Q8R4I7 (NETO1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuropilin and tolloid-like protein 1

Alternative name(s):
Brain-specific transmembrane protein containing 2 CUB and 1 LDL-receptor class A domains protein 1

Gene names

Name:	Neto1
Synonyms:	Btcl1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	533 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	Involved in the development and/or maintenance of neuronal circuitry. Accessory subunit of the neuronal N-methyl-D-aspartate receptor (NMDAR) critical for maintaining the abundance of GRIN2A-containing NMDARs in the postsynaptic density. Regulates long-term NMDA receptor-dependent synaptic plasticity and cognition, at least in the context of spatial learning and memory. Ref.2 Ref.7
Subunit structure	Interacts with PLZ domains of DLG2, DLG3 and DLG4 via its C-terminal TRV domain. Interacts with GRIN2A and GRIN2B via its CUB domains. Ref.7
Subcellular location	Membrane; Single-pass type I membrane protein Potential. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Note: Component of the postsynaptic density (PSD) of excitatory synapses. Ref.7
Tissue specificity	Expressed only in brain. Present throughout the central nervous system. Highly expressed in the hippocampal CA3 region, olfactory bulb and tubercle, caudate putamen, and neocortex in the adult brain. Ref.2 Ref.5 Ref.7
Developmental stage	Observed restrictively in brain throughout embryonic and postnatal stages. Expression pattern in brain slightly changes from E13 to postnatal day 21 (P21). Expressed in both cerebrum and cerebellum throughout P0 to P35. In the cerebrum expression reached a plateau at P14 while expression in the cerebellum remains constant throughout all postnatal stages. Ref.2 Ref.5
Disruption phenotype	Depressed long-term potentiation (LTP) at Schaffer collateral-CA1 synapses, NMDAR-dependent spatial learning and memory. Rescued by the ampakine CX546 at physiological doses. Ref.7
Sequence similarities	Contains 2 CUB domains. Contains 1 LDL-receptor class A domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	memory Inferred from mutant phenotype Ref.7. Source: UniProtKB regulation of long-term neuronal synaptic plasticity Inferred from mutant phenotype Ref.7. Source: UniProtKB visual learning Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW excitatory synapse Inferred from direct assay Ref.7. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic density Inferred from direct assay Ref.7. Source: UniProtKB postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction Ref.7. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 533	511	Neuropilin and tolloid-like protein 1		PRO_0000021800
Regions
	Topological domain	23 – 344	322	Extracellular Potential
	Transmembrane	345 – 365	21	Helical; Potential
	Topological domain	366 – 533	168	Cytoplasmic Potential
	Domain	41 – 155	115	CUB 1
	Domain	172 – 287	116	CUB 2
	Domain	291 – 327	37	LDL-receptor class A
	Motif	531 – 533	3	PDZ-binding
Amino acid modifications
	Modified residue	417	1	Phosphotyrosine Ref.6
	Glycosylation	306	1	N-linked (GlcNAc...) Potential
	Glycosylation	340	1	N-linked (GlcNAc...) Potential
	Disulfide bond	41 ↔ 68		By similarity
	Disulfide bond	96 ↔ 118		By similarity
	Disulfide bond	172 ↔ 202		By similarity
	Disulfide bond	229 ↔ 251		By similarity
	Disulfide bond	292 ↔ 304		By similarity
	Disulfide bond	299 ↔ 317		By similarity
	Disulfide bond	311 ↔ 326		By similarity
Experimental info
	Sequence conflict	80	1	I → F in BAC38196. Ref.3
	Sequence conflict	514	1	R → Q in AAM18028. Ref.1
	Sequence conflict	514	1	R → Q in BAC38196. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8R4I7 [UniParc]. Last modified February 15, 2005. Version 2. Checksum: 6375B395421D558F	FASTA	533	60,242
	10 20 30 40 50 60 MIYGRSLFHI IASLIILHSS GATKKGTEKQ ITPETQKSVQ CGTWTKHAEG GVFTSPNYPS 70 80 90 100 110 120 KYPPDRECVY IIEAAPRQCI ELYFDEKYSI EPSWECKFDH IEVRDGPFGF SPIIGRFCGQ 130 140 150 160 170 180 QNPPVIKSSG RFLWIKFFAD GELESMGFSA RYNFTPDPDF KDLGVLKPLP ACEFEMGGPE 190 200 210 220 230 240 GIVESIQILK EGKASASEAV DCKWYIRAPP RSKIYLRFLD YEMQNSNECK RNFVAVYDGS 250 260 270 280 290 300 SSVEDLKAKF CSTVANDVML RTGLGVIRMW ADEGSRNSRF QMLFTSFQEP PCEGNTFFCH 310 320 330 340 350 360 SNMCINNTLV CNGLQNCVYP WDENHCKEKR KTSLLDQLTN TSGTVIGVTS CIVIILIIVS 370 380 390 400 410 420 VIVQIKQPRK KYVQRKSDFD QTVFQEVFEP PHYELCTLRG TGATADFADV AEDFENYHKL 430 440 450 460 470 480 RRSSSKCIHD HHCGSQLSSA KGSRSNLSTR DASILAEIPT QPVKPLIPPV NRRNILVMKH 490 500 510 520 530 NYSQDAADAC DIDEIEEVPT TSHRLSRHEK SVQRFCLIGS LSKHESEYNT TRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene encoding a putative transmembrane protein with two extracellular CUB domains and a low-density lipoprotein class A module: isolation of alternatively spliced isoforms in retina and brain." Stoehr H., Berger C., Froehlich S., Weber B.H.F. Gene 286:223-231(2002) [PubMed: 11943477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[2]	"A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in restricted areas of mouse brain." Michishita M., Ikeda T., Nakashiba T., Ogawa M., Tashiro K., Honjo T., Doi K., Itohara S., Endo S. Biochem. Biophys. Res. Commun. 306:680-686(2003) [PubMed: 12810072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: C57BL/6. Tissue: Brain.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Head and Olfactory bulb.
[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]. Tissue: Brain.
[5]	"Expression of Btcl2, a novel member of Btcl gene family, during development of the central nervous system." Michishita M., Ikeda T., Nakashiba T., Ogawa M., Tashiro K., Honjo T., Doi K., Itohara S., Endo S. Brain Res. Dev. Brain Res. 153:135-142(2004) [PubMed: 15464227] [Abstract] Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY. Strain: C57BL/6. Tissue: Brain.
[6]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-417, MASS SPECTROMETRY. Tissue: Brain.
[7]	"Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning." Ng D., Pitcher G.M., Szilard R.K., Sertie A., Kanisek M., Clapcote S.J., Lipina T., Kalia L.V., Joo D., McKerlie C., Cortez M., Roder J.C., Salter M.W., McInnes R.R. PLoS Biol. 7:E41-E41(2009) [PubMed: 19243221] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH GRIN2A; GRIN2B; DLG2; DLG3 AND DLG4.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF448840 mRNA. Translation: AAM18028.1. AY138990 mRNA. Translation: AAN38318.1. AK032510 mRNA. Translation: BAC27902.1. AK081325 mRNA. Translation: BAC38196.1. BC051145 mRNA. Translation: AAH51145.1.
IPI	IPI00330652.
RefSeq	NP_659195.3. NM_144946.4.
UniGene	Mm.329578.
3D structure databases
ProteinModelPortal	Q8R4I7.
SMR	Q8R4I7. Positions 39-325.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48395N.
IntAct	Q8R4I7. 1 interaction.
STRING	Q8R4I7.
PTM databases
PhosphoSite	Q8R4I7.
Proteomic databases
PRIDE	Q8R4I7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000058829; ENSMUSP00000057340; ENSMUSG00000050321.
GeneID	246317.
KEGG	mmu:246317.
UCSC	uc008fuz.2. mouse.
Organism-specific databases
CTD	81832.
MGI	MGI:2180216. Neto1.
Phylogenomic databases
eggNOG	roNOG11571.
GeneTree	ENSGT00600000084035.
HOGENOM	HBG445620.
HOVERGEN	HBG052600.
InParanoid	Q8R4I7.
OMA	TEAVDCK.
OrthoDB	EOG42V8G1.
PhylomeDB	Q8R4I7.
Gene expression databases
ArrayExpress	Q8R4I7.
Bgee	Q8R4I7.
CleanEx	MM_NETO1.
Genevestigator	Q8R4I7.
GermOnline	ENSMUSG00000050321. Mus musculus.
Family and domain databases
InterPro	IPR000859. CUB. IPR023415. LDLR_class-A_CS. IPR002172. LDrepeatLR_classA_rpt. [Graphical view]
Gene3D	G3DSA:2.60.120.290. CUB. 2 hits. G3DSA:4.10.400.10. LDL_rcpt_classA_cys-rich. 1 hit.
Pfam	PF00431. CUB. 2 hits. PF00057. Ldl_recept_a. 1 hit. [Graphical view]
SMART	SM00042. CUB. 2 hits. SM00192. LDLa. 1 hit. [Graphical view]
SUPFAM	SSF49854. CUB. 2 hits. SSF57424. LDL_rcpt_classA_cys-rich. 1 hit.
PROSITE	PS01180. CUB. 2 hits. PS01209. LDLRA_1. 1 hit. PS50068. LDLRA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	387225.
SOURCE	Search...

Entry information

Entry name

NETO1_MOUSE

Accession

Primary (citable) accession number: Q8R4I7
Secondary accession number(s): Q80X39, Q8C4S3, Q8CCM2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	February 15, 2005
Last modified:	October 19, 2011
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program