ID SPB3_HUMAN Reviewed; 390 AA. AC P29508; A6NDM2; B2RBT5; B3W5Y6; Q53H28; Q53YB5; Q86VF3; Q86W04; Q8IWL4; AC Q8IXI3; Q96J21; Q9BYF8; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2002, sequence version 2. DT 24-JAN-2024, entry version 214. DE RecName: Full=Serpin B3; DE AltName: Full=Protein T4-A; DE AltName: Full=Squamous cell carcinoma antigen 1; DE Short=SCCA-1; GN Name=SERPINB3; Synonyms=SCCA, SCCA1; 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] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND RP VARIANT ALA-357. RX PubMed=1958219; DOI=10.1016/s0006-291x(05)81380-4; RA Suminami Y., Kishi F., Sekiguchi K., Kato H.; RT "Squamous cell carcinoma antigen is a new member of the serine protease RT inhibitors."; RL Biochem. Biophys. Res. Commun. 181:51-58(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX PubMed=7724531; DOI=10.1073/pnas.92.8.3147; RA Schneider S.S., Schick C., Fish K.E., Miller E., Pena J.C., Treter S.D., RA Hui S.M., Silverman G.A.; RT "A serine proteinase inhibitor locus at 18q21.3 contains a tandem RT duplication of the human squamous cell carcinoma antigen gene."; RL Proc. Natl. Acad. Sci. U.S.A. 92:3147-3151(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT ALA-357. RA Suminami Y., Kishi F., Murakami A., Sakaguchi Y., Kato H.; RT "Novel forms of SCC antigen transcripts produced by alternative splicing."; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-351, AND MUTAGENESIS OF RP ALA-341; PHE-352 AND 354-SER-SER-355. RC TISSUE=Hepatoma; RX PubMed=12975381; DOI=10.1074/jbc.m302842200; RA Moore P.L., Ong S., Harrison T.J.; RT "Squamous cell carcinoma antigen 1-mediated binding of hepatitis B virus to RT hepatocytes does not involve the hepatic serpin clearance system."; RL J. Biol. Chem. 278:46709-46717(2003). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hepatoma; RA Tong C., Chenyu X., Jun Z., Ningshao X.; RT "SCCA1 mRNA sequence from human hepatocellular carcinoma cell line HepG2, RT complete cds."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-351. RC TISSUE=Liver; RA Turato C., Biasiolo A., Quarta S., Beneduce L., Zuin J., Fassina G., RA Gatta A., Pontisso P.; RT "Characterization of the new isoform of squamous cell carcinoma antigen-1 RT (SCCA-PD) detected in hepatocellular carcinoma."; RL Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Trachea; 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-357. RC TISSUE=Dermoid cancer; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J., RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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). RN [13] RP PROTEIN SEQUENCE OF 1-21; 88-94; 112-125; 147-160; 215-260; 266-300; RP 322-331 AND 378-386, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Osteosarcoma; RA Bienvenut W.V., Bensaad K., Vousden K.H.; RL Submitted (FEB-2008) to UniProtKB. RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 109-390 (ISOFORM 1), VARIANT ALA-351, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Liver cancer; RX PubMed=14970861; DOI=10.1038/sj.bjc.6601543; RA Pontisso P., Calabrese F., Benvegnu L., Lise M., Belluco C., RA Ruvoletto M.G., De Falco S., Marino M., Valente M., Nitti D., Gatta A., RA Fassina G.; RT "Overexpression of squamous cell carcinoma antigen variants in RT hepatocellular carcinoma."; RL Br. J. Cancer 90:833-837(2004). RN [15] RP SUBCELLULAR LOCATION. RX PubMed=10956412; RX DOI=10.1002/1097-0215(20000720)89:4<368::aid-ijc9>3.0.co;2-6; RA Uemura Y., Pak S.C., Luke C., Cataltepe S., Tsu C., Schick C., Kamachi Y., RA Pomeroy S.L., Perlmutter D.H., Silverman G.A.; RT "Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted RT but reside in the cytosol of squamous carcinoma cells."; RL Int. J. Cancer 89:368-377(2000). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-390, FUNCTION, INDUCTION, RP MUTAGENESIS OF PHE-352, AND INTERACTION WITH MAPK8. RX PubMed=19166818; DOI=10.1016/j.bbrc.2009.01.057; RA Zheng B., Matoba Y., Kumagai T., Katagiri C., Hibino T., Sugiyama M.; RT "Crystal structure of SCCA1 and insight about the interaction with JNK1."; RL Biochem. Biophys. Res. Commun. 380:143-147(2009). RN [18] RP VARIANT ALA-351. RX PubMed=21383048; DOI=10.1258/ebm.2011.010229; RA Turato C., Biasiolo A., Pengo P., Frecer V., Quarta S., Fasolato S., RA Ruvoletto M., Beneduce L., Zuin J., Fassina G., Gatta A., Pontisso P.; RT "Increased antiprotease activity of the SERPINB3 polymorphic variant SCCA- RT PD."; RL Exp. Biol. Med. 236:281-290(2011). CC -!- FUNCTION: May act as a papain-like cysteine protease inhibitor to CC modulate the host immune response against tumor cells. Also functions CC as an inhibitor of UV-induced apoptosis via suppression of the activity CC of c-Jun NH(2)-terminal kinase (JNK1). {ECO:0000269|PubMed:19166818}. CC -!- SUBUNIT: Interacts with MAPK8/JNK1. {ECO:0000269|PubMed:19166818}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10956412, CC ECO:0000269|PubMed:14970861}. Note=Seems to also be secreted in plasma CC by cancerous cells but at a low level. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P29508-1; Sequence=Displayed; CC Name=2; Synonyms=SCCA1b; CC IsoId=P29508-2; Sequence=VSP_032657; CC -!- TISSUE SPECIFICITY: Squamous cells. Expressed in some hepatocellular CC carcinoma (at protein level). {ECO:0000269|PubMed:14970861}. CC -!- DEVELOPMENTAL STAGE: Its expression is closely related to cellular CC differentiation in both normal and malignant squamous cells. CC -!- INDUCTION: Strongly up-regulated in the upper epidermis of sun-exposed CC skin. {ECO:0000269|PubMed:19166818}. CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAO11731.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; S66896; AAB20405.1; -; mRNA. DR EMBL; U19556; AAA97552.1; -; mRNA. DR EMBL; U19568; AAA86317.1; -; Genomic_DNA. DR EMBL; U19559; AAA86317.1; JOINED; Genomic_DNA. DR EMBL; U19560; AAA86317.1; JOINED; Genomic_DNA. DR EMBL; U19562; AAA86317.1; JOINED; Genomic_DNA. DR EMBL; U19565; AAA86317.1; JOINED; Genomic_DNA. DR EMBL; U19567; AAA86317.1; JOINED; Genomic_DNA. DR EMBL; U19562; AAA86316.1; -; Genomic_DNA. DR EMBL; U19559; AAA86316.1; JOINED; Genomic_DNA. DR EMBL; U19560; AAA86316.1; JOINED; Genomic_DNA. DR EMBL; AB046399; BAB40772.1; -; mRNA. DR EMBL; AJ515706; CAD56658.1; -; mRNA. DR EMBL; AY245778; AAO92269.1; -; mRNA. DR EMBL; AY245781; AAO92272.1; -; mRNA. DR EMBL; EU852041; ACF21012.1; -; mRNA. DR EMBL; BT006748; AAP35394.1; -; mRNA. DR EMBL; AK222746; BAD96466.1; -; mRNA. DR EMBL; AK222753; BAD96473.1; -; mRNA. DR EMBL; AK314805; BAG37332.1; -; mRNA. DR EMBL; AC069356; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471096; EAW63156.1; -; Genomic_DNA. DR EMBL; CH471096; EAW63157.1; -; Genomic_DNA. DR EMBL; BC005224; AAH05224.1; -; mRNA. DR EMBL; AY190327; AAO11731.1; ALT_INIT; mRNA. DR CCDS; CCDS11987.1; -. [P29508-1] DR PIR; I38201; I38201. DR RefSeq; NP_008850.1; NM_006919.2. [P29508-1] DR PDB; 2ZV6; X-ray; 2.70 A; A/B/C=2-390. DR PDB; 4ZK0; X-ray; 2.15 A; A=1-390. DR PDB; 4ZK3; X-ray; 2.00 A; A=1-390. DR PDBsum; 2ZV6; -. DR PDBsum; 4ZK0; -. DR PDBsum; 4ZK3; -. DR AlphaFoldDB; P29508; -. DR SMR; P29508; -. DR BioGRID; 112223; 254. DR IntAct; P29508; 53. DR MINT; P29508; -. DR STRING; 9606.ENSP00000283752; -. DR DrugBank; DB03929; D-Serine. DR DrugBank; DB04522; Dexfosfoserine. DR MEROPS; I04.008; -. DR GlyCosmos; P29508; 2 sites, 1 glycan. DR GlyGen; P29508; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P29508; -. DR PhosphoSitePlus; P29508; -. DR SwissPalm; P29508; -. DR BioMuta; SERPINB3; -. DR DMDM; 20141712; -. DR EPD; P29508; -. DR jPOST; P29508; -. DR MassIVE; P29508; -. DR MaxQB; P29508; -. DR PaxDb; 9606-ENSP00000283752; -. DR PeptideAtlas; P29508; -. DR PRIDE; P29508; -. DR ProteomicsDB; 54582; -. [P29508-1] DR ProteomicsDB; 54583; -. [P29508-2] DR TopDownProteomics; P29508-1; -. [P29508-1] DR TopDownProteomics; P29508-2; -. [P29508-2] DR Antibodypedia; 4364; 812 antibodies from 38 providers. DR CPTC; P29508; 3 antibodies. DR DNASU; 6317; -. DR Ensembl; ENST00000283752.10; ENSP00000283752.5; ENSG00000057149.16. [P29508-1] DR Ensembl; ENST00000332821.8; ENSP00000329498.8; ENSG00000057149.16. [P29508-2] DR GeneID; 6317; -. DR KEGG; hsa:6317; -. DR MANE-Select; ENST00000283752.10; ENSP00000283752.5; NM_006919.3; NP_008850.1. DR UCSC; uc002lji.3; human. [P29508-1] DR AGR; HGNC:10569; -. DR CTD; 6317; -. DR DisGeNET; 6317; -. DR GeneCards; SERPINB3; -. DR HGNC; HGNC:10569; SERPINB3. DR HPA; ENSG00000057149; Group enriched (cervix, esophagus, vagina). DR MIM; 600517; gene. DR neXtProt; NX_P29508; -. DR OpenTargets; ENSG00000057149; -. DR PharmGKB; PA35538; -. DR VEuPathDB; HostDB:ENSG00000057149; -. DR eggNOG; KOG2392; Eukaryota. DR GeneTree; ENSGT00940000154520; -. DR HOGENOM; CLU_023330_0_2_1; -. DR InParanoid; P29508; -. DR OMA; NKNTHKS; -. DR OrthoDB; 3218836at2759; -. DR PhylomeDB; P29508; -. DR TreeFam; TF352619; -. DR PathwayCommons; P29508; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; P29508; -. DR BioGRID-ORCS; 6317; 15 hits in 1117 CRISPR screens. DR ChiTaRS; SERPINB3; human. DR EvolutionaryTrace; P29508; -. DR GeneWiki; SERPINB3; -. DR GenomeRNAi; 6317; -. DR Pharos; P29508; Tbio. DR PRO; PR:P29508; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; P29508; Protein. DR Bgee; ENSG00000057149; Expressed in olfactory segment of nasal mucosa and 117 other cell types or tissues. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0031982; C:vesicle; HDA:UniProtKB. DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IMP:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central. DR GO; GO:0001618; F:virus receptor activity; IDA:UniProtKB. DR GO; GO:0035425; P:autocrine signaling; IMP:UniProtKB. DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB. DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IMP:UniProtKB. DR GO; GO:0043508; P:negative regulation of JUN kinase activity; IMP:UniProtKB. DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:UniProtKB. DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB. DR GO; GO:0038001; P:paracrine signaling; IMP:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0010950; P:positive regulation of endopeptidase activity; IDA:UniProtKB. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB. DR CDD; cd19563; serpinB3_B4_SCCA1_2; 1. DR Gene3D; 2.30.39.10; Alpha-1-antitrypsin, domain 1; 1. DR Gene3D; 3.30.497.10; Antithrombin, subunit I, domain 2; 1. DR InterPro; IPR023795; Serpin_CS. DR InterPro; IPR023796; Serpin_dom. DR InterPro; IPR000215; Serpin_fam. DR InterPro; IPR036186; Serpin_sf. DR InterPro; IPR042178; Serpin_sf_1. DR InterPro; IPR042185; Serpin_sf_2. DR PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1. DR PANTHER; PTHR11461:SF320; SERPIN B3; 1. DR Pfam; PF00079; Serpin; 1. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; Serpins; 1. DR PROSITE; PS00284; SERPIN; 1. DR SWISS-2DPAGE; P29508; -. DR UCD-2DPAGE; P29508; -. DR Genevisible; P29508; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Protease inhibitor; Reference proteome; KW Serine protease inhibitor. FT CHAIN 1..390 FT /note="Serpin B3" FT /id="PRO_0000094103" FT SITE 354..355 FT /note="Reactive bond" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|Ref.13" FT VAR_SEQ 205..256 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_032657" FT VARIANT 351 FT /note="G -> A (increased antiprotease activity and FT increased MAPK8 inhibition activity; dbSNP:rs3180227)" FT /evidence="ECO:0000269|PubMed:12975381, FT ECO:0000269|PubMed:14970861, ECO:0000269|PubMed:21383048, FT ECO:0000269|Ref.6" FT /id="VAR_024351" FT VARIANT 357 FT /note="T -> A (in dbSNP:rs1065205)" FT /evidence="ECO:0000269|PubMed:1958219, ECO:0000269|Ref.3, FT ECO:0000269|Ref.9" FT /id="VAR_024352" FT MUTAGEN 341 FT /note="A->R: Loss of inhibitory activity." FT /evidence="ECO:0000269|PubMed:12975381" FT MUTAGEN 352 FT /note="F->A: Loss of inhibitory activity." FT /evidence="ECO:0000269|PubMed:12975381, FT ECO:0000269|PubMed:19166818" FT MUTAGEN 352 FT /note="F->G: Loss of inhibitory activity to papain but does FT not decrease the suppression activity to MAPK8." FT /evidence="ECO:0000269|PubMed:12975381, FT ECO:0000269|PubMed:19166818" FT MUTAGEN 354..355 FT /note="SS->PP: Loss of inhibitory activity." FT /evidence="ECO:0000269|PubMed:12975381" FT CONFLICT 16 FT /note="F -> S (in Ref. 4; CAD56658)" FT /evidence="ECO:0000305" FT CONFLICT 47 FT /note="D -> N (in Ref. 4; CAD56658)" FT /evidence="ECO:0000305" FT CONFLICT 105 FT /note="N -> T (in Ref. 4; CAD56658)" FT /evidence="ECO:0000305" FT CONFLICT 185 FT /note="Q -> R (in Ref. 5; AAO92272)" FT /evidence="ECO:0000305" FT CONFLICT 202 FT /note="P -> S (in Ref. 5; AAO92272)" FT /evidence="ECO:0000305" FT CONFLICT 278 FT /note="T -> A (in Ref. 5; AAO92269)" FT /evidence="ECO:0000305" FT CONFLICT 349 FT /note="V -> E (in Ref. 5; AAO92272)" FT /evidence="ECO:0000305" FT HELIX 4..19 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 27..29 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 31..42 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 47..56 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 81..91 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 97..110 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 117..127 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 130..134 FT /evidence="ECO:0007829|PDB:4ZK3" FT TURN 136..138 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 140..153 FT /evidence="ECO:0007829|PDB:4ZK3" FT TURN 154..157 FT /evidence="ECO:0007829|PDB:4ZK3" FT TURN 165..167 FT /evidence="ECO:0007829|PDB:2ZV6" FT STRAND 174..188 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 192..194 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 196..203 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 206..224 FT /evidence="ECO:0007829|PDB:4ZK3" FT TURN 225..228 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 229..236 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 239..250 FT /evidence="ECO:0007829|PDB:4ZK3" FT TURN 251..253 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 254..260 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 263..269 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 272..274 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 276..285 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 287..294 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 296..302 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 306..308 FT /evidence="ECO:0007829|PDB:4ZK3" FT HELIX 315..318 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 319..321 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 324..336 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 338..352 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 361..364 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 369..375 FT /evidence="ECO:0007829|PDB:4ZK3" FT TURN 376..379 FT /evidence="ECO:0007829|PDB:4ZK3" FT STRAND 380..387 FT /evidence="ECO:0007829|PDB:4ZK3" SQ SEQUENCE 390 AA; 44565 MW; E5F27F986C752CFA CRC64; MNSLSEANTK FMFDLFQQFR KSKENNIFYS PISITSALGM VLLGAKDNTA QQIKKVLHFD QVTENTTGKA ATYHVDRSGN VHHQFQKLLT EFNKSTDAYE LKIANKLFGE KTYLFLQEYL DAIKKFYQTS VESVDFANAP EESRKKINSW VESQTNEKIK NLIPEGNIGS NTTLVLVNAI YFKGQWEKKF NKEDTKEEKF WPNKNTYKSI QMMRQYTSFH FASLEDVQAK VLEIPYKGKD LSMIVLLPNE IDGLQKLEEK LTAEKLMEWT SLQNMRETRV DLHLPRFKVE ESYDLKDTLR TMGMVDIFNG DADLSGMTGS RGLVLSGVLH KAFVEVTEEG AEAAAATAVV GFGSSPTSTN EEFHCNHPFL FFIRQNKTNS ILFYGRFSSP //