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Protein

AP-2 complex subunit alpha-2

Gene

AP2A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei43Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei53Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei57Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei58Phosphatidylinositol lipid headgroupBy similarity1
Binding sitei61Phosphatidylinositol lipid headgroupBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Endocytosis, Protein transport, Transport

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciZFISH:G66-33391-MONOMER.
ReactomeiR-HSA-167590. Nef Mediated CD4 Down-regulation.
R-HSA-171052. LDL-mediated lipid transport.
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-6798695. Neutrophil degranulation.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-8866427. VLDLR internalisation and degradation.
SignaLinkiO94973.

Names & Taxonomyi

Protein namesi
Recommended name:
AP-2 complex subunit alpha-2
Alternative name(s):
100 kDa coated vesicle protein C
Adaptor protein complex AP-2 subunit alpha-2
Adaptor-related protein complex 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 namesi
Name:AP2A2
Synonyms:ADTAB, CLAPA2, HIP9, HYPJ, KIAA0899
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:562. AP2A2.

Subcellular locationi

  • Cell membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
  • Membranecoated pit By similarity; Peripheral membrane protein By similarity; 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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi161.
OpenTargetsiENSG00000183020.
PharmGKBiPA24853.

Polymorphism and mutation databases

BioMutaiAP2A2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001937322 – 939AP-2 complex subunit alpha-2Add BLAST938

Proteomic databases

EPDiO94973.
MaxQBiO94973.
PaxDbiO94973.
PeptideAtlasiO94973.
PRIDEiO94973.

PTM databases

iPTMnetiO94973.
PhosphoSitePlusiO94973.
SwissPalmiO94973.

Miscellaneous databases

PMAP-CutDBO94973.

Expressioni

Gene expression databases

BgeeiENSG00000183020.
CleanExiHS_AP2A2.
ExpressionAtlasiO94973. baseline and differential.
GenevisibleiO94973. HS.

Organism-specific databases

HPAiCAB017514.
HPA043040.

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). 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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dab2P980782EBI-1642835,EBI-1391846From a different organism.
Kcnj11Q617432EBI-1642835,EBI-8603527From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106670. 66 interactors.
IntActiO94973. 33 interactors.
MINTiMINT-1198502.
STRINGi9606.ENSP00000413234.

Structurei

3D structure databases

ProteinModelPortaliO94973.
SMRiO94973.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni5 – 80Lipid-bindingAdd BLAST76

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1077. Eukaryota.
ENOG410XNQE. LUCA.
GeneTreeiENSGT00550000074757.
HOGENOMiHOG000170596.
HOVERGENiHBG050518.
InParanoidiO94973.
KOiK11824.
OMAiQMINAEC.
OrthoDBiEOG091G01JZ.
PhylomeDBiO94973.
TreeFamiTF300308.

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
2.60.40.1030. 1 hit.
3.30.310.30. 1 hit.
InterProiIPR017104. 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]
PfamiPF01602. Adaptin_N. 1 hit.
PF02296. Alpha_adaptin_C. 1 hit.
PF02883. Alpha_adaptinC2. 1 hit.
[Graphical view]
PIRSFiPIRSF037091. AP2_complex_alpha. 1 hit.
SMARTiSM00809. Alpha_adaptinC2. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF49348. SSF49348. 1 hit.
SSF55711. SSF55711. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O94973-1) [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 NLLSSNRYTE KQIGYLFISV
110 120 130 140 150
LVNSNSELIR LINNAIKNDL ASRNPTFMGL ALHCIASVGS REMAEAFAGE
160 170 180 190 200
IPKVLVAGDT MDSVKQSAAL CLLRLYRTSP DLVPMGDWTS RVVHLLNDQH
210 220 230 240 250
LGVVTAATSL ITTLAQKNPE EFKTSVSLAV SRLSRIVTSA STDLQDYTYY
260 270 280 290 300
FVPAPWLSVK LLRLLQCYPP PDPAVRGRLT ECLETILNKA QEPPKSKKVQ
310 320 330 340 350
HSNAKNAVLF EAISLIIHHD SEPNLLVRAC NQLGQFLQHR ETNLRYLALE
360 370 380 390 400
SMCTLASSEF SHEAVKTHIE TVINALKTER DVSVRQRAVD LLYAMCDRSN
410 420 430 440 450
APQIVAEMLS YLETADYSIR EEIVLKVAIL AEKYAVDYTW YVDTILNLIR
460 470 480 490 500
IAGDYVSEEV WYRVIQIVIN RDDVQGYAAK TVFEALQAPA CHENLVKVGG
510 520 530 540 550
YILGEFGNLI AGDPRSSPLI QFHLLHSKFH LCSVPTRALL LSTYIKFVNL
560 570 580 590 600
FPEVKPTIQD VLRSDSQLRN ADVELQQRAV EYLRLSTVAS TDILATVLEE
610 620 630 640 650
MPPFPERESS ILAKLKKKKG PSTVTDLEDT KRDRSVDVNG GPEPAPASTS
660 670 680 690 700
AVSTPSPSAD LLGLGAAPPA PAGPPPSSGG SGLLVDVFSD SASVVAPLAP
710 720 730 740 750
GSEDNFARFV CKNNGVLFEN QLLQIGLKSE FRQNLGRMFI FYGNKTSTQF
760 770 780 790 800
LNFTPTLICS DDLQPNLNLQ TKPVDPTVEG GAQVQQVVNI ECVSDFTEAP
810 820 830 840 850
VLNIQFRYGG TFQNVSVQLP ITLNKFFQPT EMASQDFFQR WKQLSNPQQE
860 870 880 890 900
VQNIFKAKHP MDTEVTKAKI IGFGSALLEE VDPNPANFVG AGIIHTKTTQ
910 920 930
IGCLLRLEPN LQAQMYRLTL RTSKEAVSQR LCELLSAQF
Length:939
Mass (Da):103,960
Last modified:January 24, 2001 - v2
Checksum:iA8D3CC1B15B8C6BF
GO
Isoform 2 (identifier: O94973-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     271-271: P → PE

Note: No experimental confirmation available.
Show »
Length:940
Mass (Da):104,090
Checksum:i98F8345F9BBB149C
GO
Isoform 3 (identifier: O94973-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:656
Mass (Da):73,128
Checksum:i98E2FE160BFAC0AC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20I → T in BAB55435 (PubMed:14702039).Curated1
Sequence conflicti450R → Q in AAC27505 (PubMed:9700202).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035762271P → PE in isoform 2 and isoform 3. 2 Publications1
Alternative sequenceiVSP_035763653 – 655STP → VCL in isoform 3. 1 Publication3
Alternative sequenceiVSP_035764656 – 939Missing in isoform 3. 1 PublicationAdd BLAST284

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44512.1. [O94973-1]
CCDS73234.1. [O94973-2]
RefSeqiNP_001229766.1. NM_001242837.1. [O94973-2]
NP_036437.1. NM_012305.3. [O94973-1]
UniGeneiHs.19121.

Genome annotation databases

EnsembliENST00000332231; ENSP00000327694; ENSG00000183020. [O94973-2]
ENST00000448903; ENSP00000413234; ENSG00000183020. [O94973-1]
ENST00000528815; ENSP00000431630; ENSG00000183020. [O94973-3]
GeneIDi161.
KEGGihsa:161.
UCSCiuc001lss.4. human. [O94973-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44512.1. [O94973-1]
CCDS73234.1. [O94973-2]
RefSeqiNP_001229766.1. NM_001242837.1. [O94973-2]
NP_036437.1. NM_012305.3. [O94973-1]
UniGeneiHs.19121.

3D structure databases

ProteinModelPortaliO94973.
SMRiO94973.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106670. 66 interactors.
IntActiO94973. 33 interactors.
MINTiMINT-1198502.
STRINGi9606.ENSP00000413234.

PTM databases

iPTMnetiO94973.
PhosphoSitePlusiO94973.
SwissPalmiO94973.

Polymorphism and mutation databases

BioMutaiAP2A2.

Proteomic databases

EPDiO94973.
MaxQBiO94973.
PaxDbiO94973.
PeptideAtlasiO94973.
PRIDEiO94973.

Protocols and materials databases

DNASUi161.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332231; ENSP00000327694; ENSG00000183020. [O94973-2]
ENST00000448903; ENSP00000413234; ENSG00000183020. [O94973-1]
ENST00000528815; ENSP00000431630; ENSG00000183020. [O94973-3]
GeneIDi161.
KEGGihsa:161.
UCSCiuc001lss.4. human. [O94973-1]

Organism-specific databases

CTDi161.
DisGeNETi161.
GeneCardsiAP2A2.
HGNCiHGNC:562. AP2A2.
HPAiCAB017514.
HPA043040.
MIMi607242. gene.
neXtProtiNX_O94973.
OpenTargetsiENSG00000183020.
PharmGKBiPA24853.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1077. Eukaryota.
ENOG410XNQE. LUCA.
GeneTreeiENSGT00550000074757.
HOGENOMiHOG000170596.
HOVERGENiHBG050518.
InParanoidiO94973.
KOiK11824.
OMAiQMINAEC.
OrthoDBiEOG091G01JZ.
PhylomeDBiO94973.
TreeFamiTF300308.

Enzyme and pathway databases

BioCyciZFISH:G66-33391-MONOMER.
ReactomeiR-HSA-167590. Nef Mediated CD4 Down-regulation.
R-HSA-171052. LDL-mediated lipid transport.
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-6798695. Neutrophil degranulation.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-8866427. VLDLR internalisation and degradation.
SignaLinkiO94973.

Miscellaneous databases

ChiTaRSiAP2A2. human.
GeneWikiiAP2A2.
GenomeRNAii161.
PMAP-CutDBO94973.
PROiO94973.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183020.
CleanExiHS_AP2A2.
ExpressionAtlasiO94973. baseline and differential.
GenevisibleiO94973. HS.

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
2.60.40.1030. 1 hit.
3.30.310.30. 1 hit.
InterProiIPR017104. 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]
PfamiPF01602. Adaptin_N. 1 hit.
PF02296. Alpha_adaptin_C. 1 hit.
PF02883. Alpha_adaptinC2. 1 hit.
[Graphical view]
PIRSFiPIRSF037091. AP2_complex_alpha. 1 hit.
SMARTiSM00809. Alpha_adaptinC2. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF49348. SSF49348. 1 hit.
SSF55711. SSF55711. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiAP2A2_HUMAN
AccessioniPrimary (citable) accession number: O94973
Secondary accession number(s): O75403, Q53ET1, Q96SI8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: January 24, 2001
Last modified: November 30, 2016
This is version 164 of the entry and version 2 of the sequence. [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 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.