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Protein

T-lymphoma invasion and metastasis-inducing protein 2

Gene

TIAM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane (By similarity). Activates specifically RAC1, but not CDC42 and RHOA.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-HSA-193648 NRAGE signals death through JNK
R-HSA-194840 Rho GTPase cycle
R-HSA-1989781 PPARA activates gene expression
R-HSA-416482 G alpha (12/13) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
T-lymphoma invasion and metastasis-inducing protein 2
Short name:
TIAM-2
Alternative name(s):
SIF and TIAM1-like exchange factor
Gene namesi
Name:TIAM2
Synonyms:KIAA2016, STEF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000146426.17
HGNCiHGNC:11806 TIAM2
MIMi604709 gene
neXtProtiNX_Q8IVF5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi26230
OpenTargetsiENSG00000146426
PharmGKBiPA36515

Polymorphism and mutation databases

BioMutaiTIAM2
DMDMi296453025

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedSequence analysis
ChainiPRO_00003174672 – 1701T-lymphoma invasion and metastasis-inducing protein 2Add BLAST1700

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineSequence analysis1
Modified residuei1583PhosphoserineBy similarity1
Modified residuei1648PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylated on serine and threonine residues. Phosphorylated on Thr-1648 by Rho-kinase. Its phosphorylation by Rho-kinase inhibits its guanine nucleotide exchange activity, its interaction with MAP1A, MAP1B, PARP1 and YWHAE and reduces its ability to promote neurite growth (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiQ8IVF5
PaxDbiQ8IVF5
PeptideAtlasiQ8IVF5
PRIDEiQ8IVF5
ProteomicsDBi70693
70694 [Q8IVF5-2]
70695 [Q8IVF5-3]
70696 [Q8IVF5-4]
70697 [Q8IVF5-5]

PTM databases

iPTMnetiQ8IVF5
PhosphoSitePlusiQ8IVF5

Expressioni

Tissue specificityi

Expressed in the occipital, frontal and temporal lobes, cerebellum, putamen and testis.1 Publication

Gene expression databases

BgeeiENSG00000146426 Expressed in 186 organ(s), highest expression level in anterior cingulate cortex
CleanExiHS_TIAM2
ExpressionAtlasiQ8IVF5 baseline and differential
GenevisibleiQ8IVF5 HS

Organism-specific databases

HPAiHPA011134
HPA013903

Interactioni

Subunit structurei

Interacts with MAP1A, MAP1B, PARP1 and YWHAE. Interacts with CD44, PARD3 and MAPK8IP2 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117621, 9 interactors
IntActiQ8IVF5, 6 interactors
MINTiQ8IVF5
STRINGi9606.ENSP00000327315

Structurei

3D structure databases

ProteinModelPortaliQ8IVF5
SMRiQ8IVF5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini506 – 620PH 1PROSITE-ProRule annotationAdd BLAST115
Domaini810 – 881RBDPROSITE-ProRule annotationAdd BLAST72
Domaini890 – 976PDZPROSITE-ProRule annotationAdd BLAST87
Domaini1099 – 1293DHPROSITE-ProRule annotationAdd BLAST195
Domaini1347 – 1478PH 2PROSITE-ProRule annotationAdd BLAST132

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili628 – 695Sequence analysisAdd BLAST68

Domaini

The PH 1 domain and amino acids 621-782 (a region called TSS; otherwise known as CC-Ex) are necessary for membrane localization. The PH 1 and TSS domains are necessary for Rac1 activity. The PH 2 domain is engaged in the enhancement of the catalytic activity of the adjacent DH domain. The PH 1, TSS and DH domains are necessary to induce neurite-like structure (By similarity).By similarity

Sequence similaritiesi

Belongs to the TIAM family.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410ITS1 Eukaryota
ENOG410XPCM LUCA
GeneTreeiENSGT00920000148946
HOVERGENiHBG059279
InParanoidiQ8IVF5
KOiK16847
OMAiSHFKSNQ
OrthoDBiEOG091G00C8
PhylomeDBiQ8IVF5
TreeFamiTF319686

Family and domain databases

CDDicd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR001478 PDZ
IPR036034 PDZ_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR003116 RBD_dom
PfamiView protein in Pfam
PF00595 PDZ, 1 hit
PF00169 PH, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 1 hit
SM00233 PH, 2 hits
SM00455 RBD, 1 hit
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
SSF50156 SSF50156, 1 hit
PROSITEiView protein in PROSITE
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50106 PDZ, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS50898 RBD, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 7 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q8IVF5-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MGNSDSQYTL QGSKNHSNTI TGAKQIPCSL KIRGIHAKEE KSLHGWGHGS
60 70 80 90 100
NGAGYKSRSL ARSCLSHFKS NQPYASRLGG PTCKVSRGVA YSTHRTNAPG
110 120 130 140 150
KDFQGISAAF STENGFHSVG HELADNHITS RDCNGHLLNC YGRNESIAST
160 170 180 190 200
PPGEDRKSPR VLIKTLGKLD GCLRVEFHNG GNPSKVPAED CSEPVQLLRY
210 220 230 240 250
SPTLASETSP VPEARRGSSA DSLPSHRPSP TDSRLRSSKG SSLSSESSWY
260 270 280 290 300
DSPWGNAGEL SEAEGSFLAP GMPDPSLHAS FPPGDAKKPF NQSSSLSSLR
310 320 330 340 350
ELYKDANLGS LSPSGIRLSD EYMGTHASLS NRVSFASDID VPSRVAHGDP
360 370 380 390 400
IQYSSFTLPC RKPKAFVEDT AKKDSLKARM RRISDWTGSL SRKKRKLQEP
410 420 430 440 450
RSKEGSDYFD SRSDGLNTDV QGSSQASAFL WSGGSTQILS QRSESTHAIG
460 470 480 490 500
SDPLRQNIYE NFMRELEMSR TNTENIETST ETAESSSESL SSLEQLDLLF
510 520 530 540 550
EKEQGVVRKA GWLFFKPLVT VQKERKLELV ARRKWKQYWV TLKGCTLLFY
560 570 580 590 600
ETYGKNSMDQ SSAPRCALFA EDSIVQSVPE HPKKENVFCL SNSFGDVYLF
610 620 630 640 650
QATSQTDLEN WVTAVHSACA SLFAKKHGKE DTLRLLKNQT KNLLQKIDMD
660 670 680 690 700
SKMKKMAELQ LSVVSDPKNR KAIENQIQQW EQNLEKFHMD LFRMRCYLAS
710 720 730 740 750
LQGGELPNPK SLLAAASRPS KLALGRLGIL SVSSFHALVC SRDDSALRKR
760 770 780 790 800
TLSLTQRGRN KKGIFSSLKG LDTLARKGKE KRPSITQVDE LLHIYGSTVD
810 820 830 840 850
GVPRDNAWEI QTYVHFQDNH GVTVGIKPEH RVEDILTLAC KMRQLEPSHY
860 870 880 890 900
GLQLRKLVDD NVEYCIPAPY EYMQQQVYDE IEVFPLNVYD VQLTKTGSVC
910 920 930 940 950
DFGFAVTAQV DERQHLSRIF ISDVLPDGLA YGEGLRKGNE IMTLNGEAVS
960 970 980 990 1000
DLDLKQMEAL FSEKSVGLTL IARPPDTKAT LCTSWSDSDL FSRDQKSLLP
1010 1020 1030 1040 1050
PPNQSQLLEE FLDNFKKNTA NDFSNVPDIT TGLKRSQTDG TLDQVSHREK
1060 1070 1080 1090 1100
MEQTFRSAEQ ITALCRSFND SQANGMEGPR ENQDPPPRSL ARHLSDADRL
1110 1120 1130 1140 1150
RKVIQELVDT EKSYVKDLSC LFELYLEPLQ NETFLTQDEM ESLFGSLPEM
1160 1170 1180 1190 1200
LEFQKVFLET LEDGISASSD FNTLETPSQF RKLLFSLGGS FLYYADHFKL
1210 1220 1230 1240 1250
YSGFCANHIK VQKVLERAKT DKAFKAFLDA RNPTKQHSST LESYLIKPVQ
1260 1270 1280 1290 1300
RVLKYPLLLK ELVSLTDQES EEHYHLTEAL KAMEKVASHI NEMQKIYEDY
1310 1320 1330 1340 1350
GTVFDQLVAE QSGTEKEVTE LSMGELLMHS TVSWLNPFLS LGKARKDLEL
1360 1370 1380 1390 1400
TVFVFKRAVI LVYKENCKLK KKLPSNSRPA HNSTDLDPFK FRWLIPISAL
1410 1420 1430 1440 1450
QVRLGNPAGT ENNSIWELIH TKSEIEGRPE TIFQLCCSDS ESKTNIVKVI
1460 1470 1480 1490 1500
RSILRENFRR HIKCELPLEK TCKDRLVPLK NRVPVSAKLA SSRSLKVLKN
1510 1520 1530 1540 1550
SSSNEWTGET GKGTLLDSDE GSLSSGTQSS GCPTAEGRQD SKSTSPGKYP
1560 1570 1580 1590 1600
HPGLADFADN LIKESDILSD EDDDHRQTVK QGSPTKDIEI QFQRLRISED
1610 1620 1630 1640 1650
PDVHPEAEQQ PGPESGEGQK GGEQPKLVRG HFCPIKRKAN STKRDRGTLL
1660 1670 1680 1690 1700
KAQIRHQSLD SQSENATIDL NSVLEREFSV QSLTSVVSEE CFYETESHGK

S
Length:1,701
Mass (Da):190,103
Last modified:May 18, 2010 - v4
Checksum:iC2C9C9B1782B7823
GO
Isoform 2 (identifier: Q8IVF5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1317-1317: E → EQPEWSSEVMDVLDPRGKLTKGTLEEPRTL

Show »
Length:1,730
Mass (Da):193,398
Checksum:i05CE6315772C1B90
GO
Isoform 3 (identifier: Q8IVF5-3) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-1075: Missing.

Show »
Length:626
Mass (Da):70,774
Checksum:i782D90DF706BEC02
GO
Isoform 4 (identifier: Q8IVF5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-688: Missing.

Show »
Length:1,013
Mass (Da):114,079
Checksum:iD7C1B5D6B346E3D9
GO
Isoform 5 (identifier: Q8IVF5-5) [UniParc]FASTAAdd to basket
Also known as: Long

The sequence of this isoform differs from the canonical sequence as follows:
     787-787: Q → QIFDSSGSHGFSGTQLPQNSSNSSE

Show »
Length:1,725
Mass (Da):192,555
Checksum:iA836FE578E412A5C
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PMZ8E9PMZ8_HUMAN
T-lymphoma invasion and metastasis-...
TIAM2
1,367Annotation score:
E9PKT1E9PKT1_HUMAN
T-lymphoma invasion and metastasis-...
TIAM2
1,045Annotation score:
H7C5V6H7C5V6_HUMAN
T-lymphoma invasion and metastasis-...
TIAM2
156Annotation score:
F5H6R0F5H6R0_HUMAN
T-lymphoma invasion and metastasis-...
TIAM2
85Annotation score:
F5H6W6F5H6W6_HUMAN
T-lymphoma invasion and metastasis-...
TIAM2
195Annotation score:
H0YGV1H0YGV1_HUMAN
T-lymphoma invasion and metastasis-...
TIAM2
64Annotation score:
F5H1M3F5H1M3_HUMAN
T-lymphoma invasion and metastasis-...
TIAM2
53Annotation score:

Sequence cautioni

The sequence AAF05900 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC23112 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAC86170 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti506V → A in BAC86170 (PubMed:14702039).Curated1
Sequence conflicti633L → P in AAF05900 (PubMed:10512681).Curated1
Sequence conflicti722L → P in AAF05900 (PubMed:10512681).Curated1
Sequence conflicti807A → T in AAF05900 (PubMed:10512681).Curated1
Sequence conflicti1066R → K in BAC86170 (PubMed:14702039).Curated1
Sequence conflicti1092R → G in AAH66979 (PubMed:15489334).Curated1
Sequence conflicti1154Q → R in AAH66979 (PubMed:15489334).Curated1
Sequence conflicti1186S → P in BAC86170 (PubMed:14702039).Curated1
Sequence conflicti1306Q → R in BAC86170 (PubMed:14702039).Curated1
Sequence conflicti1365E → K in BAC86170 (PubMed:14702039).Curated1
Sequence conflicti1376N → Y in AAH66979 (PubMed:15489334).Curated1
Sequence conflicti1451R → S in AAH66979 (PubMed:15489334).Curated1
Sequence conflicti1482R → G in AAH66979 (PubMed:15489334).Curated1
Sequence conflicti1519D → Y in BAC86170 (PubMed:14702039).Curated1
Sequence conflicti1639A → T in BAC86170 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051994332R → H. Corresponds to variant dbSNP:rs931312Ensembl.1
Natural variantiVAR_051995913R → H. Corresponds to variant dbSNP:rs7770537Ensembl.1
Natural variantiVAR_0519961089S → P5 PublicationsCorresponds to variant dbSNP:rs4259257Ensembl.1
Natural variantiVAR_0385341101R → C. Corresponds to variant dbSNP:rs11751128Ensembl.1
Natural variantiVAR_0385351572D → E. Corresponds to variant dbSNP:rs1571767Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0309711 – 1075Missing in isoform 3. 2 PublicationsAdd BLAST1075
Alternative sequenceiVSP_0309721 – 688Missing in isoform 4. 1 PublicationAdd BLAST688
Alternative sequenceiVSP_030974787Q → QIFDSSGSHGFSGTQLPQNS SNSSE in isoform 5. 1 Publication1
Alternative sequenceiVSP_0309751317E → EQPEWSSEVMDVLDPRGKLT KGTLEEPRTL in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF120323 mRNA Translation: AAF05900.1 Different initiation.
AF120324 mRNA Translation: AAF05901.1
AB095936 mRNA Translation: BAC23112.2 Different initiation.
AL122086 mRNA Translation: CAB59259.2
AL139101 Genomic DNA No translation available.
AL355343 Genomic DNA No translation available.
AL596202 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW47693.1
BC066979 mRNA Translation: AAH66979.1
BC137275 mRNA Translation: AAI37276.1
AK125459 mRNA Translation: BAC86170.1 Different initiation.
CCDSiCCDS34558.1 [Q8IVF5-1]
CCDS34559.1 [Q8IVF5-3]
RefSeqiNP_001010927.1, NM_001010927.2
NP_036586.2, NM_012454.3
UniGeneiHs.586279

Genome annotation databases

EnsembliENST00000275246; ENSP00000275246; ENSG00000146426 [Q8IVF5-3]
ENST00000360366; ENSP00000353528; ENSG00000146426 [Q8IVF5-5]
ENST00000456877; ENSP00000407183; ENSG00000146426 [Q8IVF5-4]
ENST00000461783; ENSP00000437188; ENSG00000146426 [Q8IVF5-1]
ENST00000529824; ENSP00000433348; ENSG00000146426 [Q8IVF5-2]
GeneIDi26230
KEGGihsa:26230
UCSCiuc003qqb.3 human [Q8IVF5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTIAM2_HUMAN
AccessioniPrimary (citable) accession number: Q8IVF5
Secondary accession number(s): B2RP56
, C9JZV2, Q6NXN9, Q6ZUP9, Q9UFG6, Q9UKV9, Q9UKW0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: May 18, 2010
Last modified: September 12, 2018
This is version 131 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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