EKS-MUM-00469

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00469

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Syk	498.8	6.4E-150	337	586	250

Status

Reviewed

Ensembl Protein

ENSMUSP00000027291

UniProt Accession

P43404; P97455; Q80VV2; Q8CHJ3;

Protein Name

Tyrosine-protein kinase ZAP-70

Protein Synonyms/Alias

70 kDa zeta-chain associated protein; Syk-related tyrosine kinase;

Gene Name

Zap70

Gene Synonyms/Alias

Zap70; Srk, Zap-70;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000026117	ENSMUSP00000027291	ENSMUST00000027291

Organism

Mus musculus

Functional Description

Tyrosine kinase that plays an essential role inregulation 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).

Protein Length

618

Protein Sequence
(FASTA)

MPDPAAHLPF FYGSISRAEA EEHLKLAGMA DGLFLLRQCL RSLGGYVLSL VHDVRFHHFP 60

IERQLNGTYA IAGGKAHCGP AELCQFYSQD PDGLPCNLRK PCNRPPGLEP QPGVFDCLRD 120

AMVRDYVRQT WKLEGDALEQ AIISQAPQVE KLIATTAHER MPWYHSSLTR EEAERKLYSG 180

QQTDGKFLLR PRKEQGTYAL SLVYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK 240

LKADGLIYRL KEVCPNSSAS AAVAAPTLPA HPSTFTQPQR RVDTLNSDGY TPEPARLASS 300

TDKPRPMPMD TSVYESPYSD PEELKDKKLF LKRENLLVAD IELGCGNFGS VRQGVYRMRK 360

KQIDVAIKVL KQGTEKADKD EMMREAQIMH QLDNPYIVRL IGVCQAEALM LVMEMAGGGP 420

LHKFLLGKKE EIPVSNVAEL LHQVAMGMKY LEEKNFVHRD LAARNVLLVN RHYAKISDFG 480

LSKALGADDS YYTARSAGKW PLKWYAPECI NFRKFSSRSD VWSYGVTMWE AFSYGQKPYK 540

KMKGPEVLDF IKQGKRMECP PECPPEMYAL MSDCWIYKWE DRPDFLTVEQ RMRNYYYSLA 600

SRAEGPPQCE QVAEAACG 618

Nucleotide Sequence
(FASTA)

ATGCCCGATC CCGCGGCGCA CCTGCCATTC TTCTATGGCA GCATCTCGCG GGCTGAGGCC 60

GAGGAGCACC TGAAGCTGGC AGGCATGGCC GACGGGCTGT TCCTCCTGCG CCAGTGTTTG 120

CGCTCCCTGG GCGGCTACGT GCTGTCGTTG GTGCACGACG TGCGCTTCCA CCATTTCCCC 180

ATCGAGCGCC AACTCAACGG CACGTACGCC ATCGCGGGCG GGAAGGCGCA CTGCGGCCCG 240

GCCGAGCTCT GCCAGTTCTA CTCTCAGGAC CCCGACGGGC TGCCCTGCAA CCTGCGTAAG 300

CCGTGTAACC GGCCGCCCGG ACTGGAGCCA CAGCCCGGGG TCTTCGACTG CCTGCGTGAT 360

GCTATGGTGC GCGACTACGT GCGCCAGACC TGGAAGCTGG AGGGCGATGC ACTAGAGCAG 420

GCCATCATCA GCCAGGCCCC ACAGGTGGAG AAGCTCATTG CTACCACAGC CCACGAGCGA 480

ATGCCCTGGT ATCACAGCAG CCTGACTCGT GAGGAGGCCG AGCGCAAACT CTATTCCGGC 540

CAGCAGACCG ACGGCAAGTT CCTGCTGAGG CCCCGGAAGG AGCAGGGCAC ATATGCACTG 600

TCCCTGGTCT ATGGGAAAAC TGTATACCAC TATCTCATCA GCCAGGACAA GGCTGGCAAG 660

TACTGCATCC CCGAAGGCAC CAAGTTTGAC ACGCTCTGGC AGCTGGTGGA GTACCTGAAG 720

CTGAAGGCGG ATGGACTAAT TTACCGCTTG AAGGAGGTCT GTCCCAACAG CAGCGCCAGC 780

GCGGCAGTTG CTGCACCCAC CCTCCCAGCC CACCCATCCA CATTCACTCA GCCTCAGAGA 840

CGAGTGGACA CCCTGAACTC GGACGGATAC ACCCCTGAAC CAGCACGCTT AGCGTCATCG 900

ACAGACAAGC CCCGGCCGAT GCCCATGGAC ACAAGTGTGT ACGAGAGTCC CTACAGCGAC 960

CCTGAGGAAC TCAAAGACAA GAAGCTCTTC CTGAAGCGAG AGAATCTCCT CGTGGCGGAC 1020

ATCGAGCTTG GCTGTGGCAA CTTTGGCTCC GTGCGCCAGG GAGTCTATCG CATGCGCAAG 1080

AAGCAGATTG ACGTGGCCAT CAAGGTGCTG AAGCAGGGCA CAGAGAAGGC CGACAAAGAT 1140

GAGATGATGC GAGAGGCCCA GATCATGCAC CAGCTCGACA ACCCCTACAT CGTGCGGCTC 1200

ATCGGCGTGT GCCAGGCAGA AGCACTCATG CTGGTCATGG AGATGGCGGG AGGCGGGCCC 1260

CTGCACAAGT TCCTGCTGGG AAAGAAGGAG GAGATCCCTG TGAGCAATGT GGCTGAACTG 1320

CTGCACCAGG TGGCCATGGG CATGAAGTAT TTGGAGGAGA AAAACTTTGT GCACCGCGAC 1380

CTGGCAGCCC GCAATGTTCT ACTGGTCAAT CGGCACTATG CCAAGATCAG CGACTTTGGC 1440

CTGTCCAAAG CCCTGGGTGC TGACGACAGC TATTACACAG CCCGGTCTGC AGGGAAGTGG 1500

CCTCTGAAGT GGTACGCGCC AGAGTGCATC AACTTTCGGA AGTTCTCCAG CCGCAGTGAC 1560

GTCTGGAGCT ATGGGGTCAC CATGTGGGAG GCCTTCTCCT ATGGCCAGAA GCCCTACAAG 1620

AAAATGAAGG GCCCCGAGGT CCTGGACTTC ATCAAGCAGG GTAAGAGGAT GGAATGTCCG 1680

CCGGAGTGTC CTCCTGAGAT GTATGCACTT ATGAGTGACT GCTGGATCTA CAAGTGGGAG 1740

GATCGCCCCG ACTTCCTGAC TGTGGAACAA CGTATGCGGA ACTATTACTA CAGCCTGGCC 1800

AGCCGGGCCG AGGGACCCCC ACAGTGTGAA CAGGTGGCCG AGGCTGCATG TGGCTGA 1857

Domain Profile

S: 1     lvedkelGsGnfGsvkkGyyrmkkkrlevaikvlkeadekadkdellreasvmqqldnky  60

         lv+d+elG+GnfGsv++G+yrm+kk+++vaikvlk+++ekadkde++rea++m+qldn+y

Q: 337   LVADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADKDEMMREAQIMHQLDNPY  396

         699*********************************************************

S: 61    ivrliGiakaealmlvmelaelGpllkylldkreeikaknvlelvhqvamGmkyleeknf  120

         ivrliG+++aealmlvme+a++Gpl+k+ll+k+eei+++nv+el+hqvamGmkyleeknf

Q: 397   IVRLIGVCQAEALMLVMEMAGGGPLHKFLLGKKEEIPVSNVAELLHQVAMGMKYLEEKNF  456

         ************************************************************

S: 121   vhrdlaarnvllvarhyakisdfGlskalradesyykarsaGkwpvkwyapecinlrkfs  180

         vhrdlaarnvllv+rhyakisdfGlskal+ad+syy+arsaGkwp+kwyapecin+rkfs

Q: 457   VHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWPLKWYAPECINFRKFS  516

         ************************************************************

S: 181   sksdvwsfGvtlweafsyGqkpykelkgsevlalvekGerlecpaecpaelyalmsscwk  240

         s+sdvws+Gvt+weafsyGqkpyk++kg+evl+++++G+r+ecp+ecp+e+yalms+cw+

Q: 517   SRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVLDFIKQGKRMECPPECPPEMYALMSDCWI  576

         ************************************************************

S: 241   ykvedrpdfl  250

         yk+edrpdfl

Q: 577   YKWEDRPDFL  586

         *********6

Domain Sequence
(FASTA)

LVADIELGCG NFGSVRQGVY RMRKKQIDVA IKVLKQGTEK ADKDEMMREA QIMHQLDNPY 60

IVRLIGVCQA EALMLVMEMA GGGPLHKFLL GKKEEIPVSN VAELLHQVAM GMKYLEEKNF 120

VHRDLAARNV LLVNRHYAKI SDFGLSKALG ADDSYYTARS AGKWPLKWYA PECINFRKFS 180

SRSDVWSYGV TMWEAFSYGQ KPYKKMKGPE VLDFIKQGKR MECPPECPPE MYALMSDCWI 240

YKWEDRPDFL 250

Keyword

Adaptive immunity; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; SH2 domain; Transferase; Tyrosine-protein kinase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Dipodomys ordii"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Erinaceus europaeus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pongo abelii"; ?>Procavia capensis"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0001772	; C:immunological synapse
GO:0042101	; C:T cell receptor complex
GO:0005524	; F:ATP binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0004713	; F:protein tyrosine kinase activity
GO:0043366	; P:beta selection
GO:0006955	; P:immune response
GO:0035556	; P:intracellular signal transduction
GO:0045060	; P:negative thymic T cell selection
GO:0018108	; P:peptidyl-tyrosine phosphorylation
GO:0046638	; P:positive regulation of alpha-beta T cell differentiation
GO:0046641	; P:positive regulation of alpha-beta T cell proliferation
GO:0050850	; P:positive regulation of calcium-mediated signaling
GO:0045059	; P:positive thymic T cell selection
GO:0046777	; P:protein autophosphorylation
GO:0050852	; P:T cell receptor signaling pathway

KEGG

mmu:22637

;

InterPros

IPR011009	; Kinase-like_dom.
IPR023420	; Kinase_SYK/ZAP-70_inter-SH2.
IPR000719	; Prot_kinase_cat_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.

Pfam

PF07714	; Pkinase_Tyr; 1.
PF00017	; SH2; 2.

SMARTs

SM00252	; SH2; 2.
SM00219	; TyrKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50001	; SH2; 2.

Prints

PR00401	; SH2DOMAIN.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013