Q9UHC6 (CNTP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Contactin-associated protein-like 2

Alternative name(s):
Cell recognition molecule Caspr2

Gene names

Name:	CNTNAP2
Synonyms:	CASPR2, KIAA0868

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1331 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	May play a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. Seems to demarcate the juxtaparanodal region of the axo-glial junction.
Subunit structure	Associates with KCNA2 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Potential.
Tissue specificity	Predominantly expressed in nervous system.
Involvement in disease	Cortical dysplasia-focal epilepsy syndrome (CDFES) [MIM:610042]: A disease characterized by cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures begin in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and mental retardation develop. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Autism 15 (AUTS15) [MIM:612100]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. A chromosomal aberration involving CNTNAP2 is found in a patient with autism spectrum disorder. Paracentric inversion 46,XY,inv7(q11.22;q35). The inversion breakpoints disrupt the genes AUTS2 and CNTNAP2.
Sequence similarities	Belongs to the neurexin family. Contains 2 EGF-like domains. Contains 1 F5/8 type C domain. Contains 1 fibrinogen C-terminal domain. Contains 4 laminin G-like domains.
Sequence caution	The sequence BAA74891.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Epilepsy
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cellular protein localization Inferred from sequence or structural similarity. Source: BHF-UCL clustering of voltage-gated potassium channels Inferred from sequence or structural similarity. Source: BHF-UCL limbic system development Inferred from expression pattern Ref.9. Source: BHF-UCL neuron projection development Inferred from electronic annotation. Source: Compara neuron recognition Non-traceable author statement Ref.1. Source: UniProtKB protein localization to juxtaparanode region of axon Inferred from electronic annotation. Source: Compara striatum development Inferred from expression pattern PubMed 18179893. Source: BHF-UCL superior temporal gyrus development Inferred from expression pattern PubMed 18179893. Source: BHF-UCL thalamus development Inferred from expression pattern PubMed 18179893. Source: BHF-UCL transmission of nerve impulse Non-traceable author statement Ref.2. Source: UniProtKB vocalization behavior Inferred from mutant phenotype PubMed 19896112. Source: BHF-UCL
Cellular_component	Golgi apparatus Inferred from direct assay PubMed 19166515. Source: BHF-UCL axolemma Inferred from direct assay PubMed 19706678. Source: BHF-UCL cell surface Inferred from direct assay PubMed 19706678. Source: BHF-UCL dendrite Inferred from sequence or structural similarity. Source: BHF-UCL early endosome Inferred from direct assay PubMed 19706678. Source: BHF-UCL juxtaparanode region of axon Inferred from sequence or structural similarity. Source: BHF-UCL perikaryon Inferred from sequence or structural similarity. Source: BHF-UCL voltage-gated potassium channel complex Inferred from direct assay Ref.1. Source: BHF-UCL
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9UHC6-1)

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: Q9UHC6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1223: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 1331	1304	Contactin-associated protein-like 2		PRO_0000019506
Regions
	Topological domain	28 – 1262	1235	Extracellular Potential
	Transmembrane	1263 – 1283	21	Helical; Potential
	Topological domain	1284 – 1331	48	Cytoplasmic Potential
	Domain	35 – 181	147	F5/8 type C
	Domain	216 – 368	153	Laminin G-like 1
	Domain	401 – 552	152	Laminin G-like 2
	Domain	554 – 591	38	EGF-like 1
	Domain	592 – 798	207	Fibrinogen C-terminal
	Domain	799 – 963	165	Laminin G-like 3
	Domain	963 – 1002	40	EGF-like 2
	Domain	1055 – 1214	160	Laminin G-like 4
Amino acid modifications
	Modified residue	589	1	Phosphothreonine Ref.8
	Modified residue	595	1	Phosphotyrosine Ref.8
	Glycosylation	289	1	N-linked (GlcNAc...) Potential
	Glycosylation	346	1	N-linked (GlcNAc...) Potential
	Glycosylation	363	1	N-linked (GlcNAc...) Potential
	Glycosylation	379	1	N-linked (GlcNAc...) Potential
	Glycosylation	436	1	N-linked (GlcNAc...) Potential
	Glycosylation	506	1	N-linked (GlcNAc...) Potential
	Glycosylation	507	1	N-linked (GlcNAc...) Potential
	Glycosylation	546	1	N-linked (GlcNAc...) Potential
	Glycosylation	630	1	N-linked (GlcNAc...) Potential
	Glycosylation	735	1	N-linked (GlcNAc...) Potential
	Glycosylation	1116	1	N-linked (GlcNAc...) Potential
	Glycosylation	1198	1	N-linked (GlcNAc...) Potential
	Disulfide bond	35 ↔ 181		By similarity
	Disulfide bond	336 ↔ 368		By similarity
	Disulfide bond	520 ↔ 552		By similarity
	Disulfide bond	558 ↔ 569		By similarity
	Disulfide bond	563 ↔ 578		By similarity
	Disulfide bond	580 ↔ 590		By similarity
	Disulfide bond	936 ↔ 963		By similarity
	Disulfide bond	967 ↔ 980		By similarity
	Disulfide bond	974 ↔ 989		By similarity
	Disulfide bond	991 ↔ 1001		By similarity
	Disulfide bond	1178 ↔ 1214		By similarity
Natural variations
	Alternative sequence	1 – 1223	1223	Missing in isoform 2.		VSP_014976
	Natural variant	114	1	R → Q. Ref.9		VAR_046227
	Natural variant	218	1	T → M. Ref.9		VAR_046228
	Natural variant	226	1	L → M. Ref.9		VAR_046229
	Natural variant	283	1	R → C. Ref.9		VAR_046230
	Natural variant	382	1	S → N. Ref.9		VAR_046231
	Natural variant	407	1	N → S. Ref.9		VAR_046232
	Natural variant	418	1	N → D. Ref.9		VAR_046233
	Natural variant	680	1	E → K. Ref.9		VAR_046234
	Natural variant	699	1	P → Q. Ref.9		VAR_046235
	Natural variant	716	1	Y → C. Ref.9		VAR_046236
	Natural variant	731	1	G → S. Ref.9		VAR_046237
	Natural variant	779	1	G → D. Ref.9		VAR_046238
	Natural variant	869	1	I → T Associated with susceptibility to autism. Ref.9		VAR_046239
	Natural variant	906	1	R → H. Ref.9		VAR_046240
	Natural variant	1038	1	D → N. Ref.9		VAR_046241
	Natural variant	1102	1	V → A. Ref.9		VAR_046242
	Natural variant	1114	1	S → G. Ref.9		VAR_046243
	Natural variant	1119	1	R → H. Ref.9		VAR_046244
	Natural variant	1129	1	D → H. Ref.9		VAR_046245
	Natural variant	1227	1	A → T. Ref.9		VAR_046246
	Natural variant	1253	1	I → T. Ref.9		VAR_046247
	Natural variant	1278	1	T → I. Ref.9		VAR_046248

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: CFB2CB55BEFB99C2	FASTA	1,331	148,167
	10 20 30 40 50 60 MQAAPRAGCG AALLLWIVSS CLCRAWTAPS TSQKCDEPLV SGLPHVAFSS SSSISGSYSP 70 80 90 100 110 120 GYAKINKRGG AGGWSPSDSD HYQWLQVDFG NRKQISAIAT QGRYSSSDWV TQYRMLYSDT 130 140 150 160 170 180 GRNWKPYHQD GNIWAFPGNI NSDGVVRHEL QHPIIARYVR IVPLDWNGEG RIGLRIEVYG 190 200 210 220 230 240 CSYWADVINF DGHVVLPYRF RNKKMKTLKD VIALNFKTSE SEGVILHGEG QQGDYITLEL 250 260 270 280 290 300 KKAKLVLSLN LGSNQLGPIY GHTSVMTGSL LDDHHWHSVV IERQGRSINL TLDRSMQHFR 310 320 330 340 350 360 TNGEFDYLDL DYEITFGGIP FSGKPSSSSR KNFKGCMESI NYNGVNITDL ARRKKLEPSN 370 380 390 400 410 420 VGNLSFSCVE PYTVPVFFNA TSYLEVPGRL NQDLFSVSFQ FRTWNPNGLL VFSHFADNLG 430 440 450 460 470 480 NVEIDLTESK VGVHINITQT KMSQIDISSG SGLNDGQWHE VRFLAKENFA ILTIDGDEAS 490 500 510 520 530 540 AVRTNSPLQV KTGEKYFFGG FLNQMNNSSH SVLQPSFQGC MQLIQVDDQL VNLYEVAQRK 550 560 570 580 590 600 PGSFANVSID MCAIIDRCVP NHCEHGGKCS QTWDSFKCTC DETGYSGATC HNSIYEPSCE 610 620 630 640 650 660 AYKHLGQTSN YYWIDPDGSG PLGPLKVYCN MTEDKVWTIV SHDLQMQTPV VGYNPEKYSV 670 680 690 700 710 720 TQLVYSASMD QISAITDSAE YCEQYVSYFC KMSRLLNTPD GSPYTWWVGK ANEKHYYWGG 730 740 750 760 770 780 SGPGIQKCAC GIERNCTDPK YYCNCDADYK QWRKDAGFLS YKDHLPVSQV VVGDTDRQGS 790 800 810 820 830 840 EAKLSVGPLR CQGDRNYWNA ASFPNPSSYL HFSTFQGETS ADISFYFKTL TPWGVFLENM 850 860 870 880 890 900 GKEDFIKLEL KSATEVSFSF DVGNGPVEIV VRSPTPLNDD QWHRVTAERN VKQASLQVDR 910 920 930 940 950 960 LPQQIRKAPT EGHTRLELYS QLFVGGAGGQ QGFLGCIRSL RMNGVTLDLE ERAKVTSGFI 970 980 990 1000 1010 1020 SGCSGHCTSY GTNCENGGKC LERYHGYSCD CSNTAYDGTF CNKDVGAFFE EGMWLRYNFQ 1030 1040 1050 1060 1070 1080 APATNARDSS SRVDNAPDQQ NSHPDLAQEE IRFSFSTTKA PCILLYISSF TTDFLAVLVK 1090 1100 1110 1120 1130 1140 PTGSLQIRYN LGGTREPYNI DVDHRNMANG QPHSVNITRH EKTIFLKLDH YPSVSYHLPS 1150 1160 1170 1180 1190 1200 SSDTLFNSPK SLFLGKVIET GKIDQEIHKY NTPGFTGCLS RVQFNQIAPL KAALRQTNAS 1210 1220 1230 1240 1250 1260 AHVHIQGELV ESNCGASPLT LSPMSSATDP WHLDHLDSAS ADFPYNPGQG QAIRNGVNRN 1270 1280 1290 1300 1310 1320 SAIIGGVIAV VIFTILCTLV FLIRYMFRHK GTYHTNEAKG AESAESADAA IMNNDPNFTE 1330 TIDESKKEWL I
	Isoform 2 [UniParc]. Checksum: F0EB322C735B773E	FASTA	108	11,899
	10 20 30 40 50 60 MSSATDPWHL DHLDSASADF PYNPGQGQAI RNGVNRNSAI IGGVIAVVIF TILCTLVFLI 70 80 90 100 RYMFRHKGTY HTNEAKGAES AESADAAIMN NDPNFTETID ESKKEWLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels." Poliak S., Gollan L., Martinez R., Custer A., Einheber S., Salzer J.L., Trimmer J.S., Shrager P., Peles E. Neuron 24:1037-1047(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. Tissue: Brain.
[2]	"The human contactin-associated protein-like 2 gene (CNTNAP2) spans over 2 Mb of DNA at chromosome 7q35." Nakabayashi K., Scherer S.W. Genomics 73:108-112(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Retina.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[7]	"Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2." Strauss K.A., Puffenberger E.G., Huentelman M.J., Gottlieb S., Dobrin S.E., Parod J.M., Stephan D.A., Morton D.H. N. Engl. J. Med. 354:1370-1377(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CDFES.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-589 AND TYR-595, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders." Bakkaloglu B., O'Roak B.J., Louvi A., Gupta A.R., Abelson J.F., Morgan T.M., Chawarska K., Klin A., Ercan-Sencicek A.G., Stillman A.A., Tanriover G., Abrahams B.S., Duvall J.A., Robbins E.M., Geschwind D.H., Biederer T., Gunel M., Lifton R.P., State M.W. Am. J. Hum. Genet. 82:165-173(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLN-114; MET-218; MET-226; CYS-283; ASN-382; SER-407; ASP-418; LYS-680; GLN-699; CYS-716; SER-731; ASP-779; THR-869; HIS-906; ASN-1038; ALA-1102; GLY-1114; HIS-1119; HIS-1129; THR-1227; THR-1253 AND ILE-1278, CHROMOSOMAL REARRANGEMENT, ASSOCIATION WITH SUSCEPTIBILITY TO AUTISM.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF193613 mRNA. Translation: AAF25199.1. AF319045 mRNA. Translation: AAK34932.1. AF318292 Genomic DNA. Translation: AAK49902.1. AF318298 Genomic DNA. Translation: AAK49903.1. AB020675 mRNA. Translation: BAA74891.1. Different initiation. CR933671 mRNA. Translation: CAI45967.1. CH471146 Genomic DNA. Translation: EAW80084.1. BC093780 mRNA. Translation: AAH93780.1. BC113373 mRNA. Translation: AAI13374.1.
IPI	IPI00029343. IPI00646209.
RefSeq	NP_054860.1. NM_014141.5.
UniGene	Hs.655684.
3D structure databases
ProteinModelPortal	Q9UHC6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UHC6. 5 interactions.
MINT	MINT-241211.
STRING	9606.ENSP00000354778.
PTM databases
PhosphoSite	Q9UHC6.
Polymorphism databases
DMDM	17433089.
Proteomic databases
PaxDb	Q9UHC6.
PRIDE	Q9UHC6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361727; ENSP00000354778; ENSG00000174469.
GeneID	26047.
KEGG	hsa:26047.
UCSC	uc003weu.2. human. uc003wev.2. human.
Organism-specific databases
CTD	26047.
GeneCards	GC07P145863.
HGNC	HGNC:13830. CNTNAP2.
HPA	HPA002739.
MIM	604569. gene. 610042. phenotype. 612100. phenotype.
neXtProt	NX_Q9UHC6.
Orphanet	106. Autism. 163681. Cortical dysplasia - focal epilepsy syndrome. 221150. Pitt-Hopkins-like syndrome.
PharmGKB	PA26692.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG291100.
HOGENOM	HOG000230964.
HOVERGEN	HBG057718.
InParanoid	Q9UHC6.
KO	K07380.
OMA	TSQKCDE.
OrthoDB	EOG4RV2QH.
Gene expression databases
ArrayExpress	Q9UHC6.
Bgee	Q9UHC6.
CleanEx	HS_CNTNAP2.
Genevestigator	Q9UHC6.
Family and domain databases
Gene3D	2.60.120.200. 5 hits.
InterPro	IPR000421. Coagulation_fac_5/8-C_type_dom. IPR008985. ConA-like_lec_gl_sf. IPR013320. ConA-like_subgrp. IPR000742. EG-like_dom. IPR002181. Fibrinogen_a/b/g_C_dom. IPR008979. Galactose-bd-like. IPR001791. Laminin_G. IPR003585. Neurexin-like. [Graphical view]
Pfam	PF00008. EGF. 1 hit. PF00754. F5_F8_type_C. 1 hit. PF02210. Laminin_G_2. 4 hits. [Graphical view]
SMART	SM00294. 4.1m. 1 hit. SM00181. EGF. 1 hit. SM00231. FA58C. 1 hit. SM00282. LamG. 4 hits. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 4 hits. SSF56496. Fibrinogen_a/b/g_C. 1 hit. SSF49785. Gal_bind_like. 1 hit.
PROSITE	PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. EGF_3. 2 hits. PS01285. FA58C_1. 1 hit. PS01286. FA58C_2. 1 hit. PS50022. FA58C_3. 1 hit. PS00514. FIBRINOGEN_C_1. False negative. PS51406. FIBRINOGEN_C_2. 1 hit. PS50025. LAM_G_DOMAIN. 4 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CNTNAP2. human.
GenomeRNAi	26047.
NextBio	47891.
SOURCE	Search...

Entry information

Entry name

CNTP2_HUMAN

Accession

Primary (citable) accession number: Q9UHC6
Secondary accession number(s): D3DWG2 , Q14DG2, Q52LV1, Q5H9Q7, Q9UQ12

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.