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Q8IZJ1 (UNC5B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Netrin receptor UNC5B
Alternative name(s):
Protein unc-5 homolog 2
Protein unc-5 homolog B
p53-regulated receptor for death and life protein 1
Gene names
Name:UNC5B
Synonyms:P53RDL1, UNC5H2
ORF Names:UNQ1883/PRO4326
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length945 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity. Ref.2 Ref.8

Subunit structure

Interacts with the cytoplasmic part of DCC By similarity. Interacts with GNAI2 via its cytoplasmic part. Interacts (via death domain) with DAPK1 (via death domain). Ref.1 Ref.8 Ref.9

Subcellular location

Membrane; Single-pass type I membrane protein. Note: Associated with lipid raft. Ref.9

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. Ref.7

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.

Palmitoylation target the protein to the lipid rafts, and is required for pro-apoptotic activity. Ref.9

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.

Sequence caution

The sequence BAB14276.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAC04382.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Agap2Q8CGU49EBI-4409075,EBI-4409108From a different organism.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 945919Netrin receptor UNC5B
PRO_0000036071

Regions

Topological domain27 – 377351Extracellular Potential
Transmembrane378 – 39821Helical; Potential
Topological domain399 – 945547Cytoplasmic Potential
Domain48 – 14598Ig-like
Domain147 – 24296Ig-like C2-type
Domain246 – 30055TSP type-1 1
Domain302 – 35453TSP type-1 2
Domain544 – 688145ZU5
Domain865 – 94379Death
Region689 – 838150UPA domain By similarity
Region707 – 72519Interaction with DCC By similarity

Sites

Site412 – 4132Cleavage; by caspase-3

Amino acid modifications

Lipidation4031S-palmitoyl cysteine Ref.9
Glycosylation2221N-linked (GlcNAc...) Potential
Glycosylation3471N-linked (GlcNAc...) Potential
Disulfide bond69 ↔ 128 By similarity
Disulfide bond174 ↔ 225 By similarity
Disulfide bond258 ↔ 295 By similarity
Disulfide bond262 ↔ 299 By similarity
Disulfide bond273 ↔ 285 By similarity

Natural variations

Alternative sequence356 – 36712NKKTL…PNSHL → M in isoform 2.
VSP_011698
Natural variant2421I → V.
Corresponds to variant rs34957097 [ dbSNP | Ensembl ].
VAR_052472
Natural variant5161A → T.
Corresponds to variant rs10509332 [ dbSNP | Ensembl ].
VAR_019730

Experimental info

Mutagenesis4121D → N: Abolishes cleavage by caspase-3 and subsequent induction of apoptosis. Ref.2
Sequence conflict4831K → E in BAC04382. Ref.3
Sequence conflict8511L → P in BAB14276. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 11, 2004. Version 2.
Checksum: 56064E335F323447

FASTA945103,638
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 225B3F506D52B780
Show »

FASTA934102,434

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] (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. expand/collapse author list , 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].
Tissue: Amygdala, Teratocarcinoma and Testis.
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] [Europe PMC] [Abstract]
Cited for: DOWN-REGULATION IN CANCER.
[8]"The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase."
Llambi F., Lourenco F.C., Gozuacik D., Guix C., Pays L., Del Rio G., Kimchi A., Mehlen P.
EMBO J. 24:1192-1201(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DAPK1.
[9]"Lipid raft localization and palmitoylation: identification of two requirements for cell death induction by the tumor suppressors UNC5H."
Maisse C., Rossin A., Cahuzac N., Paradisi A., Klein C., Haillot M.L., Herincs Z., Mehlen P., Hueber A.O.
Exp. Cell Res. 314:2544-2552(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION AT CYS-403, SUBCELLULAR LOCATION, INTERACTION WITH DAPK1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AK128132 mRNA. Translation: BAG54634.1.
AL359384, AL359832 Genomic DNA. Translation: CAI16089.1.
AL359384, AL359832 Genomic DNA. Translation: CAI16090.1.
AL359832, AL359384 Genomic DNA. Translation: CAI16737.1.
AL359832, AL359384 Genomic DNA. Translation: CAI16738.1.
CH471083 Genomic DNA. Translation: EAW54420.1.
CH471083 Genomic DNA. Translation: EAW54421.1.
CCDSCCDS58083.1. [Q8IZJ1-2]
CCDS7309.1. [Q8IZJ1-1]
RefSeqNP_001231818.1. NM_001244889.1. [Q8IZJ1-2]
NP_734465.2. NM_170744.4. [Q8IZJ1-1]
UniGeneHs.522997.

3D structure databases

ProteinModelPortalQ8IZJ1.
SMRQ8IZJ1. Positions 48-353, 541-943.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128567. 1 interaction.
DIPDIP-46275N.
IntActQ8IZJ1. 2 interactions.
STRING9606.ENSP00000334329.

PTM databases

PhosphoSiteQ8IZJ1.

Polymorphism databases

DMDM54036589.

Proteomic databases

MaxQBQ8IZJ1.
PaxDbQ8IZJ1.
PRIDEQ8IZJ1.

Protocols and materials databases

DNASU219699.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335350; ENSP00000334329; ENSG00000107731. [Q8IZJ1-1]
ENST00000373192; ENSP00000362288; ENSG00000107731. [Q8IZJ1-2]
GeneID219699.
KEGGhsa:219699.
UCSCuc001jro.3. human. [Q8IZJ1-1]
uc001jrp.3. human. [Q8IZJ1-2]

Organism-specific databases

CTD219699.
GeneCardsGC10P072972.
HGNCHGNC:12568. UNC5B.
HPAHPA011141.
MIM607870. gene.
neXtProtNX_Q8IZJ1.
PharmGKBPA37205.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG293019.
HOGENOMHOG000060306.
HOVERGENHBG056483.
InParanoidQ8IZJ1.
KOK07521.
OMAHEVLLQC.
OrthoDBEOG7BGHJX.
PhylomeDBQ8IZJ1.
TreeFamTF316767.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_578. Apoptosis.

Gene expression databases

BgeeQ8IZJ1.
CleanExHS_UNC5B.
GenevestigatorQ8IZJ1.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
2.60.40.10. 2 hits.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR000884. Thrombospondin_1_rpt.
IPR000906. ZU5.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTSM00005. DEATH. 1 hit.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
SM00218. ZU5. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF82895. SSF82895. 2 hits.
PROSITEPS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUNC5B. human.
GenomeRNAi219699.
NextBio90721.
PMAP-CutDBQ8IZJ1.
PROQ8IZJ1.
SOURCESearch...

Entry information

Entry nameUNC5B_HUMAN
AccessionPrimary (citable) accession number: Q8IZJ1
Secondary accession number(s): Q5T3R9 expand/collapse secondary AC list , Q5T3S0, Q86SN3, Q8N1Y2, Q9H9F3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: July 9, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM