ZAP70_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: ZAP70_MOUSE
• UniProt AC: P43404
• Protein Name: Tyrosine-protein kinase ZAP-70
• Gene Name: Zap70
• Organism: Mus musculus (Mouse).
• Sequence Length: 618
• Subcellular Localization: Cytoplasm. Cell membrane; Peripheral membrane protein. In quiescent T-lymphocytes, ZAP70 is cytoplasmic. Upon TCR activation, it is recruited at the plasma membrane by interacting with CD3Z. Colocalizes together with RHOH in the immunological synapse
• Protein Description: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR)..
• Protein Sequence: MPDPAAHLPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCQFYSQDPDGLPCNLRKPCNRPPGLEPQPGVFDCLRDAMVRDYVRQTWKLEGDALEQAIISQAPQVEKLIATTAHERMPWYHSSLTREEAERKLYSGQQTDGKFLLRPRKEQGTYALSLVYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLKLKADGLIYRLKEVCPNSSASAAVAAPTLPAHPSTFTQPQRRVDTLNSDGYTPEPARLASSTDKPRPMPMDTSVYESPYSDPEELKDKKLFLKRENLLVADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADKDEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPLHKFLLGKKEEIPVSNVAELLHQVAMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVLDFIKQGKRMECPPECPPEMYALMSDCWIYKWEDRPDFLTVEQRMRNYYYSLASRAEGPPQCEQVAEAACG

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
37 (in isoform 3)	Phosphorylation	-	27.58	24759943
44 (in isoform 3)	Phosphorylation	-	26.99	24759943
68	Phosphorylation	IERQLNGTYAIAGGK CCHHCCCCEEECCCC	14.54	25367039
69	Phosphorylation	ERQLNGTYAIAGGKA CHHCCCCEEECCCCC	9.45	25367039
164	Phosphorylation	AHERMPWYHSSLTRE HHHHCCCCCCCCCHH	5.97	-
248	Phosphorylation	LKADGLIYRLKEVCP HHCCCEEEEEHHHCC	18.22	-
284	Phosphorylation	QPQRRVDTLNSDGYT CCCHHHCCCCCCCCC	25.61	28833060
287	Phosphorylation	RRVDTLNSDGYTPEP HHHCCCCCCCCCCCH	35.21	28833060
290	Phosphorylation	DTLNSDGYTPEPARL CCCCCCCCCCCHHHH	24.90	20438120
291	Phosphorylation	TLNSDGYTPEPARLA CCCCCCCCCCHHHHC	27.06	25266776
299	Phosphorylation	PEPARLASSTDKPRP CCHHHHCCCCCCCCC	38.06	25266776
300	Phosphorylation	EPARLASSTDKPRPM CHHHHCCCCCCCCCC	34.71	-
314	Phosphorylation	MPMDTSVYESPYSDP CCCCCCCCCCCCCCH	15.51	22817900
318	Phosphorylation	TSVYESPYSDPEELK CCCCCCCCCCHHHHH	34.68	15268851
490	Phosphorylation	KALGADDSYYTARSA HHHCCCCCCCCCHHC	22.16	28833060
491	Phosphorylation	ALGADDSYYTARSAG HHCCCCCCCCCHHCC	16.30	20438120
492	Phosphorylation	LGADDSYYTARSAGK HCCCCCCCCCHHCCC	9.62	21829558
493	Phosphorylation	GADDSYYTARSAGKW CCCCCCCCCHHCCCC	13.83	28833060
524	Phosphorylation	SRSDVWSYGVTMWEA CCHHHHHHCCCHHHH	10.41	-
534	Phosphorylation	TMWEAFSYGQKPYKK CHHHHHHCCCCCCCC	19.68	-

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
314	Y	Phosphorylation	Kinase	LCK	P06240	Uniprot
318	Y	Phosphorylation	Kinase	ABL1	P00520	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of ZAP70_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 ZAP70_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
LCK_MOUSE	Lck	physical	16501569
CBL_MOUSE	Cbl	physical	8551236
B3AT_MOUSE	Slc4a1	physical	8798454
B3AT_MOUSE	Slc4a1	physical	10358158
DLG1_MOUSE	Dlg1	physical	15699074
WASP_MOUSE	Was	physical	15699074
LCK_MOUSE	Lck	physical	15699074
CBL_MOUSE	Cbl	physical	20298671

Drug and Disease Associations

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