ID NCHL1_HUMAN Reviewed; 1208 AA. AC O00533; B7ZL03; Q2M3G2; Q59FY0; DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 4. DT 13-FEB-2019, entry version 154. DE RecName: Full=Neural cell adhesion molecule L1-like protein; DE AltName: Full=Close homolog of L1; DE Contains: DE RecName: Full=Processed neural cell adhesion molecule L1-like protein; DE Flags: Precursor; GN Name=CHL1; Synonyms=CALL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND RP VARIANTS ALA-287 AND VAL-1034. RX PubMed=9799093; DOI=10.1007/s004390050829; RA Wei M.-H., Karavanova I., Ivanov S.V., Popescu N.C., Keck C.L., RA Pack S., Eisen J.A., Lerman M.I.; RT "In silico-initiated cloning and molecular characterization of a novel RT human member of the L1 gene family of neural cell adhesion RT molecules."; RL Hum. Genet. 103:355-364(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS RP ALA-287 AND VAL-1034. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS RP ALA-287 AND VAL-1034. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-476; ASN-482; ASN-562; RP ASN-767; ASN-822 AND ASN-1026. 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., RA Moore R.J., 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 [6] RP VARIANT [LARGE SCALE ANALYSIS] ILE-411. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Extracellular matrix and cell adhesion protein that CC plays a role in nervous system development and in synaptic CC plasticity. Both soluble and membranous forms promote neurite CC outgrowth of cerebellar and hippocampal neurons and suppress CC neuronal cell death. Plays a role in neuronal positioning of CC pyramidal neurons and in regulation of both the number of CC interneurons and the efficacy of GABAergic synapses. May play a CC role in regulating cell migration in nerve regeneration and CC cortical development. Potentiates integrin-dependent cell CC migration towards extracellular matrix proteins. Recruits ANK3 to CC the plasma membrane (By similarity). {ECO:0000250}. CC -!- SUBUNIT: May interact with L1CAM. May interact with ITGB1/ITGA1 CC heterodimer and ITGB1/ITGA2 heterodimer as well as with ANK3 (By CC similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass CC type I membrane protein {ECO:0000250}. Note=Soluble forms produced CC by cleavage/shedding also exist. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Processed neural cell adhesion molecule L1- CC like protein: Secreted, extracellular space, extracellular matrix CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00533-1; Sequence=Displayed; CC Name=2; CC IsoId=O00533-2; Sequence=VSP_020082; CC Note=Contains a N-linked (GlcNAc...) asparagine at position 231. CC {ECO:0000255}; CC -!- TISSUE SPECIFICITY: Expressed in the fetal and adult brain as well CC as in Schwann cell culture. Also detected in adult peripheral CC tissues. {ECO:0000269|PubMed:9799093}. CC -!- DOMAIN: The FIG[AQ]Y motif seems to be an ankyrin recruitment CC region. CC -!- DOMAIN: The DGEA motif seems to be a recognition site for CC integrin. CC -!- PTM: Cleavage by metalloprotease ADAM8 in the extracellular part CC generates 2 soluble forms (125 kDa and 165 kDa) in vitro and is CC inhibited by metalloprotease inhibitors. CC -!- PTM: N-glycosylated. Contains N-linked oligosaccharides with a CC sulfated carbohydrate structure type HNK-1 (SO4-3- CC GlcUABeta1,3GalBeta1,4GlcNAc) (By similarity). {ECO:0000250}. CC -!- PTM: O-glycosylated. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. CC L1/neurofascin/NgCAM family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92566.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; 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; AF002246; AAB60937.1; -; mRNA. DR EMBL; AB209329; BAD92566.1; ALT_INIT; mRNA. DR EMBL; AC011609; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC026187; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC104918; AAI04919.1; -; mRNA. DR EMBL; BC143496; AAI43497.1; -; mRNA. DR CCDS; CCDS2556.1; -. [O00533-2] DR CCDS; CCDS58812.1; -. [O00533-1] DR RefSeq; NP_001240316.1; NM_001253387.1. [O00533-1] DR RefSeq; NP_006605.2; NM_006614.3. [O00533-2] DR RefSeq; XP_006713001.1; XM_006712938.1. [O00533-2] DR RefSeq; XP_006713002.1; XM_006712939.3. [O00533-2] DR RefSeq; XP_006713003.1; XM_006712940.3. [O00533-2] DR RefSeq; XP_011531594.1; XM_011533292.1. [O00533-2] DR RefSeq; XP_011531596.1; XM_011533294.1. [O00533-1] DR RefSeq; XP_011531597.1; XM_011533295.1. [O00533-1] DR RefSeq; XP_016861055.1; XM_017005566.1. [O00533-2] DR RefSeq; XP_016861056.1; XM_017005567.1. [O00533-2] DR RefSeq; XP_016861057.1; XM_017005568.1. [O00533-2] DR RefSeq; XP_016861058.1; XM_017005569.1. [O00533-1] DR RefSeq; XP_016861059.1; XM_017005570.1. [O00533-1] DR RefSeq; XP_016861060.1; XM_017005571.1. [O00533-1] DR UniGene; Hs.148909; -. DR UniGene; Hs.731409; -. DR ProteinModelPortal; O00533; -. DR SMR; O00533; -. DR BioGrid; 115975; 4. DR IntAct; O00533; 3. DR STRING; 9606.ENSP00000256509; -. DR GlyConnect; 1960; -. DR iPTMnet; O00533; -. DR PhosphoSitePlus; O00533; -. DR SwissPalm; O00533; -. DR BioMuta; CHL1; -. DR jPOST; O00533; -. DR MaxQB; O00533; -. DR PaxDb; O00533; -. DR PeptideAtlas; O00533; -. DR PRIDE; O00533; -. DR ProteomicsDB; 47957; -. DR ProteomicsDB; 47958; -. [O00533-2] DR Ensembl; ENST00000256509; ENSP00000256509; ENSG00000134121. [O00533-2] DR Ensembl; ENST00000397491; ENSP00000380628; ENSG00000134121. [O00533-1] DR GeneID; 10752; -. DR KEGG; hsa:10752; -. DR UCSC; uc003bot.4; human. [O00533-1] DR CTD; 10752; -. DR DisGeNET; 10752; -. DR EuPathDB; HostDB:ENSG00000134121.9; -. DR GeneCards; CHL1; -. DR H-InvDB; HIX0030810; -. DR HGNC; HGNC:1939; CHL1. DR HPA; CAB026120; -. DR HPA; HPA003345; -. DR MIM; 607416; gene. DR neXtProt; NX_O00533; -. DR OpenTargets; ENSG00000134121; -. DR PharmGKB; PA26470; -. DR eggNOG; KOG3513; Eukaryota. DR eggNOG; ENOG410XSVG; LUCA. DR GeneTree; ENSGT00940000160080; -. DR HOGENOM; HOG000231380; -. DR HOVERGEN; HBG000144; -. DR InParanoid; O00533; -. DR KO; K06758; -. DR OMA; DMQATES; -. DR OrthoDB; 157712at2759; -. DR PhylomeDB; O00533; -. DR TreeFam; TF351098; -. DR Reactome; R-HSA-447041; CHL1 interactions. DR ChiTaRS; CHL1; human. DR GeneWiki; CHL1; -. DR GenomeRNAi; 10752; -. DR PRO; PR:O00533; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; ENSG00000134121; Expressed in 204 organ(s), highest expression level in neocortex. DR ExpressionAtlas; O00533; baseline and differential. DR Genevisible; O00533; HS. DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0002020; F:protease binding; IEA:Ensembl. DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl. DR GO; GO:0007411; P:axon guidance; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0050890; P:cognition; IEA:Ensembl. DR GO; GO:0035640; P:exploration behavior; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd00063; FN3; 4. 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; IPR013151; Immunoglobulin. 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 Pfam; PF00047; ig; 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; 4. DR PROSITE; PS50835; IG_LIKE; 6. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Cell membrane; Complete proteome; KW Developmental protein; Differentiation; Disulfide bond; KW Extracellular matrix; Glycoprotein; Immunoglobulin domain; Membrane; KW Neurogenesis; Phosphoprotein; Polymorphism; Reference proteome; KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 1208 Neural cell adhesion molecule L1-like FT protein. FT /FTId=PRO_0000247896. FT CHAIN 25 ? Processed neural cell adhesion molecule FT L1-like protein. {ECO:0000255}. FT /FTId=PRO_0000314777. FT TOPO_DOM 25 1082 Extracellular. {ECO:0000255}. FT TRANSMEM 1083 1103 Helical. {ECO:0000255}. FT TOPO_DOM 1104 1208 Cytoplasmic. {ECO:0000255}. FT DOMAIN 35 124 Ig-like C2-type 1. FT DOMAIN 128 223 Ig-like C2-type 2. FT DOMAIN 235 328 Ig-like C2-type 3. FT DOMAIN 331 417 Ig-like C2-type 4. FT DOMAIN 423 510 Ig-like C2-type 5. FT DOMAIN 515 607 Ig-like C2-type 6. FT DOMAIN 614 709 Fibronectin type-III 1. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 714 807 Fibronectin type-III 2. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 809 914 Fibronectin type-III 3. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 918 1015 Fibronectin type-III 4. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT MOTIF 555 558 DGEA. FT MOTIF 1181 1185 FIG[AQ]Y. FT SITE 753 754 Cleavage; by ADAM8. {ECO:0000250}. FT SITE 1039 1040 Cleavage; by ADAM8. {ECO:0000250}. FT MOD_RES 1147 1147 Phosphoserine. FT {ECO:0000250|UniProtKB:P70232}. FT MOD_RES 1160 1160 Phosphoserine. FT {ECO:0000250|UniProtKB:P70232}. FT MOD_RES 1180 1180 Phosphoserine. FT {ECO:0000250|UniProtKB:P70232}. FT CARBOHYD 299 299 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 476 476 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 482 482 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 562 562 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 580 580 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 767 767 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 822 822 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 945 945 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1026 1026 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT DISULFID 57 109 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 153 204 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 262 310 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 352 401 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 445 494 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 536 591 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VAR_SEQ 227 227 S -> LKHANDSSSSTEIGSKA (in isoform 2). FT {ECO:0000303|PubMed:9799093}. FT /FTId=VSP_020082. FT VARIANT 17 17 L -> F (in dbSNP:rs2272522). FT /FTId=VAR_027167. FT VARIANT 287 287 T -> A (in dbSNP:rs13060847). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9799093, FT ECO:0000269|Ref.2}. FT /FTId=VAR_027168. FT VARIANT 411 411 L -> I (in a colorectal cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035505. FT VARIANT 1034 1034 I -> V (in dbSNP:rs6442827). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9799093, FT ECO:0000269|Ref.2}. FT /FTId=VAR_027169. SQ SEQUENCE 1208 AA; 135071 MW; F706F87B60A1685D CRC64; MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS EEIEFIVPSV PKFPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSSNSI KQRKPKLLLP PTESGSESSI TILKGEILLL ECFAEGLPTP QVDWNKIGGD LPKGRETKEN YGKTLKIENV SYQDKGNYRC TASNFLGTAT HDFHVIVEEP PRWTKKPQSA VYSTGSNGIL LCEAEGEPQP TIKWRVNGSP VDNHPFAGDV VFPREISFTN LQPNHTAVYQ CEASNVHGTI LANANIDVVD VRPLIQTKDG ENYATVVGYS AFLHCEFFAS PEAVVSWQKV EEVKPLEGRR YHIYENGTLQ INRTTEEDAG SYSCWVENAI GKTAVTANLD IRNATKLRVS PKNPRIPKLH MLELHCESKC DSHLKHSLKL SWSKDGEAFE INGTEDGRII IDGANLTISN VTLEDQGIYC CSAHTALDSA ADITQVTVLD VPDPPENLHL SERQNRSVRL TWEAGADHNS NISEYIVEFE GNKEEPGRWE ELTRVQGKKT TVILPLAPFV RYQFRVIAVN EVGRSQPSQP SDHHETPPAA PDRNPQNIRV QASQPKEMII KWEPLKSMEQ NGPGLEYRVT WKPQGAPVEW EEETVTNHTL RVMTPAVYAP YDVKVQAINQ LGSGPDPQSV TLYSGEDYPD TAPVIHGVDV INSTLVKVTW STVPKDRVHG RLKGYQINWW KTKSLLDGRT HPKEVNILRF SGQRNSGMVP SLDAFSEFHL TVLAYNSKGA GPESEPYIFQ TPEGVPEQPT FLKVIKVDKD TATLSWGLPK KLNGNLTGYL LQYQIINDTY EIGELNDINI TTPSKPSWHL SNLNATTKYK FYLRACTSQG CGKPITEESS TLGEGSKGIG KISGVNLTQK THPIEVFEPG AEHIVRLMTK NWGDNDSIFQ DVIETRGREY AGLYDDISTQ GWFIGLMCAI ALLTLLLLTV CFVKRNRGGK YSVKEKEDLH PDPEIQSVKD ETFGEYSDSD EKPLKGSLRS LNRDMQPTES ADSLVEYGEG DHGLFSEDGS FIGAYAGSKE KGSVESNGSS TATFPLRA //