Human Gene AP2S1 (ENST00000263270.11) from GENCODE V44
  Description: Homo sapiens adaptor related protein complex 2 subunit sigma 1 (AP2S1), transcript variant AP17, mRNA. (from RefSeq NM_004069)
RefSeq Summary (NM_004069): One of two major clathrin-associated adaptor complexes, AP-2, is a heterotetramer which is associated with the plasma membrane. This complex is composed of two large chains, a medium chain, and a small chain. This gene encodes the small chain of this complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014].
Gencode Transcript: ENST00000263270.11
Gencode Gene: ENSG00000042753.12
Transcript (Including UTRs)
   Position: hg38 chr19:46,838,167-46,850,846 Size: 12,680 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg38 chr19:46,838,447-46,850,766 Size: 12,320 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:46,838,167-46,850,846)mRNA (may differ from genome)Protein (142 aa)
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: AP2S1_HUMAN
DESCRIPTION: RecName: Full=AP-2 complex subunit sigma; AltName: Full=Adapter-related protein complex 2 sigma subunit; AltName: Full=Adaptor protein complex AP-2 subunit sigma; AltName: Full=Clathrin assembly protein 2 small chain; AltName: Full=Clathrin coat assembly protein AP17; AltName: Full=Clathrin coat-associated protein AP17; AltName: Full=HA2 17 kDa subunit; AltName: Full=Plasma membrane adaptor AP-2 17 kDa protein; AltName: Full=Sigma2-adaptin;
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 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).
SUBUNIT: 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).
SUBCELLULAR LOCATION: Cell membrane. Membrane, coated pit; Peripheral membrane protein; Cytoplasmic side. 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).
SIMILARITY: Belongs to the adaptor complexes small subunit family.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: AP2S1
Diseases sorted by gene-association score: hypocalciuric hypercalcemia, type iii* (1669), familial hypocalciuric hypercalcemia (19), hypocalciuric hypercalcemia, type i (13), hypocalciuric hypercalcemia, type ii (13), chondrocalcinosis (6), hyperparathyroidism, familial primary (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 82.94 RPKM in Cells - Cultured fibroblasts
Total median expression: 2046.18 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -36.1080-0.451 Picture PostScript Text
3' UTR -122.60280-0.438 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016635 - AP_complex_ssu
IPR022775 - AP_mu_sigma_su
IPR000804 - Clathrin_sm-chain_CS
IPR011012 - Longin-like_dom

Pfam Domains:
PF01217 - Clathrin adaptor complex small chain

ModBase Predicted Comparative 3D Structure on P53680
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsemblWormBase 
Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence 
AlignmentAlignmentAlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005215 transporter activity
GO:0005515 protein binding
GO:0008565 protein transporter activity
GO:0035615 clathrin adaptor activity

Biological Process:
GO:0006886 intracellular protein transport
GO:0006897 endocytosis
GO:0015031 protein transport
GO:0016192 vesicle-mediated transport
GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II
GO:0030100 regulation of endocytosis
GO:0032802 low-density lipoprotein particle receptor catabolic process
GO:0034383 low-density lipoprotein particle clearance
GO:0048013 ephrin receptor signaling pathway
GO:0048268 clathrin coat assembly
GO:0050690 regulation of defense response to virus by virus
GO:0060071 Wnt signaling pathway, planar cell polarity pathway
GO:0061024 membrane organization
GO:0072583 clathrin-dependent endocytosis

Cellular Component:
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005905 clathrin-coated pit
GO:0016020 membrane
GO:0030117 membrane coat
GO:0030122 AP-2 adaptor complex
GO:0030666 endocytic vesicle membrane
GO:0030669 clathrin-coated endocytic vesicle membrane
GO:0036020 endolysosome membrane
GO:0045334 clathrin-coated endocytic vesicle


-  Descriptions from all associated GenBank mRNAs
  X97074 - H.sapiens mRNS for clathrin-associated protein.
BC006337 - Homo sapiens adaptor-related protein complex 2, sigma 1 subunit, mRNA (cDNA clone MGC:12798 IMAGE:4304127), complete cds.
JD555654 - Sequence 536678 from Patent EP1572962.
JD287318 - Sequence 268342 from Patent EP1572962.
JD025895 - Sequence 6919 from Patent EP1572962.
JD035920 - Sequence 16944 from Patent EP1572962.
JD536453 - Sequence 517477 from Patent EP1572962.
JD208839 - Sequence 189863 from Patent EP1572962.
JD275766 - Sequence 256790 from Patent EP1572962.
JD523286 - Sequence 504310 from Patent EP1572962.
JD351658 - Sequence 332682 from Patent EP1572962.
JD523285 - Sequence 504309 from Patent EP1572962.
JD210393 - Sequence 191417 from Patent EP1572962.
AJ010148 - Homo sapiens mRNA for clathrin-associated protein AP17.
AJ010149 - Homo sapiens mRNA for clathrin-associated protein AP17 delta, splice variant.
AK312003 - Homo sapiens cDNA, FLJ92277, highly similar to Homo sapiens adaptor-related protein complex 2, sigma 1 subunit(AP2S1), transcript variant AP17, mRNA.
JF432568 - Synthetic construct Homo sapiens clone IMAGE:100073801 adaptor-related protein complex 2, sigma 1 subunit (AP2S1) gene, encodes complete protein.
KJ890925 - Synthetic construct Homo sapiens clone ccsbBroadEn_00319 AP2S1 gene, encodes complete protein.
JD031954 - Sequence 12978 from Patent EP1572962.
JD023870 - Sequence 4894 from Patent EP1572962.
JD025147 - Sequence 6171 from Patent EP1572962.
JD029330 - Sequence 10354 from Patent EP1572962.
JD029673 - Sequence 10697 from Patent EP1572962.
DQ597241 - Homo sapiens piRNA piR-35307, complete sequence.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04144 - Endocytosis
hsa05016 - Huntington's disease

Reactome (by CSHL, EBI, and GO)

Protein P53680 (Reactome details) participates in the following event(s):

R-HSA-167537 Formation of CD4:Nef:AP-2 Complex:v-ATPase Complex
R-HSA-182186 Formation of CD8:Nef:AP-2 Complex:v-ATPase Complex
R-HSA-8856808 Recruitment of AP-2 complex and clathrin
R-HSA-8866277 AP-2 directly binds some endocytic cargo
R-HSA-8871196 Initial binding of AP-2 and clathrin to PI(4,5)P2
R-HSA-167597 Internalization of the CD4:Nef:AP-2 Complex:v-ATPase Complex
R-HSA-182198 Internalization of the CD8:Nef:AP-2 Complex:v-ATPase Complex
R-HSA-5138433 p-DVL2 recruits AP-2 and beta-arrestin 2 to promote clathrin-mediated endocytosis
R-HSA-8856813 AAK1 phosphorylates AP-2 mu subunit at T156
R-HSA-8862280 FCHo proteins bind nascent clathrin-coated pit
R-HSA-8866283 ARBB recruits GPCRs into clathrin-coated pits
R-HSA-8867756 CLASP proteins and cargo are recruited to the nascent clathrin-coated pit
R-HSA-8871194 RAB5 and GAPVD1 bind AP-2
R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating
R-HSA-8868659 Clathrin recruits auxilins to the clathrin-coated vesicle
R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission
R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle
R-HSA-8868648 SYNJ hydrolyze PI(4,5)P2 to PI(4)P
R-HSA-177491 Formation of clathrin-coated vesicle
R-HSA-392748 L1 binds to AP-2 Clathrin complex
R-HSA-2130640 Recruitment of clathrin coated vesicle by Ii
R-HSA-6784735 PCSK9:LDLR bind to Clathrin
R-HSA-8855131 VLDLR:PCSK9 binds Clathrin-coated vesicles
R-HSA-445071 Reinsertion of L1 into the plasma membrane
R-HSA-2130486 Uncoating of clathrin-coated vesicles and fusion with endosomes
R-HSA-8868071 Clathrin recruits PIK3C2A
R-HSA-8868230 SNX9 recruits components of the actin polymerizing machinery
R-HSA-8867754 F- and N- BAR domain proteins bind the clathrin-coated pit
R-HSA-177479 Axonal transport of NGF:Trk complexes
R-HSA-177501 Endocytosis (internalization) of clathrin-coated vesicle
R-HSA-374696 Phosphorylation of L1 by p90rsk
R-HSA-392749 Transport of L1 into endosomes
R-HSA-555065 Formation of clathrin coated vesicle
R-HSA-445077 Transport of L1 from C-domain to P-domain
R-HSA-445079 Phosphorylation of L1 by ERK
R-HSA-6784729 PCSK9:LDLR:Clathrin-coated vesicle transport from plasma membrane to endolysosome
R-HSA-8868236 BAR domain proteins recruit dynamin
R-HSA-8866279 Epsin family proteins bind ubiquitinated cargo
R-HSA-8868072 Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2
R-HSA-8868651 Endophilins recruit synaptojanins to the clathrin-coated pit
R-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-182218 Nef Mediated CD8 Down-regulation
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-164938 Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-199991 Membrane Trafficking
R-HSA-177504 Retrograde neurotrophin signalling
R-HSA-437239 Recycling pathway of L1
R-HSA-2132295 MHC class II antigen presentation
R-HSA-8964038 LDL clearance
R-HSA-8866427 VLDLR internalisation and degradation
R-HSA-4086400 PCP/CE pathway
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-422475 Axon guidance
R-HSA-5653656 Vesicle-mediated transport
R-HSA-187037 Signaling by NTRK1 (TRKA)
R-HSA-373760 L1CAM interactions
R-HSA-1280218 Adaptive Immune System
R-HSA-8964043 Plasma lipoprotein clearance
R-HSA-3858494 Beta-catenin independent WNT signaling
R-HSA-162909 Host Interactions of HIV factors
R-HSA-1266738 Developmental Biology
R-HSA-166520 Signaling by NTRKs
R-HSA-168256 Immune System
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-195721 Signaling by WNT
R-HSA-162906 HIV Infection
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-382551 Transport of small molecules
R-HSA-162582 Signal Transduction
R-HSA-5663205 Infectious disease
R-HSA-1643685 Disease
R-HSA-416639 Trafficking of GluR2-containing AMPA receptors to extrasynaptic sites
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-399719 Trafficking of AMPA receptors
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315 Transmission across Chemical Synapses
R-HSA-112316 Neuronal System

-  Other Names for This Gene
  Alternate Gene Symbols: AP17, AP2S1_HUMAN, B2R4Z4, CLAPS2, ENST00000263270.1, ENST00000263270.10, ENST00000263270.2, ENST00000263270.3, ENST00000263270.4, ENST00000263270.5, ENST00000263270.6, ENST00000263270.7, ENST00000263270.8, ENST00000263270.9, NM_004069, O75977, P53680, Q6PK67, uc002pft.1, uc002pft.2, uc002pft.3
UCSC ID: ENST00000263270.11
RefSeq Accession: NM_004069
Protein: P53680 (aka AP2S1_HUMAN or A2S1_HUMAN)
CCDS: CCDS33062.1, CCDS77322.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.