Reviewed, UniProtKB/Swiss-Prot Q8IZJ1 (UNC5B_HUMAN)

Names and origin

Protein names

Recommended name:
    Netrin receptor UNC5B
Alternative name(s):
    Protein unc-5 homolog B
    Unc-5 homolog 2
    p53-regulated receptor for death and life protein 1

Gene names

Name:	UNC5B
Synonyms:	P53RDL1, UNC5H2
ORF Names:	UNQ1883/PRO4326

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	945 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 netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Ref.2
Subunit structure	Interacts with the cytoplasmic part of DCC By similarity. Interacts with GNAI2 via its cytoplasmic part.
Subcellular location	Membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Highly expressed in brain. Also expressed at lower level in developing lung, cartilage, kidney and hematopoietic and immune tissues. Ref.1
Induction	By p53/TP53.
Post-translational modification	Phosphorylated on cytoplasmic tyrosine residues By similarity. Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis.
Miscellaneous	Down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers.
Sequence similarities	Belongs to the unc-5 family. Contains 1 death domain. Contains 1 Ig-like (immunoglobulin-like) domain. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 2 TSP type-1 domains. Contains 1 ZU5 domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from electronic annotation. Source: InterPro receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8IZJ1-1)

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: Q8IZJ1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     356-367: NKKTLSDPNSHL → M

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 945	919	Netrin receptor UNC5B		PRO_0000036071
Regions
	Topological domain	27 – 377	351	Extracellular Potential
	Transmembrane	378 – 398	21	Potential
	Topological domain	399 – 945	547	Cytoplasmic Potential
	Domain	48 – 145	98	Ig-like
	Domain	147 – 242	96	Ig-like C2-type
	Domain	246 – 300	55	TSP type-1 1
	Domain	302 – 354	53	TSP type-1 2
	Domain	541 – 647	107	ZU5
	Domain	865 – 943	79	Death
	Region	707 – 725	19	Interaction with DCC By similarity
Sites
	Site	412 – 413	2	Cleavage; by caspase-3
Amino acid modifications
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Glycosylation	347	1	N-linked (GlcNAc...) Potential
	Disulfide bond	69 ↔ 128		By similarity
	Disulfide bond	174 ↔ 225		By similarity
	Disulfide bond	258 ↔ 295		By similarity
	Disulfide bond	262 ↔ 299		By similarity
	Disulfide bond	273 ↔ 285		By similarity
Natural variations
	Alternative sequence	356 – 367	12	NKKTL…PNSHL → M in isoform 2.		VSP_011698
	Natural variant	242	1	I → V: dbSNP rs34957097.		VAR_052472
	Natural variant	516	1	A → T: dbSNP rs10509332.		VAR_019730
Experimental info
	Mutagenesis	412	1	D → N: Abolishes cleavage by caspase-3 and subsequent induction of apoptosis. Ref.2
	Sequence conflict	483	1	K → E in BAC04382. Ref.3
	Sequence conflict	851	1	L → P in BAB14276. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 11, 2004. Version 2. Checksum: 56064E335F323447	FASTA	945	103,638
	10 20 30 40 50 60 MGARSGARGA LLLALLLCWD PRLSQAGTDS GSEVLPDSFP SAPAEPLPYF LQEPQDAYIV 70 80 90 100 110 120 KNKPVELRCR AFPATQIYFK CNGEWVSQND HVTQEGLDEA TGLRVREVQI EVSRQQVEEL 130 140 150 160 170 180 FGLEDYWCQC VAWSSAGTTK SRRAYVRIAY LRKNFDQEPL GKEVPLDHEV LLQCRPPEGV 190 200 210 220 230 240 PVAEVEWLKN EDVIDPTQDT NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT 250 260 270 280 290 300 VIVYVNGGWS SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAF QKTACTTICP 310 320 330 340 350 360 VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD GLCMQNKKTL 370 380 390 400 410 420 SDPNSHLLEA SGDAALYAGL VVAIFVVVAI LMAVGVVVYR RNCRDFDTDI TDSSAALTGG 430 440 450 460 470 480 FHPVNFKTAR PSNPQLLHPS VPPDLTASAG IYRGPVYALQ DSTDKIPMTN SPLLDPLPSL 490 500 510 520 530 540 KVKVYSSSTT GSGPGLADGA DLLGVLPPGT YPSDFARDTH FLHLRSASLG SQQLLGLPRD 550 560 570 580 590 600 PGSSVSGTFG CLGGRLSIPG TGVSLLVPNG AIPQGKFYEM YLLINKAEST LPLSEGTQTV 610 620 630 640 650 660 LSPSVTCGPT GLLLCRPVIL TMPHCAEVSA RDWIFQLKTQ AHQGHWEEVV TLDEETLNTP 670 680 690 700 710 720 CYCQLEPRAC HILLDQLGTY VFTGESYSRS AVKRLQLAVF APALCTSLEY SLRVYCLEDT 730 740 750 760 770 780 PVALKEVLEL ERTLGGYLVE EPKPLMFKDS YHNLRLSLHD LPHAHWRSKL LAKYQEIPFY 790 800 810 820 830 840 HIWSGSQKAL HCTFTLERHS LASTELTCKI CVRQVEGEGQ IFQLHTTLAE TPAGSLDTLC 850 860 870 880 890 900 SAPGSTVTTQ LGPYAFKIPL SIRQKICNSL DAPNSRGNDW RMLAQKLSMD RYLNYFATKA 910 920 930 940 SPTGVILDLW EALQQDDGDL NSLASALEEM GKSEMLVAVA TDGDC
	Isoform 2. Checksum: 225B3F506D52B780	FASTA	934	102,434
	10 20 30 40 50 60 MGARSGARGA LLLALLLCWD PRLSQAGTDS GSEVLPDSFP SAPAEPLPYF LQEPQDAYIV 70 80 90 100 110 120 KNKPVELRCR AFPATQIYFK CNGEWVSQND HVTQEGLDEA TGLRVREVQI EVSRQQVEEL 130 140 150 160 170 180 FGLEDYWCQC VAWSSAGTTK SRRAYVRIAY LRKNFDQEPL GKEVPLDHEV LLQCRPPEGV 190 200 210 220 230 240 PVAEVEWLKN EDVIDPTQDT NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT 250 260 270 280 290 300 VIVYVNGGWS SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAF QKTACTTICP 310 320 330 340 350 360 VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD GLCMQMLEAS 370 380 390 400 410 420 GDAALYAGLV VAIFVVVAIL MAVGVVVYRR NCRDFDTDIT DSSAALTGGF HPVNFKTARP 430 440 450 460 470 480 SNPQLLHPSV PPDLTASAGI YRGPVYALQD STDKIPMTNS PLLDPLPSLK VKVYSSSTTG 490 500 510 520 530 540 SGPGLADGAD LLGVLPPGTY PSDFARDTHF LHLRSASLGS QQLLGLPRDP GSSVSGTFGC 550 560 570 580 590 600 LGGRLSIPGT GVSLLVPNGA IPQGKFYEMY LLINKAESTL PLSEGTQTVL SPSVTCGPTG 610 620 630 640 650 660 LLLCRPVILT MPHCAEVSAR DWIFQLKTQA HQGHWEEVVT LDEETLNTPC YCQLEPRACH 670 680 690 700 710 720 ILLDQLGTYV FTGESYSRSA VKRLQLAVFA PALCTSLEYS LRVYCLEDTP VALKEVLELE 730 740 750 760 770 780 RTLGGYLVEE PKPLMFKDSY HNLRLSLHDL PHAHWRSKLL AKYQEIPFYH IWSGSQKALH 790 800 810 820 830 840 CTFTLERHSL ASTELTCKIC VRQVEGEGQI FQLHTTLAET PAGSLDTLCS APGSTVTTQL 850 860 870 880 890 900 GPYAFKIPLS IRQKICNSLD APNSRGNDWR MLAQKLSMDR YLNYFATKAS PTGVILDLWE 910 920 930 ALQQDDGDLN SLASALEEMG KSEMLVAVAT DGDC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2." Komatsuzaki K., Dalvin S., Kinane T.B. Biochem. Biophys. Res. Commun. 297:898-905(2002) [PubMed: 12359238] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH GNAI2. Tissue: Lung.
[2]	"p53RDL1 regulates of p53-dependent apoptosis." Tanikawa C., Matsuda K., Fukuda S., Nakamura Y., Arakawa H. Nat. Cell Biol. 5:216-223(2003) [PubMed: 12598906] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF ASP-412.
[3]	"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: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 361-945. Tissue: Amygdala and Teratocarcinoma.
[5]	"The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment." Thiebault K., Mazelin L., Pays L., Llambi F., Joly M.-O., Scoazec J.-Y., Saurin J.-C., Romeo G., Mehlen P. Proc. Natl. Acad. Sci. U.S.A. 100:4173-4178(2003) [PubMed: 12655055] [Abstract] Cited for: DOWN-REGULATION IN CANCER.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY126437 mRNA. Translation: AAM95701.1. AB096256 mRNA. Translation: BAC57998.1. AY358351 mRNA. Translation: AAQ88717.1. AK022859 mRNA. Translation: BAB14276.1. Different initiation. AK094595 mRNA. Translation: BAC04382.1. Different initiation.
IPI	IPI00328431. IPI00383609.
RefSeq	NP_734465.2.
UniGene	Hs.522997 Hs.585457
3D structure databases
HSSP	HSSP built from PDB template 1LSL based on UniProtKB P07996.
SMR	Q8IZJ1. Positions 854-943.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8IZJ1.
PTM databases
PhosphoSite	Q8IZJ1.
Proteomic databases
PRIDE	Q8IZJ1.
Genome annotation databases
Ensembl	ENST00000335350; ENSP00000334329; ENSG00000107731; Homo sapiens. [Genome view] ENST00000373192; ENSP00000362288; ENSG00000107731; Homo sapiens. [Genome view]
GeneID	219699.
KEGG	hsa:219699.
UCSC	uc001jro.1. human. uc001jrp.1. human.
Organism-specific databases
CTD	219699.
GeneCards	GC10P072642.
H-InvDB	HIX0008901.
HGNC	HGNC:12568. UNC5B.
HPA	HPA011141.
MIM	607870. gene.
PharmGKB	PA37205.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q8IZJ1.
HOVERGEN	Q8IZJ1.
OMA	YLRKNFD.
Gene expression databases
ArrayExpress	Q8IZJ1.
Bgee	Q8IZJ1.
CleanEx	HS_UNC5B.
Genevestigator	Q8IZJ1.
GermOnline	ENSG00000107731. Homo sapiens.
Family and domain databases
InterPro	IPR000488. Death. IPR011029. DEATH-like. IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003598. Ig_sub2. IPR000884. Thrombospondin_1_rpt. IPR008085. Thrombospondin_1_rpt_sub. IPR000906. ZU5. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit. G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
Pfam	PF00531. Death. 1 hit. PF07679. I-set. 1 hit. PF00090. TSP_1. 2 hits. PF00791. ZU5. 1 hit. [Graphical view]
PRINTS	PR01705. TSP1REPEAT.
SMART	SM00005. DEATH. 1 hit. SM00408. IGc2. 1 hit. SM00209. TSP1. 2 hits. SM00218. ZU5. 1 hit. [Graphical view]
PROSITE	PS50017. DEATH_DOMAIN. False negative. PS50835. IG_LIKE. 1 hit. PS50092. TSP1. 2 hits. PS51145. ZU5. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	90721.
PMAP-CutDB	Q8IZJ1.
SOURCE	Search...

Entry information

Entry name

UNC5B_HUMAN

Accession

Primary (citable) accession number: Q8IZJ1
Secondary accession number(s): Q86SN3, Q8N1Y2, Q9H9F3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	November 3, 2009
This is version 67 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.