AP2M1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: AP2M1_MOUSE
• UniProt AC: P84091
• Protein Name: AP-2 complex subunit mu
• Gene Name: Ap2m1
• Organism: Mus musculus (Mouse).
• Sequence Length: 435
• Subcellular Localization: Cell membrane. Membrane, coated pit; Peripheral membrane protein; Cytoplasmic side. AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV..
• Protein Description: Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity)..
• Protein Sequence: MIGGLFIYNHKGEVLISRVYRDDIGRNAVDAFRVNVIHARQQVRSPVTNIARTSFFHVKRSNIWLAAVTKQNVNAAMVFEFLYKMCDVMAAYFGKISEENIKNNFVLIYELLDEILDFGYPQNSETGALKTFITQQGIKSQHQTKEEQSQITSQVTGQIGWRREGIKYRRNELFLDVLESVNLLMSPQGQVLSAHVSGRVVMKSYLSGMPECKFGMNDKIVIEKQGKGTADETSKSGKQSIAIDDCTFHQCVRLSKFDSERSISFIPPDGEFELMRYRTTKDIILPFRVIPLVREVGRTKLEVKVVIKSNFKPSLLAQKIEVRIPTPLNTSGVQVICMKGKAKYKASENAIVWKIKRMAGMKESQISAEIELLPTNDKKKWARPPISMNFEVPFAPSGLKVRYLKVFEPKLNYSDHDVIKWVRYIGRSGIYETRC

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
17	Phosphorylation	HKGEVLISRVYRDDI CCCCEEEEEEECCCC	16.13	30482847
45	Phosphorylation	HARQQVRSPVTNIAR CHHHHHCCCCCCHHC	25.51	25521595
48	Phosphorylation	QQVRSPVTNIARTSF HHHCCCCCCHHCEEE	25.04	22324799
61	Phosphorylation	SFFHVKRSNIWLAAV EEEEEECCCEEEEEE	27.27	25521595
69	Phosphorylation	NIWLAAVTKQNVNAA CEEEEEECCCCCCHH	23.37	28059163
139	Ubiquitination	FITQQGIKSQHQTKE HHHHHHHHHCCCCHH	51.38	22790023
139	Malonylation	FITQQGIKSQHQTKE HHHHHHHHHCCCCHH	51.38	32601280
145	Ubiquitination	IKSQHQTKEEQSQIT HHHCCCCHHHHHHHH	53.32	22790023
149	Phosphorylation	HQTKEEQSQITSQVT CCCHHHHHHHHHHHH	27.16	25619855
152	Phosphorylation	KEEQSQITSQVTGQI HHHHHHHHHHHHHCC	12.89	25619855
153	Phosphorylation	EEQSQITSQVTGQIG HHHHHHHHHHHHCCC	25.04	23684622
156	Phosphorylation	SQITSQVTGQIGWRR HHHHHHHHHCCCCCC	18.74	25521595
167	Acetylation	GWRREGIKYRRNELF CCCCCCCCCCCCHHH	43.49	15618305
204	Phosphorylation	SGRVVMKSYLSGMPE CCCHHHHHHHCCCCC	17.14	20415495
205	Phosphorylation	GRVVMKSYLSGMPEC CCHHHHHHHCCCCCC	10.20	25195567
212	S-nitrosocysteine	YLSGMPECKFGMNDK HHCCCCCCCCCCCCE	3.49	-
212	S-nitrosylation	YLSGMPECKFGMNDK HHCCCCCCCCCCCCE	3.49	21278135
213	Acetylation	LSGMPECKFGMNDKI HCCCCCCCCCCCCEE	43.20	22826441
219	Ubiquitination	CKFGMNDKIVIEKQG CCCCCCCEEEEEECC	33.59	22790023
224	Malonylation	NDKIVIEKQGKGTAD CCEEEEEECCCCCCC	53.91	26320211
224	Ubiquitination	NDKIVIEKQGKGTAD CCEEEEEECCCCCCC	53.91	-
236	Phosphorylation	TADETSKSGKQSIAI CCCCCCCCCCCEEEE	51.49	29514104
238	Malonylation	DETSKSGKQSIAIDD CCCCCCCCCEEEEEC	48.22	26320211
238	Ubiquitination	DETSKSGKQSIAIDD CCCCCCCCCEEEEEC	48.22	-
240	Phosphorylation	TSKSGKQSIAIDDCT CCCCCCCEEEEECCC	19.92	25159016
246	S-nitrosylation	QSIAIDDCTFHQCVR CEEEEECCCHHHEEE	3.77	20925432
246	S-nitrosocysteine	QSIAIDDCTFHQCVR CEEEEECCCHHHEEE	3.77	-
251	S-nitrosocysteine	DDCTFHQCVRLSKFD ECCCHHHEEEHHHCC	1.12	-
251	Glutathionylation	DDCTFHQCVRLSKFD ECCCHHHEEEHHHCC	1.12	24333276
251	S-nitrosylation	DDCTFHQCVRLSKFD ECCCHHHEEEHHHCC	1.12	20925432
256	Malonylation	HQCVRLSKFDSERSI HHEEEHHHCCCCCCE	58.75	32601280
256	Ubiquitination	HQCVRLSKFDSERSI HHEEEHHHCCCCCCE	58.75	22790023
256	Acetylation	HQCVRLSKFDSERSI HHEEEHHHCCCCCCE	58.75	23806337
277	Phosphorylation	GEFELMRYRTTKDII CCEEEEEEEECCCEE	9.80	28059163
280	Phosphorylation	ELMRYRTTKDIILPF EEEEEEECCCEEEEC	20.09	28059163
281	Ubiquitination	LMRYRTTKDIILPFR EEEEEECCCEEEECC	46.44	22790023
312	Ubiquitination	VVIKSNFKPSLLAQK EEEECCCCHHHEEEE	37.64	-
312	Malonylation	VVIKSNFKPSLLAQK EEEECCCCHHHEEEE	37.64	26073543
314	Phosphorylation	IKSNFKPSLLAQKIE EECCCCHHHEEEEEE	36.28	51460349
337	S-palmitoylation	TSGVQVICMKGKAKY CCCCEEEEECCCEEE	2.12	28526873
337	S-nitrosocysteine	TSGVQVICMKGKAKY CCCCEEEEECCCEEE	2.12	-
337	S-nitrosylation	TSGVQVICMKGKAKY CCCCEEEEECCCEEE	2.12	21278135
337	Glutathionylation	TSGVQVICMKGKAKY CCCCEEEEECCCEEE	2.12	24333276
339	Ubiquitination	GVQVICMKGKAKYKA CCEEEEECCCEEEEC	53.50	22790023
345	Malonylation	MKGKAKYKASENAIV ECCCEEEECCCCCHH	44.74	32601280
345	Ubiquitination	MKGKAKYKASENAIV ECCCEEEECCCCCHH	44.74	22790023
347	Phosphorylation	GKAKYKASENAIVWK CCEEEECCCCCHHHH	27.51	22817900
354	Acetylation	SENAIVWKIKRMAGM CCCCHHHHHHHHHCC	27.70	23954790
354	Ubiquitination	SENAIVWKIKRMAGM CCCCHHHHHHHHHCC	27.70	22790023
378	Ubiquitination	ELLPTNDKKKWARPP EECCCCCCCCCCCCC	59.32	22790023
405	Acetylation	GLKVRYLKVFEPKLN CCEEEEEEEECCCCC	35.62	23806337
405	Malonylation	GLKVRYLKVFEPKLN CCEEEEEEEECCCCC	35.62	26320211
410	Ubiquitination	YLKVFEPKLNYSDHD EEEEECCCCCCCCHH	42.01	22790023
420	Acetylation	YSDHDVIKWVRYIGR CCCHHHHHHHHHHCC	39.21	22826441
420	Ubiquitination	YSDHDVIKWVRYIGR CCCHHHHHHHHHHCC	39.21	22790023
431	Phosphorylation	YIGRSGIYETRC--- HHCCCCCEECCC---	18.12	29514104

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

Oops, there are no upstream regulatory protein records of AP2M1_MOUSE !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
156	T	Phosphorylation	Phosphorylation at Thr-156 increases the affinity of the AP-2 complex for cargo membrane proteins during the initial stages of endocytosis.	21183079

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of AP2M1_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of AP2M1_MOUSE !!

Drug and Disease Associations

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