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Protein

Neuropilin and tolloid-like protein 2

Gene

NETO2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Accessory subunit of neuronal kainate-sensitive glutamate receptors, GRIK2 and GRIK3. Increases kainate-receptor channel activity, slowing the decay kinetics of the receptors, without affecting their expression at the cell surface, and increasing the open probability of the receptor channels. Modulates the agonist sensitivity of kainate receptors. Slows the decay of kainate receptor-mediated excitatory postsynaptic currents (EPSCs), thus directly influencing synaptic transmission (By similarity).By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Protein family/group databases

TCDBi8.A.47.1.2. the neuropilin and tolloid-like (neto) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuropilin and tolloid-like protein 2
Alternative name(s):
Brain-specific transmembrane protein containing 2 CUB and 1 LDL-receptor class A domains protein 2
Gene namesi
Name:NETO2
Synonyms:BTCL2
ORF Names:UNQ1926/PRO4401
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:14644. NETO2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 347325ExtracellularSequence analysisAdd
BLAST
Transmembranei348 – 36821HelicalSequence analysisAdd
BLAST
Topological domaini369 – 525157CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31559.

Polymorphism and mutation databases

BioMutaiNETO2.
DMDMi59798464.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 22221 PublicationAdd
BLAST
Chaini23 – 525503Neuropilin and tolloid-like protein 2PRO_0000021801Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi45 ↔ 72By similarity
Disulfide bondi100 ↔ 122By similarity
Disulfide bondi177 ↔ 207By similarity
Disulfide bondi234 ↔ 256By similarity
Disulfide bondi297 ↔ 309By similarity
Disulfide bondi304 ↔ 322By similarity
Glycosylationi311 – 3111N-linked (GlcNAc...)Sequence analysis
Disulfide bondi316 ↔ 331By similarity
Modified residuei409 – 4091PhosphoserineBy similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8NC67.
MaxQBiQ8NC67.
PaxDbiQ8NC67.
PeptideAtlasiQ8NC67.
PRIDEiQ8NC67.

PTM databases

iPTMnetiQ8NC67.
PhosphoSiteiQ8NC67.

Expressioni

Gene expression databases

BgeeiQ8NC67.
CleanExiHS_NETO2.
ExpressionAtlasiQ8NC67. baseline and differential.
GenevisibleiQ8NC67. HS.

Organism-specific databases

HPAiHPA013180.

Interactioni

Subunit structurei

Interacts with GRIK2 and GRIK3, but neither with AMPA-nor with NMDA-sensitive glutamate receptors.By similarity

Protein-protein interaction databases

BioGridi123589. 31 interactions.
IntActiQ8NC67. 12 interactions.
STRINGi9606.ENSP00000455169.

Structurei

3D structure databases

ProteinModelPortaliQ8NC67.
SMRiQ8NC67. Positions 42-244.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini45 – 159115CUB 1PROSITE-ProRule annotationAdd
BLAST
Domaini177 – 292116CUB 2PROSITE-ProRule annotationAdd
BLAST
Domaini296 – 33237LDL-receptor class APROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 2 CUB domains.PROSITE-ProRule annotation
Contains 1 LDL-receptor class A domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGDK. Eukaryota.
ENOG41102J7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000060303.
HOVERGENiHBG052600.
InParanoidiQ8NC67.
OMAiHIPATQC.
OrthoDBiEOG7DFXBV.
PhylomeDBiQ8NC67.

Family and domain databases

Gene3Di2.60.120.290. 2 hits.
4.10.400.10. 1 hit.
InterProiIPR000859. CUB_dom.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR028868. NETO2.
[Graphical view]
PANTHERiPTHR10127:SF314. PTHR10127:SF314. 1 hit.
PfamiPF00431. CUB. 2 hits.
PF00057. Ldl_recept_a. 1 hit.
[Graphical view]
SMARTiSM00042. CUB. 2 hits.
SM00192. LDLa. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF57424. SSF57424. 1 hit.
PROSITEiPS01180. CUB. 2 hits.
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NC67-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MALERLCSVL KVLLITVLVV EGIAVAQKTQ DGQNIGIKHI PATQCGIWVR
60 70 80 90 100
TSNGGHFASP NYPDSYPPNK ECIYILEAAP RQRIELTFDE HYYIEPSFEC
110 120 130 140 150
RFDHLEVRDG PFGFSPLIDR YCGVKSPPLI RSTGRFMWIK FSSDEELEGL
160 170 180 190 200
GFRAKYSFIP DPDFTYLGGI LNPIPDCQFE LSGADGIVRS SQVEQEEKTK
210 220 230 240 250
PGQAVDCIWT IKATPKAKIY LRFLDYQMEH SNECKRNFVA VYDGSSSIEN
260 270 280 290 300
LKAKFCSTVA NDVMLKTGIG VIRMWADEGS RLSRFRMLFT SFVEPPCTSS
310 320 330 340 350
TFFCHSNMCI NNSLVCNGVQ NCAYPWDENH CKEKKKAGVF EQITKTHGTI
360 370 380 390 400
IGITSGIVLV LLIISILVQV KQPRKKVMAC KTAFNKTGFQ EVFDPPHYEL
410 420 430 440 450
FSLRDKEISA DLADLSEELD NYQKMRRSST ASRCIHDHHC GSQASSVKQS
460 470 480 490 500
RTNLSSMELP FRNDFAQPQP MKTFNSTFKK SSYTFKQGHE CPEQALEDRV
510 520
MEEIPCEIYV RGREDSAQAS ISIDF
Length:525
Mass (Da):59,393
Last modified:October 1, 2002 - v1
Checksum:iEA6F98C3A88220EA
GO
Isoform 2 (identifier: Q8NC67-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-324: Missing.
     325-333: PWDENHCKE → MLFTSFVEQ

Show »
Length:201
Mass (Da):22,849
Checksum:iBC01389AE0203E84
GO
Isoform 3 (identifier: Q8NC67-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     169-175: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:518
Mass (Da):58,688
Checksum:iF360FA90C0A96056
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti211 – 2111I → V in CAD97994 (PubMed:17974005).Curated
Sequence conflicti278 – 2781E → G in CAD97994 (PubMed:17974005).Curated
Sequence conflicti424 – 4241K → R in BAB55247 (PubMed:14702039).Curated
Sequence conflicti461 – 4611F → L in BAB55247 (PubMed:14702039).Curated
Sequence conflicti482 – 4821S → G in CAD97994 (PubMed:17974005).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti456 – 4561S → T.
Corresponds to variant rs2231983 [ dbSNP | Ensembl ].
VAR_051232

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 324324Missing in isoform 2. 1 PublicationVSP_012856Add
BLAST
Alternative sequencei169 – 1757Missing in isoform 3. CuratedVSP_053795
Alternative sequencei325 – 3339PWDENHCKE → MLFTSFVEQ in isoform 2. 1 PublicationVSP_012857

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358718 mRNA. Translation: AAQ89080.1.
AK001292 mRNA. Translation: BAA91604.1.
AK027478 mRNA. Translation: BAB55141.1.
AK027630 mRNA. Translation: BAB55247.1.
AK074937 mRNA. Translation: BAC11303.1.
AL834404 mRNA. Translation: CAD39066.1.
BX538063 mRNA. Translation: CAD97994.1.
CR457255 mRNA. Translation: CAG33536.1.
AC007338 Genomic DNA. No translation available.
AC007494 Genomic DNA. No translation available.
BC012381 mRNA. Translation: AAH12381.1.
CCDSiCCDS10727.1. [Q8NC67-1]
CCDS58460.1. [Q8NC67-3]
RefSeqiNP_001188406.1. NM_001201477.1. [Q8NC67-3]
NP_060562.3. NM_018092.4. [Q8NC67-1]
UniGeneiHs.645802.

Genome annotation databases

EnsembliENST00000303155; ENSP00000306726; ENSG00000171208. [Q8NC67-3]
ENST00000562435; ENSP00000455169; ENSG00000171208. [Q8NC67-1]
GeneIDi81831.
KEGGihsa:81831.
UCSCiuc002eer.3. human. [Q8NC67-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358718 mRNA. Translation: AAQ89080.1.
AK001292 mRNA. Translation: BAA91604.1.
AK027478 mRNA. Translation: BAB55141.1.
AK027630 mRNA. Translation: BAB55247.1.
AK074937 mRNA. Translation: BAC11303.1.
AL834404 mRNA. Translation: CAD39066.1.
BX538063 mRNA. Translation: CAD97994.1.
CR457255 mRNA. Translation: CAG33536.1.
AC007338 Genomic DNA. No translation available.
AC007494 Genomic DNA. No translation available.
BC012381 mRNA. Translation: AAH12381.1.
CCDSiCCDS10727.1. [Q8NC67-1]
CCDS58460.1. [Q8NC67-3]
RefSeqiNP_001188406.1. NM_001201477.1. [Q8NC67-3]
NP_060562.3. NM_018092.4. [Q8NC67-1]
UniGeneiHs.645802.

3D structure databases

ProteinModelPortaliQ8NC67.
SMRiQ8NC67. Positions 42-244.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123589. 31 interactions.
IntActiQ8NC67. 12 interactions.
STRINGi9606.ENSP00000455169.

Protein family/group databases

TCDBi8.A.47.1.2. the neuropilin and tolloid-like (neto) family.

PTM databases

iPTMnetiQ8NC67.
PhosphoSiteiQ8NC67.

Polymorphism and mutation databases

BioMutaiNETO2.
DMDMi59798464.

Proteomic databases

EPDiQ8NC67.
MaxQBiQ8NC67.
PaxDbiQ8NC67.
PeptideAtlasiQ8NC67.
PRIDEiQ8NC67.

Protocols and materials databases

DNASUi81831.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303155; ENSP00000306726; ENSG00000171208. [Q8NC67-3]
ENST00000562435; ENSP00000455169; ENSG00000171208. [Q8NC67-1]
GeneIDi81831.
KEGGihsa:81831.
UCSCiuc002eer.3. human. [Q8NC67-1]

Organism-specific databases

CTDi81831.
GeneCardsiNETO2.
HGNCiHGNC:14644. NETO2.
HPAiHPA013180.
MIMi607974. gene.
neXtProtiNX_Q8NC67.
PharmGKBiPA31559.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGDK. Eukaryota.
ENOG41102J7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000060303.
HOVERGENiHBG052600.
InParanoidiQ8NC67.
OMAiHIPATQC.
OrthoDBiEOG7DFXBV.
PhylomeDBiQ8NC67.

Miscellaneous databases

ChiTaRSiNETO2. human.
GenomeRNAii81831.
PROiQ8NC67.
SOURCEiSearch...

Gene expression databases

BgeeiQ8NC67.
CleanExiHS_NETO2.
ExpressionAtlasiQ8NC67. baseline and differential.
GenevisibleiQ8NC67. HS.

Family and domain databases

Gene3Di2.60.120.290. 2 hits.
4.10.400.10. 1 hit.
InterProiIPR000859. CUB_dom.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR028868. NETO2.
[Graphical view]
PANTHERiPTHR10127:SF314. PTHR10127:SF314. 1 hit.
PfamiPF00431. CUB. 2 hits.
PF00057. Ldl_recept_a. 1 hit.
[Graphical view]
SMARTiSM00042. CUB. 2 hits.
SM00192. LDLa. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF57424. SSF57424. 1 hit.
PROSITEiPS01180. CUB. 2 hits.
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-525 (ISOFORM 1).
    Tissue: Brain.
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 378-525.
  5. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    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] OF 378-525.
    Tissue: Ovary.
  7. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 23-37.

Entry informationi

Entry nameiNETO2_HUMAN
AccessioniPrimary (citable) accession number: Q8NC67
Secondary accession number(s): J3KNF1
, Q7Z381, Q8ND51, Q96SP4, Q9NVY8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: October 1, 2002
Last modified: July 6, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.