LRRF1_MOUSE
ID LRRF1_MOUSE Reviewed; 729 AA.
AC Q3UZ39; O70323; Q3TS94;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Leucine-rich repeat flightless-interacting protein 1;
DE Short=LRR FLII-interacting protein 1;
DE AltName: Full=FLI-LRR-associated protein 1;
DE Short=Flap-1;
DE AltName: Full=H186 FLAP;
GN Name=Lrrfip1; Synonyms=Flap;
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), INTERACTION WITH FLII, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=9525888; DOI=10.1074/jbc.273.14.7920;
RA Liu Y.-T., Yin H.L.;
RT "Identification of the binding partners for flightless I, a novel protein
RT bridging the leucine-rich repeat and the gelsolin superfamilies.";
RL J. Biol. Chem. 273:7920-7927(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Egg, 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 [3]
RP IDENTIFICATION BY 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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-84; SER-88; SER-92;
RP SER-346; SER-348; SER-547 AND SER-614, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-90 AND SER-97 (ISOFORM 2), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Spleen;
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: Transcriptional repressor which preferentially binds to the
CC GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate
CC expression of TNF, EGFR and PDGFA. May control smooth muscle cells
CC proliferation following artery injury through PDGFA repression. May
CC also bind double-stranded RNA (By similarity). Positively regulates
CC Toll-like receptor (TLR) signaling in response to agonist probably by
CC competing with the negative FLII regulator for MYD88-binding (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. May also form higher oligomers. Interacts with
CC FLII. Interacts with MYD88 (By similarity). Competes with FLII for
CC MyD88-binding, even in the absence of LPS (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q3UZ39; Q925T6: Grip1; NbExp=2; IntAct=EBI-2270972, EBI-537752;
CC Q3UZ39; O42486: Bcat; Xeno; NbExp=2; IntAct=EBI-2270972, EBI-972394;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3UZ39-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UZ39-2; Sequence=VSP_020267, VSP_020268, VSP_020269,
CC VSP_020271, VSP_020272;
CC Name=3;
CC IsoId=Q3UZ39-3; Sequence=VSP_020266, VSP_020270;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:9525888}.
CC -!- DOMAIN: The DNA-binding domain is intrinsically unstructured.
CC {ECO:0000250}.
CC -!- DOMAIN: The coiled coil mediates dimerization. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the LRRFIP family. {ECO:0000305}.
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DR EMBL; AF045573; AAC40072.1; -; mRNA.
DR EMBL; AK134120; BAE22022.1; -; mRNA.
DR EMBL; AK162191; BAE36781.1; -; mRNA.
DR CCDS; CCDS35662.1; -. [Q3UZ39-2]
DR CCDS; CCDS48320.1; -. [Q3UZ39-1]
DR RefSeq; NP_001104781.1; NM_001111311.1. [Q3UZ39-1]
DR RefSeq; NP_001104782.1; NM_001111312.1.
DR RefSeq; NP_032541.1; NM_008515.4. [Q3UZ39-2]
DR AlphaFoldDB; Q3UZ39; -.
DR SMR; Q3UZ39; -.
DR BioGRID; 201207; 13.
DR IntAct; Q3UZ39; 8.
DR MINT; Q3UZ39; -.
DR STRING; 10090.ENSMUSP00000095254; -.
DR iPTMnet; Q3UZ39; -.
DR PhosphoSitePlus; Q3UZ39; -.
DR SwissPalm; Q3UZ39; -.
DR EPD; Q3UZ39; -.
DR jPOST; Q3UZ39; -.
DR MaxQB; Q3UZ39; -.
DR PaxDb; Q3UZ39; -.
DR PeptideAtlas; Q3UZ39; -.
DR PRIDE; Q3UZ39; -.
DR ProteomicsDB; 290171; -. [Q3UZ39-1]
DR ProteomicsDB; 290172; -. [Q3UZ39-2]
DR ProteomicsDB; 290173; -. [Q3UZ39-3]
DR Antibodypedia; 1000; 349 antibodies from 31 providers.
DR DNASU; 16978; -.
DR Ensembl; ENSMUST00000097649; ENSMUSP00000095254; ENSMUSG00000026305. [Q3UZ39-1]
DR Ensembl; ENSMUST00000097650; ENSMUSP00000095255; ENSMUSG00000026305. [Q3UZ39-2]
DR GeneID; 16978; -.
DR KEGG; mmu:16978; -.
DR UCSC; uc007bzr.2; mouse. [Q3UZ39-1]
DR UCSC; uc007bzs.2; mouse. [Q3UZ39-2]
DR UCSC; uc007bzu.2; mouse. [Q3UZ39-3]
DR CTD; 9208; -.
DR MGI; MGI:1342770; Lrrfip1.
DR VEuPathDB; HostDB:ENSMUSG00000026305; -.
DR eggNOG; KOG2010; Eukaryota.
DR GeneTree; ENSGT00530000063564; -.
DR HOGENOM; CLU_018924_0_0_1; -.
DR InParanoid; Q3UZ39; -.
DR OMA; KGYGFQC; -.
DR OrthoDB; 1434475at2759; -.
DR PhylomeDB; Q3UZ39; -.
DR TreeFam; TF314109; -.
DR BioGRID-ORCS; 16978; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Lrrfip1; mouse.
DR PRO; PR:Q3UZ39; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q3UZ39; protein.
DR Bgee; ENSMUSG00000026305; Expressed in secondary oocyte and 251 other tissues.
DR ExpressionAtlas; Q3UZ39; baseline and differential.
DR Genevisible; Q3UZ39; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR019139; LRRFIP1/2.
DR PANTHER; PTHR19212; PTHR19212; 3.
DR Pfam; PF09738; LRRFIP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Coiled coil; Cytoplasm; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q32MZ4"
FT CHAIN 2..729
FT /note="Leucine-rich repeat flightless-interacting protein
FT 1"
FT /id="PRO_0000248393"
FT REGION 40..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..729
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 465..567
FT /note="DNA-binding"
FT /evidence="ECO:0000250"
FT COILED 94..194
FT /evidence="ECO:0000250"
FT COMPBIAS 40..64
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..272
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..295
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..340
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..438
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 501..522
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 525..550
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 564..579
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 664..716
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:Q32MZ4"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q32MZ4"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66HF9"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q32MZ4"
FT MOD_RES 547
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66HF9"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q32MZ4"
FT VAR_SEQ 1..239
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020266"
FT VAR_SEQ 51
FT /note="E -> EIYQVQKKYYGLDTKWGDIEQWMEDSERYSRRFRRNTSASDEDERLS
FT VGSRGSLRTNGYDGDYCGSQSLSRRSGRGLSCSNLGLPSSGLASKPLSTQNGSRASMLD
FT ESSLYGARRGSACGSRAPSEYGSHLNSSSRASSRASSARASPV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9525888"
FT /id="VSP_020267"
FT VAR_SEQ 104
FT /note="I -> IKELNELKDQIQDVEGKYMQGLKEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9525888"
FT /id="VSP_020268"
FT VAR_SEQ 193
FT /note="E -> EEIRQLQQKQAGFIREISDLQETIEWKDKKIGALERQKEFFDSIRSE
FT RDDLREETVKLKEELK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9525888"
FT /id="VSP_020269"
FT VAR_SEQ 240
FT /note="L -> M (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020270"
FT VAR_SEQ 241..394
FT /note="GKAKEVEVKKEIVEKVGQRETLQNSEQEQPKPNTGKDCVDRGVSHPGEKAEN
FT QRPAEDSALSPGPLAGAKCEQQVQSQDQENTSDLKNSEQIESHKVTNKSDSRASNSPEQ
FT SSCLEGLDSEVPGPTEDLKTDLGKGSFEPCPDYILGQTAEIDK -> DVRLKKLIDERE
FT CLLEQIKKLKGQLEGRQKNNKLDLLRAEDGILENGTDAHVMDLQRDANRQISDLKFKLA
FT KSEQEITALEQNVIRLESQVTRYRSAAENAEKIEDELKAEKRKLQRELRSALDKTEELE
FT VSNGHLVKRLEKMKANRSALLSQQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9525888"
FT /id="VSP_020271"
FT VAR_SEQ 395..729
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9525888"
FT /id="VSP_020272"
FT CONFLICT 122
FT /note="N -> K (in Ref. 2; BAE22022)"
FT /evidence="ECO:0000305"
FT MOD_RES Q3UZ39-2:90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES Q3UZ39-2:97
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 729 AA; 79249 MW; 6BCCA3E8C976BF44 CRC64;
MTSPEGAQNK EIDCLSPEAQ RLAEARLAAK RAARAEAREI RMKELERQQK EVEERPDKDF
AEKGSRNMPS LSAATLASLG GTSSRRGSGD TSISMDTEAS IREIKDSLAE VEEKYKKAMV
SNAQLDNEKT NFMYQVDTLK DMLLELEEQL AESQRQYEEK NKEFEREKHA HSILQFQFAE
VKEALRQREE MLEKHGIILN SEIATNGETS DTVNDVGYQA PTKITKEELN ALKSAGEGTL
GKAKEVEVKK EIVEKVGQRE TLQNSEQEQP KPNTGKDCVD RGVSHPGEKA ENQRPAEDSA
LSPGPLAGAK CEQQVQSQDQ ENTSDLKNSE QIESHKVTNK SDSRASNSPE QSSCLEGLDS
EVPGPTEDLK TDLGKGSFEP CPDYILGQTA EIDKVTCTDS RGTGGNQRED EVQAGDTTVE
DQVGTVASGP AKQSKGTENH GESCLKDGLG QSSERELTQE VAEPEEAIVQ IPQAGGENTI
TKADDAEGRD EKPIQAEAQA SPGAPINQSG HQDTTGPGST DAQRTPPHAK ERKKQGKSEQ
QAEALDSPQK KTKNKKKKNK KKKAATPAET CRDANEELNC QDPDVGDMEE EERLQVTDKK
QASGSPEQKI RAGSREPVED PQSGSSGKQN KVEEDGPTEG PTDILDQNSP QCEDREISPV
GEKGPQCDTS QIGSEEGHVT SQHGGQAVEN HNLDNSDLSG QLEGFNSESG GQAREEVGNS
KSKEDCTMS
