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GPR35 Gene

protein-coding   GIFtS: 56
GCID: GC02P241588

G Protein-Coupled Receptor 35

  See GPR35-related disease
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
G Protein-Coupled Receptor 351 2
Kynurenic Acid Receptor2 3
KYNA Receptor2 3
G-Protein Coupled Receptor 352

External Ids:    HGNC: 44921   Entrez Gene: 28592   Ensembl: ENSG000001786237   OMIM: 6026465   UniProtKB: Q9HC973   

Export aliases for GPR35 gene to outside databases

Previous GC identifers: GC02M239906 GC02M240750 GC02P241889 GC02P241286 GC02P241215 GC02P233327


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for GPR35 Gene:
GPR35 (G protein-coupled receptor 35) is a protein-coding gene. Diseases associated with GPR35 include primary sclerosing cholangitis. GO annotations related to this gene include G-protein coupled receptor activity. An important paralog of this gene is GPR18.

UniProtKB/Swiss-Prot: GPR35_HUMAN, Q9HC97
Function: Acts as a receptor for kynurenic acid, an intermediate in the tryptophan metabolic pathway. The activity
of this receptor is mediated by G-proteins that elicit calcium mobilization and inositol phosphate production
through G(qi/o) proteins

Gene Wiki entry for GPR35 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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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NC_018913.2  NT_005403.18  
Regulatory elements:
   Regulatory transcription factor binding sites in the GPR35 gene promoter:
         ER-alpha   USF1   p300   STAT5A   MIF-1   Max   USF-1   HOXA5   ATF   c-Myc   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for GPR35

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GPR35


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

Entrez Gene cytogenetic band: 2q37.3   Ensembl cytogenetic band:  2q37.3   HGNC cytogenetic band: 2q37.3

GPR35 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GPR35 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02P241588:  view genomic region     (about GC identifiers)

Start:
241,544,825 bp from pter      End:
241,570,676 bp from pter
Size:
25,852 bases      Orientation:
plus 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., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: GPR35_HUMAN, Q9HC97 (See protein sequence)
Recommended Name: G-protein coupled receptor 35  
Size: 309 amino acids; 34072 Da
Secondary accessions: J3KR30 O43495 Q17R58 Q4VBN5 Q4ZFV2 Q6FHI8 Q86UH4
Alternative splicing: 2 isoforms:  Q9HC97-1   Q9HC97-2   (No experimental confirmation available. Ref.4 (AK172786) sequence is in conflict in position: 13:R->H)

Explore the universe of human proteins at neXtProt for GPR35: NX_Q9HC97

Explore proteomics data for GPR35 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn2

  • See GPR35 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001182310.1  NP_001182311.1  NP_005292.2  

    ENSEMBL proteins: 
     ENSP00000322731   ENSP00000385140   ENSP00000384263   ENSP00000415890   ENSP00000411788  

    GPR35 Human Recombinant Protein Products:

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    Cloud-Clone Corp. Proteins for GPR35

     
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    antibodies-online peptides for GPR35

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    antibodies-online antibodies for GPR35 (47 products) 

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    antibodies-online kits for GPR35 (5 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    GPCRAO: GPCR / Class A : Orphans

    IUPHAR Guide to PHARMACOLOGY protein family classification: GPR35
    Class A Orphans

    2 InterPro protein domains:
     IPR017452 GPCR_Rhodpsn_7TM
     IPR000276 GPCR_Rhodpsn

    Graphical View of Domain Structure for InterPro Entry Q9HC97

    ProtoNet protein and cluster: Q9HC97

    UniProtKB/Swiss-Prot: GPR35_HUMAN, Q9HC97
    Similarity: Belongs to the G-protein coupled receptor 1 family


    Find genes that share domains with GPR35           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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: GPR35_HUMAN, Q9HC97
    Function: Acts as a receptor for kynurenic acid, an intermediate in the tryptophan metabolic pathway. The activity
    of this receptor is mediated by G-proteins that elicit calcium mobilization and inositol phosphate production
    through G(qi/o) proteins

         Genatlas biochemistry entry for GPR35:
    G protein coupled receptor 35,expressed in heart,spleen,liver,lung,ovary kidney

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004930G-protein coupled receptor activity IDA16754668
         
    Find genes that share ontologies with GPR35           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for GPR35:
     Increased HPV18 LCR reporter a 

         1 MGI phenotypic allele for Gpr35 (no phenotypes)

    Find genes that share phenotypes with GPR35           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Gpr35tm1Lex for GPR35

       genOway: Develop your customized and physiologically relevant rodent model for GPR35

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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
    GPR35_HUMAN, Q9HC97: Cell membrane; Multi-pass membrane protein. Note=Internalized to the cytoplasm after
    exposure to kynurenic acid
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005887integral component of plasma membrane IDA16754668
    GO:0016021integral component of membrane ----

    Find genes that share ontologies with GPR35           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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    SuperPaths for GPR35 About    
    See pathways by source

    SuperPathContained pathways About
    1Peptide ligand-binding receptors
    GPCRs, Class A Rhodopsin-like0.43
    Neuroactive ligand-receptor interaction0.36


    Find genes that share SuperPaths with GPR35           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 BioSystems Pathway for GPR35
        GPCRs, Class A Rhodopsin-like



    1 Kegg Pathway  (Kegg details for GPR35):
        Neuroactive ligand-receptor interaction

        Pathway & Disease-focused RT2 Profiler PCR Array including GPR35: 
              G Protein Coupled Receptors 384HT in human mouse rat

    Interactions:

        Search GeneGlobe Interaction Network for GPR35

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0007186G-protein coupled receptor signaling pathway IDA16754668

    Find genes that share ontologies with GPR35           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 GPR35

    6 IUPHAR Ligands for GPR35 (GPR35)    About this table
    LigandTypeActionAffinityPubmed IDs
    2-oleoyl-LPA
    AgonistAgonist7.3 - 7.5220361937
    pamoic acid
    AgonistAgonist7.2920919992
    zaprinast
    AgonistAgonist6.116934253
    furosemide
    AgonistAgonist5.21 - 5.6322236570
    bumetanide
    AgonistAgonist5 - 5.5422236570
    kynurenic acid
    AgonistAgonist3.9 - 4.4123396314 16754668



    (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 GPR35 gene (3 alternative transcripts): 
    NM_001195381.1  NM_001195382.1  NM_005301.3  

    Unigene Cluster for GPR35:

    G protein-coupled receptor 35
    Hs.112218  [show with all ESTs]
    Unigene Representative Sequence: NM_001195381
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000319838(uc010fzi.2 uc010fzh.2 uc021vze.1) ENST00000403859
    ENST00000407714 ENST00000438013 ENST00000430267(uc002vzs.2)
    miRNA
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      QuantiFast Probe-based Assays in human, mouse, rat GPR35
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    Additional mRNA sequence: 

    AF089087.1 AK172786.1 AK290256.1 AK314002.1 BC095500.1 BC117453.1 BC117455.1 CR541765.1 

    4 DOTS entries:

    DT.40120882  DT.121644089  DT.100680822  DT.91654058 

    Selected AceView cDNA sequences (see all 153):

    BQ057475 NM_023089 CD722325 BM748220 BM927087 BM477401 BG333889 AF089095 
    BU186381 BQ187478 BM772079 AA489024 BQ947982 C00612 AI739542 BU527319 
    BM786145 AI339652 BM784104 BM742098 AA515711 CB127286 AI652032 AF089090 

    GeneLoc Exon Structure


    (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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    GPR35 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCCAAGGAGT
    GPR35 Expression
    About this image


    GPR35 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Blood (Hematopoietic System)
             Monocytes Peripheral Blood
     
     Colon (Gastrointestinal Tract)
    GPR35 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    GPR35 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.112218

    UniProtKB/Swiss-Prot: GPR35_HUMAN, Q9HC97
    Tissue specificity: Predominantly expressed in immune and gastrointestinal tissues

        Pathway & Disease-focused RT2 Profiler PCR Array including GPR35: 
              G Protein Coupled Receptors 384HT in human mouse rat

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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 chordates.

    Orthologs for GPR35 gene from Selected species (see all 10)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Gpr351 , 5 G protein-coupled receptor 351, 5 78.18(n)1
    74.01(a)1
      1 (46.65 cM)5
    640951  NM_022320.41  NP_071715.31 
     929731195 
    chicken
    (Gallus gallus)
    Aves GPR351 G protein-coupled receptor 35 51.79(n)
    40.38(a)
      424833  XM_004937026.1  XP_004937083.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    --
    36(a)
    30(a)
    1 ↔ many
    1 ↔ many
    3(28299368-28300288)
    3(28306514-28308990)
    zebrafish
    (Danio rerio)
    Actinopterygii GPR35 (1 of 3)6
    GPR35 (2 of 3)6
    (see all 3)
    G protein-coupled receptor 35
    (see all 3)
    28(a)
    27(a)
    (see all 3)
    1 ↔ many
    1 ↔ many
    (see all 3)
    22(3236776-3244103) ENSDARG00000074633
    2(49936705-49937559) ENSDARG00000075877


    ENSEMBL Gene Tree for GPR35 (if available)
    TreeFam Gene Tree for GPR35 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for GPR35 gene
    GPR182  GPR552  
    9 SIMAP similar genes for GPR35 using alignment to 1 protein entry:     GPR35_HUMAN:
    KPG_007    LPAR4    LPAR6    HCAR3    CYSLTR2    HCAR2
    KPG_011    GPR55    HCAR1

    Find genes that share paralogs with GPR35           About GenesLikeMe



    (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 GPR35 (see all 832)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs557320951,2
    C--241542923(+) ACCTGC/TGCCTT 2 -- us2k12Minor allele frequency- T:0.19NA 122
    rs1831989251,2
    --241542990(+) GCCCCC/TAGCAG 2 -- us2k10--------
    rs758256161,2
    C,F--241543110(+) GTCCTC/TATTGC 2 -- us2k13Minor allele frequency- T:0.12NA WA 240
    rs1873699841,2
    --241543217(+) TTGGGC/TGCAAG 2 -- us2k10--------
    rs1158114231,2
    C,F--241543310(+) TGAAAC/TGCCTG 2 -- us2k11Minor allele frequency- T:0.06WA 118
    rs75614491,2
    C,F,A,H--241543432(+) GGGCTC/ACCGCC 2 -- us2k110Minor allele frequency- A:0.13NA WA CSA EA 372
    rs1153784391,2
    F--241543435(+) CTACCG/ACCCCG 2 -- us2k11Minor allele frequency- A:0.01WA 118
    rs1912306531,2
    --241543527(+) ACACCC/TGCGGG 2 -- us2k10--------
    rs1148598761,2
    F--241543529(+) ACCTGC/TGGGGA 2 -- us2k11Minor allele frequency- T:0.01WA 118
    rs1831459871,2
    --241543554(+) CTGGCA/GGCTTG 2 -- us2k10--------

    HapMap Linkage Disequilibrium report for GPR35 (241544825 - 241570676 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for GPR35 (see all 25):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2721937CNV Deletion23290073
    esv2721938CNV Deletion23290073
    esv2721939CNV Deletion23290073
    nsv820464CNV Duplication20802225
    esv1170354CNV Insertion17803354
    nsv3240CNV Insertion18451855
    esv1425277CNV Insertion17803354
    nsv876116CNV Loss21882294
    esv29214CNV Loss19812545
    nsv876157CNV Loss21882294

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing GPR35
    DNA2.0 Custom Variant and Variant Library Synthesis for GPR35

    (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: 602646    OMIM disorders: --

    1 disease for GPR35:    
    About MalaCards
    primary sclerosing cholangitis


    Find genes that share disorders with GPR35           About GenesLikeMe

    Genetic Association Database (GAD): GPR35
    Human Genome Epidemiology (HuGE) Navigator: GPR35 (1 document)

    Export disorders for GPR35 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 GPR35 gene, integrated from 10 sources (see all 21):
    (articles sorted by number of sources associating them with GPR35)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Discovery of three novel G-protein-coupled receptor genes. (PubMed id 9479505)1, 2, 3 O'Dowd B.F.... George S.R. (Genomics 1998)
    2. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. (PubMed id 21297633)1, 4 Anderson C.A....Rioux J.D. (Nat. Genet. 2011)
    3. Application of machine learning algorithms to predict coronary artery calcification with a sibship-based design. (PubMed id 18271057)1, 4 Sun Y.V....Kardia S.L. (Genet. Epidemiol. 2008)
    4. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. (PubMed id 16754668)1, 2 Wang J....Ling L. (J. Biol. Chem. 2006)
    5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    6. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. (PubMed id 11017071)1, 2 Horikawa Y....Bell G.I. (Nat. Genet. 2000)
    7. GPR55 and GPR35 and their relationship to cannabinoid and lysophospholipid receptors. (PubMed id 22820167)1 Zhao P. and Abood M.E. (Life Sci. 2013)
    8. Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4. (PubMed id 22821403)1 Ellinghaus D....Karlsen T.H. (Hepatology 2013)
    9. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. (PubMed id 23128233)1 Jostins L....Cho J.H. (Nature 2012)
    10. Expression of functional GPR35 in human iNKT cells. (PubMed id 20599711)1 Fallarini S....Lombardi G. (Biochem. Biophys. Res. Commun. 2010)

    (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: 2859 HGNC: 4492 AceView: GPR35andCAPN10 Ensembl:ENSG00000178623 euGenes: HUgn2859
    ECgene: GPR35 Kegg: 2859 H-InvDB: GPR35

    (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 GPR35 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for GPR35 gene:
    Search GeneIP for patents involving GPR35

    GeneCards and IP:
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