Reviewed,
UniProtKB/Swiss-Prot O94973 (AP2A2_HUMAN)
Last modified
December 15, 2009.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: AP-2 complex subunit alpha-2 Alternative name(s): Adapter-related protein complex 2 alpha-2 subunit Adaptor protein complex AP-2 subunit alpha-2 Alpha2-adaptin Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit Alpha-adaptin C Clathrin assembly protein complex 2 alpha-C large chain 100 kDa coated vesicle protein C Huntingtin-interacting protein J Huntingtin yeast partner J | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 939 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| 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. |
| 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. |
| 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. |
| 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 |
| Coding sequence diversity | Alternative splicing |
| Ligand | Lipid-binding |
| PTM | Acetylation Phosphoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | endocytosis Inferred from electronic annotation. Source: UniProtKB-KW intracellular protein transportNon-traceable author statement. Source: UniProtKB regulation of defense response to virus by virusInferred from Experiment. Source: Reactome |
| Cellular component | AP-2 adaptor complex Non-traceable author statement. Source: UniProtKB cytosolInferred from Experiment. Source: Reactome |
| Molecular function | lipid binding Inferred from electronic annotation. Source: UniProtKB-KW protein bindingInferred from electronic annotation. Source: InterPro protein transporter activityInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O94973-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: O94973-2) The sequence of this isoform differs from the canonical sequence as follows: 271-271: P → PE | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 (identifier: O94973-3) The sequence of this isoform differs from the canonical sequence as follows: 271-271: P → PE 653-655: STP → VCL 656-939: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 939 | 939 | AP-2 complex subunit alpha-2 | PRO_0000193732 | |||||
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 Ref.13 | ||||||
| Modified residue | 808 | 1 | Phosphotyrosine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 271 | 1 | P → PE in isoform 2 and isoform 3. | VSP_035762 | |||||
| Alternative sequence | 653 – 655 | 3 | STP → VCL in isoform 3. | VSP_035763 | |||||
| Alternative sequence | 656 – 939 | 284 | Missing in isoform 3. | VSP_035764 | |||||
Experimental info | |||||||||
| Sequence conflict | 20 | 1 | I → T in BAB55435. Ref.4 | ||||||
| Sequence conflict | 450 | 1 | R → Q in AAC27505. Ref.6 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed: 10048485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain. |
| [2] | "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION. |
| [3] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [4] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain. |
| [6] | "Huntingtin interacts with a family of WW domain proteins." Faber P.W., Barnes G.T., Srinidhi J., Chen J., Gusella J.F., MacDonald M.E. Hum. Mol. Genet. 7:1463-1474(1998) [PubMed: 9700202] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 318-476. Tissue: Testis. |
| [7] | "The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis." Waelter S., Scherzinger E., Hasenbank R., Nordhoff E., Lurz R., Goehler H., Gauss C., Sathasivam K., Bates G.P., Lehrach H., Wanker E.E. Hum. Mol. Genet. 10:1807-1817(2001) [PubMed: 11532990] [Abstract] Cited for: INTERACTION WITH HIP1. |
| [8] | "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. |
| [9] | "Effect of clathrin heavy chain- and alpha-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells." Hinrichsen L., Harborth J., Andrees L., Weber K., Ungewickell E.J. J. Biol. Chem. 278:45160-45170(2003) [PubMed: 12960147] [Abstract] Cited for: FUNCTION IN CLATHRIN-MEDIATED ENDOCYTOSIS. |
| [10] | "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. |
| [11] | "The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway." Lau A.W., Chou M.M. J. Cell Sci. 121:4008-4017(2008) [PubMed: 19033387] [Abstract] Cited for: FUNCTION OF THE AP-2 COMPLEX IN NON-CLATHRIN-DEPENDENT ENDOCYTOSIS. |
| [12] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [13] | "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-35, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AB020706 mRNA. Translation: BAA74922.2. AK223558 mRNA. Translation: BAD97278.1. AK027891 mRNA. Translation: BAB55435.1. BC006155 mRNA. Translation: AAH06155.1. AF049527 mRNA. Translation: AAC27505.1. | |
| IPI | IPI00016621. IPI00914938. IPI00914952. |
| RefSeq | NP_036437.1. |
| UniGene | Hs.19121 |
3D structure databases | |
| SMR | O94973. Positions 694-939. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | O94973. |
PTM databases | |
| PhosphoSite | O94973. |
Proteomic databases | |
| PRIDE | O94973. |
Genome annotation databases | |
| Ensembl | ENST00000448903; ENSP00000413234; ENSG00000183020; Homo sapiens. [Genome view] |
| GeneID | 161. |
| KEGG | hsa:161. |
| UCSC | uc001lss.1. human. |
Organism-specific databases | |
| CTD | 161. |
| GeneCards | GC11P000915. |
| H-InvDB | HIX0020597. |
| HGNC | HGNC:562. AP2A2. |
| HPA | CAB017514. |
| MIM | 607242. gene. |
| PharmGKB | PA24853. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | O94973. |
| InParanoid | O94973. |
| OMA | FPEVKPT. |
Enzyme and pathway databases | |
| Reactome | REACT_11061. Signalling by NGF. REACT_13685. Synaptic Transmission. REACT_6185. HIV Infection. REACT_9417. Signaling by EGFR. |
Gene expression databases | |
| ArrayExpress | O94973. |
| Bgee | O94973. |
| CleanEx | HS_AP2A2. |
| Genevestigator | O94973. |
| GermOnline | ENSG00000183020. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR017104. AP2_complex_asu. IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR009028. Calthrin/coatomer_app_sub_C. IPR002553. Clathrin/coatomer_adapt-like_N. IPR013041. Clathrin/coatomer_app_Ig-like. 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. [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] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 643. |
| PMAP-CutDB | O94973. |
| SOURCE | Search... |
Entry information
| Entry name | AP2A2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O94973 Secondary accession number(s): O75403, Q53ET1, Q96SI8 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


