P18484 (AP2A2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
AP-2 complex subunit alpha-2

Alternative name(s):
100 kDa coated vesicle protein C
Adapter-related protein complex 2 alpha-2 subunit
Adaptor protein complex AP-2 subunit alpha-2
Alpha-adaptin C
Alpha2-adaptin
Clathrin assembly protein complex 2 alpha-C large chain
Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit

Gene names

Name:	Ap2a2
Synonyms:	Adtab

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	938 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 surrrounded 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 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif By similarity. Ref.4 Ref.5
Subunit structure	Adaptor protein complex 2 (AP-2) is an heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Binds EPN1, EPS15, AMPH, SNAP91 and BIN1. Interacts with HIP1. Interacts with DGKD isoform 2 By similarity. Interacts with DENND1A, DENND1B and DENND1C By similarity.
Subcellular location	Cell membrane By similarity. Membrane › coated pit; Peripheral membrane protein; Cytoplasmic side By similarity. Note: AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV By similarity.
Tissue specificity	Widely expressed.
Sequence similarities	Belongs to the adaptor complexes large subunit family.

Ontologies

Keywords
Biological process	Endocytosis Protein transport Transport
Cellular component	Cell membrane Coated pit Membrane
Ligand	Lipid-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW intracellular protein transport Inferred from electronic annotation. Source: InterPro
Cellular component	clathrin adaptor complex Inferred from electronic annotation. Source: InterPro coated pit Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Traceable author statement. Source: Reactome
Molecular function	lipid binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Syt1	P21707	5	EBI-539360,EBI-458098

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.2 Ref.3

Chain

2 – 938

937

AP-2 complex subunit alpha-2

PRO_0000193734

Regions

Region

5 – 80

76

Lipid-binding

Sites

Binding site

43

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

53

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

57

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

58

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

61

1

Phosphatidylinositol lipid headgroup By similarity

Amino acid modifications

Modified residue

35

1

N6-acetyllysine By similarity

Modified residue

807

1

Phosphotyrosine By similarity

Secondary structure

1

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938

Helix Strand Turn

Details...

Helix

701 – 706

6

Beta strand

712 – 718

7

Beta strand

720 – 731

12

Beta strand

734 – 743

10

Beta strand

745 – 747

3

Beta strand

749 – 757

9

Helix

760 – 765

6

Beta strand

766 – 769

4

Beta strand

782 – 791

10

Beta strand

800 – 807

8

Beta strand

810 – 817

8

Helix

822 – 825

4

Beta strand

826 – 828

3

Helix

833 – 842

10

Helix

846 – 848

3

Beta strand

849 – 855

7

Helix

862 – 872

11

Beta strand

875 – 877

3

Beta strand

880 – 883

4

Beta strand

887 – 894

8

Beta strand

899 – 909

11

Turn

910 – 913

4

Beta strand

914 – 922

9

Helix

924 – 935

12

Sequences

	Sequence		Length	Mass (Da)
	P18484 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 406428A9BFFB1E53	FASTA	938	104,045
	10 20 30 40 50 60 MPAVSKGEGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC 70 80 90 100 110 120 KLLFIFLLGH DIDFGHMEAV NLLSSNRYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL 130 140 150 160 170 180 ASRNPTFMGL ALHCIANVGS REMAEAFAGE IPKILVAGDT MDSVKQSAAL CLLRLYRTSP 190 200 210 220 230 240 DLVPMGDWTS RVVHLLNDQH LGVVTAATSL ITTLAQKNPE EFKTSVSLAV SRLSRIVTSA 250 260 270 280 290 300 STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PDPAVRGRLT ECLETILNKA QEPPKSKKVQ 310 320 330 340 350 360 HSNAKNAVLF EAISLIIHHD SEPNLLVRAC NQLGQFLQHR ETNLRYLALE SMCTLASSEF 370 380 390 400 410 420 SHEAVKTHIE TVINALKTER DVSVRQRAVD LLYAMCDRSN AQQIVAEMLS YLETADYSIR 430 440 450 460 470 480 EEIVLKVAIL AEKYAVDYTW YVDTILNLIR IAGDYVSEEV WYRVIQIVIN RDDVQGYAAK 490 500 510 520 530 540 TVFEALQAPA CHENLVKVGG YILGEFGNLI AGDPRSSPLI QFNLLHSKFH LCSVPTRALL 550 560 570 580 590 600 LSTYIKFVNL FPEVKATIQD VLRSDSQLKN ADVELQQRAV EYLRLSTVAS TDILATVLEE 610 620 630 640 650 660 MPPFPERESS ILAKLKKKKG PSTVTDLEET KRERSIDVNG GPEPVPASTS AASTPSPSAD 670 680 690 700 710 720 LLGLGAVPPA PTGPPPSSGG GLLVDVFSDS ASAVAPLAPG SEDNFARFVC KNNGVLFENQ 730 740 750 760 770 780 LLQIGLKSEF RQNLGRMFIF YGNKTSTQFL NFTPTLICAD DLQTNLNLQT KPVDPTVDGG 790 800 810 820 830 840 AQVQQVINIE CISDFTEAPV LNIQFRYGGT FQNVSVKLPI TLNKFFQPTE MASQDFFQRW 850 860 870 880 890 900 KQLSNPQQEV QNIFKAKHPM DTEITKAKII GFGSALLEEV DPNPANFVGA GIIHTKTTQI 910 920 930 GCLLRLEPNL QAQMYRLTLR TSKDTVSQRL CELLSEQF

References

[1]	"Sequence of the rat alpha c large chain of the clathrin associated protein complex AP-2." Tucker K.L., Nathanson K., Kirchhausen T. Nucleic Acids Res. 18:5306-5306(1990) [PubMed: 2402467] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structural and functional division into two domains of the large (100- to 115-kDa) chains of the clathrin-associated protein complex AP-2." Kirchhausen T., Nathanson K.L., Matsui W., Vaisberg A., Chow E.P., Burne C., Keen J.H., Davis A.E. Proc. Natl. Acad. Sci. U.S.A. 86:2612-2616(1989) [PubMed: 2495531] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-18. Tissue: Brain.
[3]	"Inositol hexakisphosphate receptor identified as the clathrin assembly protein AP-2." Voglmaier S.M., Keen J.H., Murphy J.E., Ferris C.D., Prestwich G.D., Snyder S.H., Theibert A.B. Biochem. Biophys. Res. Commun. 187:158-163(1992) [PubMed: 1325787] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-18.
[4]	"Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network." Nakatsu F., Ohno H. Cell Struct. Funct. 28:419-429(2003) [PubMed: 14745134] [Abstract] Cited for: FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
[5]	"Adaptors for clathrin coats: structure and function." Owen D.J., Collins B.M., Evans P.R. Annu. Rev. Cell Dev. Biol. 20:153-191(2004) [PubMed: 15473838] [Abstract] Cited for: FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X53773 mRNA. Translation: CAA37791.1.

IPI

IPI00471901.

PIR

S11276.

UniGene

Rn.34928.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VGL	X-ray	2.59	A	1-620	[»]
2XA7	X-ray	3.10	A	1-621	[»]

ProteinModelPortal

P18484.

SMR

P18484. Positions 9-607, 702-938.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29765N.

IntAct

P18484. 3 interactions.

MINT

MINT-93156.

STRING

P18484.

Proteomic databases

PRIDE

P18484.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

UCSC

BC081786. rat.

Organism-specific databases

RGD

71015. Ap2a2.

Phylogenomic databases

eggNOG

roNOG04940.

HOVERGEN

HBG050518.

InParanoid

P18484.

OrthoDB

EOG4HMJ8J.

Enzyme and pathway databases

Reactome

REACT_111984. Signal Transduction.

Gene expression databases

ArrayExpress

P18484.

Genevestigator

P18484.

GermOnline

ENSRNOG00000019534. Rattus norvegicus.

Family and domain databases

InterPro

IPR017104. AP2_complex_asu.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR002553. Clathrin/coatomer_adapt-like_N.
IPR013038. Clathrin_a-adaptin_app_Ig-like.
IPR003164. Clathrin_a-adaptin_app_sub_C.
IPR008152. Clathrin_a/b/g-adaptin_app_Ig.
IPR015873. Clathrin_a/coatomer_app_sub_C.
IPR009028. Coatomer/calthrin_app_sub_C.
IPR013041. Coatomer/clathrin_app_Ig-like.
[Graphical view]

Gene3D

G3DSA:3.30.310.30. AP2_A_adaptin_C. 1 hit.
G3DSA:1.25.10.10. ARM-like. 1 hit.
G3DSA:2.60.40.1030. Clathrin_a-adaptin_app_Ig-like. 1 hit.

Pfam

PF01602. Adaptin_N. 1 hit.
PF02296. Alpha_adaptin_C. 1 hit.
PF02883. Alpha_adaptinC2. 1 hit.
[Graphical view]

PIRSF

PIRSF037091. AP2_complex_alpha. 1 hit.

SMART

SM00809. Alpha_adaptinC2. 1 hit.
[Graphical view]

SUPFAM

SSF55711. AP2_adap_app. 1 hit.
SSF48371. ARM-type_fold. 1 hit.
SSF49348. Clath_adapt. 1 hit.

ProtoNet

Search...

Entry information

Entry name

AP2A2_RAT

Accession

Primary (citable) accession number: P18484

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	January 23, 2007
Last modified:	December 14, 2011
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program