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Protein

Netrin-4

Gene

NTN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May play an important role in neural, kidney and vascular development. Promotes neurite elongation from olfactory bulb explants.1 Publication

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-3000171. Non-integrin membrane-ECM interactions.
R-HSA-373752. Netrin-1 signaling.
SIGNORiQ9HB63.

Names & Taxonomyi

Protein namesi
Recommended name:
Netrin-4
Alternative name(s):
Beta-netrin
Hepar-derived netrin-like protein
Gene namesi
Name:NTN4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:13658. NTN4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Basement membrane, Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31815.

Polymorphism and mutation databases

BioMutaiNTN4.
DMDMi76789662.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence analysisAdd
BLAST
Chaini19 – 628610Netrin-4PRO_0000042116Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi56 – 561N-linked (GlcNAc...)Sequence analysis
Glycosylationi163 – 1631N-linked (GlcNAc...)Sequence analysis
Disulfide bondi262 ↔ 271By similarity
Disulfide bondi264 ↔ 293By similarity
Disulfide bondi295 ↔ 304By similarity
Disulfide bondi307 ↔ 329By similarity
Disulfide bondi332 ↔ 341By similarity
Disulfide bondi334 ↔ 359By similarity
Glycosylationi353 – 3531N-linked (GlcNAc...)Sequence analysis
Disulfide bondi362 ↔ 371By similarity
Disulfide bondi374 ↔ 392By similarity
Disulfide bondi395 ↔ 413By similarity
Disulfide bondi397 ↔ 420By similarity
Disulfide bondi422 ↔ 431By similarity
Disulfide bondi434 ↔ 446By similarity
Glycosylationi483 – 4831N-linked (GlcNAc...)Sequence analysis
Disulfide bondi506 ↔ 576By similarity
Disulfide bondi520 ↔ 627By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9HB63.
PaxDbiQ9HB63.
PeptideAtlasiQ9HB63.
PRIDEiQ9HB63.

PTM databases

iPTMnetiQ9HB63.
PhosphoSiteiQ9HB63.

Expressioni

Tissue specificityi

Expressed in kidney, spleen, mammary gland, aorta, heart, ovary, prostate and fetal spleen.1 Publication

Gene expression databases

BgeeiQ9HB63.
CleanExiHS_NTN4.
ExpressionAtlasiQ9HB63. baseline and differential.
GenevisibleiQ9HB63. HS.

Organism-specific databases

HPAiHPA049832.

Interactioni

Subunit structurei

May form a homodimer.

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP5-9P263713EBI-10310092,EBI-3958099

Protein-protein interaction databases

BioGridi121866. 8 interactions.
DIPiDIP-46274N.
IntActiQ9HB63. 8 interactions.
MINTiMINT-1463888.
STRINGi9606.ENSP00000340998.

Structurei

3D structure databases

ProteinModelPortaliQ9HB63.
SMRiQ9HB63. Positions 31-462.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 261232Laminin N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini262 – 33170Laminin EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini332 – 39463Laminin EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini395 – 44854Laminin EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini506 – 627122NTRPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 3 laminin EGF-like domains.PROSITE-ProRule annotation
Contains 1 laminin N-terminal domain.PROSITE-ProRule annotation
Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Laminin EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiKOG0994. Eukaryota.
ENOG410XPEG. LUCA.
GeneTreeiENSGT00780000121851.
HOVERGENiHBG082019.
InParanoidiQ9HB63.
KOiK06845.
OMAiECRTCKC.
OrthoDBiEOG7BKCT6.
PhylomeDBiQ9HB63.
TreeFamiTF352481.

Family and domain databases

InterProiIPR002049. Laminin_EGF.
IPR008211. Laminin_N.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PfamiPF00053. Laminin_EGF. 3 hits.
PF00055. Laminin_N. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00180. EGF_Lam. 3 hits.
SM00136. LamNT. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
PROSITEiPS00022. 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]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HB63-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGSCARLLLL WGCTVVAAGL SGVAGVSSRC EKACNPRMGN LALGRKLWAD
60 70 80 90 100
TTCGQNATEL YCFYSENTDL TCRQPKCDKC NAAYPHLAHL PSAMADSSFR
110 120 130 140 150
FPRTWWQSAE DVHREKIQLD LEAEFYFTHL IVMFKSPRPA AMVLDRSQDF
160 170 180 190 200
GKTWKPYKYF ATNCSATFGL EDDVVKKGAI CTSKYSSPFP CTGGEVIFKA
210 220 230 240 250
LSPPYDTENP YSAKVQEQLK ITNLRVQLLK RQSCPCQRND LNEEPQHFTH
260 270 280 290 300
YAIYDFIVKG SCFCNGHADQ CIPVHGFRPV KAPGTFHMVH GKCMCKHNTA
310 320 330 340 350
GSHCQHCAPL YNDRPWEAAD GKTGAPNECR TCKCNGHADT CHFDVNVWEA
360 370 380 390 400
SGNRSGGVCD DCQHNTEGQY CQRCKPGFYR DLRRPFSAPD ACKPCSCHPV
410 420 430 440 450
GSAVLPANSV TFCDPSNGDC PCKPGVAGRR CDRCMVGYWG FGDYGCRPCD
460 470 480 490 500
CAGSCDPITG DCISSHTDID WYHEVPDFRP VHNKSEPAWE WEDAQGFSAL
510 520 530 540 550
LHSGKCECKE QTLGNAKAFC GMKYSYVLKI KILSAHDKGT HVEVNVKIKK
560 570 580 590 600
VLKSTKLKIF RGKRTLYPES WTDRGCTCPI LNPGLEYLVA GHEDIRTGKL
610 620
IVNMKSFVQH WKPSLGRKVM DILKRECK
Length:628
Mass (Da):70,071
Last modified:September 27, 2005 - v2
Checksum:i275613B63A39B267
GO
Isoform 2 (identifier: Q9HB63-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:605
Mass (Da):67,529
Checksum:iD9FB51CC6553CF5C
GO
Isoform 3 (identifier: Q9HB63-3) [UniParc]FASTAAdd to basket

Also known as: Hetrin

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

Show »
Length:591
Mass (Da):66,352
Checksum:i912F3BA3726722A1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 681T → K in AAG30822 (PubMed:11038171).Curated
Sequence conflicti161 – 1611A → G in AAF69670 (Ref. 3) Curated
Sequence conflicti222 – 2221T → I in AAP92113 (Ref. 4) Curated
Sequence conflicti331 – 3311T → A (PubMed:11038171).Curated
Sequence conflicti331 – 3311T → A (Ref. 4) Curated
Sequence conflicti462 – 4621C → R in AAP92113 (Ref. 4) Curated
Sequence conflicti472 – 4721Y → C in AAG30822 (PubMed:11038171).Curated
Sequence conflicti472 – 4721Y → H in AAP92113 (Ref. 4) Curated
Sequence conflicti545 – 5451N → S in AAP92113 (Ref. 4) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti205 – 2051Y → H.
Corresponds to variant rs17288108 [ dbSNP | Ensembl ].
VAR_023548

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3737Missing in isoform 3. 1 PublicationVSP_015745Add
BLAST
Alternative sequencei504 – 52623Missing in isoform 2. 1 PublicationVSP_015746Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CH471054 Genomic DNA. Translation: EAW97544.1.
BC013591 mRNA. Translation: AAH13591.2.
BC136798 mRNA. Translation: AAI36799.1.
BC136799 mRNA. Translation: AAI36800.1.
AL833767 mRNA. Translation: CAH56243.1.
AK024691 mRNA. Translation: BAB14964.1.
CCDSiCCDS9054.1. [Q9HB63-1]
PIRiT46383.
RefSeqiNP_067052.2. NM_021229.3. [Q9HB63-1]
UniGeneiHs.201034.

Genome annotation databases

EnsembliENST00000343702; ENSP00000340998; ENSG00000074527. [Q9HB63-1]
ENST00000344911; ENSP00000339436; ENSG00000074527. [Q9HB63-3]
ENST00000538383; ENSP00000444432; ENSG00000074527. [Q9HB63-3]
ENST00000553059; ENSP00000447292; ENSG00000074527. [Q9HB63-2]
GeneIDi59277.
KEGGihsa:59277.
UCSCiuc001tei.3. human. [Q9HB63-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CH471054 Genomic DNA. Translation: EAW97544.1.
BC013591 mRNA. Translation: AAH13591.2.
BC136798 mRNA. Translation: AAI36799.1.
BC136799 mRNA. Translation: AAI36800.1.
AL833767 mRNA. Translation: CAH56243.1.
AK024691 mRNA. Translation: BAB14964.1.
CCDSiCCDS9054.1. [Q9HB63-1]
PIRiT46383.
RefSeqiNP_067052.2. NM_021229.3. [Q9HB63-1]
UniGeneiHs.201034.

3D structure databases

ProteinModelPortaliQ9HB63.
SMRiQ9HB63. Positions 31-462.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121866. 8 interactions.
DIPiDIP-46274N.
IntActiQ9HB63. 8 interactions.
MINTiMINT-1463888.
STRINGi9606.ENSP00000340998.

PTM databases

iPTMnetiQ9HB63.
PhosphoSiteiQ9HB63.

Polymorphism and mutation databases

BioMutaiNTN4.
DMDMi76789662.

Proteomic databases

MaxQBiQ9HB63.
PaxDbiQ9HB63.
PeptideAtlasiQ9HB63.
PRIDEiQ9HB63.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000343702; ENSP00000340998; ENSG00000074527. [Q9HB63-1]
ENST00000344911; ENSP00000339436; ENSG00000074527. [Q9HB63-3]
ENST00000538383; ENSP00000444432; ENSG00000074527. [Q9HB63-3]
ENST00000553059; ENSP00000447292; ENSG00000074527. [Q9HB63-2]
GeneIDi59277.
KEGGihsa:59277.
UCSCiuc001tei.3. human. [Q9HB63-1]

Organism-specific databases

CTDi59277.
GeneCardsiNTN4.
HGNCiHGNC:13658. NTN4.
HPAiHPA049832.
MIMi610401. gene.
neXtProtiNX_Q9HB63.
PharmGKBiPA31815.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0994. Eukaryota.
ENOG410XPEG. LUCA.
GeneTreeiENSGT00780000121851.
HOVERGENiHBG082019.
InParanoidiQ9HB63.
KOiK06845.
OMAiECRTCKC.
OrthoDBiEOG7BKCT6.
PhylomeDBiQ9HB63.
TreeFamiTF352481.

Enzyme and pathway databases

ReactomeiR-HSA-3000171. Non-integrin membrane-ECM interactions.
R-HSA-373752. Netrin-1 signaling.
SIGNORiQ9HB63.

Miscellaneous databases

ChiTaRSiNTN4. human.
GenomeRNAii59277.
PROiQ9HB63.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HB63.
CleanExiHS_NTN4.
ExpressionAtlasiQ9HB63. baseline and differential.
GenevisibleiQ9HB63. HS.

Family and domain databases

InterProiIPR002049. Laminin_EGF.
IPR008211. Laminin_N.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PfamiPF00053. Laminin_EGF. 3 hits.
PF00055. Laminin_N. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00180. EGF_Lam. 3 hits.
SM00136. LamNT. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
PROSITEiPS00022. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 160-628 (ISOFORMS 1/3).
    Tissue: Brain and Lung.
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 50-628 (ISOFORMS 1/3).
    Tissue: Stomach.
  8. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 288-628 (ISOFORMS 1/3).

Entry informationi

Entry nameiNET4_HUMAN
AccessioniPrimary (citable) accession number: Q9HB63
Secondary accession number(s): B2RNC2
, Q658K9, Q7L3F1, Q7L9D6, Q7Z5B6, Q9BZP1, Q9NT44, Q9P133
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: September 27, 2005
Last modified: July 6, 2016
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.