177 [ dbSNP | Ensembl ].		VAR_062145
	Natural variant	1369	1	Q → R. Corresponds to variant rs35723495 [ dbSNP | Ensembl ].		VAR_034475

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 21, 2004. Version 2. Checksum: 955A7300A2BDA27F	FASTA	1,386	148,209
	10 20 30 40 50 60 MLRYLLKTLL QMNLFADSLA GDISNSSELL LGFNSSLAAL NHTLLPPGDP SLNGSRVGPE 70 80 90 100 110 120 DAMPRIVEQP PDLLVSRGEP ATLPCRAEGR PRPNIEWYKN GARVATVRED PRAHRLLLPS 130 140 150 160 170 180 GALFFPRIVH GRRARPDEGV YTCVARNYLG AAASRNASLE VAVLRDDFRQ SPGNVVVAVG 190 200 210 220 230 240 EPAVLECVPP RGHPEPSVSW RKDGARLKEE EGRITIRGGK LMMSHTLKSD AGMYVCVASN 250 260 270 280 290 300 MAGERESAAA EVMVLERPSF LRRPVNQVVL ADAPVTFLCE VKGDPPPRLR WRKEDGELPT 310 320 330 340 350 360 GRYEIRSDHS LWIGHVSAED EGTYTCVAEN SVGRAEASGS LSVHVPPQLV TQPQDQMAAP 370 380 390 400 410 420 GESVAFQCET KGNPPPAIFW QKEGSQVLLF PSQSLQPTGR FSVSPRGQLN ITAVQRGDAG 430 440 450 460 470 480 YYVCQAVSVA GSILAKALLE IKGASLDGLP PVILQGPANQ TLVLGSSVWL PCRVTGNPQP 490 500 510 520 530 540 SVRWKKDGQW LQGDDLQFKT MANGTLYIAN VQEMDMGFYS CVAKSSTGEA TWSGWLKMRE 550 560 570 580 590 600 DWGVSPDPPT EPSSPPGAPS QPVVTEITKN SITLTWKPNP QTGAAVTSYV IEAFSPAAGN 610 620 630 640 650 660 TWRTVADGVQ LETHTVSGLQ PNTIYLFLVR AVGAWGLSEP SPVSEPVRTQ DSSPSRPVED 670 680 690 700 710 720 PWRGQQGLAE VAVRLQEPIV LGPRTLQVSW TVDGPVQLVQ GFRVSWRVAG PEGGSWTMLD 730 740 750 760 770 780 LQSPSQQSTV LRGLPPGTQI QIKVQAQGQE GLGAESLSVT RSIPEEAPSG PPQGVAVALG 790 800 810 820 830 840 GDGNSSITVS WEPPLPSQQN GVITEYQIWC LGNESRFHLN RSAAGWARSA MLRGLVPGLL 850 860 870 880 890 900 YRTLVAAATS AGVGVPSAPV LVQLPSPPDL EPGLEVGAGL AVRLARVLRE PAFLAGSGAA 910 920 930 940 950 960 CGALLLGLCA ALYWRRKQRK ELSHYTASFA YTPAVSFPHS EGLSGASSRP PMGLGPAPYS 970 980 990 1000 1010 1020 WLADSWPHPS RSPSAQEPRG SCCPSNPDPD DRYYNEAGIS LYLAQTARGT AAPGEGPVYS 1030 1040 1050 1060 1070 1080 TIDPAGEELQ TFHGGFPQHP SGDLGPWSQY APPEWSQGDS GAKGGKVKLL GKPVQMPSLN 1090 1100 1110 1120 1130 1140 WPEALPPPPP SCELSCLEGP EEELEGSSEP EEWCPPMPER SHLTEPSSSG GCLVTPSRRE 1150 1160 1170 1180 1190 1200 TPSPTPSYGQ QSTATLTPSP PDPPQPPTDM PHLHQMPRRV PLGPSSPLSV SQPMLGIREA 1210 1220 1230 1240 1250 1260 RPAGLGAGPA ASPHLSPSPA PSTASSAPGR TWQGNGEMTP PLQGPRARFR KKPKALPYRR 1270 1280 1290 1300 1310 1320 ENSPGDLPPP PLPPPEEEAS WALELRAAGS MSSLERERSG ERKAVQAVPL AAQRVLHPDE 1330 1340 1350 1360 1370 1380 EAWLPYSRPS FLSRGQGTST CSTAGSNSSR GSSSSRGSRG PGRSRSRSQS RSQSQRPGQK RREEPR
	Isoform 2 [UniParc]. Checksum: 95EB31C89F0531E5	FASTA	1,034	110,676
	10 20 30 40 50 60 MLRYLLKTLL QMNLFADSLA GDISNSSELL LGFNSSLAAL NHTLLPPGDP SLNGSRVGPE 70 80 90 100 110 120 DAMPRIVEQP PDLLVSRGEP ATLPCRAEGR PRPNIEWYKN GARVATVRED PRAHRLLLPS 130 140 150 160 170 180 GALFFPRIVH GRRARPDEGV YTCVARNYLG AAASRNASLE VAVLRDDFRQ SPGNVVVAVG 190 200 210 220 230 240 EPAVLECVPP RGHPEPSVSW RKDGARLKEE EGRITIRGGK LMMSHTLKSD AGMYVCVASN 250 260 270 280 290 300 MAGERESAAA EVMVLERPSF LRRPVNQVVL ADAPVTFLCE VKGDPPPRLR WRKEDGELPT 310 320 330 340 350 360 GRYEIRSDHS LWIGHVSAED EGTYTCVAEN SVGRAEASGS LSVHVPPQLV TQPQDQMAAP 370 380 390 400 410 420 GESVAFQCET KGNPPPAIFW QKEGSQVLLF PSQSLQPTGR FSVSPRGQLN ITAVQRGDAG 430 440 450 460 470 480 YYVCQAVSVA GSILAKALLE IKGASLDGLP PVILQGPANQ TLVLGSSVWL PCRVTGNPQP 490 500 510 520 530 540 SVRWKKDGQW LQGDDLQFKT MANGTLYIAN VQEMDMGFYS CVAKSSTGEA TWSGWLKMRE 550 560 570 580 590 600 DWGVSPDPPT EPSSPPGAPS QPVVTEITKN SITLTWKPNP QTGAAVTSYV IEAFSPAAGN 610 620 630 640 650 660 TWRTVADGVQ LETHTVSGLQ PNTIYLFLVR AVGAWGLSEP SPVSEPVRTQ DSSPSRPVED 670 680 690 700 710 720 PWRGQQGLAE VAVRLQEPIV LGPRTLQVSW TVDGPVQLVQ GFRVSWRVAG PEGGSWTMLD 730 740 750 760 770 780 LQSPSQQSTV LRGLPPGTQI QIKVQAQGQE GLGAESLSVT RSIPEEAPSG PPQGVAVALG 790 800 810 820 830 840 GDGNSSITVS WEPPLPSQQN GVITEYQIWC LGNESRFHLN RSAAGWARSA MLRGLVPGLL 850 860 870 880 890 900 YRTLVAAATS AGVGVPSAPV LVQLPSPPDL EPGLEVGAGL AVRLARVLRE PAFLAGSGAA 910 920 930 940 950 960 CGALLLGLCA ALYWRRKQRK ELSHYTASFA YTPAVSFPHS EGLSGASSRP PMGLGPAPYS 970 980 990 1000 1010 1020 WLADSWPHPS RSPSAQEPRG SCCPSNPDPD DRYYNEAGIS LYLAQTARGT AAPGEGPVYS 1030 TIDPLTTPLL ILTT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis." 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. Science 304:1509-1513(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS HGPPS PRO-5; LEU-66; LYS-319; GLU-361; PRO-703 AND PRO-705.
[2]	"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] (ISOFORM 2), VARIANTS MET-423 AND LEU-868.
[3]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1263, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY509035 mRNA. Translation: AAS91662.1. AK056544 mRNA. Translation: BAB71212.1.
IPI	IPI00007176. IPI00418275.
RefSeq	NP_071765.2. NM_022370.3.
UniGene	Hs.435621.
3D structure databases
ProteinModelPortal	Q96MS0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96MS0. 1 interaction.
STRING	9606.ENSP00000380903.
PTM databases
PhosphoSite	Q96MS0.
Polymorphism databases
DMDM	49036492.
Proteomic databases
PaxDb	Q96MS0.
PRIDE	Q96MS0.
Protocols and materials databases
DNASU	64221.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000397801; ENSP00000380903; ENSG00000154134.
GeneID	64221.
KEGG	hsa:64221.
UCSC	uc001qbc.3. human.
Organism-specific databases
CTD	64221.
GeneCards	GC11P124735.
HGNC	HGNC:13433. ROBO3.
HPA	HPA011310.
MIM	607313. phenotype. 608630. gene.
neXtProt	NX_Q96MS0.
Orphanet	2744. Horizontal gaze palsy with progressive scoliosis.
PharmGKB	PA134896648.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238978.
HOGENOM	HOG000010267.
HOVERGEN	HBG073476.
InParanoid	Q96MS0.
KO	K06755.
OMA	PQLVTQP.
OrthoDB	EOG41VK24.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	Q96MS0.
Bgee	Q96MS0.
CleanEx	HS_ROBO3.
Genevestigator	Q96MS0.
Family and domain databases
Gene3D	2.60.40.10. 9 hits.
InterPro	IPR003961. Fibronectin_type3. IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003598. Ig_sub2. [Graphical view]
Pfam	PF00041. fn3. 3 hits. PF07679. I-set. 4 hits. [Graphical view]
SMART	SM00060. FN3. 3 hits. SM00408. IGc2. 5 hits. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 3 hits.
PROSITE	PS50853. FN3. 3 hits. PS50835. IG_LIKE. 5 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ROBO3. human.
GenomeRNAi	64221.
NextBio	66147.
SOURCE	Search...

Entry information

Entry name

ROBO3_HUMAN

Accession

Primary (citable) accession number: Q96MS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2004
Last sequence update:	June 21, 2004
Last modified:	May 1, 2013
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.