TRIO_HUMAN
ID TRIO_HUMAN Reviewed; 3097 AA.
AC O75962; D3DTD1; Q13458; Q59EQ7; Q6PJC9; Q6ZN05; Q8IWK8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Triple functional domain protein;
DE EC=2.7.11.1;
DE AltName: Full=PTPRF-interacting protein;
GN Name=TRIO;
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 [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1686 (ISOFORM 4), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2715-3097 (ISOFORM 1).
RC TISSUE=Kidney, and Lymph;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-3097 (ISOFORM 2), FUNCTION, INTERACTION
RP WITH PTPRF, AND TISSUE SPECIFICITY.
RC TISSUE=Fibroblast;
RX PubMed=8643598; DOI=10.1073/pnas.93.11.5466;
RA Debant A., Serra-Pages C., Seipel K., O'Brien S., Tang M., Park S.-H.,
RA Streuli M.;
RT "The multidomain protein Trio binds the LAR transmembrane tyrosine
RT phosphatase, contains a protein kinase domain, and has separate rac-
RT specific and rho-specific guanine nucleotide exchange factor domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5466-5471(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-3097 (ISOFORM 1).
RA Streuli M.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 362-3097 (ISOFORM 5).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION.
RX PubMed=10341202; DOI=10.1242/jcs.112.12.1825;
RA Seipel K., Medley Q.G., Kedersha N.L., Zhang X.A., O'Brien S.P.,
RA Serra-Pages C., Hemler M.E., Streuli M.;
RT "Trio amino-terminal guanine nucleotide exchange factor domain expression
RT promotes actin cytoskeleton reorganization, cell migration and anchorage-
RT independent cell growth.";
RL J. Cell Sci. 112:1825-1834(1999).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2282 AND SER-2455, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP INTERACTION WITH CARMIL1.
RX PubMed=19846667; DOI=10.1091/mbc.e08-10-1071;
RA Liang Y., Niederstrasser H., Edwards M., Jackson C.E., Cooper J.A.;
RT "Distinct roles for CARMIL isoforms in cell migration.";
RL Mol. Biol. Cell 20:5290-5305(2009).
RN [13]
RP IDENTIFICATION BY 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2455 AND SER-2459, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SORCS2 AND NGFR,
RP MUTAGENESIS OF LYS-2917, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22155786; DOI=10.1126/scisignal.2002060;
RA Deinhardt K., Kim T., Spellman D.S., Mains R.E., Eipper B.A., Neubert T.A.,
RA Chao M.V., Hempstead B.L.;
RT "Neuronal growth cone retraction relies on proneurotrophin receptor
RT signaling through Rac.";
RL Sci. Signal. 4:RA82-RA82(2011).
RN [17]
RP INTERACTION WITH ANKRD26.
RX PubMed=22666460; DOI=10.1371/journal.pone.0038130;
RA Liu X.F., Bera T.K., Kahue C., Escobar T., Fei Z., Raciti G.A., Pastan I.;
RT "ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DIPA regulate
RT adipogenesis in 3T3-L1 cells.";
RL PLoS ONE 7:E38130-E38130(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2455; SER-2459 AND SER-2631,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [19]
RP INVOLVEMENT IN MRD44, AND VARIANTS MRD44 SER-924; HIS-1238; THR-1922;
RP ASN-1939; VAL-2201; ASP-2247 AND GLN-2707.
RX PubMed=26721934; DOI=10.1093/hmg/ddv618;
RA Ba W., Yan Y., Reijnders M.R., Schuurs-Hoeijmakers J.H., Feenstra I.,
RA Bongers E.M., Bosch D.G., De Leeuw N., Pfundt R., Gilissen C.,
RA De Vries P.F., Veltman J.A., Hoischen A., Mefford H.C., Eichler E.E.,
RA Vissers L.E., Nadif Kasri N., De Vries B.B.;
RT "TRIO loss of function is associated with mild intellectual disability and
RT affects dendritic branching and synapse function.";
RL Hum. Mol. Genet. 25:892-902(2016).
RN [20]
RP INVOLVEMENT IN MRD44, VARIANTS MRD44 GLN-1428 AND THR-1461, VARIANT MRD63
RP ILE-1080, CHARACTERIZATION OF VARIANT MRD44 GLN-1428, AND FUNCTION.
RX PubMed=27418539; DOI=10.1136/jmedgenet-2016-103942;
RA Pengelly R.J., Greville-Heygate S., Schmidt S., Seaby E.G.,
RA Jabalameli M.R., Mehta S.G., Parker M.J., Goudie D., Fagotto-Kaufmann C.,
RA Mercer C., Debant A., Ennis S., Baralle D.;
RT "Mutations specific to the Rac-GEF domain of TRIO cause intellectual
RT disability and microcephaly.";
RL J. Med. Genet. 53:735-742(2016).
RN [21]
RP STRUCTURE BY NMR OF 1286-1466, AND MUTAGENESIS.
RX PubMed=9790533; DOI=10.1016/s0092-8674(00)81757-2;
RA Liu X., Wang H., Eberstadt M., Schnuchel A., Olejniczak E.T., Meadows R.P.,
RA Schkeryantz J.M., Janowick D.A., Harlan J.E., Harris E.A.S., Staunton D.E.,
RA Fesik S.W.;
RT "NMR structure and mutagenesis of the N-terminal Dbl homology domain of the
RT nucleotide exchange factor Trio.";
RL Cell 95:269-277(1998).
RN [22]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-291; MET-1644; ARG-1690; MET-1978 AND
RP MET-2242.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [23]
RP VARIANTS VAL-1368 AND MET-2563.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [24]
RP VARIANTS MRD44 768-GLN--VAL-3097 DEL; LYS-1299; GLN-1428; THR-1461 AND
RP ARG-1469, VARIANTS MRD63 ILE-1075; GLN-1078; GLY-1078; TRP-1078; ILE-1080
RP AND LEU-1461, INVOLVEMENT IN MRD63, FUNCTION, CHARACTERIZATION OF VARIANTS
RP MRD63 ILE-1075; GLN-1078; GLY-1078; TRP-1078; ILE-1080 AND LEU-1461, AND
RP CHARACTERIZATION OF VARIANTS MRD44 LYS-1299; GLN-1428 AND ARG-1469.
RX PubMed=32109419; DOI=10.1016/j.ajhg.2020.01.018;
RG C4RCD Research Group;
RA Barbosa S., Greville-Heygate S., Bonnet M., Godwin A., Fagotto-Kaufmann C.,
RA Kajava A.V., Laouteouet D., Mawby R., Wai H.A., Dingemans A.J.M.,
RA Hehir-Kwa J., Willems M., Capri Y., Mehta S.G., Cox H., Goudie D.,
RA Vansenne F., Turnpenny P., Vincent M., Cogne B., Lesca G., Hertecant J.,
RA Rodriguez D., Keren B., Burglen L., Gerard M., Putoux A., Cantagrel V.,
RA Siquier-Pernet K., Rio M., Banka S., Sarkar A., Steeves M., Parker M.,
RA Clement E., Moutton S., Tran Mau-Them F., Piton A., de Vries B.B.A.,
RA Guille M., Debant A., Schmidt S., Baralle D.;
RT "Opposite modulation of RAC1 by mutations in TRIO is associated with
RT distinct, domain-specific neurodevelopmental disorders.";
RL Am. J. Hum. Genet. 106:338-355(2020).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for RHOA and RAC1
CC GTPases (PubMed:8643598, PubMed:22155786, PubMed:27418539). Involved in
CC coordinating actin remodeling, which is necessary for cell migration
CC and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the
CC regulation of neurite outgrowth and lamellipodia formation
CC (PubMed:32109419). In developing hippocampal neurons, limits dendrite
CC formation, without affecting the establishment of axon polarity. Once
CC dendrites are formed, involved in the control of synaptic function by
CC regulating the endocytosis of AMPA-selective glutamate receptors
CC (AMPARs) at CA1 excitatory synapses (By similarity). May act as a
CC regulator of adipogenesis (By similarity).
CC {ECO:0000250|UniProtKB:F1M0Z1, ECO:0000269|PubMed:10341202,
CC ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:27418539,
CC ECO:0000269|PubMed:32109419, ECO:0000269|PubMed:8643598}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts with CARMIL1 (PubMed:19846667). Interacts with
CC PTPRF/LAR (PubMed:8643598). Interacts with ANKRD26 (PubMed:22666460).
CC Interacts with Bassoon/BSN and Piccolo/PCLO (By similarity). Interacts
CC with the cytoplasmic region of the heterodimer formed by NGFR and
CC SORCS2. ProNGF binding mediates dissociation of TRIO from the receptor
CC complex (PubMed:22155786). {ECO:0000250|UniProtKB:F1M0Z1,
CC ECO:0000269|PubMed:19846667, ECO:0000269|PubMed:22155786,
CC ECO:0000269|PubMed:22666460, ECO:0000269|PubMed:8643598}.
CC -!- INTERACTION:
CC O75962; Q9NRI5: DISC1; NbExp=3; IntAct=EBI-718519, EBI-529989;
CC O75962-4; P63000-1: RAC1; NbExp=2; IntAct=EBI-15915736, EBI-7212896;
CC O75962-4; Q811T9-1: Disc1; Xeno; NbExp=2; IntAct=EBI-15915736, EBI-15881527;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:22155786}. Cell
CC projection {ECO:0000250|UniProtKB:Q0KL02}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O75962-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75962-2; Sequence=VSP_004467, VSP_004468;
CC Name=3;
CC IsoId=O75962-3; Sequence=VSP_023306, VSP_023307;
CC Name=4;
CC IsoId=O75962-4; Sequence=VSP_037860;
CC Name=5;
CC IsoId=O75962-5; Sequence=VSP_037861, VSP_037862;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in heart,
CC skeletal muscle, and brain. {ECO:0000269|PubMed:8643598}.
CC -!- DOMAIN: The N-terminal DBL/GEF domain specifically catalyzes nucleotide
CC exchange for RAC1, leading to the activation of Jun kinase and the
CC production of membrane ruffles. The second DBL/GEF domain is an
CC exchange factor for rhoa and induces the formation of stress fibers.
CC -!- PTM: Phosphorylated on serine residue(s).
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 44,
CC with microcephaly (MRD44) [MIM:617061]: A disorder characterized by
CC developmental delay, variable intellectual disability, distinctive
CC facial features, and abnormalities of the fingers. Most patients also
CC have microcephaly. {ECO:0000269|PubMed:26721934,
CC ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 63,
CC with macrocephaly (MRD63) [MIM:618825]: An autosomal dominant form of
CC intellectual disability, a disorder characterized by significantly
CC below average general intellectual functioning associated with
CC impairments in adaptive behavior and manifested during the
CC developmental period. MRD63 is characterized by moderate to severe
CC impaired intellectual development with poor or absent speech, global
CC developmental delay, and variable behavioral abnormalities. Variable
CC dysmorphic features are preset in half of the patients.
CC {ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC34245.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC34245.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAC43042.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 2]:
CC Sequence=AAC34245.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TRIOID43542ch5p15.html";
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DR EMBL; AK131423; BAD18570.1; -; mRNA.
DR EMBL; AC010419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC016549; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC016654; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC016656; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026456; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471102; EAX08047.1; -; Genomic_DNA.
DR EMBL; CH471102; EAX08048.1; -; Genomic_DNA.
DR EMBL; BC035585; AAH35585.1; -; mRNA.
DR EMBL; BC017268; AAH17268.1; -; mRNA.
DR EMBL; U42390; AAC34245.1; ALT_SEQ; mRNA.
DR EMBL; AF091395; AAC43042.1; ALT_INIT; mRNA.
DR EMBL; AB209754; BAD92991.1; -; mRNA.
DR CCDS; CCDS3883.1; -. [O75962-1]
DR RefSeq; NP_009049.2; NM_007118.3. [O75962-1]
DR RefSeq; XP_011512412.1; XM_011514110.2. [O75962-4]
DR PDB; 1NTY; X-ray; 1.70 A; A=1284-1594.
DR PDB; 2NZ8; X-ray; 2.00 A; B=1285-1594.
DR PDB; 6D8Z; X-ray; 2.65 A; A/B/C=1960-2275.
DR PDBsum; 1NTY; -.
DR PDBsum; 2NZ8; -.
DR PDBsum; 6D8Z; -.
DR SMR; O75962; -.
DR BioGRID; 113055; 77.
DR DIP; DIP-37578N; -.
DR IntAct; O75962; 35.
DR MINT; O75962; -.
DR STRING; 9606.ENSP00000339299; -.
DR ChEMBL; CHEMBL4523153; -.
DR iPTMnet; O75962; -.
DR PhosphoSitePlus; O75962; -.
DR BioMuta; TRIO; -.
DR EPD; O75962; -.
DR jPOST; O75962; -.
DR MassIVE; O75962; -.
DR MaxQB; O75962; -.
DR PaxDb; O75962; -.
DR PeptideAtlas; O75962; -.
DR PRIDE; O75962; -.
DR ProteomicsDB; 50323; -. [O75962-1]
DR ProteomicsDB; 50324; -. [O75962-2]
DR ProteomicsDB; 50325; -. [O75962-3]
DR ProteomicsDB; 50326; -. [O75962-4]
DR ProteomicsDB; 50327; -. [O75962-5]
DR ABCD; O75962; 4 sequenced antibodies.
DR Antibodypedia; 2116; 80 antibodies from 19 providers.
DR DNASU; 7204; -.
DR Ensembl; ENST00000344135.5; ENSP00000339291.5; ENSG00000038382.21. [O75962-3]
DR Ensembl; ENST00000344204.9; ENSP00000339299.4; ENSG00000038382.21. [O75962-1]
DR GeneID; 7204; -.
DR KEGG; hsa:7204; -.
DR MANE-Select; ENST00000344204.9; ENSP00000339299.4; NM_007118.4; NP_009049.2.
DR UCSC; uc003jff.4; human. [O75962-1]
DR CTD; 7204; -.
DR DisGeNET; 7204; -.
DR GeneCards; TRIO; -.
DR GeneReviews; TRIO; -.
DR HGNC; HGNC:12303; TRIO.
DR HPA; ENSG00000038382; Low tissue specificity.
DR MalaCards; TRIO; -.
DR MIM; 601893; gene.
DR MIM; 617061; phenotype.
DR MIM; 618825; phenotype.
DR neXtProt; NX_O75962; -.
DR OpenTargets; ENSG00000038382; -.
DR Orphanet; 476126; Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome.
DR PharmGKB; PA36982; -.
DR VEuPathDB; HostDB:ENSG00000038382; -.
DR eggNOG; KOG0032; Eukaryota.
DR eggNOG; KOG4240; Eukaryota.
DR GeneTree; ENSGT00940000154766; -.
DR HOGENOM; CLU_000288_76_3_1; -.
DR InParanoid; O75962; -.
DR OMA; HTHVKEX; -.
DR OrthoDB; 5761at2759; -.
DR PhylomeDB; O75962; -.
DR TreeFam; TF318080; -.
DR PathwayCommons; O75962; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-418885; DCC mediated attractive signaling.
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 Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; O75962; -.
DR SIGNOR; O75962; -.
DR BioGRID-ORCS; 7204; 25 hits in 1105 CRISPR screens.
DR ChiTaRS; TRIO; human.
DR EvolutionaryTrace; O75962; -.
DR GeneWiki; TRIO_(gene); -.
DR GenomeRNAi; 7204; -.
DR Pharos; O75962; Tbio.
DR PRO; PR:O75962; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O75962; protein.
DR Bgee; ENSG00000038382; Expressed in sural nerve and 195 other tissues.
DR ExpressionAtlas; O75962; baseline and differential.
DR Genevisible; O75962; HS.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019898; C:extrinsic component of membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IEA:InterPro.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007185; P:transmembrane receptor protein tyrosine phosphatase signaling pathway; TAS:ProtInc.
DR CDD; cd00160; RhoGEF; 2.
DR CDD; cd00170; SEC14; 1.
DR CDD; cd00176; SPEC; 6.
DR Gene3D; 1.20.900.10; -; 2.
DR Gene3D; 2.30.29.30; -; 2.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.40.525.10; -; 1.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR028570; Kalirin/TRIO.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR PANTHER; PTHR22826:SF104; PTHR22826:SF104; 1.
DR Pfam; PF00650; CRAL_TRIO; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF00169; PH; 2.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00621; RhoGEF; 2.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF00435; Spectrin; 4.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00325; RhoGEF; 2.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00516; SEC14; 1.
DR SMART; SM00326; SH3; 2.
DR SMART; SM00150; SPEC; 6.
DR SUPFAM; SSF48065; SSF48065; 2.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF52087; SSF52087; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
DR PROSITE; PS50010; DH_2; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS50003; PH_DOMAIN; 2.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell projection;
KW Cytoplasm; Disease variant; Disulfide bond;
KW Guanine-nucleotide releasing factor; Immunoglobulin domain;
KW Intellectual disability; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; SH3 domain;
KW Transferase.
FT CHAIN 1..3097
FT /note="Triple functional domain protein"
FT /id="PRO_0000080978"
FT DOMAIN 65..210
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT REPEAT 311..418
FT /note="Spectrin 1"
FT REPEAT 538..644
FT /note="Spectrin 2"
FT REPEAT 878..984
FT /note="Spectrin 3"
FT REPEAT 1109..1216
FT /note="Spectrin 4"
FT DOMAIN 1292..1467
FT /note="DH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1480..1591
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1656..1721
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 1969..2145
FT /note="DH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 2157..2271
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 2551..2616
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 2685..2775
FT /note="Ig-like C2-type"
FT DOMAIN 2796..3052
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1601..1650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1779..1906
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1927..1965
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2287..2552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2639..2660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1628..1650
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1806..1835
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1836..1855
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1878..1906
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1931..1955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2319..2340
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2353..2371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2372..2390
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2397..2414
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2480..2513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2524..2552
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2915
FT /evidence="ECO:0000250"
FT BINDING 2802..2810
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 2825
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q0KL02"
FT MOD_RES 1632
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M0Z1"
FT MOD_RES 1633
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M0Z1"
FT MOD_RES 1824
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:F1M0Z1"
FT MOD_RES 2282
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2455
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 2459
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2631
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT DISULFID 2696..2759
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..2501
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023306"
FT VAR_SEQ 1..59
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037860"
FT VAR_SEQ 2368
FT /note="G -> E (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8643598"
FT /id="VSP_004467"
FT VAR_SEQ 2369..2544
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8643598"
FT /id="VSP_004468"
FT VAR_SEQ 2502..2544
FT /note="FPGDSDSLQRQTPRHAAPGKDTDRMSTCSSASEQSVQSTQSNG -> MLPSQ
FT AQGLLWWVFPLFPASSLSYPPVSYRADGLARNTFLKAC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023307"
FT VAR_SEQ 2545..2563
FT /note="SESSSSSNISTMLVTHDYT -> VSASGGPRPPAPLPLSRQL (in
FT isoform 5)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_037861"
FT VAR_SEQ 2564..3097
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_037862"
FT VARIANT 291
FT /note="S -> T (in dbSNP:rs55772118)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041899"
FT VARIANT 348
FT /note="D -> E (in dbSNP:rs16903367)"
FT /id="VAR_059802"
FT VARIANT 768..3097
FT /note="Missing (in MRD44)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083915"
FT VARIANT 924
FT /note="R -> S (in MRD44; unknown pathological significance;
FT dbSNP:rs772072746)"
FT /evidence="ECO:0000269|PubMed:26721934"
FT /id="VAR_077093"
FT VARIANT 1075
FT /note="T -> I (in MRD63; slightly increased occipitofrontal
FT circumference; increased activation of RAC1-mediated
FT signaling; increased lamellipodia formation)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083916"
FT VARIANT 1078
FT /note="R -> G (in MRD63; increased activation of RAC1-
FT mediated signaling; increased neurite outgrowth)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083917"
FT VARIANT 1078
FT /note="R -> Q (in MRD63; increased activation of RAC1-
FT mediated signaling; increased neurite outgrowth)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083918"
FT VARIANT 1078
FT /note="R -> W (in MRD63; increased activation of RAC1-
FT mediated signaling; increased neurite outgrowth;
FT dbSNP:rs1554065887)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083919"
FT VARIANT 1080
FT /note="N -> I (in MRD63; slightly increased occipitofrontal
FT circumference; increased activation of RAC1-mediated
FT signaling; increased neurite outgrowth; dbSNP:rs879255628)"
FT /evidence="ECO:0000269|PubMed:27418539,
FT ECO:0000269|PubMed:32109419"
FT /id="VAR_077094"
FT VARIANT 1238
FT /note="Y -> H (in MRD44; unknown pathological significance;
FT dbSNP:rs756004023)"
FT /evidence="ECO:0000269|PubMed:26721934"
FT /id="VAR_077095"
FT VARIANT 1299
FT /note="E -> K (in MRD44; severely decreased activation of
FT RAC1-mediated signaling; severely decreased neurite
FT outgrowth)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083920"
FT VARIANT 1368
FT /note="D -> V (found in patient with severe intellectual
FT disability; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069371"
FT VARIANT 1428
FT /note="R -> Q (in MRD44; severely decreased activation of
FT RAC1-mediated signaling; severely decreased neurite
FT outgrowth; dbSNP:rs879255626)"
FT /evidence="ECO:0000269|PubMed:27418539,
FT ECO:0000269|PubMed:32109419"
FT /id="VAR_077096"
FT VARIANT 1461
FT /note="P -> L (in MRD63; slightly increased occipitofrontal
FT circumference; slightly increased RAC1-mediated signaling;
FT slightly increased neurite outgrowth)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083921"
FT VARIANT 1461
FT /note="P -> T (in MRD44; no effect on RAC1-mediated
FT signaling; no effect on neurite outgrowth;
FT dbSNP:rs879255627)"
FT /evidence="ECO:0000269|PubMed:27418539,
FT ECO:0000269|PubMed:32109419"
FT /id="VAR_077097"
FT VARIANT 1469
FT /note="H -> R (in MRD44; decreased activation of RAC1-
FT mediated signaling; severely decreased neurite outgrowth;
FT dbSNP:rs1554070777)"
FT /evidence="ECO:0000269|PubMed:32109419"
FT /id="VAR_083922"
FT VARIANT 1613
FT /note="A -> T (in dbSNP:rs16903474)"
FT /id="VAR_059803"
FT VARIANT 1644
FT /note="T -> M (in dbSNP:rs55687522)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041900"
FT VARIANT 1690
FT /note="H -> R (in dbSNP:rs56292586)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041901"
FT VARIANT 1922
FT /note="A -> T (in MRD44; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26721934"
FT /id="VAR_077098"
FT VARIANT 1939
FT /note="S -> N (in MRD44; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26721934"
FT /id="VAR_077099"
FT VARIANT 1978
FT /note="V -> M (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041902"
FT VARIANT 2201
FT /note="L -> V (in MRD44; unknown pathological significance;
FT dbSNP:rs771342869)"
FT /evidence="ECO:0000269|PubMed:26721934"
FT /id="VAR_077100"
FT VARIANT 2242
FT /note="T -> M (in dbSNP:rs55916212)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041903"
FT VARIANT 2247
FT /note="E -> D (in MRD44; unknown pathological significance;
FT dbSNP:rs1258664728)"
FT /evidence="ECO:0000269|PubMed:26721934"
FT /id="VAR_077101"
FT VARIANT 2563
FT /note="T -> M (found in patient with severe intellectual
FT disability; unknown pathological significance;
FT dbSNP:rs751663099)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069372"
FT VARIANT 2707
FT /note="R -> Q (in MRD44; unknown pathological significance;
FT dbSNP:rs768858988)"
FT /evidence="ECO:0000269|PubMed:26721934"
FT /id="VAR_077102"
FT MUTAGEN 1299
FT /note="E->A: 50% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1303
FT /note="T->A: 40% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1389
FT /note="N->A: No change in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1426
FT /note="V->A: 90% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1427
FT /note="Q->A: 80% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1428
FT /note="R->A: 80% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1430
FT /note="T->A: 80% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1431
FT /note="K->A: Loss of nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1434
FT /note="L->A: 40% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1437
FT /note="K->A: No change in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 1438
FT /note="E->A: 30% decrease in nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:9790533"
FT MUTAGEN 2917
FT /note="K->A: Expected to disrupt kinase activity. Causes
FT reorganization of the actin cytoskeleton in the absence of
FT NGF."
FT /evidence="ECO:0000269|PubMed:22155786"
FT CONFLICT 550..553
FT /note="QLEN -> HVRT (in Ref. 5; AAC34245 and 6; AAC43042)"
FT /evidence="ECO:0000305"
FT CONFLICT 574
FT /note="D -> E (in Ref. 5; AAC34245 and 6; AAC43042)"
FT /evidence="ECO:0000305"
FT CONFLICT 787..788
FT /note="QL -> HV (in Ref. 5; AAC34245 and 6; AAC43042)"
FT /evidence="ECO:0000305"
FT HELIX 1291..1316
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1318..1324
FT /evidence="ECO:0007829|PDB:1NTY"
FT TURN 1331..1335
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1337..1341
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1344..1353
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1355..1361
FT /evidence="ECO:0007829|PDB:1NTY"
FT TURN 1362..1364
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1366..1369
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1370..1375
FT /evidence="ECO:0007829|PDB:1NTY"
FT TURN 1376..1380
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1381..1400
FT /evidence="ECO:0007829|PDB:1NTY"
FT TURN 1401..1403
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1404..1412
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1418..1422
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1424..1441
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1450..1470
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1473..1475
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1481..1483
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1486..1495
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1497..1501
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1504..1523
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1529..1538
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1539..1541
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1542..1545
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1549..1552
FT /evidence="ECO:0007829|PDB:2NZ8"
FT STRAND 1554..1562
FT /evidence="ECO:0007829|PDB:1NTY"
FT TURN 1565..1567
FT /evidence="ECO:0007829|PDB:1NTY"
FT STRAND 1569..1572
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1576..1592
FT /evidence="ECO:0007829|PDB:1NTY"
FT HELIX 1968..1992
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 1995..2002
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2006..2008
FT /evidence="ECO:0007829|PDB:6D8Z"
FT TURN 2009..2011
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2012..2016
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2019..2028
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2030..2035
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2036..2038
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2043..2050
FT /evidence="ECO:0007829|PDB:6D8Z"
FT TURN 2051..2053
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2054..2056
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2057..2075
FT /evidence="ECO:0007829|PDB:6D8Z"
FT TURN 2076..2078
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2079..2087
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2093..2120
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2126..2148
FT /evidence="ECO:0007829|PDB:6D8Z"
FT STRAND 2151..2153
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2159..2161
FT /evidence="ECO:0007829|PDB:6D8Z"
FT STRAND 2164..2173
FT /evidence="ECO:0007829|PDB:6D8Z"
FT STRAND 2184..2200
FT /evidence="ECO:0007829|PDB:6D8Z"
FT STRAND 2212..2219
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2220..2222
FT /evidence="ECO:0007829|PDB:6D8Z"
FT STRAND 2223..2226
FT /evidence="ECO:0007829|PDB:6D8Z"
FT STRAND 2235..2242
FT /evidence="ECO:0007829|PDB:6D8Z"
FT STRAND 2245..2252
FT /evidence="ECO:0007829|PDB:6D8Z"
FT HELIX 2256..2270
FT /evidence="ECO:0007829|PDB:6D8Z"
SQ SEQUENCE 3097 AA; 346900 MW; EA9236DF88B0EA24 CRC64;
MSGSSGGAAA PAASSGPAAA ASAAGSGCGG GAGEGAEEAA KDLADIAAFF RSGFRKNDEM
KAMDVLPILK EKVAYLSGGR DKRGGPILTF PARSNHDRIR QEDLRRLISY LACIPSEEVC
KRGFTVIVDM RGSKWDSIKP LLKILQESFP CCIHVALIIK PDNFWQKQRT NFGSSKFEFE
TNMVSLEGLT KVVDPSQLTP EFDGCLEYNH EEWIEIRVAF EDYISNATHM LSRLEELQDI
LAKKELPQDL EGARNMIEEH SQLKKKVIKA PIEDLDLEGQ KLLQRIQSSE SFPKKNSGSG
NADLQNLLPK VSTMLDRLHS TRQHLHQMWH VRKLKLDQCF QLRLFEQDAE KMFDWITHNK
GLFLNSYTEI GTSHPHAMEL QTQHNHFAMN CMNVYVNINR IMSVANRLVE SGHYASQQIR
QIASQLEQEW KAFAAALDER STLLDMSSIF HQKAEKYMSN VDSWCKACGE VDLPSELQDL
EDAIHHHQGI YEHITLAYSE VSQDGKSLLD KLQRPLTPGS SDSLTASANY SKAVHHVLDV
IHEVLHHQRQ LENIWQHRKV RLHQRLQLCV FQQDVQQVLD WIENHGEAFL SKHTGVGKSL
HRARALQKRH EDFEEVAQNT YTNADKLLEA AEQLAQTGEC DPEEIYQAAH QLEDRIQDFV
RRVEQRKILL DMSVSFHTHV KELWTWLEEL QKELLDDVYA ESVEAVQDLI KRFGQQQQTT
LQVTVNVIKE GEDLIQQLRD SAISSNKTPH NSSINHIETV LQQLDEAQSQ MEELFQERKI
KLELFLQLRI FERDAIDIIS DLESWNDELS QQMNDFDTED LTIAEQRLQH HADKALTMNN
LTFDVIHQGQ DLLQYVNEVQ ASGVELLCDR DVDMATRVQD LLEFLHEKQQ ELDLAAEQHR
KHLEQCVQLR HLQAEVKQVL GWIRNGESML NAGLITASSL QEAEQLQREH EQFQHAIEKT
HQSALQVQQK AEAMLQANHY DMDMIRDCAE KVASHWQQLM LKMEDRLKLV NASVAFYKTS
EQVCSVLESL EQEYKREEDW CGGADKLGPN SETDHVTPMI SKHLEQKEAF LKACTLARRN
ADVFLKYLHR NSVNMPGMVT HIKAPEQQVK NILNELFQRE NRVLHYWTMR KRRLDQCQQY
VVFERSAKQA LEWIHDNGEF YLSTHTSTGS SIQHTQELLK EHEEFQITAK QTKERVKLLI
QLADGFCEKG HAHAAEIKKC VTAVDKRYRD FSLRMEKYRT SLEKALGISS DSNKSSKSLQ
LDIIPASIPG SEVKLRDAAH ELNEEKRKSA RRKEFIMAEL IQTEKAYVRD LRECMDTYLW
EMTSGVEEIP PGIVNKELII FGNMQEIYEF HNNIFLKELE KYEQLPEDVG HCFVTWADKF
QMYVTYCKNK PDSTQLILEH AGSYFDEIQQ RHGLANSISS YLIKPVQRIT KYQLLLKELL
TCCEEGKGEI KDGLEVMLSV PKRANDAMHL SMLEGFDENI ESQGELILQE SFQVWDPKTL
IRKGRERHLF LFEMSLVFSK EVKDSSGRSK YLYKSKLFTS ELGVTEHVEG DPCKFALWVG
RTPTSDNKIV LKASSIENKQ DWIKHIREVI QERTIHLKGA LKEPIHIPKT APATRQKGRR
DGEDLDSQGD GSSQPDTISI ASRTSQNTLD SDKLSGGCEL TVVIHDFTAC NSNELTIRRG
QTVEVLERPH DKPDWCLVRT TDRSPAAEGL VPCGSLCIAH SRSSMEMEGI FNHKDSLSVS
SNDASPPASV ASLQPHMIGA QSSPGPKRPG NTLRKWLTSP VRRLSSGKAD GHVKKLAHKH
KKSREVRKSA DAGSQKDSDD SAATPQDETV EERGRNEGLS SGTLSKSSSS GMQSCGEEEG
EEGADAVPLP PPMAIQQHSL LQPDSQDDKA SSRLLVRPTS SETPSAAELV SAIEELVKSK
MALEDRPSSL LVDQGDSSSP SFNPSDNSLL SSSSPIDEME ERKSSSLKRR HYVLQELVET
ERDYVRDLGY VVEGYMALMK EDGVPDDMKG KDKIVFGNIH QIYDWHRDFF LGELEKCLED
PEKLGSLFVK HERRLHMYIA YCQNKPKSEH IVSEYIDTFF EDLKQRLGHR LQLTDLLIKP
VQRIMKYQLL LKDFLKYSKK ASLDTSELER AVEVMCIVPR RCNDMMNVGR LQGFDGKIVA
QGKLLLQDTF LVTDQDAGLL PRCRERRIFL FEQIVIFSEP LDKKKGFSMP GFLFKNSIKV
SCLCLEENVE NDPCKFALTS RTGDVVETFI LHSSSPSVRQ TWIHEINQIL ENQRNFLNAL
TSPIEYQRNH SGGGGGGGSG GSGGGGGSGG GGAPSGGSGH SGGPSSCGGA PSTSRSRPSR
IPQPVRHHPP VLVSSAASSQ AEADKMSGTS TPGPSLPPPG AAPEAGPSAP SRRPPGADAE
GSEREAEPIP KMKVLESPRK GAANASGSSP DAPAKDARAS LGTLPLGKPR AGAASPLNSP
LSSAVPSLGK EPFPPSSPLQ KGGSFWSSIP ASPASRPGSF TFPGDSDSLQ RQTPRHAAPG
KDTDRMSTCS SASEQSVQST QSNGSESSSS SNISTMLVTH DYTAVKEDEI NVYQGEVVQI
LASNQQNMFL VFRAATDQCP AAEGWIPGFV LGHTSAVIVE NPDGTLKKST SWHTALRLRK
KSEKKDKDGK REGKLENGYR KSREGLSNKV SVKLLNPNYI YDVPPEFVIP LSEVTCETGE
TVVLRCRVCG RPKASITWKG PEHNTLNNDG HYSISYSDLG EATLKIVGVT TEDDGIYTCI
AVNDMGSASS SASLRVLGPG MDGIMVTWKD NFDSFYSEVA ELGRGRFSVV KKCDQKGTKR
AVATKFVNKK LMKRDQVTHE LGILQSLQHP LLVGLLDTFE TPTSYILVLE MADQGRLLDC
VVRWGSLTEG KIRAHLGEVL EAVRYLHNCR IAHLDLKPEN ILVDESLAKP TIKLADFGDA
VQLNTTYYIH QLLGNPEFAA PEIILGNPVS LTSDTWSVGV LTYVLLSGVS PFLDDSVEET
CLNICRLDFS FPDDYFKGVS QKAKEFVCFL LQEDPAKRPS AALALQEQWL QAGNGRSTGV
LDTSRLTSFI ERRKHQNDVR PIRSIKNFLQ SRLLPRV
