ARP19_HUMAN
ID ARP19_HUMAN Reviewed; 112 AA.
AC P56211; B2R497; Q6IAM2; Q86TA6; Q9UD70;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=cAMP-regulated phosphoprotein 19;
DE Short=ARPP-19;
GN Name=ARPP19;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ARPP-19).
RC TISSUE=Brain;
RX PubMed=9653196; DOI=10.1073/pnas.95.14.8387;
RA Heron L., Virsolvy A., Peyrollier K., Gribble F.M., Le Cam A.,
RA Ashcroft F.M., Bataille D.;
RT "Human alpha-endosulfine, a possible regulator of sulfonylurea-sensitive
RT K(ATP) channel: molecular cloning, expression and biological properties.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8387-8391(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ARPP-19).
RC TISSUE=Brain;
RX PubMed=10754390; DOI=10.1007/bf02256622;
RA Chin L.S., Singh S.K., Wang Q., Murray S.F.;
RT "Identification of okadaic-acid-induced genes by mRNA differential display
RT in glioma cells.";
RL J. Biomed. Sci. 7:152-159(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ARPP-16).
RC TISSUE=Brain;
RX PubMed=8120638; DOI=10.1523/jneurosci.14-03-00985.1994;
RA Brene S., Lindefors N., Ehrlich M., Taubes T., Horiuchi A., Kopp J.,
RA Hall H., Sedvall G., Greengard P., Persson H.;
RT "Expression of mRNAs encoding ARPP-16/19, ARPP-21, and DARPP-32 in human
RT brain tissue.";
RL J. Neurosci. 14:985-998(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ARPP-19).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ARPP-19).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ARPP-19).
RC TISSUE=Spinal cord;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ARPP-19).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH SNCA.
RX PubMed=17893145; DOI=10.1074/jbc.m705283200;
RA Woods W.S., Boettcher J.M., Zhou D.H., Kloepper K.D., Hartman K.L.,
RA Ladror D.T., Qi Z., Rienstra C.M., George J.M.;
RT "Conformation-specific binding of alpha-synuclein to novel protein partners
RT detected by phage display and NMR spectroscopy.";
RL J. Biol. Chem. 282:34555-34567(2007).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-109, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP INDUCTION.
RX PubMed=20218812; DOI=10.3109/10428191003629362;
RA Bruchova-Votavova H., Yoon D., Prchal J.T.;
RT "miR-451 enhances erythroid differentiation in K562 cells.";
RL Leuk. Lymphoma 51:686-693(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP FUNCTION.
RX PubMed=21164014; DOI=10.1126/science.1197048;
RA Gharbi-Ayachi A., Labbe J.C., Burgess A., Vigneron S., Strub J.M.,
RA Brioudes E., Van-Dorsselaer A., Castro A., Lorca T.;
RT "The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting
RT protein phosphatase 2A.";
RL Science 330:1673-1677(2010).
RN [16]
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., Buerckstuemmer T.,
RA 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-23 AND SER-104, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Protein phosphatase inhibitor that specifically inhibits
CC protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at
CC Ser-62 during mitosis, specifically interacts with PPP2R2D (PR55-delta)
CC and inhibits its activity, leading to inactivation of PP2A, an
CC essential condition to keep cyclin-B1-CDK1 activity high during M
CC phase. May indirectly enhance GAP-43 expression.
CC {ECO:0000269|PubMed:21164014}.
CC -!- SUBUNIT: Interacts (when phosphorylated at Ser-62) with PPP2R2D (By
CC similarity). Interacts with SNCA. {ECO:0000250,
CC ECO:0000269|PubMed:17893145}.
CC -!- INTERACTION:
CC P56211; P05067: APP; NbExp=3; IntAct=EBI-5773880, EBI-77613;
CC P56211; Q5MJ68: SPDYC; NbExp=3; IntAct=EBI-5773880, EBI-12162209;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=ARPP-19;
CC IsoId=P56211-1; Sequence=Displayed;
CC Name=ARPP-16;
CC IsoId=P56211-2; Sequence=VSP_018555;
CC -!- INDUCTION: Expression may be regulated by miR-451.
CC {ECO:0000269|PubMed:20218812}.
CC -!- PTM: Phosphorylation at Ser-62 by GWL during mitosis is essential for
CC interaction with PPP2R2D (PR55-delta) and subsequent inactivation of
CC PP2A (By similarity). Phosphorylated by PKA. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the endosulfine family. {ECO:0000305}.
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DR EMBL; AJ223091; CAA11115.1; -; mRNA.
DR EMBL; AF084555; AAD52044.1; -; mRNA.
DR EMBL; CR457132; CAG33413.1; -; mRNA.
DR EMBL; AL833077; CAD89929.1; -; mRNA.
DR EMBL; AK311751; BAG34694.1; -; mRNA.
DR EMBL; AC025917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77454.1; -; Genomic_DNA.
DR EMBL; BC003418; AAH03418.1; -; mRNA.
DR EMBL; BC100015; AAI00016.1; -; mRNA.
DR CCDS; CCDS32242.1; -. [P56211-1]
DR CCDS; CCDS81883.1; -. [P56211-2]
DR RefSeq; NP_001293120.1; NM_001306191.1.
DR RefSeq; NP_001293124.1; NM_001306195.1. [P56211-1]
DR RefSeq; NP_001293125.1; NM_001306196.1.
DR RefSeq; NP_001317238.1; NM_001330309.1. [P56211-2]
DR RefSeq; NP_006619.1; NM_006628.5. [P56211-1]
DR RefSeq; XP_016877357.1; XM_017021868.1.
DR RefSeq; XP_016877359.1; XM_017021870.1. [P56211-2]
DR AlphaFoldDB; P56211; -.
DR BMRB; P56211; -.
DR BioGRID; 115994; 15.
DR IntAct; P56211; 3.
DR STRING; 9606.ENSP00000455625; -.
DR iPTMnet; P56211; -.
DR PhosphoSitePlus; P56211; -.
DR BioMuta; ARPP19; -.
DR EPD; P56211; -.
DR jPOST; P56211; -.
DR MassIVE; P56211; -.
DR MaxQB; P56211; -.
DR PaxDb; P56211; -.
DR PeptideAtlas; P56211; -.
DR PRIDE; P56211; -.
DR ProteomicsDB; 56905; -. [P56211-1]
DR ProteomicsDB; 56906; -. [P56211-2]
DR TopDownProteomics; P56211-1; -. [P56211-1]
DR Antibodypedia; 42667; 57 antibodies from 19 providers.
DR DNASU; 10776; -.
DR Ensembl; ENST00000249822.9; ENSP00000249822.4; ENSG00000128989.11. [P56211-1]
DR Ensembl; ENST00000561650.5; ENSP00000454234.1; ENSG00000128989.11. [P56211-2]
DR Ensembl; ENST00000563277.5; ENSP00000455986.1; ENSG00000128989.11. [P56211-2]
DR Ensembl; ENST00000563566.5; ENSP00000457631.1; ENSG00000128989.11. [P56211-2]
DR Ensembl; ENST00000566423.5; ENSP00000455625.1; ENSG00000128989.11. [P56211-1]
DR Ensembl; ENST00000567669.5; ENSP00000455151.1; ENSG00000128989.11. [P56211-1]
DR Ensembl; ENST00000568196.1; ENSP00000457805.1; ENSG00000128989.11. [P56211-2]
DR Ensembl; ENST00000569281.6; ENSP00000454297.1; ENSG00000128989.11. [P56211-1]
DR GeneID; 10776; -.
DR KEGG; hsa:10776; -.
DR MANE-Select; ENST00000249822.9; ENSP00000249822.4; NM_006628.6; NP_006619.1.
DR UCSC; uc002acd.2; human. [P56211-1]
DR CTD; 10776; -.
DR DisGeNET; 10776; -.
DR GeneCards; ARPP19; -.
DR HGNC; HGNC:16967; ARPP19.
DR HPA; ENSG00000128989; Low tissue specificity.
DR MIM; 605487; gene.
DR neXtProt; NX_P56211; -.
DR OpenTargets; ENSG00000128989; -.
DR PharmGKB; PA165478498; -.
DR VEuPathDB; HostDB:ENSG00000128989; -.
DR eggNOG; KOG4076; Eukaryota.
DR GeneTree; ENSGT00940000154555; -.
DR HOGENOM; CLU_125025_1_0_1; -.
DR InParanoid; P56211; -.
DR OMA; SKYPGGM; -.
DR OrthoDB; 1494565at2759; -.
DR PhylomeDB; P56211; -.
DR TreeFam; TF314718; -.
DR PathwayCommons; P56211; -.
DR Reactome; R-HSA-2465910; MASTL Facilitates Mitotic Progression.
DR SignaLink; P56211; -.
DR SIGNOR; P56211; -.
DR BioGRID-ORCS; 10776; 185 hits in 1071 CRISPR screens.
DR ChiTaRS; ARPP19; human.
DR GeneWiki; ARPP-19; -.
DR GenomeRNAi; 10776; -.
DR Pharos; P56211; Tbio.
DR PRO; PR:P56211; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P56211; protein.
DR Bgee; ENSG00000128989; Expressed in prefrontal cortex and 218 other tissues.
DR ExpressionAtlas; P56211; baseline and differential.
DR Genevisible; P56211; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0019212; F:phosphatase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISS:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; IBA:GO_Central.
DR GO; GO:0019888; F:protein phosphatase regulator activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IDA:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; NAS:UniProtKB.
DR InterPro; IPR006760; Endosulphine.
DR PANTHER; PTHR10358; PTHR10358; 1.
DR Pfam; PF04667; Endosulfine; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell cycle; Cell division; Cytoplasm;
KW Mitosis; Phosphoprotein; Protein phosphatase inhibitor; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..112
FT /note="cAMP-regulated phosphoprotein 19"
FT /id="PRO_0000008041"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 73..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..36
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 62
FT /note="Phosphoserine; by GWL"
FT /evidence="ECO:0000305"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 109
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..16
FT /note="Missing (in isoform ARPP-16)"
FT /evidence="ECO:0000303|PubMed:8120638"
FT /id="VSP_018555"
FT MOD_RES P56211-2:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q28055"
SQ SEQUENCE 112 AA; 12323 MW; F19652B545C839AB CRC64;
MSAEVPEAAS AEEQKEMEDK VTSPEKAEEA KLKARYPHLG QKPGGSDFLR KRLQKGQKYF
DSGDYNMAKA KMKNKQLPTA APDKTEVTGD HIPTPQDLPQ RKPSLVASKL AG
