INT3_MOUSE
ID INT3_MOUSE Reviewed; 1041 AA.
AC Q7TPD0; A0A4X0; A0A4X3; Q99LK7;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Integrator complex subunit 3;
DE Short=Int3;
DE AltName: Full=SOSS complex subunit A;
DE AltName: Full=Sensor of single-strand DNA complex subunit A;
DE Short=SOSS-A;
DE Short=Sensor of ssDNA subunit A;
GN Name=Ints3;
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 [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 460-1041 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-500 AND SER-535, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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: Component of the Integrator (INT) complex. The Integrator
CC complex is involved in the small nuclear RNAs (snRNA) U1 and U2
CC transcription and in their 3'-box-dependent processing. The Integrator
CC complex is associated with the C-terminal domain (CTD) of RNA
CC polymerase II largest subunit (POLR2A) and is recruited to the U1 and
CC U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the
CC nuclear envelope, probably as component of the INT complex.
CC {ECO:0000250|UniProtKB:Q68E01}.
CC -!- FUNCTION: Component of the SOSS complex, a multiprotein complex that
CC functions downstream of the MRN complex to promote DNA repair and G2/M
CC checkpoint. The SOSS complex associates with single-stranded DNA at DNA
CC lesions and influences diverse endpoints in the cellular DNA damage
CC response including cell-cycle checkpoint activation, recombinational
CC repair and maintenance of genomic stability. The SOSS complex is
CC required for efficient homologous recombination-dependent repair of
CC double-strand breaks (DSBs) and ATM-dependent signaling pathways. In
CC the SOSS complex, it is required for the assembly of the complex and
CC for stabilization of the complex at DNA damage sites.
CC {ECO:0000250|UniProtKB:Q68E01}.
CC -!- SUBUNIT: Belongs to the multiprotein complex Integrator, at least
CC composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8,
CC INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12. Component of the SOSS
CC complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-
CC A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are
CC more abundant than complexes containing SOSS-B2/NABP1. Interacts with
CC SOSS-B1/NABP2, SOSS-B2/NABP1 and SOSS-C/INIP; the interaction is
CC direct. Interacts with NBN/NBS1. {ECO:0000250|UniProtKB:Q68E01}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q68E01}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q68E01}. Note=Localizes to nuclear foci
CC following DNA damage. {ECO:0000250|UniProtKB:Q68E01}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7TPD0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TPD0-2; Sequence=VSP_038133, VSP_038134;
CC -!- SIMILARITY: Belongs to the Integrator subunit 3 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC31492.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK040147; BAC30523.1; -; mRNA.
DR EMBL; AK043206; BAC31492.1; ALT_INIT; mRNA.
DR EMBL; BC003209; AAH03209.2; -; mRNA.
DR EMBL; BC055344; AAH55344.1; -; mRNA.
DR CCDS; CCDS17528.1; -. [Q7TPD0-1]
DR RefSeq; NP_663515.2; NM_145540.3. [Q7TPD0-1]
DR RefSeq; NP_849207.2; NM_178876.3. [Q7TPD0-1]
DR AlphaFoldDB; Q7TPD0; -.
DR SMR; Q7TPD0; -.
DR BioGRID; 230859; 11.
DR ComplexPortal; CPX-613; SOSS1 complex.
DR ComplexPortal; CPX-615; SOSS2 complex.
DR DIP; DIP-59970N; -.
DR IntAct; Q7TPD0; 2.
DR STRING; 10090.ENSMUSP00000029542; -.
DR iPTMnet; Q7TPD0; -.
DR PhosphoSitePlus; Q7TPD0; -.
DR EPD; Q7TPD0; -.
DR jPOST; Q7TPD0; -.
DR MaxQB; Q7TPD0; -.
DR PaxDb; Q7TPD0; -.
DR PeptideAtlas; Q7TPD0; -.
DR PRIDE; Q7TPD0; -.
DR ProteomicsDB; 269067; -. [Q7TPD0-1]
DR ProteomicsDB; 269068; -. [Q7TPD0-2]
DR Antibodypedia; 34136; 107 antibodies from 20 providers.
DR DNASU; 229543; -.
DR Ensembl; ENSMUST00000029542; ENSMUSP00000029542; ENSMUSG00000027933. [Q7TPD0-1]
DR Ensembl; ENSMUST00000071488; ENSMUSP00000071422; ENSMUSG00000027933. [Q7TPD0-1]
DR GeneID; 229543; -.
DR KEGG; mmu:229543; -.
DR UCSC; uc008qcd.2; mouse. [Q7TPD0-1]
DR UCSC; uc008qcf.1; mouse. [Q7TPD0-2]
DR CTD; 65123; -.
DR MGI; MGI:2140050; Ints3.
DR VEuPathDB; HostDB:ENSMUSG00000027933; -.
DR eggNOG; KOG4262; Eukaryota.
DR GeneTree; ENSGT00390000014184; -.
DR HOGENOM; CLU_007659_0_0_1; -.
DR InParanoid; Q7TPD0; -.
DR OMA; LCHEDNI; -.
DR OrthoDB; 644334at2759; -.
DR PhylomeDB; Q7TPD0; -.
DR TreeFam; TF323623; -.
DR Reactome; R-MMU-6807505; RNA polymerase II transcribes snRNA genes.
DR BioGRID-ORCS; 229543; 27 hits in 107 CRISPR screens.
DR ChiTaRS; Ints3; mouse.
DR PRO; PR:Q7TPD0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q7TPD0; protein.
DR Bgee; ENSMUSG00000027933; Expressed in embryonic post-anal tail and 260 other tissues.
DR ExpressionAtlas; Q7TPD0; baseline and differential.
DR Genevisible; Q7TPD0; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0032039; C:integrator complex; ISS:HGNC-UCL.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISO:MGI.
DR GO; GO:0070876; C:SOSS complex; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISO:MGI.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0016180; P:snRNA processing; ISS:HGNC-UCL.
DR InterPro; IPR045334; INTS3.
DR InterPro; IPR019333; INTS3_N.
DR PANTHER; PTHR13587; PTHR13587; 1.
DR Pfam; PF10189; Ints3_N; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; DNA damage; DNA repair;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..1041
FT /note="Integrator complex subunit 3"
FT /id="PRO_0000259535"
FT REGION 975..1041
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 994..1011
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1015..1041
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q68E01"
FT MOD_RES 500
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 993
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68E01"
FT VAR_SEQ 321..330
FT /note="FGQQKRYQDW -> SSVHRRRSYR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038133"
FT VAR_SEQ 331..1041
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038134"
FT CONFLICT 553
FT /note="H -> P (in Ref. 1; BAC31492)"
FT /evidence="ECO:0000305"
FT CONFLICT 948
FT /note="Q -> H (in Ref. 2; AAH55344)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1041 AA; 117938 MW; 852920EFDAA5688E CRC64;
MELQKGKGTV AAAASGAAGG GGGGAGAGAP GGGRLLLSTS LDAKDELEER LERCMSIVTS
MTAGVSEREA NDALNAYVCK GPPQHEEICL GLFTLVLTEP AQAQKCYRDL ALVSRDGMNI
VLNKINQLLM EKYLKLQDTC RTQLVWLVRE LVKSGVLGAD GVCMTFMKQI AGGDVTAKNI
WLAESVLDIL TEQREWVLKS SILIAMAVYT YLRLIVDHHG TAQLQTLRQK EVDFCISLLR
ERFMECLMIG RDLVRLLQNV ARIPEFELLW KDIIHNPQAL SPQFTGILQL LQSRTSRKFL
ACRLTPDMET KLLFMTSRVR FGQQKRYQDW FQRQYLSTPD SQSLRCDLIR YICGVVHPSN
EVLSSDILPR WAIIGWLLTT CTSNVAASNA KLALFYDWLF FSPEKDSIMN IEPAILVMHH
SMKPHPAITA TLLDFMCRII PNFYPPLEGH VRQGVFSSLN HIVEKRVLAH LAPLFDNPKL
DKELRSMLRE KFPEFCSSPS PPVEVKIEEP VSMEMDNHLS DKDESCYDNA EAAFSDDEED
LNSKGKKREF RFHPIKETVV EEPVDVTPYL DQLDESLRDK VLQLQKGSDT EAQCEVMQEI
VDQVLEEDFD SEQLSVLASC LQELFKAHFR GEVLPEEVTE ESLEESVGKP LYLIFRNLCQ
MQEDNSSFSL LLDLLSELYQ KQPKIGYHLL YYLRASKAAA GKMNLYESFA QATQLGDLHT
CLMMDMKACQ EDDVRLLCHL TPSIYTEFPD ETLRSGELLN MIVAVIDSAQ LQELVCHVMM
GNLVMFRKDS VLNILIQSLD WETFEQYCAW QLFLAHNIPL ETIIPILQHL KYKEHPEALS
CLLLQLRREK PSEEMVKMVL SRPCHPDDQF TTSILRHWCM KHDELLAEHI KALLIKNNSL
PRKRQSLRSS SSKLAQLTLE QILEHLDNLR LNLANTKQNF FSQTPILQAL QHVQASCDEA
HKMKFSDLFS LAEEYEDSST KPPKSRRKAA LSSPRSRKNA TQPPNAEEES GSSSASEEED
TKPKPTKRKR KGSSAVGSDS D
