ID   SPA3K_RAT               Reviewed;         416 AA.
AC   P05545; P14281; Q64254; Q6P6G8;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1993, sequence version 3.
DT   02-SEP-2026, entry version 162.
DE   RecName: Full=Serine protease inhibitor A3K;
DE            Short=Serpin A3K;
DE   AltName: Full=CPI-21;
DE   AltName: Full=Contrapsin-like protease inhibitor 1;
DE   AltName: Full=GHR-P63;
DE   AltName: Full=Growth hormone-regulated proteinase inhibitor;
DE   AltName: Full=Kallikrein-binding protein;
DE            Short=KBP;
DE   AltName: Full=SPI-2.3;
DE   AltName: Full=Serine protease inhibitor 2;
DE            Short=SPI-2;
DE   AltName: Full=Thyroid hormone-regulated protein;
DE   Flags: Precursor;
GN   Name=Serpina3k; Synonyms=Spin2b;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND
RP   GLYCOSYLATION.
RX   PubMed=2440672; DOI=10.1002/j.1460-2075.1987.tb02358.x;
RA   le Cam A., Pages G., Auberger P., le Cam G., Leopold P., Benarous R.,
RA   Glaichenhaus N.;
RT   "Study of a growth hormone-regulated protein secreted by rat hepatocytes:
RT   cDNA cloning, anti-protease activity and regulation of its synthesis by
RT   various hormones.";
RL   EMBO J. 6:1225-1232(1987).
RN   [2]
RP   SEQUENCE REVISION.
RA   le Cam A.;
RL   Submitted (OCT-1987) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC   TISSUE=Liver;
RX   PubMed=3494016; DOI=10.1016/s0021-9258(18)61345-6;
RA   Yoon J.-B., Towle H.C., Seelig S.;
RT   "Growth hormone induces two mRNA species of the serine protease inhibitor
RT   gene family in rat liver.";
RL   J. Biol. Chem. 262:4284-4289(1987).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, AND GLYCOSYLATION.
RC   TISSUE=Liver;
RX   PubMed=1694763; DOI=10.1111/j.1432-1033.1990.tb15587.x;
RA   Pages G., Rouayrenc J.F., le Cam G., Mariller M., le Cam A.;
RT   "Molecular characterization of three rat liver serine-protease inhibitors
RT   affected by inflammation and hypophysectomy. Protein and mRNA analysis and
RT   cDNA cloning.";
RL   Eur. J. Biochem. 190:385-391(1990).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-326.
RX   PubMed=2258058; DOI=10.1016/0378-1119(90)90398-b;
RA   Pages G., Rouayrenc J.F., Rossi V., Le Cam G., Mariller M., Szpirer J.,
RA   Szpirer C., Levan G., Le Cam A.;
RT   "Primary structure and assignment to chromosome 6 of three related rat
RT   genes encoding liver serine protease inhibitors.";
RL   Gene 94:273-282(1990).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=1864837; DOI=10.1093/oxfordjournals.jbchem.a123369;
RA   Ohkubo K., Ogata S., Misumi Y., Takami N., Ikehara Y.;
RT   "Molecular cloning and characterization of rat contrapsin-like protease
RT   inhibitor and related proteins.";
RL   J. Biochem. 109:243-250(1991).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=1874745; DOI=10.1016/s0021-9258(18)98511-x;
RA   Chai K.X., Ma J.-X., Murray S.R., Chao J., Chao L.;
RT   "Molecular cloning and analysis of the rat kallikrein-binding protein
RT   gene.";
RL   J. Biol. Chem. 266:16029-16036(1991).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pituitary;
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   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-49, PROTEIN SEQUENCE OF 21-49,
RP   CHARACTERIZATION, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=2398056; DOI=10.1016/s0021-9258(17)46236-3;
RA   Chao J., Chai K.X., Chen L.-M., Xiong W., Chao S., Woodley-Miller C.,
RA   Wang L., Lu H.S., Chao L.;
RT   "Tissue kallikrein-binding protein is a serpin. I. Purification,
RT   characterization, and distribution in normotensive and spontaneously
RT   hypertensive rats.";
RL   J. Biol. Chem. 265:16394-16401(1990).
RN   [10]
RP   PROTEIN SEQUENCE OF 155-167; 188-210 AND 312-330, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord;
RA   Lubec G., Afjehi-Sadat L., Kang S.U., Lubec S.;
RL   Submitted (SEP-2007) to UniProtKB.
RN   [11]
RP   DOMAIN 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).
CC   -!- FUNCTION: Binds to and inhibits kallikreins. Inhibits trypsin but not
CC       chymotrypsin or elastase. {ECO:0000269|PubMed:1864837,
CC       ECO:0000269|PubMed:2440672}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Liver and plasma. {ECO:0000269|PubMed:1864837,
CC       ECO:0000269|PubMed:2398056, ECO:0000269|PubMed:2440672}.
CC   -!- INDUCTION: By growth hormone, thyroid hormone and sex hormones. Its
CC       expression is reduced by inflammation. In male rats, its level is
CC       several fold higher than in female rats. Reduced during acute
CC       inflammation. {ECO:0000269|PubMed:1694763, ECO:0000269|PubMed:2398056,
CC       ECO:0000269|PubMed:2440672, ECO:0000269|PubMed:3494016}.
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, ECO:0000269|PubMed:15638460}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1694763,
CC       ECO:0000269|PubMed:2440672}.
CC   -!- MISCELLANEOUS: The single human alpha1-antichymotrypsin gene (SERPINA3)
CC       is represented by a cluster of 6 individual rat paralogs.
CC   -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH62236.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA34407.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA34409.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; X05348; CAA28958.1; -; mRNA.
DR   EMBL; M15916; AAA42173.1; -; mRNA.
DR   EMBL; X16358; CAA34407.1; ALT_INIT; mRNA.
DR   EMBL; X16362; CAA34409.1; ALT_INIT; Genomic_DNA.
DR   EMBL; D00751; BAA00648.1; -; mRNA.
DR   EMBL; M67496; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC062236; AAH62236.2; ALT_INIT; mRNA.
DR   PIR; A29035; A29035.
DR   PIR; B29131; B29131.
DR   AlphaFoldDB; P05545; -.
DR   SMR; P05545; -.
DR   BioGRID; 246917; 1.
DR   FunCoup; P05545; 131.
DR   IntAct; P05545; 2.
DR   STRING; 10116.ENSRNOP00000013896; -.
DR   MEROPS; I04.051; -.
DR   GlyCosmos; P05545; 4 sites, No reported glycans.
DR   GlyGen; P05545; 5 sites.
DR   iPTMnet; P05545; -.
DR   PhosphoSitePlus; P05545; -.
DR   SwissPalm; P05545; -.
DR   PaxDb; 10116-ENSRNOP00000013896; -.
DR   GeneID; 24794; -.
DR   KEGG; rno:24794; -.
DR   UCSC; RGD:3746; rat.
DR   AGR; RGD:2972; -.
DR   CTD; 16625; -.
DR   RGD; 3746; Serpina3k.
DR   eggNOG; KOG2392; Eukaryota.
DR   InParanoid; P05545; -.
DR   OrthoDB; 671595at2759; -.
DR   PhylomeDB; P05545; -.
DR   PRO; PR:P05545; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; IMP:RGD.
DR   GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR   GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR   CDD; cd19551; serpinA3_A1AC; 1.
DR   FunFam; 3.30.497.10:FF:000001; Serine protease inhibitor; 1.
DR   FunFam; 2.30.39.10:FF:000002; Serpin family D member 1; 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:SF195; SERINE PROTEASE INHIBITOR A3A-RELATED; 1.
DR   PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1.
DR   Pfam; PF00079; Serpin; 1.
DR   SMART; SM00093; SERPIN; 1.
DR   SUPFAM; SSF56574; Serpins; 1.
DR   PROSITE; PS00284; SERPIN; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Glycoprotein; Protease inhibitor;
KW   Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000269|PubMed:2398056"
FT   CHAIN           21..416
FT                   /note="Serine protease inhibitor A3K"
FT                   /id="PRO_0000032421"
FT   REGION          365..392
FT                   /note="RCL"
FT   SITE            379..380
FT                   /note="Reactive bond"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        102
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        182
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        220
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        267
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         326
FT                   /note="E -> D"
FT                   /evidence="ECO:0000269|PubMed:2258058"
FT   CONFLICT        30
FT                   /note="P -> S (in Ref. 9; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        47
FT                   /note="S -> A (in Ref. 9; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        98
FT                   /note="V -> G (in Ref. 3; AAA42173, 6; BAA00648 and 8;
FT                   AAH62236)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        112
FT                   /note="H -> HH (in Ref. 4; CAA34407)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        194
FT                   /note="E -> D (in Ref. 6; BAA00648)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        250
FT                   /note="I -> V (in Ref. 6; BAA00648)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        326
FT                   /note="E -> D (in Ref. 5; CAA34409)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        385
FT                   /note="I -> V (in Ref. 6; BAA00648)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        387
FT                   /note="L -> P (in Ref. 4; CAA34407)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        401
FT                   /note="N -> D (in Ref. 8; AAH62236)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   416 AA;  46562 MW;  6072BAE56BFF91B1 CRC64;
     MAFIAALGLL MAGICPAVLC DGILGRDTLP HEDQGKGRQL HSLTLASINT DFTLSLYKKL
     ALRNPDKNVV FSPLSISAAL AILSLGAKDS TMEEILEVLK FNLTEITEEE IHQGFGHLLQ
     RLSQPEDQAE INTGSALFID KEQPILSEFQ EKTRALYQAE AFVADFKQCN EAKKFINDYV
     SNQTQGKIAE LFSELDERTS MVLVNYLLFK GKWKVPFNPN DTFESEFYLD EKRSVKVPMM
     KIKDLTTPYI RDEELSCSVL ELKYTGNASA LFILPDQGKM QQVESSLQPE TLKKWKDSLR
     PRIISELRMP KFSISTDYNL EEVLPELGIR KIFSQQADLS RITGTKNLHV SQVVHKAVLD
     VDETGTEGAA ATAVTAALKS LPQTIPLLNF NRPFMLVITD NNGQSVFFMG KVTNPM
//