SPA3G_MOUSE
ID SPA3G_MOUSE Reviewed; 440 AA.
AC Q5I2A0; Q6PG99;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 25-MAY-2022, entry version 121.
DE RecName: Full=Serine protease inhibitor A3G;
DE Short=Serpin A3G;
DE AltName: Full=Serine protease inhibitor 2A;
DE Short=Serpin 2A;
GN Name=Serpina3g; Synonyms=Spi2A;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Liu N., Ashton-Rickardt P.G., Xia G.;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 91-440.
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=8978283;
RA Hampson I.N., Hampson L., Pinkoski M., Cross M., Heyworth C.M.,
RA Bleackley R.C., Atkinson E., Dexter T.M.;
RT "Identification of a serpin specifically expressed in multipotent and
RT bipotent hematopoietic progenitor cells and in activated T cells.";
RL Blood 89:108-118(1997).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=11438738; DOI=10.1073/pnas.131200898;
RA Terskikh A.V., Easterday M.C., Li L., Hood L., Kornblum H.I.,
RA Geschwind D.H., Weissman I.L.;
RT "From hematopoiesis to neuropoiesis: evidence of overlapping genetic
RT programs.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7934-7939(2001).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=12470299; DOI=10.1042/bj20021567;
RA Morris E.C., Dafforn T.R., Forsyth S.L., Missen M.A., Horvath A.J.,
RA Hampson L., Hampson I.N., Currie G., Carrell R.W., Coughlin P.B.;
RT "Murine serpin 2A is a redox-sensitive intracellular protein.";
RL Biochem. J. 371:165-173(2003).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=C57BL/6J;
RX PubMed=14517268; DOI=10.1093/emboj/cdg510;
RA Liu N., Raja S.M., Zazzeroni F., Metkar S.S., Shah R., Zhang M., Wang Y.,
RA Broemme D., Russin W.A., Lee J.C., Peter M.E., Froelich C.J., Franzoso G.,
RA Ashton-Rickardt P.G.;
RT "NF-kappaB protects from the lysosomal pathway of cell death.";
RL EMBO J. 22:5313-5322(2003).
RN [7]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=12659817; DOI=10.1016/s0888-7543(02)00041-1;
RA Forsyth S., Horvath A., Coughlin P.;
RT "A review and comparison of the murine alpha1-antitrypsin and alpha1-
RT antichymotrypsin multigene clusters with the human clade A serpins.";
RL Genomics 81:336-345(2003).
RN [8]
RP FUNCTION.
RC STRAIN=C57BL/6J;
RX PubMed=15225607; DOI=10.1016/j.febslet.2004.05.061;
RA Liu N., Wang Y., Ashton-Rickardt P.G.;
RT "Serine protease inhibitor 2A inhibits caspase-independent cell death.";
RL FEBS Lett. 569:49-53(2004).
RN [9]
RP TISSUE SPECIFICITY, AND REGION RCL.
RX PubMed=15638460; DOI=10.1007/s00239-004-2640-9;
RA Horvath A.J., Forsyth S.L., Coughlin P.B.;
RT "Expression patterns of murine antichymotrypsin-like genes reflect
RT evolutionary divergence at the Serpina3 locus.";
RL J. Mol. Evol. 59:488-497(2004).
RN [10]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J;
RX PubMed=15311278; DOI=10.1038/ni1107;
RA Liu N., Phillips T., Zhang M., Wang Y., Opferman J.T., Shah R.,
RA Ashton-Rickardt P.G.;
RT "Serine protease inhibitor 2A is a protective factor for memory T cell
RT development.";
RL Nat. Immunol. 5:919-926(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Serine and cysteine protease inhibitor. Can inhibit lysosomal
CC papain-like proteases including the cathepsins B, G, H, K, L and V.
CC Ineffective against elastase, granzyme A, granzyme B, or caspases 3, 8
CC or 9. Inhibition of cytoplasmic cathepsin B following release from the
CC lysosome may protect cells from apoptosis. This may facilitate the
CC survival of progenitor T-cells and the subsequent development of long
CC term memory CD8 T-cells. {ECO:0000269|PubMed:14517268,
CC ECO:0000269|PubMed:15225607, ECO:0000269|PubMed:15311278}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow (particularly
CC hematopoietic stem cells), heart, kidney, liver, lung, skeletal muscle,
CC spleen, testis, thymus and T-cells. {ECO:0000269|PubMed:11438738,
CC ECO:0000269|PubMed:15638460, ECO:0000269|PubMed:8978283}.
CC -!- DEVELOPMENTAL STAGE: T-cell specific expression rises during the
CC differentiation of CD8 T-cell progenitors into memory CD8 T-cells.
CC {ECO:0000269|PubMed:15311278}.
CC -!- INDUCTION: Induction during apoptosis requires NF-kappa-B, a
CC heterodimer of RELA- and NFKB1. {ECO:0000269|PubMed:14517268}.
CC -!- DOMAIN: The reactive center loop (RCL) extends out from the body of the
CC protein and directs binding to the target protease. The protease
CC cleaves the serpin at the reactive site within the RCL, establishing a
CC covalent linkage between the serpin reactive site and the protease. The
CC resulting inactive serpin-protease complex is highly stable (By
CC similarity). Variability within the reactive center loop (RCL)
CC sequences of Serpina3 paralogs may determine target protease
CC specificity. {ECO:0000250}.
CC -!- MISCELLANEOUS: The single human alpha1-antichymotrypsin gene (SERPINA3)
CC is represented by a cluster of 14 individual murine paralogs.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; AY862185; AAW56612.1; -; mRNA.
DR EMBL; BC057144; AAH57144.1; -; mRNA.
DR RefSeq; NP_033277.1; NM_009251.1.
DR AlphaFoldDB; Q5I2A0; -.
DR SMR; Q5I2A0; -.
DR IntAct; Q5I2A0; 2.
DR MINT; Q5I2A0; -.
DR STRING; 10090.ENSMUSP00000041250; -.
DR MEROPS; I04.959; -.
DR iPTMnet; Q5I2A0; -.
DR PhosphoSitePlus; Q5I2A0; -.
DR CPTAC; non-CPTAC-3747; -.
DR jPOST; Q5I2A0; -.
DR MaxQB; Q5I2A0; -.
DR PaxDb; Q5I2A0; -.
DR PeptideAtlas; Q5I2A0; -.
DR PRIDE; Q5I2A0; -.
DR ProteomicsDB; 257296; -.
DR DNASU; 20715; -.
DR GeneID; 20715; -.
DR KEGG; mmu:20715; -.
DR UCSC; uc007oxa.2; mouse.
DR CTD; 20715; -.
DR MGI; MGI:105046; Serpina3g.
DR eggNOG; KOG2392; Eukaryota.
DR InParanoid; Q5I2A0; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q5I2A0; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 20715; 0 hits in 51 CRISPR screens.
DR ChiTaRS; Serpina3g; mouse.
DR PRO; PR:Q5I2A0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q5I2A0; protein.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0034097; P:response to cytokine; IDA:MGI.
DR GO; GO:0043434; P:response to peptide hormone; IDA:MGI.
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 Adaptive immunity; Apoptosis; Cytoplasm; Immunity; Nucleus;
KW Protease inhibitor; Reference proteome; Serine protease inhibitor;
KW Thiol protease inhibitor.
FT CHAIN 1..440
FT /note="Serine protease inhibitor A3G"
FT /id="PRO_0000094098"
FT REGION 357..382
FT /note="RCL"
FT SITE 371..372
FT /note="Reactive bond"
FT /evidence="ECO:0000250"
FT CONFLICT 328
FT /note="Q -> H (in Ref. 1; AAW56612)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="T -> K (in Ref. 1; AAW56612)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="M -> T (in Ref. 1; AAW56612)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 440 AA; 49021 MW; 7F449368DC27DD05 CRC64;
MAGVSPAVFG CPDVTLGRNT AVREVQENVT SVDSLTLVSS NTDFAFSLYR KLVLKNPDEN
VVFSPFSICT ALALLSLGAK SNTLKEILEG LKFNLTETPE PDIHQGFRYL LDLLSQPGNQ
VQISTGSALF IEKHLQILAE FKEKARALYQ AEAFTADFQQ PLKATKLIND YVSNHTQGKI
KELISGLKES TLMVLVNYIY FKGKWKNPFD PNDTFKSEFY LDEKRSVIVS MMKTGYLTTP
YFRDEELSCT VVELKYTGNA SAMFILPDQG RMQQVEASLQ PETLRKWKNS LKPRMIHELR
LPKFSISTDY SLEHILPELG IREVFSTQAD LSAITGTKDL RVSQVVHKAV LDVAETGTEA
AAATGMAGVG CCAVFDFLEI FFNRPFLMII SDTKAHIALF MAKVTNPERS MNFPNGEGAS
SQRLESKRLC FGDPLCLIGQ
