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TIPIN Gene

protein-coding   GIFtS: 50
GCID: GC15M066629

TIMELESS Interacting Protein

  Search for TIPIN
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
TIMELESS Interacting Protein1 2
CSM3 Homolog (S. Cerevisiae)1
CSM3 Homolog2
TIMELESS-Interacting Protein2

External Ids:    HGNC: 307501   Entrez Gene: 549622   Ensembl: ENSG000000751317   OMIM: 6107165   UniProtKB: Q9BVW53   

Export aliases for TIPIN gene to outside databases

Previous GC identifers: GC15M064417 GC15M043465


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TIPIN Gene:
The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA
replication. It binds TIM and aids in protecting cells against DNA damage and stress. Two pseudogenes and two
transcript variants encoding different isoforms have been found for this gene. (provided by RefSeq, Feb 2014)

GeneCards Summary for TIPIN Gene:
TIPIN (TIMELESS interacting protein) is a protein-coding gene.

UniProtKB/Swiss-Prot: TIPIN_HUMAN, Q9BVW5
Function: Required for normal progression of S-phase. Important for cell survival after DNA damage or replication
stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by
hydroxyurea or ultraviolet light

Gene Wiki entry for TIPIN Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Regulatory transcription factor binding sites in the TIPIN gene promoter:
         POU2F2 (Oct-2.1)   Oct-B1   oct-B3   oct-B2   POU2F2   POU2F2C   POU2F1   POU2F1a   STAT3   POU2F2B   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTIPIN promoter sequence
   Search Chromatin IP Primers for TIPIN

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TIPIN


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 15q22.31   Ensembl cytogenetic band:  15q22.31   HGNC cytogenetic band: 15q22.31

TIPIN Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TIPIN gene location

GeneLoc information about chromosome 15         GeneLoc Exon Structure

GeneLoc location for GC15M066629:  view genomic region     (about GC identifiers)

Start:
66,628,544 bp from pter      End:
66,679,084 bp from pter
Size:
50,541 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: TIPIN_HUMAN, Q9BVW5 (See protein sequence)
Recommended Name: TIMELESS-interacting protein  
Size: 301 amino acids; 34555 Da
Subunit: Interacts with TIMELESS, which impairs TIMELESS self-association. Interacts with RPA2, PRDX2, MCM6 and
MCM7
Secondary accessions: B2CW64 Q9NWZ6

Explore the universe of human proteins at neXtProt for TIPIN: NX_Q9BVW5

Explore proteomics data for TIPIN at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys101, Lys117
  • Modification sites at PhosphoSitePlus

  • See TIPIN Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001276915.1  NP_060328.2  

    ENSEMBL proteins: 
     ENSP00000261881   ENSP00000455656   ENSP00000457406   ENSP00000457172   ENSP00000458117  
     ENSP00000356682  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    1 InterPro protein domain:
     IPR012923 Swi3

    Graphical View of Domain Structure for InterPro Entry Q9BVW5

    ProtoNet protein and cluster: Q9BVW5

    1 Blocks protein domain: IPB012923 Replication fork protection component Swi3

    UniProtKB/Swiss-Prot: TIPIN_HUMAN, Q9BVW5
    Similarity: Belongs to the CSM3 family


    Find genes that share domains with TIPIN           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TIPIN_HUMAN, Q9BVW5
    Function: Required for normal progression of S-phase. Important for cell survival after DNA damage or replication
    stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by
    hydroxyurea or ultraviolet light

         Gene Ontology (GO): 1 molecular function term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding IPI17102137
         
    Find genes that share ontologies with TIPIN           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for TIPIN:
     Decreased influenza A/WSN/33 r  Increased G2M DNA content  Increased gamma-H2AX phosphory 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TIPIN
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    miRTarBase miRNAs that target TIPIN:
    hsa-mir-484 (MIRT041905)

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    3 qRT-PCR Assays for microRNAs that regulate TIPIN:
    hsa-miR-3606 hsa-miR-4311 hsa-miR-570
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    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TIPIN_HUMAN, Q9BVW5: Cytoplasm. Nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    golgi apparatus4
    cytosol3
    extracellular2

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000790nuclear chromatin IDA17102137
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005794Golgi apparatus IDA--

    Find genes that share ontologies with TIPIN           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for TIPIN
    Interactions:

        GeneGlobe Interaction Network for TIPIN

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TIPIN (Q9BVW53 ENSP000002618814) via UniProtKB, MINT, STRING, and/or I2D (see all 153)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TIMELESSQ9UNS13, ENSP000002292014I2D: score=4 STRING: ENSP00000229201
    TCEAL1Q151703, ENSP000003617074I2D: score=2 STRING: ENSP00000361707
    RPA1P276943, ENSP000002547194I2D: score=1 STRING: ENSP00000254719
    ATRIPENSP000003230994STRING: ENSP00000323099
    CLSPNENSP000003129954STRING: ENSP00000312995
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000076DNA replication checkpoint IMP17102137
    GO:0000077DNA damage checkpoint ----
    GO:0006974cellular response to DNA damage stimulus ----
    GO:0007049cell cycle ----
    GO:0007067mitosis IEA--

    Find genes that share ontologies with TIPIN           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for TIPIN



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TIPIN gene (2 alternative transcripts): 
    NM_001289986.1  NM_017858.2  

    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000261881(uc010ujn.1 uc002apr.2 uc010ujo.1) ENST00000566524
    ENST00000562124 ENST00000568216 ENST00000570251 ENST00000561773 ENST00000367709

    miRNA
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    3 qRT-PCR Assays for microRNAs that regulate TIPIN:
    hsa-miR-3606 hsa-miR-4311 hsa-miR-570
    SwitchGear 3'UTR luciferase reporter plasmidTIPIN 3' UTR sequence
    Inhib. RNA
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      QuantiTect SYBR Green Assays in human, mouse, rat TIPIN
      QuantiFast Probe-based Assays in human, mouse, rat TIPIN

    Selected AceView cDNA sequences (see all 81):

    AI570081 AW340261 BE671788 BG028657 AA604732 BC000870 AI990358 AA604672 
    BM023124 BQ425446 BG613556 AA122394 AA122393 BQ067288 BE786170 BG500322 
    BG403764 BG527391 BU596053 BQ424304 BM023387 BP871734 BF665563 NM_017858 

    GeneLoc Exon Structure

    2 Alternative Splicing Database (ASD) splice patterns (SP) for TIPIN    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b
    SP1:                                                      
    SP2:                    -                                 


    ECgene alternative splicing isoforms for TIPIN

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TIPIN expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAATGATGCT
    TIPIN Expression
    About this image

    TIPIN Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TIPIN Protein Expression
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    In Situ
    Assay Products:
     

     
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for TIPIN gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tipin1 , 5 timeless interacting protein1, 5 82(n)1
    77.17(a)1
      9 (34.60 cM)5
    661311  NM_025372.31  NP_079648.11 
     642816075 
    chicken
    (Gallus gallus)
    Aves TIPIN1 TIMELESS interacting protein 69.62(n)
    64.16(a)
      415548  NM_001012690.1  NP_001012708.1 
    lizard
    (Anolis carolinensis)
    Reptilia TIPIN6
    TIMELESS interacting protein
    56(a)
    1 ↔ 1
    GL343671.1(1378-8364)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.82142 Xenopus laevis transcribed sequence with weak similarity more 75.34(n)    48018815 
    zebrafish
    (Danio rerio)
    Actinopterygii AL714846.12   -- 76.52(n)    AL714846.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG103366
    --
    19(a)
    1 ↔ 1
    2L(18689581-18690906)


    ENSEMBL Gene Tree for TIPIN (if available)
    TreeFam Gene Tree for TIPIN (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TIPIN gene

    Find genes that share paralogs with TIPIN           About GenesLikeMe


    2 Pseudogenes.org Pseudogenes for TIPIN
    PGOHUM00000248900 PGOHUM00000241325


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TIPIN (see all 476)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 15 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1818363361,2
    --46685832(+) AAAAAC/TTGACA 1 -- ds50010--------
    rs626256771,2
    C,F--46685885(-) ACCGCG/ACCCAG 1 -- ds50015Minor allele frequency- A:0.01NS 178
    rs96726321,2
    C--46685886(+) tgggcA/Gcggtg 1 -- ds50010--------
    rs626256761,2
    C,F--46685968(-) TGGCCA/-GGCTG 1 -- ds50015Minor allele frequency- -:0.02NS 180
    rs356451311,2
    C,F--46686021(+) CAAGCG/ATGGTG 1 -- ds50018Minor allele frequency- A:0.05NS NA 186
    rs1382061321,2
    --46686063(+) GCTAAA/GGCAGG 1 -- ds50010--------
    rs1869843461,2
    --46686093(+) AGGCAA/GAGGTT 1 -- ds50010--------
    rs116379491,2
    C,F,H--46686142(+) ccaacA/Ggagtg 1 -- ds50018Minor allele frequency- G:0.15NS NA CSA 186
    rs1914195781,2
    C--46686148(+) GAGTGA/GGACTC 1 -- ds50010--------
    rs1836415871,2
    --46686263(+) AGAAAC/GAAAAC 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for TIPIN (66628544 - 66679084 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 9 variations for TIPIN:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2590993CNV Deletion19546169
    esv5372CNV Deletion18987735
    esv2749790CNV Deletion23290073
    esv1418932CNV Deletion17803354
    esv2223439CNV Deletion18987734
    esv1006740CNV Deletion20482838
    esv2552740CNV Deletion19546169
    esv6981CNV Loss19470904
    nsv833045CNV Gain17160897

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 610716    OMIM disorders: --


    Find genes that share disorders with TIPIN           About GenesLikeMe

    Genetic Association Database (GAD): TIPIN
    Human Genome Epidemiology (HuGE) Navigator: TIPIN (1 document)

    Export disorders for TIPIN gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TIPIN gene, integrated from 10 sources (see all 30):
    (articles sorted by number of sources associating them with TIPIN)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Human Tim/Timeless-interacting protein, Tipin, is required for efficient progression of S phase and DNA replication checkpoint. (PubMed id 17102137)1, 2, 3, 9 Yoshizawa-Sugata N. and Masai H. (J. Biol. Chem. 2007)
    2. Tipin, a novel timeless-interacting protein, is developmentally co- expressed with timeless and disrupts its self-association. (PubMed id 12875843)1, 2, 3 Gotter A.L. (J. Mol. Biol. 2003)
    3. Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function. (PubMed id 17116885)1, 2, 9 Chou D.M. and Elledge S.J. (Proc. Natl. Acad. Sci. U.S.A. 2006)
    4. The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement. (PubMed id 17296725)1, 2, 9 Uensal-Kacmaz K.... Kaufmann W.K. (Mol. Cell. Biol. 2007)
    5. Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance. (PubMed id 20174623)1, 4 Utge S.J....Paunio T. (PLoS ONE 2010)
    6. Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors. (PubMed id 17141802)1, 2 Gotter A.L.... Emanuel B.S. (J. Mol. Biol. 2007)
    7. Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion. (PubMed id 20124417)1, 9 Leman A.R....Noguchi E. (J. Cell. Sci. 2010)
    8. Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress. (PubMed id 20233725)1, 9 Kemp M.G....Unsal-KaAsmaz K. (J. Biol. Chem. 2010)
    9. Human Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases. (PubMed id 23359676)1 Cho W.H....Lee J.K. (Proc. Natl. Acad. Sci. U.S.A. 2013)
    10. The human Tim-Tipin complex interacts directly with DNA polymerase epsilon and stimulates its synthetic activity. (PubMed id 23511638)1 Aria V....Pisani F.M. (J. Biol. Chem. 2013)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 54962 HGNC: 30750 AceView: FLJ20516 Ensembl:ENSG00000075131 euGenes: HUgn54962
    ECgene: TIPIN H-InvDB: TIPIN

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for TIPIN Pharmacogenomics, SNPs, Pathways
    NIEHS-SNPshttp://egp.gs.washington.edu/data/tipin/

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    Patent Information for TIPIN gene:
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