Full text data of AP1S2
AP1S2
[Confidence: low (only semi-automatic identification from reviews)]
AP-1 complex subunit sigma-2 (Adapter-related protein complex 1 subunit sigma-1B; Adaptor protein complex AP-1 subunit sigma-1B; Clathrin assembly protein complex 1 sigma-1B small chain; Golgi adaptor HA1/AP1 adaptin sigma-1B subunit; Sigma 1B subunit of AP-1 clathrin; Sigma-adaptin 1B; Sigma1B-adaptin)
AP-1 complex subunit sigma-2 (Adapter-related protein complex 1 subunit sigma-1B; Adaptor protein complex AP-1 subunit sigma-1B; Clathrin assembly protein complex 1 sigma-1B small chain; Golgi adaptor HA1/AP1 adaptin sigma-1B subunit; Sigma 1B subunit of AP-1 clathrin; Sigma-adaptin 1B; Sigma1B-adaptin)
UniProt
P56377
ID AP1S2_HUMAN Reviewed; 157 AA.
AC P56377; O95326; Q9H2N6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=AP-1 complex subunit sigma-2;
DE AltName: Full=Adapter-related protein complex 1 subunit sigma-1B;
DE AltName: Full=Adaptor protein complex AP-1 subunit sigma-1B;
DE AltName: Full=Clathrin assembly protein complex 1 sigma-1B small chain;
DE AltName: Full=Golgi adaptor HA1/AP1 adaptin sigma-1B subunit;
DE AltName: Full=Sigma 1B subunit of AP-1 clathrin;
DE AltName: Full=Sigma-adaptin 1B;
DE AltName: Full=Sigma1B-adaptin;
GN Name=AP1S2; ORFNames=DC22;
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].
RX PubMed=9733768; DOI=10.1074/jbc.273.38.24693;
RA Takatsu H., Sakurai M., Shin H.-W., Murakami K., Nakayama K.;
RT "Identification and characterization of novel clathrin adaptor-related
RT proteins.";
RL J. Biol. Chem. 273:24693-24700(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Dendritic cell;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RT "Novel genes expressed in human dendritic cell.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin, and Uterus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-98.
RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH MUC1.
RX PubMed=15471854; DOI=10.1074/jbc.M409360200;
RA Kinlough C.L., Poland P.A., Bruns J.B., Harkleroad K.L., Hughey R.P.;
RT "MUC1 membrane trafficking is modulated by multiple interactions.";
RL J. Biol. Chem. 279:53071-53077(2004).
RN [7]
RP INVOLVEMENT IN MRX59.
RX PubMed=17186471; DOI=10.1086/510137;
RA Tarpey P.S., Stevens C., Teague J., Edkins S., O'Meara S., Avis T.,
RA Barthorpe S., Buck G., Butler A., Cole J., Dicks E., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jones D., Menzies A.,
RA Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., West S., Widaa S., Yates A.,
RA Catford R., Butler J., Mallya U., Moon J., Luo Y., Dorkins H.,
RA Thompson D., Easton D.F., Wooster R., Bobrow M., Carpenter N.,
RA Simensen R.J., Schwartz C.E., Stevenson R.E., Turner G.,
RA Partington M., Gecz J., Stratton M.R., Futreal P.A., Raymond F.L.;
RT "Mutations in the gene encoding the sigma 2 subunit of the adaptor
RT protein 1 complex, AP1S2, cause X-linked mental retardation.";
RL Am. J. Hum. Genet. 79:1119-1124(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Subunit of clathrin-associated adaptor protein complex 1
CC that plays a role in protein sorting in the late-Golgi/trans-Golgi
CC network (TGN) and/or endosomes. The AP complexes mediate both the
CC recruitment of clathrin to membranes and the recognition of
CC sorting signals within the cytosolic tails of transmembrane cargo
CC molecules.
CC -!- SUBUNIT: Adaptor protein complex 1 (AP-1) is a heterotetramer
CC composed of two large adaptins (gamma-type subunit AP1G1 and beta-
CC type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or
CC AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or
CC AP1S3). Binds to MUC1.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Cytoplasmic vesicle
CC membrane; Peripheral membrane protein; Cytoplasmic side. Membrane,
CC clathrin-coated pit. Note=Component of the coat surrounding the
CC cytoplasmic face of coated vesicles located at the Golgi complex.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Mental retardation, X-linked 59 (MRX59) [MIM:300630]: A
CC disorder characterized by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period.
CC Intellectual deficiency is the only primary symptom of non-
CC syndromic X-linked mental retardation, while syndromic mental
CC retardation presents with associated physical, neurological and/or
CC psychiatric manifestations. MRX59 consists of a mild-to-profound
CC mental retardation. Other features includes hypotonia early in
CC life and delay in walking. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adaptor complexes small subunit family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG44595.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB015320; BAA33392.1; -; mRNA.
DR EMBL; AF251295; AAG44595.1; ALT_INIT; mRNA.
DR EMBL; BT006738; AAP35384.1; -; mRNA.
DR EMBL; BC001117; AAH01117.1; -; mRNA.
DR EMBL; BC071867; AAH71867.1; -; mRNA.
DR EMBL; AF091077; AAC72946.1; -; mRNA.
DR RefSeq; NP_003907.3; NM_003916.4.
DR UniGene; Hs.121592; -.
DR ProteinModelPortal; P56377; -.
DR SMR; P56377; 1-147.
DR MINT; MINT-3021368; -.
DR STRING; 9606.ENSP00000328789; -.
DR PhosphoSite; P56377; -.
DR DMDM; 3023308; -.
DR PaxDb; P56377; -.
DR PRIDE; P56377; -.
DR DNASU; 8905; -.
DR Ensembl; ENST00000329235; ENSP00000328789; ENSG00000182287.
DR GeneID; 8905; -.
DR KEGG; hsa:8905; -.
DR UCSC; uc004cxi.4; human.
DR CTD; 8905; -.
DR GeneCards; GC0XM015843; -.
DR HGNC; HGNC:560; AP1S2.
DR MIM; 300629; gene.
DR MIM; 300630; phenotype.
DR neXtProt; NX_P56377; -.
DR Orphanet; 85335; Fried syndrome.
DR Orphanet; 1568; Intellectual deficit, X-linked - Dandy-Walker malformation - basal ganglia disease - Seizures.
DR PharmGKB; PA24851; -.
DR eggNOG; COG5030; -.
DR HOGENOM; HOG000185227; -.
DR HOVERGEN; HBG050517; -.
DR KO; K12394; -.
DR OMA; DMKVVYK; -.
DR OrthoDB; EOG7S7SGC; -.
DR PhylomeDB; P56377; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; AP1S2; -.
DR GenomeRNAi; 8905; -.
DR NextBio; 33457; -.
DR PRO; PR:P56377; -.
DR ArrayExpress; P56377; -.
DR Bgee; P56377; -.
DR CleanEx; HS_AP1S2; -.
DR Genevestigator; P56377; -.
DR GO; GO:0030119; C:AP-type membrane coat adaptor complex; TAS:ProtInc.
DR GO; GO:0005905; C: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:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
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.
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 Coated pit; Complete proteome; Cytoplasmic vesicle; Golgi apparatus;
KW Membrane; Mental retardation; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 157 AP-1 complex subunit sigma-2.
FT /FTId=PRO_0000193799.
FT CONFLICT 1 1 M -> L (in Ref. 2; AAG44595).
FT CONFLICT 72 74 DQD -> ESRN (in Ref. 5; AAC72946).
FT CONFLICT 96 98 SVC -> QCL (in Ref. 5; AAC72946).
FT CONFLICT 143 143 E -> EE (in Ref. 2; AAG44595).
SQ SEQUENCE 157 AA; 18615 MW; DD9F59119909D89C CRC64;
MQFMLLFSRQ GKLRLQKWYV PLSDKEKKKI TRELVQTVLA RKPKMCSFLE WRDLKIVYKR
YASLYFCCAI EDQDNELITL EIIHRYVELL DKYFGSVCEL DIIFNFEKAY FILDEFLLGG
EVQETSKKNV LKAIEQADLL QEEAETPRSV LEEIGLT
//
ID AP1S2_HUMAN Reviewed; 157 AA.
AC P56377; O95326; Q9H2N6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=AP-1 complex subunit sigma-2;
DE AltName: Full=Adapter-related protein complex 1 subunit sigma-1B;
DE AltName: Full=Adaptor protein complex AP-1 subunit sigma-1B;
DE AltName: Full=Clathrin assembly protein complex 1 sigma-1B small chain;
DE AltName: Full=Golgi adaptor HA1/AP1 adaptin sigma-1B subunit;
DE AltName: Full=Sigma 1B subunit of AP-1 clathrin;
DE AltName: Full=Sigma-adaptin 1B;
DE AltName: Full=Sigma1B-adaptin;
GN Name=AP1S2; ORFNames=DC22;
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].
RX PubMed=9733768; DOI=10.1074/jbc.273.38.24693;
RA Takatsu H., Sakurai M., Shin H.-W., Murakami K., Nakayama K.;
RT "Identification and characterization of novel clathrin adaptor-related
RT proteins.";
RL J. Biol. Chem. 273:24693-24700(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Dendritic cell;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RT "Novel genes expressed in human dendritic cell.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin, and Uterus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-98.
RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH MUC1.
RX PubMed=15471854; DOI=10.1074/jbc.M409360200;
RA Kinlough C.L., Poland P.A., Bruns J.B., Harkleroad K.L., Hughey R.P.;
RT "MUC1 membrane trafficking is modulated by multiple interactions.";
RL J. Biol. Chem. 279:53071-53077(2004).
RN [7]
RP INVOLVEMENT IN MRX59.
RX PubMed=17186471; DOI=10.1086/510137;
RA Tarpey P.S., Stevens C., Teague J., Edkins S., O'Meara S., Avis T.,
RA Barthorpe S., Buck G., Butler A., Cole J., Dicks E., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jones D., Menzies A.,
RA Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., West S., Widaa S., Yates A.,
RA Catford R., Butler J., Mallya U., Moon J., Luo Y., Dorkins H.,
RA Thompson D., Easton D.F., Wooster R., Bobrow M., Carpenter N.,
RA Simensen R.J., Schwartz C.E., Stevenson R.E., Turner G.,
RA Partington M., Gecz J., Stratton M.R., Futreal P.A., Raymond F.L.;
RT "Mutations in the gene encoding the sigma 2 subunit of the adaptor
RT protein 1 complex, AP1S2, cause X-linked mental retardation.";
RL Am. J. Hum. Genet. 79:1119-1124(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Subunit of clathrin-associated adaptor protein complex 1
CC that plays a role in protein sorting in the late-Golgi/trans-Golgi
CC network (TGN) and/or endosomes. The AP complexes mediate both the
CC recruitment of clathrin to membranes and the recognition of
CC sorting signals within the cytosolic tails of transmembrane cargo
CC molecules.
CC -!- SUBUNIT: Adaptor protein complex 1 (AP-1) is a heterotetramer
CC composed of two large adaptins (gamma-type subunit AP1G1 and beta-
CC type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or
CC AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or
CC AP1S3). Binds to MUC1.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Cytoplasmic vesicle
CC membrane; Peripheral membrane protein; Cytoplasmic side. Membrane,
CC clathrin-coated pit. Note=Component of the coat surrounding the
CC cytoplasmic face of coated vesicles located at the Golgi complex.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Mental retardation, X-linked 59 (MRX59) [MIM:300630]: A
CC disorder characterized by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period.
CC Intellectual deficiency is the only primary symptom of non-
CC syndromic X-linked mental retardation, while syndromic mental
CC retardation presents with associated physical, neurological and/or
CC psychiatric manifestations. MRX59 consists of a mild-to-profound
CC mental retardation. Other features includes hypotonia early in
CC life and delay in walking. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adaptor complexes small subunit family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG44595.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB015320; BAA33392.1; -; mRNA.
DR EMBL; AF251295; AAG44595.1; ALT_INIT; mRNA.
DR EMBL; BT006738; AAP35384.1; -; mRNA.
DR EMBL; BC001117; AAH01117.1; -; mRNA.
DR EMBL; BC071867; AAH71867.1; -; mRNA.
DR EMBL; AF091077; AAC72946.1; -; mRNA.
DR RefSeq; NP_003907.3; NM_003916.4.
DR UniGene; Hs.121592; -.
DR ProteinModelPortal; P56377; -.
DR SMR; P56377; 1-147.
DR MINT; MINT-3021368; -.
DR STRING; 9606.ENSP00000328789; -.
DR PhosphoSite; P56377; -.
DR DMDM; 3023308; -.
DR PaxDb; P56377; -.
DR PRIDE; P56377; -.
DR DNASU; 8905; -.
DR Ensembl; ENST00000329235; ENSP00000328789; ENSG00000182287.
DR GeneID; 8905; -.
DR KEGG; hsa:8905; -.
DR UCSC; uc004cxi.4; human.
DR CTD; 8905; -.
DR GeneCards; GC0XM015843; -.
DR HGNC; HGNC:560; AP1S2.
DR MIM; 300629; gene.
DR MIM; 300630; phenotype.
DR neXtProt; NX_P56377; -.
DR Orphanet; 85335; Fried syndrome.
DR Orphanet; 1568; Intellectual deficit, X-linked - Dandy-Walker malformation - basal ganglia disease - Seizures.
DR PharmGKB; PA24851; -.
DR eggNOG; COG5030; -.
DR HOGENOM; HOG000185227; -.
DR HOVERGEN; HBG050517; -.
DR KO; K12394; -.
DR OMA; DMKVVYK; -.
DR OrthoDB; EOG7S7SGC; -.
DR PhylomeDB; P56377; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; AP1S2; -.
DR GenomeRNAi; 8905; -.
DR NextBio; 33457; -.
DR PRO; PR:P56377; -.
DR ArrayExpress; P56377; -.
DR Bgee; P56377; -.
DR CleanEx; HS_AP1S2; -.
DR Genevestigator; P56377; -.
DR GO; GO:0030119; C:AP-type membrane coat adaptor complex; TAS:ProtInc.
DR GO; GO:0005905; C: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:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
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.
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 Coated pit; Complete proteome; Cytoplasmic vesicle; Golgi apparatus;
KW Membrane; Mental retardation; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 157 AP-1 complex subunit sigma-2.
FT /FTId=PRO_0000193799.
FT CONFLICT 1 1 M -> L (in Ref. 2; AAG44595).
FT CONFLICT 72 74 DQD -> ESRN (in Ref. 5; AAC72946).
FT CONFLICT 96 98 SVC -> QCL (in Ref. 5; AAC72946).
FT CONFLICT 143 143 E -> EE (in Ref. 2; AAG44595).
SQ SEQUENCE 157 AA; 18615 MW; DD9F59119909D89C CRC64;
MQFMLLFSRQ GKLRLQKWYV PLSDKEKKKI TRELVQTVLA RKPKMCSFLE WRDLKIVYKR
YASLYFCCAI EDQDNELITL EIIHRYVELL DKYFGSVCEL DIIFNFEKAY FILDEFLLGG
EVQETSKKNV LKAIEQADLL QEEAETPRSV LEEIGLT
//
MIM
300629
*RECORD*
*FIELD* NO
300629
*FIELD* TI
*300629 ADAPTOR-RELATED PROTEIN COMPLEX 1, SIGMA-2 SUBUNIT; AP1S2
;;CLATHRIN-ASSOCIATED/ASSEMBLY/ADAPTOR PROTEIN, SMALL 1-LIKE;;
read moreCLATHRIN ADAPTOR COMPLEX AP1, SIGMA-1B SUBUNIT
*FIELD* TX
CLONING
Clathrin and its associated heterotetrameric protein complexes (APs) are
the main protein components of the coat surrounding the cytoplasmic face
of coated vesicles. AP1, which is localized at the trans-Golgi network,
is composed of 2 large chains, beta-prime-adaptin (600157) and
gamma-adaptin (603533); a medium (mu) chain, AP47 (603535); and a small
(sigma) chain, AP19 (603531). Takatsu et al. (1998) identified a human
cDNA encoding sigma-1B, a protein related to mouse AP19. The predicted
157-amino acid protein shares 87% identity with human AP19. In yeast
2-hybrid assays, sigma-1B interacted with both gamma-adaptin and
gamma-2-adaptin (603534). Northern blot analysis revealed that SIGMA1B
was expressed ubiquitously in human tissues.
GENE STRUCTURE
Tarpey et al. (2006) stated that the AP1S2 gene is composed of 5 exons.
MAPPING
Tarpey et al. (2006) identified the AP1S2 gene on chromosome Xp22 by
sequence analysis.
MOLECULAR GENETICS
In a systematic sequencing screen of the coding exons of the X
chromosome in 250 families with X-linked mental retardation (XLMR),
Tarpey et al. (2006) identified 2 nonsense mutations and 1 consensus
splice site mutation in the AP1S2 gene on Xp22 in 3 families. Affected
individuals in these families, designated MRX59 (300630), showed mild to
profound mental retardation. Other features included hypotonia early in
life and delay in walking. Tarpey et al. (2006) suggested that aberrant
endocytic processing through disruption of adaptor protein complexes was
likely to result from the AP1S2 mutations identified in the 3
XLMR-affected families. Such defects may plausibly cause abnormal
synaptic development and function. AP1S2 was the first reported XLMR
gene that encodes a protein directly involved in the assembly of
endocytic vesicles.
Saillour et al. (2007) identified 2 pathogenic mutations in the AP1S2
gene (300529.0004 and 300529.0005, respectively) in affected members of
2 unrelated families with X-linked mental retardation.
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
mutations in the AP1S2 gene in 3 families.
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED 59
AP1S2, GLN36TER
In a family described by Turner et al. (2003) with an X-linked recessive
form of mental retardation (MRX59; 300630) in 10 males in 4 generations,
Tarpey et al. (2006) demonstrated a nonsense mutation, gln36 to ter
(Q36X), that arose from a 106C-T transition in exon 2 of the AP1S2 gene.
.0002
MENTAL RETARDATION, X-LINKED 59
AP1S2, ARG52TER
In the family with X-linked mental retardation (MRX59; 300630) studied
by Carpenter et al. (1999), Tarpey et al. (2006) found that affected
members had an arg52-to-ter (R52X) mutation in the AP1S2 gene, resulting
from a 154C-T transition in exon 2.
.0003
MENTAL RETARDATION, X-LINKED 59
AP1S2, 4-BP DEL, NT180
In a family with 4 males with X-linked mental retardation (MRX59;
300630) in 2 generations, Tarpey et al. (2006) found in affected members
a 4-bp deletion in the AP1S2 gene, preceding the splice acceptor site of
exon 3 that resulted in the replacement of the invariant A at position
-2 with a T (180-5del4). The mutation was expected to cause skipping of
exon 3, which would then introduce a translational frameshift, resulting
in the inclusion of 3 novel amino acids, with termination at codon 64.
.0004
MENTAL RETARDATION, X-LINKED 59
AP1S2, IVS3DS, G-A, +5
In affected members of a French family with MRX59 (300630), Saillour et
al. (2007) identified a G-to-A transition in intron 3 of the AP1S2 gene
(IVS3AS+5G-A), resulting in the skipping of exon 3 and premature
truncation of the protein.
.0005
MENTAL RETARDATION, X-LINKED 59
AP1S2, GLN66TER
In affected members of a family with X-linked mental retardation
(300630) originally reported by Fried (1972), Saillour et al. (2007)
identified a 226G-T transversion in exon 3 of the AP1S2 gene, resulting
in a gln66-to-ter (Q66X) substitution. The mutation was not identified
in more than 160 normal X chromosomes.
*FIELD* RF
1. Carpenter, N. J.; Brown, W. T.; Qu, Y.; Keenan, K. L.: Regional
localization of a nonspecific X-linked mental retardation gene (MRX59)
to Xp21.2-p22.2. Am. J. Med. Genet. 85: 266-270, 1999.
2. Fried, K.: X-linked mental retardation and/or hydrocephalus. Clin.
Genet. 3: 258-263, 1972.
3. Saillour, Y.; Zanni, G.; Des Portes, V.; Heron, D.; Guibaud, L.;
Iba-Zizen, M. T.; Pedespan, J. L.; Poirier, K.; Castelnau, L.; Julien,
C.; Franconnet, C.; Bonthron, D.; Porteous, M. E.; Chelly, J.; Bienvenu,
T.: Mutations in the AP1S2 gene encoding the sigma 2 subunit of the
adaptor protein 1 complex are associated with syndromic X-linked mental
retardation with hydrocephalus and calcifications in basal ganglia.
(Letter) J. Med. Genet. 44: 739-744, 2007.
4. Takatsu, H.; Sakurai, M.; Shin, H.-W.; Murakami, K.; Nakayama,
K.: Identification and characterization of novel clathrin adaptor-related
proteins. J. Biol. Chem. 273: 24693-24700, 1998.
5. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins, S.;
Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
6. Tarpey, P. S.; Stevens, C.; Teague, J.; Edkins, S.; O'Meara, S.;
Avis, T.; Barthorpe, S.; Buck, G.; Butler, A.; Cole, J.; Dicks, E.;
Gray, K.; and 37 others: Mutations in the gene encoding the sigma
2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked
mental retardation. Am. J. Hum. Genet. 79: 1119-1124, 2006.
7. Turner, G.; Gedeon, A.; Kerr, B.; Bennett, R.; Mulley, J.; Partington,
M.: Syndromic form of X-linked mental retardation with marked hypotonia
in early life, severe mental handicap, and difficult adult behavior
maps to Xp22. Am. J. Med. Genet. 117A: 245-250, 2003.
*FIELD* CN
Ada Hamosh - updated: 10/01/2009
Cassandra L. Kniffin - updated: 12/28/2007
*FIELD* CD
Victor A. McKusick: 12/7/2006
*FIELD* ED
terry: 10/01/2009
wwang: 1/17/2008
ckniffin: 12/28/2007
alopez: 12/8/2006
*RECORD*
*FIELD* NO
300629
*FIELD* TI
*300629 ADAPTOR-RELATED PROTEIN COMPLEX 1, SIGMA-2 SUBUNIT; AP1S2
;;CLATHRIN-ASSOCIATED/ASSEMBLY/ADAPTOR PROTEIN, SMALL 1-LIKE;;
read moreCLATHRIN ADAPTOR COMPLEX AP1, SIGMA-1B SUBUNIT
*FIELD* TX
CLONING
Clathrin and its associated heterotetrameric protein complexes (APs) are
the main protein components of the coat surrounding the cytoplasmic face
of coated vesicles. AP1, which is localized at the trans-Golgi network,
is composed of 2 large chains, beta-prime-adaptin (600157) and
gamma-adaptin (603533); a medium (mu) chain, AP47 (603535); and a small
(sigma) chain, AP19 (603531). Takatsu et al. (1998) identified a human
cDNA encoding sigma-1B, a protein related to mouse AP19. The predicted
157-amino acid protein shares 87% identity with human AP19. In yeast
2-hybrid assays, sigma-1B interacted with both gamma-adaptin and
gamma-2-adaptin (603534). Northern blot analysis revealed that SIGMA1B
was expressed ubiquitously in human tissues.
GENE STRUCTURE
Tarpey et al. (2006) stated that the AP1S2 gene is composed of 5 exons.
MAPPING
Tarpey et al. (2006) identified the AP1S2 gene on chromosome Xp22 by
sequence analysis.
MOLECULAR GENETICS
In a systematic sequencing screen of the coding exons of the X
chromosome in 250 families with X-linked mental retardation (XLMR),
Tarpey et al. (2006) identified 2 nonsense mutations and 1 consensus
splice site mutation in the AP1S2 gene on Xp22 in 3 families. Affected
individuals in these families, designated MRX59 (300630), showed mild to
profound mental retardation. Other features included hypotonia early in
life and delay in walking. Tarpey et al. (2006) suggested that aberrant
endocytic processing through disruption of adaptor protein complexes was
likely to result from the AP1S2 mutations identified in the 3
XLMR-affected families. Such defects may plausibly cause abnormal
synaptic development and function. AP1S2 was the first reported XLMR
gene that encodes a protein directly involved in the assembly of
endocytic vesicles.
Saillour et al. (2007) identified 2 pathogenic mutations in the AP1S2
gene (300529.0004 and 300529.0005, respectively) in affected members of
2 unrelated families with X-linked mental retardation.
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
mutations in the AP1S2 gene in 3 families.
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED 59
AP1S2, GLN36TER
In a family described by Turner et al. (2003) with an X-linked recessive
form of mental retardation (MRX59; 300630) in 10 males in 4 generations,
Tarpey et al. (2006) demonstrated a nonsense mutation, gln36 to ter
(Q36X), that arose from a 106C-T transition in exon 2 of the AP1S2 gene.
.0002
MENTAL RETARDATION, X-LINKED 59
AP1S2, ARG52TER
In the family with X-linked mental retardation (MRX59; 300630) studied
by Carpenter et al. (1999), Tarpey et al. (2006) found that affected
members had an arg52-to-ter (R52X) mutation in the AP1S2 gene, resulting
from a 154C-T transition in exon 2.
.0003
MENTAL RETARDATION, X-LINKED 59
AP1S2, 4-BP DEL, NT180
In a family with 4 males with X-linked mental retardation (MRX59;
300630) in 2 generations, Tarpey et al. (2006) found in affected members
a 4-bp deletion in the AP1S2 gene, preceding the splice acceptor site of
exon 3 that resulted in the replacement of the invariant A at position
-2 with a T (180-5del4). The mutation was expected to cause skipping of
exon 3, which would then introduce a translational frameshift, resulting
in the inclusion of 3 novel amino acids, with termination at codon 64.
.0004
MENTAL RETARDATION, X-LINKED 59
AP1S2, IVS3DS, G-A, +5
In affected members of a French family with MRX59 (300630), Saillour et
al. (2007) identified a G-to-A transition in intron 3 of the AP1S2 gene
(IVS3AS+5G-A), resulting in the skipping of exon 3 and premature
truncation of the protein.
.0005
MENTAL RETARDATION, X-LINKED 59
AP1S2, GLN66TER
In affected members of a family with X-linked mental retardation
(300630) originally reported by Fried (1972), Saillour et al. (2007)
identified a 226G-T transversion in exon 3 of the AP1S2 gene, resulting
in a gln66-to-ter (Q66X) substitution. The mutation was not identified
in more than 160 normal X chromosomes.
*FIELD* RF
1. Carpenter, N. J.; Brown, W. T.; Qu, Y.; Keenan, K. L.: Regional
localization of a nonspecific X-linked mental retardation gene (MRX59)
to Xp21.2-p22.2. Am. J. Med. Genet. 85: 266-270, 1999.
2. Fried, K.: X-linked mental retardation and/or hydrocephalus. Clin.
Genet. 3: 258-263, 1972.
3. Saillour, Y.; Zanni, G.; Des Portes, V.; Heron, D.; Guibaud, L.;
Iba-Zizen, M. T.; Pedespan, J. L.; Poirier, K.; Castelnau, L.; Julien,
C.; Franconnet, C.; Bonthron, D.; Porteous, M. E.; Chelly, J.; Bienvenu,
T.: Mutations in the AP1S2 gene encoding the sigma 2 subunit of the
adaptor protein 1 complex are associated with syndromic X-linked mental
retardation with hydrocephalus and calcifications in basal ganglia.
(Letter) J. Med. Genet. 44: 739-744, 2007.
4. Takatsu, H.; Sakurai, M.; Shin, H.-W.; Murakami, K.; Nakayama,
K.: Identification and characterization of novel clathrin adaptor-related
proteins. J. Biol. Chem. 273: 24693-24700, 1998.
5. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins, S.;
Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
6. Tarpey, P. S.; Stevens, C.; Teague, J.; Edkins, S.; O'Meara, S.;
Avis, T.; Barthorpe, S.; Buck, G.; Butler, A.; Cole, J.; Dicks, E.;
Gray, K.; and 37 others: Mutations in the gene encoding the sigma
2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked
mental retardation. Am. J. Hum. Genet. 79: 1119-1124, 2006.
7. Turner, G.; Gedeon, A.; Kerr, B.; Bennett, R.; Mulley, J.; Partington,
M.: Syndromic form of X-linked mental retardation with marked hypotonia
in early life, severe mental handicap, and difficult adult behavior
maps to Xp22. Am. J. Med. Genet. 117A: 245-250, 2003.
*FIELD* CN
Ada Hamosh - updated: 10/01/2009
Cassandra L. Kniffin - updated: 12/28/2007
*FIELD* CD
Victor A. McKusick: 12/7/2006
*FIELD* ED
terry: 10/01/2009
wwang: 1/17/2008
ckniffin: 12/28/2007
alopez: 12/8/2006
MIM
300630
*RECORD*
*FIELD* NO
300630
*FIELD* TI
#300630 MENTAL RETARDATION, X-LINKED, SYNDROMIC, FRIED TYPE; MRXSF
;;MENTAL RETARDATION, X-LINKED 59; MRX59;;
read moreMENTAL RETARDATION, X-LINKED, SYNDROMIC 21; MRXS21
*FIELD* TX
A number sign (#) is used with this entry because of evidence that this
form of X-linked mental retardation (MRXSF) is caused by mutation in the
sigma-2 subunit of the adaptor protein-1 complex, AP1S2 (300629).
CLINICAL FEATURES
Fried (1972) reported a Scottish pedigree with X-linked mental
retardation, in which some affected members had hydrocephalus; the
disorder appeared to be linked to the blood group locus Xg with a most
likely recombination fraction of 0.11 (Fried and Sanger, 1973). The
family included 6 males with variable mental retardation. Two patients
had hydrocephalus, 1 of which was suspected to be the result of stenosis
of the aqueduct of Sylvius. All had delayed motor development and
difficulty walking as adults.
Carpenter et al. (1999) described a 4-generation family with nonspecific
mental retardation, designated MRX59. The 5 affected males, ranging in
age from 2 to 52 years, had a normal facial appearance and mild to
severe mental retardation. Two of the affected males displayed
aggressive behavior.
Turner et al. (2003) described an X-linked recessive form of mental
retardation in a family in which 10 males in 4 generations were
affected. The main manifestations were severe to profound intellectual
disability, muscular hypotonia in childhood, delayed walking, and in the
adults, difficult and aggressive behavior. There was moderate reduction
both in the occipitofrontal circumference and in height, and a similar
facial appearance, triangular in shape with high forehead, prominent
ears, and a small pointed chin.
Saillour et al. (2007) reported a French family in which 8 males
spanning 4 generations had mental retardation. Four living patients were
in specialized institutions. Other features included hypotonia, delayed
motor development, and poor language skills. Among 5 patients, 2 who
were examined had basal ganglia calcifications, and 2 had congenital
hydrocephalus with stenosis of the aqueduct of Sylvius.
MAPPING
Carpenter et al. (1999) performed linkage analysis on a 4-generation
MRX59 family. A maximum lod score of 2.41 at theta = 0.00 was observed
with microsatellite markers in Xp21.2, Xp22.1, and Xp22.2. Genetic
localization of this familial condition made prenatal diagnosis
informative for 1 of the obligate carriers.
Using linkage analysis in the 4-generation family with X-linked mental
retardation studied by them, Turner et al. (2003) located the gene at
Xp22 with maximum lod scores of 4.8 at theta = 0.0 for markers mapping
between the closest recombination points at DXS7104 and DXS418.
MOLECULAR GENETICS
In a systematic sequencing screen of the coding exons of the X
chromosome in 250 families with X-linked mental retardation (XLMR),
Tarpey et al. (2006) identified 2 nonsense mutations and 1 consensus
splice site mutation in the AP1S2 (300629) gene on Xp22 in 3 families,
including the families reported by Carpenter et al. (1999) and Turner et
al. (2003). AP1S2 encodes an adaptin protein that constitutes part of
the adaptor protein complex found at the cytoplasmic face of coated
vesicles located at the Golgi complex. The complex mediates the
recruitment of clathrin to the vesicle membrane. Tarpey et al. (2006)
suggested that aberrant endocytic processing through disruption of
adaptor protein complexes was likely to result from the AP1S2 mutations
identified in the 3 XLMR-affected families. Such defects may plausibly
cause abnormal synaptic development and function. AP1S2 was the first
reported XLMR gene that encodes a protein directly involved in the
assembly of endocytic vesicles.
Saillour et al. (2007) identified 2 pathogenic mutations in the AP1S2
gene (300529.0004 and 300529.0005, respectively) in affected members of
2 unrelated families with X-linked mental retardation. One of the
families had been reported by Fried (1972).
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
mutations in the AP1S2 (300629) gene in 3 families.
*FIELD* RF
1. Carpenter, N. J.; Brown, W. T.; Qu, Y.; Keenan, K. L.: Regional
localization of a nonspecific X-linked mental retardation gene (MRX59)
to Xp21.2-p22.2. Am. J. Med. Genet. 85: 266-270, 1999.
2. Fried, K.: X-linked mental retardation and/or hydrocephalus. Clin.
Genet. 3: 258-263, 1972.
3. Fried, K.; Sanger, R.: Possible linkage between Xg and the locus
for a gene causing mental retardation with or without hydrocephalus. J.
Med. Genet. 10: 17-18, 1973.
4. Saillour, Y.; Zanni, G.; Des Portes, V.; Heron, D.; Guibaud, L.;
Iba-Zizen, M. T.; Pedespan, J. L.; Poirier, K.; Castelnau, L.; Julien,
C.; Franconnet, C.; Bonthron, D.; Porteous, M. E.; Chelly, J.; Bienvenu,
T.: Mutations in the AP1S2 gene encoding the sigma 2 subunit of the
adaptor protein 1 complex are associated with syndromic X-linked mental
retardation with hydrocephalus and calcifications in basal ganglia.
(Letter) J. Med. Genet. 44: 739-744, 2007.
5. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins, S.;
Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
6. Tarpey, P. S.; Stevens, C.; Teague, J.; Edkins, S.; O'Meara, S.;
Avis, T.; Barthorpe, S.; Buck, G.; Butler, A.; Cole, J.; Dicks, E.;
Gray, K.; and 37 others: Mutations in the gene encoding the sigma
2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked
mental retardation. Am. J. Hum. Genet. 79: 1119-1124, 2006.
7. Turner, G.; Gedeon, A.; Kerr, B.; Bennett, R.; Mulley, J.; Partington,
M.: Syndromic form of X-linked mental retardation with marked hypotonia
in early life, severe mental handicap, and difficult adult behavior
maps to Xp22. Am. J. Med. Genet. 117A: 245-250, 2003.
*FIELD* CN
Ada Hamosh - updated: 10/1/2009
Cassandra L. Kniffin - updated: 12/28/2007
*FIELD* CD
Victor A. McKusick: 12/8/2006
*FIELD* ED
carol: 10/26/2011
ckniffin: 10/26/2011
ckniffin: 10/25/2011
alopez: 10/7/2009
terry: 10/1/2009
wwang: 1/17/2008
ckniffin: 12/28/2007
alopez: 12/8/2006
*RECORD*
*FIELD* NO
300630
*FIELD* TI
#300630 MENTAL RETARDATION, X-LINKED, SYNDROMIC, FRIED TYPE; MRXSF
;;MENTAL RETARDATION, X-LINKED 59; MRX59;;
read moreMENTAL RETARDATION, X-LINKED, SYNDROMIC 21; MRXS21
*FIELD* TX
A number sign (#) is used with this entry because of evidence that this
form of X-linked mental retardation (MRXSF) is caused by mutation in the
sigma-2 subunit of the adaptor protein-1 complex, AP1S2 (300629).
CLINICAL FEATURES
Fried (1972) reported a Scottish pedigree with X-linked mental
retardation, in which some affected members had hydrocephalus; the
disorder appeared to be linked to the blood group locus Xg with a most
likely recombination fraction of 0.11 (Fried and Sanger, 1973). The
family included 6 males with variable mental retardation. Two patients
had hydrocephalus, 1 of which was suspected to be the result of stenosis
of the aqueduct of Sylvius. All had delayed motor development and
difficulty walking as adults.
Carpenter et al. (1999) described a 4-generation family with nonspecific
mental retardation, designated MRX59. The 5 affected males, ranging in
age from 2 to 52 years, had a normal facial appearance and mild to
severe mental retardation. Two of the affected males displayed
aggressive behavior.
Turner et al. (2003) described an X-linked recessive form of mental
retardation in a family in which 10 males in 4 generations were
affected. The main manifestations were severe to profound intellectual
disability, muscular hypotonia in childhood, delayed walking, and in the
adults, difficult and aggressive behavior. There was moderate reduction
both in the occipitofrontal circumference and in height, and a similar
facial appearance, triangular in shape with high forehead, prominent
ears, and a small pointed chin.
Saillour et al. (2007) reported a French family in which 8 males
spanning 4 generations had mental retardation. Four living patients were
in specialized institutions. Other features included hypotonia, delayed
motor development, and poor language skills. Among 5 patients, 2 who
were examined had basal ganglia calcifications, and 2 had congenital
hydrocephalus with stenosis of the aqueduct of Sylvius.
MAPPING
Carpenter et al. (1999) performed linkage analysis on a 4-generation
MRX59 family. A maximum lod score of 2.41 at theta = 0.00 was observed
with microsatellite markers in Xp21.2, Xp22.1, and Xp22.2. Genetic
localization of this familial condition made prenatal diagnosis
informative for 1 of the obligate carriers.
Using linkage analysis in the 4-generation family with X-linked mental
retardation studied by them, Turner et al. (2003) located the gene at
Xp22 with maximum lod scores of 4.8 at theta = 0.0 for markers mapping
between the closest recombination points at DXS7104 and DXS418.
MOLECULAR GENETICS
In a systematic sequencing screen of the coding exons of the X
chromosome in 250 families with X-linked mental retardation (XLMR),
Tarpey et al. (2006) identified 2 nonsense mutations and 1 consensus
splice site mutation in the AP1S2 (300629) gene on Xp22 in 3 families,
including the families reported by Carpenter et al. (1999) and Turner et
al. (2003). AP1S2 encodes an adaptin protein that constitutes part of
the adaptor protein complex found at the cytoplasmic face of coated
vesicles located at the Golgi complex. The complex mediates the
recruitment of clathrin to the vesicle membrane. Tarpey et al. (2006)
suggested that aberrant endocytic processing through disruption of
adaptor protein complexes was likely to result from the AP1S2 mutations
identified in the 3 XLMR-affected families. Such defects may plausibly
cause abnormal synaptic development and function. AP1S2 was the first
reported XLMR gene that encodes a protein directly involved in the
assembly of endocytic vesicles.
Saillour et al. (2007) identified 2 pathogenic mutations in the AP1S2
gene (300529.0004 and 300529.0005, respectively) in affected members of
2 unrelated families with X-linked mental retardation. One of the
families had been reported by Fried (1972).
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
mutations in the AP1S2 (300629) gene in 3 families.
*FIELD* RF
1. Carpenter, N. J.; Brown, W. T.; Qu, Y.; Keenan, K. L.: Regional
localization of a nonspecific X-linked mental retardation gene (MRX59)
to Xp21.2-p22.2. Am. J. Med. Genet. 85: 266-270, 1999.
2. Fried, K.: X-linked mental retardation and/or hydrocephalus. Clin.
Genet. 3: 258-263, 1972.
3. Fried, K.; Sanger, R.: Possible linkage between Xg and the locus
for a gene causing mental retardation with or without hydrocephalus. J.
Med. Genet. 10: 17-18, 1973.
4. Saillour, Y.; Zanni, G.; Des Portes, V.; Heron, D.; Guibaud, L.;
Iba-Zizen, M. T.; Pedespan, J. L.; Poirier, K.; Castelnau, L.; Julien,
C.; Franconnet, C.; Bonthron, D.; Porteous, M. E.; Chelly, J.; Bienvenu,
T.: Mutations in the AP1S2 gene encoding the sigma 2 subunit of the
adaptor protein 1 complex are associated with syndromic X-linked mental
retardation with hydrocephalus and calcifications in basal ganglia.
(Letter) J. Med. Genet. 44: 739-744, 2007.
5. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins, S.;
Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
6. Tarpey, P. S.; Stevens, C.; Teague, J.; Edkins, S.; O'Meara, S.;
Avis, T.; Barthorpe, S.; Buck, G.; Butler, A.; Cole, J.; Dicks, E.;
Gray, K.; and 37 others: Mutations in the gene encoding the sigma
2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked
mental retardation. Am. J. Hum. Genet. 79: 1119-1124, 2006.
7. Turner, G.; Gedeon, A.; Kerr, B.; Bennett, R.; Mulley, J.; Partington,
M.: Syndromic form of X-linked mental retardation with marked hypotonia
in early life, severe mental handicap, and difficult adult behavior
maps to Xp22. Am. J. Med. Genet. 117A: 245-250, 2003.
*FIELD* CN
Ada Hamosh - updated: 10/1/2009
Cassandra L. Kniffin - updated: 12/28/2007
*FIELD* CD
Victor A. McKusick: 12/8/2006
*FIELD* ED
carol: 10/26/2011
ckniffin: 10/26/2011
ckniffin: 10/25/2011
alopez: 10/7/2009
terry: 10/1/2009
wwang: 1/17/2008
ckniffin: 12/28/2007
alopez: 12/8/2006