Full text data of ANP32A
ANP32A
(C15orf1, LANP, MAPM, PHAP1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Acidic leucine-rich nuclear phosphoprotein 32 family member A (Acidic nuclear phosphoprotein pp32; Leucine-rich acidic nuclear protein; LANP; Mapmodulin; Potent heat-stable protein phosphatase 2A inhibitor I1PP2A; Putative HLA-DR-associated protein I; PHAPI)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Acidic leucine-rich nuclear phosphoprotein 32 family member A (Acidic nuclear phosphoprotein pp32; Leucine-rich acidic nuclear protein; LANP; Mapmodulin; Potent heat-stable protein phosphatase 2A inhibitor I1PP2A; Putative HLA-DR-associated protein I; PHAPI)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P39687
ID AN32A_HUMAN Reviewed; 249 AA.
AC P39687; B2R6T4; Q53FK4; Q5J8L8; Q7M4N6;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Acidic leucine-rich nuclear phosphoprotein 32 family member A;
DE AltName: Full=Acidic nuclear phosphoprotein pp32;
DE AltName: Full=Leucine-rich acidic nuclear protein;
DE Short=LANP;
DE AltName: Full=Mapmodulin;
DE AltName: Full=Potent heat-stable protein phosphatase 2A inhibitor I1PP2A;
DE AltName: Full=Putative HLA-DR-associated protein I;
DE Short=PHAPI;
GN Name=ANP32A; Synonyms=C15orf1, LANP, MAPM, PHAP1;
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], AND PROTEIN SEQUENCE OF 1-26; 29-47; 71-97
RP AND 100-161.
RC TISSUE=B-cell lymphoma;
RX PubMed=8192856;
RA Vaesen M., Barnikol-Watanabe S., Goetz H., Adil Awni L., Cole T.,
RA Zimmermann B., Kratzin H.D., Hilschmann N.;
RT "Purification and characterization of two putative HLA class II
RT associated proteins: PHAPI and PHAPII.";
RL Biol. Chem. Hoppe-Seyler 375:113-126(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 7-12 AND 29-44.
RC TISSUE=Kidney;
RX PubMed=8679524; DOI=10.1021/bi960581y;
RA Li M., Makkinje A., Damuni Z.;
RT "Molecular identification of I1PP2A, a novel potent heat-stable
RT inhibitor protein of protein phosphatase 2A.";
RL Biochemistry 35:6998-7002(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8970164; DOI=10.1091/mbc.7.12.2045;
RA Chen T.-H., Brody J.R., Romantsev F.E., Yu J.-G., Kayler A.E.,
RA Voneiff E., Kuhajda F.P., Pasternack G.R.;
RT "Structure of pp32, an acidic nuclear protein which inhibits oncogene-
RT induced formation of transformed foci.";
RL Mol. Biol. Cell 7:2045-2056(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9353121; DOI=10.1038/40159;
RA Matilla A., Koshy B.T., Cummings C.J., Isobe T., Orr H.T.,
RA Zoghbi H.Y.;
RT "The cerebellar leucine-rich acidic nuclear protein interacts with
RT ataxin-1.";
RL Nature 389:974-978(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=15642345; DOI=10.1016/j.febslet.2004.11.097;
RA Tsujio I., Zaidi T., Xu J., Kotula L., Grundke-Iqbal I., Iqbal K.;
RT "Inhibitors of protein phosphatase-2A from human brain structures,
RT immunocytological localization and activities towards
RT dephosphorylation of the Alzheimer type hyperphosphorylated tau.";
RL FEBS Lett. 579:363-372(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovium;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10400610; DOI=10.1074/jbc.274.29.20053;
RA Brody J.R., Kadkol S.S., Mahmoud M.A., Rebel J.M., Pasternack G.R.;
RT "Identification of sequences required for inhibition of oncogene-
RT mediated transformation by pp32.";
RL J. Biol. Chem. 274:20053-20055(1999).
RN [12]
RP INTERACTION WITH THE INHAT COMPLEX, AND MASS SPECTROMETRY.
RX PubMed=11163245; DOI=10.1016/S0092-8674(01)00196-9;
RA Seo S.-B., McNamara P., Heo S., Turner A., Lane W.S., Chakravarti D.;
RT "Regulation of histone acetylation and transcription by INHAT, a human
RT cellular complex containing the Set oncoprotein.";
RL Cell 104:119-130(2001).
RN [13]
RP INTERACTION WITH SET.
RX PubMed=11555662; DOI=10.1074/jbc.M108137200;
RA Beresford P.J., Zhang D., Oh D.Y., Fan Z., Greer E.L., Russo M.L.,
RA Jaju M., Lieberman J.;
RT "Granzyme A activates an endoplasmic reticulum-associated caspase-
RT independent nuclease to induce single-stranded DNA nicks.";
RL J. Biol. Chem. 276:43285-43293(2001).
RN [14]
RP FUNCTION.
RX PubMed=11360199; DOI=10.1038/sj.onc.1204294;
RA Bai J., Brody J.R., Kadkol S.S., Pasternack G.R.;
RT "Tumor suppression and potentiation by manipulation of pp32
RT expression.";
RL Oncogene 20:2153-2160(2001).
RN [15]
RP INTERACTION WITH ELAVL1, AND SUBCELLULAR LOCATION.
RX PubMed=11729309; DOI=10.1126/science.1064693;
RA Gallouzi I.-E., Steitz J.A.;
RT "Delineation of mRNA export pathways by the use of cell-permeable
RT peptides.";
RL Science 294:1895-1901(2001).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=12524539; DOI=10.1038/ni885;
RA Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A.,
RA Pommier Y., Lieberman J.;
RT "Cleaving the oxidative repair protein Ape1 enhances cell death
RT mediated by granzyme A.";
RL Nat. Immunol. 4:145-153(2003).
RN [17]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=15895553; DOI=10.1080/14734220410019020;
RA Matilla A., Radrizzani M.;
RT "The Anp32 family of proteins containing leucine-rich repeats.";
RL Cerebellum 4:7-18(2005).
RN [18]
RP FUNCTION, AND INTERACTION WITH E4F1.
RX PubMed=17557114; DOI=10.1038/sj.embor.7400983;
RA Cvetanovic M., Rooney R.J., Garcia J.J., Toporovskaya N., Zoghbi H.Y.,
RA Opal P.;
RT "The role of LANP and ataxin 1 in E4F-mediated transcriptional
RT repression.";
RL EMBO Rep. 8:671-677(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-15 AND SER-17, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
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).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-149, AND LEUCINE-RICH
RP REPEATS.
RX PubMed=17567741; DOI=10.1110/ps.072803507;
RA Huyton T., Wolberger C.;
RT "The crystal structure of the tumor suppressor protein pp32 (Anp32a):
RT structural insights into Anp32 family of proteins.";
RL Protein Sci. 16:1308-1315(2007).
CC -!- FUNCTION: Implicated in a number of cellular processes, including
CC proliferation, differentiation, caspase-dependent and caspase-
CC independent apoptosis, suppression of transformation (tumor
CC suppressor), inhibition of protein phosphatase 2A, regulation of
CC mRNA trafficking and stability in association with ELAVL1, and
CC inhibition of acetyltransferases as part of the INHAT (inhibitor
CC of histone acetyltransferases) complex. Plays a role in E4F1-
CC mediated transcriptional repression.
CC -!- SUBUNIT: Component of the SET complex, which also contains SET,
CC APEX1, HMGB2 and NME1. Directly interacts with SET. Interacts with
CC ATXN1/SCA1. Interacts with MAP1B (By similarity). Interacts with
CC ELAVL1. Part of the INHAT (inhibitor of histone
CC acetyltransferases) complex. Interacts with E4F1.
CC -!- INTERACTION:
CC O15169:AXIN1; NbExp=2; IntAct=EBI-359234, EBI-710484;
CC Q66K89:E4F1; NbExp=3; IntAct=EBI-359234, EBI-1227043;
CC P67775:PPP2CA; NbExp=2; IntAct=EBI-359234, EBI-712311;
CC P63331:Ppp2ca (xeno); NbExp=2; IntAct=EBI-359234, EBI-7050205;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Endoplasmic reticulum.
CC Note=Translocates to the cytoplasm during the process of
CC neuritogenesis (By similarity). Shuttles between nucleus and
CC cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested. Highly
CC expressed in kidney and skeletal muscle, moderate levels of
CC expression in brain, placenta and pancreas, and weakly expressed
CC in lung. Found in all regions of the brain examined (amygdala,
CC caudate nucleus, corpus callosum, hippocampus and thalamus), with
CC highest levels in amygdala.
CC -!- PTM: Phosphorylated on serine residues.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Some glutamate residues are glycylated by TTLL8. This
CC modification occurs exclusively on glutamate residues and results
CC in a glycine chain on the gamma-carboxyl group (By similarity).
CC -!- SIMILARITY: Belongs to the ANP32 family.
CC -!- SIMILARITY: Contains 4 LRR (leucine-rich) repeats.
CC -!- SIMILARITY: Contains 1 LRRCT domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD97000.1; Type=Erroneous initiation;
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DR EMBL; X75090; CAA52981.1; -; mRNA.
DR EMBL; U60823; AAC50570.1; -; mRNA.
DR EMBL; U73477; AAB39706.1; -; mRNA.
DR EMBL; AF025684; AAB91548.1; -; mRNA.
DR EMBL; AY349171; AAQ79832.1; -; mRNA.
DR EMBL; BT007436; AAP36104.1; -; mRNA.
DR EMBL; AK223280; BAD97000.1; ALT_INIT; mRNA.
DR EMBL; AK312703; BAG35581.1; -; mRNA.
DR EMBL; CH471082; EAW77824.1; -; Genomic_DNA.
DR EMBL; BC007200; AAH07200.1; -; mRNA.
DR PIR; S36375; S36375.
DR PIR; S43309; S43309.
DR RefSeq; NP_006296.1; NM_006305.3.
DR UniGene; Hs.458747; -.
DR PDB; 2JE0; X-ray; 2.40 A; A/B/C/D/E/F=1-149.
DR PDB; 2JE1; X-ray; 2.69 A; A/B/C/D=1-149.
DR PDBsum; 2JE0; -.
DR PDBsum; 2JE1; -.
DR ProteinModelPortal; P39687; -.
DR SMR; P39687; 1-149.
DR IntAct; P39687; 15.
DR MINT; MINT-4999627; -.
DR STRING; 9606.ENSP00000417864; -.
DR PhosphoSite; P39687; -.
DR DMDM; 730318; -.
DR SWISS-2DPAGE; P39687; -.
DR PaxDb; P39687; -.
DR PRIDE; P39687; -.
DR DNASU; 8125; -.
DR Ensembl; ENST00000465139; ENSP00000417864; ENSG00000140350.
DR GeneID; 8125; -.
DR KEGG; hsa:8125; -.
DR UCSC; uc002arl.3; human.
DR CTD; 8125; -.
DR GeneCards; GC15M069070; -.
DR HGNC; HGNC:13233; ANP32A.
DR HPA; CAB005231; -.
DR MIM; 600832; gene.
DR neXtProt; NX_P39687; -.
DR PharmGKB; PA24811; -.
DR eggNOG; NOG322008; -.
DR HOGENOM; HOG000007361; -.
DR HOVERGEN; HBG053102; -.
DR InParanoid; P39687; -.
DR OMA; NCRSYEG; -.
DR OrthoDB; EOG7TJ3KH; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; ANP32A; human.
DR EvolutionaryTrace; P39687; -.
DR GenomeRNAi; 8125; -.
DR NextBio; 30786; -.
DR PMAP-CutDB; P39687; -.
DR PRO; PR:P39687; -.
DR ArrayExpress; P39687; -.
DR Bgee; P39687; -.
DR CleanEx; HS_ANP32A; -.
DR Genevestigator; P39687; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003603; U2A'_phosphoprotein32A_C.
DR SMART; SM00446; LRRcap; 1.
DR PROSITE; PS51450; LRR; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Endoplasmic reticulum; Leucine-rich repeat; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1 249 Acidic leucine-rich nuclear
FT phosphoprotein 32 family member A.
FT /FTId=PRO_0000137592.
FT REPEAT 18 38 LRR 1.
FT REPEAT 43 64 LRR 2.
FT REPEAT 65 87 LRR 3.
FT REPEAT 89 110 LRR 4.
FT DOMAIN 123 161 LRRCT.
FT REGION 150 174 Necessary for tumor-suppressive function.
FT REGION 165 249 Interaction with E4F1 (By similarity).
FT COMPBIAS 168 249 Asp/Glu-rich (highly acidic).
FT MOD_RES 15 15 Phosphothreonine.
FT MOD_RES 17 17 Phosphoserine.
FT CONFLICT 186 186 V -> A (in Ref. 8; BAD97000).
FT HELIX 3 11
FT HELIX 16 18
FT STRAND 20 23
FT STRAND 46 48
FT STRAND 68 70
FT HELIX 81 86
FT STRAND 92 94
FT HELIX 103 106
FT HELIX 107 111
FT STRAND 117 119
FT HELIX 124 127
FT HELIX 131 138
SQ SEQUENCE 249 AA; 28585 MW; CA2D1A756FBAEA04 CRC64;
MEMGRRIHLE LRNRTPSDVK ELVLDNSRSN EGKLEGLTDE FEELEFLSTI NVGLTSIANL
PKLNKLKKLE LSDNRVSGGL EVLAEKCPNL THLNLSGNKI KDLSTIEPLK KLENLKSLDL
FNCEVTNLND YRENVFKLLP QLTYLDGYDR DDKEAPDSDA EGYVEGLDDE EEDEDEEEYD
EDAQVVEDEE DEDEEEEGEE EDVSGEEEED EEGYNDGEVD DEEDEEELGE EERGQKRKRE
PEDEGEDDD
//
ID AN32A_HUMAN Reviewed; 249 AA.
AC P39687; B2R6T4; Q53FK4; Q5J8L8; Q7M4N6;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Acidic leucine-rich nuclear phosphoprotein 32 family member A;
DE AltName: Full=Acidic nuclear phosphoprotein pp32;
DE AltName: Full=Leucine-rich acidic nuclear protein;
DE Short=LANP;
DE AltName: Full=Mapmodulin;
DE AltName: Full=Potent heat-stable protein phosphatase 2A inhibitor I1PP2A;
DE AltName: Full=Putative HLA-DR-associated protein I;
DE Short=PHAPI;
GN Name=ANP32A; Synonyms=C15orf1, LANP, MAPM, PHAP1;
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], AND PROTEIN SEQUENCE OF 1-26; 29-47; 71-97
RP AND 100-161.
RC TISSUE=B-cell lymphoma;
RX PubMed=8192856;
RA Vaesen M., Barnikol-Watanabe S., Goetz H., Adil Awni L., Cole T.,
RA Zimmermann B., Kratzin H.D., Hilschmann N.;
RT "Purification and characterization of two putative HLA class II
RT associated proteins: PHAPI and PHAPII.";
RL Biol. Chem. Hoppe-Seyler 375:113-126(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 7-12 AND 29-44.
RC TISSUE=Kidney;
RX PubMed=8679524; DOI=10.1021/bi960581y;
RA Li M., Makkinje A., Damuni Z.;
RT "Molecular identification of I1PP2A, a novel potent heat-stable
RT inhibitor protein of protein phosphatase 2A.";
RL Biochemistry 35:6998-7002(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8970164; DOI=10.1091/mbc.7.12.2045;
RA Chen T.-H., Brody J.R., Romantsev F.E., Yu J.-G., Kayler A.E.,
RA Voneiff E., Kuhajda F.P., Pasternack G.R.;
RT "Structure of pp32, an acidic nuclear protein which inhibits oncogene-
RT induced formation of transformed foci.";
RL Mol. Biol. Cell 7:2045-2056(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9353121; DOI=10.1038/40159;
RA Matilla A., Koshy B.T., Cummings C.J., Isobe T., Orr H.T.,
RA Zoghbi H.Y.;
RT "The cerebellar leucine-rich acidic nuclear protein interacts with
RT ataxin-1.";
RL Nature 389:974-978(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=15642345; DOI=10.1016/j.febslet.2004.11.097;
RA Tsujio I., Zaidi T., Xu J., Kotula L., Grundke-Iqbal I., Iqbal K.;
RT "Inhibitors of protein phosphatase-2A from human brain structures,
RT immunocytological localization and activities towards
RT dephosphorylation of the Alzheimer type hyperphosphorylated tau.";
RL FEBS Lett. 579:363-372(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovium;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10400610; DOI=10.1074/jbc.274.29.20053;
RA Brody J.R., Kadkol S.S., Mahmoud M.A., Rebel J.M., Pasternack G.R.;
RT "Identification of sequences required for inhibition of oncogene-
RT mediated transformation by pp32.";
RL J. Biol. Chem. 274:20053-20055(1999).
RN [12]
RP INTERACTION WITH THE INHAT COMPLEX, AND MASS SPECTROMETRY.
RX PubMed=11163245; DOI=10.1016/S0092-8674(01)00196-9;
RA Seo S.-B., McNamara P., Heo S., Turner A., Lane W.S., Chakravarti D.;
RT "Regulation of histone acetylation and transcription by INHAT, a human
RT cellular complex containing the Set oncoprotein.";
RL Cell 104:119-130(2001).
RN [13]
RP INTERACTION WITH SET.
RX PubMed=11555662; DOI=10.1074/jbc.M108137200;
RA Beresford P.J., Zhang D., Oh D.Y., Fan Z., Greer E.L., Russo M.L.,
RA Jaju M., Lieberman J.;
RT "Granzyme A activates an endoplasmic reticulum-associated caspase-
RT independent nuclease to induce single-stranded DNA nicks.";
RL J. Biol. Chem. 276:43285-43293(2001).
RN [14]
RP FUNCTION.
RX PubMed=11360199; DOI=10.1038/sj.onc.1204294;
RA Bai J., Brody J.R., Kadkol S.S., Pasternack G.R.;
RT "Tumor suppression and potentiation by manipulation of pp32
RT expression.";
RL Oncogene 20:2153-2160(2001).
RN [15]
RP INTERACTION WITH ELAVL1, AND SUBCELLULAR LOCATION.
RX PubMed=11729309; DOI=10.1126/science.1064693;
RA Gallouzi I.-E., Steitz J.A.;
RT "Delineation of mRNA export pathways by the use of cell-permeable
RT peptides.";
RL Science 294:1895-1901(2001).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=12524539; DOI=10.1038/ni885;
RA Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A.,
RA Pommier Y., Lieberman J.;
RT "Cleaving the oxidative repair protein Ape1 enhances cell death
RT mediated by granzyme A.";
RL Nat. Immunol. 4:145-153(2003).
RN [17]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=15895553; DOI=10.1080/14734220410019020;
RA Matilla A., Radrizzani M.;
RT "The Anp32 family of proteins containing leucine-rich repeats.";
RL Cerebellum 4:7-18(2005).
RN [18]
RP FUNCTION, AND INTERACTION WITH E4F1.
RX PubMed=17557114; DOI=10.1038/sj.embor.7400983;
RA Cvetanovic M., Rooney R.J., Garcia J.J., Toporovskaya N., Zoghbi H.Y.,
RA Opal P.;
RT "The role of LANP and ataxin 1 in E4F-mediated transcriptional
RT repression.";
RL EMBO Rep. 8:671-677(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-15 AND SER-17, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
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).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-149, AND LEUCINE-RICH
RP REPEATS.
RX PubMed=17567741; DOI=10.1110/ps.072803507;
RA Huyton T., Wolberger C.;
RT "The crystal structure of the tumor suppressor protein pp32 (Anp32a):
RT structural insights into Anp32 family of proteins.";
RL Protein Sci. 16:1308-1315(2007).
CC -!- FUNCTION: Implicated in a number of cellular processes, including
CC proliferation, differentiation, caspase-dependent and caspase-
CC independent apoptosis, suppression of transformation (tumor
CC suppressor), inhibition of protein phosphatase 2A, regulation of
CC mRNA trafficking and stability in association with ELAVL1, and
CC inhibition of acetyltransferases as part of the INHAT (inhibitor
CC of histone acetyltransferases) complex. Plays a role in E4F1-
CC mediated transcriptional repression.
CC -!- SUBUNIT: Component of the SET complex, which also contains SET,
CC APEX1, HMGB2 and NME1. Directly interacts with SET. Interacts with
CC ATXN1/SCA1. Interacts with MAP1B (By similarity). Interacts with
CC ELAVL1. Part of the INHAT (inhibitor of histone
CC acetyltransferases) complex. Interacts with E4F1.
CC -!- INTERACTION:
CC O15169:AXIN1; NbExp=2; IntAct=EBI-359234, EBI-710484;
CC Q66K89:E4F1; NbExp=3; IntAct=EBI-359234, EBI-1227043;
CC P67775:PPP2CA; NbExp=2; IntAct=EBI-359234, EBI-712311;
CC P63331:Ppp2ca (xeno); NbExp=2; IntAct=EBI-359234, EBI-7050205;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Endoplasmic reticulum.
CC Note=Translocates to the cytoplasm during the process of
CC neuritogenesis (By similarity). Shuttles between nucleus and
CC cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested. Highly
CC expressed in kidney and skeletal muscle, moderate levels of
CC expression in brain, placenta and pancreas, and weakly expressed
CC in lung. Found in all regions of the brain examined (amygdala,
CC caudate nucleus, corpus callosum, hippocampus and thalamus), with
CC highest levels in amygdala.
CC -!- PTM: Phosphorylated on serine residues.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Some glutamate residues are glycylated by TTLL8. This
CC modification occurs exclusively on glutamate residues and results
CC in a glycine chain on the gamma-carboxyl group (By similarity).
CC -!- SIMILARITY: Belongs to the ANP32 family.
CC -!- SIMILARITY: Contains 4 LRR (leucine-rich) repeats.
CC -!- SIMILARITY: Contains 1 LRRCT domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD97000.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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DR EMBL; X75090; CAA52981.1; -; mRNA.
DR EMBL; U60823; AAC50570.1; -; mRNA.
DR EMBL; U73477; AAB39706.1; -; mRNA.
DR EMBL; AF025684; AAB91548.1; -; mRNA.
DR EMBL; AY349171; AAQ79832.1; -; mRNA.
DR EMBL; BT007436; AAP36104.1; -; mRNA.
DR EMBL; AK223280; BAD97000.1; ALT_INIT; mRNA.
DR EMBL; AK312703; BAG35581.1; -; mRNA.
DR EMBL; CH471082; EAW77824.1; -; Genomic_DNA.
DR EMBL; BC007200; AAH07200.1; -; mRNA.
DR PIR; S36375; S36375.
DR PIR; S43309; S43309.
DR RefSeq; NP_006296.1; NM_006305.3.
DR UniGene; Hs.458747; -.
DR PDB; 2JE0; X-ray; 2.40 A; A/B/C/D/E/F=1-149.
DR PDB; 2JE1; X-ray; 2.69 A; A/B/C/D=1-149.
DR PDBsum; 2JE0; -.
DR PDBsum; 2JE1; -.
DR ProteinModelPortal; P39687; -.
DR SMR; P39687; 1-149.
DR IntAct; P39687; 15.
DR MINT; MINT-4999627; -.
DR STRING; 9606.ENSP00000417864; -.
DR PhosphoSite; P39687; -.
DR DMDM; 730318; -.
DR SWISS-2DPAGE; P39687; -.
DR PaxDb; P39687; -.
DR PRIDE; P39687; -.
DR DNASU; 8125; -.
DR Ensembl; ENST00000465139; ENSP00000417864; ENSG00000140350.
DR GeneID; 8125; -.
DR KEGG; hsa:8125; -.
DR UCSC; uc002arl.3; human.
DR CTD; 8125; -.
DR GeneCards; GC15M069070; -.
DR HGNC; HGNC:13233; ANP32A.
DR HPA; CAB005231; -.
DR MIM; 600832; gene.
DR neXtProt; NX_P39687; -.
DR PharmGKB; PA24811; -.
DR eggNOG; NOG322008; -.
DR HOGENOM; HOG000007361; -.
DR HOVERGEN; HBG053102; -.
DR InParanoid; P39687; -.
DR OMA; NCRSYEG; -.
DR OrthoDB; EOG7TJ3KH; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; ANP32A; human.
DR EvolutionaryTrace; P39687; -.
DR GenomeRNAi; 8125; -.
DR NextBio; 30786; -.
DR PMAP-CutDB; P39687; -.
DR PRO; PR:P39687; -.
DR ArrayExpress; P39687; -.
DR Bgee; P39687; -.
DR CleanEx; HS_ANP32A; -.
DR Genevestigator; P39687; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003603; U2A'_phosphoprotein32A_C.
DR SMART; SM00446; LRRcap; 1.
DR PROSITE; PS51450; LRR; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Endoplasmic reticulum; Leucine-rich repeat; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1 249 Acidic leucine-rich nuclear
FT phosphoprotein 32 family member A.
FT /FTId=PRO_0000137592.
FT REPEAT 18 38 LRR 1.
FT REPEAT 43 64 LRR 2.
FT REPEAT 65 87 LRR 3.
FT REPEAT 89 110 LRR 4.
FT DOMAIN 123 161 LRRCT.
FT REGION 150 174 Necessary for tumor-suppressive function.
FT REGION 165 249 Interaction with E4F1 (By similarity).
FT COMPBIAS 168 249 Asp/Glu-rich (highly acidic).
FT MOD_RES 15 15 Phosphothreonine.
FT MOD_RES 17 17 Phosphoserine.
FT CONFLICT 186 186 V -> A (in Ref. 8; BAD97000).
FT HELIX 3 11
FT HELIX 16 18
FT STRAND 20 23
FT STRAND 46 48
FT STRAND 68 70
FT HELIX 81 86
FT STRAND 92 94
FT HELIX 103 106
FT HELIX 107 111
FT STRAND 117 119
FT HELIX 124 127
FT HELIX 131 138
SQ SEQUENCE 249 AA; 28585 MW; CA2D1A756FBAEA04 CRC64;
MEMGRRIHLE LRNRTPSDVK ELVLDNSRSN EGKLEGLTDE FEELEFLSTI NVGLTSIANL
PKLNKLKKLE LSDNRVSGGL EVLAEKCPNL THLNLSGNKI KDLSTIEPLK KLENLKSLDL
FNCEVTNLND YRENVFKLLP QLTYLDGYDR DDKEAPDSDA EGYVEGLDDE EEDEDEEEYD
EDAQVVEDEE DEDEEEEGEE EDVSGEEEED EEGYNDGEVD DEEDEEELGE EERGQKRKRE
PEDEGEDDD
//
MIM
600832
*RECORD*
*FIELD* NO
600832
*FIELD* TI
*600832 ACIDIC LEUCINE-RICH NUCLEAR PHOSPHOPROTEIN 32 FAMILY, MEMBER A; ANP32A
;;PUTATIVE HUMAN HLA CLASS II-ASSOCIATED PROTEIN; PHAP1;;
read morePHAP I;;
LEUCINE-RICH ACIDIC NUCLEAR PROTEIN; LANP
*FIELD* TX
CLONING
The putative HLA class II-associated proteins PHAP I and PHAP II were
purified and cloned on the basis of their ability to bind to the
cytoplasmic domain of the HLA DR-alpha chain (142860) (Vaesen et al.,
1994). They may be components of the transmembrane signaling pathway
that is activated after extracellular binding of ligands during the
immune response. Both proteins share extensive stretches of highly
acidic amino acids in their terminal regions, which suggested a nuclear
localization. Indeed, PHAP I is likely to be the human homolog of the
rat 'leucine-rich acidic nuclear protein' (LANP) (83.6% identity), which
is localized in the nuclei of Purkinje cells. Sequence identity
demonstrated that PHAP II is identical to the protein encoded by the
gene SET (600960).
Mutation in ataxin-1 (ATX1; 601556) causes spinocerebellar ataxia (SCA1;
164400). Using a yeast 2-hybrid screen of a mouse brain cDNA library
with mutant human ATX1 as bait, Matilla et al. (1997) isolated a mouse
cDNA encoding Lanp, which is 89% identical to the human protein and is
expressed in cerebellum and brainstem. Binding analysis indicated that
the strongest interaction between the proteins is with the N-terminal
147 residues on Lanp, which contain 5 leucine-rich repeats, and a
full-length ataxin-1 containing 82 glutamines. Immunohistochemical
analysis demonstrated highest levels of Lanp, like Atx1, in the nuclei
of cerebellar Purkinje cells.
MAPPING
Fink et al. (1995) mapped the PHAP1 gene to 15q22.3-q23 by fluorescence
in situ hybridization.
CYTOGENETICS
The SET gene is located on 9q34 and was found to be fused to the
putative oncogene CAN (114350) in a patient with acute undifferentiated
leukemia (von Lindern et al., 1992). The similarities between PHAP I and
SET suggested to Fink et al. (1995) that the PHAP1 gene might also form
a fusion protein with CAN. In the SET-CAN fusion gene, the breakpoint is
located 3-prime of the SET gene, but the last exon of SET is removed in
the fusion transcript. This exon encodes the last 7 amino acids
(EDEGEDD) of SET that are identical with the end of PHAP I except that
PHAP I carries an additional D (EDEGEDDD). The vast majority of cases in
which CAN is involved in acute myeloid leukemia show a specificity for
the t(6;9) translocation (Sandberg et al., 1983) that fuses the 3-prime
part of the CAN gene on 9q34 (von Lindern et al., 1990) to almost the
complete coding region of the DEK gene (125264) on 6p23 (von Lindern et
al., 1992). The translocation breakpoints always occur in intron icb-9
of CAN. The PHAP1/CAN translocation would be expected to cause acute
leukemia. Like DEK and SET, PHAP I contains an extended acidic region
that could result in a transforming capacity.
GENE FUNCTION
By micropeptide sequence analysis of a PP2A (PPP2CA; 176915) inhibitor
and database screening, Li et al. (1996) determined that the inhibitor,
termed I1PP2A, was identical to PHAP1. SDS-PAGE analysis indicated that
both proteins, which contain 249 amino acids and a highly acidic
C-terminal tail, have an apparent molecular mass of 30 kD. Functional
analysis showed that recombinant PHAP1 is a potent and specific
inhibitor of PP2A and acts by binding to the C subunit of the
phosphatase.
Jiang et al. (2003) identified a pathway that regulates
mitochondria-initiated caspase activity. In this pathway, PHAP protein
promoted caspase-9 (602234) activation after apoptosome formation,
whereas PTMA (188390) negatively regulated caspase-9 activation by
inhibiting apoptosome formation. A small molecular activator of
caspase-3 (600636), PETCM, relieved PTMA inhibition and allowed
apoptosome formation at a physiologic concentration of dATP. Elimination
of PTMA expression by RNA interference sensitized cells to ultraviolet
irradiation-induced apoptosis and negated the requirement of PETCM for
caspase activation.
*FIELD* RF
1. Fink, T. M.; Vaesen, M.; Kratzin, H. D.; Lichter, P.; Zimmer, M.
: Localization of the gene encoding the putative human HLA class II
associated protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence
in situ hybridization. Genomics 29: 309-310, 1995.
2. Jiang, X.; Kim, H.-E.; Shu, H.; Zhao, Y.; Zhang, H.; Kofron, J.;
Donnelly, J.; Burns, D.; Ng, S.; Rosenberg, S.; Wang, X.: Distinctive
roles of PHAP proteins and prothymosin-alpha in a death regulatory
pathway. Science 299: 223-226, 2003.
3. Li, M.; Makkinje, A.; Damuni, Z.: Molecular identification of
I-1(PP2A), a novel potent heat-stable inhibitor protein of protein
phosphatase 2A. Biochemistry 35: 6998-7002, 1996.
4. Matilla, A.; Koshy, B. T.; Cummings, C. J.; Isobe, T.; Orr, H.
T.; Zoghbi, H. Y.: The cerebellar leucine-rich acidic nuclear protein
interacts with ataxin-1. Nature 389: 974-978, 1997. Note: Erratum:
Nature 391: 818 only, 1998.
5. Sandberg, A. A.; Morgan, R.; McCallister, J. A.; Kaiser-McCaw,
B.; Hecht, F.: Acute myeloblastic leukemia (AML) with t(6;9)(p23;q34):
a specific subgroup of AML? Cancer Genet. Cytogenet. 10: 139-142,
1983.
6. Vaesen, M.; Barnikol-Watanabe, S.; Gotz, H.; Awni, L. A.; Cole,
T.; Zimmermann, B; Kratzin, H. D.; Hilschmann, N.: Purification and
characterization of two putative HLA class II associated proteins:
PHAPI and PHAPII. Biol. Chem. Hoppe Seyler 375: 113-126, 1994.
7. von Lindern, M.; Fornerod, M.; van Baal, S.; Jaegle, M.; de Wit,
T.; Buijs, A.; Grosveld, G.: The translocation (6;9), associated
with a specific subtype of acute myeloid leukemia, results in the
fusion of two genes, dek and can, and the expression of a chimeric,
leukemia-specific dek-can mRNA. Molec. Cell. Biol. 12: 1687-1697,
1992.
8. von Lindern, M.; Poustka, A.; Lehrach, H.; Grosveld, G.: The (6;9)
chromosome translocation, associated with a specific subtype of acute
nonlymphocytic leukemia, leads to aberrant transcription of a target
gene on 9q34. Molec. Cell. Biol. 10: 4016-4026, 1990.
9. von Lindern, M.; van Baal, S.; Wiegant, J.; Raap, A.; Hagemeijer,
A.; Grosveld, G.: Can, a putative oncogene associated with myeloid
leukemogenesis may be activated by fusion of its 3-prime half to different
genes: characterization of the set gene. Molec. Cell Biol. 12: 3346-3355,
1992.
*FIELD* CN
Ada Hamosh - updated: 2/6/2003
Paul J. Converse - updated: 3/13/2002
*FIELD* CD
Victor A. McKusick: 10/4/1995
*FIELD* ED
terry: 09/17/2010
alopez: 2/11/2003
terry: 2/6/2003
mgross: 4/1/2002
terry: 3/13/2002
carol: 2/15/2002
psherman: 8/26/1999
terry: 10/30/1995
mark: 10/4/1995
*RECORD*
*FIELD* NO
600832
*FIELD* TI
*600832 ACIDIC LEUCINE-RICH NUCLEAR PHOSPHOPROTEIN 32 FAMILY, MEMBER A; ANP32A
;;PUTATIVE HUMAN HLA CLASS II-ASSOCIATED PROTEIN; PHAP1;;
read morePHAP I;;
LEUCINE-RICH ACIDIC NUCLEAR PROTEIN; LANP
*FIELD* TX
CLONING
The putative HLA class II-associated proteins PHAP I and PHAP II were
purified and cloned on the basis of their ability to bind to the
cytoplasmic domain of the HLA DR-alpha chain (142860) (Vaesen et al.,
1994). They may be components of the transmembrane signaling pathway
that is activated after extracellular binding of ligands during the
immune response. Both proteins share extensive stretches of highly
acidic amino acids in their terminal regions, which suggested a nuclear
localization. Indeed, PHAP I is likely to be the human homolog of the
rat 'leucine-rich acidic nuclear protein' (LANP) (83.6% identity), which
is localized in the nuclei of Purkinje cells. Sequence identity
demonstrated that PHAP II is identical to the protein encoded by the
gene SET (600960).
Mutation in ataxin-1 (ATX1; 601556) causes spinocerebellar ataxia (SCA1;
164400). Using a yeast 2-hybrid screen of a mouse brain cDNA library
with mutant human ATX1 as bait, Matilla et al. (1997) isolated a mouse
cDNA encoding Lanp, which is 89% identical to the human protein and is
expressed in cerebellum and brainstem. Binding analysis indicated that
the strongest interaction between the proteins is with the N-terminal
147 residues on Lanp, which contain 5 leucine-rich repeats, and a
full-length ataxin-1 containing 82 glutamines. Immunohistochemical
analysis demonstrated highest levels of Lanp, like Atx1, in the nuclei
of cerebellar Purkinje cells.
MAPPING
Fink et al. (1995) mapped the PHAP1 gene to 15q22.3-q23 by fluorescence
in situ hybridization.
CYTOGENETICS
The SET gene is located on 9q34 and was found to be fused to the
putative oncogene CAN (114350) in a patient with acute undifferentiated
leukemia (von Lindern et al., 1992). The similarities between PHAP I and
SET suggested to Fink et al. (1995) that the PHAP1 gene might also form
a fusion protein with CAN. In the SET-CAN fusion gene, the breakpoint is
located 3-prime of the SET gene, but the last exon of SET is removed in
the fusion transcript. This exon encodes the last 7 amino acids
(EDEGEDD) of SET that are identical with the end of PHAP I except that
PHAP I carries an additional D (EDEGEDDD). The vast majority of cases in
which CAN is involved in acute myeloid leukemia show a specificity for
the t(6;9) translocation (Sandberg et al., 1983) that fuses the 3-prime
part of the CAN gene on 9q34 (von Lindern et al., 1990) to almost the
complete coding region of the DEK gene (125264) on 6p23 (von Lindern et
al., 1992). The translocation breakpoints always occur in intron icb-9
of CAN. The PHAP1/CAN translocation would be expected to cause acute
leukemia. Like DEK and SET, PHAP I contains an extended acidic region
that could result in a transforming capacity.
GENE FUNCTION
By micropeptide sequence analysis of a PP2A (PPP2CA; 176915) inhibitor
and database screening, Li et al. (1996) determined that the inhibitor,
termed I1PP2A, was identical to PHAP1. SDS-PAGE analysis indicated that
both proteins, which contain 249 amino acids and a highly acidic
C-terminal tail, have an apparent molecular mass of 30 kD. Functional
analysis showed that recombinant PHAP1 is a potent and specific
inhibitor of PP2A and acts by binding to the C subunit of the
phosphatase.
Jiang et al. (2003) identified a pathway that regulates
mitochondria-initiated caspase activity. In this pathway, PHAP protein
promoted caspase-9 (602234) activation after apoptosome formation,
whereas PTMA (188390) negatively regulated caspase-9 activation by
inhibiting apoptosome formation. A small molecular activator of
caspase-3 (600636), PETCM, relieved PTMA inhibition and allowed
apoptosome formation at a physiologic concentration of dATP. Elimination
of PTMA expression by RNA interference sensitized cells to ultraviolet
irradiation-induced apoptosis and negated the requirement of PETCM for
caspase activation.
*FIELD* RF
1. Fink, T. M.; Vaesen, M.; Kratzin, H. D.; Lichter, P.; Zimmer, M.
: Localization of the gene encoding the putative human HLA class II
associated protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence
in situ hybridization. Genomics 29: 309-310, 1995.
2. Jiang, X.; Kim, H.-E.; Shu, H.; Zhao, Y.; Zhang, H.; Kofron, J.;
Donnelly, J.; Burns, D.; Ng, S.; Rosenberg, S.; Wang, X.: Distinctive
roles of PHAP proteins and prothymosin-alpha in a death regulatory
pathway. Science 299: 223-226, 2003.
3. Li, M.; Makkinje, A.; Damuni, Z.: Molecular identification of
I-1(PP2A), a novel potent heat-stable inhibitor protein of protein
phosphatase 2A. Biochemistry 35: 6998-7002, 1996.
4. Matilla, A.; Koshy, B. T.; Cummings, C. J.; Isobe, T.; Orr, H.
T.; Zoghbi, H. Y.: The cerebellar leucine-rich acidic nuclear protein
interacts with ataxin-1. Nature 389: 974-978, 1997. Note: Erratum:
Nature 391: 818 only, 1998.
5. Sandberg, A. A.; Morgan, R.; McCallister, J. A.; Kaiser-McCaw,
B.; Hecht, F.: Acute myeloblastic leukemia (AML) with t(6;9)(p23;q34):
a specific subgroup of AML? Cancer Genet. Cytogenet. 10: 139-142,
1983.
6. Vaesen, M.; Barnikol-Watanabe, S.; Gotz, H.; Awni, L. A.; Cole,
T.; Zimmermann, B; Kratzin, H. D.; Hilschmann, N.: Purification and
characterization of two putative HLA class II associated proteins:
PHAPI and PHAPII. Biol. Chem. Hoppe Seyler 375: 113-126, 1994.
7. von Lindern, M.; Fornerod, M.; van Baal, S.; Jaegle, M.; de Wit,
T.; Buijs, A.; Grosveld, G.: The translocation (6;9), associated
with a specific subtype of acute myeloid leukemia, results in the
fusion of two genes, dek and can, and the expression of a chimeric,
leukemia-specific dek-can mRNA. Molec. Cell. Biol. 12: 1687-1697,
1992.
8. von Lindern, M.; Poustka, A.; Lehrach, H.; Grosveld, G.: The (6;9)
chromosome translocation, associated with a specific subtype of acute
nonlymphocytic leukemia, leads to aberrant transcription of a target
gene on 9q34. Molec. Cell. Biol. 10: 4016-4026, 1990.
9. von Lindern, M.; van Baal, S.; Wiegant, J.; Raap, A.; Hagemeijer,
A.; Grosveld, G.: Can, a putative oncogene associated with myeloid
leukemogenesis may be activated by fusion of its 3-prime half to different
genes: characterization of the set gene. Molec. Cell Biol. 12: 3346-3355,
1992.
*FIELD* CN
Ada Hamosh - updated: 2/6/2003
Paul J. Converse - updated: 3/13/2002
*FIELD* CD
Victor A. McKusick: 10/4/1995
*FIELD* ED
terry: 09/17/2010
alopez: 2/11/2003
terry: 2/6/2003
mgross: 4/1/2002
terry: 3/13/2002
carol: 2/15/2002
psherman: 8/26/1999
terry: 10/30/1995
mark: 10/4/1995