ZAP70 protein expression summary - The Human Protein Atlas

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ZAP70

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HUMAN PROTEIN ATLAS SUMMARYⁱ General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Proteinⁱ Full gene name according to HGNC.	Zeta chain of T cell receptor associated protein kinase 70
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	ZAP70 (SRK, STD, ZAP-70)
Tissue specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. Read more	Group enriched (blood, lymphoid tissue)
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Cell type enriched (T-cells)
Blood specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed blood cell samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Group enriched (gdT-cell, memory CD8 T-cell, NK-cell, MAIT T-cell, naive CD8 T-cell, T-reg, memory CD4 T-cell, naive CD4 T-cell)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Not detected in human brain
Cancer prognostic summary	Prognostic marker in renal cancer (unfavorable), endometrial cancer (favorable), head and neck cancer (favorable) and cervical cancer (favorable)
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location. Read more	Intracellular
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	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 CD247/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-CD247/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).... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	Kinase, Transferase, Tyrosine-protein kinase
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Adaptive immunity, Immunity
Disease involvementⁱ Disease related keywords assigned by UniProt combined with Cancer-related genes and FDA approved drug targets Read more	Disease mutation, SCID
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	ATP-binding, Nucleotide-binding
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]... show less

TISSUE ATLASⁱ Summary of data presented in the Tissue Atlas and representative images of protein expression (left) and mRNA expression (right). The images are clickable and will redirect to more Tissue Atlas data. The Tissue Atlas contains information regarding the expression profiles of protein-coding genes in normal human tissue, both on the mRNA and protein level. The protein expression data is derived from antibody-based protein profiling using immunohistochemistry. Read more

Tissue specificity (RNA)ⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. Read more	Group enriched (blood, lymphoid tissue)
Tissue distribution (RNA)ⁱ The RNA distribution category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: detected in all, detected in many, detected in some, detected in single and not detected. Read more	Detected in many
Protein expressionⁱ A summary of the overall protein expression pattern across the analyzed normal tissues. The summary is based on knowledge-based annotation. "Estimation of protein expression could not be performed. View primary data." is shown for genes analyzed with a knowledge-based approach where available RNA-seq and gene/protein characterization data has been evaluated as not sufficient in combination with immunohistochemistry data to yield a reliable estimation of the protein expression profile. Read more	Selective cytoplasmic expression in subsets of immune cells.

SINGLE CELL TYPE ATLASⁱ Summary of data presented in the Cell Type Atlas and an interactive image showing mRNA expression in cell type groups e.g. epithelial cells and germ cells. The image is clickable and will redirect to more Cell Type Atlas data. The Cell Type Atlas contains information about single cell type RNA expression based on scRNAseq of human tissues. The data also covers transcriptomics analysis of human blood and cultured cell lines. Read more

Cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Cell type enriched (T-cells)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from all cell lines in the Human Protein Atlas. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Group enriched (JURKAT, MOLT-4)

PATHOLOGY ATLASⁱ Summary of data presented in the Pathology Atlas , with representative images of protein expression in cancer (left) and correlation between mRNA expression and patient survival (right). Images are clickable and redirect to pages with more Pathology Atlas data. The Pathology Atlas contains mRNA and protein expression data from 17 different forms of human cancer, as well as correlation analysis of mRNA expression and patient survival. The protein expression data is derived from antibody-based protein profiling using immunohistochemistry. Read more
	Renal cancer p<0.001
Prognostic summary	Prognostic marker in renal cancer (unfavorable), endometrial cancer (favorable), head and neck cancer (favorable) and cervical cancer (favorable)
Cancer specificity (RNA)ⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected. Read more	Low cancer specificity
Cancer distribution (RNA)ⁱ Distribution of RNA expression in 17 cancer types is categorized as either detected in single, detected in some, detected in many, detected in all, or not detected. Read more	Detected in many

BRAIN ATLASⁱ Summary of data presented in the Brain Atlas and a representative image of mRNA expression in the human brain. The image is clickable and will redirect to more Brain Atlas data. The Brain Atlas explores the protein expression in the mammalian brain by visualization and integration of data from three mammalian species (human, pig and mouse). Transcriptomics data combined with affinity-based protein in situ localization down to single cell level is available in a brain-centric sub atlas of the Human Protein Atlas. Read more

Human regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Not detected
Pig regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Low region specificity
Mouse regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Low region specificity

BLOOD ATLASⁱ Summary of data presented in the Blood Atlas and a representative image of mRNA expression in immune cells in the blood. The image is clickable and will redirect to more Blood Atlas data. The Blood Atlas contains single cell type RNA information covering various immune cells in the blood, e.g. B-cells and granulocytes. Analysis of the human secretome (including annotation of the genes predicted to be actively secreted to human blood) and proteins detected in human blood are also presented. Read more

Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Group enriched (gdT-cell, memory CD8 T-cell, NK-cell, MAIT T-cell, naive CD8 T-cell, T-reg, memory CD4 T-cell, naive CD4 T-cell)
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search. Read more	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	No

CELL ATLASⁱ Summary of data presented in the Cell Atlas and a representative image of subcellular localization. The Cell Atlas provides RNA expression data derived from RNA sequencing of a large panel of cell lines and protein localization data derived from antibody-based profiling by immunofluorescence confocal microscopy, using a subset of cell lines selected based on RNA expression. Read more

Main locationⁱ Main subcellular location(s) and reliability score(s) for the encoded protein(s) in human cells. The main location(s) may be characterized by presence in all tested cell lines and/or ihigher staining intensity compared to the potential additional location(s). If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively. Read more	Not available
Cell cycle dependencyⁱ Cell-cycle dependance of single-cell varations in RNA and/or protein expression as observed in an additional assay for characterizing single-cell varations. "NA" indicates a lack of such data. Read more	NA

GENE INFORMATIONⁱ Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Gene name	ZAP70 (HGNC Symbol)
Synonyms	SRK, STD, ZAP-70
Description	Zeta chain of T cell receptor associated protein kinase 70 (HGNC Symbol)
Chromosome	2
Cytoband	q11.2
Chromosome location (bp)	97713560 - 97739862
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	2
Protein evidence	Evidence at protein level (all genes)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s). Read more	Disease related genes Enzymes Plasma proteins Potential drug targets RAS pathway related proteins
Ensembl	ENSG00000115085 (version 92.38)
Entrez gene	7535
UniProt	P43403 (UniProt - Evidence at protein level)
neXtProt	NX_P43403
Antibodypedia	ZAP70 antibodies

PROTEIN BROWSERⁱ

ZAP70-201

ZAP70-202

PROTEIN INFORMATIONⁱ The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database. The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein. The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class. The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
Splice variant	UniProt	Protein class	Gene ontology	Length & mass	Signal peptide (predicted)	Transmembrane regions (predicted)
ZAP70-201 ENSP00000264972 ENST00000264972	P43403 [Direct mapping] Tyrosine-protein kinase ZAP-70 Show all	Enzymes ENZYME proteins Transferases Kinases Tyr protein kinases SCAMPI predicted membrane proteins SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Plasma proteins RAS pathway related proteins Disease related genes Potential drug targets Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas) Show all	GO:0000166 [nucleotide binding] GO:0001772 [immunological synapse] GO:0002250 [adaptive immune response] GO:0002376 [immune system process] GO:0004672 [protein kinase activity] GO:0004713 [protein tyrosine kinase activity] GO:0004715 [non-membrane spanning protein tyrosine kinase activity] GO:0005102 [receptor binding] GO:0005515 [protein binding] GO:0005524 [ATP binding] GO:0005737 [cytoplasm] GO:0005829 [cytosol] GO:0005886 [plasma membrane] GO:0005911 [cell-cell junction] GO:0006468 [protein phosphorylation] GO:0006955 [immune response] GO:0007169 [transmembrane receptor protein tyrosine kinase signaling pathway] GO:0016020 [membrane] GO:0016301 [kinase activity] GO:0016310 [phosphorylation] GO:0016740 [transferase activity] GO:0018108 [peptidyl-tyrosine phosphorylation] GO:0030217 [T cell differentiation] GO:0031234 [extrinsic component of cytoplasmic side of plasma membrane] GO:0035556 [intracellular signal transduction] GO:0038083 [peptidyl-tyrosine autophosphorylation] GO:0042101 [T cell receptor complex] GO:0042110 [T cell activation] GO:0042113 [B cell activation] GO:0042127 [regulation of cell proliferation] GO:0043366 [beta selection] GO:0045059 [positive thymic T cell selection] GO:0045060 [negative thymic T cell selection] GO:0045061 [thymic T cell selection] GO:0045087 [innate immune response] GO:0045121 [membrane raft] GO:0045582 [positive regulation of T cell differentiation] GO:0046638 [positive regulation of alpha-beta T cell differentiation] GO:0046641 [positive regulation of alpha-beta T cell proliferation] GO:0046777 [protein autophosphorylation] GO:0050850 [positive regulation of calcium-mediated signaling] GO:0050852 [T cell receptor signaling pathway] GO:0070489 [T cell aggregation] GO:0072678 [T cell migration] Show all	619 aa 69.9 kDa	No	0
ZAP70-202 ENSP00000400475 ENST00000451498	P43403 [Direct mapping] Tyrosine-protein kinase ZAP-70 Show all	Enzymes ENZYME proteins Transferases Kinases Tyr protein kinases SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Plasma proteins RAS pathway related proteins Disease related genes Potential drug targets Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas) Show all	GO:0000166 [nucleotide binding] GO:0002250 [adaptive immune response] GO:0002376 [immune system process] GO:0004672 [protein kinase activity] GO:0004713 [protein tyrosine kinase activity] GO:0004715 [non-membrane spanning protein tyrosine kinase activity] GO:0005102 [receptor binding] GO:0005515 [protein binding] GO:0005524 [ATP binding] GO:0005737 [cytoplasm] GO:0005829 [cytosol] GO:0005886 [plasma membrane] GO:0006468 [protein phosphorylation] GO:0006955 [immune response] GO:0007169 [transmembrane receptor protein tyrosine kinase signaling pathway] GO:0016020 [membrane] GO:0016301 [kinase activity] GO:0016310 [phosphorylation] GO:0016740 [transferase activity] GO:0018108 [peptidyl-tyrosine phosphorylation] GO:0030217 [T cell differentiation] GO:0031234 [extrinsic component of cytoplasmic side of plasma membrane] GO:0035556 [intracellular signal transduction] GO:0038083 [peptidyl-tyrosine autophosphorylation] GO:0042101 [T cell receptor complex] GO:0042110 [T cell activation] GO:0042113 [B cell activation] GO:0042127 [regulation of cell proliferation] GO:0045059 [positive thymic T cell selection] GO:0045087 [innate immune response] GO:0045121 [membrane raft] GO:0045582 [positive regulation of T cell differentiation] GO:0050852 [T cell receptor signaling pathway] GO:0070489 [T cell aggregation] GO:0072678 [T cell migration] Show all	312 aa 35.6 kDa	No	0

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