SASDBR2: Contactin-associated protein-like 2 (Caspr2) extracellular domain...

Basic information

• Entry: Database: SASBDB / ID: SASDBR2

Sample

Contactin-associated protein-like 2 (Caspr2) extracellular domains 1-1261.

• Contactin-associated protein-like 2 extracellular domains (1-1261) (protein), Caspr2, Homo sapiens

Function / homology

Function:

limbic system development / clustering of voltage-gated potassium channels / neuron recognition / vocal learning / protein localization to juxtaparanode region of axon / paranodal junction / superior temporal gyrus development / thalamus development / vocalization behavior / paranode region of axon / striatum development / juxtaparanode region of axon / adult behavior / transmission of nerve impulse / social behavior / positive regulation of gap junction assembly / axolemma / prepulse inhibition / voltage-gated potassium channel complex / neuron projection morphogenesis / learning / synaptic membrane / brain development / cerebral cortex development / neuron projection development / protease binding / perikaryon / transmembrane transporter binding / cell population proliferation / early endosome / cell adhesion / axon / neuronal cell body / dendrite / Golgi apparatus / enzyme binding / cell surface / membrane

Domain/homology:

Neurexin/syndecan/glycophorin C / putative band 4.1 homologues' binding motif / : / Laminin G domain / Laminin G domain profile. / Laminin G domain / Laminin G domain / Coagulation factors 5/8 type C domain (FA58C) signature 2. / Fibrinogen, alpha/beta/gamma chain, C-terminal globular domain / Fibrinogen-like, C-terminal / Fibrinogen C-terminal domain profile. / Coagulation factors 5/8 type C domain (FA58C) signature 1. / Coagulation factor 5/8 C-terminal domain, discoidin domain / Coagulation factors 5/8 type C domain (FA58C) profile. / F5/8 type C domain / Coagulation factor 5/8 C-terminal domain / Epidermal growth factor-like domain. / EGF-like domain profile. / EGF-like domain / Galactose-binding-like domain superfamily / Concanavalin A-like lectin/glucanase domain superfamily

Component:

Contactin-associated protein-like 2

• Biological species: Homo sapiens (human)
• Citation: Journal: J Biol Chem / Year: 2016; Title: Structural Characterization of the Extracellular Domain of CASPR2 and Insights into Its Association with the Novel Ligand Contactin1.; Authors: Eva N Rubio-Marrero / Gabriele Vincelli / Cy M Jeffries / Tanvir R Shaikh / Irene S Pakos / Fanomezana M Ranaivoson / Sventja von Daake / Borries Demeler / Antonella De Jaco / Guy Perkins / Mark H Ellisman / Jill Trewhella / Davide Comoletti / ; Abstract: Contactin-associated protein-like 2 (CNTNAP2) encodes for CASPR2, a multidomain single transmembrane protein belonging to the neurexin superfamily that has been implicated in a broad range of human phenotypes including autism and language impairment. Using a combination of biophysical techniques, including small angle x-ray scattering, single particle electron microscopy, analytical ultracentrifugation, and bio-layer interferometry, we present novel structural and functional data that relate the architecture of the extracellular domain of CASPR2 to a previously unknown ligand, Contactin1 (CNTN1). Structurally, CASPR2 is highly glycosylated and has an overall compact architecture. Functionally, we show that CASPR2 associates with micromolar affinity with CNTN1 but, under the same conditions, it does not interact with any of the other members of the contactin family. Moreover, by using dissociated hippocampal neurons we show that microbeads loaded with CASPR2, but not with a deletion mutant, co-localize with transfected CNTN1, suggesting that CNTN1 is an endogenous ligand for CASPR2. These data provide novel insights into the structure and function of CASPR2, suggesting a complex role of CASPR2 in the nervous system.

Contact author

• Davide Comoletti (Department of Neuroscience and Cell Biology, Rutgers University., New Brunswick, NJ, United States)

Models

• Model #413: ; Type: dummy / Software: DAMMIN / Radius of dummy atoms: 3.70 A / Chi-square value: 0.594441 / P-value: 0.080000; Search similar-shape structures of this assembly by Omokage search (details)
• Model #414: ; Type: atomic / Software: CRYSOL / Radius of dummy atoms: 1.90 A / Chi-square value: 0.867 / P-value: 0.030000; Search similar-shape structures of this assembly by Omokage search (details)
• Model #415: ; Type: atomic / Software: CORAL / Radius of dummy atoms: 1.90 A / Chi-square value: 0.7056 / P-value: 0.008000; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Contactin-associated protein-like 2 (Caspr2) extracellular domains 1-1261.; Specimen concentration: 1.00-9.57
• Buffer: Name: HEPES / Concentration: 10.00 mM / pH: 7.4 / Composition: 150 mM NaCl

Entity #272

Name: Caspr2 / Type: protein
Description: Contactin-associated protein-like 2 extracellular domains (1-1261)
Formula weight: 140.4 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q9UHC6
Sequence:

MQAAPRAGCG AALLLWIVSS CLCRAWTAPS TSQKCDEPLV SGLPHVAFSS SSSISGSYSP GYAKINKRGG AGGWSPSDSD HYQWLQVDFG NRKQISAIAT QGRYSSSDWV TQYRMLYSDT GRNWKPYHQD GNIWAFPGNI NSDGVVRHEL QHPIIARYVR IVPLDWNGEG RIGLRIEVYG CSYWADVINF DGHVVLPYRF RNKKMKTLKD VIALNFKTSE SEGVILHGEG QQGDYITLEL KKAKLVLSLN LGSNQLGPIY GHTSVMTGSL LDDHHWHSVV IERQGRSINL TLDRSMQHFR TNGEFDYLDL DYEITFGGIP FSGKPSSSSR KNFKGCMESI NYNGVNITDL ARRKKLEPSN VGNLSFSCVE PYTVPVFFNA TSYLEVPGRL NQDLFSVSFQ FRTWNPNGLL VFSHFADNLG NVEIDLTESK VGVHINITQT KMSQIDISSG SGLNDGQWHE VRFLAKENFA ILTIDGDEAS AVRTNSPLQV KTGEKYFFGG FLNQMNNSSH SVLQPSFQGC MQLIQVDDQL VNLYEVAQRK PGSFANVSID MCAIIDRCVP NHCEHGGKCS QTWDSFKCTC DETGYSGATC HNSIYEPSCE AYKHLGQTSN YYWIDPDGSG PLGPLKVYCN MTEDKVWTIV SHDLQMQTPV VGYNPEKYSV TQLVYSASMD QISAITDSAE YCEQYVSYFC KMSRLLNTPD GSPYTWWVGK ANEKHYYWGG SGPGIQKCAC GIERNCTDPK YYCNCDADYK QWRKDAGFLS YKDHLPVSQV VVGDTDRQGS EAKLSVGPLR CQGDRNYWNA ASFPNPSSYL HFSTFQGETS ADISFYFKTL TPWGVFLENM GKEDFIKLEL KSATEVSFSF DVGNGPVEIV VRSPTPLNDD QWHRVTAERN VKQASLQVDR LPQQIRKAPT EGHTRLELYS QLFVGGAGGQ QGFLGCIRSL RMNGVTLDLE ERAKVTSGFI SGCSGHCTSY GTNCENGGKC LERYHGYSCD CSNTAYDGTF CNKDVGAFFE EGMWLRYNFQ APATNARDSS SRVDNAPDQQ NSHPDLAQEE IRFSFSTTKA PCILLYISSF TTDFLAVLVK PTGSLQIRYN LGGTREPYNI DVDHRNMANG QPHSVNITRH EKTIFLKLDH YPSVSYHLPS SSDTLFNSPK SLFLGKVIET GKIDQEIHKY NTPGFTGCLS RVQFNQIAPL KAALRQTNAS AHVHIQGELV ESNCGASPLT LSPMSSATDP WHLDHLDSAS ADFPYNPGQG QAIRNGVNRN S

Experimental information

• Beam: Instrument name: Anton Paar SAXSess / City: Salt Lake City, University of Utah / 国: USA / Shape: Line collimation / Type of source: X-ray in house / Wavelength: 0.1542 Å / Dist. spec. to detc.: 264.5 mm
• Detector: Name: 2D position-sensitive image plates / Pixsize x: 42.3 mm

Scan

Title: Caspr2: Contactin-associated protein-like 2 / Measurement date: Oct 4, 2010 / Storage temperature: 20 °C / Cell temperature: 20 °C / Exposure time: 1800 sec. / Number of frames: 1 / Unit: 1/nm /

	Min	Max
Q	0.12	3.008

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 349 /

	Min	Max
Q	0.01297	0.3514
P(R) point	1	349
R	0	145

Result

Type of curve: single_conc /

	Experimental	Porod
MW	160 kDa	-
Volume	-	282 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	1.004	0.004	0.984	0.004
Radius of gyration, Rg	4.62 nm	0.18	4.43 nm	0.03

	Min	Max
D	-	14.5
Guinier point	1	18