PPE2_HUMAN
ID PPE2_HUMAN Reviewed; 753 AA.
AC O14830; O14831;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Serine/threonine-protein phosphatase with EF-hands 2;
DE Short=PPEF-2;
DE EC=3.1.3.16;
GN Name=PPEF2;
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] (ISOFORMS PPEF-2(S) AND PPEF-2(L)), AND VARIANT
RP LEU-481.
RC TISSUE=Retina;
RX PubMed=9326663; DOI=10.1073/pnas.94.21.11639;
RA Sherman P.M., Sun H., Macke J.P., Williams J., Smallwood P.M., Nathans J.;
RT "Identification and characterization of a conserved family of protein
RT serine/threonine phosphatases homologous to Drosophila retinal degeneration
RT C.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11639-11644(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
CC -!- FUNCTION: May play a role in phototransduction. May dephosphorylate
CC photoactivated rhodopsin. May function as a calcium sensing regulator
CC of ionic currents, energy production or synaptic transmission.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by calcium. {ECO:0000250}.
CC -!- INTERACTION:
CC O14830; P62204: Calm3; Xeno; NbExp=2; IntAct=EBI-2931306, EBI-397460;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cell projection, cilium,
CC photoreceptor outer segment. Photoreceptor inner segment.
CC Note=Localized to photoreceptors, PPEF-2(L) is at least 2 fold more
CC abundant in rod inner segments than in the outer segments.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=PPEF-2(L);
CC IsoId=O14830-1; Sequence=Displayed;
CC Name=PPEF-2(S);
CC IsoId=O14830-2; Sequence=VSP_005103, VSP_005104;
CC -!- TISSUE SPECIFICITY: Retinal specific.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. {ECO:0000305}.
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DR EMBL; AF023456; AAB82796.1; -; mRNA.
DR EMBL; AF023457; AAB82797.1; -; mRNA.
DR EMBL; AC110615; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS34013.1; -. [O14830-1]
DR RefSeq; NP_006230.2; NM_006239.2. [O14830-1]
DR RefSeq; XP_011530341.1; XM_011532039.2. [O14830-1]
DR AlphaFoldDB; O14830; -.
DR SMR; O14830; -.
DR BioGRID; 111466; 27.
DR IntAct; O14830; 23.
DR MINT; O14830; -.
DR STRING; 9606.ENSP00000286719; -.
DR DEPOD; PPEF2; -.
DR iPTMnet; O14830; -.
DR PhosphoSitePlus; O14830; -.
DR BioMuta; PPEF2; -.
DR MassIVE; O14830; -.
DR PaxDb; O14830; -.
DR PeptideAtlas; O14830; -.
DR PRIDE; O14830; -.
DR ProteomicsDB; 48266; -. [O14830-1]
DR ProteomicsDB; 48267; -. [O14830-2]
DR Antibodypedia; 13410; 65 antibodies from 18 providers.
DR DNASU; 5470; -.
DR Ensembl; ENST00000286719.12; ENSP00000286719.6; ENSG00000156194.18. [O14830-1]
DR Ensembl; ENST00000621010.1; ENSP00000483398.1; ENSG00000156194.18. [O14830-2]
DR GeneID; 5470; -.
DR KEGG; hsa:5470; -.
DR MANE-Select; ENST00000286719.12; ENSP00000286719.6; NM_006239.3; NP_006230.2.
DR UCSC; uc003hix.4; human. [O14830-1]
DR CTD; 5470; -.
DR GeneCards; PPEF2; -.
DR HGNC; HGNC:9244; PPEF2.
DR HPA; ENSG00000156194; Tissue enriched (retina).
DR MIM; 602256; gene.
DR neXtProt; NX_O14830; -.
DR OpenTargets; ENSG00000156194; -.
DR PharmGKB; PA33565; -.
DR VEuPathDB; HostDB:ENSG00000156194; -.
DR eggNOG; KOG0377; Eukaryota.
DR GeneTree; ENSGT00940000157870; -.
DR HOGENOM; CLU_012603_1_0_1; -.
DR InParanoid; O14830; -.
DR OMA; ATHMLTM; -.
DR OrthoDB; 316811at2759; -.
DR PhylomeDB; O14830; -.
DR TreeFam; TF313342; -.
DR PathwayCommons; O14830; -.
DR SignaLink; O14830; -.
DR BioGRID-ORCS; 5470; 7 hits in 1070 CRISPR screens.
DR ChiTaRS; PPEF2; human.
DR GenomeRNAi; 5470; -.
DR Pharos; O14830; Tbio.
DR PRO; PR:O14830; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O14830; protein.
DR Bgee; ENSG00000156194; Expressed in gastrocnemius and 92 other tissues.
DR ExpressionAtlas; O14830; baseline and differential.
DR Genevisible; O14830; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0001917; C:photoreceptor inner segment; IEA:UniProtKB-SubCell.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030544; F:Hsp70 protein binding; IDA:BHF-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; IDA:BHF-UCL.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:BHF-UCL.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0050906; P:detection of stimulus involved in sensory perception; IEA:InterPro.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IDA:BHF-UCL.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR GO; GO:0043506; P:regulation of JUN kinase activity; IC:BHF-UCL.
DR GO; GO:0043405; P:regulation of MAP kinase activity; IC:BHF-UCL.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd00051; EFh; 1.
DR Gene3D; 3.60.21.10; -; 2.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR013235; PPP_dom.
DR InterPro; IPR012008; Ser/Thr-Pase_EF-hand_contain.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF00149; Metallophos; 1.
DR Pfam; PF08321; PPP5; 1.
DR PIRSF; PIRSF000912; PPEF; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00054; EFh; 3.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell projection; Cilium; Cytoplasm;
KW Hydrolase; Manganese; Metal-binding; Protein phosphatase;
KW Reference proteome; Repeat; Sensory transduction; Vision.
FT CHAIN 1..753
FT /note="Serine/threonine-protein phosphatase with EF-hands
FT 2"
FT /id="PRO_0000058901"
FT DOMAIN 21..46
FT /note="IQ"
FT DOMAIN 568..603
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 652..687
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 692..727
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 128..540
FT /note="Catalytic"
FT REGION 318..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 409..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..753
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..336
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 356..380
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..435
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 738..753
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 241
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 208
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 208
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 292
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 488
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 665
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 667
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 669
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 676
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 705
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 707
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 709
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 711
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 716
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VAR_SEQ 588..598
FT /note="ITLSDWAAAVE -> ASSQLCYYQQK (in isoform PPEF-2(S))"
FT /evidence="ECO:0000305"
FT /id="VSP_005103"
FT VAR_SEQ 599..753
FT /note="Missing (in isoform PPEF-2(S))"
FT /evidence="ECO:0000305"
FT /id="VSP_005104"
FT VARIANT 120
FT /note="S -> R"
FT /id="VAR_010230"
FT VARIANT 394
FT /note="V -> L (in dbSNP:rs34097437)"
FT /id="VAR_055121"
FT VARIANT 412
FT /note="E -> K (in dbSNP:rs35599561)"
FT /id="VAR_055122"
FT VARIANT 481
FT /note="M -> L (in dbSNP:rs6858658)"
FT /evidence="ECO:0000269|PubMed:9326663"
FT /id="VAR_061759"
FT VARIANT 553
FT /note="R -> K (in dbSNP:rs34155925)"
FT /id="VAR_055123"
FT VARIANT 575
FT /note="S -> C (in dbSNP:rs17000961)"
FT /id="VAR_055124"
FT CONFLICT 118
FT /note="R -> S (in Ref. 1; AAB82796/AAB82797)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 753 AA; 86518 MW; 28ED6E79C5B8906C CRC64;
MGSGTSTQHH FAFQNAERAF KAAALIQRWY RRYVARLEMR RRCTWSIFQS IEYAGQQDQV
KLHDFFSYLM DHFIPSSHND RDFLTRIFTE DRFAQDSEMK KCSDYESIEV PDSYTGPRLS
FPLLPDHATA LVEAFRLKQQ LHARYVLNLL YETKKHLVQL PNINRVSTCY SEEITVCGDL
HGQLDDLIFI FYKNGLPSPE RSYVFNGDFV DRGKDSVEIL MILFAFMLVY PKEFHLNRGN
HEDHMVNLRY GFTKEVMNKY KVHGKEILRT LQDVFCWLPL ATLIDEKVLI LHGGVSDITD
LELLDKIERS KIVSTMRCKT RQKSEKQMEE KRRANQKSSA QGPIPWFLPE SRSLPSSPLR
LGSYKAQKTS RSSSIPCSGS LDGRELSRQV RSSVELELER CRQQAGLLVT GEKEEPSRSA
SEADSEAGEL RKPTQEEWRQ VVDILWSDPM AQEGCKANTI RGGGCYFGPD VTQQLLQKYN
MQFLIRSHEC KPEGYEFCHN RKVLTIFSAS NYYEVGSNRG AYVKLGPALT PHIVQYQANK
VTHTLTMRQR ISRVEESALR ALREKLFAHS SDLLSEFKKH DADKVGLITL SDWAAAVESV
LHLGLPWRML RPQLVNSSAD NMLEYKSWLK NLAKEQLSRE NIQSSLLETL YRNRSNLETI
FRIIDSDHSG FISLDEFRQT WKLFSSHMNI DITDDCICDL ARSIDFNKDG HIDINEFLEA
FRLVEKSCPE GDASECPQAT NAKDSGCSSP GAH
