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Database: UniProt
Entry: O09130
LinkDB: O09130
Original site: O09130 
ID   NF2IP_MOUSE             Reviewed;         412 AA.
AC   O09130; Q8CDG2; Q9CVY5;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   29-SEP-2021, entry version 133.
DE   RecName: Full=NFATC2-interacting protein;
DE   AltName: Full=45 kDa NF-AT-interacting protein;
DE            Short=45 kDa NFAT-interacting protein;
DE   AltName: Full=Nuclear factor of activated T-cells, cytoplasmic 2-interacting protein;
GN   Name=Nfatc2ip; Synonyms=Nip45;
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], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP   INTERACTION WITH NFATC2.
RX   PubMed=8943202; DOI=10.1126/science.274.5294.1903;
RA   Hodge M.R., Chun H.J., Rengarajan J., Alt A., Lieberson R., Glimcher L.H.;
RT   "NF-AT-driven interleukin-4 transcription potentiated by NIP45.";
RL   Science 274:1903-1905(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Testis;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   INTERACTION WITH TRAF2.
RX   PubMed=11435475; DOI=10.1084/jem.194.1.89;
RA   Lieberson R., Mowen K.A., McBride K.D., Leautaud V., Zhang X., Suh W.-K.,
RA   Wu L., Glimcher L.H.;
RT   "Tumor necrosis factor receptor-associated factor (TRAF)2 represses the T
RT   helper cell type 2 response through interaction with NFAT-interacting
RT   protein (NIP45).";
RL   J. Exp. Med. 194:89-98(2001).
RN   [5]
RP   SUBCELLULAR LOCATION, AND METHYLATION.
RX   PubMed=15327772; DOI=10.1016/j.molcel.2004.06.042;
RA   Mowen K.A., Schurter B.T., Fathman J.W., David M., Glimcher L.H.;
RT   "Arginine methylation of NIP45 modulates cytokine gene expression in
RT   effector T lymphocytes.";
RL   Mol. Cell 15:559-571(2004).
RN   [6]
RP   INTERACTION WITH TRAF1, AND SUBCELLULAR LOCATION.
RX   PubMed=16352630; DOI=10.1093/intimm/dxh354;
RA   Bryce P.J., Oyoshi M.K., Kawamoto S., Oettgen H.C., Tsitsikov E.N.;
RT   "TRAF1 regulates Th2 differentiation, allergic inflammation and nuclear
RT   localization of the Th2 transcription factor, NIP45.";
RL   Int. Immunol. 18:101-111(2006).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79; SER-81; SER-83; SER-191
RP   AND SER-362, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Kidney, Liver, Lung, 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).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20133688; DOI=10.1073/pnas.0914700107;
RA   Fathman J.W., Gurish M.F., Hemmers S., Bonham K., Friend D.S., Grusby M.J.,
RA   Glimcher L.H., Mowen K.A.;
RT   "NIP45 controls the magnitude of the type 2 T helper cell response.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:3663-3668(2010).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 338-412 IN COMPLEX WITH
RP   UBE2I/UBC9, AND FUNCTION.
RX   PubMed=20077568; DOI=10.1002/prot.22667;
RA   Sekiyama N., Arita K., Ikeda Y., Hashiguchi K., Ariyoshi M., Tochio H.,
RA   Saitoh H., Shirakawa M.;
RT   "Structural basis for regulation of poly-SUMO chain by a SUMO-like domain
RT   of Nip45.";
RL   Proteins 78:1491-1502(2010).
CC   -!- FUNCTION: In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-
CC       driven transcription of a specific subset of cytokine genes, including
CC       IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4
CC       promoter; this leads to enhancement of histone H4 'Arg-3'-methylation
CC       and facilitates subsequent histone acetylation at the IL4 locus, thus
CC       promotes robust cytokine expression. Down-regulates formation of poly-
CC       SUMO chains by UBE2I/UBC9. {ECO:0000269|PubMed:20077568,
CC       ECO:0000269|PubMed:20133688}.
CC   -!- SUBUNIT: Interacts with NFATC2, TRAF1, TRAF2 and PRMT1. Interacts with
CC       UBE2I/UBC9. {ECO:0000269|PubMed:11435475, ECO:0000269|PubMed:16352630,
CC       ECO:0000269|PubMed:20077568, ECO:0000269|PubMed:8943202}.
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=TRAF1 is associated with
CC       a fraction of NFATC2IP in the cytoplasm and prevents its translocation
CC       to the nucleus.
CC   -!- TISSUE SPECIFICITY: Highest level detected in spleen, thymus and
CC       testis. {ECO:0000269|PubMed:8943202}.
CC   -!- PTM: Methylation at the N-terminus by PRMT1 modulates interaction with
CC       the NFAT complex and results in augmented cytokine production.
CC       {ECO:0000269|PubMed:15327772}.
CC   -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC       ratio and appear healthy and viable. No alteration in thymic T-cell
CC       populations, T-cell proliferation, or peripheral lymphocyte
CC       development. Inefficient type-2 antiparasitic immune response to the
CC       intestinal nematode Trichinella spiralis due to impaired IL4 and IL13
CC       cytokine production by Th2 cells. {ECO:0000269|PubMed:20133688}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB24331.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; U76759; AAC52963.1; -; mRNA.
DR   EMBL; AK005947; BAB24331.1; ALT_FRAME; mRNA.
DR   EMBL; AK030107; BAC26788.1; -; mRNA.
DR   EMBL; BC113761; AAI13762.1; -; mRNA.
DR   CCDS; CCDS21827.1; -.
DR   RefSeq; NP_035030.2; NM_010900.3.
DR   PDB; 3A4R; X-ray; 1.00 A; A/B=339-412.
DR   PDB; 3A4S; X-ray; 2.70 A; C/D=339-412.
DR   PDBsum; 3A4R; -.
DR   PDBsum; 3A4S; -.
DR   SMR; O09130; -.
DR   BioGRID; 201740; 2.
DR   CORUM; O09130; -.
DR   IntAct; O09130; 1.
DR   STRING; 10090.ENSMUSP00000075094; -.
DR   iPTMnet; O09130; -.
DR   PhosphoSitePlus; O09130; -.
DR   EPD; O09130; -.
DR   jPOST; O09130; -.
DR   MaxQB; O09130; -.
DR   PaxDb; O09130; -.
DR   PeptideAtlas; O09130; -.
DR   PRIDE; O09130; -.
DR   ProteomicsDB; 287488; -.
DR   Antibodypedia; 26645; 88 antibodies.
DR   DNASU; 18020; -.
DR   Ensembl; ENSMUST00000075671; ENSMUSP00000075094; ENSMUSG00000030722.
DR   GeneID; 18020; -.
DR   KEGG; mmu:18020; -.
DR   UCSC; uc009jra.1; mouse.
DR   CTD; 84901; -.
DR   MGI; MGI:1329015; Nfatc2ip.
DR   VEuPathDB; HostDB:ENSMUSG00000030722; -.
DR   eggNOG; KOG1769; Eukaryota.
DR   GeneTree; ENSGT00390000007119; -.
DR   HOGENOM; CLU_055132_1_0_1; -.
DR   InParanoid; O09130; -.
DR   OMA; KVRCRAD; -.
DR   OrthoDB; 979809at2759; -.
DR   PhylomeDB; O09130; -.
DR   TreeFam; TF328600; -.
DR   BioGRID-ORCS; 18020; 0 hits in 62 CRISPR screens.
DR   ChiTaRS; Nfatc2ip; mouse.
DR   EvolutionaryTrace; O09130; -.
DR   PRO; PR:O09130; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; O09130; protein.
DR   Bgee; ENSMUSG00000030722; Expressed in blastocyst and 270 other tissues.
DR   Genevisible; O09130; MM.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IC:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR   InterPro; IPR022617; Rad60/SUMO-like_dom.
DR   InterPro; IPR000626; Ubiquitin-like_dom.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   Pfam; PF11976; Rad60-SLD; 1.
DR   SMART; SM00213; UBQ; 1.
DR   SUPFAM; SSF54236; SSF54236; 2.
DR   PROSITE; PS50053; UBIQUITIN_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Coiled coil; Cytoplasm; Isopeptide bond; Methylation;
KW   Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT   CHAIN           1..412
FT                   /note="NFATC2-interacting protein"
FT                   /id="PRO_0000281009"
FT   DOMAIN          341..412
FT                   /note="Ubiquitin-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   REGION          1..38
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          58..115
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          136..206
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          168..227
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        12..27
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        146..160
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        163..187
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         49
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6AYG7"
FT   MOD_RES         51
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6AYG7"
FT   MOD_RES         79
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         81
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         83
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         118
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NCF5"
FT   MOD_RES         191
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         197
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NCF5"
FT   MOD_RES         307
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NCF5"
FT   MOD_RES         309
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NCF5"
FT   MOD_RES         311
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NCF5"
FT   MOD_RES         362
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         383
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NCF5"
FT   CROSSLNK        120
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NCF5"
FT   CONFLICT        2
FT                   /note="A -> G (in Ref. 2; BAC26788)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        200
FT                   /note="N -> D (in Ref. 2; BAC26788)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        390..391
FT                   /note="KL -> NS (in Ref. 2; BAB24331)"
FT                   /evidence="ECO:0000305"
FT   STRAND          341..346
FT                   /evidence="ECO:0007829|PDB:3A4R"
FT   STRAND          353..358
FT                   /evidence="ECO:0007829|PDB:3A4R"
FT   STRAND          360..362
FT                   /evidence="ECO:0007829|PDB:3A4S"
FT   HELIX           364..375
FT                   /evidence="ECO:0007829|PDB:3A4R"
FT   STRAND          383..386
FT                   /evidence="ECO:0007829|PDB:3A4R"
FT   HELIX           397..400
FT                   /evidence="ECO:0007829|PDB:3A4R"
FT   STRAND          407..411
FT                   /evidence="ECO:0007829|PDB:3A4R"
SQ   SEQUENCE   412 AA;  45121 MW;  DD58FE5C7055C186 CRC64;
     MAEPLRGRGP RSRGGRGARR ARGARGRCPR ARQSPARLIP DTVLVDLVSD SDEEVLEVAD
     PVEVPVARLP APAKPEQDSD SDSEGAAEGP AGAPRTLVRR RRRRLLDPGE APVVPVYSGK
     VQSSLNLIPD NSSLLKLCPS EPEDEADLTN SGSSPSEDDA LPSGSPWRKK LRKKCEKEEK
     KMEEFPDQDI SPLPQPSSRN KSRKHTEALQ KLREVNKRLQ DLRSCLSPKQ HQSPALQSTD
     DEVVLVEGPV LPQSSRLFTL KIRCRADLVR LPVRMSEPLQ NVVDHMANHL GVSPNRILLL
     FGESELSPTA TPSTLKLGVA DIIDCVVLAS SSEATETSQE LRLRVQGKEK HQMLEISLSP
     DSPLKVLMSH YEEAMGLSGH KLSFFFDGTK LSGKELPADL GLESGDLIEV WG
//
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