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P17426

- AP2A1_MOUSE

UniProt

P17426 - AP2A1_MOUSE

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Protein

AP-2 complex subunit alpha-1

Gene

Ap2a1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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 similarity

GO - Molecular functioni

  1. protein kinase binding Source: ParkinsonsUK-UCL
  2. protein transporter activity Source: InterPro

GO - Biological processi

  1. endocytosis Source: UniProtKB-KW
  2. intracellular protein transport Source: MGI
  3. negative regulation of hyaluronan biosynthetic process Source: UniProtKB
  4. vesicle-mediated transport Source: MGI
Complete GO annotation...

Keywords - Biological processi

Endocytosis, Protein transport, Transport

Enzyme and pathway databases

ReactomeiREACT_196550. MHC class II antigen presentation.
REACT_202778. Retrograde neurotrophin signalling.
REACT_203917. EGFR downregulation.
REACT_222404. WNT5A-dependent internalization of FZD4.
REACT_253367. Trafficking of GluR2-containing AMPA receptors.
REACT_257923. Recycling pathway of L1.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:101921. Ap2a1.

Subcellular locationi

Cell membrane 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

  1. apical plasma membrane Source: Ensembl
  2. basolateral plasma membrane Source: Ensembl
  3. clathrin adaptor complex Source: InterPro
  4. coated pit Source: UniProtKB-KW
  5. membrane coat Source: MGI
  6. secretory granule Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 977977AP-2 complex subunit alpha-1PRO_0000193731Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei626 – 6261PhosphoserineBy similarity
Modified residuei652 – 6521PhosphoserineBy similarity
Modified residuei653 – 6531PhosphothreonineBy similarity
Modified residuei655 – 6551PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP17426.
PaxDbiP17426.
PRIDEiP17426.

PTM databases

PhosphoSiteiP17426.

Miscellaneous databases

PMAP-CutDBP17426.

Expressioni

Tissue specificityi

Isoform A is expressed only in neuronal tissue and skeletal muscle. Isoform B is widely expressed.

Gene expression databases

BgeeiP17426.
CleanExiMM_AP2A1.
ExpressionAtlasiP17426. baseline and differential.
GenevestigatoriP17426.

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 HIP1 and RAB11FIP2 (By similarity). Interacts with SLC12A5. Interacts with clathrin. Interacts with SLC12A5. Interacts with clathrin. Interacts with SGIP1.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Grin2bQ010972EBI-775189,EBI-400125

Protein-protein interaction databases

BioGridi198129. 5 interactions.
IntActiP17426. 12 interactions.
MINTiMINT-1865011.
STRINGi10090.ENSMUSP00000082519.

Structurei

3D structure databases

ProteinModelPortaliP17426.
SMRiP17426. Positions 3-621, 746-977.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG303101.
GeneTreeiENSGT00550000074757.
HOGENOMiHOG000170596.
HOVERGENiHBG050518.
InParanoidiP17426.
KOiK11824.
OMAiNYVGAGI.
OrthoDBiEOG7GQXV2.
PhylomeDBiP17426.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform A (identifier: P17426-1) [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 DFKTCISLAV 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 GPGAASALDD SRRDTSSNDI NGGVEPTPST
660 670 680 690 700
VSTPSPSADL LGLRAAPPPA APPAPVGGNL LVDVFSDGPT AQPSLGPTPE
710 720 730 740 750
EAFLSELEPP APESPMALLA DPAPAADPGP EDIGPPIPEA DELLNKFVCK
760 770 780 790 800
NSGVLFENQL LQIGVKSEFR QNLGRMYLFY GNKTSVQFQN FLPTVVHPGD
810 820 830 840 850
LQTQLAVQTK RVAAQVDGGA QVQQVLNIEC LRDFLTPPLL SVRFRYGGTA
860 870 880 890 900
QSLTLKLPVT INKFFQPTEM AAQDFFQRWK QLSLPLQEAQ KIFKANHPMD
910 920 930 940 950
AEVTKAKLLG FGSALLDNVD PNPENFVGAG IIQTKALQVG CLLRLEPNAQ
960 970
AQMYRLTLRT SKEPVSRHLC ELLAQQF
Length:977
Mass (Da):107,664
Last modified:August 1, 1990 - v1
Checksum:iF4ED87D3F9EF230A
GO
Isoform B (identifier: P17426-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:955
Mass (Da):105,480
Checksum:iD6EB4672359D66B9
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei706 – 72722Missing in isoform B. CuratedVSP_000162Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14971 mRNA. Translation: CAA33096.1.
BC031433 mRNA. Translation: AAH31433.1.
CCDSiCCDS52238.1. [P17426-2]
CCDS52239.1. [P17426-1]
PIRiA30111.
RefSeqiNP_001070732.1. NM_001077264.1. [P17426-2]
NP_031484.1. NM_007458.2. [P17426-1]
UniGeneiMm.6877.

Genome annotation databases

EnsembliENSMUST00000085399; ENSMUSP00000082519; ENSMUSG00000060279. [P17426-1]
ENSMUST00000107857; ENSMUSP00000103489; ENSMUSG00000060279. [P17426-2]
ENSMUST00000166972; ENSMUSP00000127842; ENSMUSG00000060279. [P17426-1]
ENSMUST00000167930; ENSMUSP00000127497; ENSMUSG00000060279. [P17426-2]
GeneIDi11771.
KEGGimmu:11771.
UCSCiuc009grv.1. mouse. [P17426-1]
uc009grw.1. mouse. [P17426-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14971 mRNA. Translation: CAA33096.1 .
BC031433 mRNA. Translation: AAH31433.1 .
CCDSi CCDS52238.1. [P17426-2 ]
CCDS52239.1. [P17426-1 ]
PIRi A30111.
RefSeqi NP_001070732.1. NM_001077264.1. [P17426-2 ]
NP_031484.1. NM_007458.2. [P17426-1 ]
UniGenei Mm.6877.

3D structure databases

ProteinModelPortali P17426.
SMRi P17426. Positions 3-621, 746-977.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198129. 5 interactions.
IntActi P17426. 12 interactions.
MINTi MINT-1865011.
STRINGi 10090.ENSMUSP00000082519.

PTM databases

PhosphoSitei P17426.

Proteomic databases

MaxQBi P17426.
PaxDbi P17426.
PRIDEi P17426.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000085399 ; ENSMUSP00000082519 ; ENSMUSG00000060279 . [P17426-1 ]
ENSMUST00000107857 ; ENSMUSP00000103489 ; ENSMUSG00000060279 . [P17426-2 ]
ENSMUST00000166972 ; ENSMUSP00000127842 ; ENSMUSG00000060279 . [P17426-1 ]
ENSMUST00000167930 ; ENSMUSP00000127497 ; ENSMUSG00000060279 . [P17426-2 ]
GeneIDi 11771.
KEGGi mmu:11771.
UCSCi uc009grv.1. mouse. [P17426-1 ]
uc009grw.1. mouse. [P17426-2 ]

Organism-specific databases

CTDi 160.
MGIi MGI:101921. Ap2a1.

Phylogenomic databases

eggNOGi NOG303101.
GeneTreei ENSGT00550000074757.
HOGENOMi HOG000170596.
HOVERGENi HBG050518.
InParanoidi P17426.
KOi K11824.
OMAi NYVGAGI.
OrthoDBi EOG7GQXV2.
PhylomeDBi P17426.
TreeFami TF300308.

Enzyme and pathway databases

Reactomei REACT_196550. MHC class II antigen presentation.
REACT_202778. Retrograde neurotrophin signalling.
REACT_203917. EGFR downregulation.
REACT_222404. WNT5A-dependent internalization of FZD4.
REACT_253367. Trafficking of GluR2-containing AMPA receptors.
REACT_257923. Recycling pathway of L1.

Miscellaneous databases

ChiTaRSi Ap2a1. mouse.
NextBioi 279549.
PMAP-CutDB P17426.
PROi P17426.
SOURCEi Search...

Gene expression databases

Bgeei P17426.
CleanExi MM_AP2A1.
ExpressionAtlasi P17426. baseline and differential.
Genevestigatori P17426.

Family and domain databases

Gene3Di 1.25.10.10. 1 hit.
2.60.40.1030. 1 hit.
3.30.310.30. 1 hit.
InterProi IPR017104. 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 ]
Pfami PF01602. Adaptin_N. 1 hit.
PF02296. Alpha_adaptin_C. 1 hit.
PF02883. Alpha_adaptinC2. 1 hit.
[Graphical view ]
PIRSFi PIRSF037091. AP2_complex_alpha. 1 hit.
SMARTi SM00809. Alpha_adaptinC2. 1 hit.
[Graphical view ]
SUPFAMi SSF48371. SSF48371. 1 hit.
SSF49348. SSF49348. 1 hit.
SSF55711. SSF55711. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of cDNAs encoding two related 100-kD coated vesicle proteins (alpha-adaptins)."
    Robinson M.S.
    J. Cell Biol. 108:833-842(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "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 A).
    Tissue: Retina.
  3. "The alpha chain of the AP-2 adaptor is a clathrin binding subunit."
    Goodman O.B. Jr., Keen J.H.
    J. Biol. Chem. 270:23768-23773(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CLATHRIN.
  4. "Expression and localization of alpha-adaptin isoforms."
    Ball C.L., Hunt S.P., Robinson M.S.
    J. Cell Sci. 108:2865-2875(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF ISOFORMS A AND B.
  5. "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.
  6. "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.
  7. "SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15."
    Uezu A., Horiuchi A., Kanda K., Kikuchi N., Umeda K., Tsujita K., Suetsugu S., Araki N., Yamamoto H., Takenawa T., Nakanishi H.
    J. Biol. Chem. 282:26481-26489(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SGIP1.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  9. "Identification of a novel di-leucine motif mediating K(+)/Cl(-) cotransporter KCC2 constitutive endocytosis."
    Zhao B., Wong A.Y.C., Murshid A., Bowie D., Presley J.F., Bedford F.K.
    Cell. Signal. 20:1769-1779(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SLC12A5.

Entry informationi

Entry nameiAP2A1_MOUSE
AccessioniPrimary (citable) accession number: P17426
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 26, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3