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Protein

AP-2 complex subunit alpha-1

Gene

AP2A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processEndocytosis, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-177504 Retrograde neurotrophin signalling
R-HSA-182218 Nef Mediated CD8 Down-regulation
R-HSA-2132295 MHC class II antigen presentation
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-437239 Recycling pathway of L1
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8866427 VLDLR internalisation and degradation
R-HSA-8964038 LDL clearance
SignaLinkiO95782

Names & Taxonomyi

Protein namesi
Recommended name:
AP-2 complex subunit alpha-1
Alternative name(s):
100 kDa coated vesicle protein A
Adaptor protein complex AP-2 subunit alpha-1
Adaptor-related protein complex 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 namesi
Name:AP2A1
Synonyms:ADTAA, CLAPA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000196961.12
HGNCiHGNC:561 AP2A1
MIMi601026 gene
neXtProtiNX_O95782

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi160
OpenTargetsiENSG00000196961
PharmGKBiPA24852

Polymorphism and mutation databases

BioMutaiAP2A1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001937301 – 977AP-2 complex subunit alpha-1Add BLAST977

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei626PhosphoserineCombined sources1
Modified residuei652PhosphoserineCombined sources1
Modified residuei653PhosphothreonineCombined sources1
Modified residuei655PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95782
MaxQBiO95782
PaxDbiO95782
PeptideAtlasiO95782
PRIDEiO95782
ProteomicsDBi51043
51044 [O95782-2]

PTM databases

iPTMnetiO95782
PhosphoSitePlusiO95782
SwissPalmiO95782

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000196961
CleanExiHS_AP2A1
ExpressionAtlasiO95782 baseline and differential
GenevisibleiO95782 HS

Organism-specific databases

HPAiCAB004306

Interactioni

Subunit structurei

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 (PubMed:12364336, PubMed:11532990). Interacts with SLC12A5 (By similarity). Interacts with clathrin (By similarity). Interacts with RFTN1 (PubMed:27022195). Interacts with KIAA1107 (PubMed:29262337).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106669, 130 interactors
CORUMiO95782
DIPiDIP-33164N
ELMiO95782
IntActiO95782, 77 interactors
MINTiO95782
STRINGi9606.ENSP00000351926

Structurei

3D structure databases

ProteinModelPortaliO95782
SMRiO95782
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1077 Eukaryota
ENOG410XNQE LUCA
GeneTreeiENSGT00550000074757
HOGENOMiHOG000170596
HOVERGENiHBG050518
InParanoidiO95782
KOiK11824
OMAiHNELFNC
OrthoDBiEOG091G01JZ
PhylomeDBiO95782
TreeFamiTF300308

Family and domain databases

Gene3Di1.25.10.10, 1 hit
3.30.310.10, 1 hit
InterProiView protein in InterPro
IPR017104 AP2_complex_asu
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR002553 Clathrin/coatomer_adapt-like_N
IPR003164 Clathrin_a-adaptin_app_sub_C
IPR008152 Clathrin_a/b/g-adaptin_app_Ig
IPR013041 Clathrin_app_Ig-like_sf
IPR009028 Coatomer/calthrin_app_sub_C
IPR012295 TBP_dom_sf
PfamiView protein in Pfam
PF01602 Adaptin_N, 1 hit
PF02296 Alpha_adaptin_C, 1 hit
PF02883 Alpha_adaptinC2, 1 hit
PIRSFiPIRSF037091 AP2_complex_alpha, 1 hit
SMARTiView protein in SMART
SM00809 Alpha_adaptinC2, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
SSF49348 SSF49348, 1 hit
SSF55711 SSF55711, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: O95782-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL
60 70 80 90 100
DGYSKKKYVC KLLFIFLLGH DIDFGHMEAV NLLSSNKYTE KQIGYLFISV
110 120 130 140 150
LVNSNSELIR LINNAIKNDL ASRNPTFMCL ALHCIANVGS REMGEAFAAD
160 170 180 190 200
IPRILVAGDS MDSVKQSAAL CLLRLYKASP DLVPMGEWTA RVVHLLNDQH
210 220 230 240 250
MGVVTAAVSL ITCLCKKNPD DFKTCVSLAV SRLSRIVSSA STDLQDYTYY
260 270 280 290 300
FVPAPWLSVK LLRLLQCYPP PEDAAVKGRL VECLETVLNK AQEPPKSKKV
310 320 330 340 350
QHSNAKNAIL FETISLIIHY DSEPNLLVRA CNQLGQFLQH RETNLRYLAL
360 370 380 390 400
ESMCTLASSE FSHEAVKTHI DTVINALKTE RDVSVRQRAA DLLYAMCDRS
410 420 430 440 450
NAKQIVSEML RYLETADYAI REEIVLKVAI LAEKYAVDYS WYVDTILNLI
460 470 480 490 500
RIAGDYVSEE VWYRVLQIVT NRDDVQGYAA KTVFEALQAP ACHENMVKVG
510 520 530 540 550
GYILGEFGNL IAGDPRSSPP VQFSLLHSKF HLCSVATRAL LLSTYIKFIN
560 570 580 590 600
LFPETKATIQ GVLRAGSQLR NADVELQQRA VEYLTLSSVA STDVLATVLE
610 620 630 640 650
EMPPFPERES SILAKLKRKK GPGAGSALDD GRRDPSSNDI NGGMEPTPST
660 670 680 690 700
VSTPSPSADL LGLRAAPPPA APPASAGAGN LLVDVFDGPA AQPSLGPTPE
710 720 730 740 750
EAFLSELEPP APESPMALLA DPAPAADPGP EDIGPPIPEA DELLNKFVCK
760 770 780 790 800
NNGVLFENQL LQIGVKSEFR QNLGRMYLFY GNKTSVQFQN FSPTVVHPGD
810 820 830 840 850
LQTQLAVQTK RVAAQVDGGA QVQQVLNIEC LRDFLTPPLL SVRFRYGGAP
860 870 880 890 900
QALTLKLPVT INKFFQPTEM AAQDFFQRWK QLSLPQQEAQ KIFKANHPMD
910 920 930 940 950
AEVTKAKLLG FGSALLDNVD PNPENFVGAG IIQTKALQVG CLLRLEPNAQ
960 970
AQMYRLTLRT SKEPVSRHLC ELLAQQF
Length:977
Mass (Da):107,546
Last modified:November 3, 2009 - v3
Checksum:iD9FB569E7EDDF6ED
GO
Isoform B (identifier: O95782-2) [UniParc]FASTAAdd to basket

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

Show »
Length:955
Mass (Da):105,361
Checksum:iFCE1AEC87453B17F
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti804Q → H in AAL11039 (PubMed:12036598).Curated1
Sequence conflicti804Q → H in AAL11040 (PubMed:12036598).Curated1
Sequence conflicti924 – 977ENFVG…LAQQF → GDREDTRVWGMPGTFLRPFV FLFLFICCCLHSGGLGGVPL PPFPPQAQRGEGPGKWMSPP LPPHPVVAPPTPSPSRGCVL L in AAH14214 (PubMed:15489334).CuratedAdd BLAST54

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_060544270P → L1 PublicationCorresponds to variant dbSNP:rs17851121Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000161706 – 727Missing in isoform B. 2 PublicationsAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS46148.1 [O95782-1]
CCDS46149.1 [O95782-2]
RefSeqiNP_055018.2, NM_014203.2 [O95782-1]
NP_570603.2, NM_130787.2 [O95782-2]
UniGeneiHs.467125

Genome annotation databases

EnsembliENST00000354293; ENSP00000346246; ENSG00000196961 [O95782-2]
ENST00000359032; ENSP00000351926; ENSG00000196961 [O95782-1]
GeneIDi160
KEGGihsa:160
UCSCiuc002ppn.4 human [O95782-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAP2A1_HUMAN
AccessioniPrimary (citable) accession number: O95782
Secondary accession number(s): Q96CI7
, Q96PP6, Q96PP7, Q9H070
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 3, 2009
Last modified: July 18, 2018
This is version 174 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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