Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol PIN1 contributors: mct/shn - updated : 05-07-2015
HGNC name peptidylprolyl cis/trans isomerase, NIMA-interacting 1
HGNC id 8988
Location 19p13.2      Physical location : 9.945.998 - 9.960.358
Synonym name
  • protein (peptidyl-prolyl cis/trans isomerase)
  • NIMA-interacting 1
  • rotamase Pin1
  • PPIase Pin1
  • DODO, Drosophila, homolog of
  • protein never in mitosis gene A interacting-1
  • Synonym symbol(s) PAR18, DOD, UBL5, PIN-1
    EC.number 5.2.1.8
    DNA
    TYPE functioning gene
    STRUCTURE 14.48 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D19S865 - D19S586 - PIN1 - D19S583 - D19S584 - cen
    Physical map
    FLJ38149 19p13.2 hypothetical protein FLJ38149 OR7E16P 19p13.13 olfactory receptor, family 7, subfamily E, member 16 pseudogene LOC390884 19 similar to olfactory receptor MOR145-1 LOC125958 19p13.2 similar to seven transmembrane helix receptor OR7D1P 19p13.2 olfactory receptor, family 7, subfamily D, member 1 pseudogene OR7E24P 19p13.2 olfactory receptor, family 7, subfamily E, member 24 pseudogene LOC390885 19 similar to seven transmembrane helix receptor OR7E19P 19p13.2 olfactory receptor, family 7, subfamily E, member 19 pseudogene LOC390886 19 similar to olfactory receptor MOR141-1 FLJ38144 19p13.2 FLJ38144 protein MGC13105 19p13.2 hypothetical protein MGC13105 ZNF177 19pter-p13.3 zinc finger protein 177 ZNF266 19p32.2 zinc finger protein 266 FLJ31986 19p13.2 hypothetical protein FLJ31986 LOC342967 19p13.2 similar to actin 3 - fruit fly (Drosophila melanogaster) (fragments) ZNF426 19p13.2 zinc finger protein 426 MGC45408 19p13.2 hypothetical protein MGC45408 FLJ20079 19p13.2 hypothetical protein FLJ20079 LOC342969 19p13.2 similar to hypothetical protein MGC45408 LOC390887 19 similar to hypothetical protein MGC45408 LOC162993 19p13.2 hypothetical protein LOC162993 UBE2L4 19q13.1-q13.2 ubiquitin-conjugating enzyme E2L 4 FBXL12 19p13.2 F-box and leucine-rich repeat protein 12 PIN1 19p13.2 protein (peptidyl-prolyl cis/trans isomerase) NIMA-interacting 1 UBL5 19p13.3 ubiquitin-like 5 LOC390888 19 similar to 60S ribosomal protein L10 (QM protein homolog) OLFM2 19p13.2 olfactomedin 2 COL5A3 19p13.2 collagen, type V, alpha 3 RDH8 19p13.2-p13.3 retinol dehydrogenase 8 (all-trans) LOC388502 19 similar to Complement C3 precursor LOC388503 19 similar to Complement C3-1 LOC147740 19p13.2 similar to complement C3 protein (GPC3) precursor FLJ11286 19p13.2 hypothetical protein FLJ11286 ANGPTL6 19p13.2 angiopoietin-like 6 PPAN 19p13 peter pan homolog (Drosophila) P2RY11 19p13.2 purinergic receptor P2Y, G-protein coupled, 11 EIF3S4 19p13.2 eukaryotic translation initiation factor 3, subunit 4 delta, 44kDa DNMT1 19p13.2 DNA (cytosine-5-)-methyltransferase 1 EDG5 19p13.2 endothelial differentiation, sphingolipid G-protein-coupled receptor, 5 LOC388504 19 LOC388504 MRPL4 19p13.2 mitochondrial ribosomal protein L4 ICAM1 19p13.3-p13.2 intercellular adhesion molecule 1 (CD54), human rhinovirus receptor
    RNA
    TRANSCRIPTS type messenger
    text PIN1 promoter contains no endoplasmic reticulum stress response element (ERSE)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 997 18.1 163 - 1997 9299231
    6 splicing 860
    5 splicing 1191
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestivesalivary gland   highly
    Endocrineparathyroid   highly
    Nervousbrain   highly Homo sapiens
     nerve   highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N-terminal class IV WW domain, characterized by two tryptophan residues separated by 22 AAs, which binds to p(S/T)–P in substrate proteins
  • a peptidyl-prolyl cis-trans isomerase (PPIase) domain
  • a PpiC domain
  • HOMOLOGY
    interspecies ortholog to Pin1, Rattus norvegicus
    ortholog to Pin1, Mus musculus
    ortholog to pin1, danio rerio
    ortholog to PIN1, Pan troglodytes
    Homologene
    FAMILY
  • PPIC/PARVULIN family of rotamase
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text
  • phosphorylation of PIN1 by MAP3K11 promotes its translocation to the nucleus
  • basic FUNCTION
  • an essential nuclear peptidylprolyl cis-trans isomerase nvolved in regulation of mitosis
  • stimulating the DNA-binding activity and transactivation function of TP53 and p73 and by modulating cell proliferation through stabilization of cyclin D1, alpha catenin 18, NF-KB
  • implicated in the amplification of oncogenic signals by its cooperation with the Neu/Ras pathway in mammary tumorigenesis
  • has a role in the activation of human Notch1, through modulation of its cleavage by alpha-secretase in tumorigenesis
  • crucial activity of Pin1 in the control of DNA damage checkpoint pathways, by regulating the functions of p53
  • restoring the function of Alzheimer-associated phosphorylated tau protein (MAPT)
  • involved in the regulation of mitosis by modulating the NIMA pathway
  • may mediate the function of PRKX in kidney development
  • phosphorylation-specific isomerase regulating centrosome duplication (its deregulation can induce centrosome amplification, chromosome instability, and oncogenesis)
  • regulates diverse cellular processes, including growth-signal responses, cell-cycle progression, cellular stress responses, neuronal function and immune responses
  • essential role in maintaining cell proliferation and regulating cyclin D1 function
  • essential for activation of the apoptotic response by endogenous p73
  • enhances STAT3-mediated epithelial-mesenchymal transition in breast cancer cells induced by oncostatin M
  • specifically recognizes the pSer/Thr-Pro motifs on its target proteins, and interacts with STAT3 upon cytokine/growth factor stimulation
  • may be neuroprotective against neurodegeneration in AD (Alzheimer disease)
  • involved in neurodegeneration
  • promotes cell death in NGF-dependent neurons through a mechanism requiring c-Jun activity
  • essential regulator of TERF1 stability, telomere maintenance and ageing
  • catalyzes the cis-trans conformational changes of p27(Kip1) and further mediates its stability through the polyubiquitination mechanism
  • acts as a switch to control the degree of substrate ubiquitylation
  • critical cell cycle regulator that modulates the function of many phosphorylated proteins during G2/M transition
  • could stabilize or provide additional protein-protein interaction surfaces in a catalytic-dependent manner, thereby favoring the interaction of ADRBK1 with other E3 ligases
  • amplifies EGF signaling in breast cancer cells through its interaction with MAP2K1 and then enhances ERBB2 expression
  • regulates CRE transcriptional activity, by associating with CRTC1 or CRTC2
  • regulates the functions and subcellular localizations of CRTC family proteins, thereby altering CRE transcriptional activity
  • novel role for PIN1 as a regulator of muscle terminal differentiation and may be PIN1-mediated repression of MEF2C function could contribute to this function
  • negatively modulates skeletal muscle differentiation, a function that can be explained partly by the inhibition of stability and activity of MEF2C
  • might regulate cellular processes distinct from the cell cycle itself, such as terminal differentiation through a modulation of differentiation-specific gene expression
  • indispensable for the self-renewal and maintenance of pluripotent stem cells via the regulation of phosphorylated POU5F1 and other substrates
  • control cell-cycle progression and is required for G2/M transition
  • a putative regulator of the induction and maintenance of pluripotency via the control of phosphorylation signaling
  • could act as a molecular switch that can reversibly control the proliferation and survival of induced pluripotent stem cells, thereby reducing the risk of cell transformation and tumor formation
  • has many important spindle substrates, and this might represent a general mechanism for localization of mitotic signalling proteins
  • apparently restrains the ability of CAST to inhibit calpain, maintaining calpain activity in endothelial cell
  • recognizes specific conformations of its substrate by conformational selection
  • has an important role in cell proliferation by isomerizing NR4A1
  • nuclear protein peptidyl-prolyl isomerase PIN1-mediated prolyl isomerization is an essential and novel regulatory mechanism for protein phosphorylation
  • regulates large numbers of phospho proteins having diverse cellular functions, including in the cell cycle, cell transformation, and apoptosis
  • PIN1 is a new regulator of RUNX3 inactivation in breast cancer
  • PIN1-mediated inhibition of FBXW7 contributes to oncogenesis
  • modulates the production of many pro- and antifibrogenic cytokines and ECM
  • coordinates the production and accumulation of ECM by regulating intracellular, SMAD-dependent signaling
  • PIN1 is a new and essential factor regulating CPEB1 degradation
  • critical role for SENP1-mediated deSUMOylation in promoting PIN1 function during tumorigenesis
  • acts as a negative regulator of the G2/M transition by interacting with the AURKA-BORA complex
  • both SEPT9 and PIN1 are critical for mediating the final separation of daughter cells
  • PIN1, similar to SEPT9, is required for abscission in human cells, and its depletion causes phenotypes similar to knockdown of SEPT9, controlling a previously uncharacterized step in abscission
  • PIN1-mediated isomerization, in response to phosphorylation, may serve as an evolutionarily conserved mechanism of regulating septin function in a variety of cellular contexts
  • promotes histone H1 dephosphorylation and stabilizes its binding to chromatin
  • conserved function of HIPK2 and PIN1 in the DNA damage-induced apoptosis response
  • PIN1 mediates HIPK2 isomerization and, thereby, alters HIPK2 conformation
  • novel function of PIN1 in neurodevelopment
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    nucleotide, replication
    PHYSIOLOGICAL PROCESS
    text entry into S phase after induction by IGF1
    PATHWAY
    metabolism
    signaling
  • MAP3K11-PIN1 signaling cascade plays a critical role in regulating the cell cycle, centrosome numbers, and oncogenesis
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Cdc25, Myt1, Wee1, Plk1, and Cdc27
  • MPM-2
  • Nuclear factor of activated T cells, NFAT
  • KRMP1
  • beta-catenin
  • hSpt5
  • Phosphorylated Bcl-2
  • cyclin D1
  • protein kinase CK2
  • Phospho Bcl2
  • p53
  • p65
  • p73
  • Raf-1 kinase
  • SCL-interrupting locus protein, SIL
  • Polo-like kinase 1, Plk1
  • cyclin E-Cdk2 complex
  • Steroid receptor coactivator 3, SRC3
  • Nek6
  • phosphorylated Thr 668-Pro motif in APP
  • gephyrin, GPHN
  • phosphorylated PIM1 binds PIN1 allowing the interaction of PPP2R5B, and dephosphorylation of PIM1 then allows for ubiquitinylation and protein degradation of PIM1
  • nerve growth factor may stimulate the interaction of ATCAY with PIN1 by releasing its intramolecular inhibition, which could provide a post-translational regulation on the cellular activity of ATCAY during neuronal differentiation
  • Smad2 and Smad3
  • p27(Kip1)
  • Smad2 and Smad3
  • importin alpha 5
  • NCOR2
  • ribosomal protein S6 kinase, RPS6KB1
  • PIN1 regulates ARHGAP8 function in RHO and ERK signalling, with active MAP2K2 serving as a novel regulatory scaffold that promotes crosstalk between RhoGAP, PIN1 and ERK in the regulation of cell migration
  • NANOG
  • phosphorylated MEF2C in skeletal muscle cells
  • CRTC2
  • POU5F1
  • DAPK1
  • partnership between PIN1 and PPP1R2, providing a means for regulating PIN1 specificity and function
  • interacts with ADARB1 and is a positive regulator required for the nuclear localization and stability of ADARB1
  • binds and isomerizes proteins phosphorylated on serine/threonine before a proline
  • may act directly via phosphorylated serine/threonine–proline motifs in CAST, or indirectly via other PIN1 substrates that control CAST
  • NR4A1 is a novel PIN1 substrate, and the mitogenic function of NR4A1 depends on PIN1-induced isomerization
  • role of MAP3K11 in PIN1 regulation via direct phosphorylation that regulates PIN1 localization and activation, leading to G2/M cell-cycle transition
  • binding of PIN1 to RUNX3 suppresses the transcriptional activity of RUNX3
  • FBXW7 protein destruction and tumor suppressor function are negatively regulated by the prolyl isomerase PIN1
  • PIN1 controls SMAD6 function
  • is a novel binding partner of NR4A1, NR4A2, NR4A3
  • is an important factor mediating CPEB1 destruction
  • PRDX1, regulator of aging, is a novel PIN1 binding protein, and PIN1 is involved in regulation of PRDX1 peroxidase activity
  • PIN1 interacts with SEPT9 upon mitotic phosphorylation at Thr-24 by CDK1
  • couples HIPK2 activation to its stabilization and is essential for DNA damage-induced apoptosis in cancer cells
  • regulates SIAH1–mediated HIPK2 ubiquitination and degradation
  • PIN1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NLGN2/GPHN interaction
  • ZNF148 reduces HDAC3 by degrading IkappaB in the presence of PIN1
  • TLR8, is involved in priming of human neutrophil ROS production by inducing the phosphorylation of NCF1 and MAPK14 and PIN1 is also involved in this process
  • PIN1 is present in the growth cone, interacts with MARCKS-Phosphorylated, and regulates its dephosphorylation
  • cell & other
    REGULATION
    induced by during neuron differentiation
    inhibited by juglone
    Phosphorylated by MAP3K11 (MLK3), a MAP3K family member, that phosphorylates PIN11 on a Ser138 site to increase its catalytic activity and nuclear translocation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    leading to beta-catenin accumulation in hepatocellular carcinoma
    tumoral     --over  
    promotes STAT3 transcriptional activity and target gene expression, as well as recruitment of transcription coactivator, EP300
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 1 
    may be a new target for diabetic therapy
    respiratorylung 
    PIN1 blockade can promote an antifibrogenic pulmonary milieu capable of reducing ECM deposition during pathological lung fibrosis
    cancer  
    therapeutics that target MAP3K11 or PIN1 could prove beneficial for a subset of cancers where the MAP3K11-PIN1 pathway is dysregulated
    cancer  
    PIN1 may be a promising drug target for anticancer therapy
    ANIMAL & CELL MODELS
  • Pin1(-/-) adult females mice display etinal hypoplasia and mammary gland impairment
  • Pin1 knockout in mice causes progressive age-dependent neuropathy characterized by motor and behavioral deficits, tau hyperphosphorylation, tau filament formation, and neuronal degeneration
  • Lack of Pin1 reduces p73 stability, hampering its accumulation upon genotoxic stress
  • oligodendrocyte apoptosis and cytochrome c release are elevated in Pin1-/- mice
  • Pin1-deficient mice also show widespread premature ageing phenotypes within just one generation, similar to those in telomerase-deficient mice after 4–5 consecutive generations
  • inhibition of Pin1 by its selective inhibitor juglone leads to up-regulation of cyclinD1, phospho-tau, and caspase 3, producing apoptosis in cultured rat hippocampal neurons
  • Pin1(-/-) mouse embryonic fibroblasts show mislocalization of ADAR2 in the cytoplasm and reduced editing at the GluR2 Q/R and R/G sites
  • Pin1(-/-) mouse embryonic fibroblasts (MEFs) show higher CDK10 expression than Pin1(+/+) MEFs