NET4_HUMAN
ID NET4_HUMAN Reviewed; 628 AA.
AC Q9HB63; B2RNC2; Q658K9; Q7L3F1; Q7L9D6; Q7Z5B6; Q9BZP1; Q9NT44; Q9P133;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Netrin-4;
DE AltName: Full=Beta-netrin;
DE AltName: Full=Hepar-derived netrin-like protein;
DE Flags: Precursor;
GN Name=NTN4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=11038171; DOI=10.1083/jcb.151.2.221;
RA Koch M., Murrell J.R., Hunter D.D., Olson P.F., Jin W., Keene D.R.,
RA Brunken W.J., Burgeson R.E.;
RT "A novel member of the netrin family, beta-netrin, shares homology with the
RT beta chain of laminin. Identification, expression, and functional
RT characterization.";
RL J. Cell Biol. 151:221-234(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Niranjan B., Hohenester E., Slade M., Ali S., Kamalati T., Buluwela L.;
RT "Identification of a novel member of the netrin family, which is induced
RT during in vitro mammary tubule morphogenesis.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F.;
RT "Hetrin, an alternative splicing form of beta-netrin.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Li H., Zhou G., Shen C., Li M., Xiao W., Zhong G., Zheng G., Yu R., Ke R.,
RA Zhong J., Huang F., Lin L., Yang S.;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 160-628 (ISOFORMS 1/3).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 50-628 (ISOFORMS 1/3).
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 288-628 (ISOFORMS 1/3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
CC -!- FUNCTION: May play an important role in neural, kidney and vascular
CC development. Promotes neurite elongation from olfactory bulb explants.
CC {ECO:0000269|PubMed:11038171}.
CC -!- SUBUNIT: May form a homodimer.
CC -!- INTERACTION:
CC Q9HB63; O14936-4: CASK; NbExp=3; IntAct=EBI-743459, EBI-12007726;
CC Q9HB63; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-743459, EBI-3867333;
CC Q9HB63; P49639: HOXA1; NbExp=5; IntAct=EBI-743459, EBI-740785;
CC Q9HB63; Q5T749: KPRP; NbExp=3; IntAct=EBI-743459, EBI-10981970;
CC Q9HB63; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-743459, EBI-10171774;
CC Q9HB63; Q3LI59: KRTAP21-2; NbExp=3; IntAct=EBI-743459, EBI-18395721;
CC Q9HB63; P26371: KRTAP5-9; NbExp=4; IntAct=EBI-743459, EBI-3958099;
CC Q9HB63; Q5T751: LCE1C; NbExp=3; IntAct=EBI-743459, EBI-12224199;
CC Q9HB63; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-743459, EBI-16439278;
CC Q9HB63; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-743459, EBI-22310682;
CC Q9HB63; P16284: PECAM1; NbExp=3; IntAct=EBI-743459, EBI-716404;
CC Q9HB63-3; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-10310092, EBI-3958099;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000269|PubMed:11038171}. Note=Major
CC component.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9HB63-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HB63-2; Sequence=VSP_015746;
CC Name=3; Synonyms=Hetrin;
CC IsoId=Q9HB63-3; Sequence=VSP_015745;
CC -!- TISSUE SPECIFICITY: Expressed in kidney, spleen, mammary gland, aorta,
CC heart, ovary, prostate and fetal spleen. {ECO:0000269|PubMed:11038171}.
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DR EMBL; AF278532; AAG30822.1; -; mRNA.
DR EMBL; AF297711; AAG53651.1; -; mRNA.
DR EMBL; AF119916; AAF69670.2; -; mRNA.
DR EMBL; AY330211; AAP92113.1; -; mRNA.
DR EMBL; AL137540; CAB70800.3; -; mRNA.
DR EMBL; CH471054; EAW97544.1; -; Genomic_DNA.
DR EMBL; BC013591; AAH13591.2; -; mRNA.
DR EMBL; BC136798; AAI36799.1; -; mRNA.
DR EMBL; BC136799; AAI36800.1; -; mRNA.
DR EMBL; AL833767; CAH56243.1; -; mRNA.
DR EMBL; AK024691; BAB14964.1; -; mRNA.
DR CCDS; CCDS86324.1; -. [Q9HB63-3]
DR CCDS; CCDS86325.1; -. [Q9HB63-2]
DR CCDS; CCDS9054.1; -. [Q9HB63-1]
DR PIR; T46383; T46383.
DR RefSeq; NP_001316629.1; NM_001329700.1. [Q9HB63-2]
DR RefSeq; NP_001316630.1; NM_001329701.1. [Q9HB63-3]
DR RefSeq; NP_001316631.1; NM_001329702.1. [Q9HB63-3]
DR RefSeq; NP_067052.2; NM_021229.3. [Q9HB63-1]
DR AlphaFoldDB; Q9HB63; -.
DR SMR; Q9HB63; -.
DR BioGRID; 121866; 21.
DR DIP; DIP-46274N; -.
DR IntAct; Q9HB63; 20.
DR MINT; Q9HB63; -.
DR STRING; 9606.ENSP00000340998; -.
DR GlyGen; Q9HB63; 4 sites.
DR iPTMnet; Q9HB63; -.
DR PhosphoSitePlus; Q9HB63; -.
DR BioMuta; NTN4; -.
DR DMDM; 76789662; -.
DR MassIVE; Q9HB63; -.
DR MaxQB; Q9HB63; -.
DR PaxDb; Q9HB63; -.
DR PeptideAtlas; Q9HB63; -.
DR PRIDE; Q9HB63; -.
DR ProteomicsDB; 81495; -. [Q9HB63-1]
DR ProteomicsDB; 81496; -. [Q9HB63-2]
DR ProteomicsDB; 81497; -. [Q9HB63-3]
DR Antibodypedia; 30131; 206 antibodies from 27 providers.
DR DNASU; 59277; -.
DR Ensembl; ENST00000343702.9; ENSP00000340998.4; ENSG00000074527.13. [Q9HB63-1]
DR Ensembl; ENST00000344911.8; ENSP00000339436.4; ENSG00000074527.13. [Q9HB63-3]
DR Ensembl; ENST00000538383.5; ENSP00000444432.1; ENSG00000074527.13. [Q9HB63-3]
DR Ensembl; ENST00000553059.1; ENSP00000447292.1; ENSG00000074527.13. [Q9HB63-2]
DR GeneID; 59277; -.
DR KEGG; hsa:59277; -.
DR MANE-Select; ENST00000343702.9; ENSP00000340998.4; NM_021229.4; NP_067052.2.
DR UCSC; uc001tei.3; human. [Q9HB63-1]
DR CTD; 59277; -.
DR DisGeNET; 59277; -.
DR GeneCards; NTN4; -.
DR HGNC; HGNC:13658; NTN4.
DR HPA; ENSG00000074527; Tissue enhanced (lymphoid).
DR MIM; 610401; gene.
DR neXtProt; NX_Q9HB63; -.
DR OpenTargets; ENSG00000074527; -.
DR PharmGKB; PA31815; -.
DR VEuPathDB; HostDB:ENSG00000074527; -.
DR eggNOG; KOG0994; Eukaryota.
DR GeneTree; ENSGT00940000156615; -.
DR HOGENOM; CLU_016961_2_1_1; -.
DR InParanoid; Q9HB63; -.
DR OMA; PKAFCGM; -.
DR OrthoDB; 236390at2759; -.
DR PhylomeDB; Q9HB63; -.
DR TreeFam; TF352481; -.
DR PathwayCommons; Q9HB63; -.
DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-HSA-373752; Netrin-1 signaling.
DR SignaLink; Q9HB63; -.
DR SIGNOR; Q9HB63; -.
DR BioGRID-ORCS; 59277; 11 hits in 1063 CRISPR screens.
DR ChiTaRS; NTN4; human.
DR GenomeRNAi; 59277; -.
DR Pharos; Q9HB63; Tbio.
DR PRO; PR:Q9HB63; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9HB63; protein.
DR Bgee; ENSG00000074527; Expressed in kidney epithelium and 181 other tissues.
DR ExpressionAtlas; Q9HB63; baseline and differential.
DR Genevisible; Q9HB63; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0043256; C:laminin complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043237; F:laminin-1 binding; IEA:Ensembl.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0070831; P:basement membrane assembly; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0016322; P:neuron remodeling; IEA:Ensembl.
DR GO; GO:0060668; P:regulation of branching involved in salivary gland morphogenesis by extracellular matrix-epithelial cell signaling; IEA:Ensembl.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IBA:GO_Central.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR CDD; cd00055; EGF_Lam; 3.
DR CDD; cd03578; NTR_netrin-4_like; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR InterPro; IPR008211; Laminin_N.
DR InterPro; IPR002049; LE_dom.
DR InterPro; IPR035811; Netrin-4_NTR.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR Pfam; PF00053; Laminin_EGF; 3.
DR Pfam; PF00055; Laminin_N; 1.
DR Pfam; PF01759; NTR; 1.
DR SMART; SM00643; C345C; 1.
DR SMART; SM00180; EGF_Lam; 3.
DR SMART; SM00136; LamNT; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01248; EGF_LAM_1; 2.
DR PROSITE; PS50027; EGF_LAM_2; 3.
DR PROSITE; PS51117; LAMININ_NTER; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Basement membrane; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Laminin EGF-like domain;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..628
FT /note="Netrin-4"
FT /id="PRO_0000042116"
FT DOMAIN 30..261
FT /note="Laminin N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00466"
FT DOMAIN 262..331
FT /note="Laminin EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 332..394
FT /note="Laminin EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 395..448
FT /note="Laminin EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 506..627
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 262..271
FT /evidence="ECO:0000250"
FT DISULFID 264..293
FT /evidence="ECO:0000250"
FT DISULFID 295..304
FT /evidence="ECO:0000250"
FT DISULFID 307..329
FT /evidence="ECO:0000250"
FT DISULFID 332..341
FT /evidence="ECO:0000250"
FT DISULFID 334..359
FT /evidence="ECO:0000250"
FT DISULFID 362..371
FT /evidence="ECO:0000250"
FT DISULFID 374..392
FT /evidence="ECO:0000250"
FT DISULFID 395..413
FT /evidence="ECO:0000250"
FT DISULFID 397..420
FT /evidence="ECO:0000250"
FT DISULFID 422..431
FT /evidence="ECO:0000250"
FT DISULFID 434..446
FT /evidence="ECO:0000250"
FT DISULFID 506..576
FT /evidence="ECO:0000250"
FT DISULFID 520..627
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..37
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_015745"
FT VAR_SEQ 504..526
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_015746"
FT VARIANT 205
FT /note="Y -> H (in dbSNP:rs17288108)"
FT /id="VAR_023548"
FT CONFLICT 68
FT /note="T -> K (in Ref. 1; AAG30822)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="A -> G (in Ref. 3; AAF69670)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="T -> I (in Ref. 4; AAP92113)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="T -> A (in Ref. 1 and 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="C -> R (in Ref. 4; AAP92113)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="Y -> C (in Ref. 1; AAG30822)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="Y -> H (in Ref. 4; AAP92113)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="N -> S (in Ref. 4; AAP92113)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 628 AA; 70071 MW; 275613B63A39B267 CRC64;
MGSCARLLLL WGCTVVAAGL SGVAGVSSRC EKACNPRMGN LALGRKLWAD TTCGQNATEL
YCFYSENTDL TCRQPKCDKC NAAYPHLAHL PSAMADSSFR FPRTWWQSAE DVHREKIQLD
LEAEFYFTHL IVMFKSPRPA AMVLDRSQDF GKTWKPYKYF ATNCSATFGL EDDVVKKGAI
CTSKYSSPFP CTGGEVIFKA LSPPYDTENP YSAKVQEQLK ITNLRVQLLK RQSCPCQRND
LNEEPQHFTH YAIYDFIVKG SCFCNGHADQ CIPVHGFRPV KAPGTFHMVH GKCMCKHNTA
GSHCQHCAPL YNDRPWEAAD GKTGAPNECR TCKCNGHADT CHFDVNVWEA SGNRSGGVCD
DCQHNTEGQY CQRCKPGFYR DLRRPFSAPD ACKPCSCHPV GSAVLPANSV TFCDPSNGDC
PCKPGVAGRR CDRCMVGYWG FGDYGCRPCD CAGSCDPITG DCISSHTDID WYHEVPDFRP
VHNKSEPAWE WEDAQGFSAL LHSGKCECKE QTLGNAKAFC GMKYSYVLKI KILSAHDKGT
HVEVNVKIKK VLKSTKLKIF RGKRTLYPES WTDRGCTCPI LNPGLEYLVA GHEDIRTGKL
IVNMKSFVQH WKPSLGRKVM DILKRECK
