Q60610 (TIAM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
T-lymphoma invasion and metastasis-inducing protein 1
Short name=TIAM-1

Gene names

Name:	Tiam1
Synonyms:	Tiam-1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1591 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA By similarity. Affects invasiveness of T-lymphoma cells.
Subunit structure	Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1 By similarity. Interacts with BAIAP2 By similarity. Interacts with EPHA8; regulates clathrin-mediated endocytosis of EPHA8. Interacts with NTRK2; mediates the activation of RAC1 by BDNF. Ref.3 Ref.5
Subcellular location	Cell junction By similarity. Note: Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction By similarity.
Tissue specificity	Highly expressed in brain and testis and at low or moderate levels in almost all other normal tissues. Found in virtually all analyzed tumor cell lines including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas.
Sequence similarities	Belongs to the TIAM family. Contains 1 DH (DBL-homology) domain. Contains 1 PDZ (DHR) domain. Contains 2 PH domains. Contains 1 RBD (Ras-binding) domain.

Ontologies

Keywords
Cellular component	Cell junction
Domain	Repeat
Molecular function	Guanine-nucleotide releasing factor
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cell-cell junction Inferred from sequence or structural similarity. Source: UniProtKB intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro receptor signaling protein activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Potential

Chain

2 – 1591

1590

T-lymphoma invasion and metastasis-inducing protein 1

PRO_0000080977

Regions

Domain

434 – 549

116

PH 1

Domain

765 – 832

68

RBD

Domain

845 – 908

64

PDZ

Domain

1040 – 1234

195

DH

Domain

1261 – 1397

137

PH 2

Compositional bias

595 – 598

4

Poly-Lys

Compositional bias

1445 – 1449

5

Poly-Arg

Amino acid modifications

Modified residue

231

1

Phosphoserine Ref.2

Modified residue

356

1

Phosphoserine By similarity

Modified residue

358

1

Phosphoserine By similarity

Modified residue

829

1

Phosphotyrosine; by NTRK2 Ref.3

Modified residue

1323

1

Phosphotyrosine Ref.4

Lipidation

2

1

N-myristoyl glycine Potential

Secondary structure

1

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1591

Helix Strand Turn

Details...

Helix

1037 – 1065

29

Helix

1067 – 1071

5

Beta strand

1073 – 1076

4

Helix

1078 – 1085

8

Helix

1088 – 1106

19

Helix

1112 – 1114

3

Helix

1118 – 1121

4

Helix

1122 – 1135

14

Helix

1138 – 1141

4

Helix

1142 – 1148

7

Turn

1149 – 1151

3

Helix

1152 – 1156

5

Turn

1157 – 1161

5

Helix

1163 – 1172

10

Helix

1178 – 1180

3

Helix

1182 – 1185

4

Helix

1188 – 1193

6

Helix

1196 – 1205

10

Helix

1212 – 1249

38

Helix

1264 – 1266

3

Beta strand

1267 – 1277

11

Helix

1280 – 1283

4

Beta strand

1290 – 1296

7

Beta strand

1299 – 1304

6

Turn

1318 – 1321

4

Beta strand

1332 – 1336

5

Helix

1337 – 1339

3

Beta strand

1340 – 1343

4

Turn

1348 – 1351

4

Beta strand

1355 – 1360

6

Helix

1365 – 1367

3

Beta strand

1371 – 1379

9

Helix

1380 – 1400

21

Sequences

	Sequence		Length	Mass (Da)
	Q60610 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: ECC2BAB189A6F019	FASTA	1,591	177,533
	10 20 30 40 50 60 MGNAESQNVD HEFYGEKHAS LGRKHTSRSL RLSHKTRRTR HASSGKAIHR NSEVSTRSSS 70 80 90 100 110 120 TPSIPQSLAE NGLEPFSQEG ALDDFGDPIW VDRVDMGLRP VSYTDSSVTP SVDGSIVLTA 130 140 150 160 170 180 ASVQSMPDSE ESRLYGDDAT YLAEGGRRQC PYTSNGPTFM ETASFKKKRS KSADIWREDS 190 200 210 220 230 240 LEFSLSDLSQ EHLTSNEEIL GSAEEKDCEE ARGMETEASP RQLSTCQRAN SLGDLYAQKN 250 260 270 280 290 300 SGVKANGGPR NRFSSYCRNL VSDIPDLAKH KMPPAAAEET PPYSNYNTLP CRKSHCLSEG 310 320 330 340 350 360 ATNPQISLSK SMQGRRAKTT QDVNTGEGSE FADSGIEGAT TDTDLLSRRS NATNSSYSPP 370 380 390 400 410 420 TGRAFVGSDS GSSSTGDRAR QGVYENFRRE LEMSTTNSES LEEAGSAHSD EQSSGTLSSP 430 440 450 460 470 480 GQSDILLTAA QGTVRKAGAL AVKNFLVHKK NKKVESATRR KWKHYWVSLK GCTLFFYETD 490 500 510 520 530 540 GRSGIDHNSV PKHAVWVENS IVQAVPEHPK KDFVFCLSNS LGDAFLFQTT SQTELENWIT 550 560 570 580 590 600 AIHSACAAAV ARHHHKEDTL RLLKSEIKKL EQKIDMDEKM KKMGEMQLSS VTDSKKKKTI 610 620 630 640 650 660 LDQIFVWEQN LEQFQMDLFR FRCYLASLQG GELPNPKRLL AFASRPTKVA MGRLGIFSVS 670 680 690 700 710 720 SFHALVAART GEIGVRRRTQ AMSRSASKRR SRFSSLWGLD TTSKKKQGRP TINQVFGEGT 730 740 750 760 770 780 DAVKRSLEGI FDDTVPDGKR EKEVVLPSVH QHNPDCDIWV HEYFTPSWFC LPNNQPALTV 790 800 810 820 830 840 VRPGDTARDT LELICKTHQL DHSAHYLRLK FLMENRVQFY IPQPEEDIYE LLYKEIEICP 850 860 870 880 890 900 KVTQNIHIEK SDAAADNYGF LLSSVDEDGI RRLYVNSVKE TGLASKKGLK AGDEILEINN 910 920 930 940 950 960 RAAGTLNSSM LKDFLSQPSL GLLVRTYPEP EGGVELLENP PHRVDGPVDL GESPLAFLTS 970 980 990 1000 1010 1020 NPGHSLSSEQ GSSAETAPEE GEGPDLESSD ETDHSSKSTE QVAAFCRSLH EMSPSDSSPS 1030 1040 1050 1060 1070 1080 PQDATSPQLA TTRQLSDADK LRKVICELLE TERTYVKDLN CLMERYLKPL QKETFLTQDE 1090 1100 1110 1120 1130 1140 LDVLFGNLTE MVEFQVEFLK TLEDGVRLVP DLEKLEKVDQ FKKVLFSLGG SFLYYADRFK 1150 1160 1170 1180 1190 1200 LYSAFCASHT KVPKVLVKAK TDTAFKAFLD AQNPRQQHSS TLESYLIKPI QRVLKYPLLL 1210 1220 1230 1240 1250 1260 RELFALTDAE SEEHYHLDVA IKTMNKVASH INEMQKIHEE FGAVFDQLIA EQTGEKKEVA 1270 1280 1290 1300 1310 1320 DLSMGDLLLH TSVIWLNPPA SLGKWKKEPE LAAFVFKTAV VLVYKDGSKQ KKKLVGSHRL 1330 1340 1350 1360 1370 1380 SIYEEWDPFR FRHMIPTEAL QVRALPSADA EANAVCEIVH VKSESEGRPE RVFHLCCSSP 1390 1400 1410 1420 1430 1440 ESRKDFLKSV HSILRDKHRR QLLKTESLPS AQQYVPFGGK RLCALKGARP AMSRAVSAPS 1450 1460 1470 1480 1490 1500 KSLGRRRRRL ARNRFTIDSD AISASSPEKE PQQPAGGGDT DRWVEEQFDL AQYEEQDDIK 1510 1520 1530 1540 1550 1560 ETDILSDDDE FCESLKGASV DRDLQEQLQA ASISQRARGR RTLDSHASRM TQLKKQAALS 1570 1580 1590 GINGGLESAS EEVIWVRRED FAPSRKLNTE I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins." Habets G.G.M., Scholtes E.H.M., Zuydgeest D., van der Kammen R.A., Stam J.C., Berns A., Collard J.G. Cell 77:537-549(1994) [PubMed: 7999144] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Brain.
[2]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed: 16452087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, MASS SPECTROMETRY. Tissue: Brain.
[3]	"TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology." Miyamoto Y., Yamauchi J., Tanoue A., Wu C., Mobley W.C. Proc. Natl. Acad. Sci. U.S.A. 103:10444-10449(2006) [PubMed: 16801538] [Abstract] Cited for: INTERACTION WITH NTRK2, PHOSPHORYLATION AT TYR-829 BY NTRK2.
[4]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1323, MASS SPECTROMETRY. Tissue: Mast cell.
[5]	"EphA8-ephrinA5 signaling and clathrin-mediated endocytosis is regulated by Tiam-1, a Rac-specific guanine nucleotide exchange factor." Yoo S., Shin J., Park S. Mol. Cells 29:603-609(2010) [PubMed: 20496116] [Abstract] Cited for: INTERACTION WITH EPHA8.
[6]	"Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1." Worthylake D.K., Rossman K.L., Sondek J. Nature 408:682-688(2000) [PubMed: 11130063] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1033-1406 IN COMPLEX WITH RAC1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U05245 mRNA. Translation: AAA18830.1.

IPI

IPI00119006.

PIR

A54146.

UniGene

Mm.310902.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FOE	X-ray	2.80	A/C/E/G	1033-1406	[»]
3A8N	X-ray	4.50	A	429-702	[»]

ProteinModelPortal

Q60610.

SMR

Q60610. Positions 433-670, 835-935, 1034-1401.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q60610. 1 interaction.

STRING

Q60610.

PTM databases

PhosphoSite

Q60610.

2D gel databases

SWISS-2DPAGE

Q60610.

Proteomic databases

PRIDE

Q60610.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

UCSC

uc007zvu.2. mouse.

Organism-specific databases

MGI

MGI:103306. Tiam1.

Phylogenomic databases

GeneTree

ENSGT00600000084055.

HOGENOM

HBG506823.

HOVERGEN

HBG059279.

InParanoid

Q60610.

OrthoDB

EOG49CQ6T.

Gene expression databases

ArrayExpress

Q60610.

Bgee

Q60610.

CleanEx

MM_TIAM1.

Genevestigator

Q60610.

GermOnline

ENSMUSG00000002489. Mus musculus.

Family and domain databases

InterPro

IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001478. PDZ/DHR/GLGF.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR003116. Raf-like_ras-bd.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 2 hits.
G3DSA:1.20.900.10. RhoGEF. 1 hit.

Pfam

PF00595. PDZ. 1 hit.
PF00169. PH. 1 hit.
PF02196. RBD. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]

SMART

SM00228. PDZ. 1 hit.
SM00233. PH. 2 hits.
SM00455. RBD. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]

SUPFAM

SSF48065. DH-domain. 1 hit.
SSF50156. PDZ. 1 hit.

PROSITE

PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50898. RBD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

301314.

PMAP-CutDB

Q60610.

SOURCE

Search...

Entry information

Entry name

TIAM1_MOUSE

Accession

Primary (citable) accession number: Q60610

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program