Reviewed, UniProtKB/Swiss-Prot O00533 (CHL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Neural cell adhesion molecule L1-like protein
Alternative name(s):
    Close homolog of L1
Cleaved into the following chain:
    1- Recommended name:
            Processed neural cell adhesion molecule L1-like protein

Gene names

Name:	CHL1
Synonyms:	CALL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1208 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Extracellular matrix and cell adhesion protein that plays a role in nervous system development and in synaptic plasticity. Both soluble and membranous forms promote neurite outgrowth of cerebellar and hippocampal neurons and suppress neuronal cell death. Plays a role in neuronal positioning of pyramidal neurons and in regulation of both the number of interneurons and the efficacy of GABAergic synapses. May play a role in regulating cell migration in nerve regeneration and cortical development. Potentiates integrin-dependent cell migration towards extracellular matrix proteins. Recruits ANK3 to the plasma membrane By similarity.
Subunit structure	May interact with L1CAM. May interact with ITGB1/ITGA1 heterodimer and ITGB1/ITGA2 heterodimer as well as with ANK3 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Note: Soluble forms produced by cleavage/shedding also exist By similarity. Processed neural cell adhesion molecule L1-like protein: Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Expressed in the fetal and adult brain as well as in Schwann cell culture. Also detected in adult peripheral tissues. Ref.1
Domain	The FIG[AQ]Y motif seems to be an ankyrin recruitment region. The DGEA motif seems to be a recognition site for integrin.
Post-translational modification	Cleavage by metalloprotease ADAM8 in the extracellular part generates 2 soluble forms (125 kDa and 165 kDa) in vitro and is inhibited by metalloprotease inhibitors. N-glycosylated. Contains N-linked oligosaccharides with a sulfated carbohydrate structure type HNK-1 (SO4-3-GlcUABeta1,3GalBeta1,4GlcNAc) By similarity. O-glycosylated By similarity.
Involvement in disease	The deletion of 1 copy of the CHL1 may be responsible for mental defects in patients with 3p- syndrome. 3p- syndrome results from deletion of a terminal segment of the short arm of one chromosome 3 and is characterized by multiple congenital anomalies and mental retardation. Ref.5
Sequence similarities	Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family. Contains 4 fibronectin type-III domains. Contains 6 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Cell adhesion Differentiation Neurogenesis
Cellular component	Cell membrane Extracellular matrix Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	cell adhesion Ref.1 Traceable author statement. Source: ProtInc cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Ref.1 Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00533-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O00533-2)

The sequence of this isoform differs from the canonical sequence as follows:
     227-227: S → LKHANDSSSSTEIGSKA

Note: Contains a N-linked carbohydrate at position 231.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 1208	1184	Neural cell adhesion molecule L1-like protein		PRO_0000247896
	Chain	25 – ?		Processed neural cell adhesion molecule L1-like protein Potential		PRO_0000314777
Regions
	Topological domain	25 – 1082	1058	Extracellular Potential
	Transmembrane	1083 – 1103	21	Potential
	Topological domain	1104 – 1208	105	Cytoplasmic Potential
	Domain	35 – 124	90	Ig-like C2-type 1
	Domain	128 – 223	96	Ig-like C2-type 2
	Domain	235 – 328	94	Ig-like C2-type 3
	Domain	331 – 417	87	Ig-like C2-type 4
	Domain	423 – 510	88	Ig-like C2-type 5
	Domain	515 – 607	93	Ig-like C2-type 6
	Domain	612 – 704	93	Fibronectin type-III 1
	Domain	711 – 804	94	Fibronectin type-III 2
	Domain	809 – 911	103	Fibronectin type-III 3
	Domain	916 – 1011	96	Fibronectin type-III 4
	Motif	555 – 558	4	DGEA
	Motif	1181 – 1185	5	FIG[AQ]Y
Sites
	Site	753 – 754	2	Cleavage; by ADAM8 By similarity
	Site	1039 – 1040	2	Cleavage; by ADAM8 By similarity
Amino acid modifications
	Glycosylation	299	1	N-linked (GlcNAc...) Potential
	Glycosylation	476	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	482	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	562	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	580	1	N-linked (GlcNAc...) Potential
	Glycosylation	767	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	822	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	945	1	N-linked (GlcNAc...) Potential
	Glycosylation	1026	1	N-linked (GlcNAc...) Ref.6
	Disulfide bond	57 ↔ 109		By similarity
	Disulfide bond	153 ↔ 204		By similarity
	Disulfide bond	262 ↔ 310		By similarity
	Disulfide bond	352 ↔ 401		By similarity
	Disulfide bond	445 ↔ 494		By similarity
	Disulfide bond	536 ↔ 591		By similarity
Natural variations
	Alternative sequence	227	1	S → LKHANDSSSSTEIGSKA in isoform 2.		VSP_020082
	Natural variant	17	1	L → F: dbSNP rs2272522.		VAR_027167
	Natural variant	287	1	T → A: dbSNP rs13060847. Ref.1 Ref.2 Ref.4		VAR_027168
	Natural variant	411	1	L → I in a colorectal cancer sample; somatic mutation. Ref.7		VAR_035505
	Natural variant	1034	1	V → I: dbSNP rs6442827. Ref.3		VAR_027169

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: F2B35ADAA7AA0BDF	FASTA	1,208	135,057
	10 20 30 40 50 60 MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK 70 80 90 100 110 120 GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS 130 140 150 160 170 180 EEIEFIVPSV PKFPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV 190 200 210 220 230 240 YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSSNSI KQRKPKLLLP 250 260 270 280 290 300 PTESGSESSI TILKGEILLL ECFAEGLPTP QVDWNKIGGD LPKGRETKEN YGKTLKIENV 310 320 330 340 350 360 SYQDKGNYRC TASNFLGTAT HDFHVIVEEP PRWTKKPQSA VYSTGSNGIL LCEAEGEPQP 370 380 390 400 410 420 TIKWRVNGSP VDNHPFAGDV VFPREISFTN LQPNHTAVYQ CEASNVHGTI LANANIDVVD 430 440 450 460 470 480 VRPLIQTKDG ENYATVVGYS AFLHCEFFAS PEAVVSWQKV EEVKPLEGRR YHIYENGTLQ 490 500 510 520 530 540 INRTTEEDAG SYSCWVENAI GKTAVTANLD IRNATKLRVS PKNPRIPKLH MLELHCESKC 550 560 570 580 590 600 DSHLKHSLKL SWSKDGEAFE INGTEDGRII IDGANLTISN VTLEDQGIYC CSAHTALDSA 610 620 630 640 650 660 ADITQVTVLD VPDPPENLHL SERQNRSVRL TWEAGADHNS NISEYIVEFE GNKEEPGRWE 670 680 690 700 710 720 ELTRVQGKKT TVILPLAPFV RYQFRVIAVN EVGRSQPSQP SDHHETPPAA PDRNPQNIRV 730 740 750 760 770 780 QASQPKEMII KWEPLKSMEQ NGPGLEYRVT WKPQGAPVEW EEETVTNHTL RVMTPAVYAP 790 800 810 820 830 840 YDVKVQAINQ LGSGPDPQSV TLYSGEDYPD TAPVIHGVDV INSTLVKVTW STVPKDRVHG 850 860 870 880 890 900 RLKGYQINWW KTKSLLDGRT HPKEVNILRF SGQRNSGMVP SLDAFSEFHL TVLAYNSKGA 910 920 930 940 950 960 GPESEPYIFQ TPEGVPEQPT FLKVIKVDKD TATLSWGLPK KLNGNLTGYL LQYQIINDTY 970 980 990 1000 1010 1020 EIGELNDINI TTPSKPSWHL SNLNATTKYK FYLRACTSQG CGKPITEESS TLGEGSKGIG 1030 1040 1050 1060 1070 1080 KISGVNLTQK THPVEVFEPG AEHIVRLMTK NWGDNDSIFQ DVIETRGREY AGLYDDISTQ 1090 1100 1110 1120 1130 1140 GWFIGLMCAI ALLTLLLLTV CFVKRNRGGK YSVKEKEDLH PDPEIQSVKD ETFGEYSDSD 1150 1160 1170 1180 1190 1200 EKPLKGSLRS LNRDMQPTES ADSLVEYGEG DHGLFSEDGS FIGAYAGSKE KGSVESNGSS TATFPLRA
	Isoform 2. Checksum: 9229C1B471D2F940	FASTA	1,224	136,684
	10 20 30 40 50 60 MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK 70 80 90 100 110 120 GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS 130 140 150 160 170 180 EEIEFIVPSV PKFPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV 190 200 210 220 230 240 YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSLKHA NDSSSSTEIG 250 260 270 280 290 300 SKANSIKQRK PKLLLPPTES GSESSITILK GEILLLECFA EGLPTPQVDW NKIGGDLPKG 310 320 330 340 350 360 RETKENYGKT LKIENVSYQD KGNYRCTASN FLGTATHDFH VIVEEPPRWT KKPQSAVYST 370 380 390 400 410 420 GSNGILLCEA EGEPQPTIKW RVNGSPVDNH PFAGDVVFPR EISFTNLQPN HTAVYQCEAS 430 440 450 460 470 480 NVHGTILANA NIDVVDVRPL IQTKDGENYA TVVGYSAFLH CEFFASPEAV VSWQKVEEVK 490 500 510 520 530 540 PLEGRRYHIY ENGTLQINRT TEEDAGSYSC WVENAIGKTA VTANLDIRNA TKLRVSPKNP 550 560 570 580 590 600 RIPKLHMLEL HCESKCDSHL KHSLKLSWSK DGEAFEINGT EDGRIIIDGA NLTISNVTLE 610 620 630 640 650 660 DQGIYCCSAH TALDSAADIT QVTVLDVPDP PENLHLSERQ NRSVRLTWEA GADHNSNISE 670 680 690 700 710 720 YIVEFEGNKE EPGRWEELTR VQGKKTTVIL PLAPFVRYQF RVIAVNEVGR SQPSQPSDHH 730 740 750 760 770 780 ETPPAAPDRN PQNIRVQASQ PKEMIIKWEP LKSMEQNGPG LEYRVTWKPQ GAPVEWEEET 790 800 810 820 830 840 VTNHTLRVMT PAVYAPYDVK VQAINQLGSG PDPQSVTLYS GEDYPDTAPV IHGVDVINST 850 860 870 880 890 900 LVKVTWSTVP KDRVHGRLKG YQINWWKTKS LLDGRTHPKE VNILRFSGQR NSGMVPSLDA 910 920 930 940 950 960 FSEFHLTVLA YNSKGAGPES EPYIFQTPEG VPEQPTFLKV IKVDKDTATL SWGLPKKLNG 970 980 990 1000 1010 1020 NLTGYLLQYQ IINDTYEIGE LNDINITTPS KPSWHLSNLN ATTKYKFYLR ACTSQGCGKP 1030 1040 1050 1060 1070 1080 ITEESSTLGE GSKGIGKISG VNLTQKTHPV EVFEPGAEHI VRLMTKNWGD NDSIFQDVIE 1090 1100 1110 1120 1130 1140 TRGREYAGLY DDISTQGWFI GLMCAIALLT LLLLTVCFVK RNRGGKYSVK EKEDLHPDPE 1150 1160 1170 1180 1190 1200 IQSVKDETFG EYSDSDEKPL KGSLRSLNRD MQPTESADSL VEYGEGDHGL FSEDGSFIGA 1210 1220 YAGSKEKGSV ESNGSSTATF PLRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"In silico-initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules." Wei M.-H., Karavanova I., Ivanov S.V., Popescu N.C., Keck C.L., Pack S., Eisen J.A., Lerman M.I. Hum. Genet. 103:355-364(1998) [PubMed: 9799093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, VARIANT ALA-287.
[2]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ALA-287. Tissue: Brain.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-1034.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ALA-287. Tissue: Brain.
[5]	"CALL gene is haploinsufficient in a 3p- syndrome patient." Angeloni D., Lindor N.M., Pack S., Latif F., Wei M.-H., Lerman M.I. Am. J. Med. Genet. 86:482-485(1999) [PubMed: 10508992] [Abstract] Cited for: DISEASE.
[6]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-476; ASN-482; ASN-562; ASN-767; ASN-822 AND ASN-1026, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-411.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF002246 mRNA. Translation: AAB60937.1. AB209329 mRNA. Translation: BAD92566.1. Different initiation. AC011609 Genomic DNA. No translation available. AC026187 Genomic DNA. No translation available. BC104918 mRNA. Translation: AAI04919.1.
IPI	IPI00299059. IPI00783390.
RefSeq	NP_006605.2.
UniGene	Hs.148909
3D structure databases
HSSP	HSSP built from PDB template 1UEN based on UniProtKB Q92823.
ModBase	Search...
PTM databases
PhosphoSite	O00533.
Genome annotation databases
Ensembl	ENSG00000134121. Homo sapiens. [Contig view]
GeneID	10752.
KEGG	hsa:10752.
Organism-specific databases
GeneCards	GC03P000213.
HGNC	HGNC:1939. CHL1.
HPA	HPA003345.
MIM	607416. gene.
Orphanet	1620. Distal monosomy 3p.
PharmGKB	PA26470.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O00533.
HOVERGEN	O00533.
Gene expression databases
ArrayExpress	O00533.
Bgee	O00533.
CleanEx	HS_CHL1.
GermOnline	ENSG00000134121. Homo sapiens.
Family and domain databases
InterPro	IPR008957. Fibronectin_typ-III-like_fold. IPR003961. FN_III. IPR013151. Ig. IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003599. Ig_sub. IPR003598. Ig_sub2. IPR013106. Ig_V-set. [Graphical view]
Gene3D	G3DSA:2.60.40.30. FN_III-like. 2 hits. G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
Pfam	PF00041. fn3. 4 hits. PF07679. I-set. 2 hits. PF00047. ig. 2 hits. PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00060. FN3. 4 hits. SM00409. IG. 2 hits. SM00408. IGc2. 3 hits. [Graphical view]
PROSITE	PS50853. FN3. 4 hits. PS50835. IG_LIKE. 6 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	40833.
SOURCE	Search...

Entry information

Entry name

CHL1_HUMAN

Accession

Primary (citable) accession number: O00533
Secondary accession number(s): Q2M3G2, Q59FY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	May 5, 2009
Last modified:	June 16, 2009
This is version 64 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)