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Protein

AP-2 complex subunit sigma

Gene

AP2S1

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 and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). May also play a role in extracellular calcium homeostasis.By similarity4 Publications

GO - Molecular functioni

  • protein transporter activity Source: UniProtKB
  • transporter activity Source: ProtInc

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

Names & Taxonomyi

Protein namesi
Recommended name:
AP-2 complex subunit sigma
Alternative name(s):
Adaptor protein complex AP-2 subunit sigma
Adaptor-related protein complex 2 subunit sigma
Clathrin assembly protein 2 sigma small chain
Clathrin coat assembly protein AP17
Clathrin coat-associated protein AP17
HA2 17 kDa subunit
Plasma membrane adaptor AP-2 17 kDa protein
Sigma2-adaptin
Gene namesi
Name:AP2S1
Synonyms:AP17, CLAPS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000042753.11
HGNCiHGNC:565 AP2S1
MIMi602242 gene
neXtProtiNX_P53680

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

Involvement in diseasei

Hypocalciuric hypercalcemia, familial 3 (HHC3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults.
See also OMIM:600740
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06957015R → C in HHC3; there is a rightward shift in Ca(2+)concentration-response curves with the mutant compared to wild-type, indicating a decrease in the sensitivity of cells expressing CASR to extracellular calcium. 2 PublicationsCorresponds to variant dbSNP:rs397514498EnsemblClinVar.1
Natural variantiVAR_06957115R → H in HHC3; there is a rightward shift in Ca(2+)concentration-response curves with the mutant compared to wild-type, indicating a decrease in the sensitivity of cells expressing CASR to extracellular calcium. 1 PublicationCorresponds to variant dbSNP:rs397514499EnsemblClinVar.1
Natural variantiVAR_06957215R → L in HHC3; there is a rightward shift in Ca(2+)concentration-response curves with the mutant compared to wild-type, indicating a decrease in the sensitivity of cells expressing CASR to extracellular calcium. 2 PublicationsCorresponds to variant dbSNP:rs397514499EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1175
MalaCardsiAP2S1
MIMi600740 phenotype
OpenTargetsiENSG00000042753
Orphaneti101050 Familial hypocalciuric hypercalcemia type 3
PharmGKBiPA24856

Polymorphism and mutation databases

DMDMi51338780

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001938041 – 142AP-2 complex subunit sigmaAdd BLAST142

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei140PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP53680
MaxQBiP53680
PaxDbiP53680
PeptideAtlasiP53680
PRIDEiP53680
ProteomicsDBi56611
56612 [P53680-2]
TopDownProteomicsiP53680-1 [P53680-1]

PTM databases

iPTMnetiP53680
PhosphoSitePlusiP53680

Expressioni

Gene expression databases

BgeeiENSG00000042753
CleanExiHS_AP2S1
ExpressionAtlasiP53680 baseline and differential
GenevisibleiP53680 HS

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).

Binary interactionsi

WithEntry#Exp.IntActNotes
AAGABQ6PD745EBI-297662,EBI-719906

Protein-protein interaction databases

BioGridi107589, 48 interactors
IntActiP53680, 22 interactors
MINTiP53680
STRINGi9606.ENSP00000263270

Structurei

3D structure databases

ProteinModelPortaliP53680
SMRiP53680
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0935 Eukaryota
COG5030 LUCA
GeneTreeiENSGT00530000062839
HOGENOMiHOG000185227
HOVERGENiHBG050517
InParanoidiP53680
KOiK11827
PhylomeDBiP53680
TreeFamiTF300139

Family and domain databases

InterProiView protein in InterPro
IPR016635 AP_complex_ssu
IPR022775 AP_mu_sigma_su
IPR027156 APS2
IPR000804 Clathrin_sm-chain_CS
IPR011012 Longin-like_dom_sf
PANTHERiPTHR11753 PTHR11753, 1 hit
PTHR11753:SF6 PTHR11753:SF6, 1 hit
PfamiView protein in Pfam
PF01217 Clat_adaptor_s, 1 hit
PIRSFiPIRSF015588 AP_complex_sigma, 1 hit
SUPFAMiSSF64356 SSF64356, 1 hit
PROSITEiView protein in PROSITE
PS00989 CLAT_ADAPTOR_S, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P53680-1) [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
MIRFILIQNR AGKTRLAKWY MQFDDDEKQK LIEEVHAVVT VRDAKHTNFV
60 70 80 90 100
EFRNFKIIYR RYAGLYFCIC VDVNDNNLAY LEAIHNFVEV LNEYFHNVCE
110 120 130 140
LDLVFNFYKV YTVVDEMFLA GEIRETSQTK VLKQLLMLQS LE
Length:142
Mass (Da):17,018
Last modified:August 16, 2004 - v2
Checksum:iCA3FD868C65AEDF6
GO
Isoform 2 (identifier: P53680-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     52-89: Missing.

Show »
Length:104
Mass (Da):12,417
Checksum:i0240F8D55B64095C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti77N → K in CAA65782 (PubMed:9040778).Curated1
Sequence conflicti77N → K in CAA09018 (PubMed:9767099).Curated1
Sequence conflicti83A → G in CAA65782 (PubMed:9040778).Curated1
Sequence conflicti83A → G in CAA09018 (PubMed:9767099).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06957015R → C in HHC3; there is a rightward shift in Ca(2+)concentration-response curves with the mutant compared to wild-type, indicating a decrease in the sensitivity of cells expressing CASR to extracellular calcium. 2 PublicationsCorresponds to variant dbSNP:rs397514498EnsemblClinVar.1
Natural variantiVAR_06957115R → H in HHC3; there is a rightward shift in Ca(2+)concentration-response curves with the mutant compared to wild-type, indicating a decrease in the sensitivity of cells expressing CASR to extracellular calcium. 1 PublicationCorresponds to variant dbSNP:rs397514499EnsemblClinVar.1
Natural variantiVAR_06957215R → L in HHC3; there is a rightward shift in Ca(2+)concentration-response curves with the mutant compared to wild-type, indicating a decrease in the sensitivity of cells expressing CASR to extracellular calcium. 2 PublicationsCorresponds to variant dbSNP:rs397514499EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01735252 – 89Missing in isoform 2. 1 PublicationAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X97074 mRNA Translation: CAA65782.1
AJ010148 mRNA Translation: CAA09018.1
AJ010149 mRNA Translation: CAA09019.1
AK312003 mRNA Translation: BAG34941.1
CH471126 Genomic DNA Translation: EAW57448.1
BC006337 mRNA Translation: AAH06337.1
CCDSiCCDS12693.1 [P53680-2]
CCDS33062.1 [P53680-1]
RefSeqiNP_001288005.1, NM_001301076.1
NP_001288007.1, NM_001301078.1
NP_001288010.1, NM_001301081.1
NP_004060.2, NM_004069.4 [P53680-1]
NP_067586.1, NM_021575.3 [P53680-2]
UniGeneiHs.119591

Genome annotation databases

EnsembliENST00000263270; ENSP00000263270; ENSG00000042753 [P53680-1]
ENST00000601649; ENSP00000470898; ENSG00000042753 [P53680-2]
GeneIDi1175
KEGGihsa:1175
UCSCiuc002pft.2 human [P53680-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAP2S1_HUMAN
AccessioniPrimary (citable) accession number: P53680
Secondary accession number(s): B2R4Z4, O75977, Q6PK67
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: August 16, 2004
Last modified: June 20, 2018
This is version 155 of the entry and version 2 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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