P43404

SS
Gene name
Zap70 (Srk, Zap-70)
Protein name
Tyrosine-protein kinase ZAP-70
Names
70 kDa zeta-chain associated protein, Syk-related tyrosine kinase
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:22637
EC number
2.7.10.2: Protein-tyrosine kinases
Protein Class

Descriptions

ZAP-70, a Syk family cytoplasmic protein tyrosine kinase (PTK), is required to couple the activated T-cell antigen receptor (TCR) to downstream signaling pathways. It contains two tandem SH2 domains that bind to phosphorylated TCR subunits and a C-terminal catalytic domain. The region connecting the SH2 domains with the kinase domain, termed interdomain B, has previously been shown to have striking regulatory effects on ZAP-70 function, presumed to be due to the recruitment of key substrates.In EphB2 and several other RTKs, this autoinhibition depends upon interaction between the kinase domain and tyrosine residues within the juxtamembrane region. Autoinhibition is released when these tyrosines become phosphorylated following receptor stimulation. Sequence homology suggested analogous regulation for ZAP-70.

Autoinhibitory domains (AIDs)

103-162 (Interdomain A) SS

Target domain

337-597 (Protein kinase domain)

Relief mechanism

Partner binding, PTM

Assay

255-336 (Interdomain B) SS

Target domain

337-597 (Protein kinase domain)

Relief mechanism

Partner binding, PTM

Assay

Accessory elements

477-503 (Activation loop from InterPro)

Target domain

337-597 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for P43404

Entry ID Method Resolution Chain Position Source
AF-P43404-F1 Predicted AlphaFoldDB

4 variants for P43404

Variant ID(s) Position Change Description Diseaes Association Provenance
rs864308555 561 P>R No Ensembl
rs248085987 562 E>G No Ensembl
rs226362515 592 M>I No Ensembl
464 R>C ST; causes an absence of mature T-cells due to thymocyte development being arrested at the CD4+CD8+ stage [UniProt] No

No associated diseases with P43404

8 regional properties for P43404

Type Name Position InterPro Accession
domain Protein kinase domain 337 - 597 IPR000719
domain SH2 domain 8 - 102 IPR000980-1
domain SH2 domain 161 - 254 IPR000980-2
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 341 - 591 IPR001245
active_site Tyrosine-protein kinase, active site 456 - 468 IPR008266
binding_site Protein kinase, ATP binding site 343 - 368 IPR017441
domain Tyrosine-protein kinase, catalytic domain 337 - 592 IPR020635
domain SYK/ZAP-70, N-terminal SH2 domain 8 - 111 IPR035838

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cytoplasm
  • Cell membrane; Peripheral membrane protein
  • In quiescent T-lymphocytes, ZAP70 is cytoplasmic
  • Upon TCR activation, it is recruited at the plasma membrane by interacting with CD3Z
  • Colocalizes together with RHOH in the immunological synapse
  • RHOH is required for its proper localization to the cell membrane and cytoskeleton fractions in the thymocytes
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
cell-cell junction A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extrinsic component of cytoplasmic side of plasma membrane The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region.
immunological synapse An area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell formed through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and the target cell and facilitating activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
membrane raft Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
T cell receptor complex A protein complex that contains a disulfide-linked heterodimer of T cell receptor (TCR) chains, which are members of the immunoglobulin superfamily, and mediates antigen recognition, ultimately resulting in T cell activation. The TCR heterodimer is associated with the CD3 complex, which consists of the nonpolymorphic polypeptides gamma, delta, epsilon, zeta, and, in some cases, eta (an RNA splice variant of zeta) or Fc epsilon chains.

7 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction: ATP + protein L-tyrosine = ADP + protein L-tyrosine phosphate by a non-membrane spanning protein.
phosphotyrosine residue binding Binding to a phosphorylated tyrosine residue within a protein.
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
protein tyrosine kinase activity Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
signaling receptor binding Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.

18 GO annotations of biological process

Name Definition
adaptive immune response An immune response mediated by cells expressing specific receptors for antigen produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory).
beta selection The process in which successful recombination of a T cell receptor beta chain into a translatable protein coding sequence leads to rescue from apoptosis and subsequent proliferation of an immature T cell.
cell differentiation The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
immune response Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative thymic T cell selection The process of elimination of immature T cells in the thymus which react strongly with self-antigens.
peptidyl-tyrosine phosphorylation The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
positive regulation of alpha-beta T cell differentiation Any process that activates or increases the frequency, rate or extent of alpha-beta T cell differentiation.
positive regulation of alpha-beta T cell proliferation Any process that activates or increases the frequency, rate or extent of alpha-beta T cell proliferation.
positive regulation of calcium-mediated signaling Any process that activates or increases the frequency, rate or extent of calcium-mediated signaling.
positive regulation of T cell differentiation Any process that activates or increases the frequency, rate or extent of T cell differentiation.
positive thymic T cell selection The process of sparing immature T cells in the thymus which react with self-MHC protein complexes with low affinity levels from apoptotic death.
protein autophosphorylation The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein phosphorylation The process of introducing a phosphate group on to a protein.
T cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
thymic T cell selection The process of T cell selection that occurs in the thymus.
transmembrane receptor protein tyrosine kinase signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.

36 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
F1N9Y5 SYK Tyrosine-protein kinase SYK Gallus gallus (Chicken) SS
P43405 SYK Tyrosine-protein kinase SYK Homo sapiens (Human) EV
P43403 ZAP70 Tyrosine-protein kinase ZAP-70 Homo sapiens (Human) EV
P48025 Syk Tyrosine-protein kinase SYK Mus musculus (Mouse) SS
Q64434 Ptk6 Protein-tyrosine kinase 6 Mus musculus (Mouse) SS
P14234 Fgr Tyrosine-protein kinase Fgr Mus musculus (Mouse) SS
P25911 Lyn Tyrosine-protein kinase Lyn Mus musculus (Mouse) EV
P39688 Fyn Tyrosine-protein kinase Fyn Mus musculus (Mouse) SS
P05480 Src Proto-oncogene tyrosine-protein kinase Src Mus musculus (Mouse) EV
P06240 Lck Proto-oncogene tyrosine-protein kinase LCK Mus musculus (Mouse) SS
P16277 Blk Tyrosine-protein kinase Blk Mus musculus (Mouse) SS
P08103 Hck Tyrosine-protein kinase HCK Mus musculus (Mouse) SS
Q04736 Yes1 Tyrosine-protein kinase Yes Mus musculus (Mouse) SS
Q922K9 Frk Tyrosine-protein kinase FRK Mus musculus (Mouse) SS
Q03526 Itk Tyrosine-protein kinase ITK/TSK Mus musculus (Mouse) SS
P35991 Btk Tyrosine-protein kinase BTK Mus musculus (Mouse) EV
P24604 Tec Tyrosine-protein kinase Tec Mus musculus (Mouse) SS
P41242 Matk Megakaryocyte-associated tyrosine-protein kinase Mus musculus (Mouse) SS
P41241 Csk Tyrosine-protein kinase CSK Mus musculus (Mouse) EV
Q9QVP9 Ptk2b Protein-tyrosine kinase 2-beta Mus musculus (Mouse) PR
P34152 Ptk2 Focal adhesion kinase 1 Mus musculus (Mouse) SS
Q99ML2 Tnk1 Non-receptor tyrosine-protein kinase TNK1 Mus musculus (Mouse) PR
O54967 Tnk2 Activated CDC42 kinase 1 Mus musculus (Mouse) SS
P70451 Fer Tyrosine-protein kinase Fer Mus musculus (Mouse) PR
Q6J9G1 Styk1 Tyrosine-protein kinase STYK1 Mus musculus (Mouse) PR
P00520 Abl1 Tyrosine-protein kinase ABL1 Mus musculus (Mouse) EV
Q62270 Srms Tyrosine-protein kinase Srms Mus musculus (Mouse) SS
Q4JIM5 Abl2 Tyrosine-protein kinase ABL2 Mus musculus (Mouse) SS
Q00655 SYK Tyrosine-protein kinase SYK Sus scrofa (Pig) SS
Q64725 Syk Tyrosine-protein kinase SYK Rattus norvegicus (Rat) SS
Q9SYA0 At1g61500 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61500 Arabidopsis thaliana (Mouse-ear cress) SS
Q9FG33 LECRKS5 Probable L-type lectin-domain containing receptor kinase S.5 Arabidopsis thaliana (Mouse-ear cress) PR
F4JTP5 STY46 Serine/threonine-protein kinase STY46 Arabidopsis thaliana (Mouse-ear cress) PR
O22558 STY8 Serine/threonine-protein kinase STY8 Arabidopsis thaliana (Mouse-ear cress) PR
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWL6 STY17 Serine/threonine-protein kinase STY17 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MPDPAAHLPF FYGSISRAEA EEHLKLAGMA DGLFLLRQCL RSLGGYVLSL VHDVRFHHFP
70 80 90 100 110 120
IERQLNGTYA IAGGKAHCGP AELCQFYSQD PDGLPCNLRK PCNRPPGLEP QPGVFDCLRD
130 140 150 160 170 180
AMVRDYVRQT WKLEGDALEQ AIISQAPQVE KLIATTAHER MPWYHSSLTR EEAERKLYSG
190 200 210 220 230 240
QQTDGKFLLR PRKEQGTYAL SLVYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK
250 260 270 280 290 300
LKADGLIYRL KEVCPNSSAS AAVAAPTLPA HPSTFTQPQR RVDTLNSDGY TPEPARLASS
310 320 330 340 350 360
TDKPRPMPMD TSVYESPYSD PEELKDKKLF LKRENLLVAD IELGCGNFGS VRQGVYRMRK
370 380 390 400 410 420
KQIDVAIKVL KQGTEKADKD EMMREAQIMH QLDNPYIVRL IGVCQAEALM LVMEMAGGGP
430 440 450 460 470 480
LHKFLLGKKE EIPVSNVAEL LHQVAMGMKY LEEKNFVHRD LAARNVLLVN RHYAKISDFG
490 500 510 520 530 540
LSKALGADDS YYTARSAGKW PLKWYAPECI NFRKFSSRSD VWSYGVTMWE AFSYGQKPYK
550 560 570 580 590 600
KMKGPEVLDF IKQGKRMECP PECPPEMYAL MSDCWIYKWE DRPDFLTVEQ RMRNYYYSLA
610
SRAEGPPQCE QVAEAACG