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Showing Protein Tyrosine-protein kinase ZAP-70 (HMDBP01515)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 2 metabolites
Identification
HMDB Protein ID HMDBP01515
Secondary Accession Numbers
  • 6811
Name Tyrosine-protein kinase ZAP-70
Synonyms
  1. 70 kDa zeta-associated protein
  2. Syk-related tyrosine kinase
Gene Name ZAP70
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Plays a role in T-cell development and lymphocyte activation. Essential for TCR-mediated IL-2 production. Isoform 1 induces TCR-mediated signal transduction, isoform 2 does not
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular part
cytoplasm
Function
protein tyrosine kinase activity
non-membrane spanning protein tyrosine kinase activity
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
protein kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
immune system process
immune response
signaling process
signal transmission
cellular metabolic process
protein amino acid phosphorylation
intracellular signaling pathway
signaling
signaling pathway
phosphorylation
signal transmission via phosphorylation event
intracellular protein kinase cascade
Cellular Location
  1. Cell membrane
  2. Cytoplasm
Gene Properties
Chromosome Location Chromosome:2
Locus 2q12
SNPs ZAP70
Gene Sequence 
>1860 bp
ATGCCAGACCCCGCGGCGCACCTGCCCTTCTTCTACGGCAGCATCTCGCGTGCCGAGGCC
GAGGAGCACCTGAAGCTGGCGGGCATGGCGGACGGGCTCTTCCTGCTGCGCCAGTGCCTG
CGCTCGCTGGGCGGCTATGTGCTGTCGCTCGTGCACGATGTGCGCTTCCACCACTTTCCC
ATCGAGCGCCAGCTCAACGGCACCTACGCCATTGCCGGCGGCAAAGCGCACTGTGGACCG
GCAGAGCTCTGCGAGTTCTACTCGCGCGACCCCGACGGGCTGCCCTGCAACCTGCGCAAG
CCGTGCAACCGGCCGTCGGGCCTCGAGCCGCAGCCGGGGGTCTTCGACTGCCTGCGAGAC
GCCATGGTGCGTGACTACGTGCGCCAGACGTGGAAGCTGGAGGGCGAGGCCCTGGAGCAG
GCCATCATCAGCCAGGCCCCGCAGGTGGAGAAGCTCATTGCTACGACGGCCCACGAGCGG
ATGCCCTGGTACCACAGCAGCCTGACGCGTGAGGAGGCCGAGCGCAAACTTTACTCTGGG
GCGCAGACCGACGGCAAGTTCCTGCTGAGGCCGCGGAAGGAGCAGGGCACATACGCCCTG
TCCCTCATCTATGGGAAGACGGTGTACCACTACCTCATCAGCCAAGACAAGGCGGGCAAG
TACTGCATTCCCGAGGGCACCAAGTTTGACACGCTCTGGCAGCTGGTGGAGTATCTGAAG
CTGAAGGCGGACGGGCTCATCTACTGCCTGAAGGAGGCCTGCCCCAACAGCAGTGCCAGC
AACGCCTCAGGGGCTGCTGCTCCCACACTCCCAGCCCACCCATCCACGTTGACTCATCCT
CAGAGACGAATCGACACCCTCAACTCAGATGGATACACCCCTGAGCCAGCACGCATAACG
TCCCCAGACAAACCGCGGCCGATGCCCATGGACACGAGCGTGTATGAGAGCCCCTACAGC
GACCCAGAGGAGCTCAAGGACAAGAAGCTCTTCCTGAAGCGCGATAACCTCCTCATAGCT
GACATTGAACTTGGCTGCGGCAACTTTGGCTCAGTGCGCCAGGGCGTGTACCGCATGCGC
AAGAAGCAGATCGACGTGGCCATCAAGGTGCTGAAGCAGGGCACGGAGAAGGCAGACACG
GAAGAGATGATGCGCGAGGCGCAGATCATGCACCAGCTGGACAACCCCTACATCGTGCGG
CTCATTGGCGTCTGCCAGGCCGAGGCCCTCATGCTGGTCATGGAGATGGCTGGGGGCGGG
CCGCTGCACAAGTTCCTGGTCGGCAAGAGGGAGGAGATCCCTGTGAGCAATGTGGCCGAG
CTGCTGCACCAGGTGTCCATGGGGATGAAGTACCTGGAGGAGAAGAACTTTGTGCACCGT
GACCTGGCGGCCCGCAACGTCCTGCTGGTTAACCGGCACTACGCCAAGATCAGCGACTTT
GGCCTCTCCAAAGCACTGGGTGCCGACGACAGCTACTACACTGCCCGCTCAGCAGGGAAG
TGGCCGCTCAAGTGGTACGCACCCGAATGCATCAACTTCCGCAAGTTCTCCAGCCGCAGC
GATGTCTGGAGCTATGGGGTCACCATGTGGGAGGCCTTGTCCTACGGCCAGAAGCCCTAC
AAGAAGATGAAAGGGCCGGAGGTCATGGCCTTCATCGAGCAGGGCAAGCGGATGGAGTGC
CCACCAGAGTGTCCACCCGAACTGTACGCACTCATGAGTGACTGCTGGATCTACAAGTGG
GAGGATCGCCCCGACTTCCTGACCGTGGAGCAGCGCATGCGAGCCTGTTACTACAGCCTG
GCCAGCAAGGTGGAAGGGCCCCCAGGCAGCACACAGAAGGCTGAGGCTGCCTGTGCCTGA
Protein Properties
Number of Residues 619
Molecular Weight 69871.6
Theoretical pI 7.75
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Tyrosine-protein kinase ZAP-70
MPDPAAHLPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFP
IERQLNGTYAIAGGKAHCGPAELCEFYSRDPDGLPCNLRKPCNRPSGLEPQPGVFDCLRD
AMVRDYVRQTWKLEGEALEQAIISQAPQVEKLIATTAHERMPWYHSSLTREEAERKLYSG
AQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLK
LKADGLIYCLKEACPNSSASNASGAAAPTLPAHPSTLTHPQRRIDTLNSDGYTPEPARIT
SPDKPRPMPMDTSVYESPYSDPEELKDKKLFLKRDNLLIADIELGCGNFGSVRQGVYRMR
KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGG
PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDF
GLSKALGADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPY
KKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRACYYSL
ASKVEGPPGSTQKAEAACA
GenBank ID Protein 31455611
UniProtKB/Swiss-Prot ID P43403
UniProtKB/Swiss-Prot Entry Name ZAP70_HUMAN
PDB IDs
GenBank Gene ID NM_001079.3
GeneCard ID ZAP70
GenAtlas ID ZAP70
HGNC ID HGNC:12858
References
General References
  1. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [PubMed:15592455 ]
  4. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  5. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  6. Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R: Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. Nat Methods. 2005 Aug;2(8):591-8. [PubMed:16094384 ]
  7. Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC: Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. Anal Chem. 2004 May 15;76(10):2763-72. [PubMed:15144186 ]
  8. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  9. Wissing J, Jansch L, Nimtz M, Dieterich G, Hornberger R, Keri G, Wehland J, Daub H: Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry. Mol Cell Proteomics. 2007 Mar;6(3):537-47. Epub 2006 Dec 27. [PubMed:17192257 ]
  10. Salomon AR, Ficarro SB, Brill LM, Brinker A, Phung QT, Ericson C, Sauer K, Brock A, Horn DM, Schultz PG, Peters EC: Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):443-8. Epub 2003 Jan 9. [PubMed:12522270 ]
  11. Tang J, Sawasdikosol S, Chang JH, Burakoff SJ: SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling. Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9775-80. [PubMed:10449770 ]
  12. Xu MJ, Zhao R, Zhao ZJ: Molecular cloning and characterization of SPAP1, an inhibitory receptor. Biochem Biophys Res Commun. 2001 Jan 26;280(3):768-75. [PubMed:11162587 ]
  13. Chan AC, Iwashima M, Turck CW, Weiss A: ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell. 1992 Nov 13;71(4):649-62. [PubMed:1423621 ]
  14. Kuroyama H, Ikeda T, Kasai M, Yamasaki S, Tatsumi M, Utsuyama M, Saito T, Hirokawa K: Identification of a novel isoform of ZAP-70, truncated ZAP kinase. Biochem Biophys Res Commun. 2004 Mar 19;315(4):935-41. [PubMed:14985102 ]
  15. Arpaia E, Shahar M, Dadi H, Cohen A, Roifman CM: Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell. 1994 Mar 11;76(5):947-58. [PubMed:8124727 ]
  16. Isakov N, Wange RL, Burgess WH, Watts JD, Aebersold R, Samelson LE: ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. J Exp Med. 1995 Jan 1;181(1):375-80. [PubMed:7528772 ]
  17. Di Bartolo V, Mege D, Germain V, Pelosi M, Dufour E, Michel F, Magistrelli G, Isacchi A, Acuto O: Tyrosine 319, a newly identified phosphorylation site of ZAP-70, plays a critical role in T cell antigen receptor signaling. J Biol Chem. 1999 Mar 5;274(10):6285-94. [PubMed:10037717 ]
  18. Lindholm CK, Henriksson ML, Hallberg B, Welsh M: Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells. Eur J Biochem. 2002 Jul;269(13):3279-88. [PubMed:12084069 ]
  19. Folmer RH, Geschwindner S, Xue Y: Crystal structure and NMR studies of the apo SH2 domains of ZAP-70: two bikes rather than a tandem. Biochemistry. 2002 Dec 3;41(48):14176-84. [PubMed:12450381 ]
  20. Chan AC, Kadlecek TA, Elder ME, Filipovich AH, Kuo WL, Iwashima M, Parslow TG, Weiss A: ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science. 1994 Jun 10;264(5165):1599-601. [PubMed:8202713 ]
  21. Toyabe S, Watanabe A, Harada W, Karasawa T, Uchiyama M: Specific immunoglobulin E responses in ZAP-70-deficient patients are mediated by Syk-dependent T-cell receptor signalling. Immunology. 2001 Jun;103(2):164-71. [PubMed:11412303 ]