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Entry version 183 (22 Apr 2020)
Sequence version 3 (02 Mar 2010)
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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 2

Gene

ENPP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:15769751, PubMed:26371182, PubMed:27754931, PubMed:14500380, PubMed:12354767,). Major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:27754931, PubMed:14500380). Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, PubMed:12176993). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor (PubMed:1733949, PubMed:11559573). Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252).1 Publication10 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Protein has several cofactor binding sites:

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA (Probable).3 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=0.5 mM for 16:0-LPC (at pH 8.5)2 Publications
  2. KM=5.5 mM for pNP-TMP (at pH 8.5)2 Publications
  3. KM=11.3 mM for pNppp (isoform 1)2 Publications
  4. KM=5.7 mM for pNppp (isoform 2)2 Publications
  5. KM=19.8 mM for pNppp (isoform 3)2 Publications
  6. KM=96 µM for sn-1 lyso-PAF1 Publication
  7. KM=51 µM for sn-2 lyso-PAF1 Publication
  8. KM=0.10 mM for lysophosphatidylcholine1 Publication
  9. KM=0.23 mM for sphingosylphosphorylcholine1 Publication
  1. Vmax=1.9 nmol/min/µg enzyme with pNppp as substrate (isoform 1)2 Publications
  2. Vmax=0.67 nmol/min/µg enzyme with pNppp as substrate (isoform 2)2 Publications
  3. Vmax=1.6 nmol/min/µg enzyme with pNppp as substrate (isoform 3)2 Publications
  4. Vmax=0.11 µmol/min/mg enzyme with sn-1 lyso-PAF as substrate1 Publication
  5. Vmax=0.025 µmol/min/mg enzyme with sn-2 lyso-PAF as substrate1 Publication
  6. Vmax=11.8 nmol/min/µg enzyme with lysophosphatidylcholine as substrate1 Publication
  7. Vmax=6.1 nmol/min/µg enzyme with sphingosylphosphorylcholine as substrate1 Publication

pH dependencei

Optimum pH is 9.0 (isoform 1), 8.0 (isoform 3). Isoform 1 is less sensitive to pH. Isoform 1, isoform 2 and isoform 3 all retain some activity at pH 9.5.2 Publications

Temperature dependencei

Isoform 1 and isoform 3 are active from 45 to 60 degrees Celsius.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi172Zinc 1; catalyticCombined sources2 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei210NucleophileBy similarity1
Metal bindingi210Zinc 1; catalyticCombined sources2 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei231SubstrateCombined sources1 Publication1
Binding sitei307SubstrateBy similarity1
Metal bindingi312Zinc 2; catalyticCombined sources1 Publication1
Metal bindingi316Zinc 2; via tele nitrogen; catalyticCombined sources1 Publication1
Metal bindingi359Zinc 1; catalyticCombined sources2 Publications1
Metal bindingi360Zinc 1; via tele nitrogen; catalyticCombined sources2 Publications1
Metal bindingi475Zinc 2; via tele nitrogen; catalyticCombined sources1 Publication1
Metal bindingi740CalciumCombined sources2 Publications1
Metal bindingi742CalciumCombined sources2 Publications1
Metal bindingi744CalciumCombined sources1 Publication1
Metal bindingi746Calcium; via carbonyl oxygenCombined sources2 Publications1
Metal bindingi748CalciumCombined sources2 Publications1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei853Essential for catalytic activityBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase
Biological processChemotaxis, Lipid degradation, Lipid metabolism
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

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BioCyci
MetaCyc:HS06258-MONOMER

BRENDA Comprehensive Enzyme Information System

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BRENDAi
3.1.4.39 2681

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-199220 Vitamin B5 (pantothenate) metabolism

SABIO-RK: Biochemical Reaction Kinetics Database

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SABIO-RKi
Q13822

Chemistry databases

SwissLipids knowledge resource for lipid biology

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SwissLipidsi
SLP:000000393
SLP:000000641 [Q13822-1]

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (EC:3.1.4.395 Publications)
Short name:
E-NPP 2
Alternative name(s):
Autotaxin2 Publications
Extracellular lysophospholipase D
Short name:
LysoPLD1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ENPP2
Synonyms:ATX2 Publications, PDNP21 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 8

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:3357 ENPP2

Online Mendelian Inheritance in Man (OMIM)

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MIMi
601060 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q13822

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi170S → E: Reduces lysophospholipase activity by about 70%. 1
Mutagenesisi210T → A: Loss of lysophospholipase activity and ability to hydrolyze sphingosylphosphorylcholine. 2 Publications1
Mutagenesisi211F → Y: Reduces lysophospholipase activity by about 70%. 1 Publication1
Mutagenesisi218A → V: Reduces lysophospholipase activity by about 50%. 1 Publication1
Mutagenesisi231N → A: Strongly reduced lysophospholipase activity. 1 Publication1
Mutagenesisi307Y → Q: Reduces lysophospholipase activity by about 70%. 1 Publication1
Mutagenesisi316H → Q: Loss of ability to hydrolyze sphingosylphosphorylcholine. 1 Publication1
Mutagenesisi360H → Q: Loss of ability to hydrolyze sphingosylphosphorylcholine. 1 Publication1

Keywords - Diseasei

Obesity

Organism-specific databases

DisGeNET

More...
DisGeNETi
5168

Open Targets

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OpenTargetsi
ENSG00000136960

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA27792

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
Q13822 Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3691

DrugCentral

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DrugCentrali
Q13822

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2901

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
ENPP2

Domain mapping of disease mutations (DMDM)

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DMDMi
290457674

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 27By similarityAdd BLAST27
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_000028164928 – 35Removed by furin2 Publications8
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000018856736 – 863Ectonucleotide pyrophosphatase/phosphodiesterase family member 2Add BLAST828

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi54N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi59 ↔ 76PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi63 ↔ 94PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi74 ↔ 87PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi80 ↔ 86PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi103 ↔ 120PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi108 ↔ 138PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi118 ↔ 131PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi124 ↔ 130PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi149 ↔ 195PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi157 ↔ 351PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi367 ↔ 469PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi411N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi414 ↔ 806PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi525N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi567 ↔ 667PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi569 ↔ 652PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi775 ↔ 785PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi807N-linked (GlcNAc...) asparagineSequence analysis1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity.By similarity
The interdomain disulfide bond between Cys-414 and Cys-806 is essential for catalytic activity.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q13822

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q13822

PeptideAtlas

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PeptideAtlasi
Q13822

PRoteomics IDEntifications database

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PRIDEi
Q13822

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
20576
59692 [Q13822-1]
59693 [Q13822-2]
59694 [Q13822-3]

PTM databases

GlyConnect protein glycosylation platform

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GlyConnecti
1197

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q13822

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q13822

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Detected in blood plasma (at protein level) (PubMed:12176993, PubMed:26371182). Predominantly expressed in brain, placenta, ovary, and small intestine. Expressed in a number of carcinomas such as hepatocellular and prostate carcinoma, neuroblastoma and non-small-cell lung cancer. Expressed in body fluids such as plasma, cerebral spinal fluid (CSF), saliva, follicular and amniotic fluids. Not detected in leukocytes. Isoform 1 is more highly expressed in peripheral tissues than in the central nervous system (CNS). Adipocytes only express isoform 1. Isoform 3 is more highly expressed in the brain than in peripheral tissues.5 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Up-regulated in massively obese subjects with glucose intolerance, and during adipogenesis.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000136960 Expressed in pigmented layer of retina and 234 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q13822 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q13822 HS

Organism-specific databases

Human Protein Atlas

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HPAi
ENSG00000136960 Tissue enhanced (brain, placenta)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
111194, 3 interactors

Protein interaction database and analysis system

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IntActi
Q13822, 3 interactors

Molecular INTeraction database

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MINTi
Q13822

STRING: functional protein association networks

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STRINGi
9606.ENSP00000259486

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q13822

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
Q13822 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1863
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details