L1CAM_HUMAN
ID L1CAM_HUMAN Reviewed; 1257 AA.
AC P32004; A0AV65; A4ZYW4; B2RMU7; G3XAF4; Q8TA87;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Neural cell adhesion molecule L1;
DE Short=N-CAM-L1;
DE Short=NCAM-L1;
DE AltName: CD_antigen=CD171;
DE Flags: Precursor;
GN Name=L1CAM; Synonyms=CAML1, MIC5;
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).
RC TISSUE=Fetal brain;
RX PubMed=1932117; DOI=10.1016/0167-4781(91)90108-x;
RA Kobayashi M., Miura M., Asou H., Uyemura K.;
RT "Molecular cloning of cell adhesion molecule L1 from human nervous tissue:
RT a comparison of the primary sequences of L1 molecules of different
RT origin.";
RL Biochim. Biophys. Acta 1090:238-240(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=1769655; DOI=10.1016/0888-7543(91)90150-d;
RA Hlavin M.L., Lemmon V.;
RT "Molecular structure and functional testing of human L1CAM: an interspecies
RT comparison.";
RL Genomics 11:416-423(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1627459; DOI=10.1007/bf02919404;
RA Reid R.A., Hemperly J.J.;
RT "Variants of human L1 cell adhesion molecule arise through alternate
RT splicing of RNA.";
RL J. Mol. Neurosci. 3:127-135(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9286695; DOI=10.1006/geno.1997.4822;
RA Brenner V., Nyakatura G., Rosenthal A., Platzer M.;
RT "Genomic organization of two novel genes on human Xq28: compact head to
RT head arrangement of IDH gamma and TRAP delta is conserved in rat and
RT mouse.";
RL Genomics 44:8-14(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=9479034; DOI=10.1016/s0378-1119(97)00614-8;
RA Coutelle O., Nyakatura G., Taudien S., Elgar G., Brenner S., Platzer M.,
RA Drescher B., Jouet M., Kenwrick S., Rosenthal A.;
RT "The neural cell adhesion molecule L1: genomic organisation and
RT differential splicing is conserved between man and the pufferfish Fugu.";
RL Gene 208:7-15(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Son Y.S.;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [10]
RP PROTEIN SEQUENCE OF 20-36.
RX PubMed=3136168; DOI=10.1016/s0021-9258(18)37877-3;
RA Wolff J.M., Frank R., Mujoo K., Spiro R.C., Reisfeld R.A., Rathjen F.G.;
RT "A human brain glycoprotein related to the mouse cell adhesion molecule
RT L1.";
RL J. Biol. Chem. 263:11943-11947(1988).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 332-371.
RX PubMed=2387585; DOI=10.1016/0888-7543(90)90203-7;
RA Djabali M., Mattei M.-G., Nguyen C., Roux D., Demengeot J., Denizot F.,
RA Moos M., Schachner M., Goridis C., Jordan B.R.;
RT "The gene encoding L1, a neural adhesion molecule of the immunoglobulin
RT family, is located on the X chromosome in mouse and man.";
RL Genomics 7:587-593(1990).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 353-1176, AND NUCLEOTIDE SEQUENCE [GENOMIC
RP DNA] OF 1082-1176.
RC TISSUE=Fetal brain;
RX PubMed=1923824; DOI=10.1093/nar/19.19.5395;
RA Rosenthal A., Mackinnon R.N., Jones D.S.C.;
RT "PCR walking from microdissection clone M54 identifies three exons from the
RT human gene for the neural cell adhesion molecule L1 (CAM-L1).";
RL Nucleic Acids Res. 19:5395-5401(1991).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1030-1257.
RX PubMed=1993895; DOI=10.1111/j.1471-4159.1991.tb01994.x;
RA Harper J.R., Prince J.T., Healy P.A., Stuart J.K., Nauman S.J.,
RA Stallcup W.B.;
RT "Isolation and sequence of partial cDNA clones of human L1: homology of
RT human and rodent L1 in the cytoplasmic region.";
RL J. Neurochem. 56:797-804(1991).
RN [14]
RP PHOSPHORYLATION AT SER-1181.
RX PubMed=8592152; DOI=10.1046/j.1471-4159.1996.66020779.x;
RA Wong E.V., Schaefer A.W., Landreth G., Lemmon V.;
RT "Casein kinase II phosphorylates the neural cell adhesion molecule L1.";
RL J. Neurochem. 66:779-786(1996).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-671.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1163, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1248, AND IDENTIFICATION BY
RP 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 [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-671.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [19]
RP INVOLVEMENT IN L1 SYNDROME, VARIANTS 26-TYR--GLU-1257 DEL; ASN-37; MET-38;
RP 66-GLN--GLU-1257 DEL; 109-GLN--GLU-1257 DEL; 133-GLU--GLU-1257 DEL;
RP 138-TRP--GLU-1257 DEL; ILE-172; GLY-184; 187-MET--VAL-198 DEL; ASP-254;
RP ARG-276; PRO-313; 366-TRP--GLU-1257 DEL; LYS-369; 423-GLN--GLU-1257 DEL;
RP ARG-480; ASN-516; TYR-516; HIS-525; MET-627; PRO-645; 662-TRP--GLU-1257
RP DEL; SER-714; ARG-754; 760-ARG--GLU-1257 DEL; 789-GLN--GLU-1257 DEL;
RP 811-TYR--GLU-1257 DEL; 891-TYR--GLU-1257 DEL; 901-ARG--GLU-1257 DEL;
RP 1064-SER--GLU-1257 DEL; ASN-1071 DEL AND GLN-1080, VARIANTS HSAS/MASA
RP SER-179; ARG-335 AND MET-752, VARIANT MASA TYR-202, AND VARIANTS HSAS
RP GLN-184 AND PRO-415.
RX PubMed=19846429; DOI=10.1136/jmg.2009.071688;
RA Vos Y.J., de Walle H.E., Bos K.K., Stegeman J.A., Ten Berge A.M.,
RA Bruining M., van Maarle M.C., Elting M.W., den Hollander N.S., Hamel B.,
RA Fortuna A.M., Sunde L.E., Stolte-Dijkstra I., Schrander-Stumpel C.T.,
RA Hofstra R.M.;
RT "Genotype-phenotype correlations in L1 syndrome: a guide for genetic
RT counselling and mutation analysis.";
RL J. Med. Genet. 47:169-175(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1194, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-1177 (ISOFORM 2), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-1172 (ISOFORM 3), AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1177 (ISOFORM 2),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1172 (ISOFORM 3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP INVOLVEMENT IN L1 SYNDROME, VARIANTS CYS-635 AND ILE-768, AND
RP GLYCOSYLATION.
RX PubMed=22222883; DOI=10.1007/s10048-011-0307-4;
RA Marx M., Diestel S., Bozon M., Keglowich L., Drouot N., Bouche E.,
RA Frebourg T., Minz M., Saugier-Veber P., Castellani V., Schaefer M.K.;
RT "Pathomechanistic characterization of two exonic L1CAM variants located in
RT trans in an obligate carrier of X-linked hydrocephalus.";
RL Neurogenetics 13:49-59(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1243, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP VARIANT HSAS TYR-264.
RX PubMed=8401576; DOI=10.1038/ng0893-331;
RA Jouet M., Rosenthal A., Macfarlane J., Kenwrick S., Donnai D.;
RT "A missense mutation confirms the L1 defect in X-linked hydrocephalus
RT (HSAS).";
RL Nat. Genet. 4:331-331(1993).
RN [26]
RP VARIANT HSAS/MASA LEU-1194.
RX PubMed=7881431; DOI=10.1093/hmg/3.12.2255;
RA Fransen E., Schrander-Stumpel C., Vits L., Coucke P., van Camp G.,
RA Willems P.J.;
RT "X-linked hydrocephalus and MASA syndrome present in one family are due to
RT a single missense mutation in exon 28 of the L1CAM gene.";
RL Hum. Mol. Genet. 3:2255-2256(1994).
RN [27]
RP INVOLVEMENT IN MASA, INVOLVEMENT IN HSAS, VARIANTS HSAS GLN-184 AND
RP ARG-452, AND VARIANT MASA GLN-210.
RX PubMed=7920659; DOI=10.1038/ng0794-402;
RA Jouet M., Rosenthal A., Armstrong G., Macfarlane J., Stevenson R.,
RA Paterson J., Metzenberg A., Ionasescu V., Temple K., Kenwrick S.;
RT "X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked
RT hydrocephalus result from mutations in the L1 gene.";
RL Nat. Genet. 7:402-407(1994).
RN [28]
RP VARIANTS MASA GLN-210 AND ASN-598.
RX PubMed=7920660; DOI=10.1038/ng0794-408;
RA Vits L., van Camp G., Coucke P., Fransen E., de Boulle K., Reyniers E.,
RA Korn B., Poustka A., Wilson G., Schrander-Stumpel C., Winter R.M.,
RA Schwartz C., Willems P.J.;
RT "MASA syndrome is due to mutations in the neural cell adhesion gene
RT L1CAM.";
RL Nat. Genet. 7:408-413(1994).
RN [29]
RP VARIANT HSAS/MASA LEU-941, VARIANT MASA LYS-309, AND VARIANTS HSAS SER-9;
RP SER-121; PHE-768 AND CYS-1070.
RX PubMed=7762552;
RA Jouet M., Moncla A., Paterson J., McKeown C., Fryer A., Carpenter N.,
RA Holmberg E., Wadelius C., Kenwrick S.;
RT "New domains of neural cell-adhesion molecule L1 implicated in X-linked
RT hydrocephalus and MASA syndrome.";
RL Am. J. Hum. Genet. 56:1304-1314(1995).
RN [30]
RP VARIANT HSAS/MASA LEU-1194, VARIANTS HSAS GLN-184; TYR-264 AND ARG-452, AND
RP VARIANTS MASA GLN-210 AND ASN-598.
RX PubMed=8556302; DOI=10.1159/000472311;
RA Fransen E., Lemmon V., van Camp G., Vits L., Coucke P., Willems P.J.;
RT "CRASH syndrome: clinical spectrum of corpus callosum hypoplasia,
RT retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to
RT mutations in one single gene, L1.";
RL Eur. J. Hum. Genet. 3:273-284(1995).
RN [31]
RP ERRATUM OF PUBMED:8556302.
RA Fransen E., Lemmon V., van Camp G., Vits L., Coucke P., Willems P.J.;
RL Eur. J. Hum. Genet. 4:126-126(1996).
RN [32]
RP INVOLVEMENT IN MASA, INVOLVEMENT IN HSAS, AND VARIANTS HSAS/MASA SER-179
RP AND ARG-370.
RX PubMed=7562969; DOI=10.1136/jmg.32.7.549;
RA Ruiz J.C., Cuppens H., Legius E., Fryns J.-P., Glover T., Marynen P.,
RA Cassiman J.-J.;
RT "Mutations in L1-CAM in two families with X linked complicated spastic
RT paraplegia, MASA syndrome, and HSAS.";
RL J. Med. Genet. 32:549-552(1995).
RN [33]
RP VARIANT HSAS GLU-655.
RX PubMed=9118141; DOI=10.1007/bf00261591;
RA Izumoto S., Yamasaki M., Arita N., Hiraga S., Ohnishi T., Fujitani K.,
RA Sakoda S., Hayakawa T.;
RT "A new mutation of the L1CAM gene in an X-linked hydrocephalus family.";
RL Childs Nerv. Syst. 12:742-747(1996).
RN [34]
RP VARIANTS HSAS CYS-194 AND LEU-240.
RX PubMed=8929944; DOI=10.1136/jmg.33.2.103;
RA Gu S.-M., Orth U., Veske A., Enders H., Kluender K., Schloesser M.,
RA Engel W., Schwinger E., Gal A.;
RT "Five novel mutations in the L1CAM gene in families with X linked
RT hydrocephalus.";
RL J. Med. Genet. 33:103-106(1996).
RN [35]
RP VARIANT MASA PRO-482, VARIANTS HSAS SER-526 DEL; PRO-542 AND THR-741,
RP VARIANT HSAS/MASA MET-752, AND VARIANT ILE-768.
RX PubMed=9268105;
RX DOI=10.1002/(sici)1096-8628(19970822)71:3<336::aid-ajmg15>3.0.co;2-l;
RA Gu S.-M., Orth U., Zankl M., Schroeder J., Gal A.;
RT "Molecular analysis of the L1CAM gene in patients with X-linked
RT hydrocephalus demonstrates eight novel mutations and suggests non-allelic
RT heterogeneity of the trait.";
RL Am. J. Med. Genet. 71:336-340(1997).
RN [36]
RP VARIANTS MASA ASP-268 AND ASP-426.
RX PubMed=9300653; DOI=10.1093/hmg/6.10.1625;
RA Fransen E., Van Camp G., Vits L., Willems P.J.;
RT "L1-associated diseases: clinical geneticists divide, molecular geneticists
RT unite.";
RL Hum. Mol. Genet. 6:1625-1632(1997).
RN [37]
RP VARIANTS HSAS GLN-184; 439-VAL--THR-443 DEL; CYS-784 AND 936-LEU--LEU-948
RP DEL.
RX PubMed=9195224;
RX DOI=10.1002/(sici)1098-1004(1997)9:6<512::aid-humu3>3.0.co;2-3;
RA Macfarlane J.R., Du J.-S., Pepys M.E., Ramsden S., Donnai D., Charlton R.,
RA Garrett C., Tolmie J., Yates J.R.W., Berry C., Goudie D., Moncla A.,
RA Lunt P., Hodgson S., Jouet M., Kenwrick S.;
RT "Nine novel L1 CAM mutations in families with X-linked hydrocephalus.";
RL Hum. Mutat. 9:512-518(1997).
RN [38]
RP VARIANT HSAS/MASA ARG-698, VARIANT MASA ASP-691, AND VARIANT HSAS PRO-935.
RX PubMed=9521424;
RX DOI=10.1002/(sici)1098-1004(1998)11:3<222::aid-humu7>3.0.co;2-j;
RA Du Y.-Z., Srivastava A.K., Schwartz C.E.;
RT "Multiple exon screening using restriction endonuclease fingerprinting
RT (REF): detection of six novel mutations in the L1 cell adhesion molecule
RT (L1CAM) gene.";
RL Hum. Mutat. 11:222-230(1998).
RN [39]
RP VARIANT MASA PRO-632.
RX PubMed=9452110; DOI=10.1002/humu.1380110189;
RA Vits L., Chitayat D., van Camp G., Holden J.J.A., Fransen E., Willems P.J.;
RT "Evidence for somatic and germline mosaicism in CRASH syndrome.";
RL Hum. Mutat. Suppl. 1:S284-S287(1998).
RN [40]
RP VARIANTS HSAS/MASA ARG-335 AND CYS-473, AND VARIANTS HSAS THR-219; CYS-386
RP AND LEU-1224.
RX PubMed=9744477;
RX DOI=10.1002/(sici)1098-1004(1998)12:4<259::aid-humu7>3.0.co;2-a;
RA Saugier-Veber P., Martin C., le Meur N., Lyonnet S., Munnich A., David A.,
RA Henocq A., Heron D., Jonveaux P., Odent S., Manouvrier S., Moncla A.,
RA Morichon N., Philip N., Satge D., Tosi M., Frebourg T.;
RT "Identification of novel L1CAM mutations using fluorescence-assisted
RT mismatch analysis.";
RL Hum. Mutat. 12:259-266(1998).
RN [41]
RP VARIANTS MASA CYS-674 AND ASP-691, AND VARIANT HSAS/MASA ARG-698.
RX PubMed=9832035; DOI=10.1136/jmg.35.11.901;
RA Michaelis R.C., Du Y.-Z., Schwartz C.E.;
RT "The site of a missense mutation in the extracellular Ig or FN domains of
RT L1CAM influences infant mortality and the severity of X linked
RT hydrocephalus.";
RL J. Med. Genet. 35:901-904(1998).
RN [42]
RP VARIANTS HSAS TRP-184; CYS-335; ILE-408; ASP-421; TYR-497; THR-691 AND
RP PRO-751, VARIANTS ASN-30; TRP-739 AND GLU-1239, AND VARIANT HSAS/MASA
RP ARG-370.
RX PubMed=10797421;
RX DOI=10.1002/(sici)1096-8628(20000501)92:1<40::aid-ajmg7>3.0.co;2-r;
RA Finckh U., Schroeder J., Ressler B., Veske A., Gal A.;
RT "Spectrum and detection rate of L1CAM mutations in isolated and familial
RT cases with clinically suspected L1-disease.";
RL Am. J. Med. Genet. 92:40-46(2000).
RN [43]
RP VARIANT MASA TYR-202.
RX PubMed=10805190; DOI=10.1177/088307380001500407;
RA Sztriha L., Frossard P., Hofstra R.M., Verlind E., Nork M.;
RT "Novel missense mutation in the L1 gene in a child with corpus callosum
RT agenesis, retardation, adducted thumbs, spastic paraparesis, and
RT hydrocephalus.";
RL J. Child Neurol. 15:239-243(2000).
RN [44]
RP VARIANT HSAS/MASA MET-752, AND POSSIBLE INVOLVEMENT IN HIRSCHSPRUNG
RP DISEASE.
RX PubMed=11857550; DOI=10.1002/ajmg.10185;
RA Parisi M.A., Kapur R.P., Neilson I., Hofstra R.M.W., Holloway L.W.,
RA Michaelis R.C., Leppig K.A.;
RT "Hydrocephalus and intestinal aganglionosis: is L1CAM a modifier gene in
RT Hirschsprung disease?";
RL Am. J. Med. Genet. 108:51-56(2002).
RN [45]
RP VARIANT HSAS PRO-415.
RX PubMed=12435569; DOI=10.1016/s0887-8994(02)00440-x;
RA Sztriha L., Vos Y.J., Verlind E., Johansen J., Berg B.;
RT "X-linked hydrocephalus: a novel missense mutation in the L1CAM gene.";
RL Pediatr. Neurol. 27:293-296(2002).
RN [46]
RP CHARACTERIZATION OF VARIANT HSAS TYR-264, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=12514225; DOI=10.1523/jneurosci.23-01-00277.2003;
RA Ruenker A.E., Bartsch U., Nave K.A., Schachner M.;
RT "The C264Y missense mutation in the extracellular domain of L1 impairs
RT protein trafficking in vitro and in vivo.";
RL J. Neurosci. 23:277-286(2003).
RN [47]
RP VARIANT ACCPX LEU-240.
RX PubMed=16650080; DOI=10.1111/j.1399-0004.2006.00607.x;
RA Basel-Vanagaite L., Straussberg R., Friez M.J., Inbar D., Korenreich L.,
RA Shohat M., Schwartz C.E.;
RT "Expanding the phenotypic spectrum of L1CAM-associated disease.";
RL Clin. Genet. 69:414-419(2006).
RN [48]
RP VARIANT MASA ASN-770.
RX PubMed=16816908; DOI=10.1007/s10072-006-0610-2;
RA Simonati A., Boaretto F., Vettori A., Dabrilli P., Criscuolo L.,
RA Rizzuto N., Mostacciuolo M.L.;
RT "A novel missense mutation in the L1CAM gene in a boy with L1 disease.";
RL Neurol. Sci. 27:114-117(2006).
RN [49]
RP CHARACTERIZATION OF VARIANTS HSAS GLN-184 AND LEU-1036, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20621658; DOI=10.1016/j.nbd.2010.05.029;
RA Schaefer M.K., Nam Y.C., Moumen A., Keglowich L., Bouche E., Kueffner M.,
RA Bock H.H., Rathjen F.G., Raoul C., Frotscher M.;
RT "L1 syndrome mutations impair neuronal L1 function at different levels by
RT divergent mechanisms.";
RL Neurobiol. Dis. 40:222-237(2010).
RN [50]
RP INVOLVEMENT OF VARIANT HSAS/MASA ARG-698 IN HYDROCEPHALUS WITH HIRSCHSPRUNG
RP DISEASE.
RX PubMed=22344793; DOI=10.1002/ajmg.a.35244;
RA Fernandez R.M., Nunez-Torres R., Garcia-Diaz L., de Agustin J.C.,
RA Antinolo G., Borrego S.;
RT "Association of X-linked hydrocephalus and Hirschsprung disease: Report of
RT a new patient with a mutation in the L1CAM gene.";
RL Am. J. Med. Genet. A 158:816-820(2012).
RN [51]
RP CHARACTERIZATION OF VARIANTS MASA GLN-210 AND LYS-309, CHARACTERIZATION OF
RP VARIANTS HSAS THR-219 AND CYS-264, CHARACTERIZATION OF VARIANT HSAS/MASA
RP LEU-941, AND SUBCELLULAR LOCATION.
RX PubMed=22973895; DOI=10.1111/jnc.12015;
RA Tagliavacca L., Colombo F., Racchetti G., Meldolesi J.;
RT "L1CAM and its cell-surface mutants: new mechanisms and effects relevant to
RT the physiology and pathology of neural cells.";
RL J. Neurochem. 124:397-409(2013).
RN [52]
RP CHARACTERIZATION OF VARIANT VAL-120, CHARACTERIZATION OF VARIANTS MASA
RP GLN-210 AND LYS-309, CHARACTERIZATION OF VARIANTS HSAS GLN-184; TYR-264 AND
RP CYS-1070, AND MUTAGENESIS OF 1147-LYS--VAL-1153.
RX PubMed=24155914; DOI=10.1371/journal.pone.0076974;
RA Kudumala S., Freund J., Hortsch M., Godenschwege T.A.;
RT "Differential effects of human L1CAM mutations on complementing guidance
RT and synaptic defects in Drosophila melanogaster.";
RL PLoS ONE 8:E76974-E76974(2013).
RN [53]
RP VARIANT 789-GLN--GLU-1257 DEL, CHARACTERIZATION OF VARIANTS ASN-37; MET-38
RP AND ILE-172, CHARACTERIZATION OF VARIANT MASA TYR-202, AND SUBCELLULAR
RP LOCATION.
RX PubMed=26891472; DOI=10.1111/cge.12763;
RA Christaller W.A., Vos Y., Gebre-Medhin S., Hofstra R.M., Schaefer M.K.;
RT "L1 syndrome diagnosis complemented with functional analysis of L1CAM
RT variants located to the two N-terminal Ig-like domains.";
RL Clin. Genet. 91:115-120(2017).
CC -!- FUNCTION: Neural cell adhesion molecule involved in the dynamics of
CC cell adhesion and in the generation of transmembrane signals at
CC tyrosine kinase receptors. During brain development, critical in
CC multiple processes, including neuronal migration, axonal growth and
CC fasciculation, and synaptogenesis. In the mature brain, plays a role in
CC the dynamics of neuronal structure and function, including synaptic
CC plasticity. {ECO:0000269|PubMed:20621658, ECO:0000305}.
CC -!- SUBUNIT: Interacts with SHTN1; the interaction occurs in axonal growth
CC cones (By similarity). Interacts with isoform 2 of BSG (By similarity).
CC {ECO:0000250|UniProtKB:P11627, ECO:0000250|UniProtKB:Q05695}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12514225,
CC ECO:0000269|PubMed:20621658, ECO:0000269|PubMed:22973895,
CC ECO:0000269|PubMed:26891472}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q05695}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q05695}. Cell projection, axon
CC {ECO:0000269|PubMed:20621658}. Cell projection, dendrite.
CC Note=Colocalized with SHTN1 in close apposition with actin filaments in
CC filopodia and lamellipodia of axonalne growth cones of hippocampal
CC neurons (By similarity). In neurons, detected predominantly in axons
CC and cell body, weak localization to dendrites (PubMed:20621658).
CC {ECO:0000250|UniProtKB:Q05695, ECO:0000269|PubMed:20621658}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P32004-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32004-2; Sequence=VSP_002591;
CC Name=3;
CC IsoId=P32004-3; Sequence=VSP_046317, VSP_002591;
CC -!- DISEASE: Hydrocephalus due to stenosis of the aqueduct of Sylvius
CC (HSAS) [MIM:307000]: Hydrocephalus is a condition in which abnormal
CC accumulation of cerebrospinal fluid in the brain causes increased
CC intracranial pressure inside the skull. This is usually due to blockage
CC of cerebrospinal fluid outflow in the brain ventricles or in the
CC subarachnoid space at the base of the brain. In children is typically
CC characterized by enlargement of the head, prominence of the forehead,
CC brain atrophy, mental deterioration, and convulsions. In adults the
CC syndrome includes incontinence, imbalance, and dementia. HSAS is
CC characterized by intellectual disability and enlarged brain ventricles.
CC {ECO:0000269|PubMed:10797421, ECO:0000269|PubMed:11857550,
CC ECO:0000269|PubMed:12435569, ECO:0000269|PubMed:12514225,
CC ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:20621658,
CC ECO:0000269|PubMed:22344793, ECO:0000269|PubMed:22973895,
CC ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:7562969,
CC ECO:0000269|PubMed:7762552, ECO:0000269|PubMed:7881431,
CC ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:8401576,
CC ECO:0000269|PubMed:8556302, ECO:0000269|PubMed:8929944,
CC ECO:0000269|PubMed:9118141, ECO:0000269|PubMed:9195224,
CC ECO:0000269|PubMed:9268105, ECO:0000269|PubMed:9521424,
CC ECO:0000269|PubMed:9744477, ECO:0000269|PubMed:9832035}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. L1CAM mutations have also been found in few patients affected by
CC hydrocephalus with Hirschsprung disease, suggesting a role of this gene
CC acting either in a direct or indirect way in the pathogenesis of
CC Hirschsprung disease (PubMed:22344793). {ECO:0000269|PubMed:22344793}.
CC -!- DISEASE: MASA syndrome (MASA) [MIM:303350]: An X-linked recessive
CC syndrome with a highly variable clinical spectrum. Main clinical
CC features include spasticity and hyperreflexia of lower limbs, shuffling
CC gait, intellectual disability, aphasia and adducted thumbs. The
CC features of spasticity have been referred to as complicated spastic
CC paraplegia type 1 (SPG1). Some patients manifest corpus callosum
CC hypoplasia and hydrocephalus. Inter- and intrafamilial variability is
CC very wide, such that patients with hydrocephalus, MASA, SPG1, and
CC agenesis of corpus callosum can be present within the same family.
CC {ECO:0000269|PubMed:10797421, ECO:0000269|PubMed:10805190,
CC ECO:0000269|PubMed:11857550, ECO:0000269|PubMed:16816908,
CC ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:22344793,
CC ECO:0000269|PubMed:22973895, ECO:0000269|PubMed:24155914,
CC ECO:0000269|PubMed:26891472, ECO:0000269|PubMed:7562969,
CC ECO:0000269|PubMed:7762552, ECO:0000269|PubMed:7881431,
CC ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:7920660,
CC ECO:0000269|PubMed:8556302, ECO:0000269|PubMed:9268105,
CC ECO:0000269|PubMed:9300653, ECO:0000269|PubMed:9452110,
CC ECO:0000269|PubMed:9521424, ECO:0000269|PubMed:9744477,
CC ECO:0000269|PubMed:9832035}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in L1CAM may contribute to Hirschsprung disease
CC by modifying the effects of Hirschsprung disease-associated genes to
CC cause intestinal aganglionosis. {ECO:0000269|PubMed:11857550}.
CC -!- DISEASE: Agenesis of the corpus callosum, X-linked, partial (ACCPX)
CC [MIM:304100]: A syndrome characterized by partial corpus callosum
CC agenesis, hypoplasia of inferior vermis and cerebellum, intellectual
CC disability, seizures and spasticity. Other features include
CC microcephaly, unusual facies, and Hirschsprung disease in some
CC patients. {ECO:0000269|PubMed:16650080}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in L1CAM are associated with a wide phenotypic
CC spectrum which varies from severe hydrocephalus and prenatal death
CC (HSAS) to a milder phenotype (MASA). These variations may even occur
CC within the same family. Due to the overlap of phenotypes between HSAS
CC and MASA, many authors use the general concept of L1 syndrome which
CC covers both ends of the spectrum. {ECO:0000269|PubMed:19846429,
CC ECO:0000269|PubMed:22222883, ECO:0000269|PubMed:26891472}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily.
CC L1/neurofascin/NgCAM family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/L1CAMID44110chXq28.html";
CC -!- WEB RESOURCE: Name=L1CAM; Note=L1CAM mutation Web Page;
CC URL="http://www.l1cammutationdatabase.info/";
CC ---------------------------------------------------------------------------
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DR EMBL; X59847; CAA42508.1; -; mRNA.
DR EMBL; M77640; AAC14352.1; -; mRNA.
DR EMBL; M74387; AAA59476.1; -; mRNA.
DR EMBL; U52111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z29373; CAA82564.1; -; Genomic_DNA.
DR EMBL; EF506611; ABP88252.1; -; mRNA.
DR EMBL; U52112; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471172; EAW72787.1; -; Genomic_DNA.
DR EMBL; BC025843; AAH25843.1; -; mRNA.
DR EMBL; BC126229; AAI26230.1; -; mRNA.
DR EMBL; BC136447; AAI36448.1; -; mRNA.
DR EMBL; M55271; AAA36353.1; ALT_SEQ; mRNA.
DR EMBL; X58775; CAA41576.1; -; Genomic_DNA.
DR EMBL; X58776; CAB37831.1; -; mRNA.
DR CCDS; CCDS14733.1; -. [P32004-1]
DR CCDS; CCDS14734.1; -. [P32004-2]
DR CCDS; CCDS48192.1; -. [P32004-3]
DR PIR; A41060; A41060.
DR RefSeq; NP_000416.1; NM_000425.4. [P32004-1]
DR RefSeq; NP_001137435.1; NM_001143963.2. [P32004-3]
DR RefSeq; NP_001265045.1; NM_001278116.1. [P32004-1]
DR RefSeq; NP_076493.1; NM_024003.3. [P32004-2]
DR AlphaFoldDB; P32004; -.
DR SMR; P32004; -.
DR BioGRID; 110094; 58.
DR CORUM; P32004; -.
DR ELM; P32004; -.
DR IntAct; P32004; 11.
DR MINT; P32004; -.
DR STRING; 9606.ENSP00000359077; -.
DR DrugBank; DB00898; Ethanol.
DR GlyConnect; 1547; 18 N-Linked glycans (4 sites).
DR GlyGen; P32004; 22 sites, 20 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P32004; -.
DR PhosphoSitePlus; P32004; -.
DR SwissPalm; P32004; -.
DR BioMuta; L1CAM; -.
DR DMDM; 1705571; -.
DR EPD; P32004; -.
DR jPOST; P32004; -.
DR MassIVE; P32004; -.
DR MaxQB; P32004; -.
DR PaxDb; P32004; -.
DR PeptideAtlas; P32004; -.
DR PRIDE; P32004; -.
DR ProteomicsDB; 33733; -.
DR ProteomicsDB; 54830; -. [P32004-1]
DR ProteomicsDB; 54831; -. [P32004-2]
DR ABCD; P32004; 16 sequenced antibodies.
DR Antibodypedia; 449; 1204 antibodies from 45 providers.
DR DNASU; 3897; -.
DR Ensembl; ENST00000361699.8; ENSP00000355380.4; ENSG00000198910.14. [P32004-2]
DR Ensembl; ENST00000361981.7; ENSP00000354712.3; ENSG00000198910.14. [P32004-3]
DR Ensembl; ENST00000370055.5; ENSP00000359072.1; ENSG00000198910.14. [P32004-3]
DR Ensembl; ENST00000370060.7; ENSP00000359077.1; ENSG00000198910.14. [P32004-1]
DR GeneID; 3897; -.
DR KEGG; hsa:3897; -.
DR MANE-Select; ENST00000370060.7; ENSP00000359077.1; NM_001278116.2; NP_001265045.1.
DR UCSC; uc004fjc.5; human. [P32004-1]
DR CTD; 3897; -.
DR DisGeNET; 3897; -.
DR GeneCards; L1CAM; -.
DR GeneReviews; L1CAM; -.
DR HGNC; HGNC:6470; L1CAM.
DR HPA; ENSG00000198910; Tissue enhanced (brain, intestine).
DR MalaCards; L1CAM; -.
DR MIM; 303350; phenotype.
DR MIM; 304100; phenotype.
DR MIM; 307000; phenotype.
DR MIM; 308840; gene.
DR neXtProt; NX_P32004; -.
DR OpenTargets; ENSG00000198910; -.
DR Orphanet; 2182; Hydrocephalus with stenosis of the aqueduct of Sylvius.
DR Orphanet; 2466; MASA syndrome.
DR Orphanet; 1497; X-linked complicated corpus callosum dysgenesis.
DR Orphanet; 306617; X-linked complicated spastic paraplegia type 1.
DR PharmGKB; PA30259; -.
DR VEuPathDB; HostDB:ENSG00000198910; -.
DR eggNOG; KOG3513; Eukaryota.
DR GeneTree; ENSGT00940000157506; -.
DR HOGENOM; CLU_005756_1_1_1; -.
DR InParanoid; P32004; -.
DR OMA; HNKTLHL; -.
DR OrthoDB; 434404at2759; -.
DR PhylomeDB; P32004; -.
DR TreeFam; TF351098; -.
DR PathwayCommons; P32004; -.
DR Reactome; R-HSA-210991; Basigin interactions.
DR Reactome; R-HSA-373760; L1CAM interactions.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR Reactome; R-HSA-445144; Signal transduction by L1.
DR SignaLink; P32004; -.
DR SIGNOR; P32004; -.
DR BioGRID-ORCS; 3897; 7 hits in 695 CRISPR screens.
DR ChiTaRS; L1CAM; human.
DR GeneWiki; L1_(protein); -.
DR GenomeRNAi; 3897; -.
DR Pharos; P32004; Tbio.
DR PRO; PR:P32004; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P32004; protein.
DR Bgee; ENSG00000198910; Expressed in cortical plate and 160 other tissues.
DR ExpressionAtlas; P32004; baseline and differential.
DR Genevisible; P32004; HS.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008046; F:axon guidance receptor activity; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IDA:CAFA.
DR GO; GO:0061564; P:axon development; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; IDA:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; TAS:BHF-UCL.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0031175; P:neuron projection development; IDA:UniProtKB.
DR GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB.
DR GO; GO:0050808; P:synapse organization; IDA:UniProtKB.
DR CDD; cd00063; FN3; 4.
DR DisProt; DP00666; -.
DR Gene3D; 2.60.40.10; -; 10.
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; IPR026966; Neurofascin/L1/NrCAM_C.
DR Pfam; PF13882; Bravo_FIGEY; 1.
DR Pfam; PF00041; fn3; 4.
DR Pfam; PF07679; I-set; 1.
DR SMART; SM00060; FN3; 4.
DR SMART; SM00409; IG; 6.
DR SMART; SM00408; IGc2; 5.
DR SUPFAM; SSF48726; SSF48726; 6.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 5.
DR PROSITE; PS50835; IG_LIKE; 6.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Cell projection;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein;
KW Hereditary spastic paraplegia; Hirschsprung disease; Immunoglobulin domain;
KW Intellectual disability; Membrane; Neurodegeneration; Neurogenesis;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:3136168"
FT CHAIN 20..1257
FT /note="Neural cell adhesion molecule L1"
FT /id="PRO_0000015022"
FT TOPO_DOM 20..1120
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1121..1143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1144..1257
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..125
FT /note="Ig-like C2-type 1"
FT DOMAIN 139..226
FT /note="Ig-like C2-type 2"
FT DOMAIN 240..328
FT /note="Ig-like C2-type 3"
FT DOMAIN 333..420
FT /note="Ig-like C2-type 4"
FT DOMAIN 425..507
FT /note="Ig-like C2-type 5"
FT DOMAIN 518..607
FT /note="Ig-like C2-type 6"
FT DOMAIN 615..712
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 717..810
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 814..916
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 920..1015
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1016..1115
FT /note="Fibronectin type-III 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 698..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1176..1207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1226..1257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 554..556
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOD_RES 1163
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 1178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11627"
FT MOD_RES 1181
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:8592152"
FT MOD_RES 1194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1244
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11627"
FT MOD_RES 1248
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 490
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 588
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 671
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 726
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 777
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 825
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 849
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 876
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 979
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1022
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1030
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1071
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 57..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 158..209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 264..312
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 354..404
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 448..497
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 539..591
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 26..31
FT /note="YEGHHV -> L (in isoform 3)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_046317"
FT VAR_SEQ 1177..1180
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:1627459, ECO:0000303|Ref.6"
FT /id="VSP_002591"
FT VARIANT 9
FT /note="W -> S (in HSAS)"
FT /evidence="ECO:0000269|PubMed:7762552"
FT /id="VAR_003921"
FT VARIANT 26..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078350"
FT VARIANT 30
FT /note="H -> N"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030403"
FT VARIANT 37
FT /note="I -> N (probable disease-associated variant found in
FT L1 syndrome; loss of localization at the cell surface;
FT retention in the endoplasmic reticulum; loss of homophilic
FT interactions at the cell surface)"
FT /evidence="ECO:0000269|PubMed:19846429,
FT ECO:0000269|PubMed:26891472"
FT /id="VAR_078351"
FT VARIANT 38
FT /note="T -> M (no effect on localization at the cell
FT surface; dbSNP:rs201151358)"
FT /evidence="ECO:0000269|PubMed:19846429,
FT ECO:0000269|PubMed:26891472"
FT /id="VAR_078352"
FT VARIANT 66..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078353"
FT VARIANT 109..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078354"
FT VARIANT 120
FT /note="L -> V (no effect on axon guidance activity, nor on
FT synapse formation, when assayed in a heterologous system;
FT dbSNP:rs796052697)"
FT /evidence="ECO:0000269|PubMed:24155914"
FT /id="VAR_078355"
FT VARIANT 121
FT /note="G -> S (in HSAS)"
FT /evidence="ECO:0000269|PubMed:7762552"
FT /id="VAR_003922"
FT VARIANT 133..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078356"
FT VARIANT 138..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078357"
FT VARIANT 172
FT /note="M -> I (probable disease-associated variant found in
FT a patient with L1 syndrome; loss of homophilic interactions
FT at the cell surface; no effect on the localization at the
FT cell surface)"
FT /evidence="ECO:0000269|PubMed:19846429,
FT ECO:0000269|PubMed:26891472"
FT /id="VAR_078358"
FT VARIANT 179
FT /note="I -> S (in HSAS and MASA; dbSNP:rs137852523)"
FT /evidence="ECO:0000269|PubMed:19846429,
FT ECO:0000269|PubMed:7562969"
FT /id="VAR_003923"
FT VARIANT 184
FT /note="R -> G (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078359"
FT VARIANT 184
FT /note="R -> Q (in HSAS; severe; reduced axon arborization;
FT partial loss of localization at the cell surface; retention
FT in the endoplasmic reticulum; in neurons, restricted to
FT cell bodies and proximal segments of processes; loss of
FT axon guidance and of proper synapse formation, when assayed
FT in a heterologous system; dbSNP:rs137852521)"
FT /evidence="ECO:0000269|PubMed:19846429,
FT ECO:0000269|PubMed:20621658, ECO:0000269|PubMed:24155914,
FT ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:8556302,
FT ECO:0000269|PubMed:9195224"
FT /id="VAR_003924"
FT VARIANT 184
FT /note="R -> W (in HSAS)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030404"
FT VARIANT 187..198
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078360"
FT VARIANT 194
FT /note="Y -> C (in HSAS)"
FT /evidence="ECO:0000269|PubMed:8929944"
FT /id="VAR_003925"
FT VARIANT 202
FT /note="D -> Y (in MASA; loss of homophilic interactions at
FT the cell surface; no effect on localization at the cell
FT surface)"
FT /evidence="ECO:0000269|PubMed:10805190,
FT ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:26891472"
FT /id="VAR_030405"
FT VARIANT 210
FT /note="H -> Q (in MASA; decrease in cell-matrix adhesion;
FT decreased cell migration; loss of axon guidance and of
FT proper synapse formation, when assayed in a heterologous
FT system; no effect on the localization at the cell surface;
FT no effect on cell proliferation, when transfected in
FT pheochromocytoma PC12 cells; no effect on neurite
FT outgrowth, when assayed in NGF-treated pheochromocytoma
FT PC12 cells; dbSNP:rs28933683)"
FT /evidence="ECO:0000269|PubMed:22973895,
FT ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:7920659,
FT ECO:0000269|PubMed:7920660, ECO:0000269|PubMed:8556302"
FT /id="VAR_003926"
FT VARIANT 219
FT /note="I -> T (in HSAS; decrease in cell-matrix adhesion;
FT decreased cell migration; no effect on the localization at
FT the cell surface; no effect on cell proliferation, when
FT transfected in pheochromocytoma PC12 cells; no effect on
FT neurite outgrowth, when assayed in NGF-treated
FT pheochromocytoma PC12 cells)"
FT /evidence="ECO:0000269|PubMed:22973895,
FT ECO:0000269|PubMed:9744477"
FT /id="VAR_003927"
FT VARIANT 240
FT /note="P -> L (in HSAS and ACCPX; dbSNP:rs137852526)"
FT /evidence="ECO:0000269|PubMed:16650080,
FT ECO:0000269|PubMed:8929944"
FT /id="VAR_003928"
FT VARIANT 254
FT /note="A -> D (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078361"
FT VARIANT 264
FT /note="C -> Y (in HSAS; severe; loss of localization to the
FT cell surface; retention in the endoplasmic reticulum; loss
FT of axon guidance, when assayed in a heterologous system;
FT dbSNP:rs137852518)"
FT /evidence="ECO:0000269|PubMed:12514225,
FT ECO:0000269|PubMed:22973895, ECO:0000269|PubMed:24155914,
FT ECO:0000269|PubMed:8401576, ECO:0000269|PubMed:8556302"
FT /id="VAR_003929"
FT VARIANT 268
FT /note="G -> D (in MASA)"
FT /evidence="ECO:0000269|PubMed:9300653"
FT /id="VAR_030406"
FT VARIANT 276
FT /note="W -> R (probable disease-associated variant found in
FT L1 syndrome; dbSNP:rs1131691900)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078362"
FT VARIANT 309
FT /note="E -> K (in MASA; decrease in neurite outgrowth, when
FT assayed in NGF-treated pheochromocytoma PC12 cells;
FT decrease in cell-matrix adhesion; decreased cell migration;
FT no effect on axon guidance, on subcellular location to
FT synaptic terminals, nor on proper synapse formation, when
FT assayed in a heterologous system; no effect on the
FT localization at the cell surface; no effect on cell
FT proliferation, when transfected in pheochromocytoma PC12
FT cells; dbSNP:rs367665974)"
FT /evidence="ECO:0000269|PubMed:22973895,
FT ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:7762552"
FT /id="VAR_003930"
FT VARIANT 313
FT /note="L -> P (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078363"
FT VARIANT 335
FT /note="W -> C (in HSAS)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030407"
FT VARIANT 335
FT /note="W -> R (in HSAS and MASA; also in a patient with
FT hydrocephalus and Hirschsprung disease)"
FT /evidence="ECO:0000269|PubMed:19846429,
FT ECO:0000269|PubMed:9744477"
FT /id="VAR_003931"
FT VARIANT 366..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078364"
FT VARIANT 369
FT /note="N -> K (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078365"
FT VARIANT 370
FT /note="G -> R (in HSAS and MASA; dbSNP:rs137852524)"
FT /evidence="ECO:0000269|PubMed:10797421,
FT ECO:0000269|PubMed:7562969"
FT /id="VAR_003932"
FT VARIANT 386
FT /note="R -> C (in HSAS; dbSNP:rs1557092299)"
FT /evidence="ECO:0000269|PubMed:9744477"
FT /id="VAR_003933"
FT VARIANT 408
FT /note="N -> I (in HSAS)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030408"
FT VARIANT 415
FT /note="A -> P (in HSAS)"
FT /evidence="ECO:0000269|PubMed:12435569,
FT ECO:0000269|PubMed:19846429"
FT /id="VAR_027512"
FT VARIANT 421
FT /note="V -> D (in HSAS)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030409"
FT VARIANT 423..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078366"
FT VARIANT 426
FT /note="A -> D (in MASA)"
FT /evidence="ECO:0000269|PubMed:9300653"
FT /id="VAR_030410"
FT VARIANT 439..443
FT /note="Missing (in HSAS)"
FT /evidence="ECO:0000269|PubMed:9195224"
FT /id="VAR_003934"
FT VARIANT 452
FT /note="G -> R (in HSAS; severe; dbSNP:rs137852520)"
FT /evidence="ECO:0000269|PubMed:7920659,
FT ECO:0000269|PubMed:8556302"
FT /id="VAR_003935"
FT VARIANT 473
FT /note="R -> C (in HSAS and MASA; dbSNP:rs886039408)"
FT /evidence="ECO:0000269|PubMed:9744477"
FT /id="VAR_003936"
FT VARIANT 480
FT /note="G -> R (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078367"
FT VARIANT 482
FT /note="L -> P (in MASA; dbSNP:rs1064794246)"
FT /evidence="ECO:0000269|PubMed:9268105"
FT /id="VAR_030411"
FT VARIANT 497
FT /note="C -> Y (in HSAS)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030412"
FT VARIANT 516
FT /note="D -> N (found in a patient with L1 syndrome; unknown
FT pathological significance; dbSNP:rs782367931)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078368"
FT VARIANT 516
FT /note="D -> Y (found in a patient with L1 syndrome; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078369"
FT VARIANT 525
FT /note="R -> H (found in a patient with L1 syndrome; unknown
FT pathological significance; dbSNP:rs782401498)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078370"
FT VARIANT 526
FT /note="Missing (in HSAS)"
FT /evidence="ECO:0000269|PubMed:9268105"
FT /id="VAR_030413"
FT VARIANT 542
FT /note="S -> P (in HSAS)"
FT /evidence="ECO:0000269|PubMed:9268105"
FT /id="VAR_030414"
FT VARIANT 598
FT /note="D -> N (in MASA; dbSNP:rs137852519)"
FT /evidence="ECO:0000269|PubMed:7920660,
FT ECO:0000269|PubMed:8556302"
FT /id="VAR_003937"
FT VARIANT 627
FT /note="T -> M (in dbSNP:rs398123360)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078371"
FT VARIANT 632
FT /note="R -> P (in MASA)"
FT /evidence="ECO:0000269|PubMed:9452110"
FT /id="VAR_003938"
FT VARIANT 635
FT /note="W -> C (probable disease-associated variant found in
FT L1 syndrome; loss of localization at the cell surface;
FT retention in the endoplasmic reticulum; loss of transport
FT into axons; loss of neurite outgrowth; loss of cell-cell
FT adhesion)"
FT /evidence="ECO:0000269|PubMed:22222883"
FT /id="VAR_078372"
FT VARIANT 645
FT /note="I -> P (probable disease-associated variant found in
FT L1 syndrome; requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078373"
FT VARIANT 655
FT /note="K -> E (in HSAS; dbSNP:rs1375788131)"
FT /evidence="ECO:0000269|PubMed:9118141"
FT /id="VAR_030415"
FT VARIANT 662..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078374"
FT VARIANT 674
FT /note="S -> C (in MASA; associated with callosal agenesis)"
FT /evidence="ECO:0000269|PubMed:9832035"
FT /id="VAR_027513"
FT VARIANT 691
FT /note="A -> D (in MASA; associated with callosal agenesis)"
FT /evidence="ECO:0000269|PubMed:9521424,
FT ECO:0000269|PubMed:9832035"
FT /id="VAR_003939"
FT VARIANT 691
FT /note="A -> T (in HSAS)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030416"
FT VARIANT 698
FT /note="G -> R (in HSAS and MASA; associated with callosal
FT agenesis; also found in a patient affected by hydrocephalus
FT with Hirschsprung disease; dbSNP:rs886039409)"
FT /evidence="ECO:0000269|PubMed:9521424,
FT ECO:0000269|PubMed:9832035"
FT /id="VAR_003940"
FT VARIANT 714
FT /note="P -> S (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078375"
FT VARIANT 739
FT /note="R -> W (in dbSNP:rs142424573)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030417"
FT VARIANT 741
FT /note="M -> T (in HSAS; dbSNP:rs1557091083)"
FT /evidence="ECO:0000269|PubMed:9268105"
FT /id="VAR_030418"
FT VARIANT 751
FT /note="R -> P (in HSAS)"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030419"
FT VARIANT 752
FT /note="V -> M (in HSAS and MASA; also found in a patient
FT with the diagnosis of L1 syndrome; also in a patient with
FT hydrocephalus and Hirschsprung disease; dbSNP:rs137852525)"
FT /evidence="ECO:0000269|PubMed:11857550,
FT ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:9268105"
FT /id="VAR_014421"
FT VARIANT 754
FT /note="W -> R (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078376"
FT VARIANT 760..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078377"
FT VARIANT 768
FT /note="V -> F (in HSAS)"
FT /evidence="ECO:0000269|PubMed:7762552"
FT /id="VAR_003941"
FT VARIANT 768
FT /note="V -> I (decreased cell-cell adhesion; no effect on
FT subcellular localization; no effect on neurite outgrowth;
FT dbSNP:rs36021462)"
FT /evidence="ECO:0000269|PubMed:22222883,
FT ECO:0000269|PubMed:9268105"
FT /id="VAR_030420"
FT VARIANT 770
FT /note="D -> N (in MASA; associated with callosal agenesis;
FT dbSNP:rs148516831)"
FT /evidence="ECO:0000269|PubMed:16816908"
FT /id="VAR_027514"
FT VARIANT 784
FT /note="Y -> C (in HSAS; dbSNP:rs797045674)"
FT /evidence="ECO:0000269|PubMed:9195224"
FT /id="VAR_003942"
FT VARIANT 789..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429,
FT ECO:0000269|PubMed:26891472"
FT /id="VAR_078378"
FT VARIANT 811..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078379"
FT VARIANT 891..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078380"
FT VARIANT 901..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078381"
FT VARIANT 935
FT /note="L -> P (in HSAS)"
FT /evidence="ECO:0000269|PubMed:9521424"
FT /id="VAR_003943"
FT VARIANT 936..948
FT /note="Missing (in HSAS)"
FT /evidence="ECO:0000269|PubMed:9195224"
FT /id="VAR_003944"
FT VARIANT 941
FT /note="P -> L (in HSAS and MASA; decrease in neurite
FT outgrowth, when assayed in NGF-treated pheochromocytoma
FT PC12 cells; decrease in cell-matrix adhesion; decreased
FT cell migration; no effect on the localization at the cell
FT surface; no effect on cell proliferation, when transfected
FT in pheochromocytoma PC12 cells)"
FT /evidence="ECO:0000269|PubMed:22973895,
FT ECO:0000269|PubMed:7762552"
FT /id="VAR_003945"
FT VARIANT 958
FT /note="L -> V (in dbSNP:rs35902890)"
FT /id="VAR_059413"
FT VARIANT 1036
FT /note="W -> L (in HSAS; partial loss of localization at the
FT cell surface; retention in the endoplasmic reticulum; in
FT neurons, partial loss of localization to axons, but
FT enriched on proximal dendrites)"
FT /evidence="ECO:0000269|PubMed:20621658"
FT /id="VAR_078382"
FT VARIANT 1064..1257
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078383"
FT VARIANT 1070
FT /note="Y -> C (in HSAS; partial loss of axon guidance and
FT loss of proper synapse formation, when assayed in a
FT heterologous system)"
FT /evidence="ECO:0000269|PubMed:24155914,
FT ECO:0000269|PubMed:7762552"
FT /id="VAR_003946"
FT VARIANT 1071
FT /note="Missing (probable disease-associated variant found
FT in L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078384"
FT VARIANT 1080
FT /note="L -> Q (probable disease-associated variant found in
FT L1 syndrome)"
FT /evidence="ECO:0000269|PubMed:19846429"
FT /id="VAR_078385"
FT VARIANT 1194
FT /note="S -> L (in HSAS and MASA; dbSNP:rs137852522)"
FT /evidence="ECO:0000269|PubMed:7881431,
FT ECO:0000269|PubMed:8556302"
FT /id="VAR_003947"
FT VARIANT 1224
FT /note="S -> L (in HSAS)"
FT /evidence="ECO:0000269|PubMed:9744477"
FT /id="VAR_003948"
FT VARIANT 1239
FT /note="G -> E"
FT /evidence="ECO:0000269|PubMed:10797421"
FT /id="VAR_030421"
FT MUTAGEN 1147..1153
FT /note="KGGKYSV->AGGAASA: Loss of axon guidance, when
FT assayed in a heterologous system, but normal synapse
FT formation."
FT /evidence="ECO:0000269|PubMed:24155914"
FT CONFLICT 4
FT /note="A -> V (in Ref. 1; CAA42508)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="T -> I (in Ref. 1; CAA42508)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="S -> T (in Ref. 1; CAA42508)"
FT /evidence="ECO:0000305"
FT CONFLICT 276..277
FT /note="WL -> SV (in Ref. 1; CAA42508)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="V -> A (in Ref. 6; ABP88252)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="Q -> E (in Ref. 1; CAA42508)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="K -> T (in Ref. 6; ABP88252)"
FT /evidence="ECO:0000305"
FT CONFLICT 626
FT /note="L -> V (in Ref. 1; CAA42508)"
FT /evidence="ECO:0000305"
FT CONFLICT 660
FT /note="E -> G (in Ref. 6; ABP88252)"
FT /evidence="ECO:0000305"
FT CONFLICT 936
FT /note="L -> V (in Ref. 12; CAB37831)"
FT /evidence="ECO:0000305"
FT CONFLICT 1116..1117
FT /note="GF -> WLC (in Ref. 13; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1164
FT /note="E -> V (in Ref. 6; ABP88252)"
FT /evidence="ECO:0000305"
FT MOD_RES P32004-2:1177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES P32004-3:1172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
SQ SEQUENCE 1257 AA; 140003 MW; 5EDD764DA86C0E63 CRC64;
MVVALRYVWP LLLCSPCLLI QIPEEYEGHH VMEPPVITEQ SPRRLVVFPT DDISLKCEAS
GKPEVQFRWT RDGVHFKPKE ELGVTVYQSP HSGSFTITGN NSNFAQRFQG IYRCFASNKL
GTAMSHEIRL MAEGAPKWPK ETVKPVEVEE GESVVLPCNP PPSAEPLRIY WMNSKILHIK
QDERVTMGQN GNLYFANVLT SDNHSDYICH AHFPGTRTII QKEPIDLRVK ATNSMIDRKP
RLLFPTNSSS HLVALQGQPL VLECIAEGFP TPTIKWLRPS GPMPADRVTY QNHNKTLQLL
KVGEEDDGEY RCLAENSLGS ARHAYYVTVE AAPYWLHKPQ SHLYGPGETA RLDCQVQGRP
QPEVTWRING IPVEELAKDQ KYRIQRGALI LSNVQPSDTM VTQCEARNRH GLLLANAYIY
VVQLPAKILT ADNQTYMAVQ GSTAYLLCKA FGAPVPSVQW LDEDGTTVLQ DERFFPYANG
TLGIRDLQAN DTGRYFCLAA NDQNNVTIMA NLKVKDATQI TQGPRSTIEK KGSRVTFTCQ
ASFDPSLQPS ITWRGDGRDL QELGDSDKYF IEDGRLVIHS LDYSDQGNYS CVASTELDVV
ESRAQLLVVG SPGPVPRLVL SDLHLLTQSQ VRVSWSPAED HNAPIEKYDI EFEDKEMAPE
KWYSLGKVPG NQTSTTLKLS PYVHYTFRVT AINKYGPGEP SPVSETVVTP EAAPEKNPVD
VKGEGNETTN MVITWKPLRW MDWNAPQVQY RVQWRPQGTR GPWQEQIVSD PFLVVSNTST
FVPYEIKVQA VNSQGKGPEP QVTIGYSGED YPQAIPELEG IEILNSSAVL VKWRPVDLAQ
VKGHLRGYNV TYWREGSQRK HSKRHIHKDH VVVPANTTSV ILSGLRPYSS YHLEVQAFNG
RGSGPASEFT FSTPEGVPGH PEALHLECQS NTSLLLRWQP PLSHNGVLTG YVLSYHPLDE
GGKGQLSFNL RDPELRTHNL TDLSPHLRYR FQLQATTKEG PGEAIVREGG TMALSGISDF
GNISATAGEN YSVVSWVPKE GQCNFRFHIL FKALGEEKGG ASLSPQYVSY NQSSYTQWDL
QPDTDYEIHL FKERMFRHQM AVKTNGTGRV RLPPAGFATE GWFIGFVSAI ILLLLVLLIL
CFIKRSKGGK YSVKDKEDTQ VDSEARPMKD ETFGEYRSLE SDNEEKAFGS SQPSLNGDIK
PLGSDDSLAD YGGSVDVQFN EDGSFIGQYS GKKEKEAAGG NDSSGATSPI NPAVALE
