DEFI6_MOUSE
ID DEFI6_MOUSE Reviewed; 630 AA.
AC Q8C2K1; A1KXF9; B2KF17; Q0VBU6; Q3V3M7; Q80XA9; Q9CRJ2;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Differentially expressed in FDCP 6;
DE Short=DEF-6;
DE AltName: Full=IRF4-binding protein;
DE AltName: Full=SWAP-70-like adapter of T-cells;
GN Name=Def6; Synonyms=Ibp, Slat;
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] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP LOCATION, INDUCTION, INTERACTION WITH ZAP70, AND TISSUE SPECIFICITY.
RC STRAIN=B10.A;
RX PubMed=12648457; DOI=10.1016/s1074-7613(03)00054-2;
RA Tanaka Y., Bi K., Kitamura R., Hong S., Altman Y., Matsumoto A., Tabata H.,
RA Lebedeva S., Bushway P.J., Altman A.;
RT "SWAP-70-like adapter of T cells, an adapter protein that regulates early
RT TCR-initiated signaling in Th2 lineage cells.";
RL Immunity 18:403-414(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=12651066; DOI=10.1016/s0198-8859(03)00024-7;
RA Gupta S., Lee A.E., Hu C., Fanzo J.C., Goldberg I., Cattoretti G.,
RA Pernis A.B.;
RT "Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly
RT expressed in the immune system.";
RL Hum. Immunol. 64:389-401(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
RP FUNCTION, AND DISEASE.
RX PubMed=12923183; DOI=10.1074/jbc.m308960200;
RA Gupta S., Fanzo J.C., Hu C., Cox D., Jang S.Y., Lee A.E., Greenberg S.,
RA Pernis A.B.;
RT "T cell receptor engagement leads to the recruitment of IBP, a novel
RT guanine nucleotide exchange factor, to the immunological synapse.";
RL J. Biol. Chem. 278:43541-43549(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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: Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine
CC nucleotide exchange factor (GEF) which plays a role in the activation
CC of Rho GTPases RAC1, RhoA and CDC42 (PubMed:12648457, PubMed:12923183).
CC Can regulate cell morphology in cooperation with activated RAC1
CC (PubMed:12648457, PubMed:12923183). Involved in immune homeostasis by
CC ensuring proper trafficking and availability of T-cell regulator CTLA-4
CC at T-cell surface (By similarity). Plays a role in Th2 (T helper cells)
CC development and/or activation, perhaps by interfering with ZAP70
CC signaling. Required for optimal T-cell effector function, lymphocyte
CC homeostasis and the prevention of systemic autoimmunity (By
CC similarity). {ECO:0000250|UniProtKB:Q9H4E7,
CC ECO:0000269|PubMed:12648457, ECO:0000269|PubMed:12923183}.
CC -!- SUBUNIT: Interacts with IRF4, activated RAC1 and F-actin. Both the
CC phosphorylated and non-phosphorylated forms bind phosphatidylinositol
CC 3,4,5-trisphosphate (PtdInsP3) (By similarity). Interacts with ZAP70.
CC Interacts with RAB11A (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9H4E7, ECO:0000269|PubMed:12648457}.
CC -!- INTERACTION:
CC Q8C2K1; Q61738-6: Itga7; NbExp=3; IntAct=EBI-2121188, EBI-1786329;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12648457}. Cell
CC membrane {ECO:0000269|PubMed:12648457}. Nucleus
CC {ECO:0000250|UniProtKB:Q9H4E7}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q9H4E7}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q9H4E7}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:Q9H4E7}. Note=Recruited to the plasma membrane
CC upon binding phosphatidylinositol 3,4,5-trisphosphate. Binds to actin
CC filaments. {ECO:0000250|UniProtKB:Q9H4E7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C2K1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C2K1-2; Sequence=VSP_026671;
CC -!- TISSUE SPECIFICITY: Thymus. {ECO:0000269|PubMed:12648457}.
CC -!- INDUCTION: Up-regulated in differentiating Th2 cells and down-regulated
CC in Th1 cells. {ECO:0000269|PubMed:12648457}.
CC -!- DOMAIN: The PH domain is essential for phosphatidylinositol 3,4,5-
CC trisphosphate binding.
CC -!- PTM: Tyrosine-phosphorylated by tyrosine-protein kinase LCK in response
CC to T-cell activation. {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Def6 results in spontaneous development of a
CC lupus-like syndrome in aging female mice. It is characterized by the
CC accumulation of effector/memory T-cells and IgG B-cells, profound
CC hypergammaglobulinemia, autoantibody production, and
CC glomerulonephritis. {ECO:0000269|PubMed:12923183}.
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DR EMBL; AY278770; AAQ19048.1; -; mRNA.
DR EMBL; AF329497; AAO67354.1; -; mRNA.
DR EMBL; AY241695; AAO91768.1; -; mRNA.
DR EMBL; AK010356; BAB26876.1; -; mRNA.
DR EMBL; AK038050; BAE20528.1; -; mRNA.
DR EMBL; AK088460; BAC40366.1; -; mRNA.
DR EMBL; CT009658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC120500; AAI20501.1; -; mRNA.
DR EMBL; BC131953; AAI31954.1; -; mRNA.
DR CCDS; CCDS28574.1; -. [Q8C2K1-1]
DR RefSeq; NP_081461.2; NM_027185.3.
DR AlphaFoldDB; Q8C2K1; -.
DR SMR; Q8C2K1; -.
DR BioGRID; 204758; 1.
DR IntAct; Q8C2K1; 2.
DR STRING; 10090.ENSMUSP00000002327; -.
DR iPTMnet; Q8C2K1; -.
DR PhosphoSitePlus; Q8C2K1; -.
DR EPD; Q8C2K1; -.
DR jPOST; Q8C2K1; -.
DR MaxQB; Q8C2K1; -.
DR PaxDb; Q8C2K1; -.
DR PeptideAtlas; Q8C2K1; -.
DR PRIDE; Q8C2K1; -.
DR ProteomicsDB; 277308; -. [Q8C2K1-1]
DR ProteomicsDB; 277309; -. [Q8C2K1-2]
DR Antibodypedia; 29495; 407 antibodies from 32 providers.
DR DNASU; 23853; -.
DR Ensembl; ENSMUST00000233170; ENSMUSP00000156601; ENSMUSG00000002257. [Q8C2K1-2]
DR GeneID; 23853; -.
DR KEGG; mmu:23853; -.
DR UCSC; uc008bqi.2; mouse. [Q8C2K1-1]
DR UCSC; uc012aoe.1; mouse. [Q8C2K1-2]
DR CTD; 50619; -.
DR MGI; MGI:1346328; Def6.
DR VEuPathDB; HostDB:ENSMUSG00000002257; -.
DR eggNOG; ENOG502QUWV; Eukaryota.
DR GeneTree; ENSGT00950000183017; -.
DR InParanoid; Q8C2K1; -.
DR OrthoDB; 1185498at2759; -.
DR PhylomeDB; Q8C2K1; -.
DR TreeFam; TF333160; -.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR BioGRID-ORCS; 23853; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Def6; mouse.
DR PRO; PR:Q8C2K1; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8C2K1; protein.
DR Bgee; ENSMUSG00000002257; Expressed in thymus and 159 other tissues.
DR ExpressionAtlas; Q8C2K1; baseline and differential.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098876; P:vesicle-mediated transport to the plasma membrane; ISS:UniProtKB.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Cytoskeleton; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..630
FT /note="Differentially expressed in FDCP 6"
FT /id="PRO_0000294523"
FT DOMAIN 216..312
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 318..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 378..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 552..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..397
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 585..608
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 210
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4E7"
FT MOD_RES 225
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4E7"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4E7"
FT VAR_SEQ 33..405
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12648457"
FT /id="VSP_026671"
FT CONFLICT 48
FT /note="P -> T (in Ref. 3; BAE20528)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="P -> Q (in Ref. 3; BAE20528)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="E -> K (in Ref. 2; AAO91768, 3; BAE20528 and 4;
FT AAI20501/AAI31954)"
FT /evidence="ECO:0000305"
FT CONFLICT 279
FT /note="C -> S (in Ref. 2; AAO91768)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 630 AA; 73454 MW; 309E060522DD91E0 CRC64;
MALRKELLKS IWYAFTALDV EKSGKVSKSQ LKVLSHNLYT VLNIPHDPVA LEEHFRDDDD
GPVSSQGYMP YLNKYILDKV EEGAFVKEHF DELCWTLTAK KNYRADGIGS SPLSNQDAFR
LWCLFNFLSE DKYPLIMVPD EVEYLLKKLL GSLSLEMGLG ELEELLAQDA QSAQTAVGLS
VWQFLELFNS GRCLRGVGRD SLSMAIQEVY QELIQDVLKQ GYLWKRGHLR RNWAERWFQL
QPSSLCYFGS EECKEKRGTI PLDAHCCVEV LPDREGKRCM FCVKTASRTY EMSASDTRQR
QEWTAAIQTA IRLQAEGKTS LHKDLKQKRR EQREQRERRR AAKEEELLRL QQLQEEKERK
LQELELLQEA QRQAERLLQE EEERRRSQHK ELQQALEGQL REAEQARASM QAEMELKKEE
AARQRQRIAE LEEMQERLQE ALQLEVKARR DEEAVRLAQT RLLEEEEEKL KQLMHLKEEQ
ERYIERAQQE KQELQQEMAL QSRSLQHAQQ QLEEVRQNRQ RADEDVEAAQ RKLRQASTNV
KHWNVQMNRL MHPIEPGDKR PTTSSSFTGF QPPPLARRDS SLKRLTRWGS QGNRTLSVNS
SEQKSLNGGD ETPILALASQ EEKLDPAPGN
