Details for: PIP5K1B

Gene ID: 8395

Symbol: PIP5K1B

Ensembl ID: ENSG00000107242

Description: phosphatidylinositol-4-phosphate 5-kinase type 1 beta

Associated with

Cells (max top 100)

(Cell Significance Index and respective Thresholds are uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: polychromatophilic erythroblast (CL0000550)
    Fold Change: 134.1089
    Cell Significance Index: -20.8600
  • Cell Name: hematopoietic oligopotent progenitor cell (CL0002032)
    Fold Change: 109.7210
    Cell Significance Index: -27.8300
  • Cell Name: mucosal type mast cell (CL0000485)
    Fold Change: 58.6082
    Cell Significance Index: -23.8100
  • Cell Name: ileal goblet cell (CL1000326)
    Fold Change: 42.5619
    Cell Significance Index: -28.5600
  • Cell Name: pigmented ciliary epithelial cell (CL0002303)
    Fold Change: 28.1747
    Cell Significance Index: 4095.5200
  • Cell Name: ciliated cell of the bronchus (CL0002332)
    Fold Change: 24.9701
    Cell Significance Index: -23.8400
  • Cell Name: orthochromatic erythroblast (CL0000552)
    Fold Change: 21.2416
    Cell Significance Index: -26.1900
  • Cell Name: CD8-positive, alpha-beta regulatory T cell (CL0000795)
    Fold Change: 8.5855
    Cell Significance Index: -26.3700
  • Cell Name: stromal cell of bone marrow (CL0010001)
    Fold Change: 7.2908
    Cell Significance Index: -28.7700
  • Cell Name: Purkinje cell (CL0000121)
    Fold Change: 6.4572
    Cell Significance Index: 141.3900
  • Cell Name: retinal progenitor cell (CL0002672)
    Fold Change: 6.0065
    Cell Significance Index: 337.0600
  • Cell Name: tuft cell of small intestine (CL0009080)
    Fold Change: 3.9998
    Cell Significance Index: 40.3500
  • Cell Name: cardiac muscle myoblast (CL0000513)
    Fold Change: 3.7135
    Cell Significance Index: 284.9700
  • Cell Name: non-pigmented ciliary epithelial cell (CL0002304)
    Fold Change: 3.2897
    Cell Significance Index: 2089.2800
  • Cell Name: microfold cell of epithelium of small intestine (CL1000353)
    Fold Change: 2.8142
    Cell Significance Index: 194.6200
  • Cell Name: cortical interneuron (CL0008031)
    Fold Change: 2.7209
    Cell Significance Index: 65.2600
  • Cell Name: epithelial cell of small intestine (CL0002254)
    Fold Change: 2.2770
    Cell Significance Index: 370.3400
  • Cell Name: hippocampal interneuron (CL1001569)
    Fold Change: 2.2362
    Cell Significance Index: 29.0000
  • Cell Name: obsolete caudal ganglionic eminence derived GABAergic cortical interneuron (CL4023070)
    Fold Change: 2.1887
    Cell Significance Index: 785.0400
  • Cell Name: enterocyte of epithelium of large intestine (CL0002071)
    Fold Change: 2.0231
    Cell Significance Index: 91.7000
  • Cell Name: forebrain neuroblast (CL1000042)
    Fold Change: 2.0159
    Cell Significance Index: 123.9100
  • Cell Name: leptomeningeal cell (CL0000708)
    Fold Change: 1.8215
    Cell Significance Index: 38.9400
  • Cell Name: paneth cell of epithelium of small intestine (CL1000343)
    Fold Change: 1.7226
    Cell Significance Index: 37.3200
  • Cell Name: serous secreting cell of bronchus submucosal gland (CL4033005)
    Fold Change: 1.5609
    Cell Significance Index: 15.6200
  • Cell Name: neoplastic cell (CL0001063)
    Fold Change: 1.5259
    Cell Significance Index: 302.8200
  • Cell Name: corneal endothelial cell (CL0000132)
    Fold Change: 1.3087
    Cell Significance Index: 19.9100
  • Cell Name: pigmented epithelial cell (CL0000529)
    Fold Change: 1.2570
    Cell Significance Index: 2366.8500
  • Cell Name: intestinal crypt stem cell of colon (CL0009043)
    Fold Change: 1.2065
    Cell Significance Index: 131.2400
  • Cell Name: GABAergic interneuron (CL0011005)
    Fold Change: 1.1317
    Cell Significance Index: 782.7400
  • Cell Name: L2/3-6 intratelencephalic projecting glutamatergic neuron (CL4023040)
    Fold Change: 1.0593
    Cell Significance Index: 212.4900
  • Cell Name: epithelial cell of stomach (CL0002178)
    Fold Change: 1.0366
    Cell Significance Index: 120.8000
  • Cell Name: enteroendocrine cell of small intestine (CL0009006)
    Fold Change: 1.0089
    Cell Significance Index: 25.2200
  • Cell Name: hippocampal granule cell (CL0001033)
    Fold Change: 0.9349
    Cell Significance Index: 62.8600
  • Cell Name: skeletal muscle fiber (CL0008002)
    Fold Change: 0.8378
    Cell Significance Index: 21.5400
  • Cell Name: colon goblet cell (CL0009039)
    Fold Change: 0.6028
    Cell Significance Index: 59.6300
  • Cell Name: enterocyte of epithelium of small intestine (CL1000334)
    Fold Change: 0.4144
    Cell Significance Index: 11.9400
  • Cell Name: cerebellar granule cell (CL0001031)
    Fold Change: 0.3029
    Cell Significance Index: 5.1900
  • Cell Name: enteroendocrine cell of colon (CL0009042)
    Fold Change: 0.2945
    Cell Significance Index: 56.0500
  • Cell Name: hippocampal pyramidal neuron (CL1001571)
    Fold Change: 0.2940
    Cell Significance Index: 8.3900
  • Cell Name: small intestine goblet cell (CL1000495)
    Fold Change: 0.2809
    Cell Significance Index: 9.8700
  • Cell Name: cardiac muscle cell (CL0000746)
    Fold Change: 0.2723
    Cell Significance Index: 4.0200
  • Cell Name: tuft cell of colon (CL0009041)
    Fold Change: 0.2337
    Cell Significance Index: 210.9900
  • Cell Name: acinar cell of salivary gland (CL0002623)
    Fold Change: 0.2295
    Cell Significance Index: 10.7000
  • Cell Name: cortical cell of adrenal gland (CL0002097)
    Fold Change: 0.1780
    Cell Significance Index: 4.7700
  • Cell Name: intermediate cell of urothelium (CL4030055)
    Fold Change: 0.1070
    Cell Significance Index: 19.3000
  • Cell Name: Mueller cell (CL0000636)
    Fold Change: 0.0968
    Cell Significance Index: 0.7500
  • Cell Name: cell in vitro (CL0001034)
    Fold Change: 0.0479
    Cell Significance Index: 26.1800
  • Cell Name: pancreatic acinar cell (CL0002064)
    Fold Change: 0.0470
    Cell Significance Index: 8.0300
  • Cell Name: ciliary muscle cell (CL1000443)
    Fold Change: 0.0422
    Cell Significance Index: 19.1500
  • Cell Name: basal cell of urothelium (CL1000486)
    Fold Change: 0.0383
    Cell Significance Index: 4.7200
  • Cell Name: secondary lens fiber (CL0002225)
    Fold Change: 0.0060
    Cell Significance Index: 8.1100
  • Cell Name: anterior lens cell (CL0002223)
    Fold Change: -0.0005
    Cell Significance Index: -1.0000
  • Cell Name: placental villous trophoblast (CL2000060)
    Fold Change: -0.0037
    Cell Significance Index: -0.1000
  • Cell Name: lens epithelial cell (CL0002224)
    Fold Change: -0.0066
    Cell Significance Index: -10.2100
  • Cell Name: pulmonary alveolar epithelial cell (CL0000322)
    Fold Change: -0.0074
    Cell Significance Index: -5.6100
  • Cell Name: pancreatic A cell (CL0000171)
    Fold Change: -0.0199
    Cell Significance Index: -14.7100
  • Cell Name: kidney loop of Henle cortical thick ascending limb epithelial cell (CL1001109)
    Fold Change: -0.0221
    Cell Significance Index: -16.2300
  • Cell Name: type B pancreatic cell (CL0000169)
    Fold Change: -0.0427
    Cell Significance Index: -24.0800
  • Cell Name: sst GABAergic cortical interneuron (CL4023017)
    Fold Change: -0.0440
    Cell Significance Index: -0.8700
  • Cell Name: hair follicular keratinocyte (CL2000092)
    Fold Change: -0.0478
    Cell Significance Index: -21.1200
  • Cell Name: pancreatic PP cell (CL0002275)
    Fold Change: -0.0486
    Cell Significance Index: -30.3700
  • Cell Name: stromal cell of ovary (CL0002132)
    Fold Change: -0.0491
    Cell Significance Index: -6.7400
  • Cell Name: intestinal crypt stem cell of small intestine (CL0009017)
    Fold Change: -0.0648
    Cell Significance Index: -1.3800
  • Cell Name: dopaminergic neuron (CL0000700)
    Fold Change: -0.0829
    Cell Significance Index: -23.8500
  • Cell Name: early T lineage precursor (CL0002425)
    Fold Change: -0.0882
    Cell Significance Index: -1.2800
  • Cell Name: medial ganglionic eminence derived interneuron (CL4023063)
    Fold Change: -0.0950
    Cell Significance Index: -1.3600
  • Cell Name: microcirculation associated smooth muscle cell (CL0008035)
    Fold Change: -0.1238
    Cell Significance Index: -1.0400
  • Cell Name: transit amplifying cell of colon (CL0009011)
    Fold Change: -0.1272
    Cell Significance Index: -4.0800
  • Cell Name: lamp5 GABAergic cortical interneuron (CL4023011)
    Fold Change: -0.1296
    Cell Significance Index: -2.8000
  • Cell Name: pancreatic D cell (CL0000173)
    Fold Change: -0.1343
    Cell Significance Index: -28.2800
  • Cell Name: intestinal epithelial cell (CL0002563)
    Fold Change: -0.1500
    Cell Significance Index: -1.5500
  • Cell Name: lactocyte (CL0002325)
    Fold Change: -0.1661
    Cell Significance Index: -21.4600
  • Cell Name: abnormal cell (CL0001061)
    Fold Change: -0.1692
    Cell Significance Index: -17.2900
  • Cell Name: pvalb GABAergic cortical interneuron (CL4023018)
    Fold Change: -0.1781
    Cell Significance Index: -3.7800
  • Cell Name: OFF midget ganglion cell (CL4033047)
    Fold Change: -0.1965
    Cell Significance Index: -2.4500
  • Cell Name: tonsil germinal center B cell (CL2000006)
    Fold Change: -0.1991
    Cell Significance Index: -23.4800
  • Cell Name: odontoblast (CL0000060)
    Fold Change: -0.2026
    Cell Significance Index: -25.9700
  • Cell Name: VIP GABAergic cortical interneuron (CL4023016)
    Fold Change: -0.2085
    Cell Significance Index: -4.1900
  • Cell Name: smooth muscle cell of sphincter of pupil (CL0002243)
    Fold Change: -0.2192
    Cell Significance Index: -22.8200
  • Cell Name: pancreatic ductal cell (CL0002079)
    Fold Change: -0.2266
    Cell Significance Index: -25.9600
  • Cell Name: paneth cell of colon (CL0009009)
    Fold Change: -0.2516
    Cell Significance Index: -3.7700
  • Cell Name: kidney loop of Henle descending limb epithelial cell (CL1001021)
    Fold Change: -0.3047
    Cell Significance Index: -24.1300
  • Cell Name: luminal adaptive secretory precursor cell of mammary gland (CL4033057)
    Fold Change: -0.3114
    Cell Significance Index: -14.6400
  • Cell Name: early pro-B cell (CL0002046)
    Fold Change: -0.3157
    Cell Significance Index: -20.3700
  • Cell Name: basal epithelial cell of tracheobronchial tree (CL0002329)
    Fold Change: -0.3478
    Cell Significance Index: -9.7200
  • Cell Name: progenitor cell of mammary luminal epithelium (CL0009116)
    Fold Change: -0.3486
    Cell Significance Index: -25.9800
  • Cell Name: intestinal tuft cell (CL0019032)
    Fold Change: -0.3866
    Cell Significance Index: -23.7000
  • Cell Name: glycinergic neuron (CL1001509)
    Fold Change: -0.3878
    Cell Significance Index: -20.3600
  • Cell Name: regular ventricular cardiac myocyte (CL0002131)
    Fold Change: -0.3962
    Cell Significance Index: -5.0800
  • Cell Name: lung endothelial cell (CL1001567)
    Fold Change: -0.3976
    Cell Significance Index: -20.7100
  • Cell Name: peg cell (CL4033014)
    Fold Change: -0.4008
    Cell Significance Index: -9.2600
  • Cell Name: bladder urothelial cell (CL1001428)
    Fold Change: -0.4227
    Cell Significance Index: -21.9600
  • Cell Name: ON midget ganglion cell (CL4033046)
    Fold Change: -0.4286
    Cell Significance Index: -5.4100
  • Cell Name: eye photoreceptor cell (CL0000287)
    Fold Change: -0.4335
    Cell Significance Index: -27.3200
  • Cell Name: L6b glutamatergic cortical neuron (CL4023038)
    Fold Change: -0.4594
    Cell Significance Index: -15.0400
  • Cell Name: inhibitory interneuron (CL0000498)
    Fold Change: -0.4842
    Cell Significance Index: -5.7900
  • Cell Name: indirect pathway medium spiny neuron (CL4023029)
    Fold Change: -0.4874
    Cell Significance Index: -21.5600
  • Cell Name: L5 extratelencephalic projecting glutamatergic cortical neuron (CL4023041)
    Fold Change: -0.5227
    Cell Significance Index: -18.3100
  • Cell Name: GABAergic neuron (CL0000617)
    Fold Change: -0.5325
    Cell Significance Index: -6.7200
  • Cell Name: transit amplifying cell of small intestine (CL0009012)
    Fold Change: -0.5659
    Cell Significance Index: -11.7400

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Other Information

**Key Characteristics:** 1. **Expression Pattern:** PIP5K1B is highly expressed in neurons, including interneurons and Purkinje cells, as well as in cardiac myocytes, epithelial cells, and certain types of immune cells, such as lymphocytes and macrophages. 2. **Enzyme Activity:** PIP5K1B catalyzes the phosphorylation of phosphatidylinositol-4-phosphate (PI-4-P) to produce phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2), which is a key intermediate in the PI signaling pathway. 3. **Phosphatidylinositol Metabolism:** PIP5K1B is involved in the metabolism of PI phosphates, which are essential for various cellular processes, including cell signaling, metabolism, and cell cycle regulation. **Pathways and Functions:** 1. **PI Signaling Pathway:** PIP5K1B is involved in the PI signaling pathway, which is a critical regulator of various cellular processes, including cell growth, differentiation, and survival. 2. **Negative Regulation of PI3K/Akt Signaling:** PIP5K1B has been shown to negatively regulate the PI3K/Akt signaling pathway, which is involved in cell survival, metabolism, and inflammation. 3. **Regulation of Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling:** PIP5K1B regulates the PI3K/Akt signaling pathway by phosphorylating and activating PI3K, which is essential for cell survival and metabolism. 4. **Metabolism of Lipids:** PIP5K1B is involved in the metabolism of lipids, including PI phosphates, which are essential for various cellular processes, including cell signaling and metabolism. **Clinical Significance:** 1. **Immunological Disorders:** PIP5K1B has been implicated in various immunological disorders, including autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. 2. **Cancer:** PIP5K1B has been shown to be overexpressed in certain types of cancer, including breast, lung, and colon cancer, and has been implicated in tumor growth and metastasis. 3. **Neurological Disorders:** PIP5K1B has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). 4. **Cardiovascular Diseases:** PIP5K1B has been shown to be involved in the development of cardiovascular diseases, including atherosclerosis and hypertension. In conclusion, PIP5K1B is a critical enzyme involved in the biosynthesis of PI phosphates, which play significant roles in various cellular processes, including signaling, metabolism, and cell cycle regulation. Its dysregulation has been implicated in various immunological disorders, including autoimmune diseases, inflammatory diseases, and cancer. Further research is needed to fully understand the role of PIP5K1B in human disease and to develop therapeutic strategies to target this enzyme in the treatment of various diseases.

Genular Protein ID: 2670566407

Symbol: PI51B_HUMAN

Name: N/A

UniProtKB Accession Codes:

O14986 A8K9L9 B4DIG7 P78518 P78519 Q5T5K6 Q5T5K8 Q5T5K9 Q5VZ00 Q7KYT5 Q8NHQ5 Q92749

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CTD 1 ChEBI 35 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 21 Ensembl 3 ExpressionAtlas 1 GO 12 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 3 RefSeq 13 Rhea 14 SABIO-RK 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8841185

Title: The Friedreich's ataxia gene encodes a novel phosphatidylinositol-4-phosphate 5-kinase.

PubMed ID: 8841185

DOI: 10.1038/ng1096-157

PubMed ID: 9177790

Title: Exon-intron structure of a 2.7-kb transcript of the STM7 gene with phosphatidylinositol-4-phosphate 5-kinase activity.

PubMed ID: 9177790

DOI: 10.1006/geno.1997.4726

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8955136

Title: Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family.

PubMed ID: 8955136

DOI: 10.1074/jbc.271.51.32937

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 540
  • Mass: 61036
  • Checksum: 7A683794A39A20B6
  • Sequence:
    • MSSAAENGEA APGKQNEEKT YKKTASSAIK GAIQLGIGYT VGNLTSKPER DVLMQDFYVV 
ESVFLPSEGS NLTPAHHYPD FRFKTYAPLA FRYFRELFGI KPDDYLYSIC SEPLIELSNP 
GASGSLFFVT SDDEFIIKTV QHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCMQSGG 
INIRIVVMNN VLPRSMRMHF TYDLKGSTYK RRASRKEREK SNPTFKDLDF LQDMHEGLYF 
DTETYNALMK TLQRDCRVLE SFKIMDYSLL LGIHFLDHSL KEKEEETPQN VPDAKRTGMQ 
KVLYSTAMES IQGPGKSGDG IITENPDTMG GIPAKSHRGE KLLLFMGIID ILQSYRLMKK 
LEHSWKALVY DGDTVSVHRP SFYADRFLKF MNSRVFKKIQ ALKASPSKKR CNSIAALKAT 
SQEIVSSISQ EWKDEKRDLL TEGQSFSSLD EEALGSRHRP DLVPSTPSLF EAASLATTIS 
SSSLYVNEHY PHDRPTLYSN SKGLPSSSTF TLEEGTIYLT AEPNTLEVQD DNASVLDVYL

Genular Protein ID: 629072726

Symbol: Q7KYT6_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q7KYT6

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 Gene3D 1 InterPro 3 KEGG 1 NCBI Taxonomy 1 PANTHER 2 PROSITE 2 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 1 RefSeq 1 SMART 1 SUPFAM 1

Citations:

PubMed ID: 8955136

Title: Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family.

PubMed ID: 8955136

DOI: 10.1074/jbc.271.51.32937

Sequence Information:

  • Length: 334
  • Mass: 37787
  • Checksum: 2B36A6C0590C3F8A
  • Sequence:
    • STYKRRASRK EREKSNPTFK DLDFLQDMHE GLYFDTETYN ALMKTLQRDC RVLESFKIMD 
YSLLLGIHFL DHSLKEKEEE TPQNVPDAKR TGMQKVLYST AMESIQGPGK SGDGIITENP 
DTMGGIPAKS HRGEKLLLFM GIIDILQSYR LMKKLEHSWK ALVYDGDTVS VHRPSFYADR 
FLKFMNSRVF KKIQALKASP SKKRCNSIAA LKATSQEIVS SISQEWKDEK RDLLTEGQSF 
SSLDEEALGS RHRPDLVPST PSLFEAASLA TTISSSSLYV NEHYPHDRPT LYSNSKGLPS 
SSTFTLEEGT IYLTAEPNTL EVQDDNASVL DVYL

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. You can zoom in with the mouse wheel for a closer view, and the text will adjust automatically if necessary. For the full schema, download it here.