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P53680 (AP2S1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
AP-2 complex subunit sigma
Alternative name(s):
Adapter-related protein complex 2 subunit sigma
Adaptor protein complex AP-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 names
Name:AP2S1
Synonyms:AP17, CLAPS2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length142 AA.
Sequence statusComplete.
Protein existenceEvidence 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 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. Ref.6 Ref.7 Ref.8 Ref.11

Subunit structure

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. Membranecoated 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.

Involvement in disease

Hypocalciuric hypercalcemia, familial 3 (HHC3) [MIM:600740]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

Belongs to the adaptor complexes small subunit family.

Ontologies

Keywords
   Biological processEndocytosis
Protein transport
Transport
   Cellular componentCell membrane
Coated pit
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

clathrin coat assembly

Traceable author statement PubMed 10753805. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

intracellular protein transport

Inferred from electronic annotation. Source: InterPro

negative regulation of epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

regulation of defense response to virus by virus

Traceable author statement. Source: Reactome

regulation of endocytosis

Traceable author statement PubMed 10753805. Source: UniProtKB

synaptic transmission

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

   Cellular_componentAP-2 adaptor complex

Traceable author statement PubMed 10753805. Source: UniProtKB

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionprotein transporter activity

Non-traceable author statement PubMed 10753805. Source: UniProtKB

transporter activity

Non-traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P53680-1)

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 2 (identifier: P53680-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 142142AP-2 complex subunit sigma
PRO_0000193804

Amino acid modifications

Modified residue1401Phosphoserine Ref.9

Natural variations

Alternative sequence52 – 8938Missing in isoform 2.
VSP_017352
Natural variant151R → 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. Ref.11
VAR_069570
Natural variant151R → 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. Ref.11
VAR_069571
Natural variant151R → 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. Ref.11
VAR_069572

Experimental info

Sequence conflict771N → K in CAA65782. Ref.1
Sequence conflict771N → K in CAA09018. Ref.2
Sequence conflict831A → G in CAA65782. Ref.1
Sequence conflict831A → G in CAA09018. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 16, 2004. Version 2.
Checksum: CA3FD868C65AEDF6

FASTA14217,018
        10         20         30         40         50         60 
MIRFILIQNR AGKTRLAKWY MQFDDDEKQK LIEEVHAVVT VRDAKHTNFV EFRNFKIIYR 

        70         80         90        100        110        120 
RYAGLYFCIC VDVNDNNLAY LEAIHNFVEV LNEYFHNVCE LDLVFNFYKV YTVVDEMFLA 

       130        140 
GEIRETSQTK VLKQLLMLQS LE 

« Hide

Isoform 2 [UniParc].

Checksum: 0240F8D55B64095C
Show »

FASTA10412,417

References

« Hide 'large scale' references
[1]"Human CLAPS2 encoding AP17, a small chain of the clathrin-associated protein complex: cDNA cloning and chromosomal assignment to 19q13.2-->q13.3."
Winterpacht A., Endele S., Enklaar T., Fuhry M., Zabel B.
Cytogenet. Cell Genet. 75:132-135(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[2]"A novel spliced transcript of human CLAPS2 encoding a protein alternative to clathrin adaptor protein AP17."
Holzmann K., Poeltl A., Sauermann G.
Gene 220:39-44(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Tongue.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 1).
Tissue: Uterus.
[6]"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.
[7]"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.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION OF THE AP-2 COMPLEX IN NON-CLATHRIN-DEPENDENT ENDOCYTOSIS.
[9]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3."
Nesbit M.A., Hannan F.M., Howles S.A., Reed A.A., Cranston T., Thakker C.E., Gregory L., Rimmer A.J., Rust N., Graham U., Morrison P.J., Hunter S.J., Whyte M.P., McVean G., Buck D., Thakker R.V.
Nat. Genet. 45:93-97(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS HHC3 CYS-15; HIS-15 AND LEU-15, CHARACTERIZATION OF VARIANTS HHC3 CYS-15; HIS-15 AND LEU-15.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS12693.1. [P53680-2]
CCDS33062.1. [P53680-1]
RefSeqNP_004060.2. NM_004069.3. [P53680-1]
NP_067586.1. NM_021575.2. [P53680-2]
UniGeneHs.119591.

3D structure databases

ProteinModelPortalP53680.
SMRP53680. Positions 1-142.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107589. 13 interactions.
IntActP53680. 6 interactions.
MINTMINT-256650.
STRING9606.ENSP00000263270.

Chemistry

BindingDBP53680.

PTM databases

PhosphoSiteP53680.

Polymorphism databases

DMDM51338780.

Proteomic databases

MaxQBP53680.
PaxDbP53680.
PRIDEP53680.

Protocols and materials databases

DNASU1175.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263270; ENSP00000263270; ENSG00000042753. [P53680-1]
ENST00000601649; ENSP00000470898; ENSG00000042753. [P53680-2]
GeneID1175.
KEGGhsa:1175.
UCSCuc002pft.1. human. [P53680-1]
uc002pfu.1. human. [P53680-2]

Organism-specific databases

CTD1175.
GeneCardsGC19M047341.
HGNCHGNC:565. AP2S1.
MIM600740. phenotype.
602242. gene.
neXtProtNX_P53680.
Orphanet101050. Familial hypocalciuric hypercalcemia type 3.
PharmGKBPA24856.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5030.
HOGENOMHOG000185227.
HOVERGENHBG050517.
InParanoidP53680.
KOK11827.
OrthoDBEOG7S7SGC.
PhylomeDBP53680.
TreeFamTF300139.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP53680.
BgeeP53680.
CleanExHS_AP2S1.
GenevestigatorP53680.

Family and domain databases

InterProIPR016635. AP_complex_ssu.
IPR022775. AP_mu_sigma_su.
IPR027156. APS2.
IPR000804. Clathrin_sm-chain_CS.
IPR011012. Longin-like_dom.
[Graphical view]
PANTHERPTHR11753. PTHR11753. 1 hit.
PTHR11753:SF6. PTHR11753:SF6. 1 hit.
PfamPF01217. Clat_adaptor_s. 1 hit.
[Graphical view]
PIRSFPIRSF015588. AP_complex_sigma. 1 hit.
SUPFAMSSF64356. SSF64356. 1 hit.
PROSITEPS00989. CLAT_ADAPTOR_S. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAP2S1. human.
GeneWikiAP2S1.
GenomeRNAi1175.
NextBio4856.
PROP53680.
SOURCESearch...

Entry information

Entry nameAP2S1_HUMAN
AccessionPrimary (citable) accession number: P53680
Secondary accession number(s): B2R4Z4, O75977, Q6PK67
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: August 16, 2004
Last modified: July 9, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM