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O94973 (AP2A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
AP-2 complex subunit alpha-2
Alternative name(s):
100 kDa coated vesicle protein C
Adapter-related protein complex 2 subunit alpha-2
Adaptor protein complex AP-2 subunit alpha-2
Alpha-adaptin C
Alpha2-adaptin
Clathrin assembly protein complex 2 alpha-C large chain
Huntingtin yeast partner J
Huntingtin-interacting protein 9
Short name=HIP-9
Huntingtin-interacting protein J
Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit
Gene names
Name:AP2A2
Synonyms:ADTAB, CLAPA2, HIP9, HYPJ, KIAA0899
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length939 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 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 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.8 Ref.9 Ref.10 Ref.11

Subunit structure

Adaptor protein complex 2 (AP-2) is a 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. Interacts with FCHO1 and DAB2. Interacts with ATAT1; this interaction is required for efficient alpha-tubulin acetylation by ATAT1. Ref.7 Ref.13 Ref.14

Subcellular location

Cell membrane By similarity. Membranecoated 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 processEndocytosis
Protein transport
Transport
   Cellular componentCell membrane
Coated pit
Membrane
   Coding sequence diversityAlternative splicing
   LigandLipid-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

intracellular protein transport

Inferred from electronic annotation. Source: InterPro

negative regulation of epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

regulation of defense response to virus by virus

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

   Cellular_componentclathrin adaptor complex

Inferred from electronic annotation. Source: InterPro

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionlipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 16902404PubMed 22323290. Source: IntAct

protein kinase binding

Inferred from sequence or structural similarity. Source: ParkinsonsUK-UCL

protein transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dab2P980782EBI-1642835,EBI-1391846From a different organism.
Kcnj11Q617432EBI-1642835,EBI-8603527From a different organism.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 939938AP-2 complex subunit alpha-2
PRO_0000193732

Regions

Region5 – 8076Lipid-binding

Sites

Binding site431Phosphatidylinositol lipid headgroup By similarity
Binding site531Phosphatidylinositol lipid headgroup By similarity
Binding site571Phosphatidylinositol lipid headgroup By similarity
Binding site581Phosphatidylinositol lipid headgroup By similarity
Binding site611Phosphatidylinositol lipid headgroup By similarity

Natural variations

Alternative sequence2711P → PE in isoform 2 and isoform 3.
VSP_035762
Alternative sequence653 – 6553STP → VCL in isoform 3.
VSP_035763
Alternative sequence656 – 939284Missing in isoform 3.
VSP_035764

Experimental info

Sequence conflict201I → T in BAB55435. Ref.4
Sequence conflict4501R → Q in AAC27505. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 24, 2001. Version 2.
Checksum: A8D3CC1B15B8C6BF

FASTA939103,960
        10         20         30         40         50         60 
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC 

        70         80         90        100        110        120 
KLLFIFLLGH DIDFGHMEAV NLLSSNRYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL 

       130        140        150        160        170        180 
ASRNPTFMGL ALHCIASVGS REMAEAFAGE IPKVLVAGDT 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 APQIVAEMLS YLETADYSIR 

       430        440        450        460        470        480 
EEIVLKVAIL AEKYAVDYTW YVDTILNLIR IAGDYVSEEV WYRVIQIVIN RDDVQGYAAK 

       490        500        510        520        530        540 
TVFEALQAPA CHENLVKVGG YILGEFGNLI AGDPRSSPLI QFHLLHSKFH LCSVPTRALL 

       550        560        570        580        590        600 
LSTYIKFVNL FPEVKPTIQD VLRSDSQLRN ADVELQQRAV EYLRLSTVAS TDILATVLEE 

       610        620        630        640        650        660 
MPPFPERESS ILAKLKKKKG PSTVTDLEDT KRDRSVDVNG GPEPAPASTS AVSTPSPSAD 

       670        680        690        700        710        720 
LLGLGAAPPA PAGPPPSSGG SGLLVDVFSD SASVVAPLAP GSEDNFARFV CKNNGVLFEN 

       730        740        750        760        770        780 
QLLQIGLKSE FRQNLGRMFI FYGNKTSTQF LNFTPTLICS DDLQPNLNLQ TKPVDPTVEG 

       790        800        810        820        830        840 
GAQVQQVVNI ECVSDFTEAP VLNIQFRYGG TFQNVSVQLP ITLNKFFQPT EMASQDFFQR 

       850        860        870        880        890        900 
WKQLSNPQQE VQNIFKAKHP MDTEVTKAKI IGFGSALLEE VDPNPANFVG AGIIHTKTTQ 

       910        920        930 
IGCLLRLEPN LQAQMYRLTL RTSKEAVSQR LCELLSAQF 

« Hide

Isoform 2 [UniParc].

Checksum: 98F8345F9BBB149C
Show »

FASTA940104,090
Isoform 3 [UniParc].

Checksum: 98E2FE160BFAC0AC
Show »

FASTA65673,128

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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION OF THE AP-2 COMPLEX IN NON-CLATHRIN-DEPENDENT ENDOCYTOSIS.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning."
Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B., Tsang M., Traub L.M.
Nat. Cell Biol. 14:488-501(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCHO1.
[14]"alphaTAT1 catalyses microtubule acetylation at clathrin-coated pits."
Montagnac G., Meas-Yedid V., Irondelle M., Castro-Castro A., Franco M., Shida T., Nachury M.V., Benmerah A., Olivo-Marin J.C., Chavrier P.
Nature 502:567-570(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATAT1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS44512.1. [O94973-1]
RefSeqNP_001229766.1. NM_001242837.1. [O94973-2]
NP_036437.1. NM_012305.3. [O94973-1]
UniGeneHs.19121.

3D structure databases

ProteinModelPortalO94973.
SMRO94973. Positions 9-607, 702-939.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106670. 28 interactions.
IntActO94973. 18 interactions.
MINTMINT-1198502.
STRING9606.ENSP00000413234.

PTM databases

PhosphoSiteO94973.

Proteomic databases

MaxQBO94973.
PaxDbO94973.
PRIDEO94973.

Protocols and materials databases

DNASU161.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332231; ENSP00000327694; ENSG00000183020. [O94973-2]
ENST00000448903; ENSP00000413234; ENSG00000183020. [O94973-1]
ENST00000528815; ENSP00000431630; ENSG00000183020. [O94973-3]
GeneID161.
KEGGhsa:161.
UCSCuc001lss.3. human. [O94973-1]
uc001lst.2. human. [O94973-2]

Organism-specific databases

CTD161.
GeneCardsGC11P000915.
HGNCHGNC:562. AP2A2.
HPACAB017514.
MIM607242. gene.
neXtProtNX_O94973.
PharmGKBPA24853.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5096.
HOGENOMHOG000170596.
HOVERGENHBG050518.
InParanoidO94973.
KOK11824.
OMAQDVFRQH.
OrthoDBEOG7GQXV2.
PhylomeDBO94973.
TreeFamTF300308.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_6900. Immune System.
SignaLinkO94973.

Gene expression databases

ArrayExpressO94973.
BgeeO94973.
CleanExHS_AP2A2.
GenevestigatorO94973.

Family and domain databases

Gene3D1.25.10.10. 1 hit.
2.60.40.1030. 1 hit.
3.30.310.30. 1 hit.
InterProIPR017104. 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]
PfamPF01602. Adaptin_N. 1 hit.
PF02296. Alpha_adaptin_C. 1 hit.
PF02883. Alpha_adaptinC2. 1 hit.
[Graphical view]
PIRSFPIRSF037091. AP2_complex_alpha. 1 hit.
SMARTSM00809. Alpha_adaptinC2. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
SSF49348. SSF49348. 1 hit.
SSF55711. SSF55711. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAP2A2. human.
GeneWikiAP2A2.
GenomeRNAi161.
NextBio643.
PMAP-CutDBO94973.
PROO94973.
SOURCESearch...

Entry information

Entry nameAP2A2_HUMAN
AccessionPrimary (citable) accession number: O94973
Secondary accession number(s): O75403, Q53ET1, Q96SI8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: January 24, 2001
Last modified: July 9, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM