Full text data of SERPINB3
SERPINB3
(SCCA, SCCA1)
[Confidence: low (only semi-automatic identification from reviews)]
Serpin B3 (Protein T4-A; Squamous cell carcinoma antigen 1; SCCA-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serpin B3 (Protein T4-A; Squamous cell carcinoma antigen 1; SCCA-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P29508
ID SPB3_HUMAN Reviewed; 390 AA.
AC P29508; A6NDM2; B2RBT5; B3W5Y6; Q53H28; Q53YB5; Q86VF3; Q86W04;
read moreAC Q8IWL4; Q8IXI3; Q96J21; Q9BYF8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 138.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT protease 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.,
RA Treter S.D., 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
RT splicing.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-351, AND
RP MUTAGENESIS OF 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
RT virus to hepatocytes does not involve the hepatic serpin clearance
RT 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
RT HepG2, 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
RT antigen-1 (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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RP 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.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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 MASS 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.,
RA Gatta A., 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.,
RA Kamachi Y., Pomeroy S.L., Perlmutter D.H., Silverman G.A.;
RT "Circulating serpin tumor markers SCCA1 and SCCA2 are not actively
RT secreted 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.,
RA Buerckstuemmer T., 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
RT 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
RT SCCA-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
CC functions as an inhibitor of UV-induced apoptosis via suppression
CC of the activity of c-Jun NH(2)-terminal kinase (JNK1).
CC -!- SUBUNIT: Interacts with MAPK8/JNK1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Seems to also be secreted in
CC plasma 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
CC hepatocellular carcinoma (at protein level).
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-
CC exposed skin.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO11731.1; Type=Erroneous initiation;
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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 PIR; I38201; I38201.
DR RefSeq; NP_008850.1; NM_006919.2.
DR RefSeq; XP_005266793.1; XM_005266736.1.
DR RefSeq; XP_005266794.1; XM_005266737.1.
DR UniGene; Hs.227948; -.
DR PDB; 2ZV6; X-ray; 2.70 A; A/B/C=2-390.
DR PDBsum; 2ZV6; -.
DR ProteinModelPortal; P29508; -.
DR SMR; P29508; 2-390.
DR IntAct; P29508; 2.
DR MINT; MINT-1139917; -.
DR PhosphoSite; P29508; -.
DR DMDM; 20141712; -.
DR SWISS-2DPAGE; P29508; -.
DR UCD-2DPAGE; P29508; -.
DR PaxDb; P29508; -.
DR PRIDE; P29508; -.
DR DNASU; 6317; -.
DR Ensembl; ENST00000283752; ENSP00000283752; ENSG00000057149.
DR Ensembl; ENST00000332821; ENSP00000329498; ENSG00000057149.
DR GeneID; 6317; -.
DR KEGG; hsa:6317; -.
DR UCSC; uc002lji.3; human.
DR CTD; 6317; -.
DR GeneCards; GC18M061295; -.
DR HGNC; HGNC:10569; SERPINB3.
DR HPA; CAB018772; -.
DR MIM; 600517; gene.
DR neXtProt; NX_P29508; -.
DR PharmGKB; PA35538; -.
DR eggNOG; COG4826; -.
DR HOVERGEN; HBG005957; -.
DR InParanoid; P29508; -.
DR KO; K13963; -.
DR OMA; KSIQMMR; -.
DR OrthoDB; EOG7327PB; -.
DR EvolutionaryTrace; P29508; -.
DR GeneWiki; SERPINB3; -.
DR GenomeRNAi; 6317; -.
DR NextBio; 24512; -.
DR PRO; PR:P29508; -.
DR ArrayExpress; P29508; -.
DR Bgee; P29508; -.
DR Genevestigator; P29508; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IBA:RefGenome.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; NAS:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IDA:UniProtKB.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Polymorphism;
KW Protease inhibitor; Reference proteome; Serine protease inhibitor.
FT CHAIN 1 390 Serpin B3.
FT /FTId=PRO_0000094103.
FT SITE 354 355 Reactive bond.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 205 256 Missing (in isoform 2).
FT /FTId=VSP_032657.
FT VARIANT 351 351 G -> A (increased antiprotease activity
FT and increased MAPK8 inhibition activity;
FT dbSNP:rs3180227).
FT /FTId=VAR_024351.
FT VARIANT 357 357 T -> A (in dbSNP:rs1065205).
FT /FTId=VAR_024352.
FT MUTAGEN 341 341 A->R: Loss of inhibitory activity.
FT MUTAGEN 352 352 F->A: Loss of inhibitory activity.
FT MUTAGEN 352 352 F->G: Loss of inhibitory activity to
FT papain but does not decrease the
FT suppression activity to MAPK8.
FT MUTAGEN 354 355 SS->PP: Loss of inhibitory activity.
FT CONFLICT 16 16 F -> S (in Ref. 4; CAD56658).
FT CONFLICT 47 47 D -> N (in Ref. 4; CAD56658).
FT CONFLICT 105 105 N -> T (in Ref. 4; CAD56658).
FT CONFLICT 185 185 Q -> R (in Ref. 5; AAO92272).
FT CONFLICT 202 202 P -> S (in Ref. 5; AAO92272).
FT CONFLICT 278 278 T -> A (in Ref. 5; AAO92269).
FT CONFLICT 349 349 V -> E (in Ref. 5; AAO92272).
FT HELIX 3 22
FT STRAND 27 29
FT HELIX 31 43
FT HELIX 48 56
FT HELIX 82 93
FT STRAND 101 104
FT STRAND 107 110
FT HELIX 117 127
FT STRAND 131 134
FT TURN 136 138
FT HELIX 140 154
FT TURN 155 157
FT TURN 165 167
FT STRAND 174 182
FT STRAND 186 188
FT STRAND 194 200
FT STRAND 202 205
FT STRAND 208 221
FT TURN 225 228
FT STRAND 229 236
FT STRAND 239 250
FT HELIX 254 260
FT HELIX 263 269
FT HELIX 272 274
FT STRAND 276 285
FT STRAND 288 294
FT HELIX 296 301
FT HELIX 306 308
FT HELIX 315 318
FT STRAND 319 321
FT STRAND 325 335
FT STRAND 361 364
FT STRAND 369 373
FT TURN 376 379
FT STRAND 384 387
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
//
ID SPB3_HUMAN Reviewed; 390 AA.
AC P29508; A6NDM2; B2RBT5; B3W5Y6; Q53H28; Q53YB5; Q86VF3; Q86W04;
read moreAC Q8IWL4; Q8IXI3; Q96J21; Q9BYF8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 138.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT protease 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.,
RA Treter S.D., 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
RT splicing.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-351, AND
RP MUTAGENESIS OF 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
RT virus to hepatocytes does not involve the hepatic serpin clearance
RT 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
RT HepG2, 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
RT antigen-1 (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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RP 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.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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 MASS 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.,
RA Gatta A., 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.,
RA Kamachi Y., Pomeroy S.L., Perlmutter D.H., Silverman G.A.;
RT "Circulating serpin tumor markers SCCA1 and SCCA2 are not actively
RT secreted 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.,
RA Buerckstuemmer T., 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
RT 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
RT SCCA-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
CC functions as an inhibitor of UV-induced apoptosis via suppression
CC of the activity of c-Jun NH(2)-terminal kinase (JNK1).
CC -!- SUBUNIT: Interacts with MAPK8/JNK1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Seems to also be secreted in
CC plasma 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
CC hepatocellular carcinoma (at protein level).
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-
CC exposed skin.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO11731.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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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 PIR; I38201; I38201.
DR RefSeq; NP_008850.1; NM_006919.2.
DR RefSeq; XP_005266793.1; XM_005266736.1.
DR RefSeq; XP_005266794.1; XM_005266737.1.
DR UniGene; Hs.227948; -.
DR PDB; 2ZV6; X-ray; 2.70 A; A/B/C=2-390.
DR PDBsum; 2ZV6; -.
DR ProteinModelPortal; P29508; -.
DR SMR; P29508; 2-390.
DR IntAct; P29508; 2.
DR MINT; MINT-1139917; -.
DR PhosphoSite; P29508; -.
DR DMDM; 20141712; -.
DR SWISS-2DPAGE; P29508; -.
DR UCD-2DPAGE; P29508; -.
DR PaxDb; P29508; -.
DR PRIDE; P29508; -.
DR DNASU; 6317; -.
DR Ensembl; ENST00000283752; ENSP00000283752; ENSG00000057149.
DR Ensembl; ENST00000332821; ENSP00000329498; ENSG00000057149.
DR GeneID; 6317; -.
DR KEGG; hsa:6317; -.
DR UCSC; uc002lji.3; human.
DR CTD; 6317; -.
DR GeneCards; GC18M061295; -.
DR HGNC; HGNC:10569; SERPINB3.
DR HPA; CAB018772; -.
DR MIM; 600517; gene.
DR neXtProt; NX_P29508; -.
DR PharmGKB; PA35538; -.
DR eggNOG; COG4826; -.
DR HOVERGEN; HBG005957; -.
DR InParanoid; P29508; -.
DR KO; K13963; -.
DR OMA; KSIQMMR; -.
DR OrthoDB; EOG7327PB; -.
DR EvolutionaryTrace; P29508; -.
DR GeneWiki; SERPINB3; -.
DR GenomeRNAi; 6317; -.
DR NextBio; 24512; -.
DR PRO; PR:P29508; -.
DR ArrayExpress; P29508; -.
DR Bgee; P29508; -.
DR Genevestigator; P29508; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IBA:RefGenome.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; NAS:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IDA:UniProtKB.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Polymorphism;
KW Protease inhibitor; Reference proteome; Serine protease inhibitor.
FT CHAIN 1 390 Serpin B3.
FT /FTId=PRO_0000094103.
FT SITE 354 355 Reactive bond.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 205 256 Missing (in isoform 2).
FT /FTId=VSP_032657.
FT VARIANT 351 351 G -> A (increased antiprotease activity
FT and increased MAPK8 inhibition activity;
FT dbSNP:rs3180227).
FT /FTId=VAR_024351.
FT VARIANT 357 357 T -> A (in dbSNP:rs1065205).
FT /FTId=VAR_024352.
FT MUTAGEN 341 341 A->R: Loss of inhibitory activity.
FT MUTAGEN 352 352 F->A: Loss of inhibitory activity.
FT MUTAGEN 352 352 F->G: Loss of inhibitory activity to
FT papain but does not decrease the
FT suppression activity to MAPK8.
FT MUTAGEN 354 355 SS->PP: Loss of inhibitory activity.
FT CONFLICT 16 16 F -> S (in Ref. 4; CAD56658).
FT CONFLICT 47 47 D -> N (in Ref. 4; CAD56658).
FT CONFLICT 105 105 N -> T (in Ref. 4; CAD56658).
FT CONFLICT 185 185 Q -> R (in Ref. 5; AAO92272).
FT CONFLICT 202 202 P -> S (in Ref. 5; AAO92272).
FT CONFLICT 278 278 T -> A (in Ref. 5; AAO92269).
FT CONFLICT 349 349 V -> E (in Ref. 5; AAO92272).
FT HELIX 3 22
FT STRAND 27 29
FT HELIX 31 43
FT HELIX 48 56
FT HELIX 82 93
FT STRAND 101 104
FT STRAND 107 110
FT HELIX 117 127
FT STRAND 131 134
FT TURN 136 138
FT HELIX 140 154
FT TURN 155 157
FT TURN 165 167
FT STRAND 174 182
FT STRAND 186 188
FT STRAND 194 200
FT STRAND 202 205
FT STRAND 208 221
FT TURN 225 228
FT STRAND 229 236
FT STRAND 239 250
FT HELIX 254 260
FT HELIX 263 269
FT HELIX 272 274
FT STRAND 276 285
FT STRAND 288 294
FT HELIX 296 301
FT HELIX 306 308
FT HELIX 315 318
FT STRAND 319 321
FT STRAND 325 335
FT STRAND 361 364
FT STRAND 369 373
FT TURN 376 379
FT STRAND 384 387
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
//
MIM
600517
*RECORD*
*FIELD* NO
600517
*FIELD* TI
*600517 SERPIN PEPTIDASE INHIBITOR, CLADE B (OVALBUMIN), MEMBER 3; SERPINB3
;;SQUAMOUS CELL CARCINOMA ANTIGEN 1; SCCA1
read more*FIELD* TX
DESCRIPTION
Squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin
family of serine proteinase inhibitors. The protein was isolated from a
metastatic cervical squamous cell carcinoma by Kato and Torigoe (1977).
SCCA is detected in the superficial and intermediate layers of normal
squamous epithelium, whereas the mRNA is detected in the basal and
subbasal levels. The clinical import of SCCA has been as a circulating
tumor marker for squamous cell carcinoma, especially those of the
cervix, head and neck, lung, and esophagus. Many clinical studies of
cervical squamous cell carcinoma show that the percentage of patients
with elevated circulating levels of SCCA increases from approximately
12% at stage 0 to more than 90% at stage IV. Levels fall after tumor
resection and rise in approximately 90% of the patients with recurrent
disease. Similar trends occur in the other types of squamous cell
carcinoma, with a maximum sensitivity of approximately 60% for lung, 50%
for esophageal, and 55% for head and neck tumors. The neutral form of
SCCA (SCCA1, or SERPINB3) is detected in the cytoplasm of normal and
some malignant squamous cells, whereas the acidic form (SCCA2, or
SERPINB4; 600518) is expressed primarily in malignant cells and is the
major form found in the plasma of cancer patients. Thus, the appearance
of the acidic fraction of SCCA is correlated with more aggressive tumors
(summary by Schneider et al., 1995).
CLONING
Suminami et al. (1991) cloned the cDNA for SCCA. The deduced protein
contains 390 amino acids and belongs to the serine protease inhibitor
family. Northern blot analysis detected a transcript of about 1.7 kb in
human squamous cells.
Based on the predicted pI values and molecular masses of SCCA1 and
SCCA2, Schneider et al. (1995) suggested that the neutral and acidic
forms of SCCA are encoded by SCCA1 and SCCA2, respectively. SCCA1 shares
92% amino acid identity with SCCA2.
GENE FUNCTION
Ray et al. (2005) stated that mouse Scca2, or Serpinb3a, exhibits the
cysteine-like serine protease inhibitory function of human SCCA1 and the
trypsin-like serine protease inhibitory function of human SCCA2. Thus,
Scca2 is the mouse ortholog of both human SCCA1 and SCCA2. Ray et al.
(2005) found that challenge of uteroglobin (UGB, or SCGB1A1;
192020)-knockout mice with the allergen chicken ovalbumin (OVA) resulted
in elevated lung expression of Scca2, as well as elevated levels of the
cytokines Il4 (147780) and Il13 (147683) in lung and exacerbated airway
inflammation. These effects were countered by reintroduction of
recombinant Ugb. Treatment of cultured human bronchial epithelial cells
with IL4 or IL13 stimulated SCCA1 and SCCA2 expression via
phosphorylation of the transcription factors STAT1 (600555) and STAT6
(601512). SCCA1 and SCCA2 expression was not upregulated by IL4 or IL13
in the presence of an inhibitor of tyrosine phosphorylation. Ray et al.
(2005) proposed that UGB controls allergic asthma by downregulating
signaling through IL4 and IL13 and inhibiting SCCA1 and SCCA2
expression.
MAPPING
By fluorescence in situ hybridization, Kuwano et al. (1995) mapped the
SCCA1 gene to chromosome 18q21. They noted that the PLANH2 gene
(173390), with which the SCCA1 gene shares much homology, also maps to
chromosome 18q21. The oncogene BCL2 (151430), which is located 600 kb
centromeric to PLAH2, is also located on chromosome 18q21.
Schneider et al. (1995) found that SCCA1 and SCCA2 are tandemly arrayed
on chromosome 18q21.3 and are flanked by 2 members of the ovalbumin
family of serine proteinase inhibitors, plasminogen activator inhibitor
type-2 (SERPINB2; 173390) and maspin (SERPINB5; 154790).
*FIELD* RF
1. Kato, H.; Torigoe, T.: Radioimmunoassay for tumor antigen of human
cervical squamous cell carcinoma. Cancer 40: 1621-1628, 1977.
2. Kuwano, A.; Kondo, I.; Kishi, F.; Suminami, Y.; Kato, H.: Assignment
of the squamous cell carcinoma antigen locus (SCC) to 18q21 by in
situ hybridization. Genomics 30: 626, 1995.
3. Ray, R.; Choi, M.; Zhang, Z.; Silverman, G. A.; Askew, D.; Mukherjee,
A. B.: Uteroglobin suppresses SCCA gene expression associated with
allergic asthma. J. Biol. Chem. 280: 9761-9764, 2005.
4. Schneider, S. S.; Schick, C.; Fish, K. E.; Miller, E.; Pena, J.
C.; Treter, S. D.; Hui, S. M.; Silverman, G. A.: A serine proteinase
inhibitor locus at 18q21.3 contains a tandem duplication of the human
squamous cell carcinoma antigen gene. Proc. Nat. Acad. Sci. 92:
3147-3151, 1995.
5. Suminami, Y.; Kishi, F.; Sekiguchi, K.; Kato, H.: Squamous cell
carcinoma antigen is a new member of the serine protease inhibitors. Biochem.
Biophys. Res. Commun. 181: 51-58, 1991.
*FIELD* CN
Matthew B. Gross - updated: 4/8/2011
Patricia A. Hartz - updated: 2/25/2011
Alan F. Scott - updated: 3/26/1997
*FIELD* CD
Victor A. McKusick: 5/7/1995
*FIELD* ED
mgross: 04/08/2011
mgross: 4/8/2011
terry: 2/25/2011
psherman: 4/7/1998
mark: 3/26/1997
terry: 1/18/1996
mimadm: 11/3/1995
mark: 5/7/1995
*RECORD*
*FIELD* NO
600517
*FIELD* TI
*600517 SERPIN PEPTIDASE INHIBITOR, CLADE B (OVALBUMIN), MEMBER 3; SERPINB3
;;SQUAMOUS CELL CARCINOMA ANTIGEN 1; SCCA1
read more*FIELD* TX
DESCRIPTION
Squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin
family of serine proteinase inhibitors. The protein was isolated from a
metastatic cervical squamous cell carcinoma by Kato and Torigoe (1977).
SCCA is detected in the superficial and intermediate layers of normal
squamous epithelium, whereas the mRNA is detected in the basal and
subbasal levels. The clinical import of SCCA has been as a circulating
tumor marker for squamous cell carcinoma, especially those of the
cervix, head and neck, lung, and esophagus. Many clinical studies of
cervical squamous cell carcinoma show that the percentage of patients
with elevated circulating levels of SCCA increases from approximately
12% at stage 0 to more than 90% at stage IV. Levels fall after tumor
resection and rise in approximately 90% of the patients with recurrent
disease. Similar trends occur in the other types of squamous cell
carcinoma, with a maximum sensitivity of approximately 60% for lung, 50%
for esophageal, and 55% for head and neck tumors. The neutral form of
SCCA (SCCA1, or SERPINB3) is detected in the cytoplasm of normal and
some malignant squamous cells, whereas the acidic form (SCCA2, or
SERPINB4; 600518) is expressed primarily in malignant cells and is the
major form found in the plasma of cancer patients. Thus, the appearance
of the acidic fraction of SCCA is correlated with more aggressive tumors
(summary by Schneider et al., 1995).
CLONING
Suminami et al. (1991) cloned the cDNA for SCCA. The deduced protein
contains 390 amino acids and belongs to the serine protease inhibitor
family. Northern blot analysis detected a transcript of about 1.7 kb in
human squamous cells.
Based on the predicted pI values and molecular masses of SCCA1 and
SCCA2, Schneider et al. (1995) suggested that the neutral and acidic
forms of SCCA are encoded by SCCA1 and SCCA2, respectively. SCCA1 shares
92% amino acid identity with SCCA2.
GENE FUNCTION
Ray et al. (2005) stated that mouse Scca2, or Serpinb3a, exhibits the
cysteine-like serine protease inhibitory function of human SCCA1 and the
trypsin-like serine protease inhibitory function of human SCCA2. Thus,
Scca2 is the mouse ortholog of both human SCCA1 and SCCA2. Ray et al.
(2005) found that challenge of uteroglobin (UGB, or SCGB1A1;
192020)-knockout mice with the allergen chicken ovalbumin (OVA) resulted
in elevated lung expression of Scca2, as well as elevated levels of the
cytokines Il4 (147780) and Il13 (147683) in lung and exacerbated airway
inflammation. These effects were countered by reintroduction of
recombinant Ugb. Treatment of cultured human bronchial epithelial cells
with IL4 or IL13 stimulated SCCA1 and SCCA2 expression via
phosphorylation of the transcription factors STAT1 (600555) and STAT6
(601512). SCCA1 and SCCA2 expression was not upregulated by IL4 or IL13
in the presence of an inhibitor of tyrosine phosphorylation. Ray et al.
(2005) proposed that UGB controls allergic asthma by downregulating
signaling through IL4 and IL13 and inhibiting SCCA1 and SCCA2
expression.
MAPPING
By fluorescence in situ hybridization, Kuwano et al. (1995) mapped the
SCCA1 gene to chromosome 18q21. They noted that the PLANH2 gene
(173390), with which the SCCA1 gene shares much homology, also maps to
chromosome 18q21. The oncogene BCL2 (151430), which is located 600 kb
centromeric to PLAH2, is also located on chromosome 18q21.
Schneider et al. (1995) found that SCCA1 and SCCA2 are tandemly arrayed
on chromosome 18q21.3 and are flanked by 2 members of the ovalbumin
family of serine proteinase inhibitors, plasminogen activator inhibitor
type-2 (SERPINB2; 173390) and maspin (SERPINB5; 154790).
*FIELD* RF
1. Kato, H.; Torigoe, T.: Radioimmunoassay for tumor antigen of human
cervical squamous cell carcinoma. Cancer 40: 1621-1628, 1977.
2. Kuwano, A.; Kondo, I.; Kishi, F.; Suminami, Y.; Kato, H.: Assignment
of the squamous cell carcinoma antigen locus (SCC) to 18q21 by in
situ hybridization. Genomics 30: 626, 1995.
3. Ray, R.; Choi, M.; Zhang, Z.; Silverman, G. A.; Askew, D.; Mukherjee,
A. B.: Uteroglobin suppresses SCCA gene expression associated with
allergic asthma. J. Biol. Chem. 280: 9761-9764, 2005.
4. Schneider, S. S.; Schick, C.; Fish, K. E.; Miller, E.; Pena, J.
C.; Treter, S. D.; Hui, S. M.; Silverman, G. A.: A serine proteinase
inhibitor locus at 18q21.3 contains a tandem duplication of the human
squamous cell carcinoma antigen gene. Proc. Nat. Acad. Sci. 92:
3147-3151, 1995.
5. Suminami, Y.; Kishi, F.; Sekiguchi, K.; Kato, H.: Squamous cell
carcinoma antigen is a new member of the serine protease inhibitors. Biochem.
Biophys. Res. Commun. 181: 51-58, 1991.
*FIELD* CN
Matthew B. Gross - updated: 4/8/2011
Patricia A. Hartz - updated: 2/25/2011
Alan F. Scott - updated: 3/26/1997
*FIELD* CD
Victor A. McKusick: 5/7/1995
*FIELD* ED
mgross: 04/08/2011
mgross: 4/8/2011
terry: 2/25/2011
psherman: 4/7/1998
mark: 3/26/1997
terry: 1/18/1996
mimadm: 11/3/1995
mark: 5/7/1995