Q13009 (TIAM1_HUMAN) 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

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	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.
Subunit structure	Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with NTRK2; mediates the activation of RAC1 by BDNF By similarity. Interacts with BAIAP2. Interacts with EPHA8; regulates clathrin-mediated endocytosis of EPHA8. Ref.4 Ref.6 Ref.10 Ref.11
Subcellular location	Cell junction. Note: Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. Ref.10
Tissue specificity	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
Coding sequence diversity	Polymorphism
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	apoptotic process Traceable author statement. Source: Reactome induction of apoptosis by extracellular signals Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular component	cell-cell junction Inferred from direct assay Ref.10. Source: UniProtKB cytosol Traceable author statement. Source: Reactome
Molecular function	Rho guanyl-nucleotide exchange factor activity Traceable author statement. Source: ProtInc 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_0000080976

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.8 Ref.9

Modified residue

356

1

Phosphoserine Ref.7

Modified residue

358

1

Phosphoserine Ref.7

Modified residue

829

1

Phosphotyrosine; by NTRK2 By similarity

Modified residue

1323

1

Phosphotyrosine By similarity

Lipidation

2

1

N-myristoyl glycine Potential

Natural variations

Natural variant

247

1

G → R.
Corresponds to variant rs2070418 [ dbSNP | Ensembl ].

VAR_051991

Natural variant

247

1

G → V.
Corresponds to variant rs2070417 [ dbSNP | Ensembl ].

VAR_051992

Natural variant

678

1

R → C in a colorectal cancer sample; somatic mutation. Ref.13

VAR_035977

Natural variant

844

1

Q → H. Ref.1
Corresponds to variant rs16987932 [ dbSNP | Ensembl ].

VAR_051993

Natural variant

1339

1

A → V in a colorectal cancer sample; somatic mutation. Ref.13

VAR_035978

Experimental info

Sequence conflict

24 – 25

2

KH → ND in AAA98443. Ref.1

Sequence conflict

247

1

G → M in AAA98443. Ref.1

Sequence conflict

951

1

G → D in AAA98443. Ref.1

Sequence conflict

1018

1

S → N in AAA98443. Ref.1

Sequence conflict

1040 – 1041

2

KL → NV in AAA98443. Ref.1

Sequence conflict

1148

1

S → I in AAA98443. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1591

Helix Strand Turn

Details...

Beta strand

842 – 849

8

Turn

853 – 855

3

Beta strand

861 – 867

7

Beta strand

870 – 877

8

Helix

884 – 887

4

Beta strand

895 – 900

6

Helix

903 – 905

3

Helix

908 – 915

8

Beta strand

917 – 926

10

Sequences

	Sequence		Length	Mass (Da)
	Q13009 [UniParc]. Last modified July 10, 2007. Version 2. Checksum: 0DAFBEE9A84B3452	FASTA	1,591	177,508
	10 20 30 40 50 60 MGNAESQHVE HEFYGEKHAS LGRKHTSRSL RLSHKTRRTR HASSGKVIHR NSEVSTRSSS 70 80 90 100 110 120 TPSIPQSLAE NGLEPFSQDG TLEDFGSPIW VDRVDMGLRP VSYTDSSVTP SVDSSIVLTA 130 140 150 160 170 180 ASVQSMPDTE ESRLYGDDAT YLAEGGRRQH SYTSNGPTFM ETASFKKKRS KSADIWREDS 190 200 210 220 230 240 LEFSLSDLSQ EHLTSNEEIL GSAEEKDCEE ARGMETRASP RQLSTCQRAN SLGDLYAQKN 250 260 270 280 290 300 SGVTANGGPG SKFAGYCRNL VSDIPNLANH KMPPAAAEET PPYSNYNTLP CRKSHCLSEG 310 320 330 340 350 360 ATNPQISHSN SMQGRRAKTT QDVNAGEGSE FADSGIEGAT TDTDLLSRRS NATNSSYSPT 370 380 390 400 410 420 TGRAFVGSDS GSSSTGDAAR QGVYENFRRE LEMSTTNSES LEEAGSAHSD EQSSGTLSSP 430 440 450 460 470 480 GQSDILLTAA QGTVRKAGAL AVKNFLVHKK NKKVESATRR KWKHYWVSLK GCTLFFYESD 490 500 510 520 530 540 GRSGIDHNSI PKHAVWVENS IVQAVPEHPK KDFVFCLSNS LGDAFLFQTT SQTELENWIT 550 560 570 580 590 600 AIHSACATAV ARHHHKEDTL RLLKSEIKKL EQKIDMDEKM KKMGEMQLSS VTDSKKKKTI 610 620 630 640 650 660 LDQIFVWEQN LEQFQMDLFR FRCYLASLQG GELPNPKRLL AFASRPTKVA MGRLGIFSVS 670 680 690 700 710 720 SFHALVAART GETGVRRRTQ AMSRSASKRR SRFSSLWGLD TTSKKKQGRP SINQVFGEGT 730 740 750 760 770 780 EAVKKSLEGI FDDIVPDGKR EKEVVLPNVH QHNPDCDIWV HEYFTPSWFC LPNNQPALTV 790 800 810 820 830 840 VRPGDTARDT LELICKTHQL DHSAHYLRLK FLIENKMQLY VPQPEEDIYE LLYKEIEICP 850 860 870 880 890 900 KVTQSIHIEK SDTAADTYGF SLSSVEEDGI RRLYVNSVKE TGLASKKGLK AGDEILEINN 910 920 930 940 950 960 RAADALNSSM LKDFLSQPSL GLLVRTYPEL EEGVELLESP PHRVDGPADL GESPLAFLTS 970 980 990 1000 1010 1020 NPGHSLCSEQ GSSAETAPEE TEGPDLESSD ETDHSSKSTE QVAAFCRSLH EMNPSDQSPS 1030 1040 1050 1060 1070 1080 PQDSTGPQLA TMRQLSDADK 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 AQNPKQQHSS TLESYLIKPI QRILKYPLLL 1210 1220 1230 1240 1250 1260 RELFALTDAE SEEHYHLDVA IKTMNKVASH INEMQKIHEE FGAVFDQLIA EQTGEKKEVA 1270 1280 1290 1300 1310 1320 DLSMGDLLLH TTVIWLNPPA SLGKWKKEPE LAAFVFKTAV VLVYKDGSKQ KKKLVGSHRL 1330 1340 1350 1360 1370 1380 SIYEDWDPFR FRHMIPTEAL QVRALASADA EANAVCEIVH VKSESEGRPE RVFHLCCSSP 1390 1400 1410 1420 1430 1440 ESRKDFLKAV HSILRDKHRR QLLKTESLPS SQQYVPFGGK RLCALKGARP AMSRAVSAPS 1450 1460 1470 1480 1490 1500 KSLGRRRRRL ARNRFTIDSD AVSASSPEKE SQQPPGGGDT DRWVEEQFDL AQYEEQDDIK 1510 1520 1530 1540 1550 1560 ETDILSDDDE FCESVKGASV DRDLQERLQA TSISQRERGR KTLDSHASRM AQLKKQAALS 1570 1580 1590 GINGGLESAS EEVIWVRRED FAPSRKLNTE I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin." Habets G.G.M., van der Kammen R.A., Stam J.C., Michiels F., Collard J.G. Oncogene 10:1371-1376(1995) [PubMed: 7731688] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-844. Tissue: Fetal brain.
[2]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"A role for Rac in Tiam1-induced membrane ruffling and invasion." Michiels F., Habets G.G.M., Stam J.C., van der Kammen R.A., Collard J.G. Nature 375:338-340(1995) [PubMed: 7753201] [Abstract] Cited for: INTERACTION WITH RAC. Tissue: Brain.
[5]	"The invasion-inducing TIAM1 gene maps to human chromosome band 21q22 and mouse chromosome 16." Habets G.G.M., van der Kammen R.A., Jenkins N.A., Gilbert D.J., Copeland N.G., Hagemeijer A., Collard J.G. Cytogenet. Cell Genet. 70:48-51(1995) [PubMed: 7736788] [Abstract] Cited for: CHROMOSOMAL LOCATION.
[6]	"Tiam1-IRSp53 complex formation directs specificity of rac-mediated actin cytoskeleton regulation." Connolly B.A., Rice J., Feig L.A., Buchsbaum R.J. Mol. Cell. Biol. 25:4602-4614(2005) [PubMed: 15899863] [Abstract] Cited for: INTERACTION WITH BAIAP2.
[7]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356 AND SER-358, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, MASS SPECTROMETRY.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"CCM1 regulates vascular-lumen organization by inducing endothelial polarity." Lampugnani M.G., Orsenigo F., Rudini N., Maddaluno L., Boulday G., Chapon F., Dejana E. J. Cell Sci. 123:1073-1080(2010) [PubMed: 20332120] [Abstract] Cited for: SUBCELLULAR LOCATION, SUBUNIT.
[11]	"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.
[12]	"Solution structure of the PDZ domain of T-cell lymphoma invasion and metastasis 1 variant." RIKEN structural genomics initiative (RSGI) Submitted (JUN-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 835-935.
[13]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-678 AND VAL-1339.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U16296 mRNA. Translation: AAA98443.1.
AP000246 Genomic DNA. No translation available.
AP000247 Genomic DNA. No translation available.
BC117192 mRNA. Translation: AAI17193.1.
BC117196 mRNA. Translation: AAI17197.1.

IPI

IPI00011400.

RefSeq

NP_003244.2. NM_003253.2.

UniGene

Hs.517228.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D8I	NMR	-	A	835-935	[»]
3KZD	X-ray	1.30	A	841-930	[»]
3KZE	X-ray	1.80	A/B/C	841-930	[»]

ProteinModelPortal

Q13009.

SMR

Q13009. Positions 433-670, 769-935, 1034-1401.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13009. 6 interactions.

MINT

MINT-1746272.

STRING

Q13009.

PTM databases

PhosphoSite

Q13009.

Polymorphism databases

DMDM

152031709.

Proteomic databases

PRIDE

Q13009.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000286827; ENSP00000286827; ENSG00000156299.

GeneID

7074.

KEGG

hsa:7074.

NMPDR

fig|9606.3.peg.20867.

UCSC

uc002yow.1. human.

Organism-specific databases

CTD

7074.

GeneCards

GC21M032361.

H-InvDB

HIX0016054.

HGNC

HGNC:11805. TIAM1.

HPA

CAB010416.

MIM

600687. gene.

neXtProt

NX_Q13009.

PharmGKB

PA36514.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17976.

GeneTree

ENSGT00600000084055.

HOGENOM

HBG506823.

HOVERGEN

HBG059279.

InParanoid

Q13009.

OMA

HSLCSEQ.

OrthoDB

EOG49CQ6T.

PhylomeDB

Q13009.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6downstreampathway. Arf6 downstream pathway.
pi3kcipathway. Class I PI3K signaling events.
epha2_fwdpathway. EPHA2 forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
lysophospholipid_pathway. LPA receptor mediated events.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q13009.

Bgee

Q13009.

CleanEx

HS_TIAM1.

Genevestigator

Q13009.

GermOnline

ENSG00000156299. Homo sapiens.

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.

KO

K05731.

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

27667.

SOURCE

Search...

Entry information

Entry name

TIAM1_HUMAN

Accession

Primary (citable) accession number: Q13009
Secondary accession number(s): Q17RT7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 10, 2007
Last modified:	January 25, 2012
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.