AP1S3_HUMAN
ID AP1S3_HUMAN Reviewed; 154 AA.
AC Q96PC3; B4DQZ1; Q8WTY1; Q96DD1;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=AP-1 complex subunit sigma-3;
DE AltName: Full=Adaptor protein complex AP-1 subunit sigma-1C;
DE AltName: Full=Adaptor-related protein complex 1 subunit sigma-1C;
DE AltName: Full=Clathrin assembly protein complex 1 sigma-1C small chain;
DE AltName: Full=Golgi adaptor HA1/AP1 adaptin sigma-1C subunit;
DE AltName: Full=Sigma 1C subunit of AP-1 clathrin;
DE AltName: Full=Sigma-adaptin 1C;
DE AltName: Full=Sigma1C-adaptin;
GN Name=AP1S3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11598180; DOI=10.1091/mbc.12.10.2907;
RA Boehm M., Bonifacino J.S.;
RT "Adaptins: the final recount.";
RL Mol. Biol. Cell 12:2907-2920(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, INVOLVEMENT IN PSORS15, VARIANTS PSORS15 CYS-4 AND TRP-33,
RP CHARACTERIZATION OF VARIANTS PSORS15 CYS-4 AND TRP-33, AND VARIANTS LYS-17;
RP ALA-22; ILE-32; VAL-79; THR-83 AND GLU-124.
RX PubMed=24791904; DOI=10.1016/j.ajhg.2014.04.005;
RA Setta-Kaffetzi N., Simpson M.A., Navarini A.A., Patel V.M., Lu H.C.,
RA Allen M.H., Duckworth M., Bachelez H., Burden A.D., Choon S.E.,
RA Griffiths C.E., Kirby B., Kolios A., Seyger M.M., Prins C., Smahi A.,
RA Trembath R.C., Fraternali F., Smith C.H., Barker J.N., Capon F.;
RT "AP1S3 mutations are associated with pustular psoriasis and impaired Toll-
RT like receptor 3 trafficking.";
RL Am. J. Hum. Genet. 94:790-797(2014).
CC -!- FUNCTION: Subunit of clathrin-associated adaptor protein complex 1 that
CC plays a role in protein sorting in the late-Golgi/trans-Golgi network
CC (TGN) and/or endosomes. The AP complexes mediate both the recruitment
CC of clathrin to membranes and the recognition of sorting signals within
CC the cytosolic tails of transmembrane cargo molecules. Involved in TLR3
CC trafficking (PubMed:24791904). {ECO:0000269|PubMed:24791904}.
CC -!- SUBUNIT: Adaptor protein complex 1 (AP-1) is a heterotetramer composed
CC of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit
CC AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small
CC adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).
CC -!- INTERACTION:
CC Q96PC3; Q6PD74: AAGAB; NbExp=3; IntAct=EBI-3923129, EBI-719906;
CC Q96PC3-2; Q6PD74: AAGAB; NbExp=3; IntAct=EBI-12780485, EBI-719906;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Cytoplasmic vesicle membrane;
CC Peripheral membrane protein; Cytoplasmic side. Membrane, clathrin-
CC coated pit. Note=Component of the coat surrounding the cytoplasmic face
CC of coated vesicles located at the Golgi complex.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96PC3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96PC3-2; Sequence=VSP_015944;
CC Name=4;
CC IsoId=Q96PC3-4; Sequence=VSP_040384;
CC Name=3;
CC IsoId=Q96PC3-3; Sequence=VSP_015942, VSP_015943;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Psoriasis 15, pustular (PSORS15) [MIM:616106]: A form of
CC pustular psoriasis, a life-threatening disease defined by repeated
CC flares of sudden onset consisting of diffuse erythematous skin eruption
CC characterized by rapid coverage with pustules, high-grade fever,
CC asthenia, marked leukocytosis, and elevated serum levels of C-reactive
CC protein. {ECO:0000269|PubMed:24791904}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the adaptor complexes small subunit family.
CC {ECO:0000305}.
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DR EMBL; AF393369; AAL09586.1; -; mRNA.
DR EMBL; AK299026; BAG61103.1; -; mRNA.
DR EMBL; AC012512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009606; AAH09606.1; -; mRNA.
DR EMBL; BC021898; AAH21898.1; -; mRNA.
DR CCDS; CCDS42827.1; -. [Q96PC3-4]
DR RefSeq; NP_001034658.1; NM_001039569.1. [Q96PC3-4]
DR PDB; 4HMY; X-ray; 7.00 A; S=1-154.
DR PDB; 6CM9; EM; 3.73 A; S=1-154.
DR PDB; 6CRI; EM; 6.80 A; S/a/b=1-142.
DR PDB; 6D83; EM; 4.27 A; S=1-154.
DR PDB; 6D84; EM; 6.72 A; Q/S=1-154.
DR PDB; 6DFF; EM; 3.90 A; S=1-154.
DR PDBsum; 4HMY; -.
DR PDBsum; 6CM9; -.
DR PDBsum; 6CRI; -.
DR PDBsum; 6D83; -.
DR PDBsum; 6D84; -.
DR PDBsum; 6DFF; -.
DR AlphaFoldDB; Q96PC3; -.
DR SMR; Q96PC3; -.
DR BioGRID; 126229; 21.
DR ComplexPortal; CPX-5049; Ubiquitous AP-1 Adaptor complex, sigma1c variant.
DR CORUM; Q96PC3; -.
DR IntAct; Q96PC3; 7.
DR STRING; 9606.ENSP00000379891; -.
DR iPTMnet; Q96PC3; -.
DR PhosphoSitePlus; Q96PC3; -.
DR BioMuta; AP1S3; -.
DR DMDM; 21541959; -.
DR EPD; Q96PC3; -.
DR jPOST; Q96PC3; -.
DR MassIVE; Q96PC3; -.
DR MaxQB; Q96PC3; -.
DR PaxDb; Q96PC3; -.
DR PeptideAtlas; Q96PC3; -.
DR PRIDE; Q96PC3; -.
DR ProteomicsDB; 77660; -. [Q96PC3-1]
DR ProteomicsDB; 77661; -. [Q96PC3-2]
DR ProteomicsDB; 77662; -. [Q96PC3-3]
DR ProteomicsDB; 77663; -. [Q96PC3-4]
DR Antibodypedia; 54195; 104 antibodies from 14 providers.
DR DNASU; 130340; -.
DR Ensembl; ENST00000396654.7; ENSP00000379891.2; ENSG00000152056.17. [Q96PC3-4]
DR Ensembl; ENST00000415298.5; ENSP00000401705.1; ENSG00000152056.17. [Q96PC3-3]
DR Ensembl; ENST00000443700.5; ENSP00000397155.1; ENSG00000152056.17. [Q96PC3-2]
DR Ensembl; ENST00000446015.6; ENSP00000388738.2; ENSG00000152056.17. [Q96PC3-1]
DR GeneID; 130340; -.
DR KEGG; hsa:130340; -.
DR MANE-Select; ENST00000396654.7; ENSP00000379891.2; NM_001039569.2; NP_001034658.1. [Q96PC3-4]
DR UCSC; uc002vnn.4; human. [Q96PC3-1]
DR CTD; 130340; -.
DR DisGeNET; 130340; -.
DR GeneCards; AP1S3; -.
DR HGNC; HGNC:18971; AP1S3.
DR HPA; ENSG00000152056; Tissue enhanced (epididymis).
DR MalaCards; AP1S3; -.
DR MIM; 615781; gene.
DR MIM; 616106; phenotype.
DR neXtProt; NX_Q96PC3; -.
DR OpenTargets; ENSG00000152056; -.
DR Orphanet; 163931; Acrodermatitis continua of Hallopeau.
DR Orphanet; 247353; Generalized pustular psoriasis.
DR Orphanet; 163927; Pustulosis palmaris et plantaris.
DR VEuPathDB; HostDB:ENSG00000152056; -.
DR eggNOG; KOG0934; Eukaryota.
DR GeneTree; ENSGT00970000193372; -.
DR HOGENOM; CLU_061221_4_1_1; -.
DR InParanoid; Q96PC3; -.
DR OMA; LAKWYAT; -.
DR OrthoDB; 1307450at2759; -.
DR PhylomeDB; Q96PC3; -.
DR TreeFam; TF312921; -.
DR PathwayCommons; Q96PC3; -.
DR Reactome; R-HSA-164940; Nef mediated downregulation of MHC class I complex cell surface expression.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR SignaLink; Q96PC3; -.
DR BioGRID-ORCS; 130340; 14 hits in 1078 CRISPR screens.
DR ChiTaRS; AP1S3; human.
DR GenomeRNAi; 130340; -.
DR Pharos; Q96PC3; Tbio.
DR PRO; PR:Q96PC3; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96PC3; protein.
DR Bgee; ENSG00000152056; Expressed in islet of Langerhans and 105 other tissues.
DR ExpressionAtlas; Q96PC3; baseline and differential.
DR Genevisible; Q96PC3; HS.
DR GO; GO:0030121; C:AP-1 adaptor complex; IC:ComplexPortal.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IC:ComplexPortal.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0035615; F:clathrin adaptor activity; IEA:InterPro.
DR GO; GO:1903232; P:melanosome assembly; IC:ComplexPortal.
DR GO; GO:0060155; P:platelet dense granule organization; IC:ComplexPortal.
DR GO; GO:0006605; P:protein targeting; IMP:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd14831; AP1_sigma; 1.
DR InterPro; IPR044733; AP1_sigma.
DR InterPro; IPR016635; AP_complex_ssu.
DR InterPro; IPR022775; AP_mu_sigma_su.
DR InterPro; IPR000804; Clathrin_sm-chain_CS.
DR InterPro; IPR011012; Longin-like_dom_sf.
DR PANTHER; PTHR11753; PTHR11753; 1.
DR Pfam; PF01217; Clat_adaptor_s; 1.
DR PIRSF; PIRSF015588; AP_complex_sigma; 1.
DR SUPFAM; SSF64356; SSF64356; 1.
DR PROSITE; PS00989; CLAT_ADAPTOR_S; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coated pit; Cytoplasmic vesicle;
KW Disease variant; Golgi apparatus; Membrane; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..154
FT /note="AP-1 complex subunit sigma-3"
FT /id="PRO_0000193801"
FT VAR_SEQ 98..104
FT /note="VCELDII -> TWPFARA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015942"
FT VAR_SEQ 105..154
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015943"
FT VAR_SEQ 144..154
FT /note="VSTVSQTMGER -> NRLSPRGRDCSEPRSCHCTLA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015944"
FT VAR_SEQ 144..154
FT /note="VSTVSQTMGER -> TMEEYMNKPTF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040384"
FT VARIANT 4
FT /note="F -> C (in PSORS15; results in decreased protein
FT levels; dbSNP:rs116107386)"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072545"
FT VARIANT 17
FT /note="Q -> K (in dbSNP:rs750870128)"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072546"
FT VARIANT 22
FT /note="T -> A (in dbSNP:rs149183052)"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072547"
FT VARIANT 32
FT /note="T -> I (in dbSNP:rs78536455)"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072548"
FT VARIANT 33
FT /note="R -> W (in PSORS15; results in decreased TLR3
FT targeting to the endosomes indicating impaired function;
FT dbSNP:rs138292988)"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072549"
FT VARIANT 79
FT /note="L -> V (in dbSNP:rs34353588)"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072550"
FT VARIANT 83
FT /note="I -> T (in dbSNP:rs202157374)"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072551"
FT VARIANT 124
FT /note="Q -> E"
FT /evidence="ECO:0000269|PubMed:24791904"
FT /id="VAR_072552"
SQ SEQUENCE 154 AA; 18280 MW; 178755E8EA4E9ABE CRC64;
MIHFILLFSR QGKLRLQKWY ITLPDKERKK ITREIVQIIL SRGHRTSSFV DWKELKLVYK
RYASLYFCCA IENQDNELLT LEIVHRYVEL LDKYFGNVCE LDIIFNFEKA YFILDEFIIG
GEIQETSKKI AVKAIEDSDM LQEVSTVSQT MGER
