Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O95782 (AP2A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
AP-2 complex subunit alpha-1
Alternative name(s):
100 kDa coated vesicle protein A
Adapter-related protein complex 2 subunit alpha-1
Adaptor protein complex AP-2 subunit alpha-1
Alpha-adaptin A
Alpha1-adaptin
Clathrin assembly protein complex 2 alpha-A large chain
Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit
Gene names
Name:AP2A1
Synonyms:ADTAA, CLAPA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length977 AA.
Sequence statusComplete.
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.7 Ref.8 Ref.9

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). Interacts with SGIP1 By similarity. Interacts with HIP1 and RAB11FIP2. Interacts with SLC12A5. Interacts with clathrin. Ref.5 Ref.6

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.

Tissue specificity

Isoform A expressed in forebrain, skeletal muscle, spinal cord, cerebellum, salivary gland, heart and colon. Isoform B is widely expressed in tissues and also in breast cancer and in prostate carcinoma cells.

Sequence similarities

Belongs to the adaptor complexes large subunit family.

Sequence caution

The sequence AAD15564.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processEndocytosis
Protein transport
Transport
   Cellular componentCell membrane
Coated pit
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processGolgi to endosome transport

Non-traceable author statement Ref.1. Source: UniProtKB

antigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

endocytosis

Non-traceable author statement Ref.1. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

intracellular protein transport

Non-traceable author statement Ref.1. Source: UniProtKB

negative regulation of epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

negative regulation of hyaluronan biosynthetic process

Inferred from direct assay PubMed 24251095. Source: UniProtKB

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_componentAP-2 adaptor complex

Non-traceable author statement Ref.1. Source: UniProtKB

apical plasma membrane

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

clathrin coat of trans-Golgi network vesicle

Non-traceable author statement Ref.1. Source: UniProtKB

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionprotein transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: O95782-1)

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 B (identifier: O95782-2)

The sequence of this isoform differs from the canonical sequence as follows:
     706-727: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 977977AP-2 complex subunit alpha-1
PRO_0000193730

Amino acid modifications

Modified residue6261Phosphoserine Ref.10
Modified residue6521Phosphoserine Ref.11
Modified residue6531Phosphothreonine Ref.11 Ref.13
Modified residue6551Phosphoserine Ref.11

Natural variations

Alternative sequence706 – 72722Missing in isoform B.
VSP_000161
Natural variant2701P → L. Ref.4
Corresponds to variant rs17851121 [ dbSNP | Ensembl ].
VAR_060544

Experimental info

Sequence conflict8041Q → H in AAL11039. Ref.1
Sequence conflict8041Q → H in AAL11040. Ref.1
Sequence conflict924 – 97754ENFVG…LAQQF → GDREDTRVWGMPGTFLRPFV FLFLFICCCLHSGGLGGVPL PPFPPQAQRGEGPGKWMSPP LPPHPVVAPPTPSPSRGCVL L in AAH14214. Ref.4

Sequences

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

Last modified November 3, 2009. Version 3.
Checksum: D9FB569E7EDDF6ED

FASTA977107,546
        10         20         30         40         50         60 
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC 

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

       130        140        150        160        170        180 
ASRNPTFMCL ALHCIANVGS REMGEAFAAD IPRILVAGDS MDSVKQSAAL CLLRLYKASP 

       190        200        210        220        230        240 
DLVPMGEWTA RVVHLLNDQH MGVVTAAVSL ITCLCKKNPD DFKTCVSLAV SRLSRIVSSA 

       250        260        270        280        290        300 
STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PEDAAVKGRL VECLETVLNK AQEPPKSKKV 

       310        320        330        340        350        360 
QHSNAKNAIL FETISLIIHY DSEPNLLVRA CNQLGQFLQH RETNLRYLAL ESMCTLASSE 

       370        380        390        400        410        420 
FSHEAVKTHI DTVINALKTE RDVSVRQRAA DLLYAMCDRS NAKQIVSEML RYLETADYAI 

       430        440        450        460        470        480 
REEIVLKVAI LAEKYAVDYS WYVDTILNLI RIAGDYVSEE VWYRVLQIVT NRDDVQGYAA 

       490        500        510        520        530        540 
KTVFEALQAP ACHENMVKVG GYILGEFGNL IAGDPRSSPP VQFSLLHSKF HLCSVATRAL 

       550        560        570        580        590        600 
LLSTYIKFIN LFPETKATIQ GVLRAGSQLR NADVELQQRA VEYLTLSSVA STDVLATVLE 

       610        620        630        640        650        660 
EMPPFPERES SILAKLKRKK GPGAGSALDD GRRDPSSNDI NGGMEPTPST VSTPSPSADL 

       670        680        690        700        710        720 
LGLRAAPPPA APPASAGAGN LLVDVFDGPA AQPSLGPTPE EAFLSELEPP APESPMALLA 

       730        740        750        760        770        780 
DPAPAADPGP EDIGPPIPEA DELLNKFVCK NNGVLFENQL LQIGVKSEFR QNLGRMYLFY 

       790        800        810        820        830        840 
GNKTSVQFQN FSPTVVHPGD LQTQLAVQTK RVAAQVDGGA QVQQVLNIEC LRDFLTPPLL 

       850        860        870        880        890        900 
SVRFRYGGAP QALTLKLPVT INKFFQPTEM AAQDFFQRWK QLSLPQQEAQ KIFKANHPMD 

       910        920        930        940        950        960 
AEVTKAKLLG FGSALLDNVD PNPENFVGAG IIQTKALQVG CLLRLEPNAQ AQMYRLTLRT 

       970 
SKEPVSRHLC ELLAQQF 

« Hide

Isoform B [UniParc].

Checksum: FCE1AEC87453B17F
Show »

FASTA955105,361

References

« Hide 'large scale' references
[1]"Cloning, physical mapping and structural characterization of the human alpha(A)-adaptin gene."
Scorilas A., Levesque M.A., Ashworth L.K., Diamandis E.P.
Gene 289:191-199(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
[2]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
Tissue: Uterus.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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 B), VARIANT LEU-270.
Tissue: Muscle.
[5]"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.
[6]"Rab11-FIP2, an adaptor protein connecting cellular components involved in internalization and recycling of epidermal growth factor receptors."
Cullis D.N., Philip B., Baleja J.D., Feig L.A.
J. Biol. Chem. 277:49158-49166(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB11FIP2.
[7]"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.
[8]"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.
[9]"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.
[10]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-626, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652; THR-653 AND SER-655, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-653, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF289221 Genomic DNA. Translation: AAL11039.1.
AF289221 Genomic DNA. Translation: AAL11040.1.
AL136925 mRNA. Translation: CAB66859.1.
AC006942 Genomic DNA. Translation: AAD15564.1. Sequence problems.
AC011495 Genomic DNA. No translation available.
AC098783 Genomic DNA. No translation available.
BC014214 mRNA. Translation: AAH14214.1.
RefSeqNP_055018.2. NM_014203.2.
NP_570603.2. NM_130787.2.
UniGeneHs.467125.

3D structure databases

ProteinModelPortalO95782.
SMRO95782. Positions 3-621, 746-977.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106669. 43 interactions.
IntActO95782. 21 interactions.
MINTMINT-5002322.
STRING9606.ENSP00000351926.

PTM databases

PhosphoSiteO95782.

Proteomic databases

PaxDbO95782.
PRIDEO95782.

Protocols and materials databases

DNASU160.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354293; ENSP00000346246; ENSG00000196961. [O95782-2]
ENST00000359032; ENSP00000351926; ENSG00000196961. [O95782-1]
GeneID160.
KEGGhsa:160.
UCSCuc002ppn.3. human. [O95782-1]
uc002ppo.3. human. [O95782-2]

Organism-specific databases

CTD160.
GeneCardsGC19P050270.
HGNCHGNC:561. AP2A1.
HPACAB004306.
MIM601026. gene.
neXtProtNX_O95782.
PharmGKBPA24852.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG303101.
HOGENOMHOG000170596.
HOVERGENHBG050518.
InParanoidO95782.
KOK11824.
OMANYVGAGI.
OrthoDBEOG7GQXV2.
PhylomeDBO95782.
TreeFamTF300308.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_6900. Immune System.
SignaLinkO95782.

Gene expression databases

ArrayExpressO95782.
BgeeO95782.
CleanExHS_AP2A1.
GenevestigatorO95782.

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

ChiTaRSAP2A1. human.
GeneWikiAdaptor-related_protein_complex_2,_alpha_1.
GenomeRNAi160.
NextBio637.
PROO95782.
SOURCESearch...

Entry information

Entry nameAP2A1_HUMAN
AccessionPrimary (citable) accession number: O95782
Secondary accession number(s): Q96CI7 expand/collapse secondary AC list , Q96PP6, Q96PP7, Q9H070
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 3, 2009
Last modified: April 16, 2014
This is version 129 of the entry and version 3 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM