NDNF_MOUSE
ID NDNF_MOUSE Reviewed; 568 AA.
AC Q8C119; Q80VN3; Q8BWV6;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Protein NDNF;
DE AltName: Full=Epidermacan;
DE AltName: Full=Neuron-derived neurotrophic factor;
DE Flags: Precursor;
GN Name=Ndnf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [3]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=18757743; DOI=10.1073/pnas.0803640105;
RA Manabe R., Tsutsui K., Yamada T., Kimura M., Nakano I., Shimono C.,
RA Sanzen N., Furutani Y., Fukuda T., Oguri Y., Shimamoto K., Kiyozumi D.,
RA Sato Y., Sado Y., Senoo H., Yamashina S., Fukuda S., Kawai J., Sugiura N.,
RA Kimata K., Hayashizaki Y., Sekiguchi K.;
RT "Transcriptome-based systematic identification of extracellular matrix
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12849-12854(2008).
RN [4]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND GLYCOSYLATION.
RX PubMed=20969804; DOI=10.1186/1471-2202-11-137;
RA Kuang X.L., Zhao X.M., Xu H.F., Shi Y.Y., Deng J.B., Sun G.T.;
RT "Spatio-temporal expression of a novel neuron-derived neurotrophic factor
RT (NDNF) in mouse brains during development.";
RL BMC Neurosci. 11:137-137(2010).
RN [5]
RP INDUCTION, AND FUNCTION.
RX PubMed=24706764; DOI=10.1074/jbc.m114.555789;
RA Ohashi K., Enomoto T., Joki Y., Shibata R., Ogura Y., Kataoka Y.,
RA Shimizu Y., Kambara T., Uemura Y., Yuasa D., Matsuo K., Hayakawa S.,
RA Hiramatsu-Ito M., Murohara T., Ouchi N.;
RT "Neuron-derived neurotrophic factor functions as a novel modulator that
RT enhances endothelial cell function and revascularization processes.";
RL J. Biol. Chem. 289:14132-14144(2014).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=31883645; DOI=10.1016/j.ajhg.2019.12.003;
RA Messina A., Pulli K., Santini S., Acierno J., Kaensaekoski J.,
RA Cassatella D., Xu C., Casoni F., Malone S.A., Ternier G., Conte D.,
RA Sidis Y., Tommiska J., Vaaralahti K., Dwyer A., Gothilf Y., Merlo G.R.,
RA Santoni F., Niederlaender N.J., Giacobini P., Raivio T., Pitteloud N.;
RT "Neuron-derived neurotrophic factor is mutated in congenital
RT hypogonadotropic hypogonadism.";
RL Am. J. Hum. Genet. 106:58-70(2020).
CC -!- FUNCTION: Secretory protein that plays a role in various cellular
CC processes. Acts as a chemorepellent acting on gonadotropin-releasing
CC hormone (GnRH) expressing neurons regulating their migration to the
CC hypothalamus (PubMed:31883645). Also promotes neuron migration, growth
CC and survival as well as neurite outgrowth and is involved in the
CC development of the olfactory system (PubMed:31883645). May also act
CC through the regulation of growth factors activity and downstream
CC signaling (By similarity). Also regulates extracellular matrix assembly
CC and cell adhesiveness (PubMed:18757743). Promotes endothelial cell
CC survival, vessel formation and plays an important role in the process
CC of revascularization through NOS3-dependent mechanisms
CC (PubMed:24706764). {ECO:0000250|UniProtKB:Q8TB73,
CC ECO:0000269|PubMed:18757743, ECO:0000269|PubMed:24706764,
CC ECO:0000269|PubMed:31883645}.
CC -!- SUBUNIT: Binds heparin and chondroitin sulfate.
CC {ECO:0000269|PubMed:18757743}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18757743}.
CC -!- TISSUE SPECIFICITY: Expressed in brain and spinal cord with no
CC expression detected in heart, kidney or liver. Expressed by neurons but
CC not by astrocytes. In the brain, detected in the cerebrum, cerebellum
CC and olfactory bulbs. In the cerebral cortex, highly expressed in Cajal-
CC Retzius cells. Also expressed in hippocampal neurons and in Purkinje
CC and granule cells of the cerebellum (at protein level)
CC (PubMed:20969804). Expressed in neurons along the GnRH migratory route.
CC {ECO:0000269|PubMed:20969804, ECO:0000269|PubMed:31883645}.
CC -!- DEVELOPMENTAL STAGE: At 16.5 dpc, specifically expressed in the
CC interfollicular basal cells of the epidermis (at protein level).
CC Detected in the marginal cells and cortical plate of the brain cortex
CC from 16 dpc to P90 with high levels between 16 dpc and P0 and lower
CC levels from P7 to adulthood (at protein level).
CC {ECO:0000269|PubMed:18757743, ECO:0000269|PubMed:20969804}.
CC -!- INDUCTION: Up-regulated in endothelial cells of muscles after hind limb
CC ischemic surgery. {ECO:0000269|PubMed:24706764}.
CC -!- PTM: O-glycosylated; contains heparan sulfate and chondroitin sulfate.
CC {ECO:0000269|PubMed:20969804}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20969804}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice lacking Ndnf are grossly normal and
CC able to produce viable pups (PubMed:31883645). Absence of Ndnf in 13.5
CC dpc embryos results in abnormal development of the olfactory system and
CC defective gonadotropin-releasing hormone (GnRH) expressing neurons
CC migration to the hypothalamus (PubMed:31883645).
CC {ECO:0000269|PubMed:31883645}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC33925.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK029210; BAC26349.1; -; mRNA.
DR EMBL; AK049802; BAC33925.1; ALT_FRAME; mRNA.
DR EMBL; BC047154; AAH47154.1; -; mRNA.
DR CCDS; CCDS20207.1; -.
DR RefSeq; NP_765987.2; NM_172399.3.
DR RefSeq; XP_006506591.1; XM_006506528.3.
DR AlphaFoldDB; Q8C119; -.
DR IntAct; Q8C119; 1.
DR STRING; 10090.ENSMUSP00000051297; -.
DR GlyGen; Q8C119; 2 sites.
DR PhosphoSitePlus; Q8C119; -.
DR MaxQB; Q8C119; -.
DR PaxDb; Q8C119; -.
DR PRIDE; Q8C119; -.
DR ProteomicsDB; 287461; -.
DR Antibodypedia; 52933; 92 antibodies from 17 providers.
DR DNASU; 68169; -.
DR Ensembl; ENSMUST00000054351; ENSMUSP00000051297; ENSMUSG00000049001.
DR GeneID; 68169; -.
DR KEGG; mmu:68169; -.
DR UCSC; uc009cei.1; mouse.
DR CTD; 79625; -.
DR MGI; MGI:1915419; Ndnf.
DR VEuPathDB; HostDB:ENSMUSG00000049001; -.
DR eggNOG; KOG4806; Eukaryota.
DR GeneTree; ENSGT00390000007586; -.
DR HOGENOM; CLU_041753_0_0_1; -.
DR InParanoid; Q8C119; -.
DR OMA; YCVVINR; -.
DR OrthoDB; 294977at2759; -.
DR PhylomeDB; Q8C119; -.
DR TreeFam; TF313245; -.
DR BioGRID-ORCS; 68169; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q8C119; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8C119; protein.
DR Bgee; ENSMUSG00000049001; Expressed in vault of skull and 186 other tissues.
DR Genevisible; Q8C119; MM.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005539; F:glycosaminoglycan binding; IDA:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:MGI.
DR GO; GO:0021828; P:gonadotrophin-releasing hormone neuronal migration to the hypothalamus; IMP:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; ISS:UniProtKB.
DR GO; GO:0019800; P:peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan; IDA:MGI.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IDA:UniProtKB.
DR GO; GO:0061042; P:vascular wound healing; IMP:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR019326; NDNF.
DR InterPro; IPR045805; NDNF_C.
DR PANTHER; PTHR14619; PTHR14619; 1.
DR Pfam; PF10179; NDNF; 1.
DR Pfam; PF19433; NDNF_C; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF49265; SSF49265; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Neurogenesis; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..568
FT /note="Protein NDNF"
FT /id="PRO_0000301966"
FT DOMAIN 261..331
FT /note="Fibronectin type-III 1"
FT DOMAIN 445..564
FT /note="Fibronectin type-III 2"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 58
FT /note="R -> T (in Ref. 1; BAC33925)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="R -> K (in Ref. 1; BAC26349)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 568 AA; 65027 MW; 3928EAA45CA8DE4B CRC64;
MELFYWCLLC LLLPLTSRTQ KLPTRDEELF QMQIRDKEFF HDSSVIPDGA EVSSYLFRDT
PRRYFFMVEE DNTPLSVTVT PCDAPLEWKL SLQELHEGSS ADGSGDPELL DQQKQQMTDV
EGTELFSYKG NDVEYFLSSS SPSGLYQLEL LSTEKDTHFK VYATTTPESD QPYPELPYDP
RVDVTSFGRT TVTLAWKPSP TASILKQPIE YCVVINKEHN FKSLCAAETK MNADDAFMVA
PKPGLDFNPF DFAHFGFPTD NLGKDRSLLA KPSPKVGRHV YWRPKVDIQK ICIGNKNIFT
VSDLKPDTQY YFDVFMVNTN TNMSTAYVGA FVRTKEEAKQ KTVELKDGRV TDVFVKRKGK
KFLRFAPVSS HQKVTFFIHS CMDAVQVQVR RDGRLLLSQN VEGIRQFQLR GKPKGKYLIR
LKGNRKGASK LKILATTRPS KHAFPSLPED TRIKAFDKLR TCSSVTVAWL GTQERRKFCI
YRKEVDGNYS EDQKRREQNQ CLGPDTRKKS EKVLCKYFHS QNLQKAVTTE TIRDLQPGKS
YLLDVYVVGH GGHSVKYQSK IVKTRKVC
