dbPTM

ITB3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	ITB3_HUMAN
UniProt AC	P05106
Protein Name	Integrin beta-3
Gene Name	ITGB3
Organism	Homo sapiens (Human).
Sequence Length	788
Subcellular Localization	Cell membrane Single-pass type I membrane protein . Cell projection, lamellipodium membrane . Cell junction, focal adhesion .
Protein Description	Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets (By similarity). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling. [PubMed: 23125415]
Protein Sequence	MRARPRPRPLWATVLALGALAGVGVGGPNICTTRGVSSCQQCLAVSPMCAWCSDEALPLGSPRCDLKENLLKDNCAPESIEFPVSEARVLEDRPLSDKGSGDSSQVTQVSPQRIALRLRPDDSKNFSIQVRQVEDYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFGAFVDKPVSPYMYISPPEALENPCYDMKTTCLPMFGYKHVLTLTDQVTRFNEEVKKQSVSRNRDAPEGGFDAIMQATVCDEKIGWRNDASHLLVFTTDAKTHIALDGRLAGIVQPNDGQCHVGSDNHYSASTTMDYPSLGLMTEKLSQKNINLIFAVTENVVNLYQNYSELIPGTTVGVLSMDSSNVLQLIVDAYGKIRSKVELEVRDLPEELSLSFNATCLNNEVIPGLKSCMGLKIGDTVSFSIEAKVRGCPQEKEKSFTIKPVGFKDSLIVQVTFDCDCACQAQAEPNSHRCNNGNGTFECGVCRCGPGWLGSQCECSEEDYRPSQQDECSPREGQPVCSQRGECLCGQCVCHSSDFGKITGKYCECDDFSCVRYKGEMCSGHGQCSCGDCLCDSDWTGYYCNCTTRTDTCMSSNGLLCSGRGKCECGSCVCIQPGSYGDTCEKCPTCPDACTFKKECVECKKFDRGALHDENTCNRYCRDEIESVKELKDTGKDAVNCTYKNEDDCVVRFQYYEDSSGKSILYVVEEPECPKGPDILVVLLSVMGAILLIGLAALLIWKLLITIHDRKEFAKFEEERARAKWDTANNPLYKEATSTFTNITYRGT

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
61	Phosphorylation	DEALPLGSPRCDLKE CCCCCCCCCCCCCCC	19.49	20562096
67	Ubiquitination	GSPRCDLKENLLKDN CCCCCCCCCCCCCCC	31.16	29967540
100	Phosphorylation	RPLSDKGSGDSSQVT CCCCCCCCCCHHHCE	45.21	28270605
103	Phosphorylation	SDKGSGDSSQVTQVS CCCCCCCHHHCEEEC	26.62	28270605
104	Phosphorylation	DKGSGDSSQVTQVSP CCCCCCHHHCEEECC	33.15	28270605
107	Phosphorylation	SGDSSQVTQVSPQRI CCCHHHCEEECCCEE	18.67	28270605
110	Phosphorylation	SSQVTQVSPQRIALR HHHCEEECCCEEEEE	12.90	28787133
125	N-linked_Glycosylation	LRPDDSKNFSIQVRQ ECCCCCCCEEEEEEE	39.59	16263699
127	Phosphorylation	PDDSKNFSIQVRQVE CCCCCCEEEEEEEEC	22.85	27794612
208	Phosphorylation	NPCYDMKTTCLPMFG CCCCCCCCCEECCCC	18.99	-
221	Phosphorylation	FGYKHVLTLTDQVTR CCCCEEEEHHHHHHH	26.90	28060719
223	Phosphorylation	YKHVLTLTDQVTRFN CCEEEEHHHHHHHCC	21.10	28060719
227	Phosphorylation	LTLTDQVTRFNEEVK EEHHHHHHHCCHHHH	24.74	-
346	N-linked_Glycosylation	NVVNLYQNYSELIPG HHHHHHHHHHHHCCC	28.83	11546839
397	N-linked_Glycosylation	EELSLSFNATCLNNE CHHEEEEEEEECCCC	30.85	11546839
422	Phosphorylation	LKIGDTVSFSIEAKV CCCCCEEEEEEEEEE	18.50	28634298
424	Phosphorylation	IGDTVSFSIEAKVRG CCCEEEEEEEEEECC	16.41	28634298
439	Phosphorylation	CPQEKEKSFTIKPVG CCCCCCCCEEEECCC	28.81	-
441	Phosphorylation	QEKEKSFTIKPVGFK CCCCCCEEEECCCCC	34.87	-
478	N-linked_Glycosylation	SHRCNNGNGTFECGV CCCCCCCCCEEECCE	48.75	17660510
585	N-linked_Glycosylation	DWTGYYCNCTTRTDT CCCCEECCCCCCCCC	15.28	11546839
611	Phosphorylation	RGKCECGSCVCIQPG CCCEECCCEEEECCC	18.29	28387310
619	Phosphorylation	CVCIQPGSYGDTCEK EEEECCCCCCCCCCC	32.40	28387310
623	Phosphorylation	QPGSYGDTCEKCPTC CCCCCCCCCCCCCCC	20.43	28387310
660	Phosphorylation	DENTCNRYCRDEIES CCCHHHHHCHHHHHH	4.28	-
667	Phosphorylation	YCRDEIESVKELKDT HCHHHHHHHHHHHHC	44.12	28060719
669	Ubiquitination	RDEIESVKELKDTGK HHHHHHHHHHHHCCC	67.61	29967540
680	N-linked_Glycosylation	DTGKDAVNCTYKNED HCCCCCCCCEECCCC	17.71	11546839
767	Phosphorylation	RARAKWDTANNPLYK HHHHHHCCCCCHHHH	30.12	29970186
773	Phosphorylation	DTANNPLYKEATSTF CCCCCHHHHCHHHCC	14.19	11723131
777	Phosphorylation	NPLYKEATSTFTNIT CHHHHCHHHCCCCCE	29.41	29255136
778	O-linked_Glycosylation	PLYKEATSTFTNITY HHHHCHHHCCCCCEE	28.68	22530207
778	Phosphorylation	PLYKEATSTFTNITY HHHHCHHHCCCCCEE	28.68	29255136
779	Phosphorylation	LYKEATSTFTNITYR HHHCHHHCCCCCEEC	30.08	29255136
781	Phosphorylation	KEATSTFTNITYRGT HCHHHCCCCCEECCC	26.29	29255136
784	O-linked_Glycosylation	TSTFTNITYRGT--- HHCCCCCEECCC---	14.83	22530201
784	Phosphorylation	TSTFTNITYRGT--- HHCCCCCEECCC---	14.83	28060719
785	Phosphorylation	STFTNITYRGT---- HCCCCCEECCC----	11.84	11546839
788	Phosphorylation	TNITYRGT------- CCCEECCC-------	26.83	28857561

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

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
773	Y	Phosphorylation	Kinase	SRC	P12931	PSP
773	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
777	T	Phosphorylation	Kinase	PDK1	Q15118	GPS
777	T	Phosphorylation	Kinase	PDPK1	O15530	PhosphoELM
779	T	Phosphorylation	Kinase	AKT1	P31749	Uniprot
779	T	Phosphorylation	Kinase	PDK1	Q15118	GPS
779	T	Phosphorylation	Kinase	PDK1	O15530	PSP
779	T	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
785	Y	Phosphorylation	Kinase	SYK	P43405	GPS
785	Y	Phosphorylation	Kinase	SRC	P12931	PSP
785	Y	Phosphorylation	Kinase	SYK	Q15046	PhosphoELM
785	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
779	T	Phosphorylation		10896934
Phosphorylation of Thr-779 inhibits SHC binding.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of ITB3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ITAV_HUMAN	ITGAV	physical	11884718
FAK1_HUMAN	PTK2	physical	11927607
CENPR_HUMAN	ITGB3BP	physical	11864709
PECA1_HUMAN	PECAM1	physical	10982404
FAK1_HUMAN	PTK2	physical	9169439
PGFRB_HUMAN	PDGFRB	physical	10964931
TLN1_HUMAN	TLN1	physical	11932255
CENPR_HUMAN	ITGB3BP	physical	7593198
PGFRA_HUMAN	PDGFRA	physical	11953315
KSYK_HUMAN	SYK	physical	11042121
TSP1_HUMAN	THBS1	physical	14963009
EPHA2_HUMAN	EPHA2	physical	23874206
ITA5_HUMAN	ITGA5	physical	22470492
PDIA1_HUMAN	P4HB	physical	21670307
PA24A_HUMAN	PLA2G4A	physical	18840708
VIME_HUMAN	VIM	physical	18840708
KPCB_HUMAN	PRKCB	physical	18840708
SHC1_HUMAN	SHC1	physical	19889638
FAK1_HUMAN	PTK2	physical	19889638
VGFR2_HUMAN	KDR	physical	25644401
ITA4_HUMAN	ITGA4	physical	25792870
ITAV_HUMAN	ITGAV	physical	25792870
ITB1_HUMAN	ITGB1	physical	25792870
ITA2B_HUMAN	ITGA2B	physical	9351872
GCN4_YEAST	GCN4	physical	11412103
ITA2B_HUMAN	ITGA2B	physical	15219201
CIB1_HUMAN	CIB1	physical	24163826
SHC1_HUMAN	SHC1	physical	10896934
FINC_HUMAN	FN1	physical	11478883
FIBG_HUMAN	FGG	physical	16877710
ITAV_HUMAN	ITGAV	physical	10891446
ITA2B_HUMAN	ITGA2B	physical	10891446

Drug and Disease Associations

Kegg Disease
H00083	Allograft rejection
H00226	Glanzmann thrombasthenia
OMIM Disease
273800	Glanzmann thrombasthenia (GT)
187800	Bleeding disorder, platelet-type 16 (BDPLT16)
Kegg Drug
D01029	Tirofiban hydrochloride (USAN); Tirofiban hydrochloride hydrate; Aggrastat (TN)
D02778	Abciximab (genetical recombination) (JAN); Abciximab (USAN/INN); Reopro (TN)
D03497	Cilengitide (USAN/INN)
D03971	Elarofiban (USAN)
D04659	Lamifiban (USAN/INN)
D04660	Lamifiban hydrochloride (USAN)
D04785	Lotrafiban hydrochloride (USAN)
D05267	Orbofiban acetate (USAN)
D05772	Roxifiban acetate (USAN)
D05834	Sibrafiban (USAN/INN)
D06335	Xemilofiban hydrochloride (USAN)
D06649	Tadocizumab (USAN)
D06888	Eptifibatide (INN); Integrilin (TN)
D08607	Tirofiban (INN); Agrastat (TN)
D09342	Etaracizumab (USAN/INN); Abegrin (TN)
D09903	Fluciclatide F 18 (USAN/INN)
D09929	Maraciclatide (USAN/INN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of ITB3_HUMAN

Related Literatures of Post-Translational Modification

N-linked Glycosylation
Reference	PubMed
"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry."; Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; J. Proteome Res. 8:651-661(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-680, AND MASSSPECTROMETRY.	19159218 [Abstract]
"Elucidation of N-glycosylation sites on human platelet proteins: aglycoproteomic approach."; Lewandrowski U., Moebius J., Walter U., Sickmann A.; Mol. Cell. Proteomics 5:226-233(2006). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125, AND MASSSPECTROMETRY.	16263699 [Abstract]
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,hydrazide chemistry, and mass spectrometry."; Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,Moore R.J., Smith R.D.; J. Proteome Res. 4:2070-2080(2005). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125, AND MASSSPECTROMETRY.	16335952 [Abstract]
Phosphorylation
Reference	PubMed
"Threonine phosphorylation of the beta 3 integrin cytoplasmic tail, ata site recognized by PDK1 and Akt/PKB in vitro, regulates Shcbinding."; Kirk R.I., Sanderson M.R., Lerea K.M.; J. Biol. Chem. 275:30901-30906(2000). Cited for: PHOSPHORYLATION AT THR-779.	10896934 [Abstract]
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-773, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Phosphoproteome of resting human platelets."; Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.; J. Proteome Res. 7:526-534(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-773 AND TYR-785, ANDMASS SPECTROMETRY.	18088087 [Abstract]
"Outside-in integrin signal transduction. Alpha IIb beta 3-(GP IIbIIIa) tyrosine phosphorylation induced by platelet aggregation."; Law D.A., Nannizzi-Alaimo L., Phillips D.R.; J. Biol. Chem. 271:10811-10815(1996). Cited for: PHOSPHORYLATION AT TYR-773 AND TYR-785 (ISOFORM BETA-3A).	8631894 [Abstract]

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