NF2IP_MOUSE
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 03-AUG-2022, entry version 136.
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 AlphaFoldDB; O09130; -.
DR SMR; O09130; -.
DR BioGRID; 201740; 2.
DR CORUM; O09130; -.
DR IntAct; O09130; 1.
DR MINT; O09130; -.
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; 89 antibodies from 23 providers.
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; NVVDHMA; -.
DR OrthoDB; 979809at2759; -.
DR PhylomeDB; O09130; -.
DR TreeFam; TF328600; -.
DR BioGRID-ORCS; 18020; 1 hit in 73 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 cumulus cell and 227 other tissues.
DR ExpressionAtlas; O09130; baseline and differential.
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
