PJA2_PONAB
ID PJA2_PONAB Reviewed; 708 AA.
AC Q5R4R1; Q5R5Y8;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 109.
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;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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}.
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. Cell membrane {ECO:0000250}.
CC Endoplasmic reticulum membrane; Peripheral membrane protein. Golgi
CC apparatus membrane; Peripheral membrane protein. Synapse {ECO:0000250}.
CC Postsynaptic density {ECO:0000250}. Note=Localizes at the cytoplasmic
CC side of endoplasmic reticulum and Golgi apparatus. Expressed in the
CC postsynaptic density region of synapses. Co-localizes with PRKAR2A and
CC PRKAR2B in the cytoplasm and the cell membrane (By similarity).
CC {ECO:0000250}.
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DR EMBL; CR860713; CAH92828.1; -; mRNA.
DR EMBL; CR861183; CAH93255.1; -; mRNA.
DR RefSeq; NP_001124566.1; NM_001131094.1.
DR AlphaFoldDB; Q5R4R1; -.
DR SMR; Q5R4R1; -.
DR STRING; 9601.ENSPPYP00000017525; -.
DR GeneID; 100169739; -.
DR KEGG; pon:100169739; -.
DR CTD; 9867; -.
DR eggNOG; KOG0800; Eukaryota.
DR InParanoid; Q5R4R1; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Unplaced.
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:0005886; C:plasma membrane; ISS:UniProtKB.
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; IEA:InterPro.
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; ISS: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:0010738; P:regulation of protein kinase A signaling; ISS: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..708
FT /note="E3 ubiquitin-protein ligase Praja-2"
FT /id="PRO_0000278232"
FT ZN_FING 634..675
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 53..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 425..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 531..708
FT /note="Interaction with PRKAR1A, PRKAR2A and PRKAR2B"
FT /evidence="ECO:0000250"
FT REGION 685..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..71
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..91
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..277
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 448..471
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 478..493
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 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 246
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 342
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 389
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43164"
FT CONFLICT 111
FT /note="P -> Q (in Ref. 1; CAH92828)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="T -> I (in Ref. 1; CAH92828)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="S -> L (in Ref. 1; CAH92828)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 708 AA; 78139 MW; 48411F1AF4B3785A CRC64;
MSQYTEKEPA AMDQESGKAV WPKPAGGYQT ITGRRYGRRH AYVSFKPCMT RHERSLGRAG
DDYEVLELDD VPKENSSGSS PLDQVDSSLP NEPIFEKSET EIPTCGSALN PTTESSQSFV
AVHHSEEGRD TLGSSTNLHN HSEGEYTPGA CNASGVQNGI ALVHTDSYDP DGKHGEDNDR
LQLSAEVVEG SRYQESSGNT LFELENREAE AYTGLSPPVP SFNCEVRDEF EGLDSVPLVK
SSAGDTEFVH QNSQEIQRSS QDEMVSTKQQ NNTSQERQTE HSPEDSACGP GRICSEQNTN
DREKNHGSSP EQVVRPKVRK LISSSQVDQE TGFNRHEAKQ RSVQRWREAL EVEESGSDDL
LIKCEEYDGE HDCMFLDPPY SRVITQRETE NNQVTPESGA TAGRQEVDNP FWNGCGDYYQ
LYDKDEDSSE CSDGEWSASL PHRFSGTEKD QSSSDESWET LPGKDENEPE LQSDSSGPEE
ENQELSLQEG EQTSLEEGEI PWLQYNEVNE SSSDEGNEPA NEFAQPAFML DGNNNLEDDS
SVSEDLDVDW SLFDGFADGL GVAEAISYVD PQFLTYMALE ERLAQAMETA LAHLESLAVD
VEVANPPASK ESIDGLPETL VLEDHTAIGQ EQCCPICCSE YIKDDIATEL PCHHFFHKPC
VSIWLQKSGT CPVCRRHFPP AVIEASAAPS SEPDPDAPPS NDSIAEAP
