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Protein

Tyrosine-protein kinase ZAP-70

Gene

Zap70

Organism
Mus musculus (Mouse)
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

Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).5 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 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 phosphorylation at Tyr-492 in the activation loop.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 sitei368ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ 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 sitei460Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 bindingi343 – 351ATPPROSITE-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, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
2.7.10.2 3474

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-202430 Translocation of ZAP-70 to Immunological synapse
R-MMU-202433 Generation of second messenger molecules

<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_and_taxonomy_section">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:
Tyrosine-protein kinase ZAP-70 (EC:2.7.10.2)
Alternative name(s):
70 kDa zeta-chain associated protein
Syk-related tyrosine kinase
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:Zap70
Synonyms:Srk, Zap-70
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">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 1

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:99613 Zap70

<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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

<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

<p>This subsection of the ‘Pathology and Biotech’ section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Mice lack both CD4 and CD8 positive mature T-lymphocytes. Displays a complete block in B-Cell development at the pro-B cell stage in the absence of both SYK and ZAP70.2 Publications

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL2034801

<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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000881691 – 618Tyrosine-protein kinase ZAP-70Add BLAST618

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 residuei248PhosphotyrosineBy similarity1
Modified residuei287PhosphoserineBy similarity1
Modified residuei290PhosphotyrosineBy similarity1
Modified residuei314Phosphotyrosine; by LCKBy similarity1
Modified residuei318PhosphotyrosineBy similarity1
Modified residuei491PhosphotyrosineBy similarity1
Modified residuei492PhosphotyrosineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki543Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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

Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Phosphorylation of Tyr-314 and Tyr-314 are essential for ZAP70 positive function on T-lymphocyte activation whereas Tyr-290 has a negative regulatory role. Within the C-terminal kinase domain, Tyr-491 and Tyr-492 are phosphorylated after TCR induction, Tyr-491 playing a negative regulatory role and Tyr-492 a positive. Tyr-492 is dephosphorylated by PTN22.
Ubiquitinated in response to T cell activation. Deubiquitinated by OTUD7B.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P43404

MaxQB - The MaxQuant DataBase

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MaxQBi
P43404

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

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PaxDbi
P43404

PRoteomics IDEntifications database

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PRIDEi
P43404

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P43404

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

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PhosphoSitePlusi
P43404

<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

Isoform 1 and isoform 2 are expressed in thymus, spleen and lymph nodes.1 Publication

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Isoform 2 is expressed in developing thymocytes from the CD44+CD25- stage up to mature T-cells. Isoform 1 is not expressed in thymocytes at the CD44+CD25- or CD44+CD25+ stages.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSMUSG00000026117 Expressed in 71 organ(s), highest expression level in spleen

CleanEx database of gene expression profiles

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CleanExi
MM_ZAP70

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P43404 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P43404 MM

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with CD247/CD3Z; this interaction docks ZAP70 at the stimulated TCR (By similarity). Interacts with NFAM1 (PubMed:15143214). Interacts with adapter protein SLA; this interaction negatively regulates T-cell receptor signaling (PubMed:10662792). Interacts with VAV1 (By similarity). Interacts with CBL; this interaction promotes ubiquitination, internalization and subsequent degradation of CD247/CD3Z (By similarity). Identified in a complex with CBL and UBE2L3 (By similarity). Interacts with SHB (By similarity). Interacts with adapter protein SLA2; this interaction negatively regulates T-cell receptor signaling (PubMed:11891219). Interacts with CBLB (PubMed:10646608). Interacts (via SH2 domains) with RHOH; this interaction regulates ZAP70 subcellular localization (PubMed:17028588). Interacts with DEF6 (PubMed:12648457). Interacts (ubiquitinated form) with OTUD7B and UBASH3B (PubMed:26903241).By similarity7 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">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="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
Cd247P241614EBI-3862932,EBI-7803400

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
204628, 10 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P43404

Protein interaction database and analysis system

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IntActi
P43404, 39 interactors

Molecular INTeraction database

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MINTi
P43404

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000027291

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P43404

<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

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P43404

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P43404

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini10 – 102SH2 1PROSITE-ProRule annotationAdd BLAST93
Domaini163 – 254SH2 2PROSITE-ProRule annotationAdd BLAST92
Domaini337 – 597Protein kinasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni103 – 162Interdomain AAdd BLAST60
Regioni255 – 336Interdomain BAdd BLAST82

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Composed of 2 N-terminal SH2 domains and a C-terminal kinase domain. The tandem SH2 domains bind to the doubly phosphorylated tyrosine-based activation motif (ITAM) of CD247/CD3Z and the non-canonical phosphorylated tyrosine-based activation motif (TAM) of RHOH (By similarity). The interdomain B located between the second SH2 and the kinase domain has been implicated in binding to other signaling molecules including CBL or VAV1. Thus, ZAP70 can also function as a scaffold by recruiting additional factors to the stimulated TCR complex (By similarity).By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410IH0T Eukaryota
COG0515 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000159185

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000113264

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG001540

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P43404

KEGG Orthology (KO)

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KOi
K07360

Identification of Orthologs from Complete Genome Data

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OMAi
ADKDEMM

Database of Orthologous Groups

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OrthoDBi
EOG091G07KU

TreeFam database of animal gene trees

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TreeFami
TF351629

Family and domain databases

Conserved Domains Database

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CDDi
cd09938 SH2_N-SH2_Zap70_Syk_like, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.930.10, 1 hit
3.30.505.10, 2 hits

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR023420 Kinase_SYK/ZAP-70_inter-SH2_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR035838 SYK/ZAP-70_N_SH2
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR012234 Tyr_kinase_non-rcpt_SYK/ZAP70

Pfam protein domain database

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Pfami
View protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 2 hits

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF000604 TyrPK_SYK, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00401 SH2DOMAIN
PR00109 TYRKINASE

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00252 SH2, 2 hits
SM00219 TyrKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF55550 SSF55550, 2 hits
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P43404-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MPDPAAHLPF FYGSISRAEA EEHLKLAGMA DGLFLLRQCL RSLGGYVLSL
60 70 80 90 100
VHDVRFHHFP IERQLNGTYA IAGGKAHCGP AELCQFYSQD PDGLPCNLRK
110 120 130 140 150
PCNRPPGLEP QPGVFDCLRD AMVRDYVRQT WKLEGDALEQ AIISQAPQVE
160 170 180 190 200
KLIATTAHER MPWYHSSLTR EEAERKLYSG QQTDGKFLLR PRKEQGTYAL
210 220 230 240 250
SLVYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK LKADGLIYRL
260 270 280 290 300
KEVCPNSSAS AAVAAPTLPA HPSTFTQPQR RVDTLNSDGY TPEPARLASS
310 320 330 340 350
TDKPRPMPMD TSVYESPYSD PEELKDKKLF LKRENLLVAD IELGCGNFGS
360 370 380 390 400
VRQGVYRMRK KQIDVAIKVL KQGTEKADKD EMMREAQIMH QLDNPYIVRL
410 420 430 440 450
IGVCQAEALM LVMEMAGGGP LHKFLLGKKE EIPVSNVAEL LHQVAMGMKY
460 470 480 490 500
LEEKNFVHRD LAARNVLLVN RHYAKISDFG LSKALGADDS YYTARSAGKW
510 520 530 540 550
PLKWYAPECI NFRKFSSRSD VWSYGVTMWE AFSYGQKPYK KMKGPEVLDF
560 570 580 590 600
IKQGKRMECP PECPPEMYAL MSDCWIYKWE DRPDFLTVEQ RMRNYYYSLA
610
SRAEGPPQCE QVAEAACG
Length:618
Mass (Da):70,112
Last modified:December 14, 2011 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i9E0D18B240B28392
GO
Isoform 2 (identifier: P43404-2) [UniParc]FASTAAdd to basket
Also known as: TZK

The sequence of this isoform differs from the canonical sequence as follows:
     1-306: Missing.

Show »
Length:312
Mass (Da):35,883
Checksum:i12CCA3AA2C3B1CF2
GO
Isoform 3 (identifier: P43404-3) [UniParc]FASTAAdd to basket
Also known as: TZK-2

The sequence of this isoform differs from the canonical sequence as follows:
     1-309: Missing.
     310-360: DTSVYESPYS...VRQGVYRMRK → MAYGRVSGVS...MLSVASHLGR

Note: No experimental confirmation available.
Show »
Length:309
Mass (Da):35,255
Checksum:iD1A230395CA2AFE4
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WQ05A0A087WQ05_MOUSE
Tyrosine-protein kinase ZAP-70
Zap70
85Annotation score:

Annotation score:2 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 Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti124R → C in AAA19250 (PubMed:8196616).Curated1
Sequence conflicti526 – 529VTMW → GHHV in BAC67015 (Ref. 4) Curated4
Sequence conflicti546E → Q in AAA19250 (PubMed:8196616).Curated1
Sequence conflicti599L → P in AAA19250 (PubMed:8196616).Curated1
Sequence conflicti599L → P in AAB36538 (PubMed:9208839).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural varianti464R → C in ST; causes an absence of mature T-cells due to thymocyte development being arrested at the CD4+CD8+ stage. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0311601 – 309Missing in isoform 3. 1 PublicationAdd BLAST309
Alternative sequenceiVSP_0311591 – 306Missing in isoform 2. 1 PublicationAdd BLAST306
Alternative sequenceiVSP_031161310 – 360DTSVY…YRMRK → MAYGRVSGVSELSRVLYVPF PPPPFLSNPGVHDTRMYTQH AMLSVASHLGR in isoform 3. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
U04379 mRNA Translation: AAA19250.1
U77667 mRNA Translation: AAB36538.1
AB083210 mRNA Translation: BAC43746.1
AB084383 mRNA Translation: BAC67015.1
AK039883 mRNA Translation: BAC30471.1
AC084389 mRNA No translation available.
BC029727 mRNA Translation: AAH29727.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS14888.1 [P43404-1]

Protein sequence database of the Protein Information Resource

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PIRi
I48914

NCBI Reference Sequences

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RefSeqi
NP_001276541.1, NM_001289612.1 [P43404-2]
NP_001276694.1, NM_001289765.1 [P43404-1]
NP_033565.2, NM_009539.3 [P43404-1]
XP_006495959.1, XM_006495896.2 [P43404-1]

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Mm.8038

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENSMUST00000027291; ENSMUSP00000027291; ENSMUSG00000026117 [P43404-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
22637

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
mmu:22637

UCSC genome browser

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UCSCi
uc007aqz.2 mouse [P43404-1]
uc007arb.2 mouse [P43404-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U04379 mRNA Translation: AAA19250.1
U77667 mRNA Translation: AAB36538.1
AB083210 mRNA Translation: BAC43746.1
AB084383 mRNA Translation: BAC67015.1
AK039883 mRNA Translation: BAC30471.1
AC084389 mRNA No translation available.
BC029727 mRNA Translation: AAH29727.1
CCDSiCCDS14888.1 [P43404-1]
PIRiI48914
RefSeqiNP_001276541.1, NM_001289612.1 [P43404-2]
NP_001276694.1, NM_001289765.1 [P43404-1]
NP_033565.2, NM_009539.3 [P43404-1]
XP_006495959.1, XM_006495896.2 [P43404-1]
UniGeneiMm.8038

3D structure databases

ProteinModelPortaliP43404
SMRiP43404
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204628, 10 interactors
CORUMiP43404
IntActiP43404, 39 interactors
MINTiP43404
STRINGi10090.ENSMUSP00000027291

Chemistry databases

BindingDBiP43404
ChEMBLiCHEMBL2034801

PTM databases

iPTMnetiP43404
PhosphoSitePlusiP43404

Proteomic databases

EPDiP43404
MaxQBiP43404
PaxDbiP43404
PRIDEiP43404

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027291; ENSMUSP00000027291; ENSMUSG00000026117 [P43404-1]
GeneIDi22637
KEGGimmu:22637
UCSCiuc007aqz.2 mouse [P43404-1]
uc007arb.2 mouse [P43404-3]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
7535
MGIiMGI:99613 Zap70

Phylogenomic databases

eggNOGiENOG410IH0T Eukaryota
COG0515 LUCA
GeneTreeiENSGT00940000159185
HOGENOMiHOG000113264
HOVERGENiHBG001540
InParanoidiP43404
KOiK07360
OMAiADKDEMM
OrthoDBiEOG091G07KU
TreeFamiTF351629

Enzyme and pathway databases

BRENDAi2.7.10.2 3474
ReactomeiR-MMU-202430 Translocation of ZAP-70 to Immunological synapse
R-MMU-202433 Generation of second messenger molecules

Miscellaneous databases

Protein Ontology

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PROi
PR:P43404

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000026117 Expressed in 71 organ(s), highest expression level in spleen
CleanExiMM_ZAP70
ExpressionAtlasiP43404 baseline and differential
GenevisibleiP43404 MM

Family and domain databases

CDDicd09938 SH2_N-SH2_Zap70_Syk_like, 1 hit
Gene3Di1.10.930.10, 1 hit
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR023420 Kinase_SYK/ZAP-70_inter-SH2_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR035838 SYK/ZAP-70_N_SH2
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR012234 Tyr_kinase_non-rcpt_SYK/ZAP70
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 2 hits
PIRSFiPIRSF000604 TyrPK_SYK, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF55550 SSF55550, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 2 hits

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiZAP70_MOUSE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P43404
Secondary accession number(s): P97455, Q80VV2, Q8CHJ3
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 14, 2011
Last modified: December 5, 2018
This is version 175 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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