DEFI6_HUMAN
ID DEFI6_HUMAN Reviewed; 631 AA.
AC Q9H4E7; Q86VF4;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Differentially expressed in FDCP 6 homolog;
DE Short=DEF-6;
DE AltName: Full=IRF4-binding protein;
GN Name=DEF6; Synonyms=IBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INTERACTION WITH IRF4, AND VARIANT THR-287.
RC TISSUE=Lymph node;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION
RP WITH F-ACTIN, AND PTDINSP3-BINDING.
RX PubMed=15023524; DOI=10.1016/j.yexcr.2003.12.004;
RA Mavrakis K.J., McKinlay K.J., Jones P., Sablitzky F.;
RT "DEF6, a novel PH-DH-like domain protein, is an upstream activator of the
RT Rho GTPases Rac1, Cdc42, and RhoA.";
RL Exp. Cell Res. 294:335-344(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP PHOSPHORYLATION AT TYR-210, PTDINSP3-BINDING, AND MUTAGENESIS OF TYR-210
RP AND ARG-236.
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 [5]
RP INTERACTION WITH RAC1, PTDINSP3-BINDING, DOMAIN, AND MUTAGENESIS OF LEU-18;
RP 31-LEU--VAL-33; 225-LYS-ARG-226 AND 230-ARG-ARG-231.
RX PubMed=17121847; DOI=10.1074/jbc.m605153200;
RA Oka T., Ihara S., Fukui Y.;
RT "Cooperation of DEF6 with activated Rac in regulating cell morphology.";
RL J. Biol. Chem. 282:2011-2018(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-590, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-225, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-590, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP VARIANTS IMD87 ASP-210 AND LYS-331, INVOLVEMENT IN IMD87, FUNCTION,
RP INTERACTION WITH RAB11A, TISSUE SPECIFICITY, AND CHARACTERIZATION OF
RP VARIANTS IMD87 ASP-210 AND LYS-331.
RX PubMed=31308374; DOI=10.1038/s41467-019-10812-x;
RA Serwas N.K., Hoeger B., Ardy R.C., Stulz S.V., Sui Z., Memaran N.,
RA Meeths M., Krolo A., Yuece Petronczki O., Pfajfer L., Hou T.Z.,
RA Halliday N., Santos-Valente E., Kalinichenko A., Kennedy A., Mace E.M.,
RA Mukherjee M., Tesi B., Schrempf A., Pickl W.F., Loizou J.I., Kain R.,
RA Bidmon-Fliegenschnee B., Schickel J.N., Glauzy S., Huemer J., Garncarz W.,
RA Salzer E., Pierides I., Bilic I., Thiel J., Priftakis P., Banerjee P.P.,
RA Foerster-Waldl E., Medgyesi D., Huber W.D., Orange J.S., Meffre E.,
RA Sansom D.M., Bryceson Y.T., Altman A., Boztug K.;
RT "Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic
RT autoimmunity and aberrant CTLA-4 homeostasis.";
RL Nat. Commun. 10:3106-3106(2019).
RN [12]
RP ERRATUM OF PUBMED:31308374.
RX PubMed=31578334; DOI=10.1038/s41467-019-12454-5;
RA Serwas N.K., Hoeger B., Ardy R.C., Stulz S.V., Sui Z., Memaran N.,
RA Meeths M., Krolo A., Petronczki O.Y., Pfajfer L., Hou T.Z., Halliday N.,
RA Santos-Valente E., Kalinichenko A., Kennedy A., Mace E.M., Mukherjee M.,
RA Tesi B., Schrempf A., Pickl W.F., Loizou J.I., Kain R.,
RA Bidmon-Fliegenschnee B., Schickel J.N., Glauzy S., Huemer J., Garncarz W.,
RA Salzer E., Pierides I., Bilic I., Thiel J., Priftakis P., Banerjee P.P.,
RA Foerster-Waldl E., Medgyesi D., Huber W.D., Orange J.S., Meffre E.,
RA Sansom D.M., Bryceson Y.T., Altman A., Boztug K.;
RL Nat. Commun. 10:4555-4555(2019).
RN [13]
RP VARIANT IMD87 314-GLN--ASN-631 DEL, AND CHARACTERIZATION OF VARIANT IMD87
RP 314-GLN--ASN-631 DEL.
RX PubMed=32562707; DOI=10.1016/j.jaci.2020.05.052;
RA Fournier B., Tusseau M., Villard M., Malcus C., Chopin E., Martin E.,
RA Jorge Cordeiro D., Fabien N., Fusaro M., Gauthier A., Garnier N.,
RA Goncalves D., Lounis S., Lenoir C., Mathieu A.L., Moreews M., Perret M.,
RA Picard C., Picard C., Poitevin F., Viel S., Bertrand Y., Walzer T.,
RA Belot A., Latour S.;
RT "DEF6 deficiency, a mendelian susceptibility to EBV infection, lymphoma,
RT and autoimmunity.";
RL J. Allergy Clin. Immunol. 147:740-743(2021).
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:12651066, PubMed:15023524).
CC Can regulate cell morphology in cooperation with activated RAC1 (By
CC similarity). Involved in immune homeostasis by ensuring proper
CC trafficking and availability of T-cell regulator CTLA-4 at T-cell
CC surface (PubMed:31308374). Plays a role in Th2 (T helper cells)
CC development and/or activation, perhaps by interfering with ZAP70
CC signaling (By similarity). {ECO:0000250|UniProtKB:Q8C2K1,
CC ECO:0000269|PubMed:12651066, ECO:0000269|PubMed:15023524,
CC ECO:0000269|PubMed:31308374}.
CC -!- SUBUNIT: Interacts with ZAP70 (By similarity). Interacts with IRF4,
CC activated RAC1 and F-actin. Both the phosphorylated and non-
CC phosphorylated forms bind phosphatidylinositol 3,4,5-trisphosphate
CC (PtdInsP3). Interacts with RAB11A (PubMed:31308374). {ECO:0000250,
CC ECO:0000269|PubMed:12651066, ECO:0000269|PubMed:15023524,
CC ECO:0000269|PubMed:17121847, ECO:0000269|PubMed:31308374}.
CC -!- INTERACTION:
CC Q9H4E7; Q7Z5H3-2: ARHGAP22; NbExp=3; IntAct=EBI-745369, EBI-12084490;
CC Q9H4E7; A6NC98: CCDC88B; NbExp=3; IntAct=EBI-745369, EBI-347573;
CC Q9H4E7; Q00587: CDC42EP1; NbExp=3; IntAct=EBI-745369, EBI-744130;
CC Q9H4E7; Q9NRA8: EIF4ENIF1; NbExp=3; IntAct=EBI-745369, EBI-301024;
CC Q9H4E7; Q9NYA3: GOLGA6A; NbExp=3; IntAct=EBI-745369, EBI-11163335;
CC Q9H4E7; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-745369, EBI-5916454;
CC Q9H4E7; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-745369, EBI-10172004;
CC Q9H4E7; Q0VD86: INCA1; NbExp=3; IntAct=EBI-745369, EBI-6509505;
CC Q9H4E7; Q9H0H0: INTS2; NbExp=3; IntAct=EBI-745369, EBI-8471507;
CC Q9H4E7; Q86T90: KIAA1328; NbExp=3; IntAct=EBI-745369, EBI-3437878;
CC Q9H4E7; Q15323: KRT31; NbExp=3; IntAct=EBI-745369, EBI-948001;
CC Q9H4E7; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-745369, EBI-11985629;
CC Q9H4E7; Q96AQ6: PBXIP1; NbExp=3; IntAct=EBI-745369, EBI-740845;
CC Q9H4E7; O15162: PLSCR1; NbExp=3; IntAct=EBI-745369, EBI-740019;
CC Q9H4E7; P25786: PSMA1; NbExp=3; IntAct=EBI-745369, EBI-359352;
CC Q9H4E7; I6L996: PTK2; NbExp=6; IntAct=EBI-745369, EBI-10181089;
CC Q9H4E7; Q8WZA2: RAPGEF4; NbExp=3; IntAct=EBI-745369, EBI-948476;
CC Q9H4E7; Q86YV0: RASAL3; NbExp=3; IntAct=EBI-745369, EBI-3437896;
CC Q9H4E7; Q04864-2: REL; NbExp=3; IntAct=EBI-745369, EBI-10829018;
CC Q9H4E7; O00422: SAP18; NbExp=3; IntAct=EBI-745369, EBI-1044156;
CC Q9H4E7; O95391: SLU7; NbExp=3; IntAct=EBI-745369, EBI-750559;
CC Q9H4E7; P15884: TCF4; NbExp=4; IntAct=EBI-745369, EBI-533224;
CC Q9H4E7; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-745369, EBI-11139477;
CC Q9H4E7; P0C7X2: ZNF688; NbExp=3; IntAct=EBI-745369, EBI-4395732;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15023524}. Cell
CC membrane {ECO:0000269|PubMed:15023524, ECO:0000305|PubMed:12651066}.
CC Nucleus {ECO:0000269|PubMed:15023524}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:15023524}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:15023524}. Cell projection, filopodium
CC {ECO:0000269|PubMed:15023524}. Note=Recruited to the plasma membrane
CC upon binding phosphatidylinositol 3,4,5-trisphosphate
CC (PubMed:15023524). Binds to actin filaments (PubMed:15023524).
CC {ECO:0000269|PubMed:15023524}.
CC -!- TISSUE SPECIFICITY: Broadly expressed in the immune system. Highly
CC expressed in T cells (PubMed:31308374). {ECO:0000269|PubMed:12651066,
CC ECO:0000269|PubMed:31308374}.
CC -!- DOMAIN: The PH domain is essential for phosphatidylinositol 3,4,5-
CC trisphosphate binding. {ECO:0000269|PubMed:17121847}.
CC -!- PTM: Tyrosine-phosphorylated by tyrosine-protein kinase LCK in response
CC to T-cell activation. {ECO:0000269|PubMed:12923183}.
CC -!- DISEASE: Immunodeficiency 87 and autoimmunity (IMD87) [MIM:619573]: An
CC autosomal recessive disorder with onset in infancy or early childhood.
CC It is characterized by increased susceptibility to infections, often
CC Epstein-Barr virus, as well as lymphadenopathy or autoimmune
CC manifestations, predominantly hemolytic anemia. The disorder results
CC primarily from defects in T-cell function.
CC {ECO:0000269|PubMed:31308374, ECO:0000269|PubMed:32562707}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; AY241694; AAO91767.1; -; mRNA.
DR EMBL; AJ276095; CAC08450.1; -; mRNA.
DR EMBL; Z97832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS4802.1; -.
DR RefSeq; NP_071330.3; NM_022047.3.
DR AlphaFoldDB; Q9H4E7; -.
DR SMR; Q9H4E7; -.
DR BioGRID; 119099; 58.
DR IntAct; Q9H4E7; 46.
DR STRING; 9606.ENSP00000319831; -.
DR iPTMnet; Q9H4E7; -.
DR MetOSite; Q9H4E7; -.
DR PhosphoSitePlus; Q9H4E7; -.
DR BioMuta; DEF6; -.
DR DMDM; 74761430; -.
DR EPD; Q9H4E7; -.
DR jPOST; Q9H4E7; -.
DR MassIVE; Q9H4E7; -.
DR MaxQB; Q9H4E7; -.
DR PaxDb; Q9H4E7; -.
DR PeptideAtlas; Q9H4E7; -.
DR PRIDE; Q9H4E7; -.
DR ProteomicsDB; 80827; -.
DR Antibodypedia; 29495; 407 antibodies from 32 providers.
DR DNASU; 50619; -.
DR Ensembl; ENST00000316637.7; ENSP00000319831.5; ENSG00000023892.11.
DR GeneID; 50619; -.
DR KEGG; hsa:50619; -.
DR MANE-Select; ENST00000316637.7; ENSP00000319831.5; NM_022047.4; NP_071330.3.
DR UCSC; uc003okk.4; human.
DR CTD; 50619; -.
DR DisGeNET; 50619; -.
DR GeneCards; DEF6; -.
DR HGNC; HGNC:2760; DEF6.
DR HPA; ENSG00000023892; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 610094; gene.
DR MIM; 619573; phenotype.
DR neXtProt; NX_Q9H4E7; -.
DR OpenTargets; ENSG00000023892; -.
DR PharmGKB; PA27237; -.
DR VEuPathDB; HostDB:ENSG00000023892; -.
DR eggNOG; ENOG502QUWV; Eukaryota.
DR GeneTree; ENSGT00950000183017; -.
DR HOGENOM; CLU_029358_1_0_1; -.
DR InParanoid; Q9H4E7; -.
DR OMA; VSHQDAF; -.
DR OrthoDB; 1185498at2759; -.
DR PhylomeDB; Q9H4E7; -.
DR TreeFam; TF333160; -.
DR PathwayCommons; Q9H4E7; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR SignaLink; Q9H4E7; -.
DR SIGNOR; Q9H4E7; -.
DR BioGRID-ORCS; 50619; 12 hits in 1083 CRISPR screens.
DR ChiTaRS; DEF6; human.
DR GeneWiki; DEF6; -.
DR GenomeRNAi; 50619; -.
DR Pharos; Q9H4E7; Tbio.
DR PRO; PR:Q9H4E7; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9H4E7; protein.
DR Bgee; ENSG00000023892; Expressed in granulocyte and 140 other tissues.
DR ExpressionAtlas; Q9H4E7; baseline and differential.
DR Genevisible; Q9H4E7; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0098876; P:vesicle-mediated transport to the plasma membrane; IMP: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; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Disease variant; Membrane; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..631
FT /note="Differentially expressed in FDCP 6 homolog"
FT /id="PRO_0000294522"
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 397..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..515
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..531
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:0000305|PubMed:12923183"
FT MOD_RES 225
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT VARIANT 210
FT /note="Y -> D (in IMD87; affects function in vesicle-
FT mediated protein transport as shown by impaired CTLA4
FT trafficking to cell surface in homozygous patient T cells;
FT severely decreased protein levels in patient T cells;
FT increased protein degradation)"
FT /evidence="ECO:0000269|PubMed:31308374"
FT /id="VAR_086410"
FT VARIANT 287
FT /note="N -> T (in dbSNP:rs2395617)"
FT /evidence="ECO:0000269|PubMed:12651066"
FT /id="VAR_033193"
FT VARIANT 314..631
FT /note="Missing (in IMD87; protein not detected in
FT homozygous patient T cells or when the mutant is expressed
FT in a heterologous system)"
FT /evidence="ECO:0000269|PubMed:32562707"
FT /id="VAR_086411"
FT VARIANT 331
FT /note="E -> K (in IMD87; affects function in vesicle-
FT mediated protein transport as shown by impaired CTLA4
FT trafficking to cell surface in homozygous patient T cells;
FT decreased interaction with RAB11A)"
FT /evidence="ECO:0000269|PubMed:31308374"
FT /id="VAR_086412"
FT VARIANT 578
FT /note="R -> H (in dbSNP:rs9296146)"
FT /id="VAR_033194"
FT MUTAGEN 18
FT /note="L->N: Abolishes interaction with RAC1."
FT /evidence="ECO:0000269|PubMed:17121847"
FT MUTAGEN 31..33
FT /note="LKV->NKS: Abolishes interaction with RAC1."
FT /evidence="ECO:0000269|PubMed:17121847"
FT MUTAGEN 210
FT /note="Y->F: Loss of phosphorylation by LCK and abolition
FT of PtdInsP3 binding."
FT /evidence="ECO:0000269|PubMed:12923183"
FT MUTAGEN 225..226
FT /note="KR->AA: Abolishes PtdInsP3 binding."
FT /evidence="ECO:0000269|PubMed:17121847"
FT MUTAGEN 230..231
FT /note="RR->AA: Abolishes PtdInsP3 binding."
FT /evidence="ECO:0000269|PubMed:17121847"
FT MUTAGEN 236
FT /note="R->C: Abolishes PtdInsP3 binding."
FT /evidence="ECO:0000269|PubMed:12923183"
SQ SEQUENCE 631 AA; 73910 MW; 466A9A3D6D5CB8D8 CRC64;
MALRKELLKS IWYAFTALDV EKSGKVSKSQ LKVLSHNLYT VLHIPHDPVA LEEHFRDDDD
GPVSSQGYMP YLNKYILDKV EEGAFVKEHF DELCWTLTAK KNYRADSNGN SMLSNQDAFR
LWCLFNFLSE DKYPLIMVPD EVEYLLKKVL SSMSLEVSLG ELEELLAQEA QVAQTTGGLS
VWQFLELFNS GRCLRGVGRD TLSMAIHEVY QELIQDVLKQ GYLWKRGHLR RNWAERWFQL
QPSCLCYFGS EECKEKRGII PLDAHCCVEV LPDRDGKRCM FCVKTANRTY EMSASDTRQR
QEWTAAIQMA IRLQAEGKTS LHKDLKQKRR EQREQRERRR AAKEEELLRL QQLQEEKERK
LQELELLQEA QRQAERLLQE EEERRRSQHR ELQQALEGQL REAEQARASM QAEMELKEEE
AARQRQRIKE LEEMQQRLQE ALQLEVKARR DEESVRIAQT RLLEEEEEKL KQLMQLKEEQ
ERYIERAQQE KEELQQEMAQ QSRSLQQAQQ QLEEVRQNRQ RADEDVEAAQ RKLRQASTNV
KHWNVQMNRL MHPIEPGDKR PVTSSSFSGF QPPLLAHRDS SLKRLTRWGS QGNRTPSPNS
NEQQKSLNGG DEAPAPASTP QEDKLDPAPE N
