Reviewed, UniProtKB/Swiss-Prot O95782 (AP2A1_HUMAN)

Names and origin

Protein names

Recommended name:
    AP-2 complex subunit alpha-1
Alternative name(s):
    Adapter-related protein complex 2 alpha-1 subunit
    Adaptor protein complex AP-2 subunit alpha-1
    Alpha1-adaptin
    Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit
    Alpha-adaptin A
    Clathrin assembly protein complex 2 alpha-A large chain
    100 kDa coated vesicle protein A

Gene names

Name:	AP2A1
Synonyms:	ADTAA, CLAPA1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	977 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 surrrounded 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.
Subunit structure	Adaptor protein complex 2 (AP-2) is an 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. Interacts with SLC12A5. Interacts with clathrin By similarity.
Subcellular location	Cell membrane By similarity. Membrane › coated 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 process	Endocytosis Protein transport Transport
Cellular component	Cell membrane Coated pit Membrane
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	Golgi to endosome transport Ref.1 Non-traceable author statement. Source: UniProtKB endocytosis Ref.1 Non-traceable author statement. Source: UniProtKB intracellular protein transport Ref.1 Non-traceable author statement. Source: UniProtKB regulation of defense response to virus by virus Inferred from Experiment. Source: Reactome
Cellular component	AP-2 adaptor complex Ref.1 Non-traceable author statement. Source: UniProtKB clathrin coat of trans-Golgi network vesicle Ref.1 Non-traceable author statement. Source: UniProtKB cytosol Inferred from Experiment. Source: Reactome
Molecular function	protein binding Inferred from electronic annotation. Source: InterPro protein 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 977	977	AP-2 complex subunit alpha-1		PRO_0000193730
Amino acid modifications
	Modified residue	626	1	Phosphoserine Ref.10
	Modified residue	650	1	Phosphothreonine By similarity
	Modified residue	652	1	Phosphoserine Ref.10 Ref.11
	Modified residue	653	1	Phosphothreonine Ref.10 Ref.11
	Modified residue	655	1	Phosphoserine Ref.10 Ref.11
	Modified residue	657	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	706 – 727	22	Missing in isoform B.		VSP_000161
	Natural variant	270	1	P → L: dbSNP rs17851121. Ref.2		VAR_060544
Experimental info
	Sequence conflict	804	1	Q → H in AAL11039. Ref.1
	Sequence conflict	804	1	Q → H in AAL11040. Ref.1
	Sequence conflict	924 – 977	54	ENFVG…LAQQF → GDREDTRVWGMPGTFLRPFV FLFLFICCCLHSGGLGGVPL PPFPPQAQRGEGPGKWMSPP LPPHPVVAPPTPSPSRGCVL L in AAH14214. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified November 3, 2009. Version 3. Checksum: D9FB569E7EDDF6ED	FASTA	977	107,546
	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
	Isoform B. Checksum: FCE1AEC87453B17F	FASTA	955	105,361
	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 EAFLSPGPED IGPPIPEADE 730 740 750 760 770 780 LLNKFVCKNN GVLFENQLLQ IGVKSEFRQN LGRMYLFYGN KTSVQFQNFS PTVVHPGDLQ 790 800 810 820 830 840 TQLAVQTKRV AAQVDGGAQV QQVLNIECLR DFLTPPLLSV RFRYGGAPQA LTLKLPVTIN 850 860 870 880 890 900 KFFQPTEMAA QDFFQRWKQL SLPQQEAQKI FKANHPMDAE VTKAKLLGFG SALLDNVDPN 910 920 930 940 950 PENFVGAGII QTKALQVGCL LRLEPNAQAQ MYRLTLRTSK EPVSRHLCEL LAQQF

References

	« Hide 'large scale' referencesShow '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: 12036598] [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. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [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. , 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: 15057824] [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: 15489334] [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: 11532990] [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: 12364336] [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: 14745134] [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: 15473838] [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: 19033387] [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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-626; SER-652; THR-653; SER-655 AND SER-657, MASS SPECTROMETRY.
[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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652; THR-653 AND SER-655, MASS SPECTROMETRY.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00256684. IPI00304577.
RefSeq	NP_055018.2. NP_570603.2.
UniGene	Hs.467125
3D structure databases
SMR	O95782. Positions 746-977.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95782. 9 interactions.
STRING	O95782.
PTM databases
PhosphoSite	O95782.
Proteomic databases
PRIDE	O95782.
Genome annotation databases
Ensembl	ENST00000456192; ENSP00000399384; ENSG00000196961; Homo sapiens. [Genome view]
GeneID	160.
UCSC	uc002ppn.1. human. uc002ppo.1. human.
Organism-specific databases
CTD	160.
GeneCards	GC19P054961.
HGNC	HGNC:561. AP2A1.
HPA	CAB004306.
MIM	601026. gene.
PharmGKB	PA24852.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95782.
HOVERGEN	O95782.
Enzyme and pathway databases
Pathway_Interaction_DB	arf_3pathway. Arf1 pathway.
Reactome	REACT_11061. Signalling by NGF. REACT_13685. Synaptic Transmission. REACT_6185. HIV Infection. REACT_9417. Signaling by EGFR.
Gene expression databases
ArrayExpress	O95782.
Bgee	O95782.
CleanEx	HS_AP2A1.
Genevestigator	O95782.
GermOnline	ENSG00000196961. Homo sapiens.
Family and domain databases
InterPro	IPR017104. AP2_complex_asu. IPR016024. ARM-type_fold. IPR009028. Calthrin/coatomer_app_sub_C. IPR002553. Clathrin/coatomer_adapt-like_N. IPR013041. Clathrin/coatomer_app_Ig-like. 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. [Graphical view]
Gene3D	G3DSA:3.30.310.30. AP2_A_adaptin_C. 1 hit. G3DSA:2.60.40.1030. Clathrin_a-adaptin_app_Ig-like. 1 hit.
Pfam	PF01602. Adaptin_N. 1 hit. PF02296. Alpha_adaptin_C. 1 hit. PF02883. Alpha_adaptinC2. 1 hit. [Graphical view]
PIRSF	PIRSF037091. AP2_complex_alpha. 1 hit.
SMART	SM00809. Alpha_adaptinC2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

AP2A1_HUMAN

Accession

Primary (citable) accession number: O95782
Secondary accession number(s): Q96CI7 , Q96PP6, Q96PP7, Q9H070

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	November 3, 2009
Last modified:	November 24, 2009
This is version 87 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.