Reviewed, UniProtKB/Swiss-Prot O95185 (UNC5C_HUMAN)

Names and origin

Protein names

Recommended name:
    Netrin receptor UNC5C
Alternative name(s):
    Protein unc-5 homolog C
    Unc-5 homolog 3

Gene names

Name:	UNC5C
Synonyms:	UNC5H3

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	931 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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. Also involved in corticospinal tract axon guidances independently of DCC. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand By similarity.
Subunit structure	Interacts with the cytoplasmic part of DCC By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Mainly expressed in brain. Also expressed in kidney. Not expressed in developing or adult lung. Ref.1
Post-translational modification	Phosphorylated on different cytoplasmic tyrosine residues. Phosphorylation of Tyr-568 leads to an interaction with PTPN11 phosphatase, suggesting that its activity is regulated by phosphorylation/dephosphorylation. Tyrosine phosphorylation is netrin-dependent 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.
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 axon guidance Traceable author statement. Source: ProtInc brain development Ref.1 Traceable author statement. Source: ProtInc signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	netrin receptor activity Ref.1 Traceable author statement. Source: ProtInc protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O95185-1)

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: O95185-2)

The sequence of this isoform differs from the canonical sequence as follows:
     370-370: T → SFIYPISTEQRTQNEYGFSS
     579-931: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 40	40	Potential
	Chain	41 – 931	891	Netrin receptor UNC5C		PRO_0000036075
Regions
	Topological domain	41 – 380	340	Extracellular Potential
	Transmembrane	381 – 401	21	Potential
	Topological domain	402 – 931	530	Cytoplasmic Potential
	Domain	62 – 159	98	Ig-like
	Domain	161 – 256	96	Ig-like C2-type
	Domain	260 – 314	55	TSP type-1 1
	Domain	316 – 368	53	TSP type-1 2
	Domain	528 – 634	107	ZU5
	Domain	850 – 929	80	Death
	Region	694 – 712	19	Interaction with DCC By similarity
Sites
	Site	415 – 416	2	Cleavage; by caspase-3 By similarity
Amino acid modifications
	Modified residue	568	1	Phosphotyrosine By similarity
	Glycosylation	236	1	N-linked (GlcNAc...) Potential
	Glycosylation	361	1	N-linked (GlcNAc...) Potential
	Disulfide bond	83 ↔ 142		By similarity
	Disulfide bond	188 ↔ 239		By similarity
	Disulfide bond	272 ↔ 309		By similarity
	Disulfide bond	276 ↔ 313		By similarity
	Disulfide bond	287 ↔ 299		By similarity
Natural variations
	Alternative sequence	370	1	T → SFIYPISTEQRTQNEYGFSS in isoform 2.		VSP_011700
	Alternative sequence	579 – 931	353	Missing in isoform 2.		VSP_011701
	Natural variant	37	1	G → V: dbSNP rs2306715.		VAR_019731
	Natural variant	721	1	M → T: dbSNP rs2289043.		VAR_019732
	Natural variant	841	1	A → T: dbSNP rs34585936.		VAR_055327
Experimental info
	Sequence conflict	219	1	T → I in AAH41156. Ref.3
	Sequence conflict	489	1	T → S in AAC67491. Ref.1
	Sequence conflict	651	1	Q → K in AAC67491. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 98A95995129532A7	FASTA	931	103,146
	10 20 30 40 50 60 MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDDFFHELP ETFPSDPPEP 70 80 90 100 110 120 LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV HQKDHIVDER VDETSGLIVR 130 140 150 160 170 180 EVSIEISRQQ VEELFGPEDY WCQCVAWSSA GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL 190 200 210 220 230 240 EQEVLLQCRP PEGIPVAEVE WLKNEDIIDP VEDRNFYITI DHNLIIKQAR LSDTANYTCV 250 260 270 280 290 300 AKNIVAKRKS TTATVIVYVN GGWSTWTEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE 310 320 330 340 350 360 GQSVQKIACT TLCPVDGRWT PWSKWSTCGT ECTHWRRREC TAPAPKNGGK DCDGLVLQSK 370 380 390 400 410 420 NCTDGLCMQT APDSDDVALY VGIVIAVIVC LAISVVVALF VYRKNHRDFE SDIIDSSALN 430 440 450 460 470 480 GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR GPVYALHDVS DKIPMTNSPI LDPLPNLKIK 490 500 510 520 530 540 VYNTSGAVTP QDDLSEFTSK LSPQMTQSLL ENEALSLKNQ SLARQTDPSC TAFGSFNSLG 550 560 570 580 590 600 GHLIVPNSGV SLLIPAGAIP QGRVYEMYVT VHRKETMRPP MDDSQTLLTP VVSCGPPGAL 610 620 630 640 650 660 LTRPVVLTMH HCADPNTEDW KILLKNQAAQ GQWEDVVVVG EENFTTPCYI QLDAEACHIL 670 680 690 700 710 720 TENLSTYALV GHSTTKAAAK RLKLAIFGPL CCSSLEYSIR VYCLDDTQDA LKEILHLERQ 730 740 750 760 770 780 MGGQLLEEPK ALHFKGSTHN LRLSIHDIAH SLWKSKLLAK YQEIPFYHVW SGSQRNLHCT 790 800 810 820 830 840 FTLERFSLNT VELVCKLCVR QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA NTITTVTGPS 850 860 870 880 890 900 AFSIPLPIRQ KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN 910 920 930 FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y
	Isoform 2. Checksum: 994086225416B9A2	FASTA	597	66,079
	10 20 30 40 50 60 MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDDFFHELP ETFPSDPPEP 70 80 90 100 110 120 LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV HQKDHIVDER VDETSGLIVR 130 140 150 160 170 180 EVSIEISRQQ VEELFGPEDY WCQCVAWSSA GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL 190 200 210 220 230 240 EQEVLLQCRP PEGIPVAEVE WLKNEDIIDP VEDRNFYITI DHNLIIKQAR LSDTANYTCV 250 260 270 280 290 300 AKNIVAKRKS TTATVIVYVN GGWSTWTEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE 310 320 330 340 350 360 GQSVQKIACT TLCPVDGRWT PWSKWSTCGT ECTHWRRREC TAPAPKNGGK DCDGLVLQSK 370 380 390 400 410 420 NCTDGLCMQS FIYPISTEQR TQNEYGFSSA PDSDDVALYV GIVIAVIVCL AISVVVALFV 430 440 450 460 470 480 YRKNHRDFES DIIDSSALNG GFQPVNIKAA RQDLLAVPPD LTSAAAMYRG PVYALHDVSD 490 500 510 520 530 540 KIPMTNSPIL DPLPNLKIKV YNTSGAVTPQ DDLSEFTSKL SPQMTQSLLE NEALSLKNQS 550 560 570 580 590 LARQTDPSCT AFGSFNSLGG HLIVPNSGVS LLIPAGAIPQ GRVYEMYVTV HRKETMR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and mapping of the UNC5C gene to human chromosome 4q21-q23." Ackerman S.L., Knowles B.B. Genomics 52:205-208(1998) [PubMed: 9782087] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT THR-721. Tissue: Brain.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Lung.
[4]	"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	AF055634 mRNA. Translation: AAC67491.1. AC098584 Genomic DNA. No translation available. AC105395 Genomic DNA. No translation available. AC106881 Genomic DNA. No translation available. BC041156 mRNA. Translation: AAH41156.1.
IPI	IPI00293757. IPI00470749.
RefSeq	NP_003719.2.
UniGene	Hs.584831
3D structure databases
HSSP	HSSP built from PDB template 1LSL based on UniProtKB P07996.
ModBase	Search...
Proteomic databases
PRIDE	O95185.
Genome annotation databases
Ensembl	ENSG00000182168. Homo sapiens. [Contig view]
GeneID	8633.
KEGG	hsa:8633.
UCSC	uc003htq.1. human.
Organism-specific databases
GeneCards	GC04M096308.
H-InvDB	HIX0024552.
HGNC	HGNC:12569. UNC5C.
HPA	HPA012086.
MIM	603610. gene.
PharmGKB	PA37206.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95185.
HOVERGEN	O95185.
Gene expression databases
ArrayExpress	O95185.
Bgee	O95185.
CleanEx	HS_UNC5C.
GermOnline	ENSG00000182168. 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	32363.
SOURCE	Search...

Entry information

Entry name

UNC5C_HUMAN

Accession

Primary (citable) accession number: O95185
Secondary accession number(s): Q8IUT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	May 5, 2009
Last modified:	July 7, 2009
This is version 74 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)