TRIO trio Rho guanine nucleotide exchange factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: TRIOprovided by HGNC
Official Full Name: trio Rho guanine nucleotide exchange factorprovided by HGNC
Primary source: HGNC:HGNC:12303
See related: Ensembl:ENSG00000038382 MIM:601893; AllianceGenome:HGNC:12303
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: tgat; MEBAS; MRD44; MRD63; ARHGEF23
Summary: 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]
Expression: Ubiquitous expression in brain (RPKM 8.0), spleen (RPKM 6.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5p15.2

Exon count:: 61

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (14143342..14510204)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (14080499..14449245)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (14143451..14510313)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach.
Title: Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach.
Pathogenic TRIO variants associated with neurodevelopmental disorders perturb the molecular regulation of TRIO and axon pathfinding in vivo.
Title: Pathogenic TRIO variants associated with neurodevelopmental disorders perturb the molecular regulation of TRIO and axon pathfinding in vivo.
Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants.
Title: Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants.
Structural/functional studies of Trio provide insights into its configuration and show that conserved linker elements enhance its activity for Rac1.
Title: Structural/functional studies of Trio provide insights into its configuration and show that conserved linker elements enhance its activity for Rac1.
Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA.
Title: Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA.
More evidence on TRIO missense mutations in the spectrin repeat domain causing severe developmental delay and recognizable facial dysmorphism with macrocephaly.
Title: More evidence on TRIO missense mutations in the spectrin repeat domain causing severe developmental delay and recognizable facial dysmorphism with macrocephaly.
Complex interactions between the angiotensin II type 1 receptor, the epidermal growth factor receptor and TRIO-dependent signaling partners.
Title: Complex interactions between the angiotensin II type 1 receptor, the epidermal growth factor receptor and TRIO-dependent signaling partners.
Genetics of physiological dysregulation: findings from the long life family study using joint models.
Title: Genetics of physiological dysregulation: findings from the long life family study using joint models.
Novel loss-of-function variants in TRIO are associated with neurodevelopmental disorder: case report.
Title: Novel loss-of-function variants in TRIO are associated with neurodevelopmental disorder: case report.
The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled.
Title: The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled.

Submit: New GeneRIF Correction See all GeneRIFs (43)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual developmental disorder, autosomal dominant 63, with macrocephaly MedGen: C5394205 OMIM: 618825 GeneReviews: TRIO-Related Neurodevelopmental Disorder	Compare labs
Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome MedGen: C4310740 OMIM: 617061 GeneReviews: TRIO-Related Neurodevelopmental Disorder	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2018-01-24) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2018-01-24) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-15185 (e-PCR)
- UniSTS:50176

RH16320 (e-PCR)
- UniSTS:23853

STS-H82060 (e-PCR)
- UniSTS:28979

G66896 (e-PCR)
- UniSTS:166965

RH121821 (e-PCR)
- UniSTS:134970

RH45695 (e-PCR)
- UniSTS:91451

RH12640 (e-PCR)
- UniSTS:15424

NoName (e-PCR)
- UniSTS:37221

HSC2LD052 (e-PCR)
- UniSTS:76647

RH80554 (e-PCR)
- UniSTS:85106

D5S2889 (e-PCR)
- UniSTS:75384

SGC35149 (e-PCR)
- UniSTS:60286

G32800 (e-PCR)
- UniSTS:117379

WI-11436 (e-PCR)
- UniSTS:54405

SHGC-35052 (e-PCR)
- UniSTS:61317

D5S2903 (e-PCR)
- UniSTS:2446

D5S2906 (e-PCR)
- UniSTS:5267

WI-15727 (e-PCR)
- UniSTS:7844

WI-18318 (e-PCR)
- UniSTS:35240

RH78758 (e-PCR)
- UniSTS:51385

SHGC-78779 (e-PCR)
- UniSTS:95677

D5S2635 (e-PCR)
- UniSTS:25543

D5S2891 (e-PCR)
- UniSTS:61663

A007A12 (e-PCR)
- UniSTS:10214

A009S08 (e-PCR)
- UniSTS:17643

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor protein tyrosine phosphatase signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in postsynaptic modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in postsynaptic modulation of chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in cell projection	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in extrinsic component of membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in postsynapse	IEA Inferred from Electronic Annotation more info
is_active_in presynaptic active zone	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic active zone	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: triple functional domain protein

Names: PTPRF-interacting protein; triple functional domain (PTPRF interacting)

NP_009049.2

EC 2.7.11.1

XP_011512409.1

EC 2.7.11.1

XP_011512410.1

EC 2.7.11.1

XP_011512411.1

EC 2.7.11.1

XP_011512412.1

EC 2.7.11.1

XP_016865290.1

EC 2.7.11.1

XP_016865291.1

EC 2.7.11.1

XP_016865292.1

EC 2.7.11.1

XP_047273635.1

EC 2.7.11.1

XP_047273637.1

EC 2.7.11.1

XP_054209360.1

EC 2.7.11.1

XP_054209361.1

EC 2.7.11.1

XP_054209362.1

EC 2.7.11.1

XP_054209363.1

EC 2.7.11.1

XP_054209364.1

EC 2.7.11.1

XP_054209365.1

EC 2.7.11.1

XP_054209366.1

EC 2.7.11.1

XP_054209367.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052962.1 RefSeqGene

Range

4641..371503

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_007118.4 → NP_009049.2 triple functional domain protein

See identical proteins and their annotated locations for NP_009049.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the protein.

Source sequence(s)

AC010419, AF091395, AI478154, AK131423, BC017268, BC035585, BF058117, BQ184284, BQ691537, U42390

Consensus CDS

CCDS3883.1

UniProtKB/Swiss-Prot

D3DTD1, O75962, Q13458, Q59EQ7, Q6PJC9, Q6ZN05, Q8IWK8

UniProtKB/TrEMBL

A0A2X0SFJ0

Related

ENSP00000339299.4, ENST00000344204.9

Conserved Domains (14) summary

smart00150
Location:1143 → 1243

SPEC; Spectrin repeats

cd11852
Location:1659 → 1718

SH3_Kalirin_1; First Src homology 3 domain of the RhoGEF kinase, Kalirin

cd11853
Location:2555 → 2613

SH3_Kalirin_2; Second Src homology 3 domain of the RhoGEF kinase, Kalirin

smart00220
Location:2796 → 3050

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00516
Location:69 → 204

SEC14; Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p)

cd00160
Location:1970 → 2143

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00176
Location:567 → 783

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam07679
Location:2685 → 2776

I-set; Immunoglobulin I-set domain

cd13240
Location:1472 → 1594

PH1_Kalirin_Trio_like; Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1

cd13241
Location:2148 → 2286

PH2_Kalirin_Trio_p63RhoGEF; p63RhoGEF pleckstrin homology (PH) domain, repeat 2

cd14113
Location:2788 → 3050

STKc_Trio_C; C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein

pfam00169
Location:2175 → 2271

PH; PH domain

pfam16609
Location:1715 → 1972

SH3-RhoG_link; SH3-RhoGEF linking unstructured region

cl11960
Location:2699 → 2776

Ig; Immunoglobulin domain

RNA

NR_134469.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site at an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC010419, AF091395, AI478154, AK131423, BC017268, BC035585, BF058117, BQ184284, BQ691537, U42390

Related

ENST00000512070.6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

14143342..14510204

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047417679.1 → XP_047273635.1 triple functional domain protein isoform X2
XM_017009802.2 → XP_016865291.1 triple functional domain protein isoform X6

UniProtKB/TrEMBL

A0A2X0SFJ0

Related

ENSP00000426342.2, ENST00000513206.5
XM_017009801.2 → XP_016865290.1 triple functional domain protein isoform X1

UniProtKB/TrEMBL

A0A2X0SFJ0
XM_047417681.1 → XP_047273637.1 triple functional domain protein isoform X7
XM_011514110.4 → XP_011512412.1 triple functional domain protein isoform X5

See identical proteins and their annotated locations for XP_011512412.1

UniProtKB/TrEMBL

A0A2X0SFJ0

Conserved Domains (14) summary

smart00150
Location:1084 → 1184

SPEC; Spectrin repeats

cd11852
Location:1600 → 1659

SH3_Kalirin_1; First Src homology 3 domain of the RhoGEF kinase, Kalirin

cd11853
Location:2496 → 2554

SH3_Kalirin_2; Second Src homology 3 domain of the RhoGEF kinase, Kalirin

smart00220
Location:2737 → 2991

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00516
Location:10 → 145

SEC14; Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p)

cd00160
Location:1911 → 2084

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00176
Location:508 → 724

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam07679
Location:2626 → 2717

I-set; Immunoglobulin I-set domain

cd13240
Location:1413 → 1535

PH1_Kalirin_Trio_like; Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1

cd13241
Location:2089 → 2227

PH2_Kalirin_Trio_p63RhoGEF; p63RhoGEF pleckstrin homology (PH) domain, repeat 2

cd14113
Location:2729 → 2991

STKc_Trio_C; C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein

pfam00169
Location:2116 → 2212

PH; PH domain

pfam16609
Location:1656 → 1913

SH3-RhoG_link; SH3-RhoGEF linking unstructured region

cl11960
Location:2640 → 2717

Ig; Immunoglobulin domain
XM_011514108.2 → XP_011512410.1 triple functional domain protein isoform X3

UniProtKB/TrEMBL

A0A2X0SFJ0

Conserved Domains (14) summary

smart00150
Location:1104 → 1204

SPEC; Spectrin repeats

cd11852
Location:1620 → 1679

SH3_Kalirin_1; First Src homology 3 domain of the RhoGEF kinase, Kalirin

cd11853
Location:2516 → 2574

SH3_Kalirin_2; Second Src homology 3 domain of the RhoGEF kinase, Kalirin

smart00220
Location:2757 → 3011

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00516
Location:30 → 165

SEC14; Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p)

cd00160
Location:1931 → 2104

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00176
Location:528 → 744

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam07679
Location:2646 → 2737

I-set; Immunoglobulin I-set domain

cd13240
Location:1433 → 1555

PH1_Kalirin_Trio_like; Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1

cd13241
Location:2109 → 2247

PH2_Kalirin_Trio_p63RhoGEF; p63RhoGEF pleckstrin homology (PH) domain, repeat 2

cd14113
Location:2749 → 3011

STKc_Trio_C; C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein

pfam00169
Location:2136 → 2232

PH; PH domain

pfam16609
Location:1676 → 1933

SH3-RhoG_link; SH3-RhoGEF linking unstructured region

cl11960
Location:2660 → 2737

Ig; Immunoglobulin domain
XM_011514109.4 → XP_011512411.1 triple functional domain protein isoform X4

UniProtKB/TrEMBL

A0A2X0SFJ0

Conserved Domains (14) summary

smart00150
Location:1094 → 1194

SPEC; Spectrin repeats

cd11852
Location:1610 → 1669

SH3_Kalirin_1; First Src homology 3 domain of the RhoGEF kinase, Kalirin

cd11853
Location:2506 → 2564

SH3_Kalirin_2; Second Src homology 3 domain of the RhoGEF kinase, Kalirin

smart00220
Location:2747 → 3001

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00516
Location:20 → 155

SEC14; Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p)

cd00160
Location:1921 → 2094

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00176
Location:518 → 734

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam07679
Location:2636 → 2727

I-set; Immunoglobulin I-set domain

cd13240
Location:1423 → 1545

PH1_Kalirin_Trio_like; Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1

cd13241
Location:2099 → 2237

PH2_Kalirin_Trio_p63RhoGEF; p63RhoGEF pleckstrin homology (PH) domain, repeat 2

cd14113
Location:2739 → 3001

STKc_Trio_C; C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein

pfam00169
Location:2126 → 2222

PH; PH domain

pfam16609
Location:1666 → 1923

SH3-RhoG_link; SH3-RhoGEF linking unstructured region

cl11960
Location:2650 → 2727

Ig; Immunoglobulin domain
XM_011514107.3 → XP_011512409.1 triple functional domain protein isoform X2

UniProtKB/TrEMBL

A0A2X0SFJ0

Conserved Domains (14) summary

smart00150
Location:1122 → 1222

SPEC; Spectrin repeats

cd11852
Location:1638 → 1697

SH3_Kalirin_1; First Src homology 3 domain of the RhoGEF kinase, Kalirin

cd11853
Location:2534 → 2592

SH3_Kalirin_2; Second Src homology 3 domain of the RhoGEF kinase, Kalirin

smart00220
Location:2775 → 3029

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00516
Location:48 → 183

SEC14; Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p)

cd00160
Location:1949 → 2122

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00176
Location:546 → 762

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam07679
Location:2664 → 2755

I-set; Immunoglobulin I-set domain

cd13240
Location:1451 → 1573

PH1_Kalirin_Trio_like; Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1

cd13241
Location:2127 → 2265

PH2_Kalirin_Trio_p63RhoGEF; p63RhoGEF pleckstrin homology (PH) domain, repeat 2

cd14113
Location:2767 → 3029

STKc_Trio_C; C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein

pfam00169
Location:2154 → 2250

PH; PH domain

pfam16609
Location:1694 → 1951

SH3-RhoG_link; SH3-RhoGEF linking unstructured region

cl11960
Location:2678 → 2755

Ig; Immunoglobulin domain
XM_017009803.2 → XP_016865292.1 triple functional domain protein isoform X8

UniProtKB/TrEMBL

A0A2X0SFJ0