ID   NPTX1_HUMAN             Reviewed;         432 AA.
AC   Q15818; B3KXH3; Q5FWE6;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 2.
DT   27-MAR-2024, entry version 183.
DE   RecName: Full=Neuronal pentraxin-1;
DE            Short=NP1;
DE   AltName: Full=Neuronal pentraxin I;
DE            Short=NP-I;
DE   Flags: Precursor;
GN   Name=NPTX1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8884281; DOI=10.1006/geno.1996.0503;
RA   Omeis I.A., Hsu Y.-C., Perin M.S.;
RT   "Mouse and human neuronal pentraxin 1 (NPTX1): conservation, genomic
RT   structure, and chromosomal localization.";
RL   Genomics 36:543-545(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Hippocampus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Chondrosarcoma;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   INVOLVEMENT IN SCA50, VARIANTS SCA50 GLY-327 AND ARG-389, CHARACTERIZATION
RP   OF VARIANTS SCA50 GLY-327 AND ARG-389, AND SUBCELLULAR LOCATION.
RX   PubMed=34788392; DOI=10.1093/brain/awab407;
RA   Coutelier M., Jacoupy M., Janer A., Renaud F., Auger N., Saripella G.V.,
RA   Ancien F., Pucci F., Rooman M., Gilis D., Lariviere R., Sgarioto N.,
RA   Valter R., Guillot-Noel L., Le Ber I., Sayah S., Charles P., Nuemann A.,
RA   Pauly M.G., Helmchen C., Deininger N., Haack T.B., Brais B., Brice A.,
RA   Tregouet D.A., El Hachimi K.H., Shoubridge E.A., Durr A., Stevanin G.;
RT   "NPTX1 mutations trigger endoplasmic reticulum stress and cause autosomal
RT   dominant cerebellar ataxia.";
RL   Brain 145:1519-1534(2022).
RN   [5]
RP   VARIANT SCA50 LEU-143.
RX   PubMed=35285082; DOI=10.1002/mds.28985;
RA   Deppe J., Deininger N., Lingor P., Haack T.B., Haslinger B., Deschauer M.;
RT   "A Novel NPTX1 de novo Variant in a Late-Onset Ataxia Patient.";
RL   Mov. Disord. 37:1319-1321(2022).
RN   [6]
RP   VARIANT SCA50 ARG-370.
RX   PubMed=35560436; DOI=10.1002/mds.29054;
RA   Schoeggl J., Siegert S., Boltshauser E., Freilinger M., Schmidt W.M.;
RT   "A De Novo Missense NPTX1 Variant in an Individual with Infantile-Onset
RT   Cerebellar Ataxia.";
RL   Mov. Disord. 37:1774-1776(2022).
CC   -!- FUNCTION: May be involved in mediating uptake of synaptic material
CC       during synapse remodeling or in mediating the synaptic clustering of
CC       AMPA glutamate receptors at a subset of excitatory synapses.
CC       {ECO:0000250|UniProtKB:P47971}.
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC       Note=Binds 2 calcium ions per subunit. {ECO:0000250};
CC   -!- SUBUNIT: Homooligomer or heterooligomer (probably pentamer) with
CC       neuronal pentraxin receptor (NPTXR). {ECO:0000250|UniProtKB:P47971}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:34788392}.
CC       Cytoplasmic vesicle, secretory vesicle {ECO:0000269|PubMed:34788392,
CC       ECO:0000305}. Endoplasmic reticulum {ECO:0000269|PubMed:34788392,
CC       ECO:0000305}.
CC   -!- DISEASE: Spinocerebellar ataxia 50 (SCA50) [MIM:620158]: A form of
CC       spinocerebellar ataxia, a clinically and genetically heterogeneous
CC       group of cerebellar disorders. Patients show progressive incoordination
CC       of gait and often poor coordination of hands, speech and eye movements,
CC       due to degeneration of the cerebellum with variable involvement of the
CC       brainstem and spinal cord. SCA50 is an autosomal dominant form
CC       characterized by cerebellar ataxia, oculomotor apraxia and other eye
CC       movement abnormalities, and cerebellar atrophy on brain imaging.
CC       {ECO:0000269|PubMed:34788392, ECO:0000269|PubMed:35285082,
CC       ECO:0000269|PubMed:35560436}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; U61849; AAC50727.1; -; mRNA.
DR   EMBL; AK127335; BAG54485.1; -; mRNA.
DR   EMBL; BC089441; AAH89441.1; -; mRNA.
DR   CCDS; CCDS32762.1; -.
DR   RefSeq; NP_002513.2; NM_002522.3.
DR   PDB; 6YPE; X-ray; 1.45 A; A/B=225-429.
DR   PDBsum; 6YPE; -.
DR   AlphaFoldDB; Q15818; -.
DR   SMR; Q15818; -.
DR   BioGRID; 110944; 79.
DR   IntAct; Q15818; 37.
DR   MINT; Q15818; -.
DR   STRING; 9606.ENSP00000307549; -.
DR   TCDB; 1.C.92.1.3; the pentraxin (pentraxin) family.
DR   UniLectin; Q15818; -.
DR   GlyCosmos; Q15818; 2 sites, No reported glycans.
DR   GlyGen; Q15818; 2 sites.
DR   iPTMnet; Q15818; -.
DR   PhosphoSitePlus; Q15818; -.
DR   BioMuta; NPTX1; -.
DR   DMDM; 77416871; -.
DR   EPD; Q15818; -.
DR   jPOST; Q15818; -.
DR   MassIVE; Q15818; -.
DR   MaxQB; Q15818; -.
DR   PaxDb; 9606-ENSP00000307549; -.
DR   PeptideAtlas; Q15818; -.
DR   ProteomicsDB; 60774; -.
DR   Pumba; Q15818; -.
DR   Antibodypedia; 32766; 470 antibodies from 32 providers.
DR   DNASU; 4884; -.
DR   Ensembl; ENST00000306773.5; ENSP00000307549.4; ENSG00000171246.7.
DR   GeneID; 4884; -.
DR   KEGG; hsa:4884; -.
DR   MANE-Select; ENST00000306773.5; ENSP00000307549.4; NM_002522.4; NP_002513.2.
DR   UCSC; uc002jyp.2; human.
DR   AGR; HGNC:7952; -.
DR   CTD; 4884; -.
DR   DisGeNET; 4884; -.
DR   GeneCards; NPTX1; -.
DR   HGNC; HGNC:7952; NPTX1.
DR   HPA; ENSG00000171246; Tissue enriched (brain).
DR   MalaCards; NPTX1; -.
DR   MIM; 602367; gene.
DR   MIM; 620158; phenotype.
DR   neXtProt; NX_Q15818; -.
DR   OpenTargets; ENSG00000171246; -.
DR   PharmGKB; PA31738; -.
DR   VEuPathDB; HostDB:ENSG00000171246; -.
DR   eggNOG; ENOG502QTID; Eukaryota.
DR   GeneTree; ENSGT01060000248591; -.
DR   HOGENOM; CLU_032051_0_0_1; -.
DR   InParanoid; Q15818; -.
DR   OMA; IAWSETN; -.
DR   OrthoDB; 4219275at2759; -.
DR   PhylomeDB; Q15818; -.
DR   TreeFam; TF330208; -.
DR   PathwayCommons; Q15818; -.
DR   SignaLink; Q15818; -.
DR   SIGNOR; Q15818; -.
DR   BioGRID-ORCS; 4884; 11 hits in 1152 CRISPR screens.
DR   ChiTaRS; NPTX1; human.
DR   GeneWiki; NPTX1; -.
DR   GenomeRNAi; 4884; -.
DR   Pharos; Q15818; Tbio.
DR   PRO; PR:Q15818; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q15818; Protein.
DR   Bgee; ENSG00000171246; Expressed in cerebellar vermis and 162 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0043083; C:synaptic cleft; IEA:Ensembl.
DR   GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0060385; P:axonogenesis involved in innervation; IBA:GO_Central.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR   GO; GO:0035865; P:cellular response to potassium ion; IEA:Ensembl.
DR   GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR   GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR   GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IEA:Ensembl.
DR   GO; GO:0006839; P:mitochondrial transport; IEA:Ensembl.
DR   GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl.
DR   GO; GO:0097107; P:postsynaptic density assembly; IEA:Ensembl.
DR   CDD; cd00152; PTX; 1.
DR   Gene3D; 2.60.120.200; -; 1.
DR   InterPro; IPR013320; ConA-like_dom_sf.
DR   InterPro; IPR030476; Pentaxin_CS.
DR   InterPro; IPR001759; Pentraxin-related.
DR   PANTHER; PTHR19277:SF24; NEURONAL PENTRAXIN-1; 1.
DR   PANTHER; PTHR19277; PENTRAXIN; 1.
DR   Pfam; PF00354; Pentaxin; 1.
DR   PRINTS; PR00895; PENTAXIN.
DR   SMART; SM00159; PTX; 1.
DR   SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR   PROSITE; PS00289; PTX_1; 1.
DR   PROSITE; PS51828; PTX_2; 1.
DR   Genevisible; Q15818; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Cytoplasmic vesicle; Disease variant;
KW   Disulfide bond; Endoplasmic reticulum; Glycoprotein; Metal-binding;
KW   Neurodegeneration; Reference proteome; Secreted; Signal;
KW   Spinocerebellar ataxia.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..432
FT                   /note="Neuronal pentraxin-1"
FT                   /id="PRO_0000023547"
FT   DOMAIN          226..428
FT                   /note="Pentraxin (PTX)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01172"
FT   REGION          90..122
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         280
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         358
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         358
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01172"
FT   BINDING         359
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         360
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         360
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01172"
FT   BINDING         370
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01172"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        256..316
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01172"
FT   VARIANT         143
FT                   /note="R -> L (in SCA50; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:35285082"
FT                   /id="VAR_087974"
FT   VARIANT         327
FT                   /note="E -> G (in SCA50; uncertain significance; abolishes
FT                   secretion; loss of multimerization ability)"
FT                   /evidence="ECO:0000269|PubMed:34788392"
FT                   /id="VAR_087975"
FT   VARIANT         370
FT                   /note="Q -> R (in SCA50)"
FT                   /evidence="ECO:0000269|PubMed:35560436"
FT                   /id="VAR_087976"
FT   VARIANT         389
FT                   /note="G -> R (in SCA50; does not affect secretion; does
FT                   not affect multimerization; dbSNP:rs1466750124)"
FT                   /evidence="ECO:0000269|PubMed:34788392"
FT                   /id="VAR_087977"
FT   CONFLICT        7
FT                   /note="Missing (in Ref. 1; AAC50727)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        20..22
FT                   /note="AGA -> P (in Ref. 1; AAC50727)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        57
FT                   /note="S -> SN (in Ref. 1; AAC50727)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        192
FT                   /note="R -> K (in Ref. 1; AAC50727)"
FT                   /evidence="ECO:0000305"
FT   STRAND          228..232
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          240..245
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          250..260
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          268..275
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          278..286
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          288..290
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          293..296
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          299..302
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          309..311
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          313..320
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   TURN            321..324
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          325..330
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          333..338
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          352..357
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   HELIX           368..370
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          374..384
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   HELIX           388..395
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          405..407
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   HELIX           411..413
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          414..417
FT                   /evidence="ECO:0007829|PDB:6YPE"
FT   STRAND          421..424
FT                   /evidence="ECO:0007829|PDB:6YPE"
SQ   SEQUENCE   432 AA;  47122 MW;  B881AC19F7C8F74A CRC64;
     MPAGRAARTC ALLALCLLGA GAQDFGPTRF ICTSVPVDAD MCAASVAAGG AEELRSSVLQ
     LRETVLQQKE TILSQKETIR ELTAKLGRCE SQSTLDPGAG EARAGGGRKQ PGSGKNTMGD
     LSRTPAAETL SQLGQTLQSL KTRLENLEQY SRLNSSSQTN SLKDLLQSKI DELERQVLSR
     VNTLEEGKGG PRNDTEERVK IETALTSLHQ RISELEKGQK DNRPGDKFQL TFPLRTNYMY
     AKVKKSLPEM YAFTVCMWLK SSATPGVGTP FSYAVPGQAN ELVLIEWGNN PMEILINDKV
     AKLPFVINDG KWHHICVTWT TRDGVWEAYQ DGTQGGSGEN LAPYHPIKPQ GVLVLGQEQD
     TLGGGFDATQ AFVGELAHFN IWDRKLTPGE VYNLATCSTK ALSGNVIAWA ESHIEIYGGA
     TKWTFEACRQ IN
//