Q6ZN44 (UNC5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Netrin receptor UNC5A

Alternative name(s):
Protein unc-5 homolog 1
Protein unc-5 homolog A

Gene names

Name:	UNC5A
Synonyms:	KIAA1976, UNC5H1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	842 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. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand.
Subunit structure	Interacts with the cytoplasmic part of DCC. Interacts with MAGED1. Interacts with PRKCABP, possibly mediating some interaction with PKC By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Note: The interaction with PRKCABP regulates its surface expression and leads to its removal from surface of neurons and growth cones By similarity.
Induction	By p53/TP53. Ref.5 Ref.6
Domain	The ZU5 domain mediates the interaction with MAGED1, which participates in the induction of apoptosis By similarity.
Post-translational modification	Phosphorylated on cytoplasmic tyrosine residues. Phosphorylated by PKC in vitro 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 1 TSP type-1 domain. Contains 1 ZU5 domain.
Sequence caution	The sequence BAB85562.1 differs from that shown. Reason: Intron retention.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Traceable author statement. Source: Reactome axon guidance Traceable author statement. Source: Reactome regulation of apoptotic process Traceable author statement. Source: Reactome
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q6ZN44-1)

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.

Note: No experimental confirmation available.

Isoform 2 (identifier: Q6ZN44-2)

The sequence of this isoform differs from the canonical sequence as follows:
     296-301: TASGPE → SESSLP
     302-842: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q6ZN44-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-97: MAVRPGLWPA...VIERSTDGSS → MAGTSERSLI...PKPETFCGQT

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 842	817	Netrin receptor UNC5A		PRO_0000036068
Regions
	Topological domain	26 – 306	281	Extracellular Potential
	Transmembrane	307 – 327	21	Helical; Potential
	Topological domain	328 – 842	515	Cytoplasmic Potential
	Domain	44 – 141	98	Ig-like
	Domain	155 – 234	80	Ig-like C2-type
	Domain	242 – 294	53	TSP type-1
	Domain	439 – 545	107	ZU5
	Domain	761 – 841	81	Death
	Region	605 – 623	19	Interaction with DCC By similarity
Sites
	Site	340 – 341	2	Cleavage; by caspase-3 By similarity
Amino acid modifications
	Glycosylation	107	1	N-linked (GlcNAc...) Potential
	Glycosylation	218	1	N-linked (GlcNAc...) Potential
	Glycosylation	287	1	N-linked (GlcNAc...) Potential
	Disulfide bond	65 ↔ 124		By similarity
	Disulfide bond	170 ↔ 221		By similarity
Natural variations
	Alternative sequence	1 – 97	97	MAVRP…TDGSS → MAGTSERSLISSISQPKAIE CFEVKKKAFLTHGRYHGSGA TPPKTKDPKPETFCGQT in isoform 3.		VSP_011693
	Alternative sequence	296 – 301	6	TASGPE → SESSLP in isoform 2.		VSP_011694
	Alternative sequence	302 – 842	541	Missing in isoform 2.		VSP_011695
Experimental info
	Sequence conflict	97	1	S → N in BAD18531. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 7B209042977FE524	FASTA	842	92,932
	10 20 30 40 50 60 MAVRPGLWPA LLGIVLAAWL RGSGAQQSAT VANPVPGANP DLLPHFLVEP EDVYIVKNKP 70 80 90 100 110 120 VLLVCKAVPA TQIFFKCNGE WVRQVDHVIE RSTDGSSGLP TMEVRINVSR QQVEKVFGLE 130 140 150 160 170 180 EYWCQCVAWS SSGTTKSQKA YIRIAYLRKN FEQEPLAKEV SLEQGIVLPC RPPEGIPPAE 190 200 210 220 230 240 VEWLRNEDLV DPSLDPNVYI TREHSLVVRQ ARLADTANYT CVAKNIVARR RSASAAVIVY 250 260 270 280 290 300 VDGSWSPWSK WSACGLDCTH WRSRECSDPA PRNGGEECQG TDLDTRNCTS DLCVHTASGP 310 320 330 340 350 360 EDVALYVGLI AVAVCLVLLL LVLILVYCRK KEGLDSDVAD SSILTSGFQP VSIKPSKADN 370 380 390 400 410 420 PHLLTIQPDL STTTTTYQGS LCPRQDGPSP KFQLTNGHLL SPLGGGRHTL HHSSPTSEAE 430 440 450 460 470 480 EFVSRLSTQN YFRSLPRGTS NMTYGTFNFL GGRLMIPNTG ISLLIPPDAI PRGKIYEIYL 490 500 510 520 530 540 TLHKPEDVRL PLAGCQTLLS PIVSCGPPGV LLTRPVILAM DHCGEPSPDS WSLRLKKQSC 550 560 570 580 590 600 EGSWEDVLHL GEEAPSHLYY CQLEASACYV FTEQLGRFAL VGEALSVAAA KRLKLLLFAP 610 620 630 640 650 660 VACTSLEYNI RVYCLHDTHD ALKEVVQLEK QLGGQLIQEP RVLHFKDSYH NLRLSIHDVP 670 680 690 700 710 720 SSLWKSKLLV SYQEIPFYHI WNGTQRYLHC TFTLERVSPS TSDLACKLWV WQVEGDGQSF 730 740 750 760 770 780 SINFNITKDT RFAELLALES EAGVPALVGP SAFKIPFLIR QKIISSLDPP CRRGADWRTL 790 800 810 820 830 840 AQKLHLDSHL SFFASKPSPT AMILNLWEAR HFPNGNLSQL AAAVAGLGQP DAGLFTVSEA EC
	Isoform 2 [UniParc]. Checksum: 255472A1B083799A	FASTA	301	33,342
	10 20 30 40 50 60 MAVRPGLWPA LLGIVLAAWL RGSGAQQSAT VANPVPGANP DLLPHFLVEP EDVYIVKNKP 70 80 90 100 110 120 VLLVCKAVPA TQIFFKCNGE WVRQVDHVIE RSTDGSSGLP TMEVRINVSR QQVEKVFGLE 130 140 150 160 170 180 EYWCQCVAWS SSGTTKSQKA YIRIAYLRKN FEQEPLAKEV SLEQGIVLPC RPPEGIPPAE 190 200 210 220 230 240 VEWLRNEDLV DPSLDPNVYI TREHSLVVRQ ARLADTANYT CVAKNIVARR RSASAAVIVY 250 260 270 280 290 300 VDGSWSPWSK WSACGLDCTH WRSRECSDPA PRNGGEECQG TDLDTRNCTS DLCVHSESSL P
	Isoform 3 [UniParc]. Checksum: 122B6B66DBE9AE29	FASTA	802	88,640
	10 20 30 40 50 60 MAGTSERSLI SSISQPKAIE CFEVKKKAFL THGRYHGSGA TPPKTKDPKP ETFCGQTGLP 70 80 90 100 110 120 TMEVRINVSR QQVEKVFGLE EYWCQCVAWS SSGTTKSQKA YIRIAYLRKN FEQEPLAKEV 130 140 150 160 170 180 SLEQGIVLPC RPPEGIPPAE VEWLRNEDLV DPSLDPNVYI TREHSLVVRQ ARLADTANYT 190 200 210 220 230 240 CVAKNIVARR RSASAAVIVY VDGSWSPWSK WSACGLDCTH WRSRECSDPA PRNGGEECQG 250 260 270 280 290 300 TDLDTRNCTS DLCVHTASGP EDVALYVGLI AVAVCLVLLL LVLILVYCRK KEGLDSDVAD 310 320 330 340 350 360 SSILTSGFQP VSIKPSKADN PHLLTIQPDL STTTTTYQGS LCPRQDGPSP KFQLTNGHLL 370 380 390 400 410 420 SPLGGGRHTL HHSSPTSEAE EFVSRLSTQN YFRSLPRGTS NMTYGTFNFL GGRLMIPNTG 430 440 450 460 470 480 ISLLIPPDAI PRGKIYEIYL TLHKPEDVRL PLAGCQTLLS PIVSCGPPGV LLTRPVILAM 490 500 510 520 530 540 DHCGEPSPDS WSLRLKKQSC EGSWEDVLHL GEEAPSHLYY CQLEASACYV FTEQLGRFAL 550 560 570 580 590 600 VGEALSVAAA KRLKLLLFAP VACTSLEYNI RVYCLHDTHD ALKEVVQLEK QLGGQLIQEP 610 620 630 640 650 660 RVLHFKDSYH NLRLSIHDVP SSLWKSKLLV SYQEIPFYHI WNGTQRYLHC TFTLERVSPS 670 680 690 700 710 720 TSDLACKLWV WQVEGDGQSF SINFNITKDT RFAELLALES EAGVPALVGP SAFKIPFLIR 730 740 750 760 770 780 QKIISSLDPP CRRGADWRTL AQKLHLDSHL SFFASKPSPT AMILNLWEAR HFPNGNLSQL 790 800 AAAVAGLGQP DAGLFTVSEA EC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 2). Tissue: Brain.
[2]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [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 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-404 (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 302-842 (ISOFORMS 1/2/3). Tissue: Brain.
[4]	"Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins." Nagase T., Kikuno R., Ohara O. DNA Res. 8:319-327(2001) [PubMed: 11853319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 624-728. Tissue: Brain.
[5]	"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: INDUCTION.
[6]	"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
EMBL GenBank DDBJ	AK131380 mRNA. Translation: BAD18531.1. AC027318 Genomic DNA. No translation available. AC091897 Genomic DNA. No translation available. AC091902 Genomic DNA. No translation available. BC009333 mRNA. Translation: AAH09333.2. BC033727 mRNA. No translation available. BC157824 mRNA. Translation: AAI57825.1. AB075856 mRNA. Translation: BAB85562.1. Sequence problems.
IPI	IPI00176345. IPI00418573. IPI00470692.
RefSeq	NP_588610.2. NM_133369.2.
UniGene	Hs.33191.
3D structure databases
ProteinModelPortal	Q6ZN44.
SMR	Q6ZN44. Positions 41-321, 439-839.
ModBase	Search...
Protein-protein interaction databases
STRING	Q6ZN44.
PTM databases
PhosphoSite	Q6ZN44.
Polymorphism databases
DMDM	296453000.
Proteomic databases
PRIDE	Q6ZN44.
Protocols and materials databases
DNASU	90249.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000329542; ENSP00000332737; ENSG00000113763.
GeneID	90249.
KEGG	hsa:90249.
UCSC	uc003mex.1. human. uc003mey.3. human. uc010jkg.1. human.
Organism-specific databases
CTD	90249.
GeneCards	GC05P176237.
H-InvDB	HIX0005448.
HGNC	HGNC:12567. UNC5A.
MIM	607869. gene.
neXtProt	NX_Q6ZN44.
PharmGKB	PA37204.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG293019.
GeneTree	ENSGT00640000091083.
HOGENOM	HOG000060306.
HOVERGEN	HBG056483.
InParanoid	Q6ZN44.
KO	K07521.
OMA	LHHSSPT.
OrthoDB	EOG4SJ5D5.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_578. Apoptosis.
Gene expression databases
ArrayExpress	Q6ZN44.
Bgee	Q6ZN44.
CleanEx	HS_UNC5A.
Genevestigator	Q6ZN44.
GermOnline	ENSG00000113763. Homo sapiens.
Family and domain databases
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit. G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
InterPro	IPR000488. Death. IPR011029. DEATH-like. IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003599. Ig_sub. IPR000884. Thrombospondin_1_rpt. IPR000906. ZU5. [Graphical view]
Pfam	PF00531. Death. 1 hit. PF07679. I-set. 1 hit. PF00791. ZU5. 1 hit. [Graphical view]
SMART	SM00005. DEATH. 1 hit. SM00409. IG. 1 hit. SM00209. TSP1. 1 hit. SM00218. ZU5. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit. SSF82895. TSP1. 1 hit.
PROSITE	PS50017. DEATH_DOMAIN. False negative. PS50835. IG_LIKE. 1 hit. PS50092. TSP1. 1 hit. PS51145. ZU5. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	76616.
SOURCE	Search...

Entry information

Entry name

UNC5A_HUMAN

Accession

Primary (citable) accession number: Q6ZN44
Secondary accession number(s): B2RXE6, Q8TF26, Q96GP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	May 18, 2010
Last modified:	May 16, 2012
This is version 90 of the entry and version 3 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.