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Protein

Triple functional domain protein

Gene

Trio

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases. Involved in coordinating actin remodeling, which is necessary for cell migration and growth (By similarity). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (PubMed:22666460).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei2828ATPPROSITE-ProRule annotation1
Active sitei2918Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi2805 – 2813ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • negative regulation of fat cell differentiation Source: UniProtKB
  • regulation of Rho protein signal transduction Source: InterPro

Keywordsi

Molecular functionGuanine-nucleotide releasing factor, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-193648 NRAGE signals death through JNK
R-MMU-194840 Rho GTPase cycle
R-MMU-416476 G alpha (q) signalling events
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-418885 DCC mediated attractive signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Triple functional domain protein (EC:2.7.11.1)
Gene namesi
Name:Trio
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1927230 Trio

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1427Q → A: Abolishes Rac1 activation; when associated with E-1435. 1 Publication1
Mutagenesisi1435L → E: Abolishes Rac1 activation; when associated with A-1427. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002784741 – 3102Triple functional domain proteinAdd BLAST3102

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1627PhosphoserineCombined sources1
Modified residuei1632PhosphoserineBy similarity1
Modified residuei1633PhosphoserineBy similarity1
Modified residuei1824PhosphothreonineBy similarity1
Modified residuei2282PhosphoserineCombined sources1
Modified residuei2458PhosphoserineCombined sources1
Modified residuei2462PhosphoserineCombined sources1
Modified residuei2634PhosphoserineBy similarity1
Disulfide bondi2709 ↔ 2762PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBiQ0KL02
PaxDbiQ0KL02
PeptideAtlasiQ0KL02
PRIDEiQ0KL02

PTM databases

iPTMnetiQ0KL02
PhosphoSitePlusiQ0KL02

Expressioni

Tissue specificityi

Widespread in the brain, with more intense signals in the hippocampus, olfactory bulb, cortical layers and cerebellum. Isoform 2 is predominantly expressed in Purkinje neurons of brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000022263
CleanExiMM_TRIO
GenevisibleiQ0KL02 MM

Interactioni

Subunit structurei

Interacts with CARMIL1 (By similarity). Interacts with PTPRF/LAR (By similarity). Interacts with ANKRD26 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230148, 6 interactors
IntActiQ0KL02, 2 interactors
STRINGi10090.ENSMUSP00000087714

Structurei

3D structure databases

ProteinModelPortaliQ0KL02
SMRiQ0KL02
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 210CRAL-TRIOPROSITE-ProRule annotationAdd BLAST146
Repeati218 – 338Spectrin 1Add BLAST121
Repeati340 – 446Spectrin 2Add BLAST107
Repeati566 – 672Spectrin 3Add BLAST107
Repeati673 – 784Spectrin 4Add BLAST112
Repeati907 – 1012Spectrin 5Add BLAST106
Repeati1138 – 1244Spectrin 6Add BLAST107
Domaini1292 – 1467DH 1PROSITE-ProRule annotationAdd BLAST176
Domaini1479 – 1591PH 1PROSITE-ProRule annotationAdd BLAST113
Domaini1656 – 1721SH3 1PROSITE-ProRule annotationAdd BLAST66
Domaini1969 – 2145DH 2PROSITE-ProRule annotationAdd BLAST177
Domaini2157 – 2271PH 2PROSITE-ProRule annotationAdd BLAST115
Domaini2554 – 2619SH3 2PROSITE-ProRule annotationAdd BLAST66
Domaini2688 – 2778Ig-like C2-typeAdd BLAST91
Domaini2799 – 3053Protein kinasePROSITE-ProRule annotationAdd BLAST255

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi715 – 718Poly-Gln4
Compositional biasi1845 – 1850Poly-Ser6
Compositional biasi1951 – 1954Poly-Ser4
Compositional biasi2292 – 2324Gly-richAdd BLAST33
Compositional biasi2296 – 2557Ser-richAdd BLAST262

Domaini

The N-terminal DBL/GEF domain specifically catalyzes nucleotide exchange for RAC1, leading to the activation of Jun kinase and the production of membrane ruffles. The second DBL/GEF domain is an exchange factor for rhoa and induces the formation of stress fibers (By similarity).By similarity

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
KOG4240 Eukaryota
ENOG410XPCA LUCA
GeneTreeiENSGT00760000119030
HOGENOMiHOG000044462
HOVERGENiHBG108598
InParanoidiQ0KL02
KOiK08810
OMAiAEPIPKM
OrthoDBiEOG091G00JY
PhylomeDBiQ0KL02
TreeFamiTF318080

Family and domain databases

CDDicd00160 RhoGEF, 2 hits
cd00170 SEC14, 1 hit
Gene3Di1.20.900.10, 2 hits
2.30.29.30, 2 hits
2.60.40.10, 1 hit
3.40.525.10, 1 hit
InterProiView protein in InterPro
IPR001251 CRAL-TRIO_dom
IPR036865 CRAL-TRIO_dom_sf
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR018159 Spectrin/alpha-actinin
IPR002017 Spectrin_repeat
IPR028570 TRIO
PANTHERiPTHR22826:SF104 PTHR22826:SF104, 8 hits
PfamiView protein in Pfam
PF00650 CRAL_TRIO, 1 hit
PF07679 I-set, 1 hit
PF00169 PH, 2 hits
PF00069 Pkinase, 1 hit
PF00621 RhoGEF, 2 hits
PF00018 SH3_1, 1 hit
PF00435 Spectrin, 4 hits
SMARTiView protein in SMART
SM00409 IG, 1 hit
SM00408 IGc2, 1 hit
SM00233 PH, 2 hits
SM00325 RhoGEF, 2 hits
SM00220 S_TKc, 1 hit
SM00516 SEC14, 1 hit
SM00326 SH3, 2 hits
SM00150 SPEC, 6 hits
SUPFAMiSSF48065 SSF48065, 2 hits
SSF48726 SSF48726, 1 hit
SSF50044 SSF50044, 2 hits
SSF52087 SSF52087, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50191 CRAL_TRIO, 1 hit
PS50010 DH_2, 2 hits
PS50835 IG_LIKE, 1 hit
PS50003 PH_DOMAIN, 2 hits
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50002 SH3, 2 hits

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q0KL02-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGSSGGATA PAASSGPAAA ASAAGSGCGG GAGEGAEEAA KDLADIAAFF
60 70 80 90 100
RSGFRKNDEM KAMDVLPILK EKVAYLSGGR DKRGGPILTF PARSNHDRIR
110 120 130 140 150
QEDLRRLISY LACIPSEEVC KRGFTVIVDM RGSKWDSIKP LLKILQESFP
160 170 180 190 200
CCIHIALIIK PDNFWQKQRT NFGSSKFEFE TNMVSLEGLT KVVDPSQLTP
210 220 230 240 250
EFDGCLEYNH EEWIEIRVAF EEYISNAAHM LSRLEELQDV LAKKELPQDL
260 270 280 290 300
EGARNMIDEH SQLKKKVIKA PIEDLDLEGQ KLLQRIQSSD SFPKKNSGSG
310 320 330 340 350
NADLQNLLPK VSTMLDRLHS TRQHLHQMWH VRKLKLDQCF QLRLFEQDAE
360 370 380 390 400
KMFDWITHNK GLFLNSYTEI GTSHPHAMEL QTQHNHFAMN CMNVYVNINR
410 420 430 440 450
IMSVANRLVE SGHYASQQIK QIANQLEQEW KAFAAALDER STLLDMSSIF
460 470 480 490 500
HQKAEKYMSN VDSWCKACGE VDLPSELQDL EDAIHHHQGI YEHITLAYSE
510 520 530 540 550
VSQDGKSLLD KLQRPLTPGS SDSLTASANY SKAVHHVLDV IHEVLHHQRQ
560 570 580 590 600
LENIWQHRKV RLHQRLQLCV FQQDVQQVLD WIENHGEAFL SKHTGVGKSL
610 620 630 640 650
HRARALQKRH EDFEEVAQNT YTNADKLLEA AEQLAQTGEC DPEEIYQAAH
660 670 680 690 700
QLEDRIQDFV RRVEQRKILL DMSVSFHTHV KELWTWLEEL QKELLDDVYA
710 720 730 740 750
ESVEAVQDLI KRFGQQQQTT LQVTVNVIKE GEDLIQQLRD SAISSNKTPH
760 770 780 790 800
NSSINHIETV LQQLDEAQSQ MEELFQERKI KLELFLQLRI FERDAIDIIS
810 820 830 840 850
DLESWNDELS QQMNDFDTED LTIAEQRLQH HADKALTMNN LTFDVIHQGQ
860 870 880 890 900
DLLQYVNEVQ ASGVELLCDR DVDMATRVQD LLEFLHEKQQ ELDLAAEQHR
910 920 930 940 950
KHLEQCVQLR HLQAEVKQVL GWIRNGESML NAGLITASSL QEAEQLQREH
960 970 980 990 1000
EQFQHAIEKT HQSALQVQQK AEAMLQANHY DMDMIRDCAE KVASHWQQLM
1010 1020 1030 1040 1050
LKMEDRLKLV NASVAFYKTS EQVCSVLESL EQEYKREEDW CGGADKLGPN
1060 1070 1080 1090 1100
SETDHVTPMI SKHLEQKEAF LKACTLARRN ADVFLKYLHR NSVSMPGMVT
1110 1120 1130 1140 1150
HIKAPEQQVK NILNELFQRE NRVLHYWTMR KRRLDQCQQY VVFERSAKQA
1160 1170 1180 1190 1200
LEWIHDNGEF YLSTHTSTGS SIQHTQELLK EHEEFQITAK QTKERVKLLI
1210 1220 1230 1240 1250
QLADGFCEKG HAHAAEIKKC VTAVDKRYRD FSLRMEKYRT SLEKALGISS
1260 1270 1280 1290 1300
DSNKSSKSLQ LDIIPASIPG SEVKLRDAAH ELNEEKRKSA RRKEFIMAEL
1310 1320 1330 1340 1350
IQTEKAYVRD LRECMDTYLW EMTSGVEEIP PGIVNKELII FGNMQEIYEF
1360 1370 1380 1390 1400
HNNIFLKELE KYEQLPEDVG HCFVTWADKF QMYVTYCKNK PDSTQLILEH
1410 1420 1430 1440 1450
AGSYFDEIQQ RHGLANSISS YLIKPVQRIT KYQLLLKELL TCCEEGKGEI
1460 1470 1480 1490 1500
KDGLEVMLSV PKRANDAMHL SMLEGFDENI ESQGELILQE SFQVWDPKTL
1510 1520 1530 1540 1550
IRKGRERHLF LFEMSLVFSK EVKDSSGRSK YLYKSKLFTS ELGVTEHVEG
1560 1570 1580 1590 1600
DPCKFALWVG RTPTSDNKIV LKASSIENKQ DWIKHIREVI QERTVHLRGA
1610 1620 1630 1640 1650
LKEPIHIPKT APAARQKGRR DGEDLDSQGD GSSQPDTISI ASRTSQNTLD
1660 1670 1680 1690 1700
SDKLSGGCEL TVVIHDFTAC NSNELTIRRG QTVEVLERPH DKPDWCLVRT
1710 1720 1730 1740 1750
TDRSPAAEGL VPCGSLCIAH SRSSMEMEGI FNHKDSLSVS SNDASPPASV
1760 1770 1780 1790 1800
ASLQPHMIGA QSSPGPKRPG NTLRKWLTSP VRRLSSGKAD GHAKKLAHKH
1810 1820 1830 1840 1850
KKSREVRKSA DAGSQKDSDD SAATPQDETI EERGRNEGLS SGTLSKSSSS
1860 1870 1880 1890 1900
GMQSCGEEEG EEGADAVPLP PPMAIQQHSL LQPDSQDDKA SSRLLVRPTS
1910 1920 1930 1940 1950
SETPSAAELV SAIEELVKSK MALEDRPSSL LVDQGDSSSP SFNPSDNSLL
1960 1970 1980 1990 2000
SSSSPIDEME ERKCSSLKRR HYVLQELVET ERDYVRDLGC VVEGYMALMK
2010 2020 2030 2040 2050
EDGVPDDMKG KDKIVFGNIH QIYDWHRDFF LGELEKCLED PEKLGSLFVK
2060 2070 2080 2090 2100
HERRLHMYIV YCQNKPKSEH IVSEYIDTFF EDLKQRLGHR LQLTDLLIKP
2110 2120 2130 2140 2150
VQRIMKYQLL LKDFLKYSKK ASLDTSELEK AVEVMCIVPK RCNDMMNVGR
2160 2170 2180 2190 2200
LQGFDGKIVA QGKLLLQDTF LVTDQDAGLL PRCKERRVFL FEQIVIFSEP
2210 2220 2230 2240 2250
LDKKKGFSMP GFLFKNSIKV SCLCLEENVE SDPCKFALTS RTGDAVETFV
2260 2270 2280 2290 2300
LHSSSPSVRQ TWIHEINQIL ENQRNFLNAL TSPIEYQRNH SGGGGSGSGG
2310 2320 2330 2340 2350
SSGGGGGSGG SGASSGGSSS HGSGPSSCSS GPSSSRSRPS RIPQPVRHHP
2360 2370 2380 2390 2400
PMLVSSAASS QAEADKMSGM SAPSPSLPTP SSSLALEASL GQPSRLPLSG
2410 2420 2430 2440 2450
DSEGHERETE PIPKMKVMES PRKAPGSTSG TSQDGNTKDA RGNLGSLPLG
2460 2470 2480 2490 2500
KTRPGAVSPL NSPLSTTFPS PFGKEAFPPS SPLQKGGSFW SSIPASPASR
2510 2520 2530 2540 2550
PSSFTFPGDS DSLQRQTHRH AAPSKDTDRM STCSSASEQS VQSTQSNGEG
2560 2570 2580 2590 2600
SSSSNISTML VTHEYTAVKE DEINVYQGEV VQILASNQQN MFLVFRAATD
2610 2620 2630 2640 2650
QCPAAEGWIP GFVLGHTSAV IMENPDGTLK KSTSWHTALR LRKKSEKKDK
2660 2670 2680 2690 2700
DGKRDGKLEN GYRKPREGLS NKVSVKLLNP NYIYDVPPEF VIPLSEVTCE
2710 2720 2730 2740 2750
TGETVVFRCR VCGRPKASIT WKGPEHNTLN NDDHYSISYS DIGEATLKII
2760 2770 2780 2790 2800
GVSTEDDGIY TCIAVNDMGS ASSSASLRVL GPGSDGIVVT WKDNFDAFYS
2810 2820 2830 2840 2850
EVAELGRGRF AVVKKCDQKG TKRAVATKFV NKKLMKRDQV THELGILQNL
2860 2870 2880 2890 2900
QHPLLVSLLD TFETPTSYVL VLEMADQGRL LDCVVRWGSL TEGKVRAHLG
2910 2920 2930 2940 2950
EVLEAVRYLH NCRIAHLDLK PENILVDQSL AKPTIKLADF GDAVQLNTTY
2960 2970 2980 2990 3000
YIHQLLGNPE FAAPEIILGN PVSLTADTWS VGVLTYVLLS GVSPFLDDSV
3010 3020 3030 3040 3050
EETCLNICRL DFSFPEDYFQ GVSQKAKEFV CFLLQEDPAK RPSAALALQE
3060 3070 3080 3090 3100
QWLQAGNGSG KGTGVLDTSR LTSFIERRKH QNDVRPIRSI KNFLQSRLLP

RV
Length:3,102
Mass (Da):347,861
Last modified:September 1, 2009 - v3
Checksum:i8E8F7C44CB4F72D0
GO
Isoform 2 (identifier: Q0KL02-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1890-1908: ASSRLLVRPTSSETPSAAE → HYVDLCSVSVLAQFPYLSI
     1909-3102: Missing.

Note: No experimental confirmation available.
Show »
Length:1,908
Mass (Da):217,005
Checksum:iCB3E6B6BB738F7F1
GO
Isoform 3 (identifier: Q0KL02-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2548-2548: G → GS
     2549-2568: EGSSSSNISTMLVTHEYTAV → VRVPGSLRPSTPPPLSRQLF
     2569-3102: Missing.

Note: No experimental confirmation available.
Show »
Length:2,569
Mass (Da):288,709
Checksum:i5869317875FB1134
GO
Isoform 4 (identifier: Q0KL02-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2548-2548: G → GS

Note: No experimental confirmation available.
Show »
Length:3,103
Mass (Da):347,948
Checksum:i3471FAD8B46480A6
GO

Sequence cautioni

The sequence BAE32258 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2863E → K in BAE32258 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0233081890 – 1908ASSRL…PSAAE → HYVDLCSVSVLAQFPYLSI in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_0233091909 – 3102Missing in isoform 2. 1 PublicationAdd BLAST1194
Alternative sequenceiVSP_0378632548G → GS in isoform 3 and isoform 4. 2 Publications1
Alternative sequenceiVSP_0378642549 – 2568EGSSS…EYTAV → VRVPGSLRPSTPPPLSRQLF in isoform 3. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_0378652569 – 3102Missing in isoform 3. 1 PublicationAdd BLAST534

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB106872 mRNA Translation: BAF30811.1
AC107452 Genomic DNA No translation available.
AC116808 Genomic DNA No translation available.
AC120373 Genomic DNA No translation available.
AC130219 Genomic DNA No translation available.
BC051169 mRNA Translation: AAH51169.1
BC060724 mRNA No translation available.
AK153924 mRNA Translation: BAE32258.1 Different initiation.
CCDSiCCDS49587.1 [Q0KL02-4]
RefSeqiNP_001074771.1, NM_001081302.1 [Q0KL02-4]
XP_006520117.1, XM_006520054.3 [Q0KL02-2]
UniGeneiMm.485422

Genome annotation databases

EnsembliENSMUST00000090247; ENSMUSP00000087714; ENSMUSG00000022263 [Q0KL02-4]
GeneIDi223435
KEGGimmu:223435
UCSCiuc007vjw.1 mouse [Q0KL02-4]
uc007vjx.1 mouse [Q0KL02-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRIO_MOUSE
AccessioniPrimary (citable) accession number: Q0KL02
Secondary accession number(s): Q3U522, Q6P9K6, Q80W23
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: September 1, 2009
Last modified: March 28, 2018
This is version 106 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health