TIAM1_HUMAN
ID TIAM1_HUMAN Reviewed; 1591 AA.
AC Q13009; B7ZLR6; F5GZ53; Q17RT7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Rho guanine nucleotide exchange factor TIAM1 {ECO:0000305|PubMed:25684205};
DE AltName: Full=T-lymphoma invasion and metastasis-inducing protein 1 {ECO:0000250|UniProtKB:Q60610};
DE Short=TIAM-1 {ECO:0000250|UniProtKB:Q60610};
GN Name=TIAM1 {ECO:0000303|PubMed:7731688, ECO:0000312|HGNC:HGNC:11805};
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 [MRNA] (ISOFORM 1), AND VARIANT HIS-844.
RC TISSUE=Fetal brain;
RX PubMed=7731688;
RA Habets G.G.M., van der Kammen R.A., Stam J.C., Michiels F., Collard J.G.;
RT "Sequence of the human invasion-inducing TIAM1 gene, its conservation in
RT evolution and its expression in tumor cell lines of different tissue
RT origin.";
RL Oncogene 10:1371-1376(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-1023.
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 [4]
RP INTERACTION WITH RAC.
RC TISSUE=Brain;
RX PubMed=7753201; DOI=10.1038/375338a0;
RA Michiels F., Habets G.G.M., Stam J.C., van der Kammen R.A., Collard J.G.;
RT "A role for Rac in Tiam1-induced membrane ruffling and invasion.";
RL Nature 375:338-340(1995).
RN [5]
RP CHROMOSOMAL LOCATION.
RX PubMed=7736788; DOI=10.1159/000133989;
RA Habets G.G.M., van der Kammen R.A., Jenkins N.A., Gilbert D.J.,
RA Copeland N.G., Hagemeijer A., Collard J.G.;
RT "The invasion-inducing TIAM1 gene maps to human chromosome band 21q22 and
RT mouse chromosome 16.";
RL Cytogenet. Cell Genet. 70:48-51(1995).
RN [6]
RP INTERACTION WITH BAIAP2.
RX PubMed=15899863; DOI=10.1128/mcb.25.11.4602-4614.2005;
RA Connolly B.A., Rice J., Feig L.A., Buchsbaum R.J.;
RT "Tiam1-IRSp53 complex formation directs specificity of rac-mediated actin
RT cytoskeleton regulation.";
RL Mol. Cell. Biol. 25:4602-4614(2005).
RN [7]
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY
RP 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 [10]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=20332120; DOI=10.1242/jcs.059329;
RA Lampugnani M.G., Orsenigo F., Rudini N., Maddaluno L., Boulday G.,
RA Chapon F., Dejana E.;
RT "CCM1 regulates vascular-lumen organization by inducing endothelial
RT polarity.";
RL J. Cell Sci. 123:1073-1080(2010).
RN [11]
RP INTERACTION WITH EPHA8.
RX PubMed=20496116; DOI=10.1007/s10059-010-0075-2;
RA Yoo S., Shin J., Park S.;
RT "EphA8-ephrinA5 signaling and clathrin-mediated endocytosis is regulated by
RT Tiam-1, a Rac-specific guanine nucleotide exchange factor.";
RL Mol. Cells 29:603-609(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP FUNCTION, UBIQUITINATION AT LYS-1404 AND LYS-1420, AND MUTAGENESIS OF
RP LYS-1404 AND LYS-1420.
RX PubMed=25684205; DOI=10.1016/j.molcel.2014.12.040;
RA Genau H.M., Huber J., Baschieri F., Akutsu M., Doetsch V., Farhan H.,
RA Rogov V., Behrends C.;
RT "CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to
RT spatially restrict TIAM1-RAC1 signaling.";
RL Mol. Cell 57:995-1010(2015).
RN [14]
RP STRUCTURE BY NMR OF 835-935.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PDZ domain of T-cell lymphoma invasion and
RT metastasis 1 variant.";
RL Submitted (JUN-2006) to the PDB data bank.
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 841-930 IN COMPLEX WITH SYNTHETIC
RP MODEL PEPTIDE, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SDC1
RP AND CNTNAP4.
RX PubMed=20361982; DOI=10.1016/j.jmb.2010.03.047;
RA Shepherd T.R., Klaus S.M., Liu X., Ramaswamy S., DeMali K.A., Fuentes E.J.;
RT "The Tiam1 PDZ domain couples to Syndecan1 and promotes cell-matrix
RT adhesion.";
RL J. Mol. Biol. 398:730-746(2010).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 429-702, AND INTERACTION WITH
RP PARD3.
RX PubMed=23832200; DOI=10.1107/s1744309113014206;
RA Joshi M., Gakhar L., Fuentes E.J.;
RT "High-resolution structure of the Tiam1 PHn-CC-Ex domain.";
RL Acta Crystallogr. F 69:744-752(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 841-930 IN COMPLEX WITH SDC1,
RP MUTAGENESIS OF LYS-879 AND LYS-912, AND INTERACTION WITH CNTNAP4; SDC1 AND
RP SDC3.
RX PubMed=23395182; DOI=10.1016/j.str.2013.01.004;
RA Liu X., Shepherd T.R., Murray A.M., Xu Z., Fuentes E.J.;
RT "The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a
RT ligand conformation that modulates protein dynamics.";
RL Structure 21:342-354(2013).
RN [18]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-678 AND VAL-1339.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [19]
RP VARIANT HIS-1007.
RX PubMed=22100072; DOI=10.1016/j.ajhg.2011.10.011;
RA Aldahmesh M.A., Mohamed J.Y., Alkuraya H.S., Verma I.C., Puri R.D.,
RA Alaiya A.A., Rizzo W.B., Alkuraya F.S.;
RT "Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability,
RT and spastic quadriplegia.";
RL Am. J. Hum. Genet. 89:745-750(2011).
CC -!- FUNCTION: Guanyl-nucleotide exchange factor that activates RHO-like
CC proteins and connects extracellular signals to cytoskeletal activities.
CC Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream
CC signaling to regulate processes like cell adhesion and cell migration.
CC {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}.
CC -!- SUBUNIT: Component of the Par polarity complex, composed of at least
CC phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with NTRK2; mediates
CC the activation of RAC1 by BDNF. Interacts with MAPK8IP2 and CD44 (By
CC similarity). Interacts with BAIAP2. Interacts with EPHA8; regulates
CC clathrin-mediated endocytosis of EPHA8. Interacts with PARD3. Interacts
CC (via PDZ domain) with CNTNAP4, SDC1 and SDC3 (via C-terminus).
CC {ECO:0000250, ECO:0000269|PubMed:15899863, ECO:0000269|PubMed:20332120,
CC ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:20496116,
CC ECO:0000269|PubMed:23395182, ECO:0000269|PubMed:23832200,
CC ECO:0000269|PubMed:7753201}.
CC -!- INTERACTION:
CC Q13009; O14936: CASK; NbExp=2; IntAct=EBI-1050007, EBI-1215506;
CC Q13009; Q9C0A0-1: CNTNAP4; NbExp=2; IntAct=EBI-1050007, EBI-16035743;
CC Q13009; P18827: SDC1; NbExp=5; IntAct=EBI-1050007, EBI-2855248;
CC Q13009; P54763: Ephb2; Xeno; NbExp=3; IntAct=EBI-1050007, EBI-537711;
CC -!- SUBCELLULAR LOCATION: Cell junction. Cell membrane; Peripheral membrane
CC protein; Cytoplasmic side. Note=Detected at the boundary between cells
CC with actin-rich protrusions (By similarity). Presence of KRIT1, CDH5
CC and RAP1B is required for its localization to the cell junction.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13009-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13009-2; Sequence=VSP_055865, VSP_055866;
CC -!- TISSUE SPECIFICITY: Found in virtually all analyzed tumor cell lines
CC including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas.
CC -!- DOMAIN: The first PH domain mediates interaction with membranes
CC enriched in phosphoinositides. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Undergoes 'Lys-48' ubiquitination at Lys-1404 and
CC Lys-1420 by a CUL3(KBTBD6/7) E3 ubiquitin ligase complex composed of
CC CUL3, RBX1, KBTBD6 and KBTBD7. 'Lys-48' ubiquitination at Lys-1404 and
CC Lys-1420 triggers proteasomal degradation (PubMed:25684205).
CC Ubiquitination at Lys-1404 and Lys-1420 by CUL3(KBTBD6/7) also requires
CC the membrane-associated protein GABARAP and may therefore be spatially
CC restricted within the cell (PubMed:25684205).
CC {ECO:0000269|PubMed:25684205}.
CC -!- SIMILARITY: Belongs to the TIAM family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TIAM1ID42557ch21q22.html";
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DR EMBL; U16296; AAA98443.1; -; mRNA.
DR EMBL; AP000246; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000248; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000250; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000563; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117192; AAI17193.1; -; mRNA.
DR EMBL; BC117196; AAI17197.1; -; mRNA.
DR EMBL; BC143980; AAI43981.1; -; mRNA.
DR CCDS; CCDS13609.1; -. [Q13009-1]
DR RefSeq; NP_003244.2; NM_003253.2. [Q13009-1]
DR RefSeq; XP_005261094.1; XM_005261037.1.
DR RefSeq; XP_005261095.1; XM_005261038.2. [Q13009-1]
DR RefSeq; XP_011528013.1; XM_011529711.1.
DR RefSeq; XP_011528014.1; XM_011529712.1. [Q13009-1]
DR RefSeq; XP_011528015.1; XM_011529713.1. [Q13009-1]
DR RefSeq; XP_016883936.1; XM_017028447.1.
DR RefSeq; XP_016883937.1; XM_017028448.1. [Q13009-1]
DR RefSeq; XP_016883938.1; XM_017028449.1.
DR RefSeq; XP_016883939.1; XM_017028450.1. [Q13009-1]
DR RefSeq; XP_016883940.1; XM_017028451.1. [Q13009-1]
DR RefSeq; XP_016883941.1; XM_017028452.1.
DR RefSeq; XP_016883942.1; XM_017028453.1.
DR PDB; 2D8I; NMR; -; A=835-935.
DR PDB; 3KZD; X-ray; 1.30 A; A=841-930.
DR PDB; 3KZE; X-ray; 1.80 A; A/B/C=841-930.
DR PDB; 4GVC; X-ray; 1.54 A; A=841-930.
DR PDB; 4GVD; X-ray; 1.85 A; A/B=841-930.
DR PDB; 4K2O; X-ray; 2.15 A; A=429-702.
DR PDB; 4K2P; X-ray; 1.98 A; A/B/C/D=429-702.
DR PDB; 4NXP; X-ray; 2.30 A; A=841-930.
DR PDB; 4NXQ; X-ray; 2.10 A; A/B/C=841-930.
DR PDB; 4NXR; X-ray; 1.90 A; A=841-930.
DR PDBsum; 2D8I; -.
DR PDBsum; 3KZD; -.
DR PDBsum; 3KZE; -.
DR PDBsum; 4GVC; -.
DR PDBsum; 4GVD; -.
DR PDBsum; 4K2O; -.
DR PDBsum; 4K2P; -.
DR PDBsum; 4NXP; -.
DR PDBsum; 4NXQ; -.
DR PDBsum; 4NXR; -.
DR AlphaFoldDB; Q13009; -.
DR BMRB; Q13009; -.
DR SMR; Q13009; -.
DR BioGRID; 112930; 145.
DR CORUM; Q13009; -.
DR DIP; DIP-38309N; -.
DR ELM; Q13009; -.
DR IntAct; Q13009; 29.
DR MINT; Q13009; -.
DR STRING; 9606.ENSP00000286827; -.
DR ChEMBL; CHEMBL3232697; -.
DR iPTMnet; Q13009; -.
DR PhosphoSitePlus; Q13009; -.
DR BioMuta; TIAM1; -.
DR DMDM; 152031709; -.
DR EPD; Q13009; -.
DR jPOST; Q13009; -.
DR MassIVE; Q13009; -.
DR MaxQB; Q13009; -.
DR PaxDb; Q13009; -.
DR PeptideAtlas; Q13009; -.
DR PRIDE; Q13009; -.
DR ProteomicsDB; 24940; -.
DR ProteomicsDB; 59099; -. [Q13009-1]
DR Antibodypedia; 4172; 222 antibodies from 30 providers.
DR DNASU; 7074; -.
DR Ensembl; ENST00000286827.7; ENSP00000286827.3; ENSG00000156299.14. [Q13009-1]
DR Ensembl; ENST00000455508.2; ENSP00000388217.2; ENSG00000156299.14. [Q13009-2]
DR Ensembl; ENST00000541036.6; ENSP00000441570.2; ENSG00000156299.14. [Q13009-1]
DR GeneID; 7074; -.
DR KEGG; hsa:7074; -.
DR MANE-Select; ENST00000541036.6; ENSP00000441570.2; NM_001353694.2; NP_001340623.1.
DR UCSC; uc002yow.2; human. [Q13009-1]
DR CTD; 7074; -.
DR DisGeNET; 7074; -.
DR GeneCards; TIAM1; -.
DR HGNC; HGNC:11805; TIAM1.
DR HPA; ENSG00000156299; Tissue enriched (brain).
DR MIM; 600687; gene.
DR neXtProt; NX_Q13009; -.
DR OpenTargets; ENSG00000156299; -.
DR PharmGKB; PA36514; -.
DR VEuPathDB; HostDB:ENSG00000156299; -.
DR eggNOG; KOG3519; Eukaryota.
DR GeneTree; ENSGT00940000156294; -.
DR HOGENOM; CLU_000494_3_0_1; -.
DR InParanoid; Q13009; -.
DR OMA; QMQFYVP; -.
DR OrthoDB; 34437at2759; -.
DR PhylomeDB; Q13009; -.
DR TreeFam; TF319686; -.
DR PathwayCommons; Q13009; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
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-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9032845; Activated NTRK2 signals through CDK5.
DR SignaLink; Q13009; -.
DR SIGNOR; Q13009; -.
DR BioGRID-ORCS; 7074; 22 hits in 1083 CRISPR screens.
DR ChiTaRS; TIAM1; human.
DR EvolutionaryTrace; Q13009; -.
DR GenomeRNAi; 7074; -.
DR Pharos; Q13009; Tbio.
DR PRO; PR:Q13009; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q13009; protein.
DR Bgee; ENSG00000156299; Expressed in cerebellar vermis and 198 other tissues.
DR ExpressionAtlas; Q13009; baseline and differential.
DR Genevisible; Q13009; HS.
DR GO; GO:0044291; C:cell-cell contact zone; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019900; F:kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0090630; P:activation of GTPase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; NAS:BHF-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016601; P:Rac protein signal transduction; IMP:UniProtKB.
DR GO; GO:1904338; P:regulation of dopaminergic neuron differentiation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; IDA:BHF-UCL.
DR GO; GO:2000050; P:regulation of non-canonical Wnt signaling pathway; ISS:ParkinsonsUK-UCL.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IBA:GO_Central.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; NAS:ParkinsonsUK-UCL.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR003116; RBD_dom.
DR InterPro; IPR033360; Tiam1.
DR InterPro; IPR043537; Tiam1/Tiam2/Sif.
DR InterPro; IPR040655; TIAM1_CC-Ex.
DR PANTHER; PTHR46001; PTHR46001; 1.
DR PANTHER; PTHR46001:SF1; PTHR46001:SF1; 1.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF00169; PH; 2.
DR Pfam; PF02196; RBD; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF18385; Tiam_CC_Ex; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00455; RBD; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50898; RBD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Guanine-nucleotide releasing factor; Isopeptide bond; Lipid-binding;
KW Lipoprotein; Membrane; Myristate; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..1591
FT /note="Rho guanine nucleotide exchange factor TIAM1"
FT /id="PRO_0000080976"
FT DOMAIN 434..549
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 765..832
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 845..908
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1040..1234
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1261..1397
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 393..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 939..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1456..1482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..45
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..379
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 958..977
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1011..1032
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1458..1473
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60610"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60610"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60610"
FT MOD_RES 829
FT /note="Phosphotyrosine; by NTRK2"
FT /evidence="ECO:0000250|UniProtKB:Q60610"
FT MOD_RES 1323
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q60610"
FT MOD_RES 1519
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60610"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT CROSSLNK 1404
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25684205"
FT CROSSLNK 1420
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25684205"
FT VAR_SEQ 715..739
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055865"
FT VAR_SEQ 797..831
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055866"
FT VARIANT 247
FT /note="G -> R (in dbSNP:rs2070418)"
FT /id="VAR_051991"
FT VARIANT 247
FT /note="G -> V (in dbSNP:rs2070417)"
FT /id="VAR_051992"
FT VARIANT 678
FT /note="R -> C (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1192824496)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035977"
FT VARIANT 844
FT /note="Q -> H (in dbSNP:rs16987932)"
FT /evidence="ECO:0000269|PubMed:7731688"
FT /id="VAR_051993"
FT VARIANT 1007
FT /note="R -> H (in dbSNP:rs77092908)"
FT /evidence="ECO:0000269|PubMed:22100072"
FT /id="VAR_067424"
FT VARIANT 1023
FT /note="D -> V (in dbSNP:rs75483199)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_071102"
FT VARIANT 1339
FT /note="A -> V (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1319513413)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035978"
FT MUTAGEN 879
FT /note="K->E: Strongly reduces affinity for SDC1."
FT /evidence="ECO:0000269|PubMed:23395182"
FT MUTAGEN 912
FT /note="K->E: Strongly reduces affinity for SDC1."
FT /evidence="ECO:0000269|PubMed:23395182"
FT MUTAGEN 1404
FT /note="K->R: Decreased ubiquitination and increased
FT abundance."
FT /evidence="ECO:0000269|PubMed:25684205"
FT MUTAGEN 1420
FT /note="K->R: Decreased ubiquitination and increased
FT abundance."
FT /evidence="ECO:0000269|PubMed:25684205"
FT CONFLICT 24..25
FT /note="KH -> ND (in Ref. 1; AAA98443)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="G -> M (in Ref. 1; AAA98443)"
FT /evidence="ECO:0000305"
FT CONFLICT 881
FT /note="T -> I (in Ref. 3; AAI43981)"
FT /evidence="ECO:0000305"
FT CONFLICT 951
FT /note="G -> D (in Ref. 1; AAA98443)"
FT /evidence="ECO:0000305"
FT CONFLICT 1018
FT /note="S -> N (in Ref. 1; AAA98443)"
FT /evidence="ECO:0000305"
FT CONFLICT 1040..1041
FT /note="KL -> NV (in Ref. 1; AAA98443)"
FT /evidence="ECO:0000305"
FT CONFLICT 1148
FT /note="S -> I (in Ref. 1; AAA98443)"
FT /evidence="ECO:0000305"
FT STRAND 435..449
FT /evidence="ECO:0007829|PDB:4K2P"
FT TURN 450..452
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 463..470
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 473..477
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 492..496
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 501..504
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 512..518
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 524..528
FT /evidence="ECO:0007829|PDB:4K2P"
FT HELIX 532..554
FT /evidence="ECO:0007829|PDB:4K2P"
FT HELIX 559..587
FT /evidence="ECO:0007829|PDB:4K2P"
FT TURN 588..590
FT /evidence="ECO:0007829|PDB:4K2P"
FT HELIX 594..629
FT /evidence="ECO:0007829|PDB:4K2P"
FT HELIX 636..640
FT /evidence="ECO:0007829|PDB:4K2P"
FT HELIX 645..654
FT /evidence="ECO:0007829|PDB:4K2P"
FT HELIX 659..667
FT /evidence="ECO:0007829|PDB:4K2P"
FT STRAND 842..849
FT /evidence="ECO:0007829|PDB:3KZD"
FT HELIX 850..852
FT /evidence="ECO:0007829|PDB:4NXR"
FT TURN 855..858
FT /evidence="ECO:0007829|PDB:3KZE"
FT STRAND 859..865
FT /evidence="ECO:0007829|PDB:3KZD"
FT STRAND 867..870
FT /evidence="ECO:0007829|PDB:3KZD"
FT STRAND 872..878
FT /evidence="ECO:0007829|PDB:3KZD"
FT HELIX 883..886
FT /evidence="ECO:0007829|PDB:3KZD"
FT STRAND 894..898
FT /evidence="ECO:0007829|PDB:3KZD"
FT HELIX 903..905
FT /evidence="ECO:0007829|PDB:3KZD"
FT HELIX 908..916
FT /evidence="ECO:0007829|PDB:3KZD"
FT STRAND 917..926
FT /evidence="ECO:0007829|PDB:3KZD"
SQ SEQUENCE 1591 AA; 177508 MW; 0DAFBEE9A84B3452 CRC64;
MGNAESQHVE HEFYGEKHAS LGRKHTSRSL RLSHKTRRTR HASSGKVIHR NSEVSTRSSS
TPSIPQSLAE NGLEPFSQDG TLEDFGSPIW VDRVDMGLRP VSYTDSSVTP SVDSSIVLTA
ASVQSMPDTE ESRLYGDDAT YLAEGGRRQH SYTSNGPTFM ETASFKKKRS KSADIWREDS
LEFSLSDLSQ EHLTSNEEIL GSAEEKDCEE ARGMETRASP RQLSTCQRAN SLGDLYAQKN
SGVTANGGPG SKFAGYCRNL VSDIPNLANH KMPPAAAEET PPYSNYNTLP CRKSHCLSEG
ATNPQISHSN SMQGRRAKTT QDVNAGEGSE FADSGIEGAT TDTDLLSRRS NATNSSYSPT
TGRAFVGSDS GSSSTGDAAR QGVYENFRRE LEMSTTNSES LEEAGSAHSD EQSSGTLSSP
GQSDILLTAA QGTVRKAGAL AVKNFLVHKK NKKVESATRR KWKHYWVSLK GCTLFFYESD
GRSGIDHNSI PKHAVWVENS IVQAVPEHPK KDFVFCLSNS LGDAFLFQTT SQTELENWIT
AIHSACATAV ARHHHKEDTL RLLKSEIKKL EQKIDMDEKM KKMGEMQLSS VTDSKKKKTI
LDQIFVWEQN LEQFQMDLFR FRCYLASLQG GELPNPKRLL AFASRPTKVA MGRLGIFSVS
SFHALVAART GETGVRRRTQ AMSRSASKRR SRFSSLWGLD TTSKKKQGRP SINQVFGEGT
EAVKKSLEGI FDDIVPDGKR EKEVVLPNVH QHNPDCDIWV HEYFTPSWFC LPNNQPALTV
VRPGDTARDT LELICKTHQL DHSAHYLRLK FLIENKMQLY VPQPEEDIYE LLYKEIEICP
KVTQSIHIEK SDTAADTYGF SLSSVEEDGI RRLYVNSVKE TGLASKKGLK AGDEILEINN
RAADALNSSM LKDFLSQPSL GLLVRTYPEL EEGVELLESP PHRVDGPADL GESPLAFLTS
NPGHSLCSEQ GSSAETAPEE TEGPDLESSD ETDHSSKSTE QVAAFCRSLH EMNPSDQSPS
PQDSTGPQLA TMRQLSDADK LRKVICELLE TERTYVKDLN CLMERYLKPL QKETFLTQDE
LDVLFGNLTE MVEFQVEFLK TLEDGVRLVP DLEKLEKVDQ FKKVLFSLGG SFLYYADRFK
LYSAFCASHT KVPKVLVKAK TDTAFKAFLD AQNPKQQHSS TLESYLIKPI QRILKYPLLL
RELFALTDAE SEEHYHLDVA IKTMNKVASH INEMQKIHEE FGAVFDQLIA EQTGEKKEVA
DLSMGDLLLH TTVIWLNPPA SLGKWKKEPE LAAFVFKTAV VLVYKDGSKQ KKKLVGSHRL
SIYEDWDPFR FRHMIPTEAL QVRALASADA EANAVCEIVH VKSESEGRPE RVFHLCCSSP
ESRKDFLKAV HSILRDKHRR QLLKTESLPS SQQYVPFGGK RLCALKGARP AMSRAVSAPS
KSLGRRRRRL ARNRFTIDSD AVSASSPEKE SQQPPGGGDT DRWVEEQFDL AQYEEQDDIK
ETDILSDDDE FCESVKGASV DRDLQERLQA TSISQRERGR KTLDSHASRM AQLKKQAALS
GINGGLESAS EEVIWVRRED FAPSRKLNTE I
