ID   CATW_HUMAN              Reviewed;         376 AA.
AC   P56202; Q86VT4;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   22-SEP-2009, sequence version 2.
DT   24-JAN-2024, entry version 167.
DE   RecName: Full=Cathepsin W;
DE            EC=3.4.22.-;
DE   AltName: Full=Lymphopain;
DE   Flags: Precursor;
GN   Name=CTSW;
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 [GENOMIC DNA / MRNA], AND VARIANT GLY-139.
RX   PubMed=9823953; DOI=10.1038/sj.leu.2401164;
RA   Brown J., Matutes E., Singleton A., Price C., Molgaard H., Buttle D.,
RA   Enver T.;
RT   "Lymphopain, a cytotoxic T and natural killer cell-associated cysteine
RT   proteinase.";
RL   Leukemia 12:1771-1781(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-139.
RX   PubMed=9108299; DOI=10.1016/s0014-5793(97)00118-x;
RA   Linnevers C., Smeekens S.P., Broemme D.;
RT   "Human cathepsin W, a putative cysteine protease predominantly expressed in
RT   CD8+ T-lymphocytes.";
RL   FEBS Lett. 405:253-259(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-139.
RX   PubMed=9675123; DOI=10.1006/bbrc.1998.8954;
RA   Wex T., Levy B., Smeekens S.P., Ansorge S., Desnick R.J., Bromme D.;
RT   "Genomic structure, chromosomal localization, and expression of human
RT   cathepsin W.";
RL   Biochem. Biophys. Res. Commun. 248:255-261(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-139.
RC   TISSUE=Pancreas;
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   [6]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=11490002; DOI=10.4049/jimmunol.167.4.2172;
RA   Wex T., Buehling F., Wex H., Guenther D., Malfertheiner P., Weber E.,
RA   Broemme D.;
RT   "Human cathepsin W, a cysteine protease predominantly expressed in NK
RT   cells, is mainly localized in the endoplasmic reticulum.";
RL   J. Immunol. 167:2172-2178(2001).
RN   [7]
RP   PROTEIN SEQUENCE OF 22-36.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [8]
RP   FUNCTION (MICROBIAL INFECTION), AND TISSUE SPECIFICITY.
RX   PubMed=26060270; DOI=10.1128/mbio.00297-15;
RA   Edinger T.O., Pohl M.O., Yangueez E., Stertz S.;
RT   "Cathepsin W Is Required for Escape of Influenza A Virus from Late
RT   Endosomes.";
RL   MBio 6:E00297-E00297(2015).
CC   -!- FUNCTION: May have a specific function in the mechanism or regulation
CC       of T-cell cytolytic activity.
CC   -!- FUNCTION: (Microbial infection) Plays a role during influenza virus
CC       infection in lungs cells ex vivo. Acts at the level of virus entering
CC       host cytoplasm from late endosome. {ECO:0000269|PubMed:15340161}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC       {ECO:0000269|PubMed:11490002}.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in natural killer cells,
CC       and in cytotoxic T cells. {ECO:0000269|PubMed:11490002}.
CC   -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090}.
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DR   EMBL; AF013611; AAB82449.1; -; mRNA.
DR   EMBL; AF015954; AAB82457.1; -; Genomic_DNA.
DR   EMBL; AF055903; AAC32181.1; -; Genomic_DNA.
DR   EMBL; AP001201; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC048255; AAH48255.1; -; mRNA.
DR   CCDS; CCDS8117.1; -.
DR   RefSeq; NP_001326.2; NM_001335.3.
DR   AlphaFoldDB; P56202; -.
DR   SMR; P56202; -.
DR   BioGRID; 107901; 2.
DR   IntAct; P56202; 2.
DR   MINT; P56202; -.
DR   STRING; 9606.ENSP00000311300; -.
DR   MEROPS; C01.037; -.
DR   GlyCosmos; P56202; 2 sites, No reported glycans.
DR   GlyGen; P56202; 2 sites.
DR   iPTMnet; P56202; -.
DR   PhosphoSitePlus; P56202; -.
DR   BioMuta; CTSW; -.
DR   DMDM; 259016196; -.
DR   EPD; P56202; -.
DR   MassIVE; P56202; -.
DR   MaxQB; P56202; -.
DR   PaxDb; 9606-ENSP00000311300; -.
DR   PeptideAtlas; P56202; -.
DR   ProteomicsDB; 56904; -.
DR   Antibodypedia; 4281; 110 antibodies from 24 providers.
DR   DNASU; 1521; -.
DR   Ensembl; ENST00000307886.8; ENSP00000311300.3; ENSG00000172543.9.
DR   GeneID; 1521; -.
DR   KEGG; hsa:1521; -.
DR   MANE-Select; ENST00000307886.8; ENSP00000311300.3; NM_001335.4; NP_001326.3.
DR   UCSC; uc001ogc.2; human.
DR   AGR; HGNC:2546; -.
DR   CTD; 1521; -.
DR   DisGeNET; 1521; -.
DR   GeneCards; CTSW; -.
DR   HGNC; HGNC:2546; CTSW.
DR   HPA; ENSG00000172543; Tissue enhanced (bone marrow, lymphoid tissue).
DR   MIM; 602364; gene.
DR   neXtProt; NX_P56202; -.
DR   OpenTargets; ENSG00000172543; -.
DR   PharmGKB; PA27042; -.
DR   VEuPathDB; HostDB:ENSG00000172543; -.
DR   eggNOG; KOG1542; Eukaryota.
DR   GeneTree; ENSGT00940000161630; -.
DR   HOGENOM; CLU_012184_4_1_1; -.
DR   InParanoid; P56202; -.
DR   OMA; NTCGITR; -.
DR   OrthoDB; 1085298at2759; -.
DR   PhylomeDB; P56202; -.
DR   TreeFam; TF337736; -.
DR   PathwayCommons; P56202; -.
DR   Reactome; R-HSA-114608; Platelet degranulation.
DR   SignaLink; P56202; -.
DR   BioGRID-ORCS; 1521; 15 hits in 1144 CRISPR screens.
DR   ChiTaRS; CTSW; human.
DR   GeneWiki; Cathepsin_W; -.
DR   GenomeRNAi; 1521; -.
DR   Pharos; P56202; Tbio.
DR   PRO; PR:P56202; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P56202; Protein.
DR   Bgee; ENSG00000172543; Expressed in granulocyte and 101 other cell types or tissues.
DR   ExpressionAtlas; P56202; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0031089; C:platelet dense granule lumen; TAS:Reactome.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; TAS:ProtInc.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR   CDD; cd02248; Peptidase_C1A; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR025661; Pept_asp_AS.
DR   InterPro; IPR025660; Pept_his_AS.
DR   InterPro; IPR013128; Peptidase_C1A.
DR   InterPro; IPR000668; Peptidase_C1A_C.
DR   InterPro; IPR039417; Peptidase_C1A_papain-like.
DR   InterPro; IPR013201; Prot_inhib_I29.
DR   PANTHER; PTHR12411:SF101; CATHEPSIN W; 1.
DR   PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1.
DR   Pfam; PF08246; Inhibitor_I29; 1.
DR   Pfam; PF00112; Peptidase_C1; 1.
DR   PRINTS; PR00705; PAPAIN.
DR   SMART; SM00848; Inhibitor_I29; 1.
DR   SMART; SM00645; Pept_C1; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR   PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
DR   Genevisible; P56202; HS.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW   Glycoprotein; Hydrolase; Protease; Reference proteome; Signal;
KW   Thiol protease; Zymogen.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   PROPEP          22..127
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000026327"
FT   CHAIN           128..376
FT                   /note="Cathepsin W"
FT                   /id="PRO_0000026328"
FT   ACT_SITE        153
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        291
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        331
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        50
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        205
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        150..191
FT                   /evidence="ECO:0000250"
FT   DISULFID        184..226
FT                   /evidence="ECO:0000250"
FT   DISULFID        284..352
FT                   /evidence="ECO:0000250"
FT   VARIANT         139
FT                   /note="S -> G (in dbSNP:rs604630)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:9108299, ECO:0000269|PubMed:9675123,
FT                   ECO:0000269|PubMed:9823953"
FT                   /id="VAR_058847"
FT   VARIANT         218
FT                   /note="Q -> R (in dbSNP:rs606830)"
FT                   /id="VAR_057041"
FT   CONFLICT        179
FT                   /note="Q -> H (in Ref. 1; AAB82449/AAB82457 and 3;
FT                   AAC32181)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   376 AA;  42120 MW;  D2956524D17B593A CRC64;
     MALTAHPSCL LALLVAGLAQ GIRGPLRAQD LGPQPLELKE AFKLFQIQFN RSYLSPEEHA
     HRLDIFAHNL AQAQRLQEED LGTAEFGVTP FSDLTEEEFG QLYGYRRAAG GVPSMGREIR
     SEEPEESVPF SCDWRKVASA ISPIKDQKNC NCCWAMAAAG NIETLWRISF WDFVDVSVQE
     LLDCGRCGDG CHGGFVWDAF ITVLNNSGLA SEKDYPFQGK VRAHRCHPKK YQKVAWIQDF
     IMLQNNEHRI AQYLATYGPI TVTINMKPLQ LYRKGVIKAT PTTCDPQLVD HSVLLVGFGS
     VKSEEGIWAE TVSSQSQPQP PHPTPYWILK NSWGAQWGEK GYFRLHRGSN TCGITKFPLT
     ARVQKPDMKP RVSCPP
//