LOCUS       NP_060562                525 aa            linear   PRI 27-APR-2025
DEFINITION  neuropilin and tolloid-like protein 2 isoform 1 precursor [Homo
            sapiens].
ACCESSION   NP_060562
VERSION     NP_060562.3
DBSOURCE    REFSEQ: accession NM_018092.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 525)
  AUTHORS   Zhu,S., Zhang,X., Guo,Y., Tang,L., Zhou,Z., Chen,X. and Peng,C.
  TITLE     NETO2 promotes melanoma progression via activation of the
            Ca2+/CaMKII signaling pathway
  JOURNAL   Front Med 17 (2), 263-274 (2023)
   PUBMED   36738427
  REMARK    GeneRIF: NETO2 promotes melanoma progression via activation of the
            Ca[2+]/CaMKII signaling pathway.
REFERENCE   2  (residues 1 to 525)
  AUTHORS   Li,Y., Wang,W., Hou,X., Huang,W., Zhang,P., He,Y., Wang,B.,
            Duan,Q., Mao,F. and Guo,D.
  TITLE     Glioma-derived LRIG3 interacts with NETO2 in tumor-associated
            macrophages to modulate microenvironment and suppress tumor growth
  JOURNAL   Cell Death Dis 14 (1), 28 (2023)
   PUBMED   36639372
  REMARK    GeneRIF: Glioma-derived LRIG3 interacts with NETO2 in
            tumor-associated macrophages to modulate microenvironment and
            suppress tumor growth.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 525)
  AUTHORS   He,L., Sun,J., Gao,Y., Li,B., Wang,Y., Dong,Y., An,W., Li,H.,
            Yang,B., Ge,Y., Zhang,X.C., Shi,Y.S. and Zhao,Y.
  TITLE     Kainate receptor modulation by NETO2
  JOURNAL   Nature 599 (7884), 325-329 (2021)
   PUBMED   34552241
  REMARK    GeneRIF: Kainate receptor modulation by NETO2.
REFERENCE   4  (residues 1 to 525)
  AUTHORS   Xu,J.C., Chen,T.Y., Liao,L.T., Chen,T., Li,Q.L., Xu,J.X., Hu,J.W.,
            Zhou,P.H. and Zhang,Y.Q.
  TITLE     NETO2 promotes esophageal cancer progression by inducing
            proliferation and metastasis via PI3K/AKT and ERK pathway
  JOURNAL   Int J Biol Sci 17 (1), 259-270 (2021)
   PUBMED   33390848
  REMARK    GeneRIF: NETO2 promotes esophageal cancer progression by inducing
            proliferation and metastasis via PI3K/AKT and ERK pathway.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 525)
  AUTHORS   Calicchio,M.L., Collins,T. and Kozakewich,H.P.
  TITLE     Identification of signaling systems in proliferating and involuting
            phase infantile hemangiomas by genome-wide transcriptional
            profiling
  JOURNAL   Am J Pathol 174 (5), 1638-1649 (2009)
   PUBMED   19349369
REFERENCE   6  (residues 1 to 525)
  AUTHORS   Zhang,W., St-Gelais,F., Grabner,C.P., Trinidad,J.C., Sumioka,A.,
            Morimoto-Tomita,M., Kim,K.S., Straub,C., Burlingame,A.L., Howe,J.R.
            and Tomita,S.
  TITLE     A transmembrane accessory subunit that modulates kainate-type
            glutamate receptors
  JOURNAL   Neuron 61 (3), 385-396 (2009)
   PUBMED   19217376
  REMARK    GeneRIF: Rat neto2 plays a role in glutamate signaling in the brain
            by modulating the function of kainate receptors.
REFERENCE   7  (residues 1 to 525)
  AUTHORS   Sanford,J.R., Coutinho,P., Hackett,J.A., Wang,X., Ranahan,W. and
            Caceres,J.F.
  TITLE     Identification of nuclear and cytoplasmic mRNA targets for the
            shuttling protein SF2/ASF
  JOURNAL   PLoS One 3 (10), e3369 (2008)
   PUBMED   18841201
  REMARK    Publication Status: Online-Only
REFERENCE   8  (residues 1 to 525)
  AUTHORS   Horak,C.E., Lee,J.H., Elkahloun,A.G., Boissan,M., Dumont,S.,
            Maga,T.K., Arnaud-Dabernat,S., Palmieri,D., Stetler-Stevenson,W.G.,
            Lacombe,M.L., Meltzer,P.S. and Steeg,P.S.
  TITLE     Nm23-H1 suppresses tumor cell motility by down-regulating the
            lysophosphatidic acid receptor EDG2
  JOURNAL   Cancer Res 67 (15), 7238-7246 (2007)
   PUBMED   17671192
REFERENCE   9  (residues 1 to 525)
  AUTHORS   Zhang,Z. and Henzel,W.J.
  TITLE     Signal peptide prediction based on analysis of experimentally
            verified cleavage sites
  JOURNAL   Protein Sci 13 (10), 2819-2824 (2004)
   PUBMED   15340161
  REMARK    GeneRIF: Determination of the neuropilin and tolloid-like protein 2
            signal peptide cleavage site by N-terminal sequencing.
REFERENCE   10 (residues 1 to 525)
  AUTHORS   Stohr,H., Berger,C., Frohlich,S. and Weber,B.H.
  TITLE     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
  JOURNAL   Gene 286 (2), 223-231 (2002)
   PUBMED   11943477
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK074937.1 and AC007338.6.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Oct 16, 2002 this sequence version replaced NP_060562.2.
            
            Summary: This gene encodes a predicted transmembrane protein
            containing two extracellular CUB domains followed by a low-density
            lipoprotein class A (LDLa) domain. A similar gene in rats encodes a
            protein that modulates glutamate signaling in the brain by
            regulating kainate receptor function. Expression of this gene may
            be a biomarker for proliferating infantile hemangiomas. A
            pseudogene of this gene is located on the long arm of chromosome 8.
            Alternatively spliced transcript variants encoding multiple
            isoforms have been observed for this gene. [provided by RefSeq, Jan
            2011].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AY358718.1, BC098380.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000562435.6/ ENSP00000455169.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..525
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q12.1"
     Protein         1..525
                     /product="neuropilin and tolloid-like protein 2 isoform 1
                     precursor"
                     /note="brain-specific transmembrane protein containing 2
                     CUB and 1 LDL-receptor class A domains protein 2;
                     neuropilin (NRP) and tolloid (TLL)-like 2"
                     /calculated_mol_wt=57012
     sig_peptide     1..22
                     /note="/evidence=ECO:0000269|PubMed:15340161; propagated
                     from UniProtKB/Swiss-Prot (Q8NC67.1)"
                     /calculated_mol_wt=2399
     mat_peptide     23..525
                     /product="Neuropilin and tolloid-like protein 2.
                     /id=PRO_0000021801"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8NC67.1)"
                     /calculated_mol_wt=57012
     Region          45..158
                     /region_name="CUB"
                     /note="CUB domain; extracellular domain; present in
                     proteins mostly known to be involved in development; not
                     found in prokaryotes, plants and yeast; cd00041"
                     /db_xref="CDD:238001"
     Site            order(54,56,58,85,91,129,153,155,157..158)
                     /site_type="other"
                     /note="heterodimerization interface [polypeptide binding]"
                     /db_xref="CDD:238001"
     Region          <205..291
                     /region_name="CUB"
                     /note="CUB domain; extracellular domain; present in
                     proteins mostly known to be involved in development; not
                     found in prokaryotes, plants and yeast; cd00041"
                     /db_xref="CDD:238001"
     Region          297..331
                     /region_name="LDLa"
                     /note="Low Density Lipoprotein Receptor Class A domain, a
                     cysteine-rich repeat that plays a central role in
                     mammalian cholesterol metabolism; the receptor protein
                     binds LDL and transports it into cells by endocytosis; 7
                     successive cysteine-rich repeats of about...; cd00112"
                     /db_xref="CDD:238060"
     Site            order(302,310,321..322)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            311
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q8NC67.1)"
     Site            order(314,317,321,327..328)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            324..328
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Site            348..368
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8NC67.1)"
     Site            409
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q8BNJ6; propagated from
                     UniProtKB/Swiss-Prot (Q8NC67.1)"
     CDS             1..525
                     /gene="NETO2"
                     /gene_synonym="BTCL2; NEOT2"
                     /coded_by="NM_018092.5:334..1911"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS10727.1"
                     /db_xref="GeneID:81831"
                     /db_xref="HGNC:HGNC:14644"
                     /db_xref="MIM:607974"
ORIGIN      
        1 malerlcsvl kvllitvlvv egiavaqktq dgqnigikhi patqcgiwvr tsngghfasp
       61 nypdsyppnk eciyileaap rqrieltfde hyyiepsfec rfdhlevrdg pfgfsplidr
      121 ycgvksppli rstgrfmwik fssdeelegl gfrakysfip dpdftylggi lnpipdcqfe
      181 lsgadgivrs sqveqeektk pgqavdciwt ikatpkakiy lrfldyqmeh sneckrnfva
      241 vydgsssien lkakfcstva ndvmlktgig virmwadegs rlsrfrmlft sfveppctss
      301 tffchsnmci nnslvcngvq ncaypwdenh ckekkkagvf eqitkthgti igitsgivlv
      361 lliisilvqv kqprkkvmac ktafnktgfq evfdpphyel fslrdkeisa dladlseeld
      421 nyqkmrrsst asrcihdhhc gsqassvkqs rtnlssmelp frndfaqpqp mktfnstfkk
      481 ssytfkqghe cpeqaledrv meeipceiyv rgredsaqas isidf
//
