Q8WZ75 (ROBO4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Roundabout homolog 4

Alternative name(s):
Magic roundabout

Gene names

Name:	ROBO4
ORF Names:	UNQ421/PRO3674

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	1007 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	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.
Subunit structure	Interacts with SLIT2 and ENAH By similarity.
Tissue specificity	Specifically expressed in endothelial cells. Expressed at sites of angiogenesis in different tumor types. Ref.1
Sequence similarities	Belongs to the immunoglobulin superfamily. ROBO family. Contains 2 fibronectin type-III domains. Contains 2 Ig-like C2-type (immunoglobulin-like) domains.
Sequence caution	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. The sequence BAB55411.1 differs from that shown. Reason: Frameshift at position 706.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from genetic interaction PubMed 15849270. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell migration Inferred from electronic annotation. Source: Compara regulation of cell migration Non-traceable author statement PubMed 15894287. Source: UniProtKB
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Traceable author statement PubMed 14527427. Source: UniProtKB
Molecular_function	receptor activity Traceable author statement PubMed 14527427. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WZ75-1)

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: Q8WZ75-2)

The sequence of this isoform differs from the canonical sequence as follows:
     932-933: DA → GM
     934-1007: Missing.

Isoform 3 (identifier: Q8WZ75-3)

The sequence of this isoform differs from the canonical sequence as follows:
     24-133: Missing.
     813-1007: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 1007	980	Roundabout homolog 4		PRO_0000031040
Regions
	Domain	32 – 131	100	Ig-like C2-type 1
	Domain	137 – 224	88	Ig-like C2-type 2
	Domain	252 – 340	89	Fibronectin type-III 1
	Domain	347 – 438	92	Fibronectin type-III 2
	Compositional bias	715 – 784	70	Pro/Ser-rich
Amino acid modifications
	Glycosylation	246	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	360	1	N-linked (GlcNAc...) Potential
	Glycosylation	389	1	N-linked (GlcNAc...) Potential
	Glycosylation	396	1	N-linked (GlcNAc...) Potential
	Glycosylation	680	1	N-linked (GlcNAc...) Potential
	Disulfide bond	53 ↔ 114		Potential
	Disulfide bond	158 ↔ 207		Potential
Natural variations
	Alternative sequence	24 – 133	110	Missing in isoform 3.		VSP_010654
	Alternative sequence	813 – 1007	195	Missing in isoform 3.		VSP_010657
	Alternative sequence	932 – 933	2	DA → GM in isoform 2.		VSP_010658
	Alternative sequence	934 – 1007	74	Missing in isoform 2.		VSP_010659
	Natural variant	54	1	Q → R. Corresponds to variant rs59648931 [ dbSNP | Ensembl ].		VAR_062146
	Natural variant	103	1	Q → P. Corresponds to variant rs4995424 [ dbSNP | Ensembl ].		VAR_053643
	Natural variant	669	1	R → Q. Corresponds to variant rs4408324 [ dbSNP | Ensembl ].		VAR_053644
Experimental info
	Sequence conflict	175	1	G → E in BAB55411. Ref.3
	Sequence conflict	498	1	H → L in BAA91382. Ref.3
	Sequence conflict	652	1	Q → P in BAB55411. Ref.3
	Sequence conflict	662	1	G → D in BAB84989. Ref.3
	Sequence conflict	860	1	P → L in BAB15082. Ref.3
	Sequence conflict	864	1	L → F in BAB15082. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: E43F246C59BE1415	FASTA	1,007	107,457
	10 20 30 40 50 60 MGSGGDSLLG GRGSLPLLLL LIMGGMAQDS PPQILVHPQD QLFQGPGPAR MSCQASGQPP 70 80 90 100 110 120 PTIRWLLNGQ PLSMVPPDPH HLLPDGTLLL LQPPARGHAH DGQALSTDLG VYTCEASNRL 130 140 150 160 170 180 GTAVSRGARL SVAVLREDFQ IQPRDMVAVV GEQFTLECGP PWGHPEPTVS WWKDGKPLAL 190 200 210 220 230 240 QPGRHTVSGG SLLMARAEKS DEGTYMCVAT NSAGHRESRA ARVSIQEPQD YTEPVELLAV 250 260 270 280 290 300 RIQLENVTLL NPDPAEGPKP RPAVWLSWKV SGPAAPAQSY TALFRTQTAP GGQGAPWAEE 310 320 330 340 350 360 LLAGWQSAEL GGLHWGQDYE FKVRPSSGRA RGPDSNVLLL RLPEKVPSAP PQEVTLKPGN 370 380 390 400 410 420 GTVFVSWVPP PAENHNGIIR GYQVWSLGNT SLPPANWTVV GEQTQLEIAT HMPGSYCVQV 430 440 450 460 470 480 AAVTGAGAGE PSRPVCLLLE QAMERATQEP SEHGPWTLEQ LRATLKRPEV IATCGVALWL 490 500 510 520 530 540 LLLGTAVCIH RRRRARVHLG PGLYRYTSED AILKHRMDHS DSQWLADTWR STSGSRDLSS 550 560 570 580 590 600 SSSLSSRLGA DARDPLDCRR SLLSWDSRSP GVPLLPDTST FYGSLIAELP SSTPARPSPQ 610 620 630 640 650 660 VPAVRRLPPQ LAQLSSPCSS SDSLCSRRGL SSPRLSLAPA EAWKAKKKQE LQHANSSPLL 670 680 690 700 710 720 RGSHSLELRA CELGNRGSKN LSQSPGAVPQ ALVAWRALGP KLLSSSNELV TRHLPPAPLF 730 740 750 760 770 780 PHETPPTQSQ QTQPPVAPQA PSSILLPAAP IPILSPCSPP SPQASSLSGP SPASSRLSSS 790 800 810 820 830 840 SLSSLGEDQD SVLTPEEVAL CLELSEGEET PRNSVSPMPR APSPPTTYGY ISVPTASEFT 850 860 870 880 890 900 DMGRTGGGVG PKGGVLLCPP RPCLTPTPSE GSLANGWGSA SEDNAASARA SLVSSSDGSF 910 920 930 940 950 960 LADAHFARAL AVAVDSFGFG LEPREADCVF IDASSPPSPR DEIFLTPNLS LPLWEWRPDW 970 980 990 1000 LEDMEVSHTQ RLGRGMPPWP PDSQISSQRS QLHCRMPKAG ASPVDYS
	Isoform 2 [UniParc]. Checksum: 1939F45D34AB81FA	FASTA	933	98,994
	10 20 30 40 50 60 MGSGGDSLLG GRGSLPLLLL LIMGGMAQDS PPQILVHPQD QLFQGPGPAR MSCQASGQPP 70 80 90 100 110 120 PTIRWLLNGQ PLSMVPPDPH HLLPDGTLLL LQPPARGHAH DGQALSTDLG VYTCEASNRL 130 140 150 160 170 180 GTAVSRGARL SVAVLREDFQ IQPRDMVAVV GEQFTLECGP PWGHPEPTVS WWKDGKPLAL 190 200 210 220 230 240 QPGRHTVSGG SLLMARAEKS DEGTYMCVAT NSAGHRESRA ARVSIQEPQD YTEPVELLAV 250 260 270 280 290 300 RIQLENVTLL NPDPAEGPKP RPAVWLSWKV SGPAAPAQSY TALFRTQTAP GGQGAPWAEE 310 320 330 340 350 360 LLAGWQSAEL GGLHWGQDYE FKVRPSSGRA RGPDSNVLLL RLPEKVPSAP PQEVTLKPGN 370 380 390 400 410 420 GTVFVSWVPP PAENHNGIIR GYQVWSLGNT SLPPANWTVV GEQTQLEIAT HMPGSYCVQV 430 440 450 460 470 480 AAVTGAGAGE PSRPVCLLLE QAMERATQEP SEHGPWTLEQ LRATLKRPEV IATCGVALWL 490 500 510 520 530 540 LLLGTAVCIH RRRRARVHLG PGLYRYTSED AILKHRMDHS DSQWLADTWR STSGSRDLSS 550 560 570 580 590 600 SSSLSSRLGA DARDPLDCRR SLLSWDSRSP GVPLLPDTST FYGSLIAELP SSTPARPSPQ 610 620 630 640 650 660 VPAVRRLPPQ LAQLSSPCSS SDSLCSRRGL SSPRLSLAPA EAWKAKKKQE LQHANSSPLL 670 680 690 700 710 720 RGSHSLELRA CELGNRGSKN LSQSPGAVPQ ALVAWRALGP KLLSSSNELV TRHLPPAPLF 730 740 750 760 770 780 PHETPPTQSQ QTQPPVAPQA PSSILLPAAP IPILSPCSPP SPQASSLSGP SPASSRLSSS 790 800 810 820 830 840 SLSSLGEDQD SVLTPEEVAL CLELSEGEET PRNSVSPMPR APSPPTTYGY ISVPTASEFT 850 860 870 880 890 900 DMGRTGGGVG PKGGVLLCPP RPCLTPTPSE GSLANGWGSA SEDNAASARA SLVSSSDGSF 910 920 930 LADAHFARAL AVAVDSFGFG LEPREADCVF IGM
	Isoform 3 [UniParc]. Checksum: 3988CDE4BF9FEE9B	FASTA	702	75,282
	10 20 30 40 50 60 MGSGGDSLLG GRGSLPLLLL LIMVLREDFQ IQPRDMVAVV GEQFTLECGP PWGHPEPTVS 70 80 90 100 110 120 WWKDGKPLAL QPGRHTVSGG SLLMARAEKS DEGTYMCVAT NSAGHRESRA ARVSIQEPQD 130 140 150 160 170 180 YTEPVELLAV RIQLENVTLL NPDPAEGPKP RPAVWLSWKV SGPAAPAQSY TALFRTQTAP 190 200 210 220 230 240 GGQGAPWAEE LLAGWQSAEL GGLHWGQDYE FKVRPSSGRA RGPDSNVLLL RLPEKVPSAP 250 260 270 280 290 300 PQEVTLKPGN GTVFVSWVPP PAENHNGIIR GYQVWSLGNT SLPPANWTVV GEQTQLEIAT 310 320 330 340 350 360 HMPGSYCVQV AAVTGAGAGE PSRPVCLLLE QAMERATQEP SEHGPWTLEQ LRATLKRPEV 370 380 390 400 410 420 IATCGVALWL LLLGTAVCIH RRRRARVHLG PGLYRYTSED AILKHRMDHS DSQWLADTWR 430 440 450 460 470 480 STSGSRDLSS SSSLSSRLGA DARDPLDCRR SLLSWDSRSP GVPLLPDTST FYGSLIAELP 490 500 510 520 530 540 SSTPARPSPQ VPAVRRLPPQ LAQLSSPCSS SDSLCSRRGL SSPRLSLAPA EAWKAKKKQE 550 560 570 580 590 600 LQHANSSPLL RGSHSLELRA CELGNRGSKN LSQSPGAVPQ ALVAWRALGP KLLSSSNELV 610 620 630 640 650 660 TRHLPPAPLF PHETPPTQSQ QTQPPVAPQA PSSILLPAAP IPILSPCSPP SPQASSLSGP 670 680 690 700 SPASSRLSSS SLSSLGEDQD SVLTPEEVAL CLELSEGEET PR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] 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, MASS SPECTROMETRY. Tissue: Plasma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00103871. IPI00418144. IPI00418145.
RefSeq	NP_061928.4. NM_019055.5.
UniGene	Hs.524121.
3D structure databases
ProteinModelPortal	Q8WZ75.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WZ75. 5 interactions.
STRING	9606.ENSP00000304945.
Protein family/group databases
MEROPS	I43.001.
PTM databases
PhosphoSite	Q8WZ75.
Polymorphism databases
DMDM	49036490.
Proteomic databases
PaxDb	Q8WZ75.
PRIDE	Q8WZ75.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000306534; ENSP00000304945; ENSG00000154133.
GeneID	54538.
KEGG	hsa:54538.
UCSC	uc001qbg.3. human. uc001qbh.2. human. uc001qbi.3. human.
Organism-specific databases
CTD	54538.
GeneCards	GC11M124753.
HGNC	HGNC:17985. ROBO4.
MIM	607528. gene.
neXtProt	NX_Q8WZ75.
PharmGKB	PA34622.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG325715.
HOVERGEN	HBG061836.
InParanoid	Q8WZ75.
KO	K06784.
OMA	WGQDYEF.
OrthoDB	EOG4MW85Q.
PhylomeDB	Q8WZ75.
Gene expression databases
ArrayExpress	Q8WZ75.
Bgee	Q8WZ75.
CleanEx	HS_ROBO4.
Genevestigator	Q8WZ75.
GermOnline	ENSG00000154133. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 4 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. 1 hit. PF07679. I-set. 2 hits. [Graphical view]
SMART	SM00060. FN3. 2 hits. SM00408. IGc2. 2 hits. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits.
PROSITE	PS50853. FN3. 2 hits. PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	54538.
NextBio	56970.
SOURCE	Search...

Entry information

Entry name

ROBO4_HUMAN

Accession

Primary (citable) accession number: Q8WZ75
Secondary accession number(s): A8K154 , Q14DU7, Q8TEG1, Q96JV6, Q9H718, Q9NWJ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2004
Last sequence update:	March 1, 2002
Last modified:	May 29, 2013
This is version 98 of the entry and version 1 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.