PIN1_MACFA
ID PIN1_MACFA Reviewed; 163 AA.
AC Q4R383;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1;
DE EC=5.2.1.8 {ECO:0000250|UniProtKB:Q13526};
DE AltName: Full=Peptidyl-prolyl cis-trans isomerase Pin1;
DE Short=PPIase Pin1;
GN Name=PIN1; ORFNames=QtsA-18773;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to
CC and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro)
CC motifs. By inducing conformational changes in a subset of
CC phosphorylated proteins, acts as a molecular switch in multiple
CC cellular processes. Displays a preference for acidic residues located
CC N-terminally to the proline bond to be isomerized. Regulates mitosis
CC presumably by interacting with NIMA and attenuating its mitosis-
CC promoting activity. Down-regulates kinase activity of BTK. Can
CC transactivate multiple oncogenes and induce centrosome amplification,
CC chromosome instability and cell transformation. Required for the
CC efficient dephosphorylation and recycling of RAF1 after mitogen
CC activation. Binds and targets PML and BCL6 for degradation in a
CC phosphorylation-dependent manner. Acts as a regulator of JNK cascade by
CC binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and
CC promoting FBXW7 autoubiquitination and degradation: degradation of
CC FBXW7 leads to subsequent stabilization of JUN. May facilitate the
CC ubiquitination and proteasomal degradation of RBBP8/CtIP through
CC CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA
CC double-strand repair through error-prone non-homologous end joining
CC (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR).
CC Upon IL33-induced lung inflammation, catalyzes cis-trans isomerization
CC of phosphorylated IRAK3/IRAK-M, inducing IRAK3 stabilization, nuclear
CC translocation and expression of pro-inflammatory genes in dendritic
CC cells. {ECO:0000250|UniProtKB:Q13526}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-peptidylproline (omega=180) = [protein]-
CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA-
CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833,
CC ChEBI:CHEBI:83834; EC=5.2.1.8;
CC Evidence={ECO:0000250|UniProtKB:Q13526};
CC -!- SUBUNIT: Interacts with STIL (By similarity). Interacts with KIF20B.
CC Interacts with NEK6. Interacts (via WW domain) with PRKX. Interacts
CC with BTK. Interacts (via PpiC domain) with DAPK1. Interacts with the
CC phosphorylated form of RAF1. Interacts (via WW domain) with ATCAY; upon
CC NGF stimulation. Interacts with PML (isoform PML-4). Interacts with
CC BCL6. Interacts with FBXW7, disrupting FBXW7 dimerization and promoting
CC FBXW7 autoubiquitination and degradation. Directly interacts with
CC RBBP8/CtIP; this interaction depends upon RBBP8 phosphorylation.
CC Interacts (via WW domain) with IRAK3/IRAK-M (when phosphorylated at
CC 'Ser-110') in response to IL33-mediated (but not TLR4 ligand LPS)
CC dendritic cell stimulation (By similarity).
CC {ECO:0000250|UniProtKB:Q13526, ECO:0000250|UniProtKB:Q9QUR7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13526}. Nucleus
CC speckle {ECO:0000250|UniProtKB:Q13526}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q13526}. Note=Colocalizes with NEK6 in the
CC nucleus. Mainly localized in the nucleus but phosphorylation at Ser-71
CC by DAPK1 results in inhibition of its nuclear localization.
CC {ECO:0000250|UniProtKB:Q13526}.
CC -!- DOMAIN: The WW domain is required for the interaction with STIL and
CC KIF20B. {ECO:0000250|UniProtKB:Q13526}.
CC -!- PTM: Phosphorylation at Ser-71 by DAPK1 results in inhibition of its
CC catalytic activity, nuclear localization, and its ability to induce
CC centrosome amplification, chromosome instability and cell
CC transformation (By similarity). Ser-71 is dephosphorylated upon IL33-
CC stimulation of dendritic cells (By similarity).
CC {ECO:0000250|UniProtKB:Q13526, ECO:0000250|UniProtKB:Q9QUR7}.
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DR EMBL; AB179383; BAE02434.1; -; mRNA.
DR RefSeq; NP_001270625.1; NM_001283696.1.
DR AlphaFoldDB; Q4R383; -.
DR BMRB; Q4R383; -.
DR SMR; Q4R383; -.
DR STRING; 9541.XP_005587972.1; -.
DR GeneID; 101866324; -.
DR CTD; 5300; -.
DR eggNOG; KOG3259; Eukaryota.
DR OrthoDB; 1437969at2759; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016859; F:cis-trans isomerase activity; ISS:UniProtKB.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR CDD; cd00201; WW; 1.
DR Gene3D; 3.10.50.40; -; 1.
DR InterPro; IPR046357; PPIase_dom_sf.
DR InterPro; IPR000297; PPIase_PpiC.
DR InterPro; IPR023058; PPIase_PpiC_CS.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00639; Rotamase; 1.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF51045; SSF51045; 1.
DR PROSITE; PS01096; PPIC_PPIASE_1; 1.
DR PROSITE; PS50198; PPIC_PPIASE_2; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell cycle; Cytoplasm; Isomerase; Nucleus; Phosphoprotein;
KW Reference proteome; Rotamase.
FT CHAIN 1..163
FT /note="Peptidyl-prolyl cis-trans isomerase NIMA-interacting
FT 1"
FT /id="PRO_0000236244"
FT DOMAIN 5..39
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 52..163
FT /note="PpiC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00278"
FT REGION 33..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13526"
FT MOD_RES 46
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13526"
FT MOD_RES 71
FT /note="Phosphoserine; by DAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q13526"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13526"
SQ SEQUENCE 163 AA; 18301 MW; D89877640B7F7382 CRC64;
MADEEKLPPG WEKRMSRSSD RVYYFNHITN ASQWERPSGN SSSGGKNGQG EPARVRCSHL
LVKHSQSRRP SSWRQEKITR TKEEALELIN GYIQKIKSGE EDFESLASQF SDCSSAKARG
DLGAFSRGQM QKPFEDASFA LRTGEMSGPV FTDSGIHIIL RTE
