ID NFASC_HUMAN Reviewed; 1347 AA. AC O94856; B2RNN8; B3KQZ1; B5MDP6; B5MDR6; B7ZMD8; Q149P5; Q5T2F0; Q5T2F1; AC Q5T2F2; Q5T2F3; Q5T2F4; Q5T2F5; Q5T2F6; Q5T2F7; Q5T2F9; Q5T2G0; Q5W9F8; AC Q68DH3; Q6ZQV6; Q7Z3K1; Q96HT1; Q96K50; DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 4. DT 02-SEP-2026, entry version 210. DE RecName: Full=Neurofascin; DE Flags: Precursor; GN Name=NFASC; Synonyms=KIAA0756; 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 [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [2] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 804-1347 (ISOFORMS 3/4), NUCLEOTIDE SEQUENCE [LARGE RP SCALE MRNA] OF 931-1347 (ISOFORM 6), AND NUCLEOTIDE SEQUENCE [LARGE SCALE RP MRNA] OF 972-1347 (ISOFORM 1). RC TISSUE=Teratocarcinoma, and Uterus; 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). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 9), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 326-1347 (ISOFORM 2). RC TISSUE=Brain; 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 193-1347 (ISOFORM 5). RX PubMed=15491607; DOI=10.1016/j.jmb.2004.09.028; RA Homma K., Kikuno R.F., Nagase T., Ohara O., Nishikawa K.; RT "Alternative splice variants encoding unstable protein domains exist in the RT human brain."; RL J. Mol. Biol. 343:1207-1220(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1040-1347 (ISOFORM 7), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1204-1347 (ISOFORMS 1/3/4/6/7). RC TISSUE=Amygdala, and Esophageal carcinoma; 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-481 AND SER-485, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP INTERACTION WITH MYOC. RX PubMed=23897819; DOI=10.1074/jbc.m112.446138; RA Kwon H.S., Johnson T.V., Joe M.K., Abu-Asab M., Zhang J., Chan C.C., RA Tomarev S.I.; RT "Myocilin mediates myelination in the peripheral nervous system through RT ErbB2/3 signaling."; RL J. Biol. Chem. 288:26357-26371(2013). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 25-428, GLYCOSYLATION AT ASN-409, RP SUBUNIT, AND DISULFIDE BONDS. RX PubMed=21047790; DOI=10.1074/jbc.m110.180281; RA Liu H., Focia P.J., He X.; RT "Homophilic adhesion mechanism of neurofascin, a member of the L1 family of RT neural cell adhesion molecules."; RL J. Biol. Chem. 286:797-805(2011). RN [11] RP INVOLVEMENT IN NEDCPMD, AND VARIANT NEDCPMD PRO-359. RX PubMed=28940097; DOI=10.1007/s00439-017-1843-2; RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A., RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M., RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A., RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S., RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T., RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C., RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M., RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.; RT "Expanding the genetic heterogeneity of intellectual disability."; RL Hum. Genet. 136:1419-1429(2017). RN [12] RP ERRATUM OF PUBMED:28940097. RX PubMed=29288388; DOI=10.1007/s00439-017-1859-7; RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A., RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M., RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A., RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S., RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T., RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C., RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M., RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.; RT "Correction to: Expanding the genetic heterogeneity of intellectual RT disability."; RL Hum. Genet. 137:105-109(2018). RN [13] RP VARIANT NEDCPMD 835-VAL--ALA-1347 DEL, CHARACTERIZATION OF VARIANT NEDCPMD RP 835-ARG--ALA-1347 DEL, AND SUBCELLULAR LOCATION (ISOFORM 8). RX PubMed=30124836; DOI=10.1093/hmg/ddy277; RA Smigiel R., Sherman D.L., Rydzanicz M., Walczak A., Mikolajkow D., RA Krolak-Olejnik B., Kosinska J., Gasperowicz P., Biernacka A., Stawinski P., RA Marciniak M., Andrzejewski W., Boczar M., Krajewski P., Sasiadek M.M., RA Brophy P.J., Ploski R.; RT "Homozygous mutation in the Neurofascin gene affecting the glial isoform of RT Neurofascin causes severe neurodevelopment disorder with hypotonia, amimia RT and areflexia."; RL Hum. Mol. Genet. 27:3669-3674(2018). RN [14] RP INVOLVEMENT IN NEDCPMD, VARIANT NEDCPMD GLU-1229, CHARACTERIZATION OF RP VARIANT NEDCPMD GLU-1229, AND SUBCELLULAR LOCATION. RX PubMed=30850329; DOI=10.1016/j.parkreldis.2019.02.045; RA Monfrini E., Straniero L., Bonato S., Monzio Compagnoni G., Bordoni A., RA Dilena R., Rinchetti P., Silipigni R., Ronchi D., Corti S., Comi G.P., RA Bresolin N., Duga S., Di Fonzo A.; RT "Neurofascin (NFASC) gene mutation causes autosomal recessive ataxia with RT demyelinating neuropathy."; RL Parkinsonism Relat. Disord. 63:66-72(2019). CC -!- FUNCTION: Cell adhesion, ankyrin-binding protein which may be involved CC in neurite extension, axonal guidance, synaptogenesis, myelination and CC neuron-glial cell interactions. {ECO:0000250}. CC -!- SUBUNIT: Horseshoe-shaped homodimer. Probable constituent of a CC NFASC/NRCAM/ankyrin-G complex. Associates with the sodium channel beta- CC 1 (SCN1B) and beta-3 (SCN3B) subunits. Interacts with GLDN/gliomedin CC (By similarity). Interacts with MYOC. {ECO:0000250, CC ECO:0000269|PubMed:21047790, ECO:0000269|PubMed:23897819}. CC -!- INTERACTION: CC O94856-3; Q8IZP0-5: ABI1; NbExp=3; IntAct=EBI-12035911, EBI-11743294; CC O94856-3; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-12035911, EBI-11096309; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30850329}; CC Single-pass type I membrane protein {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [Isoform 8]: Cell junction, paranodal septate CC junction {ECO:0000269|PubMed:30124836}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=13; CC Name=1; CC IsoId=O94856-1; Sequence=Displayed; CC Name=2; CC IsoId=O94856-2; Sequence=VSP_016426, VSP_008938; CC Name=3; CC IsoId=O94856-3; Sequence=VSP_016424, VSP_016425, VSP_008937, CC VSP_008940; CC Name=4; CC IsoId=O94856-4; Sequence=VSP_016427, VSP_016428, VSP_008940; CC Name=5; CC IsoId=O94856-5; Sequence=VSP_008937, VSP_016429; CC Name=6; CC IsoId=O94856-6; Sequence=VSP_016430, VSP_016434; CC Name=7; CC IsoId=O94856-7; Sequence=VSP_016433; CC Name=8; Synonyms=Nfasc155 {ECO:0000303|PubMed:30124836}; CC IsoId=O94856-8; Sequence=VSP_016424, VSP_016425, VSP_008937, CC VSP_016432; CC Name=9; CC IsoId=O94856-9; Sequence=VSP_016427, VSP_016428; CC Name=10; CC IsoId=O94856-10; Sequence=VSP_016424, VSP_008937, VSP_016432; CC Name=11; CC IsoId=O94856-11; Sequence=VSP_016424, VSP_016425, VSP_016432; CC Name=12; CC IsoId=O94856-12; Sequence=VSP_016427, VSP_016428, VSP_016432; CC Name=13; CC IsoId=O94856-13; Sequence=VSP_016431; CC -!- DOMAIN: Homophilic adhesion is primarily mediated by the interaction of CC the second Ig-like domains. CC -!- DISEASE: Neurodevelopmental disorder with central and peripheral motor CC dysfunction (NEDCPMD) [MIM:618356]: An autosomal recessive CC neurodevelopmental disorder with early onset and a highly variable CC phenotype. Disease features include hypotonia apparent from birth, poor CC feeding, global developmental delay with absence of reaction to touch CC and no eye contact, infantile-onset progressive ataxia and CC demyelinating peripheral neuropathy. {ECO:0000269|PubMed:28940097, CC ECO:0000269|PubMed:30124836, ECO:0000269|PubMed:30850329}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: May be due to intron retention. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. CC L1/neurofascin/NgCAM family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA34476.3; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB55195.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAC87577.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB018299; BAA34476.3; ALT_INIT; mRNA. DR EMBL; AK027553; BAB55195.1; ALT_INIT; mRNA. DR EMBL; AK090639; BAG52203.1; -; mRNA. DR EMBL; AK127424; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK128699; BAC87577.1; ALT_INIT; mRNA. DR EMBL; AC096675; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391822; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008124; AAH08124.2; -; mRNA. DR EMBL; BC117674; AAI17675.2; -; mRNA. DR EMBL; BC137013; AAI37014.1; -; mRNA. DR EMBL; BC144454; AAI44455.1; -; mRNA. DR EMBL; AB177861; BAD66839.1; -; mRNA. DR EMBL; BX537841; CAD97852.1; -; mRNA. DR EMBL; CR749402; CAH18247.1; -; mRNA. DR CCDS; CCDS30982.1; -. [O94856-3] DR CCDS; CCDS53460.1; -. [O94856-9] DR CCDS; CCDS53461.1; -. [O94856-2] DR CCDS; CCDS53462.1; -. [O94856-8] DR CCDS; CCDS91149.1; -. [O94856-11] DR RefSeq; NP_001005388.2; NM_001005388.3. [O94856-9] DR RefSeq; NP_001005389.2; NM_001005389.2. [O94856-2] DR RefSeq; NP_001153803.1; NM_001160331.2. [O94856-11] DR RefSeq; NP_001153804.1; NM_001160332.2. [O94856-8] DR RefSeq; NP_001153805.1; NM_001160333.2. DR RefSeq; NP_001365258.1; NM_001378329.1. [O94856-1] DR RefSeq; NP_055905.2; NM_015090.4. [O94856-3] DR RefSeq; XP_011507630.3; XM_011509328.3. DR RefSeq; XP_024310068.1; XM_024454300.2. [O94856-9] DR RefSeq; XP_047305911.1; XM_047449955.1. [O94856-1] DR RefSeq; XP_047305973.1; XM_047450017.1. [O94856-4] DR RefSeq; XP_054191270.1; XM_054335295.1. [O94856-1] DR RefSeq; XP_054191281.1; XM_054335306.1. [O94856-9] DR PDB; 3P3Y; X-ray; 2.60 A; A=25-428. DR PDB; 3P40; X-ray; 3.20 A; A=25-428. DR AlphaFoldDB; O94856; -. DR EMDB; EMD-16540; -. DR SMR; O94856; -. DR BioGRID; 116737; 25. DR FunCoup; O94856; 690. DR IntAct; O94856; 12. DR STRING; 9606.ENSP00000344786; -. DR CarbonylDB; O94856; -. DR GlyConnect; O94856; 15 N-Linked glycans (7 sites). DR GlyCosmos; O94856; 9 sites, 15 glycans. DR GlyGen; O94856; 16 sites, 32 N-linked glycans (8 sites), 2 O-linked glycans (5 sites). DR iPTMnet; O94856; -. DR PhosphoSitePlus; O94856; -. DR SwissPalm; O94856; -. DR BioMuta; NFASC; -. DR jPOST; O94856; -. DR MassIVE; O94856; -. DR PaxDb; 9606-ENSP00000344786; -. DR PeptideAtlas; O94856; -. DR ProteomicsDB; 50490; -. [O94856-1] DR ProteomicsDB; 50491; -. [O94856-10] DR ProteomicsDB; 50492; -. [O94856-11] DR ProteomicsDB; 50493; -. [O94856-12] DR ProteomicsDB; 50494; -. [O94856-13] DR ProteomicsDB; 50495; -. [O94856-2] DR ProteomicsDB; 50496; -. [O94856-3] DR ProteomicsDB; 50497; -. [O94856-4] DR ProteomicsDB; 50498; -. [O94856-5] DR ProteomicsDB; 50499; -. [O94856-6] DR ProteomicsDB; 50500; -. [O94856-7] DR ProteomicsDB; 50501; -. [O94856-8] DR ProteomicsDB; 50502; -. [O94856-9] DR TopDownProteomics; O94856-2; -. [O94856-2] DR ABCD; O94856; 1 sequenced antibody. DR Antibodypedia; 2194; 236 antibodies from 37 providers. DR DNASU; 23114; -. DR Ensembl; ENST00000339876.11; ENSP00000344786.6; ENSG00000163531.18. [O94856-9] DR Ensembl; ENST00000401399.5; ENSP00000385637.1; ENSG00000163531.18. [O94856-9] DR Ensembl; ENST00000403080.5; ENSP00000384875.1; ENSG00000163531.18. [O94856-2] DR Ensembl; ENST00000404076.5; ENSP00000385676.1; ENSG00000163531.18. [O94856-10] DR Ensembl; ENST00000430393.7; ENSP00000415031.3; ENSG00000163531.18. [O94856-8] DR Ensembl; ENST00000513543.6; ENSP00000425908.1; ENSG00000163531.18. [O94856-3] DR Ensembl; ENST00000539706.6; ENSP00000438614.2; ENSG00000163531.18. [O94856-11] DR GeneID; 23114; -. DR KEGG; hsa:23114; -. DR MANE-Select; ENST00000339876.11; ENSP00000344786.6; NM_001005388.3; NP_001005388.2. [O94856-9] DR UCSC; uc001hbh.4; human. [O94856-1] DR AGR; HGNC:29866; -. DR ClinPGx; PA128395771; -. DR CTD; 23114; -. DR DisGeNET; 23114; -. DR GeneCards; NFASC; -. DR HGNC; HGNC:29866; NFASC. DR HPA; ENSG00000163531; Tissue enhanced (brain). DR MalaCards; NFASC; -. DR MIM; 609145; gene. DR MIM; 618356; phenotype. DR OpenTargets; ENSG00000163531; -. DR VEuPathDB; HostDB:ENSG00000163531; -. DR eggNOG; KOG3513; Eukaryota. DR GeneTree; ENSGT00940000157024; -. DR HOGENOM; CLU_005756_2_0_1; -. DR InParanoid; O94856; -. DR OMA; NHSSYPG; -. DR OrthoDB; 10010359at2759; -. DR PAN-GO; O94856; 6 GO annotations based on evolutionary models. DR PhylomeDB; O94856; -. DR PathwayCommons; O94856; -. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-447043; Neurofascin interactions. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; O94856; -. DR SIGNOR; O94856; -. DR Agora; ENSG00000163531; -. DR BioGRID-ORCS; 23114; 14 hits in 1147 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NFASC; human. DR EvolutionaryTrace; O94856; -. DR GeneWiki; NFASC; -. DR GenomeRNAi; 23114; -. DR Pharos; O94856; Tbio. DR PRO; PR:O94856; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O94856; protein. DR Bgee; ENSG00000163531; Expressed in inferior olivary complex and 187 other cell types or tissues. DR ExpressionAtlas; O94856; baseline and differential. DR GO; GO:0030424; C:axon; IBA:GO_Central. DR GO; GO:0043194; C:axon initial segment; ISS:ARUK-UCL. DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL. DR GO; GO:0033010; C:paranodal junction; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098632; F:cell-cell adhesion mediator activity; IBA:GO_Central. DR GO; GO:0007411; P:axon guidance; IBA:GO_Central. DR GO; GO:0007420; P:brain development; IBA:GO_Central. DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central. DR GO; GO:0042552; P:myelination; ISS:BHF-UCL. DR GO; GO:0007422; P:peripheral nervous system development; ISS:BHF-UCL. DR CDD; cd00063; FN3; 5. DR CDD; cd05731; Ig3_L1-CAM_like; 1. DR CDD; cd05845; IgI_2_L1-CAM_like; 1. DR CDD; cd05875; IgI_hNeurofascin_like; 1. DR FunFam; 2.60.40.10:FF:000057; neural cell adhesion molecule L1; 1. DR FunFam; 2.60.40.10:FF:000363; neurofascin isoform X1; 1. DR FunFam; 2.60.40.10:FF:000512; neurofascin isoform X1; 1. DR FunFam; 2.60.40.10:FF:000574; neurofascin isoform X1; 1. DR FunFam; 2.60.40.10:FF:001360; neurofascin isoform X1; 1. DR FunFam; 2.60.40.10:FF:000525; neurofascin isoform X2; 1. DR FunFam; 2.60.40.10:FF:000005; Neuronal cell adhesion molecule; 1. DR FunFam; 2.60.40.10:FF:000038; Neuronal cell adhesion molecule; 1. DR FunFam; 2.60.40.10:FF:000078; Neuronal cell adhesion molecule; 1. DR FunFam; 2.60.40.10:FF:000114; Neuronal cell adhesion molecule; 1. DR FunFam; 2.60.40.10:FF:000347; Neuronal cell adhesion molecule; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 11. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR013151; Immunoglobulin_dom. DR InterPro; IPR026966; Neurofascin/L1/NrCAM_C. DR InterPro; IPR026965; NFASC_Ig-like. DR PANTHER; PTHR44170:SF12; NEUROFASCIN; 1. DR PANTHER; PTHR44170; PROTEIN SIDEKICK; 1. DR Pfam; PF13882; Bravo_FIGEY; 1. DR Pfam; PF00041; fn3; 4. DR Pfam; PF07679; I-set; 3. DR Pfam; PF00047; ig; 1. DR Pfam; PF13927; Ig_3; 2. DR SMART; SM00060; FN3; 5. DR SMART; SM00409; IG; 6. DR SMART; SM00408; IGc2; 6. DR SUPFAM; SSF49265; Fibronectin type III; 3. DR SUPFAM; SSF48726; Immunoglobulin; 6. DR PROSITE; PS50853; FN3; 5. DR PROSITE; PS50835; IG_LIKE; 6. DR PDBsum; 3P3Y; -. DR PDBsum; 3P40; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; Cell junction; KW Cell membrane; Disease variant; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Membrane; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..1347 FT /note="Neurofascin" FT /id="PRO_0000015049" FT TOPO_DOM 25..1217 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1218..1238 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1239..1347 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 41..137 FT /note="Ig-like C2-type 1" FT DOMAIN 143..230 FT /note="Ig-like C2-type 2" FT DOMAIN 244..332 FT /note="Ig-like C2-type 3" FT DOMAIN 337..424 FT /note="Ig-like C2-type 4" FT DOMAIN 429..517 FT /note="Ig-like C2-type 5" FT DOMAIN 521..603 FT /note="Ig-like C2-type 6" FT DOMAIN 630..725 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 730..823 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 828..930 FT /note="Fibronectin type-III 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 934..1030 FT /note="Fibronectin type-III 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1114..1206 FT /note="Fibronectin type-III 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT REGION 713..740 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 915..934 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1011..1040 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1090..1111 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1248..1347 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 916..926 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1024..1040 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1090..1105 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1261..1272 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1278..1291 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 481 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 485 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1267 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q810U3" FT MOD_RES 1281 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97685" FT MOD_RES 1294 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97685" FT MOD_RES 1297 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97685" FT MOD_RES 1333 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q810U3" FT MOD_RES 1334 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q810U3" FT MOD_RES 1338 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q810U3" FT CARBOHYD 305 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 409 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21047790" FT CARBOHYD 446 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 483 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 752 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 778 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 973 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 988 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 63..118 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:21047790" FT DISULFID 162..213 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:21047790" FT DISULFID 268..316 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:21047790" FT DISULFID 358..408 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:21047790" FT DISULFID 452..501 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 543..592 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 31..36 FT /note="Missing (in isoform 3, isoform 8, isoform 10 and FT isoform 11)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9872452" FT /id="VSP_016424" FT VAR_SEQ 236 FT /note="T -> NHPYNDSSLRNHPDMYSA (in isoform 3, isoform 8 and FT isoform 11)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9872452" FT /id="VSP_016425" FT VAR_SEQ 611..625 FT /note="Missing (in isoform 3, isoform 5, isoform 8 and FT isoform 10)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:15491607, ECO:0000303|PubMed:9872452" FT /id="VSP_008937" FT VAR_SEQ 611..619 FT /note="ADQATPTNR -> GNCPCSPWH (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_016426" FT VAR_SEQ 620..1347 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_008938" FT VAR_SEQ 824..930 FT /note="Missing (in isoform 4, isoform 9 and isoform 12)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_016427" FT VAR_SEQ 931 FT /note="V -> L (in isoform 4, isoform 9 and isoform 12)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_016428" FT VAR_SEQ 1030..1203 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9872452" FT /id="VSP_008940" FT VAR_SEQ 1030..1152 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_016430" FT VAR_SEQ 1030..1043 FT /note="ATPTAAPPTLPPTT -> GRCMAAAPGVKGPS (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15491607" FT /id="VSP_016429" FT VAR_SEQ 1035..1203 FT /note="Missing (in isoform 8, isoform 10, isoform 11 and FT isoform 12)" FT /evidence="ECO:0000305" FT /id="VSP_016432" FT VAR_SEQ 1035..1113 FT /note="Missing (in isoform 13)" FT /evidence="ECO:0000305" FT /id="VSP_016431" FT VAR_SEQ 1114..1203 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_016433" FT VAR_SEQ 1153 FT /note="S -> G (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_016434" FT VARIANT 159 FT /note="T -> M (in dbSNP:rs3795564)" FT /id="VAR_017251" FT VARIANT 359 FT /note="R -> P (in NEDCPMD; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28940097" FT /id="VAR_083116" FT VARIANT 835..1347 FT /note="Missing (in NEDCPMD; uncertain significance; no FT protein expression)" FT /evidence="ECO:0000269|PubMed:30124836" FT /id="VAR_083117" FT VARIANT 1229 FT /note="V -> E (in NEDCPMD; uncertain significance; FT decreased protein abundance in patient-derived cells; FT decreased cell surface localization)" FT /evidence="ECO:0000269|PubMed:30850329" FT /id="VAR_083118" FT CONFLICT 807 FT /note="F -> L (in Ref. 3; BAB55195)" FT /evidence="ECO:0000305" FT CONFLICT 972 FT /note="F -> V (in Ref. 3; AK127424)" FT /evidence="ECO:0000305" FT STRAND 43..46 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 49..53 FT /evidence="ECO:0007829|PDB:3P40" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 63..65 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 72..77 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 84..86 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:3P3Y" FT TURN 104..106 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 109..112 FT /evidence="ECO:0007829|PDB:3P40" FT STRAND 114..121 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 126..136 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 140..144 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 147..149 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 150..153 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 172..176 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 187..191 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 197..201 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 205..207 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 211..216 FT /evidence="ECO:0007829|PDB:3P3Y" FT TURN 218..220 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 223..225 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 231..234 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:3P40" FT STRAND 246..249 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 251..259 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 264..267 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 277..282 FT /evidence="ECO:0007829|PDB:3P3Y" FT TURN 289..291 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 300..305 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 308..310 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 312..319 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 324..341 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 346..348 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 354..357 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 359..364 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 367..372 FT /evidence="ECO:0007829|PDB:3P3Y" FT HELIX 377..379 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 386..389 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 392..397 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 405..412 FT /evidence="ECO:0007829|PDB:3P3Y" FT STRAND 415..425 FT /evidence="ECO:0007829|PDB:3P3Y" SQ SEQUENCE 1347 AA; 150027 MW; 4DC555E5AA06C223 CRC64; MARQPPPPWV HAAFLLCLLS LGGAIEIPMD PSIQNELTQP PTITKQSAKD HIVDPRDNIL IECEAKGNPA PSFHWTRNSR FFNIAKDPRV SMRRRSGTLV IDFRSGGRPE EYEGEYQCFA RNKFGTALSN RIRLQVSKSP LWPKENLDPV VVQEGAPLTL QCNPPPGLPS PVIFWMSSSM EPITQDKRVS QGHNGDLYFS NVMLQDMQTD YSCNARFHFT HTIQQKNPFT LKVLTTRGVA ERTPSFMYPQ GTASSQMVLR GMDLLLECIA SGVPTPDIAW YKKGGDLPSD KAKFENFNKA LRITNVSEED SGEYFCLASN KMGSIRHTIS VRVKAAPYWL DEPKNLILAP GEDGRLVCRA NGNPKPTVQW MVNGEPLQSA PPNPNREVAG DTIIFRDTQI SSRAVYQCNT SNEHGYLLAN AFVSVLDVPP RMLSPRNQLI RVILYNRTRL DCPFFGSPIP TLRWFKNGQG SNLDGGNYHV YENGSLEIKM IRKEDQGIYT CVATNILGKA ENQVRLEVKD PTRIYRMPED QVARRGTTVQ LECRVKHDPS LKLTVSWLKD DEPLYIGNRM KKEDDSLTIF GVAERDQGSY TCVASTELDQ DLAKAYLTVL ADQATPTNRL AALPKGRPDR PRDLELTDLA ERSVRLTWIP GDANNSPITD YVVQFEEDQF QPGVWHDHSK YPGSVNSAVL RLSPYVNYQF RVIAINEVGS SHPSLPSERY RTSGAPPESN PGDVKGEGTR KNNMEITWTP MNATSAFGPN LRYIVKWRRR ETREAWNNVT VWGSRYVVGQ TPVYVPYEIR VQAENDFGKG PEPESVIGYS GEDYPRAAPT EVKVRVMNST AISLQWNRVY SDTVQGQLRE YRAYYWRESS LLKNLWVSQK RQQASFPGDR LRGVVSRLFP YSNYKLEMVV VNGRGDGPRS ETKEFTTPEG VPSAPRRFRV RQPNLETINL EWDHPEHPNG IMIGYTLKYV AFNGTKVGKQ IVENFSPNQT KFTVQRTDPV SRYRFTLSAR TQVGSGEAVT EESPAPPNEA TPTAAPPTLP PTTVGATGAV SSTDATAIAA TTEATTVPII PTVAPTTIAT TTTVATTTTT TAAATTTTES PPTTTSGTKI HESAPDEQSI WNVTVLPNSK WANITWKHNF GPGTDFVVEY IDSNHTKKTV PVKAQAQPIQ LTDLYPGMTY TLRVYSRDNE GISSTVITFM TSTAYTNNQA DIATQGWFIG LMCAIALLVL ILLIVCFIKR SRGGKYPVRE KKDVPLGPED PKEEDGSFDY SDEDNKPLQG SQTSLDGTIK QQESDDSLVD YGEGGEGQFN EDGSFIGQYT VKKDKEETEG NESSEATSPV NAIYSLA //