SENP2_MOUSE
ID SENP2_MOUSE Reviewed; 588 AA.
AC Q91ZX6; Q544T8; Q811R3; Q9D4Z0;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Sentrin-specific protease 2 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000269|PubMed:11489887, ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:27637147};
DE AltName: Full=Axam2 {ECO:0000303|PubMed:12419228};
DE AltName: Full=SUMO-1 protease 1;
DE Short=SuPr-1;
DE AltName: Full=SUMO-1/Smt3-specific isopeptidase 2 {ECO:0000303|PubMed:11489887};
DE Short=Smt3ip2 {ECO:0000303|PubMed:11489887};
DE AltName: Full=Sentrin/SUMO-specific protease SENP2;
GN Name=Senp2; Synonyms=Smt3ip2 {ECO:0000303|PubMed:11489887}, Supr1;
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] (ISOFORM 2), FUNCTION, MUTAGENESIS OF CYS-547,
RP ACTIVE SITE, AND SUBCELLULAR LOCATION.
RC TISSUE=Osteoblast;
RX PubMed=11489887; DOI=10.1074/jbc.m103955200;
RA Nishida T., Kaneko F., Kitagawa M., Yasuda H.;
RT "Characterization of a novel mammalian SUMO-1/Smt3-specific isopeptidase, a
RT homologue of rat Axam, which is an Axin-binding protein promoting beta-
RT Catenin degradation.";
RL J. Biol. Chem. 276:39060-39066(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), MUTAGENESIS OF CYS-547, ACTIVE
RP SITE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND FUNCTION (ISOFORM 3).
RX PubMed=12419228; DOI=10.1016/s1097-2765(02)00699-8;
RA Best J.L., Ganiatsas S., Agarwal S., Changou A., Salomoni P., Shirihai O.,
RA Meluh P.B., Pandolfi P.P., Zon L.I.;
RT "SUMO-1 protease-1 regulates gene transcription through PML.";
RL Mol. Cell 10:843-855(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Testis, and Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary tumor;
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 [5]
RP PROTEIN SEQUENCE OF 342-348 AND 489-499, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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).
RN [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=20194620; DOI=10.1128/mcb.00852-09;
RA Chung S.S., Ahn B.Y., Kim M., Choi H.H., Park H.S., Kang S., Park S.G.,
RA Kim Y.B., Cho Y.M., Lee H.K., Chung C.H., Park K.S.;
RT "Control of adipogenesis by the SUMO-specific protease SENP2.";
RL Mol. Cell. Biol. 30:2135-2146(2010).
RN [8]
RP FUNCTION.
RX PubMed=27637147; DOI=10.1016/j.immuni.2016.08.014;
RA Hu M.M., Yang Q., Xie X.Q., Liao C.Y., Lin H., Liu T.T., Yin L., Shu H.B.;
RT "Sumoylation promotes the stability of the DNA sensor cGAS and the adaptor
RT STING to regulate the kinetics of response to DNA virus.";
RL Immunity 45:555-569(2016).
CC -!- FUNCTION: Protease that catalyzes two essential functions in the SUMO
CC pathway (PubMed:11489887, PubMed:20194620). The first is the hydrolysis
CC of an alpha-linked peptide bond at the C-terminal end of the small
CC ubiquitin-like modifier (SUMO) propeptides, SUMO1, SUMO2 and SUMO3
CC leading to the mature form of the proteins (By similarity). The second
CC is the deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins,
CC by cleaving an epsilon-linked peptide bond between the C-terminal
CC glycine of the mature SUMO and the lysine epsilon-amino group of the
CC target protein (PubMed:11489887, PubMed:20194620, PubMed:27637147). May
CC down-regulate CTNNB1 levels and thereby modulate the Wnt pathway
CC (PubMed:11489887). Deconjugates SUMO2 from MTA1 (By similarity). Plays
CC a dynamic role in adipogenesis by desumoylating and promoting the
CC stabilization of CEBPB (PubMed:20194620). Acts as a regulator of the
CC cGAS-STING pathway by catalyzing desumoylation of CGAS and STING1
CC during the late phase of viral infection (PubMed:27637147).
CC {ECO:0000250|UniProtKB:Q9HC62, ECO:0000269|PubMed:11489887,
CC ECO:0000269|PubMed:20194620, ECO:0000269|PubMed:27637147}.
CC -!- FUNCTION: [Isoform 3]: Activates transcription.
CC {ECO:0000269|PubMed:12419228}.
CC -!- SUBUNIT: Binds to SUMO2 and SUMO3 (By similarity). Interacts with the
CC C-terminal domain of NUP153 via its N-terminus (By similarity).
CC Interacts with MTA1 (By similarity). {ECO:0000250|UniProtKB:Q9HC62}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nuclear pore complex
CC {ECO:0000250|UniProtKB:Q9HC62}. Nucleus membrane
CC {ECO:0000250|UniProtKB:Q9HC62}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9HC62}; Nucleoplasmic side
CC {ECO:0000250|UniProtKB:Q9HC62}. Note=Shuttles between cytoplasm and
CC nucleus. {ECO:0000250|UniProtKB:Q9HC62}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:11489887}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:11489887}. Note=Found in the cytoplasm and in
CC cytoplasmic vesicles, together with axin.
CC {ECO:0000269|PubMed:11489887}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, PML body
CC {ECO:0000269|PubMed:12419228}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q91ZX6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91ZX6-2; Sequence=VSP_005273;
CC Name=3;
CC IsoId=Q91ZX6-3; Sequence=VSP_021942;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Detected in brain,
CC heart and thymus. {ECO:0000269|PubMed:12419228}.
CC -!- DEVELOPMENTAL STAGE: In 3T3-L1 cells, expression is transiently induced
CC during early adipocyte differentiation (PubMed:20194620).
CC {ECO:0000269|PubMed:20194620}.
CC -!- DOMAIN: The N-terminus is necessary and sufficient for nuclear envelope
CC targeting. {ECO:0000250|UniProtKB:Q9HC62}.
CC -!- PTM: Polyubiquitinated; which leads to proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q9HC62}.
CC -!- SIMILARITY: Belongs to the peptidase C48 family. {ECO:0000305}.
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DR EMBL; AF368904; AAL14437.1; -; mRNA.
DR EMBL; AY188288; AAO27902.1; -; mRNA.
DR EMBL; AK015987; BAB30067.1; -; mRNA.
DR EMBL; AK031030; BAC27222.1; -; mRNA.
DR EMBL; BC031652; AAH31652.1; -; mRNA.
DR CCDS; CCDS28065.1; -. [Q91ZX6-1]
DR RefSeq; NP_083733.1; NM_029457.3. [Q91ZX6-1]
DR RefSeq; XP_006522753.1; XM_006522690.1.
DR AlphaFoldDB; Q91ZX6; -.
DR SMR; Q91ZX6; -.
DR BioGRID; 217772; 6.
DR STRING; 10090.ENSMUSP00000023561; -.
DR MEROPS; C48.007; -.
DR iPTMnet; Q91ZX6; -.
DR PhosphoSitePlus; Q91ZX6; -.
DR EPD; Q91ZX6; -.
DR MaxQB; Q91ZX6; -.
DR PaxDb; Q91ZX6; -.
DR PeptideAtlas; Q91ZX6; -.
DR PRIDE; Q91ZX6; -.
DR ProteomicsDB; 256542; -. [Q91ZX6-1]
DR ProteomicsDB; 256543; -. [Q91ZX6-2]
DR ProteomicsDB; 256544; -. [Q91ZX6-3]
DR Antibodypedia; 33840; 768 antibodies from 35 providers.
DR DNASU; 75826; -.
DR Ensembl; ENSMUST00000023561; ENSMUSP00000023561; ENSMUSG00000022855. [Q91ZX6-1]
DR GeneID; 75826; -.
DR KEGG; mmu:75826; -.
DR UCSC; uc007yrw.2; mouse. [Q91ZX6-1]
DR UCSC; uc007yrx.2; mouse. [Q91ZX6-2]
DR UCSC; uc007yry.2; mouse. [Q91ZX6-3]
DR CTD; 59343; -.
DR MGI; MGI:1923076; Senp2.
DR VEuPathDB; HostDB:ENSMUSG00000022855; -.
DR eggNOG; KOG0778; Eukaryota.
DR GeneTree; ENSGT00940000154951; -.
DR HOGENOM; CLU_024324_4_0_1; -.
DR InParanoid; Q91ZX6; -.
DR OMA; PGMYRWL; -.
DR OrthoDB; 1480705at2759; -.
DR PhylomeDB; Q91ZX6; -.
DR TreeFam; TF316289; -.
DR BRENDA; 3.4.22.B71; 3474.
DR Reactome; R-MMU-3065679; SUMO is proteolytically processed.
DR BioGRID-ORCS; 75826; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Senp2; mouse.
DR PRO; PR:Q91ZX6; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q91ZX6; protein.
DR Bgee; ENSMUSG00000022855; Expressed in spermatocyte and 249 other tissues.
DR ExpressionAtlas; Q91ZX6; baseline and differential.
DR Genevisible; Q91ZX6; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; IDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005643; C:nuclear pore; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0016929; F:deSUMOylase activity; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0070139; F:SUMO-specific endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0009950; P:dorsal/ventral axis specification; ISO:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0060711; P:labyrinthine layer development; IMP:MGI.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0035562; P:negative regulation of chromatin binding; IMP:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0031648; P:protein destabilization; ISO:MGI.
DR GO; GO:0016926; P:protein desumoylation; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0032875; P:regulation of DNA endoreduplication; IMP:MGI.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0051246; P:regulation of protein metabolic process; ISO:MGI.
DR GO; GO:0060712; P:spongiotrophoblast layer development; IMP:MGI.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; IMP:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR003653; Peptidase_C48_C.
DR Pfam; PF02902; Peptidase_C48; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50600; ULP_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Hydrolase; Membrane; mRNA transport;
KW Nuclear pore complex; Nucleus; Phosphoprotein; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transcription;
KW Transcription regulation; Translocation; Transport; Ubl conjugation;
KW Ubl conjugation pathway; Wnt signaling pathway.
FT CHAIN 1..588
FT /note="Sentrin-specific protease 2"
FT /id="PRO_0000101719"
FT REGION 157..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..558
FT /note="Protease"
FT /evidence="ECO:0000250|UniProtKB:Q9HC62"
FT MOTIF 28..31
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 47..52
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 316..331
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q9HC62"
FT COMPBIAS 170..184
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 477
FT /evidence="ECO:0000250|UniProtKB:Q9HC62"
FT ACT_SITE 494
FT /evidence="ECO:0000250|UniProtKB:Q9HC62"
FT ACT_SITE 547
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:11489887,
FT ECO:0000305|PubMed:12419228"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HC62"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HC62"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HC62"
FT VAR_SEQ 1..81
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12419228"
FT /id="VSP_021942"
FT VAR_SEQ 1..53
FT /note="MYRWLAKVLGTILRLCERPAPGARALLKRRRSSSTLFSTAVDTDEIPAKRPR
FT L -> MEQNSK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11489887"
FT /id="VSP_005273"
FT MUTAGEN 547
FT /note="C->A: Abolishes protease activity."
FT /evidence="ECO:0000269|PubMed:11489887,
FT ECO:0000269|PubMed:12419228"
FT CONFLICT 220
FT /note="L -> F (in Ref. 1; AAL14437)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="W -> C (in Ref. 1; AAL14437)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 588 AA; 67579 MW; 09B56796CA194847 CRC64;
MYRWLAKVLG TILRLCERPA PGARALLKRR RSSSTLFSTA VDTDEIPAKR PRLDCFIHQV
KNSLYNAASL FGFPFQLTTK PMVSSACNGT RNVAPSGEVF SNSSSCELMS SGSCSSMLKL
GNKSPNGISD YPKIRVTVTR DQPRRVLPSF GFTLKSEGYN RRPSGRRHSK SNPESSLTWK
PQEQGVTEMI SEEGGKGVRR PHCTVEEGVQ KDEREKYRKL LERLKEGAHG STFPPTVSHH
SSQRIQMDTL KTKGWVEEQN HGVRTTHFVP KQYRVVETRG PLCSMRSEKR YSKGKADTEK
VVGLRFEKEG TRGHQMEPDL SEEVSARLRL GSGSNGLLRR KISVLEIKEK NFPSKEKDRR
TEDLFEFTED MEKEISNALG HGPPDEILSS AFKLRITRGD IQTLKNYHWL NDEVINFYMN
LLVERSKKQG YPALHAFSTF FYPKLKSGGY QAVKRWTKGV NLFEQELVLV PIHRKVHWSL
VVMDLRKKCL KYLDSMGQKG HRICEILLQY LQDESKTKRN TDLNLLEWTH YSMKPHEIPQ
QLNGSDCGMF TCKYADYISR DKPITFTQHQ MPLFRKKMVW EILHQQLL
