AP4S1_HUMAN
ID AP4S1_HUMAN Reviewed; 144 AA.
AC Q9Y587; G3V2N8; Q6IAQ4; Q86U36; Q9BVE7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=AP-4 complex subunit sigma-1 {ECO:0000305};
DE AltName: Full=AP-4 adaptor complex subunit sigma-1;
DE AltName: Full=Adaptor-related protein complex 4 subunit sigma-1;
DE AltName: Full=Sigma-1 subunit of AP-4;
DE AltName: Full=Sigma-4-adaptin;
DE Short=Sigma4-adaptin;
GN Name=AP4S1 {ECO:0000312|HGNC:HGNC:575};
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), FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, AND TOPOLOGY.
RC TISSUE=Placenta;
RX PubMed=10436028; DOI=10.1091/mbc.10.8.2787;
RA Hirst J., Bright N.A., Rous B., Robinson M.S.;
RT "Characterization of a fourth adaptor-related protein complex.";
RL Mol. Biol. Cell 10:2787-2802(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Takatsu H., Sakurai M., Shiba Y., Yoshida Y., Nakayama K.;
RT "Identification and characterization of epsilon-adaptin that constitutes
RT AP-4 clathrin adaptor-related complex.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=B-cell, and Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) System Donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=10066790; DOI=10.1074/jbc.274.11.7278;
RA Dell'Angelica E.C., Mullins C., Bonifacino J.S.;
RT "AP-4, a novel protein complex related to clathrin adaptors.";
RL J. Biol. Chem. 274:7278-7285(1999).
RN [11]
RP INVOLVEMENT IN SPG52.
RX PubMed=21620353; DOI=10.1016/j.ajhg.2011.04.019;
RA Abou Jamra R., Philippe O., Raas-Rothschild A., Eck S.H., Graf E.,
RA Buchert R., Borck G., Ekici A., Brockschmidt F.F., Nothen M.M., Munnich A.,
RA Strom T.M., Reis A., Colleaux L.;
RT "Adaptor protein complex 4 deficiency causes severe autosomal-recessive
RT intellectual disability, progressive spastic paraplegia, shy character, and
RT short stature.";
RL Am. J. Hum. Genet. 88:788-795(2011).
CC -!- FUNCTION: Component of the adaptor protein complex 4 (AP-4). Adaptor
CC protein complexes are vesicle coat components involved both in vesicle
CC formation and cargo selection. They control the vesicular transport of
CC proteins in different trafficking pathways (PubMed:10066790,
CC PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles
CC departing the trans-Golgi network (TGN) and may be involved in the
CC targeting of proteins from the trans-Golgi network (TGN) to the
CC endosomal-lysosomal system. It is also involved in protein sorting to
CC the basolateral membrane in epithelial cells and the proper asymmetric
CC localization of somatodendritic proteins in neurons. AP-4 is involved
CC in the recognition and binding of tyrosine-based sorting signals found
CC in the cytoplasmic part of cargos, but may also recognize other types
CC of sorting signal (Probable). {ECO:0000269|PubMed:10066790,
CC ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790,
CC ECO:0000305|PubMed:10436028}.
CC -!- SUBUNIT: Adaptor protein complex 4 (AP-4) is a heterotetramer composed
CC of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit
CC AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin
CC (sigma-type AP4S1). {ECO:0000269|PubMed:10066790,
CC ECO:0000269|PubMed:10436028}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000305|PubMed:10436028}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9Y587-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y587-2; Sequence=VSP_040023;
CC Name=3;
CC IsoId=Q9Y587-3; Sequence=VSP_046364;
CC Name=4;
CC IsoId=Q9Y587-4; Sequence=VSP_046941;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Spastic paraplegia 52, autosomal recessive (SPG52)
CC [MIM:614067]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. SPG52 is characterized by neonatal
CC hypotonia that progresses to hypertonia and spasticity, and severe
CC intellectual disability with poor or absent speech development. Some
CC patients may have seizures. {ECO:0000269|PubMed:21620353}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the adaptor complexes small subunit family.
CC {ECO:0000305}.
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DR EMBL; AF155159; AAD43329.1; -; mRNA.
DR EMBL; AB030654; BAA82970.1; -; mRNA.
DR EMBL; BX247969; CAD62307.1; -; mRNA.
DR EMBL; BX388185; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BT006701; AAP35347.1; -; mRNA.
DR EMBL; CR457100; CAG33381.1; -; mRNA.
DR EMBL; AK304115; BAG65016.1; -; mRNA.
DR EMBL; AL049830; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121808; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65953.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65954.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65955.1; -; Genomic_DNA.
DR EMBL; BC001259; AAH01259.1; -; mRNA.
DR CCDS; CCDS45093.1; -. [Q9Y587-1]
DR CCDS; CCDS58309.1; -. [Q9Y587-4]
DR CCDS; CCDS58310.1; -. [Q9Y587-3]
DR CCDS; CCDS9642.1; -. [Q9Y587-2]
DR RefSeq; NP_001121598.1; NM_001128126.2. [Q9Y587-1]
DR RefSeq; NP_001241655.1; NM_001254726.1. [Q9Y587-3]
DR RefSeq; NP_001241656.1; NM_001254727.1. [Q9Y587-4]
DR RefSeq; NP_001241657.1; NM_001254728.1. [Q9Y587-1]
DR RefSeq; NP_001241658.1; NM_001254729.1. [Q9Y587-1]
DR RefSeq; NP_009008.2; NM_007077.4. [Q9Y587-2]
DR RefSeq; XP_005267350.1; XM_005267293.4. [Q9Y587-2]
DR RefSeq; XP_011534673.1; XM_011536371.2. [Q9Y587-2]
DR RefSeq; XP_011534674.1; XM_011536372.2. [Q9Y587-2]
DR AlphaFoldDB; Q9Y587; -.
DR SMR; Q9Y587; -.
DR BioGRID; 116325; 27.
DR ComplexPortal; CPX-5151; AP-4 Adaptor complex.
DR CORUM; Q9Y587; -.
DR IntAct; Q9Y587; 23.
DR MINT; Q9Y587; -.
DR STRING; 9606.ENSP00000216366; -.
DR BindingDB; Q9Y587; -.
DR TCDB; 9.B.278.1.5; the organellar-targeting adaptor protein complex (o-apc) family.
DR GlyGen; Q9Y587; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y587; -.
DR PhosphoSitePlus; Q9Y587; -.
DR BioMuta; AP4S1; -.
DR DMDM; 13431288; -.
DR EPD; Q9Y587; -.
DR jPOST; Q9Y587; -.
DR MassIVE; Q9Y587; -.
DR MaxQB; Q9Y587; -.
DR PaxDb; Q9Y587; -.
DR PeptideAtlas; Q9Y587; -.
DR PRIDE; Q9Y587; -.
DR ProteomicsDB; 32694; -.
DR ProteomicsDB; 69763; -.
DR ProteomicsDB; 86316; -. [Q9Y587-1]
DR ProteomicsDB; 86317; -. [Q9Y587-2]
DR Antibodypedia; 51162; 31 antibodies from 11 providers.
DR DNASU; 11154; -.
DR Ensembl; ENST00000334725.8; ENSP00000334484.4; ENSG00000100478.16. [Q9Y587-4]
DR Ensembl; ENST00000542754.7; ENSP00000438170.2; ENSG00000100478.16. [Q9Y587-1]
DR Ensembl; ENST00000554345.6; ENSP00000450768.2; ENSG00000100478.16. [Q9Y587-2]
DR Ensembl; ENST00000554609.6; ENSP00000452383.2; ENSG00000100478.16. [Q9Y587-3]
DR Ensembl; ENST00000555417.6; ENSP00000451609.2; ENSG00000100478.16. [Q9Y587-1]
DR Ensembl; ENST00000557346.6; ENSP00000451479.2; ENSG00000100478.16. [Q9Y587-1]
DR GeneID; 11154; -.
DR KEGG; hsa:11154; -.
DR MANE-Select; ENST00000542754.7; ENSP00000438170.2; NM_001128126.3; NP_001121598.1.
DR UCSC; uc001wqw.5; human. [Q9Y587-1]
DR CTD; 11154; -.
DR DisGeNET; 11154; -.
DR GeneCards; AP4S1; -.
DR GeneReviews; AP4S1; -.
DR HGNC; HGNC:575; AP4S1.
DR HPA; ENSG00000100478; Low tissue specificity.
DR MalaCards; AP4S1; -.
DR MIM; 607243; gene.
DR MIM; 614067; phenotype.
DR neXtProt; NX_Q9Y587; -.
DR OpenTargets; ENSG00000100478; -.
DR Orphanet; 280763; Severe intellectual disability and progressive spastic paraplegia.
DR PharmGKB; PA24867; -.
DR VEuPathDB; HostDB:ENSG00000100478; -.
DR eggNOG; KOG0934; Eukaryota.
DR GeneTree; ENSGT00970000193421; -.
DR InParanoid; Q9Y587; -.
DR OMA; KDQCSFI; -.
DR OrthoDB; 1307450at2759; -.
DR PhylomeDB; Q9Y587; -.
DR TreeFam; TF331913; -.
DR PathwayCommons; Q9Y587; -.
DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis.
DR SignaLink; Q9Y587; -.
DR BioGRID-ORCS; 11154; 23 hits in 1052 CRISPR screens.
DR ChiTaRS; AP4S1; human.
DR GeneWiki; AP4S1; -.
DR GenomeRNAi; 11154; -.
DR Pharos; Q9Y587; Tdark.
DR PRO; PR:Q9Y587; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9Y587; protein.
DR Bgee; ENSG00000100478; Expressed in endothelial cell and 204 other tissues.
DR ExpressionAtlas; Q9Y587; baseline and differential.
DR Genevisible; Q9Y587; HS.
DR GO; GO:0030124; C:AP-4 adaptor complex; IDA:UniProtKB.
DR GO; GO:0031904; C:endosome lumen; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005802; C:trans-Golgi network; IC:ComplexPortal.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0008104; P:protein localization; IC:UniProtKB.
DR GO; GO:0006605; P:protein targeting; IC:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR InterPro; IPR016635; AP_complex_ssu.
DR InterPro; IPR022775; AP_mu_sigma_su.
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.
PE 1: Evidence at protein level;
KW Alternative splicing; Golgi apparatus; Hereditary spastic paraplegia;
KW Membrane; Neurodegeneration; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..144
FT /note="AP-4 complex subunit sigma-1"
FT /id="PRO_0000193820"
FT VAR_SEQ 99..144
FT /note="SELDIMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILDKMSES -> EP
FT IDELPKICSALEPQQTCFSPDSSSFKGAASTTPIY (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_046364"
FT VAR_SEQ 103..144
FT /note="IMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILDKMSES -> VSFFNT
FT VFHSTWQMHSGPYQEPIDELPKICSALEPQQTCFSPDSSSFKGAASTTPIY (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_040023"
FT VAR_SEQ 103..144
FT /note="IMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILDKMSES -> VSFFNT
FT VFHSTWQMHSGPYQTRSCSVTQAGVQRCDHGSLHPGSPGLK (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_046941"
SQ SEQUENCE 144 AA; 17005 MW; 0B620AFBB3B7F8A1 CRC64;
MIKFFLMVNK QGQTRLSKYY EHVDINKRTL LETEVIKSCL SRSNEQCSFI EYKDFKLIYR
QYAALFIVVG VNDTENEMAI YEFIHNFVEV LDEYFSRVSE LDIMFNLDKV HIILDEMVLN
GCIVETNRAR ILAPLLILDK MSES
