TRIO_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: TRIO_MOUSE
• UniProt AC: Q0KL02
• Protein Name: Triple functional domain protein
• Gene Name: Trio
• Organism: Mus musculus (Mouse).
• Sequence Length: 3102
• Subcellular Localization: Cytoplasm . Isoform 2 localizes to early endosomes.
• Protein Description: Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases. Involved in coordinating actin remodeling, which is necessary for cell migration and growth (By similarity). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis. [PubMed: 22666460]
• Protein Sequence: MSGSSGGATAPAASSGPAAAASAAGSGCGGGAGEGAEEAAKDLADIAAFFRSGFRKNDEMKAMDVLPILKEKVAYLSGGRDKRGGPILTFPARSNHDRIRQEDLRRLISYLACIPSEEVCKRGFTVIVDMRGSKWDSIKPLLKILQESFPCCIHIALIIKPDNFWQKQRTNFGSSKFEFETNMVSLEGLTKVVDPSQLTPEFDGCLEYNHEEWIEIRVAFEEYISNAAHMLSRLEELQDVLAKKELPQDLEGARNMIDEHSQLKKKVIKAPIEDLDLEGQKLLQRIQSSDSFPKKNSGSGNADLQNLLPKVSTMLDRLHSTRQHLHQMWHVRKLKLDQCFQLRLFEQDAEKMFDWITHNKGLFLNSYTEIGTSHPHAMELQTQHNHFAMNCMNVYVNINRIMSVANRLVESGHYASQQIKQIANQLEQEWKAFAAALDERSTLLDMSSIFHQKAEKYMSNVDSWCKACGEVDLPSELQDLEDAIHHHQGIYEHITLAYSEVSQDGKSLLDKLQRPLTPGSSDSLTASANYSKAVHHVLDVIHEVLHHQRQLENIWQHRKVRLHQRLQLCVFQQDVQQVLDWIENHGEAFLSKHTGVGKSLHRARALQKRHEDFEEVAQNTYTNADKLLEAAEQLAQTGECDPEEIYQAAHQLEDRIQDFVRRVEQRKILLDMSVSFHTHVKELWTWLEELQKELLDDVYAESVEAVQDLIKRFGQQQQTTLQVTVNVIKEGEDLIQQLRDSAISSNKTPHNSSINHIETVLQQLDEAQSQMEELFQERKIKLELFLQLRIFERDAIDIISDLESWNDELSQQMNDFDTEDLTIAEQRLQHHADKALTMNNLTFDVIHQGQDLLQYVNEVQASGVELLCDRDVDMATRVQDLLEFLHEKQQELDLAAEQHRKHLEQCVQLRHLQAEVKQVLGWIRNGESMLNAGLITASSLQEAEQLQREHEQFQHAIEKTHQSALQVQQKAEAMLQANHYDMDMIRDCAEKVASHWQQLMLKMEDRLKLVNASVAFYKTSEQVCSVLESLEQEYKREEDWCGGADKLGPNSETDHVTPMISKHLEQKEAFLKACTLARRNADVFLKYLHRNSVSMPGMVTHIKAPEQQVKNILNELFQRENRVLHYWTMRKRRLDQCQQYVVFERSAKQALEWIHDNGEFYLSTHTSTGSSIQHTQELLKEHEEFQITAKQTKERVKLLIQLADGFCEKGHAHAAEIKKCVTAVDKRYRDFSLRMEKYRTSLEKALGISSDSNKSSKSLQLDIIPASIPGSEVKLRDAAHELNEEKRKSARRKEFIMAELIQTEKAYVRDLRECMDTYLWEMTSGVEEIPPGIVNKELIIFGNMQEIYEFHNNIFLKELEKYEQLPEDVGHCFVTWADKFQMYVTYCKNKPDSTQLILEHAGSYFDEIQQRHGLANSISSYLIKPVQRITKYQLLLKELLTCCEEGKGEIKDGLEVMLSVPKRANDAMHLSMLEGFDENIESQGELILQESFQVWDPKTLIRKGRERHLFLFEMSLVFSKEVKDSSGRSKYLYKSKLFTSELGVTEHVEGDPCKFALWVGRTPTSDNKIVLKASSIENKQDWIKHIREVIQERTVHLRGALKEPIHIPKTAPAARQKGRRDGEDLDSQGDGSSQPDTISIASRTSQNTLDSDKLSGGCELTVVIHDFTACNSNELTIRRGQTVEVLERPHDKPDWCLVRTTDRSPAAEGLVPCGSLCIAHSRSSMEMEGIFNHKDSLSVSSNDASPPASVASLQPHMIGAQSSPGPKRPGNTLRKWLTSPVRRLSSGKADGHAKKLAHKHKKSREVRKSADAGSQKDSDDSAATPQDETIEERGRNEGLSSGTLSKSSSSGMQSCGEEEGEEGADAVPLPPPMAIQQHSLLQPDSQDDKASSRLLVRPTSSETPSAAELVSAIEELVKSKMALEDRPSSLLVDQGDSSSPSFNPSDNSLLSSSSPIDEMEERKCSSLKRRHYVLQELVETERDYVRDLGCVVEGYMALMKEDGVPDDMKGKDKIVFGNIHQIYDWHRDFFLGELEKCLEDPEKLGSLFVKHERRLHMYIVYCQNKPKSEHIVSEYIDTFFEDLKQRLGHRLQLTDLLIKPVQRIMKYQLLLKDFLKYSKKASLDTSELEKAVEVMCIVPKRCNDMMNVGRLQGFDGKIVAQGKLLLQDTFLVTDQDAGLLPRCKERRVFLFEQIVIFSEPLDKKKGFSMPGFLFKNSIKVSCLCLEENVESDPCKFALTSRTGDAVETFVLHSSSPSVRQTWIHEINQILENQRNFLNALTSPIEYQRNHSGGGGSGSGGSSGGGGGSGGSGASSGGSSSHGSGPSSCSSGPSSSRSRPSRIPQPVRHHPPMLVSSAASSQAEADKMSGMSAPSPSLPTPSSSLALEASLGQPSRLPLSGDSEGHERETEPIPKMKVMESPRKAPGSTSGTSQDGNTKDARGNLGSLPLGKTRPGAVSPLNSPLSTTFPSPFGKEAFPPSSPLQKGGSFWSSIPASPASRPSSFTFPGDSDSLQRQTHRHAAPSKDTDRMSTCSSASEQSVQSTQSNGEGSSSSNISTMLVTHEYTAVKEDEINVYQGEVVQILASNQQNMFLVFRAATDQCPAAEGWIPGFVLGHTSAVIMENPDGTLKKSTSWHTALRLRKKSEKKDKDGKRDGKLENGYRKPREGLSNKVSVKLLNPNYIYDVPPEFVIPLSEVTCETGETVVFRCRVCGRPKASITWKGPEHNTLNNDDHYSISYSDIGEATLKIIGVSTEDDGIYTCIAVNDMGSASSSASLRVLGPGSDGIVVTWKDNFDAFYSEVAELGRGRFAVVKKCDQKGTKRAVATKFVNKKLMKRDQVTHELGILQNLQHPLLVSLLDTFETPTSYVLVLEMADQGRLLDCVVRWGSLTEGKVRAHLGEVLEAVRYLHNCRIAHLDLKPENILVDQSLAKPTIKLADFGDAVQLNTTYYIHQLLGNPEFAAPEIILGNPVSLTADTWSVGVLTYVLLSGVSPFLDDSVEETCLNICRLDFSFPEDYFQGVSQKAKEFVCFLLQEDPAKRPSAALALQEQWLQAGNGSGKGTGVLDTSRLTSFIERRKHQNDVRPIRSIKNFLQSRLLPRV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
89	Phosphorylation	KRGGPILTFPARSNH CCCCCCCEEECCCCC	28.43	-
281	Ubiquitination	DLDLEGQKLLQRIQS HCCCCHHHHHHHHHC	63.12	22790023
281 (in isoform 4)	Ubiquitination	-	63.12	22790023
288	Phosphorylation	KLLQRIQSSDSFPKK HHHHHHHCCCCCCCC	33.47	21183079
313	Phosphorylation	NLLPKVSTMLDRLHS HHHHHHHHHHHHHHH	25.41	28507225
520	Phosphorylation	QRPLTPGSSDSLTAS CCCCCCCCCCCCCCC	31.98	25521595
521	Phosphorylation	RPLTPGSSDSLTASA CCCCCCCCCCCCCCC	36.81	19060867
523	Phosphorylation	LTPGSSDSLTASANY CCCCCCCCCCCCCCH	29.57	19060867
525	Phosphorylation	PGSSDSLTASANYSK CCCCCCCCCCCCHHH	23.63	25521595
527	Phosphorylation	SSDSLTASANYSKAV CCCCCCCCCCHHHHH	16.29	29899451
1092	Phosphorylation	LKYLHRNSVSMPGMV HHHHHHCCCCCCCCC	18.61	25338131
1255	Phosphorylation	ISSDSNKSSKSLQLD CCCCCCCCCCCCCCE	47.45	25338131
1258	Phosphorylation	DSNKSSKSLQLDIIP CCCCCCCCCCCEEEC	24.24	29899451
1271	Phosphorylation	IPASIPGSEVKLRDA ECCCCCCCCHHHHHH	33.58	-
1562	Phosphorylation	FALWVGRTPTSDNKI EEEEEECCCCCCCEE	25.62	19060867
1627	Phosphorylation	RDGEDLDSQGDGSSQ CCCCCCCCCCCCCCC	43.28	19060867
1632	Phosphorylation	LDSQGDGSSQPDTIS CCCCCCCCCCCCCEE	30.46	25338131
1633	Phosphorylation	DSQGDGSSQPDTISI CCCCCCCCCCCCEEE	51.79	19060867
1639	Phosphorylation	SSQPDTISIASRTSQ CCCCCCEEEEECCCC	17.75	29899451
1723	Phosphorylation	LCIAHSRSSMEMEGI EEEEECCCCCHHCCC	36.73	26239621
1724	Phosphorylation	CIAHSRSSMEMEGIF EEEECCCCCHHCCCC	20.04	25521595
1736	Phosphorylation	GIFNHKDSLSVSSND CCCCCCCCCCCCCCC	27.61	25619855
1738	Phosphorylation	FNHKDSLSVSSNDAS CCCCCCCCCCCCCCC	24.73	25619855
1740	Phosphorylation	HKDSLSVSSNDASPP CCCCCCCCCCCCCCC	21.76	25619855
1741	Phosphorylation	KDSLSVSSNDASPPA CCCCCCCCCCCCCCC	36.25	25619855
1745	Phosphorylation	SVSSNDASPPASVAS CCCCCCCCCCCHHHH	33.99	25619855
1749	Phosphorylation	NDASPPASVASLQPH CCCCCCCHHHHCCCH	24.80	25619855
1752	Phosphorylation	SPPASVASLQPHMIG CCCCHHHHCCCHHCC	25.94	25619855
1762	Phosphorylation	PHMIGAQSSPGPKRP CHHCCCCCCCCCCCC	37.66	25619855
1763	Phosphorylation	HMIGAQSSPGPKRPG HHCCCCCCCCCCCCC	23.07	25619855
1778	Phosphorylation	NTLRKWLTSPVRRLS CHHHHHHHCHHHHHH	29.84	29472430
1779	Phosphorylation	TLRKWLTSPVRRLSS HHHHHHHCHHHHHHC	21.16	26824392
1785	Phosphorylation	TSPVRRLSSGKADGH HCHHHHHHCCCCCHH	34.92	26824392
1786	Phosphorylation	SPVRRLSSGKADGHA CHHHHHHCCCCCHHH	49.24	26824392
1809	Phosphorylation	KSREVRKSADAGSQK HHHHHHHHCCCCCCC	22.33	25521595
1814	Phosphorylation	RKSADAGSQKDSDDS HHHCCCCCCCCCCCC	35.46	23684622
1818	Phosphorylation	DAGSQKDSDDSAATP CCCCCCCCCCCCCCC	50.80	22322096
1821	Phosphorylation	SQKDSDDSAATPQDE CCCCCCCCCCCCCCH	25.46	22322096
1824	Phosphorylation	DSDDSAATPQDETIE CCCCCCCCCCCHHHH	22.62	25521595
1840	Phosphorylation	RGRNEGLSSGTLSKS HCCCCCCCCCCCCCC	37.26	29550500
1841	Phosphorylation	GRNEGLSSGTLSKSS CCCCCCCCCCCCCCC	40.62	18846507
1843	Phosphorylation	NEGLSSGTLSKSSSS CCCCCCCCCCCCCCC	29.79	24899341
1845	Phosphorylation	GLSSGTLSKSSSSGM CCCCCCCCCCCCCCC	30.26	27841257
1849	Phosphorylation	GTLSKSSSSGMQSCG CCCCCCCCCCCCCCC	37.69	25338131
1854	Phosphorylation	SSSSGMQSCGEEEGE CCCCCCCCCCCCCCC	18.39	25338131
1899	Phosphorylation	SRLLVRPTSSETPSA CCEEECCCCCCCCCH	34.03	26239621
1900	Phosphorylation	RLLVRPTSSETPSAA CEEECCCCCCCCCHH	28.94	26239621
1901	Phosphorylation	LLVRPTSSETPSAAE EEECCCCCCCCCHHH	48.22	26239621
1903	Phosphorylation	VRPTSSETPSAAELV ECCCCCCCCCHHHHH	25.21	23984901
1905	Phosphorylation	PTSSETPSAAELVSA CCCCCCCCHHHHHHH	47.75	23984901
1911	Phosphorylation	PSAAELVSAIEELVK CCHHHHHHHHHHHHH	35.83	20139300
1919	Phosphorylation	AIEELVKSKMALEDR HHHHHHHHCCCCCCC	21.86	20139300
1928	Phosphorylation	MALEDRPSSLLVDQG CCCCCCCCCCEECCC	34.22	29514104
1929	Phosphorylation	ALEDRPSSLLVDQGD CCCCCCCCCEECCCC	28.53	29514104
1937	Phosphorylation	LLVDQGDSSSPSFNP CEECCCCCCCCCCCC	39.27	29899451
1938	Phosphorylation	LVDQGDSSSPSFNPS EECCCCCCCCCCCCC	51.51	25338131
1939	Phosphorylation	VDQGDSSSPSFNPSD ECCCCCCCCCCCCCC	28.63	19060867
1941	Phosphorylation	QGDSSSPSFNPSDNS CCCCCCCCCCCCCCC	39.33	25338131
1945	Phosphorylation	SSPSFNPSDNSLLSS CCCCCCCCCCCCCCC	50.99	20415495
1948	Phosphorylation	SFNPSDNSLLSSSSP CCCCCCCCCCCCCCC	35.36	23649490
1951	Phosphorylation	PSDNSLLSSSSPIDE CCCCCCCCCCCCCHH	33.20	20415495
1952	Phosphorylation	SDNSLLSSSSPIDEM CCCCCCCCCCCCHHH	34.50	23649490
1953	Phosphorylation	DNSLLSSSSPIDEME CCCCCCCCCCCHHHH	36.44	19060867
1954	Phosphorylation	NSLLSSSSPIDEMEE CCCCCCCCCCHHHHH	28.02	20415495
2099	Ubiquitination	QLTDLLIKPVQRIMK HHHHHHHHHHHHHHH	38.82	22790023
2099 (in isoform 4)	Ubiquitination	-	38.82	22790023
2122	Phosphorylation	LKYSKKASLDTSELE HHHHHHCCCCHHHHH	35.34	29899451
2198	Phosphorylation	FEQIVIFSEPLDKKK EEEEEEECCCCCCCC	27.47	-
2254	Phosphorylation	ETFVLHSSSPSVRQT EEEEEECCCCCHHHH	35.20	30635358
2255	Phosphorylation	TFVLHSSSPSVRQTW EEEEECCCCCHHHHH	24.98	30635358
2281	Phosphorylation	RNFLNALTSPIEYQR HHHHHHHCCCCCCCC	30.01	24925903
2282	Phosphorylation	NFLNALTSPIEYQRN HHHHHHCCCCCCCCC	25.40	25521595
2286	Phosphorylation	ALTSPIEYQRNHSGG HHCCCCCCCCCCCCC	17.31	29514104
2291	Phosphorylation	IEYQRNHSGGGGSGS CCCCCCCCCCCCCCC	42.56	30387612
2314	Phosphorylation	GSGGSGASSGGSSSH CCCCCCCCCCCCCCC	32.80	-
2329	Phosphorylation	GSGPSSCSSGPSSSR CCCCCCCCCCCCCCC	40.03	-
2330	Phosphorylation	SGPSSCSSGPSSSRS CCCCCCCCCCCCCCC	60.08	-
2335	Phosphorylation	CSSGPSSSRSRPSRI CCCCCCCCCCCCCCC	38.32	-
2359	Phosphorylation	MLVSSAASSQAEADK CEECCCCCCHHHHHH	23.77	25338131
2360	Phosphorylation	LVSSAASSQAEADKM EECCCCCCHHHHHHH	28.78	29899451
2374	Phosphorylation	MSGMSAPSPSLPTPS HCCCCCCCCCCCCCC	27.17	29514104
2376	Phosphorylation	GMSAPSPSLPTPSSS CCCCCCCCCCCCCCH	51.85	25338131
2379	Phosphorylation	APSPSLPTPSSSLAL CCCCCCCCCCCHHHH	40.89	25338131
2399	Phosphorylation	QPSRLPLSGDSEGHE CCCCCCCCCCCCCCC	38.32	25338131
2402	Phosphorylation	RLPLSGDSEGHERET CCCCCCCCCCCCCCC	49.34	25338131
2409	Phosphorylation	SEGHERETEPIPKMK CCCCCCCCCCCCCCC	53.97	25338131
2420	Phosphorylation	PKMKVMESPRKAPGS CCCCCCCCCCCCCCC	16.35	24453211
2420 (in isoform 4)	Phosphorylation	-	16.35	24719451
2427	Phosphorylation	SPRKAPGSTSGTSQD CCCCCCCCCCCCCCC	20.52	23684622
2428	Phosphorylation	PRKAPGSTSGTSQDG CCCCCCCCCCCCCCC	36.77	29550500
2429	Phosphorylation	RKAPGSTSGTSQDGN CCCCCCCCCCCCCCC	41.59	29550500
2431	Phosphorylation	APGSTSGTSQDGNTK CCCCCCCCCCCCCCC	24.00	29899451
2432	Phosphorylation	PGSTSGTSQDGNTKD CCCCCCCCCCCCCCC	29.78	29899451
2446	Phosphorylation	DARGNLGSLPLGKTR CCCCCCCCCCCCCCC	29.94	29233185
2452	O-linked_Glycosylation	GSLPLGKTRPGAVSP CCCCCCCCCCCCCCC	40.05	41305787
2452	Phosphorylation	GSLPLGKTRPGAVSP CCCCCCCCCCCCCCC	40.05	27087446
2458	Phosphorylation	KTRPGAVSPLNSPLS CCCCCCCCCCCCCCC	24.12	27087446
2458 (in isoform 4)	Phosphorylation	-	24.12	24719451
2462	Phosphorylation	GAVSPLNSPLSTTFP CCCCCCCCCCCCCCC	34.60	27087446
2462 (in isoform 4)	Phosphorylation	-	34.60	24719451
2465	Phosphorylation	SPLNSPLSTTFPSPF CCCCCCCCCCCCCCC	28.87	25168779
2466	Phosphorylation	PLNSPLSTTFPSPFG CCCCCCCCCCCCCCC	39.89	25619855
2467	Phosphorylation	LNSPLSTTFPSPFGK CCCCCCCCCCCCCCC	30.12	25619855
2470	Phosphorylation	PLSTTFPSPFGKEAF CCCCCCCCCCCCCCC	28.77	25619855
2480	Phosphorylation	GKEAFPPSSPLQKGG CCCCCCCCCCCCCCC	44.84	25619855
2481	Phosphorylation	KEAFPPSSPLQKGGS CCCCCCCCCCCCCCC	35.09	26824392
2488	Phosphorylation	SPLQKGGSFWSSIPA CCCCCCCCCCCCCCC	32.01	25777480
2491	Phosphorylation	QKGGSFWSSIPASPA CCCCCCCCCCCCCCC	19.17	25777480
2492	Phosphorylation	KGGSFWSSIPASPAS CCCCCCCCCCCCCCC	24.16	28066266
2496	Phosphorylation	FWSSIPASPASRPSS CCCCCCCCCCCCCCC	18.68	26824392
2496 (in isoform 4)	Phosphorylation	-	18.68	24719451
2499	Phosphorylation	SIPASPASRPSSFTF CCCCCCCCCCCCCCC	48.37	26643407
2502	Phosphorylation	ASPASRPSSFTFPGD CCCCCCCCCCCCCCC	36.65	26643407
2503	Phosphorylation	SPASRPSSFTFPGDS CCCCCCCCCCCCCCC	30.87	26643407
2505	Phosphorylation	ASRPSSFTFPGDSDS CCCCCCCCCCCCCHH	30.76	29233185
2510	Phosphorylation	SFTFPGDSDSLQRQT CCCCCCCCHHHHHHH	34.71	26643407
2512	Phosphorylation	TFPGDSDSLQRQTHR CCCCCCHHHHHHHHC	30.29	29514104
2527	Phosphorylation	HAAPSKDTDRMSTCS CCCCCCCCCCCCCCC	29.28	-
2527 (in isoform 4)	Phosphorylation	-	29.28	-
2535	Phosphorylation	DRMSTCSSASEQSVQ CCCCCCCCHHHHHCH	37.65	-
2535 (in isoform 4)	Phosphorylation	-	37.65	-
2540	Phosphorylation	CSSASEQSVQSTQSN CCCHHHHHCHHCCCC	20.33	-
2540 (in isoform 4)	Phosphorylation	-	20.33	-
2555 (in isoform 3)	Phosphorylation	-	33.89	25338131
2559 (in isoform 3)	Phosphorylation	-	1.95	29899451
2560 (in isoform 3)	Phosphorylation	-	3.99	29899451
2631	Acetylation	NPDGTLKKSTSWHTA CCCCCCCCCCCHHHH	63.18	7625255
2632	Phosphorylation	PDGTLKKSTSWHTAL CCCCCCCCCCHHHHH	26.53	25159016
2633	Phosphorylation	DGTLKKSTSWHTALR CCCCCCCCCHHHHHH	44.72	25159016
2634	Phosphorylation	GTLKKSTSWHTALRL CCCCCCCCHHHHHHH	24.77	25159016
2637	Phosphorylation	KKSTSWHTALRLRKK CCCCCHHHHHHHHHH	22.56	28066266
2650	Acetylation	KKSEKKDKDGKRDGK HHHHCCCCCCCCCCC	76.80	7385599
2670	Phosphorylation	RKPREGLSNKVSVKL CCCCCCCCCCCEEEE	45.52	29550500
2674	Phosphorylation	EGLSNKVSVKLLNPN CCCCCCCEEEECCCC	18.36	29176673
2929	Phosphorylation	ENILVDQSLAKPTIK HHEEECCHHCCCEEE	26.32	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of TRIO_MOUSE !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of TRIO_MOUSE !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of TRIO_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NAV1_MOUSE	Nav1	physical	25065758

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry.";
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
Mol. Cell. Proteomics 8:904-912(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2458, AND MASSSPECTROMETRY.
PubMed: 19131326