SPB4_HUMAN
ID SPB4_HUMAN Reviewed; 390 AA.
AC P48594; A8K847;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Serpin B4;
DE AltName: Full=Leupin;
DE AltName: Full=Peptidase inhibitor 11;
DE Short=PI-11;
DE AltName: Full=Squamous cell carcinoma antigen 2;
DE Short=SCCA-2;
GN Name=SERPINB4; Synonyms=PI11, SCCA2;
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=7589435; DOI=10.1016/0014-5793(95)01015-7;
RA Barnes R.C., Worrall D.M.;
RT "Identification of a novel human serpin gene; cloning sequencing and
RT expression of leupin.";
RL FEBS Lett. 373:61-65(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
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 [GENOMIC DNA].
RX PubMed=11267667; DOI=10.1016/s0167-4781(01)00174-9;
RA Hamada K., Shinomiya H., Asano Y., Kihana T., Iwamoto M., Hanakawa Y.,
RA Hashimoto K., Hirose S., Kyo S., Ito M.;
RT "Molecular cloning of human squamous cell carcinoma antigen 1 gene and
RT characterization of its promoter.";
RL Biochim. Biophys. Acta 1518:124-131(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Esophagus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
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 PROTEIN SEQUENCE OF 1-21; 56-69; 88-94; 147-160; 215-260; 266-276 AND
RP 378-386, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Bensaad K., Vousden K.H.;
RL Submitted (FEB-2008) to UniProtKB.
RN [7]
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).
CC -!- FUNCTION: May act as a protease inhibitor to modulate the host immune
CC response against tumor cells.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10956412}.
CC Note=Seems to also be secreted in plasma by cancerous cells but at a
CC low level.
CC -!- TISSUE SPECIFICITY: Squamous cells.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC {ECO:0000305}.
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DR EMBL; X89015; CAA61420.1; -; mRNA.
DR EMBL; U19557; AAA97553.1; -; mRNA.
DR EMBL; U19576; AAA92602.1; -; Genomic_DNA.
DR EMBL; U19570; AAA92602.1; JOINED; Genomic_DNA.
DR EMBL; U19571; AAA92602.1; JOINED; Genomic_DNA.
DR EMBL; U19572; AAA92602.1; JOINED; Genomic_DNA.
DR EMBL; U19574; AAA92602.1; JOINED; Genomic_DNA.
DR EMBL; U19575; AAA92602.1; JOINED; Genomic_DNA.
DR EMBL; AB035089; BAB21525.1; -; Genomic_DNA.
DR EMBL; AK292212; BAF84901.1; -; mRNA.
DR EMBL; BC017401; AAH17401.1; -; mRNA.
DR CCDS; CCDS11986.1; -.
DR PIR; I38202; I38202.
DR RefSeq; NP_002965.1; NM_002974.3.
DR RefSeq; NP_778206.1; NM_175041.1.
DR RefSeq; XP_011524440.1; XM_011526138.1.
DR AlphaFoldDB; P48594; -.
DR SMR; P48594; -.
DR BioGRID; 112224; 220.
DR IntAct; P48594; 71.
DR MINT; P48594; -.
DR STRING; 9606.ENSP00000343445; -.
DR MEROPS; I04.008; -.
DR MEROPS; I04.009; -.
DR GlyGen; P48594; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P48594; -.
DR PhosphoSitePlus; P48594; -.
DR SwissPalm; P48594; -.
DR BioMuta; SERPINB4; -.
DR DMDM; 1710877; -.
DR UCD-2DPAGE; P48594; -.
DR EPD; P48594; -.
DR jPOST; P48594; -.
DR MassIVE; P48594; -.
DR MaxQB; P48594; -.
DR PaxDb; P48594; -.
DR PeptideAtlas; P48594; -.
DR PRIDE; P48594; -.
DR ProteomicsDB; 55911; -.
DR Antibodypedia; 53439; 442 antibodies from 27 providers.
DR DNASU; 6318; -.
DR Ensembl; ENST00000341074.10; ENSP00000343445.5; ENSG00000206073.11.
DR GeneID; 6318; -.
DR KEGG; hsa:6318; -.
DR MANE-Select; ENST00000341074.10; ENSP00000343445.5; NM_002974.4; NP_002965.1.
DR UCSC; uc002ljf.4; human.
DR CTD; 6318; -.
DR DisGeNET; 6318; -.
DR GeneCards; SERPINB4; -.
DR HGNC; HGNC:10570; SERPINB4.
DR HPA; ENSG00000206073; Tissue enhanced (esophagus, vagina).
DR MIM; 600518; gene.
DR neXtProt; NX_P48594; -.
DR OpenTargets; ENSG00000206073; -.
DR PharmGKB; PA35539; -.
DR VEuPathDB; HostDB:ENSG00000206073; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000154520; -.
DR InParanoid; P48594; -.
DR OMA; FRQEYME; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; P48594; -.
DR TreeFam; TF352619; -.
DR PathwayCommons; P48594; -.
DR SignaLink; P48594; -.
DR BioGRID-ORCS; 6318; 12 hits in 1037 CRISPR screens.
DR ChiTaRS; SERPINB4; human.
DR GeneWiki; SERPINB4; -.
DR GenomeRNAi; 6318; -.
DR Pharos; P48594; Tbio.
DR PRO; PR:P48594; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P48594; protein.
DR Bgee; ENSG00000206073; Expressed in nasal cavity epithelium and 103 other tissues.
DR ExpressionAtlas; P48594; baseline and differential.
DR Genevisible; P48594; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:UniProtKB.
DR GO; GO:0042270; P:protection from natural killer cell mediated cytotoxicity; IMP:UniProtKB.
DR GO; GO:0030162; P:regulation of proteolysis; NAS:UniProtKB.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 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; 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 Acetylation; Cytoplasm; Direct protein sequencing; Protease inhibitor;
KW Reference proteome; Serine protease inhibitor.
FT CHAIN 1..390
FT /note="Serpin B4"
FT /id="PRO_0000094104"
FT SITE 354..355
FT /note="Reactive bond"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.6"
FT CONFLICT 353
FT /note="E -> K (in Ref. 4; BAF84901)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 390 AA; 44854 MW; 04E213CD892587D5 CRC64;
MNSLSEANTK FMFDLFQQFR KSKENNIFYS PISITSALGM VLLGAKDNTA QQISKVLHFD
QVTENTTEKA ATYHVDRSGN VHHQFQKLLT EFNKSTDAYE LKIANKLFGE KTYQFLQEYL
DAIKKFYQTS VESTDFANAP EESRKKINSW VESQTNEKIK NLFPDGTIGN DTTLVLVNAI
YFKGQWENKF KKENTKEEKF WPNKNTYKSV QMMRQYNSFN FALLEDVQAK VLEIPYKGKD
LSMIVLLPNE IDGLQKLEEK LTAEKLMEWT SLQNMRETCV DLHLPRFKME ESYDLKDTLR
TMGMVNIFNG DADLSGMTWS HGLSVSKVLH KAFVEVTEEG VEAAAATAVV VVELSSPSTN
EEFCCNHPFL FFIRQNKTNS ILFYGRFSSP