Full text data of PSENEN
PSENEN
(PEN2)
[Confidence: low (only semi-automatic identification from reviews)]
Gamma-secretase subunit PEN-2 (Presenilin enhancer protein 2)
Gamma-secretase subunit PEN-2 (Presenilin enhancer protein 2)
UniProt
Q9NZ42
ID PEN2_HUMAN Reviewed; 101 AA.
AC Q9NZ42; B2R5L9;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 109.
DE RecName: Full=Gamma-secretase subunit PEN-2;
DE AltName: Full=Presenilin enhancer protein 2;
GN Name=PSENEN; Synonyms=PEN2; ORFNames=MDS033;
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 [LARGE SCALE MRNA].
RC TISSUE=Hematopoietic stem cell;
RA Zhao M., Gu J., Li N., Peng Y., Han Z., Chen Z.;
RT "Novel genes expressed in hematopoietic stem/progenitor cells from
RT myelodysplastic syndrome patients.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP INTERACTION WITH NCSTN; PSEN1 AND PSEN2.
RX PubMed=12198112; DOI=10.1074/jbc.C200469200;
RA Steiner H., Winkler E., Edbauer D., Prokop S., Basset G., Yamasaki A.,
RA Kostka M., Haass C.;
RT "PEN-2 is an integral component of the gamma-secretase complex
RT required for coordinated expression of presenilin and nicastrin.";
RL J. Biol. Chem. 277:39062-39065(2002).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12110170; DOI=10.1016/S1534-5807(02)00189-2;
RA Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J.,
RA Nicoll M., Maxwell M., Hai B., Ellis M.C., Parks A.L., Xu W., Li J.,
RA Gurney M., Myers R.L., Himes C.S., Hiebsch R., Ruble C., Nye J.S.,
RA Curtis D.;
RT "aph-1 and pen-2 are required for Notch pathway signaling, gamma-
RT secretase cleavage of betaAPP, and presenilin protein accumulation.";
RL Dev. Cell 3:85-97(2002).
RN [6]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=12522139; DOI=10.1074/jbc.C200648200;
RA Luo W.-J., Wang H., Li H., Kim B.S., Shah S., Lee H.-J.,
RA Thinakaran G., Kim T.-W., Yu G., Xu H.;
RT "PEN-2 and APH-1 coordinately regulate proteolytic processing of
RT presenilin 1.";
RL J. Biol. Chem. 278:7850-7854(2003).
RN [7]
RP MEMBRANE TOPOLOGY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-10;
RP ALA-46 AND SER-93.
RX PubMed=12639958; DOI=10.1074/jbc.M213107200;
RA Crystal A.S., Morais V.A., Pierson T.C., Pijak D.S., Carlin D.,
RA Lee V.M., Doms R.W.;
RT "Membrane topology of gamma-secretase component PEN-2.";
RL J. Biol. Chem. 278:20117-20123(2003).
RN [8]
RP FUNCTION IN THE GAMMA-SECRETASE COMPLEX.
RX PubMed=12763021; DOI=10.1016/S0006-291X(03)00797-6;
RA Marlow L., Canet R.M., Haugabook S.J., Hardy J.A., Lahiri D.K.,
RA Sambamurti K.;
RT "APH1, PEN2, and nicastrin increase Abeta levels and gamma-secretase
RT activity.";
RL Biochem. Biophys. Res. Commun. 305:502-509(2003).
RN [9]
RP TISSUE SPECIFICITY, AND COMPONENT OF A GAMMA-SECRETASE COMPLEX WITH
RP APH1A; PSEN1/PSEN2 AND NCSTN.
RX PubMed=12740439; DOI=10.1073/pnas.1037392100;
RA Kimberly W.T., LaVoie M.J., Ostaszewski B.L., Ye W., Wolfe M.S.,
RA Selkoe D.J.;
RT "Gamma-secretase is a membrane protein complex comprised of
RT presenilin, nicastrin, Aph-1, and Pen-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6382-6387(2003).
RN [10]
RP ENZYME ACTIVITY OF A GAMMA-SECRETASE COMPLEX.
RX PubMed=12679784; DOI=10.1038/ncb960;
RA Edbauer D., Winkler E., Regula J.T., Pesold B., Steiner H., Haass C.;
RT "Reconstitution of gamma-secretase activity.";
RL Nat. Cell Biol. 5:486-488(2003).
RN [11]
RP INVOLVEMENT IN ACNINV2.
RX PubMed=20929727; DOI=10.1126/science.1196284;
RA Wang B., Yang W., Wen W., Sun J., Su B., Liu B., Ma D., Lv D., Wen Y.,
RA Qu T., Chen M., Sun M., Shen Y., Zhang X.;
RT "Gamma-secretase gene mutations in familial acne inversa.";
RL Science 330:1065-1065(2010).
CC -!- FUNCTION: Essential subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral membrane proteins such as Notch receptors and APP (beta-
CC amyloid precursor protein). Probably represents the last step of
CC maturation of gamma-secretase, facilitating endoproteolysis of
CC presenilin and conferring gamma-secretase activity.
CC -!- SUBUNIT: Component of the gamma-secretase complex, a complex
CC composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin
CC (NCSTN), APH1 (APH1A or APH1B) and PSENEN/PEN2. Such minimal
CC complex is sufficient for secretase activity, although other
CC components may exist.
CC -!- INTERACTION:
CC Q92542:NCSTN; NbExp=3; IntAct=EBI-998468, EBI-998440;
CC P49755:TMED10; NbExp=3; IntAct=EBI-998468, EBI-998422;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Golgi apparatus, Golgi stack membrane; Multi-
CC pass membrane protein. Note=Predominantly located in the
CC endoplasmic reticulum and in the cis-Golgi.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in leukocytes,
CC lung, placenta, small intestine, liver, kidney, spleen thymus,
CC skeletal muscle, heart and brain.
CC -!- DISEASE: Acne inversa, familial, 2 (ACNINV2) [MIM:613736]: A
CC chronic relapsing inflammatory disease of the hair follicles
CC characterized by recurrent draining sinuses, painful skin
CC abscesses, and disfiguring scars. Manifestations typically appear
CC after puberty. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PEN-2 family.
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; AF220053; AAF67646.1; -; mRNA.
DR EMBL; AK312233; BAG35166.1; -; mRNA.
DR EMBL; BC009575; AAH09575.1; -; mRNA.
DR RefSeq; NP_001268461.1; NM_001281532.1.
DR RefSeq; NP_758844.1; NM_172341.2.
DR UniGene; Hs.534465; -.
DR ProteinModelPortal; Q9NZ42; -.
DR IntAct; Q9NZ42; 5.
DR MINT; MINT-5207259; -.
DR STRING; 9606.ENSP00000222266; -.
DR BindingDB; Q9NZ42; -.
DR ChEMBL; CHEMBL2094135; -.
DR PhosphoSite; Q9NZ42; -.
DR DMDM; 37081820; -.
DR PaxDb; Q9NZ42; -.
DR PRIDE; Q9NZ42; -.
DR DNASU; 55851; -.
DR Ensembl; ENST00000222266; ENSP00000222266; ENSG00000205155.
DR Ensembl; ENST00000587708; ENSP00000468411; ENSG00000205155.
DR GeneID; 55851; -.
DR KEGG; hsa:55851; -.
DR UCSC; uc002obi.1; human.
DR CTD; 55851; -.
DR GeneCards; GC19P036236; -.
DR H-InvDB; HIX0080122; -.
DR HGNC; HGNC:30100; PSENEN.
DR HPA; CAB013471; -.
DR MIM; 607632; gene.
DR MIM; 613736; phenotype.
DR neXtProt; NX_Q9NZ42; -.
DR Orphanet; 387; Hidradenitis suppurativa.
DR PharmGKB; PA142671122; -.
DR eggNOG; NOG279333; -.
DR HOGENOM; HOG000006914; -.
DR HOVERGEN; HBG045628; -.
DR InParanoid; Q9NZ42; -.
DR KO; K06170; -.
DR OMA; WGATADY; -.
DR OrthoDB; EOG7ZSHW4; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_691; A third proteolytic cleavage releases NICD.
DR SignaLink; Q9NZ42; -.
DR ChiTaRS; PSENEN; human.
DR GenomeRNAi; 55851; -.
DR NextBio; 61115; -.
DR PRO; PR:Q9NZ42; -.
DR ArrayExpress; Q9NZ42; -.
DR Bgee; Q9NZ42; -.
DR CleanEx; HS_PSENEN; -.
DR Genevestigator; Q9NZ42; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HGNC.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:HGNC.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; TAS:HGNC.
DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:HGNC.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; TAS:Reactome.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007220; P:Notch receptor processing; TAS:HGNC.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:Reactome.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IDA:HGNC.
DR GO; GO:0016485; P:protein processing; IDA:HGNC.
DR InterPro; IPR019379; Gamma_Secretase_Asp_P_PEN2.
DR Pfam; PF10251; PEN-2; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Endoplasmic reticulum; Golgi apparatus; Membrane;
KW Notch signaling pathway; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 101 Gamma-secretase subunit PEN-2.
FT /FTId=PRO_0000190900.
FT TOPO_DOM 1 17 Lumenal (Potential).
FT TRANSMEM 18 38 Helical; (Potential).
FT TOPO_DOM 39 60 Cytoplasmic (Potential).
FT TRANSMEM 61 81 Helical; (Potential).
FT TOPO_DOM 82 101 Lumenal (Potential).
FT MUTAGEN 10 10 E->S: Induces a N-linked glycosylation on
FT N-8.
FT MUTAGEN 46 46 A->N: No effect.
FT MUTAGEN 93 93 S->N: Induces a N-linked glycosylation.
SQ SEQUENCE 101 AA; 12029 MW; FDBA4D299488EA02 CRC64;
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLVPAYTEQ SQIKGYVWRS
AVGFLFWVIV LTSWITIFQI YRPRWGALGD YLSFTIPLGT P
//
ID PEN2_HUMAN Reviewed; 101 AA.
AC Q9NZ42; B2R5L9;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 109.
DE RecName: Full=Gamma-secretase subunit PEN-2;
DE AltName: Full=Presenilin enhancer protein 2;
GN Name=PSENEN; Synonyms=PEN2; ORFNames=MDS033;
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 [LARGE SCALE MRNA].
RC TISSUE=Hematopoietic stem cell;
RA Zhao M., Gu J., Li N., Peng Y., Han Z., Chen Z.;
RT "Novel genes expressed in hematopoietic stem/progenitor cells from
RT myelodysplastic syndrome patients.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP INTERACTION WITH NCSTN; PSEN1 AND PSEN2.
RX PubMed=12198112; DOI=10.1074/jbc.C200469200;
RA Steiner H., Winkler E., Edbauer D., Prokop S., Basset G., Yamasaki A.,
RA Kostka M., Haass C.;
RT "PEN-2 is an integral component of the gamma-secretase complex
RT required for coordinated expression of presenilin and nicastrin.";
RL J. Biol. Chem. 277:39062-39065(2002).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12110170; DOI=10.1016/S1534-5807(02)00189-2;
RA Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J.,
RA Nicoll M., Maxwell M., Hai B., Ellis M.C., Parks A.L., Xu W., Li J.,
RA Gurney M., Myers R.L., Himes C.S., Hiebsch R., Ruble C., Nye J.S.,
RA Curtis D.;
RT "aph-1 and pen-2 are required for Notch pathway signaling, gamma-
RT secretase cleavage of betaAPP, and presenilin protein accumulation.";
RL Dev. Cell 3:85-97(2002).
RN [6]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=12522139; DOI=10.1074/jbc.C200648200;
RA Luo W.-J., Wang H., Li H., Kim B.S., Shah S., Lee H.-J.,
RA Thinakaran G., Kim T.-W., Yu G., Xu H.;
RT "PEN-2 and APH-1 coordinately regulate proteolytic processing of
RT presenilin 1.";
RL J. Biol. Chem. 278:7850-7854(2003).
RN [7]
RP MEMBRANE TOPOLOGY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-10;
RP ALA-46 AND SER-93.
RX PubMed=12639958; DOI=10.1074/jbc.M213107200;
RA Crystal A.S., Morais V.A., Pierson T.C., Pijak D.S., Carlin D.,
RA Lee V.M., Doms R.W.;
RT "Membrane topology of gamma-secretase component PEN-2.";
RL J. Biol. Chem. 278:20117-20123(2003).
RN [8]
RP FUNCTION IN THE GAMMA-SECRETASE COMPLEX.
RX PubMed=12763021; DOI=10.1016/S0006-291X(03)00797-6;
RA Marlow L., Canet R.M., Haugabook S.J., Hardy J.A., Lahiri D.K.,
RA Sambamurti K.;
RT "APH1, PEN2, and nicastrin increase Abeta levels and gamma-secretase
RT activity.";
RL Biochem. Biophys. Res. Commun. 305:502-509(2003).
RN [9]
RP TISSUE SPECIFICITY, AND COMPONENT OF A GAMMA-SECRETASE COMPLEX WITH
RP APH1A; PSEN1/PSEN2 AND NCSTN.
RX PubMed=12740439; DOI=10.1073/pnas.1037392100;
RA Kimberly W.T., LaVoie M.J., Ostaszewski B.L., Ye W., Wolfe M.S.,
RA Selkoe D.J.;
RT "Gamma-secretase is a membrane protein complex comprised of
RT presenilin, nicastrin, Aph-1, and Pen-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6382-6387(2003).
RN [10]
RP ENZYME ACTIVITY OF A GAMMA-SECRETASE COMPLEX.
RX PubMed=12679784; DOI=10.1038/ncb960;
RA Edbauer D., Winkler E., Regula J.T., Pesold B., Steiner H., Haass C.;
RT "Reconstitution of gamma-secretase activity.";
RL Nat. Cell Biol. 5:486-488(2003).
RN [11]
RP INVOLVEMENT IN ACNINV2.
RX PubMed=20929727; DOI=10.1126/science.1196284;
RA Wang B., Yang W., Wen W., Sun J., Su B., Liu B., Ma D., Lv D., Wen Y.,
RA Qu T., Chen M., Sun M., Shen Y., Zhang X.;
RT "Gamma-secretase gene mutations in familial acne inversa.";
RL Science 330:1065-1065(2010).
CC -!- FUNCTION: Essential subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral membrane proteins such as Notch receptors and APP (beta-
CC amyloid precursor protein). Probably represents the last step of
CC maturation of gamma-secretase, facilitating endoproteolysis of
CC presenilin and conferring gamma-secretase activity.
CC -!- SUBUNIT: Component of the gamma-secretase complex, a complex
CC composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin
CC (NCSTN), APH1 (APH1A or APH1B) and PSENEN/PEN2. Such minimal
CC complex is sufficient for secretase activity, although other
CC components may exist.
CC -!- INTERACTION:
CC Q92542:NCSTN; NbExp=3; IntAct=EBI-998468, EBI-998440;
CC P49755:TMED10; NbExp=3; IntAct=EBI-998468, EBI-998422;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Golgi apparatus, Golgi stack membrane; Multi-
CC pass membrane protein. Note=Predominantly located in the
CC endoplasmic reticulum and in the cis-Golgi.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in leukocytes,
CC lung, placenta, small intestine, liver, kidney, spleen thymus,
CC skeletal muscle, heart and brain.
CC -!- DISEASE: Acne inversa, familial, 2 (ACNINV2) [MIM:613736]: A
CC chronic relapsing inflammatory disease of the hair follicles
CC characterized by recurrent draining sinuses, painful skin
CC abscesses, and disfiguring scars. Manifestations typically appear
CC after puberty. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PEN-2 family.
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; AF220053; AAF67646.1; -; mRNA.
DR EMBL; AK312233; BAG35166.1; -; mRNA.
DR EMBL; BC009575; AAH09575.1; -; mRNA.
DR RefSeq; NP_001268461.1; NM_001281532.1.
DR RefSeq; NP_758844.1; NM_172341.2.
DR UniGene; Hs.534465; -.
DR ProteinModelPortal; Q9NZ42; -.
DR IntAct; Q9NZ42; 5.
DR MINT; MINT-5207259; -.
DR STRING; 9606.ENSP00000222266; -.
DR BindingDB; Q9NZ42; -.
DR ChEMBL; CHEMBL2094135; -.
DR PhosphoSite; Q9NZ42; -.
DR DMDM; 37081820; -.
DR PaxDb; Q9NZ42; -.
DR PRIDE; Q9NZ42; -.
DR DNASU; 55851; -.
DR Ensembl; ENST00000222266; ENSP00000222266; ENSG00000205155.
DR Ensembl; ENST00000587708; ENSP00000468411; ENSG00000205155.
DR GeneID; 55851; -.
DR KEGG; hsa:55851; -.
DR UCSC; uc002obi.1; human.
DR CTD; 55851; -.
DR GeneCards; GC19P036236; -.
DR H-InvDB; HIX0080122; -.
DR HGNC; HGNC:30100; PSENEN.
DR HPA; CAB013471; -.
DR MIM; 607632; gene.
DR MIM; 613736; phenotype.
DR neXtProt; NX_Q9NZ42; -.
DR Orphanet; 387; Hidradenitis suppurativa.
DR PharmGKB; PA142671122; -.
DR eggNOG; NOG279333; -.
DR HOGENOM; HOG000006914; -.
DR HOVERGEN; HBG045628; -.
DR InParanoid; Q9NZ42; -.
DR KO; K06170; -.
DR OMA; WGATADY; -.
DR OrthoDB; EOG7ZSHW4; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_691; A third proteolytic cleavage releases NICD.
DR SignaLink; Q9NZ42; -.
DR ChiTaRS; PSENEN; human.
DR GenomeRNAi; 55851; -.
DR NextBio; 61115; -.
DR PRO; PR:Q9NZ42; -.
DR ArrayExpress; Q9NZ42; -.
DR Bgee; Q9NZ42; -.
DR CleanEx; HS_PSENEN; -.
DR Genevestigator; Q9NZ42; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HGNC.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:HGNC.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; TAS:HGNC.
DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:HGNC.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; TAS:Reactome.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007220; P:Notch receptor processing; TAS:HGNC.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:Reactome.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IDA:HGNC.
DR GO; GO:0016485; P:protein processing; IDA:HGNC.
DR InterPro; IPR019379; Gamma_Secretase_Asp_P_PEN2.
DR Pfam; PF10251; PEN-2; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Endoplasmic reticulum; Golgi apparatus; Membrane;
KW Notch signaling pathway; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 101 Gamma-secretase subunit PEN-2.
FT /FTId=PRO_0000190900.
FT TOPO_DOM 1 17 Lumenal (Potential).
FT TRANSMEM 18 38 Helical; (Potential).
FT TOPO_DOM 39 60 Cytoplasmic (Potential).
FT TRANSMEM 61 81 Helical; (Potential).
FT TOPO_DOM 82 101 Lumenal (Potential).
FT MUTAGEN 10 10 E->S: Induces a N-linked glycosylation on
FT N-8.
FT MUTAGEN 46 46 A->N: No effect.
FT MUTAGEN 93 93 S->N: Induces a N-linked glycosylation.
SQ SEQUENCE 101 AA; 12029 MW; FDBA4D299488EA02 CRC64;
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLVPAYTEQ SQIKGYVWRS
AVGFLFWVIV LTSWITIFQI YRPRWGALGD YLSFTIPLGT P
//
MIM
607632
*RECORD*
*FIELD* NO
607632
*FIELD* TI
*607632 PRESENILIN ENHANCER 2, C. ELEGANS, HOMOLOG OF; PSENEN
;;PEN2
*FIELD* TX
DESCRIPTION
read more
PEN2 is a component of the gamma-secretase complex, which also includes
presenilin (see PSEN1; 104311) and nicastrin (APH2; 605254). The
gamma-secretase complex is required for the intramembrane proteolysis of
a number of membrane proteins, including the amyloid-beta precursor
protein (APP; 104760) and Notch (190198).
CLONING
Francis et al. (2002) identified 2 presenilin enhancers in C. elegans,
Aph1 (see APH1A; 607629) and Pen2. By searching sequence databases, they
identified human, mouse, zebrafish, Drosophila, and Arabidopsis homologs
of PEN2. The predicted 101-amino acid human PEN2 protein contains 2
transmembrane domains and shares 43% and 96% identity with C. elegans
and mouse Pen2, respectively.
GENE FUNCTION
By analyzing C. elegans mutant phenotypes, Francis et al. (2002)
determined that Aph1 and Pen2 were required for Glp1/Notch-mediated
signaling, both in embryonic patterning and in postembryonic germline
proliferation. They observed that the human APH1 and PEN2 genes
partially rescued the C. elegans mutant phenotypes, demonstrating
conserved functions. Human APH1 and PEN2 had to be provided together to
rescue the mutant phenotypes, and inclusion of PSEN1 improved rescue.
Francis et al. (2002) concluded that APH1 and PEN2 cooperate closely in
the same process to promote presenilin activity. Using RNA-mediated
interference assays to inactivate Aph1, Pen2, or nicastrin in cultured
Drosophila cells, Francis et al. (2002) observed reduction in
gamma-secretase cleavage of beta-APP and Notch substrates and reduction
in the levels of processed presenilin. They concluded that APH1 and PEN2
are required for Notch pathway signaling, gamma-secretase cleavage of
beta-APP, and presenilin protein accumulation. In a commentary, Goutte
(2002) discussed the contribution of Francis et al. (2002) to current
understanding of how presenilins mediate the gamma-secretase cleavage of
Notch transmembrane receptors and transmembrane beta-APP.
Using coimmunoprecipitation experiments, Steiner et al. (2002) showed
that PEN2 binds to nicastrin, PSEN1, and PSEN2 (600759), and they
concluded that PEN2 is a critical component of PSEN1/gamma-secretase and
PSEN2/gamma-secretase complexes. Steiner et al. (2002) observed that
Pen2 levels were reduced in mice lacking Psen1 or both Psen1 and Psen2.
They also observed that PEN2 levels were reduced upon RNA
interference-mediated downregulation of nicastrin. Steiner et al. (2002)
concluded that PEN2 expression requires the presence of presenilins and
nicastrin. Additionally, they reported that downregulation of PEN2 by
RNA interference was associated with reduced presenilin levels, impaired
nicastrin maturation, and deficient gamma-secretase complex formation.
Gamma-secretase activity requires the formation of a stable, high
molecular mass protein complex that, in addition to the endoproteolyzed
fragmented form of presenilin, contains essential cofactors including
nicastrin (605254), APH1 (607629, 607630), and PEN2. Takasugi et al.
(2003) showed that Drosophila APH1 increases the stability of Drosophila
presenilin holoprotein in the complex. Depletion of PEN2 by RNA
interference prevented endoproteolysis of presenilin and promoted
stabilization of the holoprotein in both Drosophila and mammalian cells,
including primary neurons. Coexpression of Drosophila Pen2 with Aph1 and
nicastrin increased the formation of presenilin fragments as well as
gamma-secretase activity. Thus, Takasugi et al. (2003) concluded that
APH1 stabilizes the presenilin holoprotein in the complex, whereas PEN2
is required for endoproteolytic processing of presenilin and conferring
gamma-secretase activity to the complex.
MOLECULAR GENETICS
Wang et al. (2010) identified two 4-generation pedigrees segregating
autosomal dominant acne inversa (ACNINV2; 613736). Each family carried a
different heterozygous single-basepair substitution leading to
haploinsufficiency in affected individuals (607632.0001-607632.0002).
MAPPING
By radiation hybrid analysis, Francis et al. (2002) mapped the PEN2 gene
to chromosome 19.
ANIMAL MODEL
By screening a library of about 80,000 chemical compounds, Kounnas et
al. (2010) identified a class of gamma-secretase modulators (GSMs),
diarylaminothiazoles, or series A GSMs, that could target production of
the fibrillogenic peptides amyloid (A)-beta-42 and A-beta-40 (see
104760) in cell lines and in Tg 2576 transgenic Alzheimer disease (AD;
104300) mice. Immobilized series A GSMs bound to Pen2 and, to a lesser
degree, Psen1. Series A GSMs reduced gamma-secretase activity without
interfering with related off-target reactions, lowered A-beta-42 levels
in both plasma and brain of Tg 2576 mice, and reduced plaque density and
amyloid in Tg 2576 hippocampus and cortex. Daily dosing was well
tolerated over the 7-month study.
*FIELD* AV
.0001
ACNE INVERSA, FAMILIAL, 2
PSENEN, 1-BP DEL, 66G
In a 4-generation Han Chinese family segregating autosomal dominant acne
inversa (ACNINV2; 613736), Wang et al. (2010) identified a
single-basepair deletion of a guanine in the PSENEN gene (66delG)
resulting in frameshift and a premature termination codon (F23LfsX46).
This mutation was not identified in chromosomes from 200 ethnically
matched control individuals.
.0002
ACNE INVERSA, FAMILIAL, 2
PSENEN, 1-BP DEL, 279C
In a 4-generation Han Chinese family segregating autosomal dominant acne
inversa (613736), Wang et al. (2010) identified a single-basepair
deletion at nucleotide 279 of the PSENEN gene (279delC), resulting in a
frameshift and delayed termination codon (F94SfsX51). This mutation was
not detected in chromosomes from 200 ethnically matched control
individuals.
*FIELD* RF
1. Francis, R.; McGrath, G.; Zhang, J.; Ruddy, D. A.; Sym, M.; Apfeld,
J.; Nicoll, M.; Maxwell, M.; Hai, B.; Ellis, M. C.; Parks, A. L.;
Xu, W.; Li, J.; Gurney, M.; Myers, R. L.; Himes, C. S.; Hiebsch, R.;
Ruble, C.; Nye, J. S.; Curtis, D.: aph-1 and pen-2 are required for
Notch pathway signaling, gamma-secretase cleavage of beta-APP, and
presenilin protein accumulation. Dev. Cell 3: 85-97, 2002.
2. Goutte, C.: Genetics leads the way to the accomplices of presenilins.
(Commentary) Dev. Cell 3: 6-7, 2002.
3. Kounnas, M. Z.; Danks, A. M.; Cheng, S.; Tyree, C.; Ackerman, E.;
Zhang, X.; Ahn, K.; Nguyen, P.; Comer, D.; Mao, L.; Yu, C.; Pleynet,
D.; and 9 others: Modulation of gamma-secretase reduces beta-amyloid
deposition in a transgenic mouse model of Alzheimer's disease. Neuron 67:
769-780, 2010.
4. Steiner, H.; Winkler, E.; Edbauer, D.; Prokop, S.; Basset, G.;
Yamasaki, A.; Kostka, M.; Haass, C.: PEN-2 is an integral component
of the gamma-secretase complex required for coordinated expression
of presenilin and nicastrin. J. Biol. Chem. 277: 39062-39065, 2002.
5. Takasugi, N.; Tomita, T.; Hayashi, I.; Tsuruoka, M.; Niimura, M.;
Takahashi, Y.; Thinakaran, G.; Iwatsubo, T.: The role of presenilin
cofactors in the gamma-secretase complex. Nature 422: 438-441, 2003.
6. Wang, B.; Yang, W.; Wen, W.; Sun, J.; Su, B.; Liu, B.; Ma, D.;
Lv, D.; Wen, Y.; Qu, T.; Chen, M.; Sun, M.; Shen, Y.; Zhang, X.:
Gamma-secretase gene mutations in familial acne inversa. Science 330:
1065 only, 2010.
*FIELD* CN
Patricia A. Hartz - updated: 3/20/2012
Ada Hamosh - updated: 2/2/2011
Ada Hamosh - updated: 4/3/2003
*FIELD* CD
Dawn Watkins-Chow: 3/17/2003
*FIELD* ED
mgross: 04/09/2012
mgross: 4/9/2012
terry: 3/20/2012
carol: 12/12/2011
alopez: 2/8/2011
terry: 2/2/2011
carol: 3/1/2005
alopez: 4/8/2003
terry: 4/3/2003
mgross: 3/17/2003
*RECORD*
*FIELD* NO
607632
*FIELD* TI
*607632 PRESENILIN ENHANCER 2, C. ELEGANS, HOMOLOG OF; PSENEN
;;PEN2
*FIELD* TX
DESCRIPTION
read more
PEN2 is a component of the gamma-secretase complex, which also includes
presenilin (see PSEN1; 104311) and nicastrin (APH2; 605254). The
gamma-secretase complex is required for the intramembrane proteolysis of
a number of membrane proteins, including the amyloid-beta precursor
protein (APP; 104760) and Notch (190198).
CLONING
Francis et al. (2002) identified 2 presenilin enhancers in C. elegans,
Aph1 (see APH1A; 607629) and Pen2. By searching sequence databases, they
identified human, mouse, zebrafish, Drosophila, and Arabidopsis homologs
of PEN2. The predicted 101-amino acid human PEN2 protein contains 2
transmembrane domains and shares 43% and 96% identity with C. elegans
and mouse Pen2, respectively.
GENE FUNCTION
By analyzing C. elegans mutant phenotypes, Francis et al. (2002)
determined that Aph1 and Pen2 were required for Glp1/Notch-mediated
signaling, both in embryonic patterning and in postembryonic germline
proliferation. They observed that the human APH1 and PEN2 genes
partially rescued the C. elegans mutant phenotypes, demonstrating
conserved functions. Human APH1 and PEN2 had to be provided together to
rescue the mutant phenotypes, and inclusion of PSEN1 improved rescue.
Francis et al. (2002) concluded that APH1 and PEN2 cooperate closely in
the same process to promote presenilin activity. Using RNA-mediated
interference assays to inactivate Aph1, Pen2, or nicastrin in cultured
Drosophila cells, Francis et al. (2002) observed reduction in
gamma-secretase cleavage of beta-APP and Notch substrates and reduction
in the levels of processed presenilin. They concluded that APH1 and PEN2
are required for Notch pathway signaling, gamma-secretase cleavage of
beta-APP, and presenilin protein accumulation. In a commentary, Goutte
(2002) discussed the contribution of Francis et al. (2002) to current
understanding of how presenilins mediate the gamma-secretase cleavage of
Notch transmembrane receptors and transmembrane beta-APP.
Using coimmunoprecipitation experiments, Steiner et al. (2002) showed
that PEN2 binds to nicastrin, PSEN1, and PSEN2 (600759), and they
concluded that PEN2 is a critical component of PSEN1/gamma-secretase and
PSEN2/gamma-secretase complexes. Steiner et al. (2002) observed that
Pen2 levels were reduced in mice lacking Psen1 or both Psen1 and Psen2.
They also observed that PEN2 levels were reduced upon RNA
interference-mediated downregulation of nicastrin. Steiner et al. (2002)
concluded that PEN2 expression requires the presence of presenilins and
nicastrin. Additionally, they reported that downregulation of PEN2 by
RNA interference was associated with reduced presenilin levels, impaired
nicastrin maturation, and deficient gamma-secretase complex formation.
Gamma-secretase activity requires the formation of a stable, high
molecular mass protein complex that, in addition to the endoproteolyzed
fragmented form of presenilin, contains essential cofactors including
nicastrin (605254), APH1 (607629, 607630), and PEN2. Takasugi et al.
(2003) showed that Drosophila APH1 increases the stability of Drosophila
presenilin holoprotein in the complex. Depletion of PEN2 by RNA
interference prevented endoproteolysis of presenilin and promoted
stabilization of the holoprotein in both Drosophila and mammalian cells,
including primary neurons. Coexpression of Drosophila Pen2 with Aph1 and
nicastrin increased the formation of presenilin fragments as well as
gamma-secretase activity. Thus, Takasugi et al. (2003) concluded that
APH1 stabilizes the presenilin holoprotein in the complex, whereas PEN2
is required for endoproteolytic processing of presenilin and conferring
gamma-secretase activity to the complex.
MOLECULAR GENETICS
Wang et al. (2010) identified two 4-generation pedigrees segregating
autosomal dominant acne inversa (ACNINV2; 613736). Each family carried a
different heterozygous single-basepair substitution leading to
haploinsufficiency in affected individuals (607632.0001-607632.0002).
MAPPING
By radiation hybrid analysis, Francis et al. (2002) mapped the PEN2 gene
to chromosome 19.
ANIMAL MODEL
By screening a library of about 80,000 chemical compounds, Kounnas et
al. (2010) identified a class of gamma-secretase modulators (GSMs),
diarylaminothiazoles, or series A GSMs, that could target production of
the fibrillogenic peptides amyloid (A)-beta-42 and A-beta-40 (see
104760) in cell lines and in Tg 2576 transgenic Alzheimer disease (AD;
104300) mice. Immobilized series A GSMs bound to Pen2 and, to a lesser
degree, Psen1. Series A GSMs reduced gamma-secretase activity without
interfering with related off-target reactions, lowered A-beta-42 levels
in both plasma and brain of Tg 2576 mice, and reduced plaque density and
amyloid in Tg 2576 hippocampus and cortex. Daily dosing was well
tolerated over the 7-month study.
*FIELD* AV
.0001
ACNE INVERSA, FAMILIAL, 2
PSENEN, 1-BP DEL, 66G
In a 4-generation Han Chinese family segregating autosomal dominant acne
inversa (ACNINV2; 613736), Wang et al. (2010) identified a
single-basepair deletion of a guanine in the PSENEN gene (66delG)
resulting in frameshift and a premature termination codon (F23LfsX46).
This mutation was not identified in chromosomes from 200 ethnically
matched control individuals.
.0002
ACNE INVERSA, FAMILIAL, 2
PSENEN, 1-BP DEL, 279C
In a 4-generation Han Chinese family segregating autosomal dominant acne
inversa (613736), Wang et al. (2010) identified a single-basepair
deletion at nucleotide 279 of the PSENEN gene (279delC), resulting in a
frameshift and delayed termination codon (F94SfsX51). This mutation was
not detected in chromosomes from 200 ethnically matched control
individuals.
*FIELD* RF
1. Francis, R.; McGrath, G.; Zhang, J.; Ruddy, D. A.; Sym, M.; Apfeld,
J.; Nicoll, M.; Maxwell, M.; Hai, B.; Ellis, M. C.; Parks, A. L.;
Xu, W.; Li, J.; Gurney, M.; Myers, R. L.; Himes, C. S.; Hiebsch, R.;
Ruble, C.; Nye, J. S.; Curtis, D.: aph-1 and pen-2 are required for
Notch pathway signaling, gamma-secretase cleavage of beta-APP, and
presenilin protein accumulation. Dev. Cell 3: 85-97, 2002.
2. Goutte, C.: Genetics leads the way to the accomplices of presenilins.
(Commentary) Dev. Cell 3: 6-7, 2002.
3. Kounnas, M. Z.; Danks, A. M.; Cheng, S.; Tyree, C.; Ackerman, E.;
Zhang, X.; Ahn, K.; Nguyen, P.; Comer, D.; Mao, L.; Yu, C.; Pleynet,
D.; and 9 others: Modulation of gamma-secretase reduces beta-amyloid
deposition in a transgenic mouse model of Alzheimer's disease. Neuron 67:
769-780, 2010.
4. Steiner, H.; Winkler, E.; Edbauer, D.; Prokop, S.; Basset, G.;
Yamasaki, A.; Kostka, M.; Haass, C.: PEN-2 is an integral component
of the gamma-secretase complex required for coordinated expression
of presenilin and nicastrin. J. Biol. Chem. 277: 39062-39065, 2002.
5. Takasugi, N.; Tomita, T.; Hayashi, I.; Tsuruoka, M.; Niimura, M.;
Takahashi, Y.; Thinakaran, G.; Iwatsubo, T.: The role of presenilin
cofactors in the gamma-secretase complex. Nature 422: 438-441, 2003.
6. Wang, B.; Yang, W.; Wen, W.; Sun, J.; Su, B.; Liu, B.; Ma, D.;
Lv, D.; Wen, Y.; Qu, T.; Chen, M.; Sun, M.; Shen, Y.; Zhang, X.:
Gamma-secretase gene mutations in familial acne inversa. Science 330:
1065 only, 2010.
*FIELD* CN
Patricia A. Hartz - updated: 3/20/2012
Ada Hamosh - updated: 2/2/2011
Ada Hamosh - updated: 4/3/2003
*FIELD* CD
Dawn Watkins-Chow: 3/17/2003
*FIELD* ED
mgross: 04/09/2012
mgross: 4/9/2012
terry: 3/20/2012
carol: 12/12/2011
alopez: 2/8/2011
terry: 2/2/2011
carol: 3/1/2005
alopez: 4/8/2003
terry: 4/3/2003
mgross: 3/17/2003
MIM
613736
*RECORD*
*FIELD* NO
613736
*FIELD* TI
#613736 ACNE INVERSA, FAMILIAL, 2; ACNINV2
*FIELD* TX
A number sign (#) is used with this entry because acne inversa-2
read more(ACNINV2) is caused by haploinsufficiency for the PSENEN gene (607632)
on chromosome 19q13.1.
DESCRIPTION
Acne inversa is a chronic inflammatory disease of the hair follicles
whose characteristic features include draining sinuses, painful skin
abscesses, and disfiguring scars. Manifestations typically appear after
puberty. Familial acne inversa is genetically heterogeneous (summary by
Wang et al., 2010).
For a general phenotypic description and a discussion of genetic
heterogeneity of acne inversa, see 142690.
MOLECULAR GENETICS
Wang et al. (2010) mapped an acne inversa locus to an interval on
chromosome 19q13 using 2 large 4-generation Han Chinese families. Each
family had a frameshift mutation in the PSENEN gene (607632.0001,
607632.0002).
*FIELD* RF
1. Wang, B.; Yang, W.; Wen, W.; Sun, J.; Su, B.; Liu, B.; Ma, D.;
Lv, D.; Wen, Y.; Qu, T.; Chen, M.; Sun, M.; Shen, Y.; Zhang, X.:
Gamma-secretase gene mutations in familial acne inversa. Science 330:
1065 only, 2010.
*FIELD* CD
Ada Hamosh: 2/8/2011
*FIELD* ED
carol: 11/08/2013
carol: 12/12/2011
carol: 2/9/2011
alopez: 2/8/2011
*RECORD*
*FIELD* NO
613736
*FIELD* TI
#613736 ACNE INVERSA, FAMILIAL, 2; ACNINV2
*FIELD* TX
A number sign (#) is used with this entry because acne inversa-2
read more(ACNINV2) is caused by haploinsufficiency for the PSENEN gene (607632)
on chromosome 19q13.1.
DESCRIPTION
Acne inversa is a chronic inflammatory disease of the hair follicles
whose characteristic features include draining sinuses, painful skin
abscesses, and disfiguring scars. Manifestations typically appear after
puberty. Familial acne inversa is genetically heterogeneous (summary by
Wang et al., 2010).
For a general phenotypic description and a discussion of genetic
heterogeneity of acne inversa, see 142690.
MOLECULAR GENETICS
Wang et al. (2010) mapped an acne inversa locus to an interval on
chromosome 19q13 using 2 large 4-generation Han Chinese families. Each
family had a frameshift mutation in the PSENEN gene (607632.0001,
607632.0002).
*FIELD* RF
1. Wang, B.; Yang, W.; Wen, W.; Sun, J.; Su, B.; Liu, B.; Ma, D.;
Lv, D.; Wen, Y.; Qu, T.; Chen, M.; Sun, M.; Shen, Y.; Zhang, X.:
Gamma-secretase gene mutations in familial acne inversa. Science 330:
1065 only, 2010.
*FIELD* CD
Ada Hamosh: 2/8/2011
*FIELD* ED
carol: 11/08/2013
carol: 12/12/2011
carol: 2/9/2011
alopez: 2/8/2011