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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

ZAP70 Gene

protein-coding GIFtS: 76
GCID: GC02P098331

zeta-chain (TCR) associated protein kinase 70kDa

(Previous name: zeta-chain (TCR) associated protein kinase (70 kD) )
(Previous symbol: SRK)

Explore 50 diseases affiliated with
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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Zeta-Chain (TCR) Associated Protein Kinase 70kDa¹ ²		Zeta-Chain (TCR) Associated Protein Kinase (70 KD)¹
SRK¹ ² ³ ⁵		70 KDa Zeta-Associated Protein²
STD¹ ² ⁵		STCD²
ZAP-70¹ ²		TZK²
Syk-Related Tyrosine Kinase² ³		Tyrosine-Protein Kinase ZAP-70²
70 KDa Zeta-Chain Associated Protein² ³		Zeta-Chain Associated Protein Kinase, 70kD²
EC 2.7.10.2³ ⁸		EC 2.7.10⁸

External Ids:	HGNC: 12858¹	Entrez Gene: 7535²	Ensembl: ENSG00000115085⁷	OMIM: 176947⁵	UniProtKB: P43403³

Export aliases for ZAP70 gene to outside databases

Previous GC identifers: GC02P096211 GC02P096782 GC02P097934 GC02P097951 GC02P097788 GC02P097696 GC02P092095

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for ZAP70:

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)

UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403

Function: 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)

Gene Wiki entry for ZAP70

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.1 NT_022171.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the ZAP70 gene promoter:
GR STAT1 AP-1 STAT3 GR-alpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: ZAP70 promoter sequence

Search SABiosciences Chromatin IP Primers for ZAP70

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ZAP70

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q12 Ensembl cytogenetic band: 2q11.2 HGNC cytogenetic band: 2q11-q13

ZAP70 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ZAP70 gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02P098331: view genomic region (about GC identifiers)

Start:	98,330,023 bp from pter	End:	98,356,325 bp from pter
Size:	26,303 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403 (See protein sequence)

Recommended Name: Tyrosine-protein kinase ZAP-70

Size: 619 amino acids; 69872 Da

Subunit: Interacts with NFAM1. Interacts with adapter proteins SLA and SLA2; these interactions negatively regulates

T-cell receptor signaling. Interacts with CBLB (By similarity). Interacts with DEF6. Interacts (via SH2 domains) with

RHOH; this interaction regulates ZAP70 subcellular localization (By similarity). Interacts with FCRL3. Interacts with

VAV1. Interacts with CD247/CD3Z; this interaction docks ZAP70 at the stimulated TCR. Interacts with CBL; this

interaction promotes ubiquitination, internalization and subsequent degradation of CD247/CD3Z. Identified in a complex

with CBL and UBE2L3

Subcellular location: Cytoplasm. Cell membrane; Peripheral membrane protein. Note=In quiescent T-lymphocytes, it is

cytoplasmic. Upon TCR activation, it is recruited at the plasma membrane by interacting with CD247/CD3Z. Co-localizes

together with RHOH in the immunological synapse. RHOH is required for its proper localization to the cell membrane and

cytoskeleton fractions in the thymocytes (By similarity)

6/9 PDB 3D structures from and Proteopedia for ZAP70 (see all 9):

1FBV (3D)

1M61 (3D)

1U59 (3D)

2CBL (3D)

2OQ1 (3D)

2OZO (3D)

Secondary accessions: A6NFP4 Q6PIA4 Q8IXD6 Q9UBS6

Alternative splicing: 3 isoforms: P43403-1 P43403-2 P43403-3 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ZAP70: NX_P43403

Post-translational modifications:

Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Phosphorylation of Tyr-315 and

Tyr-319 are essential for ZAP70 positive function on T-lymphocyte activation whereas Tyr-292 has a negative regulatory

role. Within the C-terminal kinase domain, Tyr-492 and Tyr-493 are phosphorylated after TCR induction, Tyr-492 playing

a negative regulatory role and Tyr-493 a positive. Tyr-493 is dephosphorylated by PTN22¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P43403

4/12 DME Specific Peptides for ZAP70 (P43403) (see all 12)

FVHRDLA

AARNVLL

RDLAARN

SYGQKPY

ZAP70 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001070.2 NP_997402.1

ENSEMBL proteins:

ENSP00000264972 ENSP00000400475 ENSP00000411141

Reactome Protein details: P43403
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant ZAP70 Protein
	R&D Systems Recombinant & Natural Proteins for ZAP70
	Enzo Life Sciences proteins for ZAP70
	OriGene Purified Protein: ZAP70 OriGene Protein Over-expression Lysate: ZAP70 OriGene Custom Protein Services for ZAP70
	GenScript Custom Purified and Recombinant Proteins Services for ZAP70
	Novus Biologicals ZAP70 Proteins Novus Biologicals ZAP70 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for ZAP70

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001772	immunological synapse	IEA	--
GO:0005622	intracellular	--	--
GO:0005737	cytoplasm	TAS	12359715
GO:0005829	cytosol	TAS	--
GO:0005886	plasma membrane	TAS	--

ZAP70 for ontologies About GeneDecksing

ZAP70 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of ZAP70
	R&D Systems Antibodies for ZAP70
	Cell Signaling Technology (CST) Antibodies for ZAP70
	OriGene Antibodies (see all 7): ZAP70 OriGene Custom Antibody Services for ZAP70
	GenScript Custom Superior Antibodies Services for ZAP70
	Novus Biologicals ZAP70 Antibodies
	Abcam antibodies for ZAP70
	Uscn Antibodies for ZAP70
	ThermoFisher Antibody for ZAP70

Assay Products for ZAP70:

	EMD Millipore Kits and Assays for the Analysis of ZAP70
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for ZAP70
	GenScript ZAP70-Activity-based Kinase Assay for Compound Screening
	Cell Signaling Technology (CST) Sandwich ELISA Kits for ZAP70
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for ZAP70

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

ZAP70 for domains About GeneDecksing

5/9 InterPro domains/families (see all 9):

IPR012234 Tyr_kinase_non-rcpt_SYK/ZAP70

IPR017441 Protein_kinase_ATP_BS

IPR001245 Ser-Thr/Tyr_kinase_cat_dom

IPR011009 Kinase-like_dom

IPR000980 SH2

Graphical View of Domain Structure for InterPro Entry P43403

ProtoNet protein and cluster: P43403

2 Blocks protein families:

IPB000980 SH2 domain signature

IPB008266 Tyrosine protein kinase

UniProtKB/Swiss-Prot: ZAP70_HUMAN, P43403

Domain: 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 contains 3 tyrosines (Tyr-292, Tyr-315, Tyr-319) that are phosphorylated following TCR activation.

These sites have 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

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily

Similarity: Contains 1 protein kinase domain

Similarity: Contains 2 SH2 domains

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: