TRIO

Protein identityUniProt · HPA

UniProt accession

O75962

Gene

TRIO

Ensembl

ENSG00000038382

Chromosome

5

Canonical length

3097 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles,Plasma membrane,Primary cilium,Primary cilium tip,Basal body,Cytosol

OverviewNCBI Gene

This gene encodes a large protein that functions as a GDP to GTP exchange factor. This protein promotes the reorganization of the actin cytoskeleton, thereby playing a role in cell migration and growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Canonical amino-acid sequenceUniProt

3097 residues, UniProt reviewed canonical sequence.

>O75962|TRIO
     1  MSGSSGGAAA PAASSGPAAA ASAAGSGCGG GAGEGAEEAA KDLADIAAFF RSGFRKNDEM
    61  KAMDVLPILK EKVAYLSGGR DKRGGPILTF PARSNHDRIR QEDLRRLISY LACIPSEEVC
   121  KRGFTVIVDM RGSKWDSIKP LLKILQESFP CCIHVALIIK PDNFWQKQRT NFGSSKFEFE
   181  TNMVSLEGLT KVVDPSQLTP EFDGCLEYNH EEWIEIRVAF EDYISNATHM LSRLEELQDI
   241  LAKKELPQDL EGARNMIEEH SQLKKKVIKA PIEDLDLEGQ KLLQRIQSSE SFPKKNSGSG
   301  NADLQNLLPK VSTMLDRLHS TRQHLHQMWH VRKLKLDQCF QLRLFEQDAE KMFDWITHNK
   361  GLFLNSYTEI GTSHPHAMEL QTQHNHFAMN CMNVYVNINR IMSVANRLVE SGHYASQQIR
   421  QIASQLEQEW KAFAAALDER STLLDMSSIF HQKAEKYMSN VDSWCKACGE VDLPSELQDL
   481  EDAIHHHQGI YEHITLAYSE VSQDGKSLLD KLQRPLTPGS SDSLTASANY SKAVHHVLDV
   541  IHEVLHHQRQ LENIWQHRKV RLHQRLQLCV FQQDVQQVLD WIENHGEAFL SKHTGVGKSL
   601  HRARALQKRH EDFEEVAQNT YTNADKLLEA AEQLAQTGEC DPEEIYQAAH QLEDRIQDFV
   661  RRVEQRKILL DMSVSFHTHV KELWTWLEEL QKELLDDVYA ESVEAVQDLI KRFGQQQQTT
   721  LQVTVNVIKE GEDLIQQLRD SAISSNKTPH NSSINHIETV LQQLDEAQSQ MEELFQERKI
   781  KLELFLQLRI FERDAIDIIS DLESWNDELS QQMNDFDTED LTIAEQRLQH HADKALTMNN
   841  LTFDVIHQGQ DLLQYVNEVQ ASGVELLCDR DVDMATRVQD LLEFLHEKQQ ELDLAAEQHR
   901  KHLEQCVQLR HLQAEVKQVL GWIRNGESML NAGLITASSL QEAEQLQREH EQFQHAIEKT
   961  HQSALQVQQK AEAMLQANHY DMDMIRDCAE KVASHWQQLM LKMEDRLKLV NASVAFYKTS
  1021  EQVCSVLESL EQEYKREEDW CGGADKLGPN SETDHVTPMI SKHLEQKEAF LKACTLARRN
  1081  ADVFLKYLHR NSVNMPGMVT HIKAPEQQVK NILNELFQRE NRVLHYWTMR KRRLDQCQQY
  1141  VVFERSAKQA LEWIHDNGEF YLSTHTSTGS SIQHTQELLK EHEEFQITAK QTKERVKLLI
  1201  QLADGFCEKG HAHAAEIKKC VTAVDKRYRD FSLRMEKYRT SLEKALGISS DSNKSSKSLQ
  1261  LDIIPASIPG SEVKLRDAAH ELNEEKRKSA RRKEFIMAEL IQTEKAYVRD LRECMDTYLW
  1321  EMTSGVEEIP PGIVNKELII FGNMQEIYEF HNNIFLKELE KYEQLPEDVG HCFVTWADKF
  1381  QMYVTYCKNK PDSTQLILEH AGSYFDEIQQ RHGLANSISS YLIKPVQRIT KYQLLLKELL
  1441  TCCEEGKGEI KDGLEVMLSV PKRANDAMHL SMLEGFDENI ESQGELILQE SFQVWDPKTL
  1501  IRKGRERHLF LFEMSLVFSK EVKDSSGRSK YLYKSKLFTS ELGVTEHVEG DPCKFALWVG
  1561  RTPTSDNKIV LKASSIENKQ DWIKHIREVI QERTIHLKGA LKEPIHIPKT APATRQKGRR
  1621  DGEDLDSQGD GSSQPDTISI ASRTSQNTLD SDKLSGGCEL TVVIHDFTAC NSNELTIRRG
  1681  QTVEVLERPH DKPDWCLVRT TDRSPAAEGL VPCGSLCIAH SRSSMEMEGI FNHKDSLSVS
  1741  SNDASPPASV ASLQPHMIGA QSSPGPKRPG NTLRKWLTSP VRRLSSGKAD GHVKKLAHKH
  1801  KKSREVRKSA DAGSQKDSDD SAATPQDETV EERGRNEGLS SGTLSKSSSS GMQSCGEEEG
  1861  EEGADAVPLP PPMAIQQHSL LQPDSQDDKA SSRLLVRPTS SETPSAAELV SAIEELVKSK
  1921  MALEDRPSSL LVDQGDSSSP SFNPSDNSLL SSSSPIDEME ERKSSSLKRR HYVLQELVET
  1981  ERDYVRDLGY VVEGYMALMK EDGVPDDMKG KDKIVFGNIH QIYDWHRDFF LGELEKCLED
  2041  PEKLGSLFVK HERRLHMYIA YCQNKPKSEH IVSEYIDTFF EDLKQRLGHR LQLTDLLIKP
  2101  VQRIMKYQLL LKDFLKYSKK ASLDTSELER AVEVMCIVPR RCNDMMNVGR LQGFDGKIVA
  2161  QGKLLLQDTF LVTDQDAGLL PRCRERRIFL FEQIVIFSEP LDKKKGFSMP GFLFKNSIKV
  2221  SCLCLEENVE NDPCKFALTS RTGDVVETFI LHSSSPSVRQ TWIHEINQIL ENQRNFLNAL
  2281  TSPIEYQRNH SGGGGGGGSG GSGGGGGSGG GGAPSGGSGH SGGPSSCGGA PSTSRSRPSR
  2341  IPQPVRHHPP VLVSSAASSQ AEADKMSGTS TPGPSLPPPG AAPEAGPSAP SRRPPGADAE
  2401  GSEREAEPIP KMKVLESPRK GAANASGSSP DAPAKDARAS LGTLPLGKPR AGAASPLNSP
  2461  LSSAVPSLGK EPFPPSSPLQ KGGSFWSSIP ASPASRPGSF TFPGDSDSLQ RQTPRHAAPG
  2521  KDTDRMSTCS SASEQSVQST QSNGSESSSS SNISTMLVTH DYTAVKEDEI NVYQGEVVQI
  2581  LASNQQNMFL VFRAATDQCP AAEGWIPGFV LGHTSAVIVE NPDGTLKKST SWHTALRLRK
  2641  KSEKKDKDGK REGKLENGYR KSREGLSNKV SVKLLNPNYI YDVPPEFVIP LSEVTCETGE
  2701  TVVLRCRVCG RPKASITWKG PEHNTLNNDG HYSISYSDLG EATLKIVGVT TEDDGIYTCI
  2761  AVNDMGSASS SASLRVLGPG MDGIMVTWKD NFDSFYSEVA ELGRGRFSVV KKCDQKGTKR
  2821  AVATKFVNKK LMKRDQVTHE LGILQSLQHP LLVGLLDTFE TPTSYILVLE MADQGRLLDC
  2881  VVRWGSLTEG KIRAHLGEVL EAVRYLHNCR IAHLDLKPEN ILVDESLAKP TIKLADFGDA
  2941  VQLNTTYYIH QLLGNPEFAA PEIILGNPVS LTSDTWSVGV LTYVLLSGVS PFLDDSVEET
  3001  CLNICRLDFS FPDDYFKGVS QKAKEFVCFL LQEDPAKRPS AALALQEQWL QAGNGRSTGV
  3061  LDTSRLTSFI ERRKHQNDVR PIRSIKNFLQ SRLLPRV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TRIO can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TRIO.

Disease | AllUniProt

Conditions TRIO is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal dominant 44, with microcephaly (MRD44) MIM:617061
• Intellectual developmental disorder, autosomal dominant 63, with macrocephaly (MRD63) MIM:618825

Disease | GeneticClinVar

183 pathogenic / likely-pathogenic of 1,943 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
• Intellectual developmental disorder, autosomal dominant 63, with macrocephaly
• Inborn genetic diseases
• TRIO-related disorder
• Intellectual disability

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.14

gnomAD pLI

1

gnomAD missense Z

5.32

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon guidance
• cell surface receptor protein tyrosine phosphatase signaling pathway
• negative regulation of fat cell differentiation
• neuron projection morphogenesis
• postsynaptic modulation of chemical synaptic transmission
• regulation of small GTPase mediated signal transduction

Molecular functions

• ATP binding
• guanyl-nucleotide exchange factor activity
• protein serine kinase activity
• protein serine/threonine kinase activity

Cellular components

• cell projection
• cytoplasm
• cytosol
• extrinsic component of membrane
• glutamatergic synapse
• postsynapse
• presynaptic active zone

Protein domainsUniProt · Pfam · InterPro

• Dbl homology domain
• Protein kinase domain
• CRAL-TRIO lipid binding domain
• SH3 domain
• Pleckstrin homology domain
• Spectrin repeat
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• PH-like domain superfamily
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Spectrin/alpha-actinin
• Kalirin/Triple functional domain protein, SH3 domain 1
• Dbl homology (DH) domain superfamily
• SH3-like domain superfamily
• Immunoglobulin-like domain superfamily
• CRAL-TRIO lipid binding domain superfamily
• Kalirin/Triple functional domain protein, SH3 domain 2
• Kalirin/Triple functional domain protein, pleckstrin homology (PH) domain 1
• Rho GTPase-activating Guanine Nucleotide Exchange Factors
• SOS1/NGEF-like, PH domain
• Kalirin/TRIO-like, spectrin repeats
• SH3 domain
• Protein kinase domain
• Spectrin repeat
• RhoGEF domain
• Immunoglobulin I-set domain
• Divergent CRAL/TRIO domain
• SH3-RhoGEF linking unstructured region
• SOS1/NGEF-like PH domain
• Kalirin-like, spectrin repeats
• Kalirin, SH3

KeywordsUniProt

• ATP-binding
• Cell projection
• Cytoplasm
• Disulfide bond
• Guanine-nucleotide releasing factor
• Immunoglobulin domain
• Intellectual disability
• Kinase
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Serine/threonine-protein kinase
• SH3 domain
• Transferase

InteractionsUniProt · HPA

Protein binding partners of TRIO in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ANKRD26
• CARMIL1
• SORCS2
• MAPRE1