Full text data of AP4S1
AP4S1
[Confidence: low (only semi-automatic identification from reviews)]
AP-4 complex subunit sigma-1 (AP-4 adapter complex subunit sigma-1; Adapter-related protein complex 4 subunit sigma-1; Sigma-1 subunit of AP-4; Sigma-4-adaptin; Sigma4-adaptin)
AP-4 complex subunit sigma-1 (AP-4 adapter complex subunit sigma-1; Adapter-related protein complex 4 subunit sigma-1; Sigma-1 subunit of AP-4; Sigma-4-adaptin; Sigma4-adaptin)
UniProt
Q9Y587
ID AP4S1_HUMAN Reviewed; 144 AA.
AC Q9Y587; G3V2N8; Q6IAQ4; Q86U36; Q9BVE7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 106.
DE RecName: Full=AP-4 complex subunit sigma-1;
DE AltName: Full=AP-4 adapter complex subunit sigma-1;
DE AltName: Full=Adapter-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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT constitutes 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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA 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.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INVOLVEMENT IN CPSQ6.
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.,
RA Munnich A., Strom T.M., Reis A., Colleaux L.;
RT "Adaptor protein complex 4 deficiency causes severe autosomal-
RT recessive intellectual disability, progressive spastic paraplegia, shy
RT character, and short stature.";
RL Am. J. Hum. Genet. 88:788-795(2011).
CC -!- FUNCTION: Subunit of novel type of clathrin- or non-clathrin-
CC associated protein coat involved in targeting proteins from the
CC trans-Golgi network (TGN) to the endosomal-lysosomal system.
CC -!- SUBUNIT: Adaptor protein complex 4 (AP-4) is a heterotetramer
CC composed of two large adaptins (epsilon-type subunit AP4E1 and
CC beta-type subunitAP4B1), a medium adaptin (mu-type subunit AP4M1)
CC and a small adaptin (sigma-type AP4S1).
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network.
CC Membrane, coated pit. Note=Associated with the trans-Golgi
CC network. Found in soma and dendritic shafts of neuronal cells.
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 Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9Y587-4; Sequence=VSP_046941;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Cerebral palsy, spastic quadriplegic 6 (CPSQ6)
CC [MIM:614067]: A neurodevelopmental disorder characterized by
CC neonatal hypotonia that progresses to hypertonia and spasticity,
CC and severe mental retardation with poor or absent speech
CC development. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adaptor complexes small subunit family.
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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 RefSeq; NP_001121598.1; NM_001128126.2.
DR RefSeq; NP_001241655.1; NM_001254726.1.
DR RefSeq; NP_001241656.1; NM_001254727.1.
DR RefSeq; NP_001241657.1; NM_001254728.1.
DR RefSeq; NP_001241658.1; NM_001254729.1.
DR RefSeq; NP_009008.2; NM_007077.4.
DR RefSeq; XP_005267350.1; XM_005267293.1.
DR UniGene; Hs.293411; -.
DR ProteinModelPortal; Q9Y587; -.
DR SMR; Q9Y587; 1-141.
DR IntAct; Q9Y587; 4.
DR STRING; 9606.ENSP00000216366; -.
DR BindingDB; Q9Y587; -.
DR PhosphoSite; Q9Y587; -.
DR DMDM; 13431288; -.
DR PaxDb; Q9Y587; -.
DR PRIDE; Q9Y587; -.
DR DNASU; 11154; -.
DR Ensembl; ENST00000216366; ENSP00000216366; ENSG00000100478.
DR Ensembl; ENST00000334725; ENSP00000334484; ENSG00000100478.
DR Ensembl; ENST00000542754; ENSP00000438170; ENSG00000100478.
DR Ensembl; ENST00000554345; ENSP00000450768; ENSG00000100478.
DR GeneID; 11154; -.
DR KEGG; hsa:11154; -.
DR UCSC; uc010amh.3; human.
DR CTD; 11154; -.
DR GeneCards; GC14P031494; -.
DR HGNC; HGNC:575; AP4S1.
DR HPA; HPA039963; -.
DR MIM; 607243; gene.
DR MIM; 614067; phenotype.
DR neXtProt; NX_Q9Y587; -.
DR Orphanet; 280763; Severe intellectual deficit and progressive spastic paraplegia.
DR PharmGKB; PA24867; -.
DR eggNOG; COG5030; -.
DR HOGENOM; HOG000185227; -.
DR HOVERGEN; HBG050517; -.
DR KO; K12403; -.
DR OMA; KLVYRQY; -.
DR ChiTaRS; AP4S1; human.
DR GeneWiki; AP4S1; -.
DR GenomeRNAi; 11154; -.
DR NextBio; 42409; -.
DR PRO; PR:Q9Y587; -.
DR ArrayExpress; Q9Y587; -.
DR Bgee; Q9Y587; -.
DR CleanEx; HS_AP4S1; -.
DR Genevestigator; Q9Y587; -.
DR GO; GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0005215; F:transporter activity; TAS:ProtInc.
DR InterPro; IPR016635; AP_complex_ssu.
DR InterPro; IPR022775; AP_mu_sigma_su.
DR InterPro; IPR011012; Longin-like_dom.
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; FALSE_NEG.
PE 2: Evidence at transcript level;
KW Alternative splicing; Coated pit; Complete proteome; Golgi apparatus;
KW Membrane; Protein transport; Reference proteome; Transport.
FT CHAIN 1 144 AP-4 complex subunit sigma-1.
FT /FTId=PRO_0000193820.
FT VAR_SEQ 99 144 SELDIMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILD
FT KMSES -> EPIDELPKICSALEPQQTCFSPDSSSFKGAAS
FT TTPIY (in isoform 3).
FT /FTId=VSP_046364.
FT VAR_SEQ 103 144 IMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILDKMSE
FT S -> VSFFNTVFHSTWQMHSGPYQEPIDELPKICSALEPQ
FT QTCFSPDSSSFKGAASTTPIY (in isoform 2).
FT /FTId=VSP_040023.
FT VAR_SEQ 103 144 IMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILDKMSE
FT S -> VSFFNTVFHSTWQMHSGPYQTRSCSVTQAGVQRCDH
FT GSLHPGSPGLK (in isoform 4).
FT /FTId=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
//
ID AP4S1_HUMAN Reviewed; 144 AA.
AC Q9Y587; G3V2N8; Q6IAQ4; Q86U36; Q9BVE7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 106.
DE RecName: Full=AP-4 complex subunit sigma-1;
DE AltName: Full=AP-4 adapter complex subunit sigma-1;
DE AltName: Full=Adapter-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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT constitutes 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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA 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.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INVOLVEMENT IN CPSQ6.
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.,
RA Munnich A., Strom T.M., Reis A., Colleaux L.;
RT "Adaptor protein complex 4 deficiency causes severe autosomal-
RT recessive intellectual disability, progressive spastic paraplegia, shy
RT character, and short stature.";
RL Am. J. Hum. Genet. 88:788-795(2011).
CC -!- FUNCTION: Subunit of novel type of clathrin- or non-clathrin-
CC associated protein coat involved in targeting proteins from the
CC trans-Golgi network (TGN) to the endosomal-lysosomal system.
CC -!- SUBUNIT: Adaptor protein complex 4 (AP-4) is a heterotetramer
CC composed of two large adaptins (epsilon-type subunit AP4E1 and
CC beta-type subunitAP4B1), a medium adaptin (mu-type subunit AP4M1)
CC and a small adaptin (sigma-type AP4S1).
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network.
CC Membrane, coated pit. Note=Associated with the trans-Golgi
CC network. Found in soma and dendritic shafts of neuronal cells.
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 Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9Y587-4; Sequence=VSP_046941;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Cerebral palsy, spastic quadriplegic 6 (CPSQ6)
CC [MIM:614067]: A neurodevelopmental disorder characterized by
CC neonatal hypotonia that progresses to hypertonia and spasticity,
CC and severe mental retardation with poor or absent speech
CC development. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adaptor complexes small subunit family.
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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 RefSeq; NP_001121598.1; NM_001128126.2.
DR RefSeq; NP_001241655.1; NM_001254726.1.
DR RefSeq; NP_001241656.1; NM_001254727.1.
DR RefSeq; NP_001241657.1; NM_001254728.1.
DR RefSeq; NP_001241658.1; NM_001254729.1.
DR RefSeq; NP_009008.2; NM_007077.4.
DR RefSeq; XP_005267350.1; XM_005267293.1.
DR UniGene; Hs.293411; -.
DR ProteinModelPortal; Q9Y587; -.
DR SMR; Q9Y587; 1-141.
DR IntAct; Q9Y587; 4.
DR STRING; 9606.ENSP00000216366; -.
DR BindingDB; Q9Y587; -.
DR PhosphoSite; Q9Y587; -.
DR DMDM; 13431288; -.
DR PaxDb; Q9Y587; -.
DR PRIDE; Q9Y587; -.
DR DNASU; 11154; -.
DR Ensembl; ENST00000216366; ENSP00000216366; ENSG00000100478.
DR Ensembl; ENST00000334725; ENSP00000334484; ENSG00000100478.
DR Ensembl; ENST00000542754; ENSP00000438170; ENSG00000100478.
DR Ensembl; ENST00000554345; ENSP00000450768; ENSG00000100478.
DR GeneID; 11154; -.
DR KEGG; hsa:11154; -.
DR UCSC; uc010amh.3; human.
DR CTD; 11154; -.
DR GeneCards; GC14P031494; -.
DR HGNC; HGNC:575; AP4S1.
DR HPA; HPA039963; -.
DR MIM; 607243; gene.
DR MIM; 614067; phenotype.
DR neXtProt; NX_Q9Y587; -.
DR Orphanet; 280763; Severe intellectual deficit and progressive spastic paraplegia.
DR PharmGKB; PA24867; -.
DR eggNOG; COG5030; -.
DR HOGENOM; HOG000185227; -.
DR HOVERGEN; HBG050517; -.
DR KO; K12403; -.
DR OMA; KLVYRQY; -.
DR ChiTaRS; AP4S1; human.
DR GeneWiki; AP4S1; -.
DR GenomeRNAi; 11154; -.
DR NextBio; 42409; -.
DR PRO; PR:Q9Y587; -.
DR ArrayExpress; Q9Y587; -.
DR Bgee; Q9Y587; -.
DR CleanEx; HS_AP4S1; -.
DR Genevestigator; Q9Y587; -.
DR GO; GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0005215; F:transporter activity; TAS:ProtInc.
DR InterPro; IPR016635; AP_complex_ssu.
DR InterPro; IPR022775; AP_mu_sigma_su.
DR InterPro; IPR011012; Longin-like_dom.
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; FALSE_NEG.
PE 2: Evidence at transcript level;
KW Alternative splicing; Coated pit; Complete proteome; Golgi apparatus;
KW Membrane; Protein transport; Reference proteome; Transport.
FT CHAIN 1 144 AP-4 complex subunit sigma-1.
FT /FTId=PRO_0000193820.
FT VAR_SEQ 99 144 SELDIMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILD
FT KMSES -> EPIDELPKICSALEPQQTCFSPDSSSFKGAAS
FT TTPIY (in isoform 3).
FT /FTId=VSP_046364.
FT VAR_SEQ 103 144 IMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILDKMSE
FT S -> VSFFNTVFHSTWQMHSGPYQEPIDELPKICSALEPQ
FT QTCFSPDSSSFKGAASTTPIY (in isoform 2).
FT /FTId=VSP_040023.
FT VAR_SEQ 103 144 IMFNLDKVHIILDEMVLNGCIVETNRARILAPLLILDKMSE
FT S -> VSFFNTVFHSTWQMHSGPYQTRSCSVTQAGVQRCDH
FT GSLHPGSPGLK (in isoform 4).
FT /FTId=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
//
MIM
607243
*RECORD*
*FIELD* NO
607243
*FIELD* TI
*607243 ADAPTOR-RELATED PROTEIN COMPLEX 4, SIGMA-1 SUBUNIT; AP4S1
*FIELD* TX
DESCRIPTION
read more
The heterotetrameric adaptor protein (AP) complexes sort integral
membrane proteins at various stages of the endocytic and secretory
pathways. AP4 is composed of 2 large chains, beta-4 (AP4B1; 607245) and
epsilon-4 (AP4E1; 607244), a medium chain, mu-4 (AP4M1; 602296), and a
small chain, sigma-4 (AP4S1) (summary by Hirst et al., 1999).
CLONING
Dell'Angelica et al. (1999) cloned mouse Ap4s1. The predicted 144-amino
acid Ap4s1 protein has a calculated molecular mass of 16.8 kD. Northern
blot analysis revealed a 1.2- to 1.4-kb transcript in all mouse tissues
examined. By gel filtration and Western blot analysis of human
fibroblast cytosol, Dell'Angelica et al. (1999) found that AP4S1 shows
an apparent molecular mass of about 17 kD and is part of a 280-kD
complex containing AP4B1, AP4E1, and AP4M1. Immunolocalization of the
AP4B1 subunit in HeLa cells indicated that the AP4 complex associates
with the trans-Golgi network or an adjacent structure. The association
was sensitive to brefeldin-A treatment, indicating that the membrane
localization of AP4 is dependent upon the small GTP-binding protein ARF1
(103180).
Hirst et al. (1999) identified AP4S1 within an EST from human placenta.
The deduced AP4S1 protein contains 144 amino acids and shares 30 to 40%
sequence identity with AP1S (see 603531), AP2S (602242), and AP3S (see
601507). Using a yeast 2-hybrid analysis, Hirst et al. (1999) found
strong and specific interaction between AP4E1 and AP4S1.
Abou Jamra et al. (2011) found ubiquitous AP4S1 expression in all fetal
and adult brain structures examined.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the AP4S1
gene to chromosome 14 (TMAP H00269).
MOLECULAR GENETICS
By linkage analysis followed by exome sequencing of a consanguineous
Syrian family with autosomal recessive mental retardation and spasticity
(SPG52; 614067), Abou Jamra et al. (2011) identified a homozygous
truncating mutation in the AP4S1 gene (R42X; 607243.0001).
*FIELD* AV
.0001
SPASTIC PARAPLEGIA 52, AUTOSOMAL RECESSIVE
AP4S1, ARG42TER
By linkage analysis followed by exome sequencing of a consanguineous
Syrian family with autosomal recessive mental retardation and
spasticity, (SPG52; 614067), Abou Jamra et al. (2011) identified a
homozygous 124C-T transition in exon 2 of the AP4S1 gene, resulting in
an arg42-to-ter (R42X) substitution. The mutation was not found in 740
control chromosomes of Syrian descent.
*FIELD* RF
1. Abou Jamra, R.; Philippe, O.; Raas-Rothschild, A.; Eck, S. H.;
Graf, E.; Buchert, R.; Borck, G.; Ekici, A.; Brockschmidt, F. F.;
Nothen, M. M.; Munnich, A.; Strom, T. M.; Reis, A.; Colleaux, L.:
Adaptor protein complex 4 deficiency causes severe autosomal-recessive
intellectual disability, progressive spastic paraplegia, shy character,
and short stature. Am. J. Hum. Genet. 88: 788-795, 2011.
2. Dell'Angelica, E. C.; Mullins, C.; Bonifacino, J. S.: AP-4, a
novel protein complex related to clathrin adaptors. J. Biol. Chem. 274:
7278-7285, 1999.
3. Hirst, J.; Bright, N. A.; Rous, B.; Robinson, M. S.: Characterization
of a fourth adaptor-related protein complex. Molec. Biol. Cell 10:
2787-2802, 1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/29/2011
*FIELD* CD
Patricia A. Hartz: 9/19/2002
*FIELD* ED
carol: 04/24/2012
ckniffin: 4/24/2012
carol: 12/29/2011
wwang: 7/5/2011
ckniffin: 6/29/2011
carol: 5/28/2003
mgross: 9/19/2002
*RECORD*
*FIELD* NO
607243
*FIELD* TI
*607243 ADAPTOR-RELATED PROTEIN COMPLEX 4, SIGMA-1 SUBUNIT; AP4S1
*FIELD* TX
DESCRIPTION
read more
The heterotetrameric adaptor protein (AP) complexes sort integral
membrane proteins at various stages of the endocytic and secretory
pathways. AP4 is composed of 2 large chains, beta-4 (AP4B1; 607245) and
epsilon-4 (AP4E1; 607244), a medium chain, mu-4 (AP4M1; 602296), and a
small chain, sigma-4 (AP4S1) (summary by Hirst et al., 1999).
CLONING
Dell'Angelica et al. (1999) cloned mouse Ap4s1. The predicted 144-amino
acid Ap4s1 protein has a calculated molecular mass of 16.8 kD. Northern
blot analysis revealed a 1.2- to 1.4-kb transcript in all mouse tissues
examined. By gel filtration and Western blot analysis of human
fibroblast cytosol, Dell'Angelica et al. (1999) found that AP4S1 shows
an apparent molecular mass of about 17 kD and is part of a 280-kD
complex containing AP4B1, AP4E1, and AP4M1. Immunolocalization of the
AP4B1 subunit in HeLa cells indicated that the AP4 complex associates
with the trans-Golgi network or an adjacent structure. The association
was sensitive to brefeldin-A treatment, indicating that the membrane
localization of AP4 is dependent upon the small GTP-binding protein ARF1
(103180).
Hirst et al. (1999) identified AP4S1 within an EST from human placenta.
The deduced AP4S1 protein contains 144 amino acids and shares 30 to 40%
sequence identity with AP1S (see 603531), AP2S (602242), and AP3S (see
601507). Using a yeast 2-hybrid analysis, Hirst et al. (1999) found
strong and specific interaction between AP4E1 and AP4S1.
Abou Jamra et al. (2011) found ubiquitous AP4S1 expression in all fetal
and adult brain structures examined.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the AP4S1
gene to chromosome 14 (TMAP H00269).
MOLECULAR GENETICS
By linkage analysis followed by exome sequencing of a consanguineous
Syrian family with autosomal recessive mental retardation and spasticity
(SPG52; 614067), Abou Jamra et al. (2011) identified a homozygous
truncating mutation in the AP4S1 gene (R42X; 607243.0001).
*FIELD* AV
.0001
SPASTIC PARAPLEGIA 52, AUTOSOMAL RECESSIVE
AP4S1, ARG42TER
By linkage analysis followed by exome sequencing of a consanguineous
Syrian family with autosomal recessive mental retardation and
spasticity, (SPG52; 614067), Abou Jamra et al. (2011) identified a
homozygous 124C-T transition in exon 2 of the AP4S1 gene, resulting in
an arg42-to-ter (R42X) substitution. The mutation was not found in 740
control chromosomes of Syrian descent.
*FIELD* RF
1. Abou Jamra, R.; Philippe, O.; Raas-Rothschild, A.; Eck, S. H.;
Graf, E.; Buchert, R.; Borck, G.; Ekici, A.; Brockschmidt, F. F.;
Nothen, M. M.; Munnich, A.; Strom, T. M.; Reis, A.; Colleaux, L.:
Adaptor protein complex 4 deficiency causes severe autosomal-recessive
intellectual disability, progressive spastic paraplegia, shy character,
and short stature. Am. J. Hum. Genet. 88: 788-795, 2011.
2. Dell'Angelica, E. C.; Mullins, C.; Bonifacino, J. S.: AP-4, a
novel protein complex related to clathrin adaptors. J. Biol. Chem. 274:
7278-7285, 1999.
3. Hirst, J.; Bright, N. A.; Rous, B.; Robinson, M. S.: Characterization
of a fourth adaptor-related protein complex. Molec. Biol. Cell 10:
2787-2802, 1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/29/2011
*FIELD* CD
Patricia A. Hartz: 9/19/2002
*FIELD* ED
carol: 04/24/2012
ckniffin: 4/24/2012
carol: 12/29/2011
wwang: 7/5/2011
ckniffin: 6/29/2011
carol: 5/28/2003
mgross: 9/19/2002
MIM
614067
*RECORD*
*FIELD* NO
614067
*FIELD* TI
#614067 SPASTIC PARAPLEGIA 52, AUTOSOMAL RECESSIVE; SPG52
;;CEREBRAL PALSY, SPASTIC QUADRIPLEGIC, 6, FORMERLY; CPSQ6, FORMERLY
read more*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
spastic paraplegia-52 (SPG52) is caused by homozygous mutation in the
AP4S1 gene (607243) on chromosome 14q12.
DESCRIPTION
Spastic quadriplegia-52 is an autosomal recessive neurodevelopmental
disorder characterized by neonatal hypotonia that progresses to
hypertonia and spasticity and severe mental retardation with poor or
absent speech development (summary by Abou Jamra et al., 2011).
CLINICAL FEATURES
Abou Jamra et al. (2011) reported a consanguineous Syrian kindred
(MR061) in which 5 individuals had severe mental retardation and
spasticity. They had delayed motor development in infancy, but lost the
ability to walk in early childhood due to spasticity. Physical
examination showed muscular hypertonia, especially of lower limbs,
contractures, talipes equinovarus, decreased shank muscle mass, short
stature, and microcephaly. All had a severe cognitive deficit and absent
speech and could only express basic needs. Dysmorphic features included
a prominent and bulbous nose, wide mouth, and coarse features. All were
markedly shy, amicable, and calm, and kept smiling or laughing for no
obvious reason, but did not have laughter bursts. None of the patients
had seizures, a hearing impairment, or any anomalies of inner organs.
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing of a Syrian
family with autosomal recessive mental retardation and spasticity, Abou
Jamra et al. (2011) identified a homozygous truncating mutation in the
AP4S1 gene (607243.0001). The authors concluded that
AP4-complex-mediated vesicular trafficking plays a crucial role in brain
development and function.
*FIELD* RF
1. Abou Jamra, R.; Philippe, O.; Raas-Rothschild, A.; Eck, S. H.;
Graf, E.; Buchert, R.; Borck, G.; Ekici, A.; Brockschmidt, F. F.;
Nothen, M. M.; Munnich, A.; Strom, T. M.; Reis, A.; Colleaux, L.:
Adaptor protein complex 4 deficiency causes severe autosomal-recessive
intellectual disability, progressive spastic paraplegia, shy character,
and short stature. Am. J. Hum. Genet. 88: 788-795, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Head];
Microcephaly;
[Face];
Coarse facial features;
[Nose];
Prominent nose;
Bulbous nose;
[Mouth];
Wide mouth
SKELETAL:
Joint contractures;
[Feet];
Talipes equinovarus
MUSCLE, SOFT TISSUE:
Hypertonia;
Decreased shank muscle mass
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Mental retardation, severe;
Spasticity;
Hyperreflexia;
Loss of ability to walk;
Extensor plantar responses;
Lack of speech development;
[Behavioral/psychiatric manifestations];
Stereotypic laughter;
Shy character;
Amicable character
MISCELLANEOUS:
Onset at birth;
One family has been reported (as of June 2011)
MOLECULAR BASIS:
Caused by mutation in the adaptor-related protein complex 4, sigma-1
subunit (AP4S1, 607243.0001)
*FIELD* CD
Cassandra L. Kniffin: 6/29/2011
*FIELD* ED
joanna: 12/30/2011
ckniffin: 6/29/2011
*FIELD* CD
Cassandra L. Kniffin: 6/29/2011
*FIELD* ED
carol: 04/24/2012
carol: 4/24/2012
ckniffin: 4/24/2012
wwang: 7/7/2011
wwang: 7/5/2011
ckniffin: 6/29/2011
*RECORD*
*FIELD* NO
614067
*FIELD* TI
#614067 SPASTIC PARAPLEGIA 52, AUTOSOMAL RECESSIVE; SPG52
;;CEREBRAL PALSY, SPASTIC QUADRIPLEGIC, 6, FORMERLY; CPSQ6, FORMERLY
read more*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
spastic paraplegia-52 (SPG52) is caused by homozygous mutation in the
AP4S1 gene (607243) on chromosome 14q12.
DESCRIPTION
Spastic quadriplegia-52 is an autosomal recessive neurodevelopmental
disorder characterized by neonatal hypotonia that progresses to
hypertonia and spasticity and severe mental retardation with poor or
absent speech development (summary by Abou Jamra et al., 2011).
CLINICAL FEATURES
Abou Jamra et al. (2011) reported a consanguineous Syrian kindred
(MR061) in which 5 individuals had severe mental retardation and
spasticity. They had delayed motor development in infancy, but lost the
ability to walk in early childhood due to spasticity. Physical
examination showed muscular hypertonia, especially of lower limbs,
contractures, talipes equinovarus, decreased shank muscle mass, short
stature, and microcephaly. All had a severe cognitive deficit and absent
speech and could only express basic needs. Dysmorphic features included
a prominent and bulbous nose, wide mouth, and coarse features. All were
markedly shy, amicable, and calm, and kept smiling or laughing for no
obvious reason, but did not have laughter bursts. None of the patients
had seizures, a hearing impairment, or any anomalies of inner organs.
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing of a Syrian
family with autosomal recessive mental retardation and spasticity, Abou
Jamra et al. (2011) identified a homozygous truncating mutation in the
AP4S1 gene (607243.0001). The authors concluded that
AP4-complex-mediated vesicular trafficking plays a crucial role in brain
development and function.
*FIELD* RF
1. Abou Jamra, R.; Philippe, O.; Raas-Rothschild, A.; Eck, S. H.;
Graf, E.; Buchert, R.; Borck, G.; Ekici, A.; Brockschmidt, F. F.;
Nothen, M. M.; Munnich, A.; Strom, T. M.; Reis, A.; Colleaux, L.:
Adaptor protein complex 4 deficiency causes severe autosomal-recessive
intellectual disability, progressive spastic paraplegia, shy character,
and short stature. Am. J. Hum. Genet. 88: 788-795, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Head];
Microcephaly;
[Face];
Coarse facial features;
[Nose];
Prominent nose;
Bulbous nose;
[Mouth];
Wide mouth
SKELETAL:
Joint contractures;
[Feet];
Talipes equinovarus
MUSCLE, SOFT TISSUE:
Hypertonia;
Decreased shank muscle mass
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Mental retardation, severe;
Spasticity;
Hyperreflexia;
Loss of ability to walk;
Extensor plantar responses;
Lack of speech development;
[Behavioral/psychiatric manifestations];
Stereotypic laughter;
Shy character;
Amicable character
MISCELLANEOUS:
Onset at birth;
One family has been reported (as of June 2011)
MOLECULAR BASIS:
Caused by mutation in the adaptor-related protein complex 4, sigma-1
subunit (AP4S1, 607243.0001)
*FIELD* CD
Cassandra L. Kniffin: 6/29/2011
*FIELD* ED
joanna: 12/30/2011
ckniffin: 6/29/2011
*FIELD* CD
Cassandra L. Kniffin: 6/29/2011
*FIELD* ED
carol: 04/24/2012
carol: 4/24/2012
ckniffin: 4/24/2012
wwang: 7/7/2011
wwang: 7/5/2011
ckniffin: 6/29/2011