Reviewed, UniProtKB/Swiss-Prot Q9HB63 (NET4_HUMAN)

Names and origin

Protein names

Recommended name:
    Netrin-4
Alternative name(s):
    Beta-netrin
    Hepar-derived netrin-like protein

Gene names

Name:

NTN4

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	628 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	May play an important role in neural, kidney and vascular development. Promotes neurite elongation from olfactory bulb explants. Ref.1
Subunit structure	May form a homodimer.
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane. Note: Major component. Ref.1
Tissue specificity	Expressed in kidney, spleen, mammary gland, aorta, heart, ovary, prostate and fetal spleen. Ref.1
Sequence similarities	Contains 3 laminin EGF-like domains. Contains 1 laminin N-terminal domain. Contains 1 NTR domain.

Ontologies

Keywords
Cellular component	Basement membrane Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Laminin EGF-like domain Repeat Signal
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Cellular component	basement membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9HB63-1)

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: Q9HB63-2)

The sequence of this isoform differs from the canonical sequence as follows:
     504-526: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9HB63-3)

Also known as: Hetrin;

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 628	610	Netrin-4		PRO_0000042116
Regions
	Domain	30 – 261	232	Laminin N-terminal
	Domain	262 – 331	70	Laminin EGF-like 1
	Domain	332 – 394	63	Laminin EGF-like 2
	Domain	395 – 448	54	Laminin EGF-like 3
	Domain	506 – 627	122	NTR
Amino acid modifications
	Glycosylation	56	1	N-linked (GlcNAc...) Potential
	Glycosylation	163	1	N-linked (GlcNAc...) Potential
	Glycosylation	353	1	N-linked (GlcNAc...) Potential
	Glycosylation	483	1	N-linked (GlcNAc...) Potential
	Disulfide bond	262 ↔ 271		By similarity
	Disulfide bond	264 ↔ 293		By similarity
	Disulfide bond	295 ↔ 304		By similarity
	Disulfide bond	307 ↔ 329		By similarity
	Disulfide bond	332 ↔ 341		By similarity
	Disulfide bond	334 ↔ 359		By similarity
	Disulfide bond	362 ↔ 371		By similarity
	Disulfide bond	374 ↔ 392		By similarity
	Disulfide bond	395 ↔ 413		By similarity
	Disulfide bond	397 ↔ 420		By similarity
	Disulfide bond	422 ↔ 431		By similarity
	Disulfide bond	434 ↔ 446		By similarity
	Disulfide bond	506 ↔ 576		By similarity
	Disulfide bond	520 ↔ 627		By similarity
Natural variations
	Alternative sequence	1 – 37	37	Missing in isoform 3.		VSP_015745
	Alternative sequence	504 – 526	23	Missing in isoform 2.		VSP_015746
	Natural variant	205	1	Y → H: dbSNP rs17288108.		VAR_023548
Experimental info
	Sequence conflict	68	1	T → K in AAG30822. Ref.1
	Sequence conflict	161	1	A → G in AAF69670. Ref.3
	Sequence conflict	222	1	T → I in AAP92113. Ref.4
	Sequence conflict	331	1	T → A Ref.1
	Sequence conflict	331	1	T → A Ref.4
	Sequence conflict	462	1	C → R in AAP92113. Ref.4
	Sequence conflict	472	1	Y → C in AAG30822. Ref.1
	Sequence conflict	472	1	Y → H in AAP92113. Ref.4
	Sequence conflict	545	1	N → S in AAP92113. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: 275613B63A39B267	FASTA	628	70,071
	10 20 30 40 50 60 MGSCARLLLL WGCTVVAAGL SGVAGVSSRC EKACNPRMGN LALGRKLWAD TTCGQNATEL 70 80 90 100 110 120 YCFYSENTDL TCRQPKCDKC NAAYPHLAHL PSAMADSSFR FPRTWWQSAE DVHREKIQLD 130 140 150 160 170 180 LEAEFYFTHL IVMFKSPRPA AMVLDRSQDF GKTWKPYKYF ATNCSATFGL EDDVVKKGAI 190 200 210 220 230 240 CTSKYSSPFP CTGGEVIFKA LSPPYDTENP YSAKVQEQLK ITNLRVQLLK RQSCPCQRND 250 260 270 280 290 300 LNEEPQHFTH YAIYDFIVKG SCFCNGHADQ CIPVHGFRPV KAPGTFHMVH GKCMCKHNTA 310 320 330 340 350 360 GSHCQHCAPL YNDRPWEAAD GKTGAPNECR TCKCNGHADT CHFDVNVWEA SGNRSGGVCD 370 380 390 400 410 420 DCQHNTEGQY CQRCKPGFYR DLRRPFSAPD ACKPCSCHPV GSAVLPANSV TFCDPSNGDC 430 440 450 460 470 480 PCKPGVAGRR CDRCMVGYWG FGDYGCRPCD CAGSCDPITG DCISSHTDID WYHEVPDFRP 490 500 510 520 530 540 VHNKSEPAWE WEDAQGFSAL LHSGKCECKE QTLGNAKAFC GMKYSYVLKI KILSAHDKGT 550 560 570 580 590 600 HVEVNVKIKK VLKSTKLKIF RGKRTLYPES WTDRGCTCPI LNPGLEYLVA GHEDIRTGKL 610 620 IVNMKSFVQH WKPSLGRKVM DILKRECK
	Isoform 2. Checksum: D9FB51CC6553CF5C	FASTA	605	67,529
	10 20 30 40 50 60 MGSCARLLLL WGCTVVAAGL SGVAGVSSRC EKACNPRMGN LALGRKLWAD TTCGQNATEL 70 80 90 100 110 120 YCFYSENTDL TCRQPKCDKC NAAYPHLAHL PSAMADSSFR FPRTWWQSAE DVHREKIQLD 130 140 150 160 170 180 LEAEFYFTHL IVMFKSPRPA AMVLDRSQDF GKTWKPYKYF ATNCSATFGL EDDVVKKGAI 190 200 210 220 230 240 CTSKYSSPFP CTGGEVIFKA LSPPYDTENP YSAKVQEQLK ITNLRVQLLK RQSCPCQRND 250 260 270 280 290 300 LNEEPQHFTH YAIYDFIVKG SCFCNGHADQ CIPVHGFRPV KAPGTFHMVH GKCMCKHNTA 310 320 330 340 350 360 GSHCQHCAPL YNDRPWEAAD GKTGAPNECR TCKCNGHADT CHFDVNVWEA SGNRSGGVCD 370 380 390 400 410 420 DCQHNTEGQY CQRCKPGFYR DLRRPFSAPD ACKPCSCHPV GSAVLPANSV TFCDPSNGDC 430 440 450 460 470 480 PCKPGVAGRR CDRCMVGYWG FGDYGCRPCD CAGSCDPITG DCISSHTDID WYHEVPDFRP 490 500 510 520 530 540 VHNKSEPAWE WEDAQGFSAL LHSVLKIKIL SAHDKGTHVE VNVKIKKVLK STKLKIFRGK 550 560 570 580 590 600 RTLYPESWTD RGCTCPILNP GLEYLVAGHE DIRTGKLIVN MKSFVQHWKP SLGRKVMDIL KRECK
	Isoform 3 (Hetrin). Checksum: 912F3BA3726722A1	FASTA	591	66,352
	10 20 30 40 50 60 MGNLALGRKL WADTTCGQNA TELYCFYSEN TDLTCRQPKC DKCNAAYPHL AHLPSAMADS 70 80 90 100 110 120 SFRFPRTWWQ SAEDVHREKI QLDLEAEFYF THLIVMFKSP RPAAMVLDRS QDFGKTWKPY 130 140 150 160 170 180 KYFATNCSAT FGLEDDVVKK GAICTSKYSS PFPCTGGEVI FKALSPPYDT ENPYSAKVQE 190 200 210 220 230 240 QLKITNLRVQ LLKRQSCPCQ RNDLNEEPQH FTHYAIYDFI VKGSCFCNGH ADQCIPVHGF 250 260 270 280 290 300 RPVKAPGTFH MVHGKCMCKH NTAGSHCQHC APLYNDRPWE AADGKTGAPN ECRTCKCNGH 310 320 330 340 350 360 ADTCHFDVNV WEASGNRSGG VCDDCQHNTE GQYCQRCKPG FYRDLRRPFS APDACKPCSC 370 380 390 400 410 420 HPVGSAVLPA NSVTFCDPSN GDCPCKPGVA GRRCDRCMVG YWGFGDYGCR PCDCAGSCDP 430 440 450 460 470 480 ITGDCISSHT DIDWYHEVPD FRPVHNKSEP AWEWEDAQGF SALLHSGKCE CKEQTLGNAK 490 500 510 520 530 540 AFCGMKYSYV LKIKILSAHD KGTHVEVNVK IKKVLKSTKL KIFRGKRTLY PESWTDRGCT 550 560 570 580 590 CPILNPGLEY LVAGHEDIRT GKLIVNMKSF VQHWKPSLGR KVMDILKREC K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel member of the netrin family, beta-netrin, shares homology with the beta chain of laminin. Identification, expression, and functional characterization." Koch M., Murrell J.R., Hunter D.D., Olson P.F., Jin W., Keene D.R., Brunken W.J., Burgeson R.E. J. Cell Biol. 151:221-234(2000) [PubMed: 11038171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Identification of a novel member of the netrin family, which is induced during in vitro mammary tubule morphogenesis." Niranjan B., Hohenester E., Slade M., Ali S., Kamalati T., Buluwela L. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Hetrin, an alternative splicing form of beta-netrin." Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Fetal liver.
[4]	Li H., Zhou G., Shen C., Li M., Xiao W., Zhong G., Zheng G., Yu R., Ke R., Zhong J., Huang F., Lin L., Yang S. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 50-628 (ISOFORMS 1/3). Tissue: Stomach.
[6]	"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] OF 160-628 (ISOFORMS 1/3). Tissue: Lung.
[7]	"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 288-628 (ISOFORMS 1/3).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF278532 mRNA. Translation: AAG30822.1. AF297711 mRNA. Translation: AAG53651.1. AF119916 mRNA. Translation: AAF69670.2. AY330211 mRNA. Translation: AAP92113.1. AL137540 mRNA. Translation: CAB70800.3. AL833767 mRNA. Translation: CAH56243.1. BC013591 mRNA. Translation: AAH13591.2. AK024691 mRNA. Translation: BAB14964.1.
IPI	IPI00328091. IPI00385236. IPI00472613.
PIR	T46383.
RefSeq	NP_067052.2.
UniGene	Hs.201034
3D structure databases
HSSP	HSSP built from PDB template 1NPE based on UniProtKB P02468.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HB63. 2 interactions.
Proteomic databases
PRIDE	Q9HB63.
Genome annotation databases
Ensembl	ENSG00000074527. Homo sapiens. [Contig view]
GeneID	59277.
KEGG	hsa:59277.
Organism-specific databases
GeneCards	GC12M094554.
H-InvDB	HIX0010897.
HGNC	HGNC:13658. NTN4.
MIM	610401. gene.
PharmGKB	PA26688.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9HB63.
OMA	Q9HB63. ATFGLED.
Gene expression databases
ArrayExpress	Q9HB63.
Bgee	Q9HB63.
CleanEx	HS_NTN4.
GermOnline	ENSG00000074527. Homo sapiens.
Family and domain databases
InterPro	IPR013032. EGF-like_reg_CS. IPR002049. EGF_laminin. IPR008211. Laminin_N. IPR001134. Netrin_domain. IPR018933. Netrin_module_non-TIMP. [Graphical view]
Pfam	PF00053. Laminin_EGF. 3 hits. PF00055. Laminin_N. 1 hit. PF01759. NTR. 1 hit. [Graphical view]
PRINTS	PR00011. EGFLAMININ.
SMART	SM00643. C345C. 1 hit. SM00180. EGF_Lam. 3 hits. SM00136. LamNT. 1 hit. [Graphical view]
PROSITE	PS00022. EGF_1. 2 hits. PS01248. EGF_LAM_1. 2 hits. PS50027. EGF_LAM_2. 3 hits. PS51117. LAMININ_NTER. 1 hit. PS50189. NTR. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	65162.
SOURCE	Search...

Entry information

Entry name

NET4_HUMAN

Accession

Primary (citable) accession number: Q9HB63
Secondary accession number(s): Q658K9 , Q7L3F1, Q7L9D6, Q7Z5B6, Q9BZP1, Q9NT44, Q9P133

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2005
Last sequence update:	September 27, 2005
Last modified:	June 16, 2009
This is version 55 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)