PDE4C_MOUSE
ID PDE4C_MOUSE Reviewed; 686 AA.
AC Q3UEI1; Q8K0P4;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase 4C;
DE EC=3.1.4.53 {ECO:0000250|UniProtKB:Q08493};
GN Name=Pde4c {ECO:0000312|MGI:MGI:99556};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Kidney;
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-9; SER-28; SER-40; SER-83 AND
RP SER-642, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH AKAP5; ADCY5; ADCY6 AND PKD2.
RX PubMed=21670265; DOI=10.1073/pnas.1016214108;
RA Choi Y.H., Suzuki A., Hajarnis S., Ma Z., Chapin H.C., Caplan M.J.,
RA Pontoglio M., Somlo S., Igarashi P.;
RT "Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase
RT anchoring protein complex that is disrupted in cystic kidney diseases.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:10679-10684(2011).
CC -!- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key
CC regulator of many important physiological processes.
CC {ECO:0000250|UniProtKB:Q08493}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; EC=3.1.4.53;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions. {ECO:0000250|UniProtKB:Q08493};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q07343};
CC Note=Binds 2 divalent metal cations per subunit (By similarity). Site 2
CC has a preference for magnesium and/or manganese ions (By similarity).
CC {ECO:0000250|UniProtKB:Q07343, ECO:0000250|UniProtKB:Q08493};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1. {ECO:0000250|UniProtKB:Q08493}.
CC -!- SUBUNIT: Part of a complex containing AKAP5, ADCY5, ADCY6 and PKD2.
CC {ECO:0000269|PubMed:21670265}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:21670265}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UEI1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UEI1-2; Sequence=VSP_016663;
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE4 subfamily. {ECO:0000305}.
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DR EMBL; AK149514; BAE28930.1; -; mRNA.
DR EMBL; BC030873; AAH30873.1; -; mRNA.
DR CCDS; CCDS22378.1; -. [Q3UEI1-2]
DR CCDS; CCDS80891.1; -. [Q3UEI1-1]
DR RefSeq; NP_001297394.1; NM_001310465.1. [Q3UEI1-1]
DR RefSeq; NP_963901.1; NM_201607.2. [Q3UEI1-2]
DR AlphaFoldDB; Q3UEI1; -.
DR SMR; Q3UEI1; -.
DR IntAct; Q3UEI1; 1.
DR STRING; 10090.ENSMUSP00000105722; -.
DR BindingDB; Q3UEI1; -.
DR ChEMBL; CHEMBL2111373; -.
DR iPTMnet; Q3UEI1; -.
DR PhosphoSitePlus; Q3UEI1; -.
DR MaxQB; Q3UEI1; -.
DR PaxDb; Q3UEI1; -.
DR PRIDE; Q3UEI1; -.
DR ProteomicsDB; 287809; -. [Q3UEI1-1]
DR ProteomicsDB; 287810; -. [Q3UEI1-2]
DR DNASU; 110385; -.
DR Ensembl; ENSMUST00000034307; ENSMUSP00000034307; ENSMUSG00000031842. [Q3UEI1-2]
DR Ensembl; ENSMUST00000110095; ENSMUSP00000105722; ENSMUSG00000031842. [Q3UEI1-1]
DR Ensembl; ENSMUST00000239487; ENSMUSP00000159330; ENSMUSG00000031842. [Q3UEI1-2]
DR GeneID; 110385; -.
DR KEGG; mmu:110385; -.
DR UCSC; uc009mbg.1; mouse. [Q3UEI1-2]
DR UCSC; uc009mbh.1; mouse. [Q3UEI1-1]
DR CTD; 5143; -.
DR MGI; MGI:99556; Pde4c.
DR VEuPathDB; HostDB:ENSMUSG00000031842; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000162285; -.
DR HOGENOM; CLU_005940_5_3_1; -.
DR InParanoid; Q3UEI1; -.
DR OMA; LQAENCN; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q3UEI1; -.
DR TreeFam; TF314638; -.
DR Reactome; R-MMU-180024; DARPP-32 events.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR UniPathway; UPA00762; UER00747.
DR BioGRID-ORCS; 110385; 1 hit in 61 CRISPR screens.
DR ChiTaRS; Pde4c; mouse.
DR PRO; PR:Q3UEI1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q3UEI1; protein.
DR Bgee; ENSMUSG00000031842; Expressed in cortex of kidney and 47 other tissues.
DR ExpressionAtlas; Q3UEI1; baseline and differential.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR040844; PDE4_UCR.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF18100; PDE4_UCR; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; cAMP; Cell projection; Cilium; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..686
FT /note="cAMP-specific 3',5'-cyclic phosphodiesterase 4C"
FT /id="PRO_0000198812"
FT DOMAIN 313..642
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 88..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 389
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 389
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 389
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 393
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 393
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 429
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 430
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 430
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 430
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 430
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 430
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 547
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 547
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 598
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 598
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 601
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 601
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 642
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 537..570
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016663"
SQ SEQUENCE 686 AA; 76090 MW; 4B510001564A2A08 CRC64;
MRRSGTALSF LWTERVREPV DSGVAPVSPL GGGVILRRFS GTLLLPPLSS RLGSSGEAES
AAHVVFTIGT QGTQRNLGSA QSSFDLENGL PGGKGLLDAQ SGPSLGRALQ PPVHHVQRRE
SFLYRSDSDH EPSPKAVSRT SSAASDLHGE DMIVTPFAQV LASLRTVRNN VAALAHGPGS
ATRQVLLGTP PHSSQQAAPT EDSGLQLVQE TLEELDWCLE QLETLQTRRS VGEMASNKFK
RMLNRELSYL SETSRSGNQV SEYISQTFLD QQAEVELPQP PTEDDPWPMA QITELRRSSH
TSLPTAAIPR FGVQTDQEEQ LAKELEDTNK WGLDVFKVAE LSGNRPLTAV IFSVFQERDL
LKTFQIPADT LLAYLLTLEG HYHSDVAYHN SMHAADVVQS AHVLLGTPAL EAVFTDLEVL
AAIFACAIHD VDHPGVSNQF LINTNSELAL MYNDSSVLEN HHLAVGFKLL QGENCDIFRN
LSTKQRLSLR RMVIDMVLAT DMSKHMSLLA DLKTMVETKK VTSLGVLLLD NYSDRIQVLQ
SLVHCADLSN PAKPLPLYRQ WTERIMAEFF QQGDRERESG LDISPMCDKH TASMEKSQVG
FIDYIAQPLW ETWADLVHPD AQELLDTLED NREWYQSRIP CSPPHTMGSD RFKFELTLEE
AEEEEEEEDE GQCTALNRES SELPST
