Q8K1S3 (UNC5B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Netrin receptor UNC5B

Alternative name(s):
Protein unc-5 homolog 2
Protein unc-5 homolog B

Gene names

Name:	Unc5b
Synonyms:	Unc5h2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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 By similarity. 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 By similarity. Ref.5
Subunit structure	Interacts with the cytoplasmic part of DCC. Interacts with GNAI2 via its cytoplasmic part By similarity. Interacts (via death domain) with DAPK1 (via death domain) By similarity. Ref.5
Subcellular location	Membrane; Single-pass type I membrane protein By similarity. Note: Associated with lipid raft.
Tissue specificity	Highly expressed in brain. Expressed in lung during late development. Expressed during early blood vessel formation, in the semicircular canal and in a dorsal to ventral gradient in the retina. Ref.1 Ref.4
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 By similarity. Palmitoylation target the protein to the lipid rafts, and is required for pro-apoptotic activity By similarity.
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 AAH48162.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anterior/posterior axon guidance Inferred from mutant phenotype PubMed 18479186. Source: MGI apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Inferred from electronic annotation. Source: Compara signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytosol Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ppp2r1b	Q7TNP2	2	EBI-4396886,EBI-4396871

Alternative products

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

Isoform 1 (identifier: Q8K1S3-1)

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: Q8K1S3-2)

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

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_0000036072

Regions

Topological domain

27 – 377

351

Extracellular Potential

Transmembrane

378 – 398

21

Helical; Potential

Topological domain

399 – 945

547

Cytoplasmic Potential

Domain

48 – 145

98

Ig-like

Domain

153 – 242

90

Ig-like C2-type

Domain

246 – 300

55

TSP type-1 1

Domain

302 – 354

53

TSP type-1 2

Domain

544 – 688

145

ZU5

Domain

865 – 943

79

Death

Region

689 – 838

150

UPA domain By similarity

Region

707 – 725

19

Interaction with DCC By similarity

Sites

Site

412 – 413

2

Cleavage; by caspase-3 By similarity

Amino acid modifications

Lipidation

403

1

S-palmitoyl cysteine By similarity

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

NQRTL…PKSHP → T in isoform 2.

VSP_011699

Experimental info

Sequence conflict

238

1

T → A in BAB31108. Ref.2

Sequence conflict

394

1

V → E in BAB31108. Ref.2

Sequence conflict

679

1

T → S in BAB31108. Ref.2

Sequence conflict

874

1

N → D in BAB31108. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

945

Helix Strand Turn

Details...

Helix

860 – 871

12

Helix

873 – 875

3

Helix

880 – 886

7

Helix

890 – 892

3

Helix

893 – 897

5

Helix

902 – 913

12

Turn

917 – 919

3

Helix

920 – 929

10

Helix

933 – 941

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 80E896F0F0E06012	FASTA	945	103,739
	10 20 30 40 50 60 MRARSGVRSA LLLALLLCWD PTPSLAGVDS AGQVLPDSYP SAPAEQLPYF LLEPQDAYIV 70 80 90 100 110 120 KNKPVELHCR AFPATQIYFK CNGEWVSQND HVTQESLDEA TGLRVREVQI EVSRQQVEEL 130 140 150 160 170 180 FGLEDYWCQC VAWSSSGTTK SRRAYIRIAY LRKNFDQEPL AKEVPLDHEV LLQCRPPEGV 190 200 210 220 230 240 PVAEVEWLKN EDVIDPAQDT NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT 250 260 270 280 290 300 VIVYVNGGWS SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAF QKTACTTVCP 310 320 330 340 350 360 VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD GLCVLNQRTL 370 380 390 400 410 420 NDPKSHPLET SGDVALYAGL VVAVFVVVAV LMAVGVIVYR RNCRDFDTDI TDSSAALTGG 430 440 450 460 470 480 FHPVNFKTAR PNNPQLLHPS APPDLTASAG IYRGPVYALQ DSADKIPMTN SPLLDPLPSL 490 500 510 520 530 540 KIKVYNSSTI GSGSGLADGA DLLGVLPPGT YPGDFSRDTH FLHLRSASLG SQHLLGLPRD 550 560 570 580 590 600 PSSSVSGTFG CLGGRLSLPG TGVSLLVPNG AIPQGKFYDL YLHINKAEST LPLSEGSQTV 610 620 630 640 650 660 LSPSVTCGPT GLLLCRPVVL TVPHCAEVIA GDWIFQLKTQ AHQGHWEEVV TLDEETLNTP 670 680 690 700 710 720 CYCQLEAKSC HILLDQLGTY VFMGESYSRS AVKRLQLAIF APALCTSLEY SLRVYCLEDT 730 740 750 760 770 780 PVALKEVLEL ERTLGGYLVE EPKPLLFKDS YHNLRLSLHD IPHAHWRSKL LAKYQEIPFY 790 800 810 820 830 840 HVWNGSQRAL HCTFTLERHS LASTEFTCKV CVRQVEGEGQ IFQLHTTLAE TPAGSLDALC 850 860 870 880 890 900 SAPGNAITTQ LGPYAFKIPL SIRQKICSSL DAPNSRGNDW RLLAQKLSMD RYLNYFATKA 910 920 930 940 SPTGVILDLW EARQQDDGDL NSLASALEEM GKSEMLVAMA TDGDC
	Isoform 2 [UniParc]. Checksum: E92DB6288F013C98	FASTA	934	102,452
	10 20 30 40 50 60 MRARSGVRSA LLLALLLCWD PTPSLAGVDS AGQVLPDSYP SAPAEQLPYF LLEPQDAYIV 70 80 90 100 110 120 KNKPVELHCR AFPATQIYFK CNGEWVSQND HVTQESLDEA TGLRVREVQI EVSRQQVEEL 130 140 150 160 170 180 FGLEDYWCQC VAWSSSGTTK SRRAYIRIAY LRKNFDQEPL AKEVPLDHEV LLQCRPPEGV 190 200 210 220 230 240 PVAEVEWLKN EDVIDPAQDT NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT 250 260 270 280 290 300 VIVYVNGGWS SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAF QKTACTTVCP 310 320 330 340 350 360 VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD GLCVLTLETS 370 380 390 400 410 420 GDVALYAGLV VAVFVVVAVL MAVGVIVYRR NCRDFDTDIT DSSAALTGGF HPVNFKTARP 430 440 450 460 470 480 NNPQLLHPSA PPDLTASAGI YRGPVYALQD SADKIPMTNS PLLDPLPSLK IKVYNSSTIG 490 500 510 520 530 540 SGSGLADGAD LLGVLPPGTY PGDFSRDTHF LHLRSASLGS QHLLGLPRDP SSSVSGTFGC 550 560 570 580 590 600 LGGRLSLPGT GVSLLVPNGA IPQGKFYDLY LHINKAESTL PLSEGSQTVL SPSVTCGPTG 610 620 630 640 650 660 LLLCRPVVLT VPHCAEVIAG DWIFQLKTQA HQGHWEEVVT LDEETLNTPC YCQLEAKSCH 670 680 690 700 710 720 ILLDQLGTYV FMGESYSRSA VKRLQLAIFA PALCTSLEYS LRVYCLEDTP VALKEVLELE 730 740 750 760 770 780 RTLGGYLVEE PKPLLFKDSY HNLRLSLHDI PHAHWRSKLL AKYQEIPFYH VWNGSQRALH 790 800 810 820 830 840 CTFTLERHSL ASTEFTCKVC VRQVEGEGQI FQLHTTLAET PAGSLDALCS APGNAITTQL 850 860 870 880 890 900 GPYAFKIPLS IRQKICSSLD APNSRGNDWR LLAQKLSMDR YLNYFATKAS PTGVILDLWE 910 920 930 ARQQDDGDLN SLASALEEMG KSEMLVAMAT DGDC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of three mouse Unc5 genes and their expression patterns at mid-gestation." Engelkamp D. Mech. Dev. 118:191-197(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J and NOD. Tissue: Medulla oblongata.
[3]	"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 2). Strain: C57BL/6. Tissue: Brain.
[4]	"Expression of Netrin-1 and its two receptors DCC and UNC5H2 in the developing mouse lung." Dalvin S., Anselmo M.A., Prodhan P., Komatsuzaki K., Schnitzer J.J., Kinane T.B. Gene Expr. Patterns 3:279-283(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"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.
[6]	"Structure of the UNC5H2 death domain." Handa N., Kukimoto-Niino M., Akasaka R., Murayama K., Terada T., Inoue M., Yabuki T., Aoki M., Seki E., Matsuda T., Nunokawa E., Tanaka A., Hayashizaki Y., Kigawa T., Shirouzu M., Yokoyama S. Acta Crystallogr. D 62:1502-1509(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 854-943.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ487853 mRNA. Translation: CAD32251.1.
AK018177 mRNA. Translation: BAB31108.1.
AK154271 mRNA. Translation: BAE32479.1.
BC048162 mRNA. Translation: AAH48162.1. Different initiation.
BC057560 mRNA. Translation: AAH57560.1.

IPI

IPI00378122.
IPI00471418.

RefSeq

NP_084046.2. NM_029770.2.

UniGene

Mm.290433.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WMG	X-ray	2.10	A/B/C/D/E/F	854-943	[»]

ProteinModelPortal

Q8K1S3.

SMR

Q8K1S3. Positions 46-353, 541-943.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8K1S3. 2 interactions.

PTM databases

PhosphoSite

Q8K1S3.

Proteomic databases

PaxDb

Q8K1S3.

PRIDE

Q8K1S3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000077925; ENSMUSP00000077080; ENSMUSG00000020099.

GeneID

107449.

KEGG

mmu:107449.

UCSC

uc007ffd.1. mouse.
uc007ffe.1. mouse.

Organism-specific databases

CTD

219699.

MGI

MGI:894703. Unc5b.

Phylogenomic databases

eggNOG

NOG293019.

GeneTree

ENSGT00640000091083.

HOGENOM

HOG000060306.

HOVERGEN

HBG056483.

InParanoid

Q8K1S3.

KO

K07521.

OMA

HEVLLQC.

OrthoDB

EOG4ZW598.

Enzyme and pathway databases

Reactome

REACT_100962. Apoptosis.

Gene expression databases

ArrayExpress

Q8K1S3.

Bgee

Q8K1S3.

CleanEx

MM_UNC5B.

Genevestigator

Q8K1S3.

GermOnline

ENSMUSG00000020099. Mus musculus.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.
2.60.40.10. 2 hits.

InterPro

IPR011029. 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]

Pfam

PF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF00791. ZU5. 1 hit.
[Graphical view]

SMART

SM00005. DEATH. 1 hit.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
SM00218. ZU5. 1 hit.
[Graphical view]

SUPFAM

SSF47986. DEATH_like. 1 hit.
SSF82895. TSP1. 2 hits.

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
PS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

UNC5B. mouse.

EvolutionaryTrace

Q8K1S3.

NextBio

358822.

SOURCE

Search...

Entry information

Entry name

UNC5B_MOUSE

Accession

Primary (citable) accession number: Q8K1S3
Secondary accession number(s): Q3U4F2 , Q6PFH0, Q80Y85, Q9D398

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 1, 2002
Last modified:	April 3, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program