PJA2_RAT
ID PJA2_RAT Reviewed; 707 AA.
AC Q63364;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=E3 ubiquitin-protein ligase Praja-2;
DE Short=Praja2;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase Praja-2 {ECO:0000305};
GN Name=Pja2; Synonyms=Neurodap1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7623148; DOI=10.1523/jneurosci.15-07-05238.1995;
RA Nakayama M., Miyake T., Gahara Y., Ohara O., Kitamura T.;
RT "A novel RING-H2 motif protein downregulated by axotomy: its characteristic
RT localization at the postsynaptic density of axosomatic synapse.";
RL J. Neurosci. 15:5238-5248(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21423175; DOI=10.1038/ncb2209;
RA Lignitto L., Carlucci A., Sepe M., Stefan E., Cuomo O., Nistico R.,
RA Scorziello A., Savoia C., Garbi C., Annunziato L., Feliciello A.;
RT "Control of PKA stability and signalling by the RING ligase praja2.";
RL Nat. Cell Biol. 13:412-422(2011).
CC -!- FUNCTION: Has E2-dependent E3 ubiquitin-protein ligase activity.
CC Responsible for ubiquitination of cAMP-dependent protein kinase type I
CC and type II-alpha/beta regulatory subunits and for targeting them for
CC proteasomal degradation. Essential for PKA-mediated long-term memory
CC processes. Through the ubiquitination of MFHAS1, positively regulates
CC the TLR2 signaling pathway that leads to the activation of the
CC downstream p38 and JNK MAP kinases and promotes the polarization of
CC macrophages toward the pro-inflammatory M1 phenotype.
CC {ECO:0000250|UniProtKB:O43164, ECO:0000269|PubMed:21423175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Binds ubiquitin-conjugating enzymes (E2s). In vitro, interacts
CC with the ubiquitin-conjugating enzyme, UBE2D2. The phosphorylated form
CC interacts with PRKAR1A, PRKAR2A and PRKAR2B. Binds the catalytic
CC subunits of cAMP-dependent protein kinase. Interacts with MFHAS1.
CC {ECO:0000250|UniProtKB:O43164}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7623148}. Cell
CC membrane {ECO:0000250}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:7623148}; Peripheral membrane protein
CC {ECO:0000269|PubMed:7623148}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:7623148}; Peripheral membrane protein
CC {ECO:0000269|PubMed:7623148}. Synapse {ECO:0000269|PubMed:7623148}.
CC Postsynaptic density {ECO:0000269|PubMed:7623148}. Note=Localizes at
CC the cytoplasmic side of endoplasmic reticulum and Golgi apparatus.
CC Expressed in the postsynaptic density region of synapses. Colocalizes
CC with PRKAR2A and PRKAR2B in the cytoplasm and the cell membrane (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, in nerve cells but
CC not in glial cells. Abundantly expressed in pyramidal neurons and in
CC the CA3 region of apical dendrites. Colocalizes with PRKAR2B in dentate
CC granule cells and at postsynaptic sites of primary hippocampal neurons.
CC {ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:7623148}.
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DR EMBL; D32249; BAA06979.1; -; mRNA.
DR EMBL; BC074015; AAH74015.1; -; mRNA.
DR RefSeq; NP_001264207.1; NM_001277278.1.
DR RefSeq; NP_620251.1; NM_138896.2.
DR RefSeq; XP_017451755.1; XM_017596266.1.
DR AlphaFoldDB; Q63364; -.
DR SMR; Q63364; -.
DR STRING; 10116.ENSRNOP00000021258; -.
DR iPTMnet; Q63364; -.
DR PhosphoSitePlus; Q63364; -.
DR PaxDb; Q63364; -.
DR PRIDE; Q63364; -.
DR Ensembl; ENSRNOT00000080962; ENSRNOP00000072362; ENSRNOG00000015528.
DR GeneID; 192256; -.
DR KEGG; rno:192256; -.
DR CTD; 9867; -.
DR RGD; 620273; Pja2.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000154585; -.
DR InParanoid; Q63364; -.
DR OMA; HFSAREK; -.
DR OrthoDB; 1249953at2759; -.
DR PhylomeDB; Q63364; -.
DR TreeFam; TF330711; -.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q63364; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000015528; Expressed in frontal cortex and 19 other tissues.
DR ExpressionAtlas; Q63364; baseline and differential.
DR Genevisible; Q63364; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISS:UniProtKB.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0035329; P:hippo signaling; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; IMP:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0043030; P:regulation of macrophage activation; ISO:RGD.
DR GO; GO:0010738; P:regulation of protein kinase A signaling; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR030639; Praja-2.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR15710:SF5; PTHR15710:SF5; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell membrane; Cytoplasm; Endoplasmic reticulum;
KW Golgi apparatus; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Synapse; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT CHAIN 2..707
FT /note="E3 ubiquitin-protein ligase Praja-2"
FT /id="PRO_0000278233"
FT ZN_FING 633..674
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 75..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 242..290
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 530..707
FT /note="Interaction with PRKAR1A, PRKAR2A and PRKAR2B"
FT /evidence="ECO:0000250"
FT REGION 686..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..280
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..469
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 476..491
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 339
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
SQ SEQUENCE 707 AA; 77921 MW; CB41D41F39C36C70 CRC64;
MSQYTEKEPS VMDQDSSKAA WPRAAGGYQT ITGRRYGRRH AYVSFKPCMT RHERSLGRAG
DDYEVLELDD VAKENTAGSS SLDQVHPSLP SETTVEKSET EIPTCGPALN QSTESNPSVA
TVCHSEEVRE TLDSSTNLQN HAERECTPAV CNASSVQNGI VLVHTDSYDP DSKHDENDSL
QLCAQAVEGG RRQKVLGNAV FELENGEVER YADLCPSVPS LSGEIREESE ELGSALLEKN
SAGDAEAVHQ DGQEFQRSSE DGIVRKRRQD DTDQGRQTEN STEDADCVPG HVEQNTSERA
NHHGSSPEQV VRPKVRKVIS SSQVDQESGF NRHEAKQRSV QRWREALEVE ECSSDDPIIK
CDDYDGDHDC MFLTPSYSRV TPREAERHRA TAENGATASG RQEARENAFW NACGEYYQLF
DKDEDSSECS DGEWSASLPH RFSGTEKDQS SSDESWETLP GKDENEPELQ SDSSGPEEEN
QELSLQEGEQ TSLEEGEIPW LQYNEVNESS SDEGNEPANE FAQPEAFMLD GNNNLEDDSS
VSEDLDVDWS LFDGFADGLG VAEAISYVDP QFLTYMALEE RLAQAMETAL AHLESLAVDV
EVANPPASKE SIDGLPETLV LEDHTAIGQE QCCPICCSEY IKDDIATELP CHHFFHKPCV
SIWLQKSGTC PVCRRHFPPA VIDASAAASS EPDLDASPAN DNAEEAP
