AP2M1_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: AP2M1_RAT
• UniProt AC: P84092
• Protein Name: AP-2 complex subunit mu
• Gene Name: Ap2m1
• Organism: Rattus norvegicus (Rat).
• 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..
• 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
8	Phosphorylation	MIGGLFIYNHKGEVL CCCCEEEECCCCCEE	12.13	25575281
17	Phosphorylation	HKGEVLISRVYRDDI CCCCEEEEEEECCCC	16.13	25575281
45	Phosphorylation	HARQQVRSPVTNIAR CHHHHHCCCCCCHHC	25.51	27097102
59	Acetylation	RTSFFHVKRSNIWLA CEEEEEEECCCEEEE	41.35	22902405
149	Phosphorylation	HQTKEEQSQITSQVT CCCHHHHHHHHHHHH	27.16	23984901
152	Phosphorylation	KEEQSQITSQVTGQI HHHHHHHHHHHHHCC	12.89	27097102
153	Phosphorylation	EEQSQITSQVTGQIG HHHHHHHHHHHHCCC	25.04	27097102
156	Phosphorylation	SQITSQVTGQIGWRR HHHHHHHHHCCCCCC	18.74	27097102
204	Phosphorylation	SGRVVMKSYLSGMPE CCCHHHHHHHCCCCC	17.14	25575281
205	Phosphorylation	GRVVMKSYLSGMPEC CCHHHHHHHCCCCCC	10.20	25575281
213	Acetylation	LSGMPECKFGMNDKI HCCCCCCCCCCCCEE	43.20	22902405
219	Acetylation	CKFGMNDKIVIEKQG CCCCCCCEEEEEECC	33.59	22902405
224	Ubiquitination	NDKIVIEKQGKGTAD CCEEEEEECCCCCCC	53.91	-
229	Phosphorylation	IEKQGKGTADETSKS EEECCCCCCCCCCCC	34.13	25575281
233	Phosphorylation	GKGTADETSKSGKQS CCCCCCCCCCCCCCE	41.84	25575281
234	Phosphorylation	KGTADETSKSGKQSI CCCCCCCCCCCCCEE	23.83	25575281
235	Ubiquitination	GTADETSKSGKQSIA CCCCCCCCCCCCEEE	71.32	-
236	Phosphorylation	TADETSKSGKQSIAI CCCCCCCCCCCEEEE	51.49	25575281
240	Phosphorylation	TSKSGKQSIAIDDCT CCCCCCCEEEEECCC	19.92	25575281
256	Ubiquitination	HQCVRLSKFDSERSI HHEEEHHHCCCCCCE	58.75	-
256	Acetylation	HQCVRLSKFDSERSI HHEEEHHHCCCCCCE	58.75	22902405
281	Acetylation	LMRYRTTKDIILPFR EEEEEECCCEEEECC	46.44	22902405
308	Acetylation	LEVKVVIKSNFKPSL EEEEEEEECCCCHHH	27.95	22902405
309	Phosphorylation	EVKVVIKSNFKPSLL EEEEEEECCCCHHHE	36.05	28689409
312	Acetylation	VVIKSNFKPSLLAQK EEEECCCCHHHEEEE	37.64	22902405
314	Phosphorylation	IKSNFKPSLLAQKIE EECCCCHHHEEEEEE	36.28	25575281
319	Acetylation	KPSLLAQKIEVRIPT CHHHEEEEEEEECCC	34.92	22902405
347	Phosphorylation	GKAKYKASENAIVWK CCEEEECCCCCHHHH	27.51	25575281
354	Acetylation	SENAIVWKIKRMAGM CCCCHHHHHHHHHCC	27.70	22902405
378	Ubiquitination	ELLPTNDKKKWARPP EECCCCCCCCCCCCC	59.32	-
400	Acetylation	PFAPSGLKVRYLKVF CCCCCCCEEEEEEEE	28.35	22902405
405	Acetylation	GLKVRYLKVFEPKLN CCEEEEEEEECCCCC	35.62	22902405
410	Acetylation	YLKVFEPKLNYSDHD EEEEECCCCCCCCHH	42.01	22902405
420	Acetylation	YSDHDVIKWVRYIGR CCCHHHHHHHHHHCC	39.21	22902405
424	Phosphorylation	DVIKWVRYIGRSGIY HHHHHHHHHCCCCCE	9.71	22673903
428	Phosphorylation	WVRYIGRSGIYETRC HHHHHCCCCCEECCC	25.08	22673903
431	Phosphorylation	YIGRSGIYETRC--- HHCCCCCEECCC---	18.12	22673903
433	Phosphorylation	GRSGIYETRC----- CCCCCEECCC-----	21.99	22673903

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

Oops, there are no upstream regulatory protein records of AP2M1_RAT !!

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.	11516654

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_RAT !!

Protein-Protein Interaction

Oops, there are no PPI records of AP2M1_RAT !!

Drug and Disease Associations

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