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Entry version 209 (07 Apr 2021)
Sequence version 3 (28 Mar 2018)
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Protein

Serine/threonine-protein kinase D2

Gene

PRKD2

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

Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:15604256, PubMed:14743217, PubMed:17077180, PubMed:16928771, PubMed:17962809, PubMed:17951978, PubMed:18262756, PubMed:19192391, PubMed:19001381, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467).By similarity11 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

Mg2+3 Publications

<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

Activated by DAG and phorbol esters (PubMed:12058027, PubMed:17962809, PubMed:28428613). Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes (PubMed:17962809). Autophosphorylation of Ser-710 and phosphorylation of Ser-706 by PKC relieves auto-inhibition by the PH domain (PubMed:17962809). Catalytic activity is further increased by phosphorylation at Tyr-717 in response to oxidative stress (PubMed:28428613).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 sitei580ATPPROSITE-ProRule annotation1
<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 sitei674Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri138 – 188Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri264 – 314Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi557 – 565ATPPROSITE-ProRule annotation9

<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 functionKinase, Serine/threonine-protein kinase, Transferase
Biological processAdaptive immunity, Angiogenesis, Cell adhesion, Immunity
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.11.13, 2681

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
Q9BZL6

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-1660661, Sphingolipid de novo biosynthesis

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q9BZL6

SIGNOR Signaling Network Open Resource

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SIGNORi
Q9BZL6

<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:
Serine/threonine-protein kinase D2 (EC:2.7.11.134 Publications)
Alternative name(s):
nPKC-D2
<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:PRKD2
Synonyms:PKD2
ORF Names:HSPC187
<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 19

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:17293, PRKD2

Online Mendelian Inheritance in Man (OMIM)

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MIMi
607074, gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q9BZL6

Eukaryotic Pathogen, Vector and Host Database Resources

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VEuPathDBi
HostDB:ENSG00000105287.12

<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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

<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>Mutagenesisi87Y → F: Loss of phosphorylation. No effect on the interaction with PRKCD. No effect on Ser-706 or/and Ser-710 phosphorylation. 1 Publication1
Mutagenesisi244S → E: Constitutive kinase activity; when associated with E-706 and E-710. 1 Publication1
Mutagenesisi275P → G: Increase in ability to bind phorbol ester, slight increase in ability to bind DAG. 1 Publication1
Mutagenesisi438Y → D: Slight increase in Tyr-717 phosphorylation. No effect on Ser-706 or/and Ser-710 phosphorylation. Increase in Tyr-717 phosphorylation; when associated with E-706 and E-710. 1 Publication1
Mutagenesisi438Y → F: Loss of phosphorylation. No effect on phosphorylation of Tyr-717 and on Ser-706 or/and Ser-710 phosphorylation. 2 Publications1
Mutagenesisi695D → A: Loss of kinase activity. 1 Publication1
Mutagenesisi706S → A: Abolishes phosphorylation. Loss of Tyr-717 phosphorylation and any other tyrosine phosphorylation, and increases NF-kappa-B activation in response to oxidative stress; when associated with A-710. 1 Publication1
Mutagenesisi706S → E: Constitutive kinase activity; when associated with E-710 or with E-244 and E-710. Increases Tyr-717 phosphorylation; when associated with E-710 or with E-710 and D-438. 2 Publications1
Mutagenesisi710S → A: Abolishes phosphorylation. Loss of Tyr-717 phosphorylation and any other tyrosine phosphorylation, and increases NF-kappa-B activation in response to oxidative stress; when associated with A-706. 1 Publication1
Mutagenesisi710S → E: Constitutive kinase activity; when associated with E-706 or with E-244 and E-706. when associated with E-710 or with E-244 and E-710. Increases Tyr-717 phosphorylation; when associated with E-710 or with E-710 and D-438. 2 Publications1
Mutagenesisi717Y → F: Abolishes phosphorylation. Decreases substrate affinity and increases catalytic efficiency. Increases Ser-706 or/and Ser-710 phosphorylation. Increases NF-kappa-B activation in response to oxidative stress. 1 Publication1
Mutagenesisi724 – 726LNQ → RNK: Reduced catalytic activity. Severe reduction in Tyr-717 phosphorylation by ABL1 in response to oxidative stress. No effect on Ser-706 or/and Ser-710 phosphorylation and on NF-kappa-B activation in response to oxidative stress. 1 Publication3

Organism-specific databases

DisGeNET

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DisGeNETi
25865

Open Targets

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OpenTargetsi
ENSG00000105287

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA134903505

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
Q9BZL6, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL4900

DrugCentral

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DrugCentrali
Q9BZL6

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2173

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
PRKD2

Domain mapping of disease mutations (DMDM)

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DMDMi
296434570

<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 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_00000557161 – 878Serine/threonine-protein kinase D2Add BLAST878

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei30PhosphoserineBy similarity1
Modified residuei87PhosphotyrosineBy similarity1
Modified residuei197PhosphoserineCombined sources1
Modified residuei198PhosphoserineCombined sources1
Modified residuei200PhosphoserineCombined sources1
Modified residuei203PhosphoserineCombined sources1
Modified residuei206PhosphoserineCombined sources1
Modified residuei212PhosphoserineBy similarity1
Modified residuei214PhosphoserineCombined sources1
Modified residuei244Phosphoserine; by CSNK1D and CSNK1E1 Publication1
Modified residuei407PhosphotyrosineBy similarity1
Modified residuei438Phosphotyrosine; by ABL11 Publication1 Publication1
Modified residuei518PhosphoserineCombined sources1
Modified residuei706Phosphoserine; by PKC2 Publications1
Modified residuei710PhosphoserineCombined sources2 Publications1
Modified residuei717Phosphotyrosine; by ABL1Combined sources1 Publication1
Modified residuei876Phosphoserine; by autocatalysisCombined sources2 Publications1

<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

Phosphorylation of Ser-876 correlates with the activation status of the kinase (PubMed:11062248). Ser-706 or/and Ser-710 are probably phosphorylated by PKC (PubMed:12058027, PubMed:28428613). Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear localization and substrate targeting (PubMed:17962809). Phosphorylation at Ser-244, Ser-706 and Ser-710 is required for nuclear localization (PubMed:17962809). Phosphorylated at Tyr-438 by ABL1 in response to oxidative stress (PubMed:15604256). Phosphorylated at Tyr-717 by ABL1 specifically in response to oxidative stress; requires prior phosphorylation at Ser-706 or/and Ser-710 (PubMed:28428613).5 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

The CPTAC Assay portal

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CPTACi
CPTAC-1364

Encyclopedia of Proteome Dynamics

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EPDi
Q9BZL6

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q9BZL6

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q9BZL6

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9BZL6

PeptideAtlas

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PeptideAtlasi
Q9BZL6

PRoteomics IDEntifications database

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PRIDEi
Q9BZL6

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
79872 [Q9BZL6-1]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9BZL6

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

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PhosphoSitePlusi
Q9BZL6

<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

Widely expressed.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000105287, Expressed in cerebellum and 238 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9BZL6, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9BZL6, HS

Organism-specific databases

Human Protein Atlas

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HPAi
ENSG00000105287, Low tissue specificity

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts (via C-terminus) with LCK (PubMed:19192391).

Interacts (via N-terminal AP-rich region) with CIB1 isoform 2 (PubMed:23503467).

Interacts (via N-terminus and zing-finger domain 1 and 2) with PRKCD in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation (PubMed:28428613).

3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
117384, 167 interactors

Protein interaction database and analysis system

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IntActi
Q9BZL6, 47 interactors

Molecular INTeraction database

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MINTi
Q9BZL6

STRING: functional protein association networks

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STRINGi
9606.ENSP00000393978

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q9BZL6

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
Q9BZL6, 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

1878
Legend: HelixTurnBeta strandPDB Structure known for this area
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