ID   NAPSA_HUMAN             Reviewed;         420 AA.
AC   O96009; Q8WWD9;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 177.
DE   RecName: Full=Napsin-A;
DE            EC=3.4.23.-;
DE   AltName: Full=Aspartyl protease 4;
DE            Short=ASP4;
DE            Short=Asp 4;
DE   AltName: Full=Napsin-1;
DE   AltName: Full=TA01/TA02;
DE   Flags: Precursor;
GN   Name=NAPSA; Synonyms=NAP1, NAPA;
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].
RC   TISSUE=Kidney, and Lung;
RX   PubMed=9877162; DOI=10.1016/s0014-5793(98)01522-1;
RA   Tatnell P.J., Powell D.J., Hill J., Smith T.S., Tew D.G., Kay J.;
RT   "Napsins: new human aspartic proteinases. Distinction between two closely
RT   related genes.";
RL   FEBS Lett. 441:43-48(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RC   TISSUE=Fetal lung;
RX   PubMed=10580105; DOI=10.1016/s0014-5793(99)01493-3;
RA   Chuman Y., Bergman A.-C., Ueno T., Saito S., Sakaguchi K., Alaiya A.A.,
RA   Franzen B., Bergman T., Arnott D., Auer G., Appella E., Joernvall H.,
RA   Linder S.;
RT   "Napsin A, a member of the aspartic protease family, is abundantly
RT   expressed in normal lung and kidney tissue and is expressed in lung
RT   adenocarcinomas.";
RL   FEBS Lett. 462:129-134(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10591213; DOI=10.1038/990107;
RA   Yan R., Bienkowski M.J., Shuck M.E., Miao H., Tory M.C., Pauley A.M.,
RA   Brashier J.R., Stratman N.C., Mathews W.R., Buhl A.E., Carter D.B.,
RA   Tomasselli A.G., Parodi L.A., Heinrikson R.L., Gurney M.E.;
RT   "Membrane-anchored aspartyl protease with Alzheimer's disease beta-
RT   secretase activity.";
RL   Nature 402:533-537(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RA   Koelsch G., Wu S., Henthorn J., Tang J., Lin X.;
RT   "New human aspartic proteases napsin 1 and napsin 2: molecular cloning and
RT   intracellular localization of napsin 1.";
RL   Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-40.
RC   TISSUE=Lung;
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).
CC   -!- FUNCTION: May be involved in processing of pneumocyte surfactant
CC       precursors.
CC   -!- INTERACTION:
CC       O96009; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-7196415, EBI-10245913;
CC       O96009; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-7196415, EBI-9394625;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in adult lung (type II
CC       pneumocytes) and kidney and in fetal lung. Low levels in adult spleen
CC       and very low levels in peripheral blood leukocytes.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR   EMBL; AF090386; AAD04917.1; -; mRNA.
DR   EMBL; AF200345; AAF17081.1; -; mRNA.
DR   EMBL; AF098484; AAD13215.1; -; mRNA.
DR   EMBL; BC017842; AAH17842.1; -; mRNA.
DR   CCDS; CCDS12794.1; -.
DR   RefSeq; NP_004842.1; NM_004851.2.
DR   RefSeq; XP_011525842.1; XM_011527540.1.
DR   AlphaFoldDB; O96009; -.
DR   SMR; O96009; -.
DR   BioGRID; 114861; 11.
DR   IntAct; O96009; 8.
DR   MINT; O96009; -.
DR   STRING; 9606.ENSP00000253719; -.
DR   MEROPS; A01.046; -.
DR   GlyCosmos; O96009; 3 sites, No reported glycans.
DR   GlyGen; O96009; 3 sites.
DR   iPTMnet; O96009; -.
DR   PhosphoSitePlus; O96009; -.
DR   SwissPalm; O96009; -.
DR   BioMuta; NAPSA; -.
DR   EPD; O96009; -.
DR   jPOST; O96009; -.
DR   MassIVE; O96009; -.
DR   PaxDb; 9606-ENSP00000253719; -.
DR   PeptideAtlas; O96009; -.
DR   ProteomicsDB; 51189; -.
DR   Antibodypedia; 3755; 999 antibodies from 40 providers.
DR   DNASU; 9476; -.
DR   Ensembl; ENST00000253719.7; ENSP00000253719.1; ENSG00000131400.9.
DR   GeneID; 9476; -.
DR   KEGG; hsa:9476; -.
DR   MANE-Select; ENST00000253719.7; ENSP00000253719.1; NM_004851.3; NP_004842.1.
DR   UCSC; uc002prx.4; human.
DR   AGR; HGNC:13395; -.
DR   CTD; 9476; -.
DR   DisGeNET; 9476; -.
DR   GeneCards; NAPSA; -.
DR   HGNC; HGNC:13395; NAPSA.
DR   HPA; ENSG00000131400; Tissue enriched (lung).
DR   MIM; 605631; gene.
DR   neXtProt; NX_O96009; -.
DR   OpenTargets; ENSG00000131400; -.
DR   PharmGKB; PA134891814; -.
DR   VEuPathDB; HostDB:ENSG00000131400; -.
DR   eggNOG; KOG1339; Eukaryota.
DR   GeneTree; ENSGT00940000160179; -.
DR   InParanoid; O96009; -.
DR   OMA; DYVIQIS; -.
DR   OrthoDB; 1120702at2759; -.
DR   PhylomeDB; O96009; -.
DR   TreeFam; TF314990; -.
DR   BRENDA; 3.4.23.B1; 2681.
DR   PathwayCommons; O96009; -.
DR   Reactome; R-HSA-5683826; Surfactant metabolism.
DR   SignaLink; O96009; -.
DR   BioGRID-ORCS; 9476; 9 hits in 1156 CRISPR screens.
DR   GeneWiki; NAPSA; -.
DR   GenomeRNAi; 9476; -.
DR   Pharos; O96009; Tbio.
DR   PRO; PR:O96009; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O96009; Protein.
DR   Bgee; ENSG00000131400; Expressed in lower lobe of lung and 112 other cell types or tissues.
DR   ExpressionAtlas; O96009; baseline and differential.
DR   GO; GO:0097208; C:alveolar lamellar body; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR   GO; GO:0097486; C:multivesicular body lumen; TAS:Reactome.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR   GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR   GO; GO:0033619; P:membrane protein proteolysis; IDA:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0043129; P:surfactant homeostasis; IDA:UniProtKB.
DR   Gene3D; 2.40.70.10; Acid Proteases; 3.
DR   InterPro; IPR001461; Aspartic_peptidase_A1.
DR   InterPro; IPR001969; Aspartic_peptidase_AS.
DR   InterPro; IPR033121; PEPTIDASE_A1.
DR   InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR   PANTHER; PTHR47966; BETA-SITE APP-CLEAVING ENZYME, ISOFORM A-RELATED; 1.
DR   PANTHER; PTHR47966:SF94; NAPSIN-A; 1.
DR   Pfam; PF00026; Asp; 1.
DR   PRINTS; PR00792; PEPSIN.
DR   SUPFAM; SSF50630; Acid proteases; 1.
DR   PROSITE; PS00141; ASP_PROTEASE; 2.
DR   PROSITE; PS51767; PEPTIDASE_A1; 1.
DR   Genevisible; O96009; HS.
PE   1: Evidence at protein level;
KW   Aspartyl protease; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Hydrolase; Protease; Reference proteome; Secreted; Signal; Zymogen.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..63
FT                   /note="Activation peptide"
FT                   /id="PRO_0000025996"
FT   CHAIN           64..420
FT                   /note="Napsin-A"
FT                   /id="PRO_0000025997"
FT   DOMAIN          78..399
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        96
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   ACT_SITE        283
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   CARBOHYD        90
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        133
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        109..116
FT                   /evidence="ECO:0000250"
FT   DISULFID        274..278
FT                   /evidence="ECO:0000250"
FT   DISULFID        317..354
FT                   /evidence="ECO:0000250"
FT   VARIANT         40
FT                   /note="I -> T (in dbSNP:rs676314)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_051510"
FT   VARIANT         310
FT                   /note="A -> T (in dbSNP:rs11670727)"
FT                   /id="VAR_024586"
SQ   SEQUENCE   420 AA;  45387 MW;  018B86AE5BD0C865 CRC64;
     MSPPPLLQPL LLLLPLLNVE PSGATLIRIP LHRVQPGRRI LNLLRGWREP AELPKLGAPS
     PGDKPIFVPL SNYRDVQYFG EIGLGTPPQN FTVAFDTGSS NLWVPSRRCH FFSVPCWLHH
     RFDPKASSSF QANGTKFAIQ YGTGRVDGIL SEDKLTIGGI KGASVIFGEA LWEPSLVFAF
     AHFDGILGLG FPILSVEGVR PPMDVLVEQG LLDKPVFSFY LNRDPEEPDG GELVLGGSDP
     AHYIPPLTFV PVTVPAYWQI HMERVKVGPG LTLCAKGCAA ILDTGTSLIT GPTEEIRALH
     AAIGGIPLLA GEYIILCSEI PKLPAVSFLL GGVWFNLTAH DYVIQTTRNG VRLCLSGFQA
     LDVPPPAGPF WILGDVFLGT YVAVFDRGDM KSSARVGLAR ARTRGADLGW GETAQAQFPG
//