PBIR1_HUMAN
ID PBIR1_HUMAN Reviewed; 287 AA.
AC Q96E09;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 {ECO:0000303|PubMed:33108758, ECO:0000312|HGNC:HGNC:23490};
DE AltName: Full=PABIR family member 1 {ECO:0000305};
GN Name=PABIR1 {ECO:0000303|PubMed:33108758, ECO:0000312|HGNC:HGNC:23490};
GN Synonyms=C9orf42, FAM122A {ECO:0000303|PubMed:33108758};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND SER-143, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; SER-48; SER-143; SER-147;
RP THR-149 AND SER-270, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; SER-37; THR-47; SER-48;
RP SER-76; SER-143; SER-270 AND SER-276, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62; SER-76; SER-143 AND
RP SER-147, AND 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; SER-143 AND SER-147, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; SER-48; SER-76; SER-143;
RP SER-147; SER-187 AND SER-189, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45 AND SER-76, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-89, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [14]
RP FUNCTION, AND INTERACTION WITH PPP2CA; PPP2R2A AND PPP2R1A.
RX PubMed=27588481; DOI=10.18632/oncotarget.11698;
RA Fan L., Liu M.H., Guo M., Hu C.X., Yan Z.W., Chen J., Chen G.Q., Huang Y.;
RT "FAM122A, a new endogenous inhibitor of protein phosphatase 2A.";
RL Oncotarget 7:63887-63900(2016).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-37, MUTAGENESIS OF
RP SER-37, AND INTERACTION WITH PPP2R2A AND 14-3-3 PROTEINS.
RX PubMed=33108758; DOI=10.1016/j.molcel.2020.10.008;
RA Li F., Kozono D., Deraska P., Branigan T., Dunn C., Zheng X.F., Parmar K.,
RA Nguyen H., DeCaprio J., Shapiro G.I., Chowdhury D., D'Andrea A.D.;
RT "CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication
RT Stress.";
RL Mol. Cell 0:0-0(2020).
CC -!- FUNCTION: Acts as an inhibitor of serine/threonine-protein phosphatase
CC 2A (PP2A) activity (PubMed:27588481, PubMed:33108758). Potentiates
CC ubiquitin-mediated proteasomal degradation of serine/threonine-protein
CC phosphatase 2A catalytic subunit alpha (PPP2CA) (PubMed:27588481).
CC Inhibits PP2A-mediated dephosphorylation of WEE1, promoting ubiquitin-
CC mediated proteolysis of WEE1, thereby releasing G2/M checkpoint
CC (PubMed:33108758). {ECO:0000269|PubMed:27588481,
CC ECO:0000269|PubMed:33108758}.
CC -!- SUBUNIT: Interacts with PPP2CA and PPP2R1A (PubMed:27588481). Interacts
CC with PPP2R2A (PubMed:27588481, PubMed:33108758). The CHEK1-mediated
CC Ser-37 phosphorylated form interacts with 14-3-3 proteins
CC (PubMed:33108758). {ECO:0000269|PubMed:27588481,
CC ECO:0000269|PubMed:33108758}.
CC -!- INTERACTION:
CC Q96E09; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-9355758, EBI-750109;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:33108758}. Cytoplasm
CC {ECO:0000269|PubMed:33108758}. Note=The CHEK1-mediated Ser-37
CC phosphorylated form is sequestered by 14-3-3 proteins in the cytoplasm
CC and fails to translocate to the nucleus, where it otherwise inhibits
CC serine/threonine-protein phosphatase 2A. {ECO:0000269|PubMed:33108758}.
CC -!- PTM: CHEK1-mediated phosphorylation at Ser-37 negatively regulates its
CC ability to inhibit serine/threonine-protein phosphatase 2A (PP2A)
CC activity. Phosphorylation leads to its release from the PP2A complex
CC and its sequestration by 14-3-3 proteins in the cytoplasm resulting in
CC its inability to translocate to the nucleus, where it otherwise
CC inhibits PP2A. {ECO:0000269|PubMed:33108758}.
CC -!- SIMILARITY: Belongs to the FAM122 family. {ECO:0000305}.
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DR EMBL; AL354794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013062; AAH13062.1; -; mRNA.
DR CCDS; CCDS6623.2; -.
DR RefSeq; NP_612206.4; NM_138333.4.
DR AlphaFoldDB; Q96E09; -.
DR BioGRID; 125489; 29.
DR IntAct; Q96E09; 21.
DR MINT; Q96E09; -.
DR STRING; 9606.ENSP00000377807; -.
DR GlyGen; Q96E09; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96E09; -.
DR PhosphoSitePlus; Q96E09; -.
DR BioMuta; FAM122A; -.
DR DMDM; 68565254; -.
DR EPD; Q96E09; -.
DR jPOST; Q96E09; -.
DR MassIVE; Q96E09; -.
DR MaxQB; Q96E09; -.
DR PaxDb; Q96E09; -.
DR PeptideAtlas; Q96E09; -.
DR PRIDE; Q96E09; -.
DR ProteomicsDB; 76353; -.
DR Antibodypedia; 26789; 54 antibodies from 14 providers.
DR DNASU; 116224; -.
DR Ensembl; ENST00000394264.7; ENSP00000377807.5; ENSG00000187866.10.
DR GeneID; 116224; -.
DR KEGG; hsa:116224; -.
DR MANE-Select; ENST00000394264.7; ENSP00000377807.5; NM_138333.5; NP_612206.5.
DR UCSC; uc004agw.2; human.
DR CTD; 116224; -.
DR DisGeNET; 116224; -.
DR GeneCards; PABIR1; -.
DR HGNC; HGNC:23490; PABIR1.
DR HPA; ENSG00000187866; Low tissue specificity.
DR neXtProt; NX_Q96E09; -.
DR OpenTargets; ENSG00000187866; -.
DR VEuPathDB; HostDB:ENSG00000187866; -.
DR eggNOG; ENOG502QTCH; Eukaryota.
DR GeneTree; ENSGT00390000015476; -.
DR HOGENOM; CLU_083344_0_0_1; -.
DR InParanoid; Q96E09; -.
DR OMA; MNLMNRE; -.
DR OrthoDB; 1406067at2759; -.
DR PhylomeDB; Q96E09; -.
DR TreeFam; TF330808; -.
DR PathwayCommons; Q96E09; -.
DR SignaLink; Q96E09; -.
DR SIGNOR; Q96E09; -.
DR BioGRID-ORCS; 116224; 173 hits in 1094 CRISPR screens.
DR GenomeRNAi; 116224; -.
DR Pharos; Q96E09; Tbio.
DR PRO; PR:Q96E09; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q96E09; protein.
DR Bgee; ENSG00000187866; Expressed in secondary oocyte and 171 other tissues.
DR Genevisible; Q96E09; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004865; F:protein serine/threonine phosphatase inhibitor activity; IMP:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IMP:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR InterPro; IPR026716; PBIR1/2/3.
DR PANTHER; PTHR22227; PTHR22227; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Isopeptide bond; Nucleus; Phosphoprotein;
KW Protein phosphatase inhibitor; Reference proteome; Ubl conjugation.
FT CHAIN 1..287
FT /note="PPP2R1A-PPP2R2A-interacting phosphatase regulator 1"
FT /id="PRO_0000089689"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 167..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 236..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..272
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 37
FT /note="Phosphoserine; by CHEK1"
FT /evidence="ECO:0000269|PubMed:33108758,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 47
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 149
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DB52"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT CROSSLNK 89
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT MUTAGEN 37
FT /note="S->A: Loss of phosphorylation and interaction with
FT 14-3-3 proteins. Enhanced interaction with PPP2R2A."
FT /evidence="ECO:0000269|PubMed:33108758"
SQ SEQUENCE 287 AA; 30529 MW; D5517157F72C398F CRC64;
MAQEKMELDL ELPPGTGGSP AEGGGSGGGG GLRRSNSAPL IHGLSDTSPV FQAEAPSARR
NSTTFPSRHG LLLPASPVRM HSSRLHQIKQ EEGMDLINRE TVHEREVQTA MQISHSWEES
FSLSDNDVEK SASPKRIDFI PVSPAPSPTR GIGKQCFSPS LQSFVSSNGL PPSPIPSPTT
RFTTRRSQSP INCIRPSVLG PLKRKCEMET EYQPKRFFQG ITNMLSSDVA QLSDPGVCVS
SDTLDGNSSS AGSSCNSPAK VSTTTDSPVS PAQAASPFIP LDELSSK
