SPA3K_RAT
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 25-MAY-2022, entry version 150.
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;
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;
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 RefSeq; NP_036789.2; NM_012657.2.
DR RefSeq; XP_006240520.1; XM_006240458.3.
DR AlphaFoldDB; P05545; -.
DR SMR; P05545; -.
DR BioGRID; 246917; 1.
DR IntAct; P05545; 2.
DR STRING; 10116.ENSRNOP00000013896; -.
DR MEROPS; I04.051; -.
DR GlyGen; P05545; 4 sites.
DR iPTMnet; P05545; -.
DR PhosphoSitePlus; P05545; -.
DR SwissPalm; P05545; -.
DR PaxDb; P05545; -.
DR PRIDE; P05545; -.
DR GeneID; 24794; -.
DR KEGG; rno:24794; -.
DR UCSC; RGD:3746; rat.
DR CTD; 16625; -.
DR RGD; 3746; Serpina3k.
DR eggNOG; KOG2392; Eukaryota.
DR InParanoid; P05545; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; P05545; -.
DR TreeFam; TF343201; -.
DR PRO; PR:P05545; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
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 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
