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Protein

Tyrosine-protein kinase ZAP-70

Gene

ZAP70

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 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).6 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Enzyme regulationi

Activated by phosphorylation at Tyr-493 in the activation loop. Inhibited by staurosporine.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei369ATP1
Active sitei461Proton acceptorPROSITE-ProRule annotation2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi345 – 352ATP8

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor binding Source: GO_Central

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • B cell activation Source: UniProtKB
  • B cell receptor signaling pathway Source: GO_Central
  • beta selection Source: Ensembl
  • immune response Source: UniProtKB
  • inflammatory response Source: GO_Central
  • innate immune response Source: GO_Central
  • intracellular signal transduction Source: UniProtKB
  • macrophage activation involved in immune response Source: GO_Central
  • negative thymic T cell selection Source: Ensembl
  • neutrophil activation involved in immune response Source: GO_Central
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of alpha-beta T cell differentiation Source: Ensembl
  • positive regulation of alpha-beta T cell proliferation Source: GO_Central
  • positive regulation of B cell differentiation Source: GO_Central
  • positive regulation of calcium-mediated signaling Source: Ensembl
  • positive regulation of cell adhesion mediated by integrin Source: GO_Central
  • positive regulation of mast cell degranulation Source: GO_Central
  • positive regulation of T cell differentiation Source: MGI
  • positive thymic T cell selection Source: MGI
  • protein phosphorylation Source: UniProtKB
  • regulation of platelet aggregation Source: GO_Central
  • T cell activation Source: UniProtKB
  • T cell aggregation Source: UniProtKB
  • T cell differentiation Source: UniProtKB
  • T cell migration Source: UniProtKB
  • T cell receptor signaling pathway Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS03830-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
R-HSA-202433. Generation of second messenger molecules.
SignaLinkiP43403.
SIGNORiP43403.

Names & Taxonomyi

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
Gene namesi
Name:ZAP70
Synonyms:SRK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:12858. ZAP70.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • cytoplasm Source: HGNC
  • cytosol Source: Reactome
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • immunological synapse Source: Ensembl
  • plasma membrane Source: UniProtKB
  • T cell receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 48 (IMD48)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of severe immunodeficiency characterized by a selective absence of CD8+ T-cells.
See also OMIM:269840
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065623337L → R in IMD48. 1 Publication1
Natural variantiVAR_065624465R → C in IMD48. 1 PublicationCorresponds to variant rs113994174dbSNPEnsembl.1
Natural variantiVAR_015538465R → H in IMD48. 1 PublicationCorresponds to variant rs137853201dbSNPEnsembl.1
Natural variantiVAR_065625507A → V in IMD48. 1 Publication1
Natural variantiVAR_006351518S → R in IMD48. 1 PublicationCorresponds to variant rs104893674dbSNPEnsembl.1
Natural variantiVAR_038688541K → KLEQ in IMD48. 1 Publication1
Natural variantiVAR_065626564C → R in IMD48. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi131W → A: Increased constitutive kinase activity. 1 Publication1
Mutagenesisi133L → A: Increased constitutive kinase activity. 1 Publication1
Mutagenesisi141A → E: Increased constitutive kinase activity. 1 Publication1
Mutagenesisi144S → A: Increased kinase activity after activation by LCK. 1 Publication1
Mutagenesisi145Q → A: Increased kinase activity after activation by LCK. 1 Publication1
Mutagenesisi147P → A: Increased kinase activity after activation by LCK. 1 Publication1
Mutagenesisi292Y → F: Induces constitutive TCR stimulation-independent NFAT induction. 1 Publication1
Mutagenesisi314V → A: Increased constitutive kinase activity. 1
Mutagenesisi315Y → A: Increased constitutive kinase activity; when associated with F-319. 4 Publications1
Mutagenesisi315Y → F: Increased constitutive kinase activity; when associated with F-319. About 75% loss of CD247/CD3Z-binding in stimulated TCR and complete loss of VAV1 interaction. 4 Publications1
Mutagenesisi319Y → A: Increased constitutive kinase activity; when associated with F-315. 2 Publications1
Mutagenesisi319Y → F: Increased constitutive kinase activity; when associated with F-315. About 80% loss of TCR-induced NFAT activation. 2 Publications1
Mutagenesisi461D → N: Abolishes kinase activity. 1 Publication1
Mutagenesisi479D → N: Abolishes kinase activity. 1 Publication1
Mutagenesisi492Y → F: Increases kinase activity. 1 Publication1
Mutagenesisi493Y → F: Impairs kinase activity. 1 Publication1
Mutagenesisi597Y → A: Increased kinase activity after activation by LCK. 1 Publication1
Mutagenesisi598Y → A: Increased kinase activity after activation by LCK. 1 Publication1

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

DisGeNETi7535.
MalaCardsiZAP70.
MIMi269840. phenotype.
OpenTargetsiENSG00000115085.
Orphaneti911. Combined immunodeficiency due to ZAP70 deficiency.
PharmGKBiPA37447.

Chemistry databases

ChEMBLiCHEMBL2803.
GuidetoPHARMACOLOGYi2285.

Polymorphism and mutation databases

BioMutaiZAP70.
DMDMi1177044.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881681 – 619Tyrosine-protein kinase ZAP-70Add BLAST619

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei248PhosphotyrosineCombined sources1
Modified residuei289PhosphoserineCombined sources1
Modified residuei292PhosphotyrosineCombined sources1 Publication1
Modified residuei315Phosphotyrosine; by LCK1 Publication1
Modified residuei319Phosphotyrosine1 Publication1
Modified residuei492Phosphotyrosine1 Publication1
Modified residuei493Phosphotyrosine1 Publication1
Modified residuei603N6-acetyllysineCombined sources1

Post-translational modificationi

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 PTN22.4 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP43403.
PaxDbiP43403.
PeptideAtlasiP43403.
PRIDEiP43403.

PTM databases

iPTMnetiP43403.
PhosphoSitePlusiP43403.

Miscellaneous databases

PMAP-CutDBP43403.

Expressioni

Tissue specificityi

Expressed in T- and natural killer cells. Also present in early thymocytes and pro/pre B-cells.3 Publications

Gene expression databases

BgeeiENSG00000115085.
CleanExiHS_ZAP70.
GenevisibleiP43403. HS.

Organism-specific databases

HPAiCAB002625.
HPA003134.

Interactioni

Subunit structurei

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.By similarity11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD247P2096322EBI-1211276,EBI-1165705
CD3EP077663EBI-1211276,EBI-1211297
EGFRP005332EBI-1211276,EBI-297353
KITP107212EBI-1211276,EBI-1379503
LCKP062392EBI-1211276,EBI-1348
METP085812EBI-1211276,EBI-1039152
PTPN22Q9Y2R24EBI-1211276,EBI-1211241
Ubash3bQ8BGG710EBI-1211276,EBI-8846415From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113367. 50 interactors.
DIPiDIP-38781N.
IntActiP43403. 20 interactors.
MINTiMINT-110540.
STRINGi9606.ENSP00000264972.

Chemistry databases

BindingDBiP43403.

Structurei

Secondary structure

1619
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni4 – 7Combined sources4
Beta strandi11 – 14Combined sources4
Helixi17 – 26Combined sources10
Beta strandi34 – 38Combined sources5
Beta strandi40 – 42Combined sources3
Beta strandi46 – 52Combined sources7
Beta strandi55 – 63Combined sources9
Beta strandi69 – 71Combined sources3
Beta strandi77 – 79Combined sources3
Helixi80 – 89Combined sources10
Beta strandi94 – 96Combined sources3
Helixi114 – 131Combined sources18
Helixi135 – 156Combined sources22
Helixi157 – 160Combined sources4
Helixi170 – 178Combined sources9
Turni179 – 181Combined sources3
Beta strandi186 – 191Combined sources6
Beta strandi197 – 204Combined sources8
Beta strandi207 – 215Combined sources9
Turni217 – 219Combined sources3
Beta strandi221 – 223Combined sources3
Beta strandi229 – 231Combined sources3
Helixi232 – 241Combined sources10
Beta strandi246 – 248Combined sources3
Helixi309 – 311Combined sources3
Beta strandi316 – 320Combined sources5
Helixi322 – 326Combined sources5
Helixi334 – 336Combined sources3
Beta strandi337 – 345Combined sources9
Beta strandi350 – 357Combined sources8
Beta strandi364 – 371Combined sources8
Helixi377 – 392Combined sources16
Beta strandi401 – 415Combined sources15
Helixi422 – 426Combined sources5
Turni430 – 432Combined sources3
Helixi435 – 454Combined sources20
Helixi464 – 466Combined sources3
Beta strandi467 – 471Combined sources5
Beta strandi474 – 477Combined sources4
Turni482 – 485Combined sources4
Helixi503 – 505Combined sources3
Helixi508 – 513Combined sources6
Helixi518 – 533Combined sources16
Turni534 – 536Combined sources3
Turni539 – 542Combined sources4
Helixi546 – 553Combined sources8
Helixi566 – 574Combined sources9
Helixi580 – 582Combined sources3
Helixi586 – 601Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FBVX-ray2.90B289-297[»]
1M61X-ray2.50A1-256[»]
1U59X-ray2.30A327-606[»]
2CBLX-ray2.10B286-297[»]
2OQ1X-ray1.90A3-256[»]
2OZOX-ray2.60A1-606[»]
2Y1NX-ray2.00B/D286-297[»]
3ZNIX-ray2.21B/F/J/N286-297[»]
4A4BX-ray2.79B286-297[»]
4A4CX-ray2.70B286-297[»]
4K2RX-ray3.00A1-606[»]
4XZ0X-ray2.00A1-259[»]
4XZ1X-ray2.80A1-259[»]
ProteinModelPortaliP43403.
SMRiP43403.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43403.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 102SH2 1PROSITE-ProRule annotationAdd BLAST93
Domaini163 – 254SH2 2PROSITE-ProRule annotationAdd BLAST92
Domaini338 – 600Protein kinasePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 162Interdomain AAdd BLAST60
Regioni255 – 337Interdomain BAdd BLAST83

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 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.By similarity1 Publication

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 2 SH2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiENOG410IH0T. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000113264.
HOVERGENiHBG001540.
InParanoidiP43403.
KOiK07360.
OMAiYKARTAG.
OrthoDBiEOG091G07KU.
PhylomeDBiP43403.
TreeFamiTF351629.

Family and domain databases

Gene3Di1.10.930.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR023420. Kinase_SYK/ZAP-70_inter-SH2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR012234. Tyr_kinase_non-rcpt_SYK/ZAP70.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PIRSFiPIRSF000604. TyrPK_SYK. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P43403-1) [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 AELCEFYSRD PDGLPCNLRK
110 120 130 140 150
PCNRPSGLEP QPGVFDCLRD AMVRDYVRQT WKLEGEALEQ AIISQAPQVE
160 170 180 190 200
KLIATTAHER MPWYHSSLTR EEAERKLYSG AQTDGKFLLR PRKEQGTYAL
210 220 230 240 250
SLIYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK LKADGLIYCL
260 270 280 290 300
KEACPNSSAS NASGAAAPTL PAHPSTLTHP QRRIDTLNSD GYTPEPARIT
310 320 330 340 350
SPDKPRPMPM DTSVYESPYS DPEELKDKKL FLKRDNLLIA DIELGCGNFG
360 370 380 390 400
SVRQGVYRMR KKQIDVAIKV LKQGTEKADT EEMMREAQIM HQLDNPYIVR
410 420 430 440 450
LIGVCQAEAL MLVMEMAGGG PLHKFLVGKR EEIPVSNVAE LLHQVSMGMK
460 470 480 490 500
YLEEKNFVHR DLAARNVLLV NRHYAKISDF GLSKALGADD SYYTARSAGK
510 520 530 540 550
WPLKWYAPEC INFRKFSSRS DVWSYGVTMW EALSYGQKPY KKMKGPEVMA
560 570 580 590 600
FIEQGKRMEC PPECPPELYA LMSDCWIYKW EDRPDFLTVE QRMRACYYSL
610
ASKVEGPPGS TQKAEAACA
Length:619
Mass (Da):69,872
Last modified:November 1, 1995 - v1
Checksum:iD1E1A8EC66FA116F
GO
Isoform 2 (identifier: P43403-2) [UniParc]FASTAAdd to basket
Also known as: TZK

The sequence of this isoform differs from the canonical sequence as follows:
     1-307: Missing.

Show »
Length:312
Mass (Da):35,647
Checksum:iB1D7A63A61D63215
GO
Isoform 3 (identifier: P43403-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-126: Missing.
     127-134: VRQTWKLE → MRLGPRWK

Note: No experimental confirmation available.
Show »
Length:493
Mass (Da):55,873
Checksum:i14F1841C3F898EEF
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041846175R → L.1 PublicationCorresponds to variant rs55964305dbSNPEnsembl.1
Natural variantiVAR_041847191P → L.1 PublicationCorresponds to variant rs56403250dbSNPEnsembl.1
Natural variantiVAR_065623337L → R in IMD48. 1 Publication1
Natural variantiVAR_041848448G → E in a head and neck squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_065624465R → C in IMD48. 1 PublicationCorresponds to variant rs113994174dbSNPEnsembl.1
Natural variantiVAR_015538465R → H in IMD48. 1 PublicationCorresponds to variant rs137853201dbSNPEnsembl.1
Natural variantiVAR_065625507A → V in IMD48. 1 Publication1
Natural variantiVAR_006351518S → R in IMD48. 1 PublicationCorresponds to variant rs104893674dbSNPEnsembl.1
Natural variantiVAR_041849523W → L.1 PublicationCorresponds to variant rs56189815dbSNPEnsembl.1
Natural variantiVAR_038688541K → KLEQ in IMD48. 1 Publication1
Natural variantiVAR_065626564C → R in IMD48. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0311561 – 307Missing in isoform 2. 1 PublicationAdd BLAST307
Alternative sequenceiVSP_0311571 – 126Missing in isoform 3. 1 PublicationAdd BLAST126
Alternative sequenceiVSP_031158127 – 134VRQTWKLE → MRLGPRWK in isoform 3. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05148 mRNA. No translation available.
AB083211 mRNA. Translation: BAC43747.1.
AC016699 Genomic DNA. Translation: AAX93187.1.
BC039039 mRNA. Translation: AAH39039.1.
BC053878 mRNA. Translation: AAH53878.1.
CCDSiCCDS33254.1. [P43403-1]
CCDS33255.1. [P43403-2]
PIRiA44266.
A49955.
RefSeqiNP_001070.2. NM_001079.3. [P43403-1]
NP_997402.1. NM_207519.1. [P43403-2]
UniGeneiHs.234569.

Genome annotation databases

EnsembliENST00000264972; ENSP00000264972; ENSG00000115085. [P43403-1]
ENST00000451498; ENSP00000400475; ENSG00000115085. [P43403-2]
GeneIDi7535.
KEGGihsa:7535.
UCSCiuc002syd.2. human. [P43403-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

ZAP70base

ZAP70 mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05148 mRNA. No translation available.
AB083211 mRNA. Translation: BAC43747.1.
AC016699 Genomic DNA. Translation: AAX93187.1.
BC039039 mRNA. Translation: AAH39039.1.
BC053878 mRNA. Translation: AAH53878.1.
CCDSiCCDS33254.1. [P43403-1]
CCDS33255.1. [P43403-2]
PIRiA44266.
A49955.
RefSeqiNP_001070.2. NM_001079.3. [P43403-1]
NP_997402.1. NM_207519.1. [P43403-2]
UniGeneiHs.234569.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FBVX-ray2.90B289-297[»]
1M61X-ray2.50A1-256[»]
1U59X-ray2.30A327-606[»]
2CBLX-ray2.10B286-297[»]
2OQ1X-ray1.90A3-256[»]
2OZOX-ray2.60A1-606[»]
2Y1NX-ray2.00B/D286-297[»]
3ZNIX-ray2.21B/F/J/N286-297[»]
4A4BX-ray2.79B286-297[»]
4A4CX-ray2.70B286-297[»]
4K2RX-ray3.00A1-606[»]
4XZ0X-ray2.00A1-259[»]
4XZ1X-ray2.80A1-259[»]
ProteinModelPortaliP43403.
SMRiP43403.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113367. 50 interactors.
DIPiDIP-38781N.
IntActiP43403. 20 interactors.
MINTiMINT-110540.
STRINGi9606.ENSP00000264972.

Chemistry databases

BindingDBiP43403.
ChEMBLiCHEMBL2803.
GuidetoPHARMACOLOGYi2285.

PTM databases

iPTMnetiP43403.
PhosphoSitePlusiP43403.

Polymorphism and mutation databases

BioMutaiZAP70.
DMDMi1177044.

Proteomic databases

MaxQBiP43403.
PaxDbiP43403.
PeptideAtlasiP43403.
PRIDEiP43403.

Protocols and materials databases

DNASUi7535.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264972; ENSP00000264972; ENSG00000115085. [P43403-1]
ENST00000451498; ENSP00000400475; ENSG00000115085. [P43403-2]
GeneIDi7535.
KEGGihsa:7535.
UCSCiuc002syd.2. human. [P43403-1]

Organism-specific databases

CTDi7535.
DisGeNETi7535.
GeneCardsiZAP70.
GeneReviewsiZAP70.
HGNCiHGNC:12858. ZAP70.
HPAiCAB002625.
HPA003134.
MalaCardsiZAP70.
MIMi176947. gene.
269840. phenotype.
neXtProtiNX_P43403.
OpenTargetsiENSG00000115085.
Orphaneti911. Combined immunodeficiency due to ZAP70 deficiency.
PharmGKBiPA37447.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH0T. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000113264.
HOVERGENiHBG001540.
InParanoidiP43403.
KOiK07360.
OMAiYKARTAG.
OrthoDBiEOG091G07KU.
PhylomeDBiP43403.
TreeFamiTF351629.

Enzyme and pathway databases

BioCyciZFISH:HS03830-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
R-HSA-202433. Generation of second messenger molecules.
SignaLinkiP43403.
SIGNORiP43403.

Miscellaneous databases

EvolutionaryTraceiP43403.
GeneWikiiZAP70.
GenomeRNAii7535.
PMAP-CutDBP43403.
PROiP43403.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115085.
CleanExiHS_ZAP70.
GenevisibleiP43403. HS.

Family and domain databases

Gene3Di1.10.930.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR023420. Kinase_SYK/ZAP-70_inter-SH2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR012234. Tyr_kinase_non-rcpt_SYK/ZAP70.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PIRSFiPIRSF000604. TyrPK_SYK. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiZAP70_HUMAN
AccessioniPrimary (citable) accession number: P43403
Secondary accession number(s): A6NFP4
, Q6PIA4, Q8IXD6, Q9UBS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 2, 2016
This is version 198 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.