SPB8_HUMAN
ID SPB8_HUMAN Reviewed; 374 AA.
AC P50452; B4DTW2; Q7Z2V6; Q8N178;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Serpin B8;
DE AltName: Full=Cytoplasmic antiproteinase 2;
DE Short=CAP-2;
DE Short=CAP2;
DE AltName: Full=Peptidase inhibitor 8;
DE Short=PI-8;
GN Name=SERPINB8; Synonyms=PI8;
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), AND VARIANT ARG-359.
RC TISSUE=Placenta;
RX PubMed=8530382; DOI=10.1074/jbc.270.50.29854;
RA Sprecher C.A., Morgenstern K.A., Mathewes S., Dahlen J.R., Schrader S.K.,
RA Foster D.C., Kisiel W.;
RT "Molecular cloning, expression, and partial characterization of two novel
RT members of the ovalbumin family of serine proteinase inhibitors.";
RL J. Biol. Chem. 270:29854-29861(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-304.
RC TISSUE=Esophagus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
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 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 [7]
RP FUNCTION, AND INVOLVEMENT IN PSS5.
RX PubMed=27476651; DOI=10.1016/j.ajhg.2016.06.004;
RA Pigors M., Sarig O., Heinz L., Plagnol V., Fischer J., Mohamad J.,
RA Malchin N., Rajpopat S., Kharfi M., Lestringant G.G., Sprecher E.,
RA Kelsell D.P., Blaydon D.C.;
RT "Loss-of-function mutations in SERPINB8 linked to exfoliative ichthyosis
RT with impaired mechanical stability of intercellular adhesions.";
RL Am. J. Hum. Genet. 99:430-436(2016).
CC -!- FUNCTION: Has an important role in epithelial desmosome-mediated cell-
CC cell adhesion. {ECO:0000269|PubMed:27476651}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P50452-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P50452-2; Sequence=VSP_043097;
CC Name=3;
CC IsoId=P50452-3; Sequence=VSP_055135;
CC -!- DISEASE: Peeling skin syndrome 5 (PSS5) [MIM:617115]: A form of peeling
CC skin syndrome, a genodermatosis characterized by generalized,
CC continuous shedding of the outer layers of the epidermis. Two main PSS
CC subtypes have been suggested. Patients with non-inflammatory PSS (type
CC A) manifest white scaling, with painless and easy removal of the skin,
CC irritation when in contact with water, dust and sand, and no history of
CC erythema, pruritis or atopy. Inflammatory PSS (type B) is associated
CC with generalized erythema, pruritus and atopy. It is an ichthyosiform
CC erythroderma characterized by lifelong patchy peeling of the entire
CC skin with onset at birth or shortly after. Several patients have been
CC reported with high IgE levels. PSS5 patients manifest hyperkeratosis
CC and superficial peeling of areas of the palmar and dorsal faces of
CC hands and feet. Additional variable features include erythema,
CC superficial scaling of forearms and legs and diffuse yellowish
CC hyperkeratotic palmoplantar plaques. PSS5 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:27476651}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC {ECO:0000305}.
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DR EMBL; L40377; AAC41939.1; -; mRNA.
DR EMBL; AK300391; BAG62124.1; -; mRNA.
DR EMBL; BX571754; CAE11879.1; -; mRNA.
DR EMBL; AC009802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034528; AAH34528.1; -; mRNA.
DR CCDS; CCDS11991.1; -. [P50452-1]
DR CCDS; CCDS42442.1; -. [P50452-2]
DR CCDS; CCDS62460.1; -. [P50452-3]
DR PIR; A59273; A59273.
DR RefSeq; NP_001027018.1; NM_001031848.1. [P50452-2]
DR RefSeq; NP_001263419.1; NM_001276490.1. [P50452-3]
DR RefSeq; NP_002631.3; NM_002640.3. [P50452-1]
DR RefSeq; NP_942130.1; NM_198833.1. [P50452-1]
DR AlphaFoldDB; P50452; -.
DR SMR; P50452; -.
DR BioGRID; 111289; 97.
DR IntAct; P50452; 17.
DR STRING; 9606.ENSP00000381072; -.
DR MEROPS; I04.013; -.
DR iPTMnet; P50452; -.
DR MetOSite; P50452; -.
DR PhosphoSitePlus; P50452; -.
DR SwissPalm; P50452; -.
DR BioMuta; SERPINB8; -.
DR DMDM; 212276474; -.
DR EPD; P50452; -.
DR jPOST; P50452; -.
DR MassIVE; P50452; -.
DR MaxQB; P50452; -.
DR PaxDb; P50452; -.
DR PeptideAtlas; P50452; -.
DR PRIDE; P50452; -.
DR ProteomicsDB; 5132; -.
DR ProteomicsDB; 56226; -. [P50452-1]
DR ProteomicsDB; 56227; -. [P50452-2]
DR Antibodypedia; 23169; 307 antibodies from 31 providers.
DR DNASU; 5271; -.
DR Ensembl; ENST00000353706.6; ENSP00000331368.3; ENSG00000166401.15. [P50452-1]
DR Ensembl; ENST00000397985.7; ENSP00000381072.2; ENSG00000166401.15. [P50452-1]
DR Ensembl; ENST00000397988.7; ENSP00000381075.3; ENSG00000166401.15. [P50452-2]
DR Ensembl; ENST00000542677.5; ENSP00000438328.1; ENSG00000166401.15. [P50452-3]
DR GeneID; 5271; -.
DR KEGG; hsa:5271; -.
DR MANE-Select; ENST00000397985.7; ENSP00000381072.2; NM_002640.4; NP_002631.3.
DR UCSC; uc002ljt.4; human. [P50452-1]
DR CTD; 5271; -.
DR DisGeNET; 5271; -.
DR GeneCards; SERPINB8; -.
DR HGNC; HGNC:8952; SERPINB8.
DR HPA; ENSG00000166401; Tissue enhanced (skin).
DR MalaCards; SERPINB8; -.
DR MIM; 601697; gene.
DR MIM; 617115; phenotype.
DR neXtProt; NX_P50452; -.
DR OpenTargets; ENSG00000166401; -.
DR Orphanet; 289586; Exfoliative ichthyosis.
DR PharmGKB; PA35517; -.
DR VEuPathDB; HostDB:ENSG00000166401; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000154835; -.
DR HOGENOM; CLU_023330_0_2_1; -.
DR InParanoid; P50452; -.
DR OMA; NCIFFCG; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; P50452; -.
DR TreeFam; TF352619; -.
DR PathwayCommons; P50452; -.
DR Reactome; R-HSA-75205; Dissolution of Fibrin Clot.
DR SABIO-RK; P50452; -.
DR SignaLink; P50452; -.
DR BioGRID-ORCS; 5271; 5 hits in 1068 CRISPR screens.
DR GeneWiki; SERPINB8; -.
DR GenomeRNAi; 5271; -.
DR Pharos; P50452; Tbio.
DR PRO; PR:P50452; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P50452; protein.
DR Bgee; ENSG00000166401; Expressed in monocyte and 108 other tissues.
DR ExpressionAtlas; P50452; baseline and differential.
DR Genevisible; P50452; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0090136; P:epithelial cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA: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 Alternative splicing; Cytoplasm; Protease inhibitor; Reference proteome;
KW Serine protease inhibitor.
FT CHAIN 1..374
FT /note="Serpin B8"
FT /id="PRO_0000094111"
FT SITE 339..340
FT /note="Reactive bond"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..182
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055135"
FT VAR_SEQ 241..374
FT /note="VEKALTYEKFKAWTNSEKLTKSKVQVFLPRLKLEESYDLEPFLRRLGMIDAF
FT DEAKADFSGMSTEKNVPLSKVAHKCFVEVNEEGTEAAAATAVVRNSRCSRMEPRFCADH
FT PFLFFIRHHKTNCILFCGRFSSP -> KE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043097"
FT VARIANT 68
FT /note="R -> Q (in dbSNP:rs1944270)"
FT /id="VAR_047110"
FT VARIANT 158
FT /note="K -> N (in dbSNP:rs1648493)"
FT /id="VAR_047111"
FT VARIANT 304
FT /note="T -> A (in dbSNP:rs3169983)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_051947"
FT VARIANT 359
FT /note="H -> R (in dbSNP:rs3826616)"
FT /evidence="ECO:0000269|PubMed:8530382"
FT /id="VAR_051948"
SQ SEQUENCE 374 AA; 42767 MW; 7235A033519AC612 CRC64;
MDDLCEANGT FAISLFKILG EEDNSRNVFF SPMSISSALA MVFMGAKGST AAQMSQALCL
YKDGDIHRGF QSLLSEVNRT GTQYLLRTAN RLFGEKTCDF LPDFKEYCQK FYQAELEELS
FAEDTEECRK HINDWVAEKT EGKISEVLDA GTVDPLTKLV LVNAIYFKGK WNEQFDRKYT
RGMLFKTNEE KKTVQMMFKE AKFKMGYADE VHTQVLELPY VEEELSMVIL LPDDNTDLAV
VEKALTYEKF KAWTNSEKLT KSKVQVFLPR LKLEESYDLE PFLRRLGMID AFDEAKADFS
GMSTEKNVPL SKVAHKCFVE VNEEGTEAAA ATAVVRNSRC SRMEPRFCAD HPFLFFIRHH
KTNCILFCGR FSSP
