Reviewed, UniProtKB/Swiss-Prot O75962 (TRIO_HUMAN)

Names and origin

Protein names

Recommended name:
    Triple functional domain protein
    EC=2.7.11.1
Alternative name(s):
    PTPRF-interacting protein

Gene names

Name:

TRIO

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	3038 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Promotes the exchange of GDP by GTP. Together with leukocyte antigen-related (LAR) protein, it could play a role in coordinating cell-matrix and cytoskeletal rearrangements necessary for cell migration and cell growth.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts to form a complex with leukocyte antigen related protein.
Subcellular location	CytoplasmBy similarity.
Tissue specificity	Highly expressed in heart, skeletal muscle, brain, pancreas, placenta, liver, kidney and lung.
Domain	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.
Post-translational modification	Phosphorylated on serine residue(s).
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 CRAL-TRIO domain. Contains 2 DH (DBL-homology) domains. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 2 PH domains. Contains 1 protein kinase domain. Contains 2 SH3 domains. Contains 4 spectrin repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Guanine-nucleotide releasing factor Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine phosphatase signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75962-1)

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.

Isoform 2 (identifier: O75962-2)

The sequence of this isoform differs from the canonical sequence as follows:
     2309-2309: G → E
     2310-3038: Missing.

Notes: Ref.1 (AAC43042) sequence differs from that shown due to a frameshift in position 2241.

Isoform 3 (identifier: O75962-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-2442: Missing.
     2443-2485: FPGDSDSLQR...QSVQSTQSNG → MLPSQAQGLL...LARNTFLKAC

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 3038

3038

Triple functional domain protein

PRO_0000080978

Regions

Domain

6 – 151

146

CRAL-TRIO

Repeat

252 – 359

108

Spectrin 1

Repeat

479 – 585

107

Spectrin 2

Repeat

819 – 925

107

Spectrin 3

Repeat

1050 – 1157

108

Spectrin 4

Domain

1233 – 1408

176

DH 1

Domain

1421 – 1532

112

PH 1

Domain

1597 – 1653

57

SH3 1

Domain

1910 – 2086

177

DH 2

Domain

2098 – 2212

115

PH 2

Domain

2492 – 2557

66

SH3 2

Domain

2626 – 2716

91

Ig-like C2-type

Domain

2737 – 2993

257

Protein kinase

Nucleotide binding

2743 – 2751

9

ATP By similarity

Compositional bias

656 – 659

4

Poly-Gln

Compositional bias

1786 – 1791

6

Poly-Ser

Compositional bias

2233 – 2253

21

Poly-Gly

Compositional bias

2486 – 2492

7

Poly-Ser

Sites

Active site

2856

1

By similarity

Binding site

2766

1

ATP By similarity

Amino acid modifications

Modified residue

1486

1

Phosphothreonine

Modified residue

1844

1

Phosphothreonine

Disulfide bond

2637 ↔ 2700

Potential

Natural variations

Alternative sequence

1 – 2442

2442

Missing in isoform 3.

VSP_023306

Alternative sequence

2309

1

G → E in isoform 2.

VSP_004467

Alternative sequence

2310 – 3038

729

Missing in isoform 2.

VSP_004468

Alternative sequence

2443 – 2485

43

FPGDS…TQSNG → MLPSQAQGLLWWVFPLFPAS SLSYPPVSYRADGLARNTFL KAC in isoform 3.

VSP_023307

Natural variant

232

1

S → T

VAR_041899

Natural variant

1585

1

T → M

VAR_041900

Natural variant

1631

1

H → R

VAR_041901

Natural variant

1919

1

V → M in a metastatic melanoma sample; somatic mutation.

VAR_041902

Natural variant

2183

1

T → M

VAR_041903

Experimental info

Mutagenesis

1240

1

E → A: 50% decrease in nucleotide exchange activity

Mutagenesis

1244

1

T → A: 40% decrease in nucleotide exchange activity

Mutagenesis

1330

1

N → A: No change in nucleotide exchange activity

Mutagenesis

1367

1

V → A: 90% decrease in nucleotide exchange activity

Mutagenesis

1368

1

Q → A: 80% decrease in nucleotide exchange activity

Mutagenesis

1369

1

R → A: 80% decrease in nucleotide exchange activity

Mutagenesis

1371

1

T → A: 80% decrease in nucleotide exchange activity

Mutagenesis

1372

1

K → A: Loss of nucleotide exchange activity

Mutagenesis

1375

1

L → A: 40% decrease in nucleotide exchange activity

Mutagenesis

1378

1

K → A: No change in nucleotide exchange activity

Mutagenesis

1379

1

E → A: 30% decrease in nucleotide exchange activity

Sequence conflict

491 – 494

4

HVRT → QLEN in AAH35585. Ref.4

Sequence conflict

491 – 494

4

HVRT → QLEN in BAD92991. Ref.5

Sequence conflict

515

1

E → D in AAH35585. Ref.4

Sequence conflict

515

1

E → D in BAD92991. Ref.5

Sequence conflict

728 – 729

2

HV → QL in AAH35585. Ref.4

Sequence conflict

728 – 729

2

HV → QL in BAD92991. Ref.5

Sequence conflict

2486 – 2504

19

SESSS…THDYT → VSASGGPRPPAPLPLSRQL in BAD92991. Ref.5

Secondary structure

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3038

Helix Strand Turn

Details...

Helix

1232 – 1257

26

Helix

1259 – 1265

7

Turn

1272 – 1276

5

Helix

1278 – 1282

5

Helix

1285 – 1294

10

Helix

1296 – 1302

7

Turn

1303 – 1305

3

Helix

1307 – 1310

4

Helix

1311 – 1316

6

Turn

1317 – 1321

5

Helix

1322 – 1341

20

Turn

1342 – 1344

3

Helix

1345 – 1353

9

Helix

1359 – 1363

5

Helix

1365 – 1382

18

Helix

1391 – 1411

21

Beta strand

1414 – 1416

3

Helix

1422 – 1424

3

Beta strand

1427 – 1436

10

Beta strand

1438 – 1442

5

Beta strand

1445 – 1464

20

Beta strand

1470 – 1479

10

Helix

1480 – 1482

3

Beta strand

1483 – 1486

4

Beta strand

1495 – 1503

9

Turn

1506 – 1508

3

Beta strand

1510 – 1513

4

Helix

1517 – 1533

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 28620F3B513EB74B	FASTA	3,038	341,617
	10 20 30 40 50 60 MKAMDVLPIL KEKVAYLSGG RDKRGGPILT FPARSNHDRI RQEDLRRLIS YLACIPSEEV 70 80 90 100 110 120 CKRGFTVIVD MRGSKWDSIK PLLKILQESF PCCIHVALII KPDNFWQKQR TNFGSSKFEF 130 140 150 160 170 180 ETNMVSLEGL TKVVDPSQLT PEFDGCLEYN HEEWIEIRVA FEDYISNATH MLSRLEE