SPA12_MOUSE
ID SPA12_MOUSE Reviewed; 413 AA.
AC Q7TMF5; Q9CQ32;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Serpin A12;
DE AltName: Full=Visceral adipose tissue-derived serine protease inhibitor;
DE Short=Vaspin;
DE AltName: Full=Visceral adipose-specific serpin;
DE Flags: Precursor;
GN Name=Serpina12;
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], FUNCTION, PROTEIN SEQUENCE OF N-TERMINUS, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Swiss Webster;
RX PubMed=16030142; DOI=10.1073/pnas.0504703102;
RA Hida K., Wada J., Eguchi J., Zhang H., Baba M., Seida A., Hashimoto I.,
RA Okada T., Yasuhara A., Nakatsuka A., Shikata K., Hourai S., Futami J.,
RA Watanabe E., Matsuki Y., Hiramatsu R., Akagi S., Makino H., Kanwar Y.S.;
RT "Visceral adipose tissue-derived serine protease inhibitor: a unique
RT insulin-sensitizing adipocytokine in obesity.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10610-10615(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23370777; DOI=10.1007/s00018-013-1258-8;
RA Heiker J.T., Kloting N., Kovacs P., Kuettner E.B., Strater N., Schultz S.,
RA Kern M., Stumvoll M., Bluher M., Beck-Sickinger A.G.;
RT "Vaspin inhibits kallikrein 7 by serpin mechanism.";
RL Cell. Mol. Life Sci. 70:2569-2583(2013).
CC -!- FUNCTION: Adipokine that modulates insulin action by specifically
CC inhibiting its target protease KLK7 in white adipose tissues.
CC {ECO:0000269|PubMed:16030142, ECO:0000269|PubMed:23370777}.
CC -!- ACTIVITY REGULATION: Inhibition of KLK7 is enhanced by heparin.
CC {ECO:0000250|UniProtKB:Q8IW75}.
CC -!- SUBUNIT: Forms a stable complex with KLK7.
CC {ECO:0000250|UniProtKB:Q8IW75}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23370777}.
CC -!- TISSUE SPECIFICITY: Expressed in visceral adipose tissues.
CC {ECO:0000269|PubMed:16030142}.
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 carboxyl group of the serpin reactive site
CC and the serine hydroxyl of the protease. The resulting inactive serpin-
CC protease complex is highly stable. {ECO:0000250|UniProtKB:Q8IW75}.
CC -!- PTM: Glycosylation slightly decreases affinity for heparin, but
CC otherwise has no significant effect on KLK7 inhibitory activity or
CC thermal stability of the protein. {ECO:0000250|UniProtKB:Q8IW75}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; AY326419; AAP88383.1; -; mRNA.
DR EMBL; AK014346; BAB29287.1; -; mRNA.
DR EMBL; AK014589; BAB29447.1; -; mRNA.
DR CCDS; CCDS26145.1; -.
DR RefSeq; NP_080811.1; NM_026535.2.
DR AlphaFoldDB; Q7TMF5; -.
DR SMR; Q7TMF5; -.
DR BioGRID; 212632; 7.
DR STRING; 10090.ENSMUSP00000045572; -.
DR MEROPS; I04.091; -.
DR GlyGen; Q7TMF5; 2 sites.
DR PhosphoSitePlus; Q7TMF5; -.
DR PaxDb; Q7TMF5; -.
DR PRIDE; Q7TMF5; -.
DR ProteomicsDB; 261489; -.
DR Antibodypedia; 27079; 375 antibodies from 33 providers.
DR DNASU; 68054; -.
DR Ensembl; ENSMUST00000043915; ENSMUSP00000045572; ENSMUSG00000041567.
DR GeneID; 68054; -.
DR KEGG; mmu:68054; -.
DR UCSC; uc007owp.1; mouse.
DR CTD; 145264; -.
DR MGI; MGI:1915304; Serpina12.
DR VEuPathDB; HostDB:ENSMUSG00000041567; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000161977; -.
DR HOGENOM; CLU_023330_2_1_1; -.
DR InParanoid; Q7TMF5; -.
DR OMA; VPMMFRG; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q7TMF5; -.
DR TreeFam; TF343201; -.
DR BioGRID-ORCS; 68054; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Serpina12; mouse.
DR PRO; PR:Q7TMF5; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q7TMF5; protein.
DR Bgee; ENSMUSG00000041567; Expressed in tail skin and 25 other tissues.
DR Genevisible; Q7TMF5; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0006094; P:gluconeogenesis; IDA:MGI.
DR GO; GO:0008610; P:lipid biosynthetic process; IDA:MGI.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IDA:MGI.
DR GO; GO:0051055; P:negative regulation of lipid biosynthetic process; IDA:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:MGI.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:MGI.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IMP:MGI.
DR GO; GO:0090207; P:regulation of triglyceride metabolic process; IMP: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 Direct protein sequencing; Glycoprotein; Protease inhibitor;
KW Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:16030142"
FT CHAIN 21..413
FT /note="Serpin A12"
FT /id="PRO_0000041977"
FT REGION 364..382
FT /note="Reactive center loop"
FT /evidence="ECO:0000250|UniProtKB:Q8IW75"
FT SITE 378..379
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q8IW75"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 69
FT /note="Q -> R (in Ref. 1; AAP88383)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="W -> R (in Ref. 1; AAP88383)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="Q -> R (in Ref. 1; AAP88383)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="V -> I (in Ref. 1; AAP88383)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 413 AA; 47634 MW; D0AE8E1EE24FD60A CRC64;
MTRMLDLGLF LAGLLTVKGL LQDRDAPDMY DSPVRVQEWR GKKDARQLAR HNMEFGFKLL
QRLASNSPQG NIFLSPLSIS TAFSMLSLGA QNSTLEEIRE GFNFKEMSNW DVHAAFHYLL
HKLNQETEDT KMNLGNALFM DQKLRPQQRF LNLAKNVYDA DMVLTNFQDL ENTQKDINRY
ISQKTHSRIK NMVKSIDPGT VMILTNYIYF RGRWQYEFDP KQTKEEEFFI EKGKTVKVPM
MFQRGLYDMA YDSQLSCTIL EIPYRGNITA TFVLPDNGKL KLLEQGLQAD IFAKWKSLLS
KRVVDVWVPK LRISSTYNMK KVLSRLGISK IFEENGDLTR ISSHRSLKVG EAVHKAELKM
DEKGMEGAAG SGAQTLPMET PRHMKLDRPF LMMIYENFMP SMVFLARIYD PSG
