Reviewed, UniProtKB/Swiss-Prot P43403 (ZAP70_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase ZAP-70
    EC=2.7.10.2
Alternative name(s):
    70 kDa zeta-associated protein
    Syk-related tyrosine kinase

Gene names

Name:	ZAP70
Synonyms:	SRK

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	619 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. Ref.1 Ref.5
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with SLA2 when it is phosphorylated. Interacts with CD3Z and with phosphorylated NFAM1. Interacts with CBLB By similarity. Interacts with CBL and SLA when it is phosphorylated. The association with SLA (or SLA2) and CBL probably leads to its destruction. Interacts with SHB. Interacts with DEF6. Interacts (via SH2 domains) with RHOH By similarity. Interacts with FCRL3. Ref.1 Ref.8 Ref.9 Ref.10
Subcellular location	Cytoplasm By similarity. Cell membrane By similarity. Note: After antigen stimulation, isoform 1 concentrates at the immunological synapse and isoform 2 remains cytoplasmic. 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.
Tissue specificity	Expressed in T- and natural killer cells. Ref.1
Domain	The SH2 domains bind to the phosphorylated tyrosine-based activation motif (TAM) of CD3Z and the non-canonical phosphorylated tyrosine-based activation motif (TAM) of RHOH By similarity.
Post-translational modification	Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Tyr-319 phosphorylation is essential for full activity. Ref.1 Ref.7 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
Involvement in disease	Defects in ZAP70 are the cause of selective T-cell defect (STD) [MIM:176947]. STD is an autosomal recessive form of severe combined immunodeficiency characterized by a selective absence of CD8-type T-cells. Ref.5 Ref.19 Ref.20
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily. Contains 1 protein kinase domain. Contains 2 SH2 domains.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation SCID
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	immune response Ref.1 Inferred from direct assay. Source: UniProtKB positive thymic T cell selection Inferred from direct assay. Source: MGI protein kinase cascade Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	T cell receptor complex Inferred from direct assay. Source: MGI cytosol Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Ref.1 Non-traceable author statement. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LCK	P06239	1	EBI-1211276,EBI-1348
PTPN22	Q9Y2R2	2	EBI-1211276,EBI-1211241

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P43403-1)

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.

Isoform 2 (identifier: P43403-2)

Also known as: TZK;

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

Isoform 3 (identifier: P43403-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 619

619

Tyrosine-protein kinase ZAP-70

PRO_0000088168

Regions

Domain

10 – 102

93

SH2 1

Domain

163 – 254

92

SH2 2

Domain

338 – 600

263

Protein kinase

Nucleotide binding

344 – 352

9

ATP By similarity

Sites

Active site

461

1

Proton acceptor By similarity

Binding site

369

1

ATP By similarity

Amino acid modifications

Modified residue

248

1

Phosphotyrosine Ref.13 Ref.15

Modified residue

289

1

Phosphoserine Ref.12

Modified residue

292

1

Phosphotyrosine Ref.11 Ref.13 Ref.14 Ref.15 Ref.16

Modified residue

315

1

Phosphotyrosine Ref.7 Ref.11 Ref.13 Ref.14

Modified residue

319

1

Phosphotyrosine Ref.7 Ref.11 Ref.13 Ref.14

Modified residue

492

1

Phosphotyrosine; by autocatalysis Ref.11 Ref.13 Ref.14 Ref.15 Ref.16

Modified residue

493

1

Phosphotyrosine Ref.11 Ref.13 Ref.14

Modified residue

603

1

N6-acetyllysine Ref.17

Natural variations

Alternative sequence

1 – 307

307

Missing in isoform 2.

VSP_031156

Alternative sequence

1 – 126

126

Missing in isoform 3.

VSP_031157

Alternative sequence

127 – 134

8

VRQTWKLE → MRLGPRWK in isoform 3.

VSP_031158

Natural variant

175

1

R → L: dbSNP rs55964305. Ref.21

VAR_041846

Natural variant

191

1

P → L: dbSNP rs56403250. Ref.21

VAR_041847

Natural variant

448

1

G → E in a head and neck squamous cell carcinoma sample; somatic mutation. Ref.21

VAR_041848

Natural variant

465

1

R → H in STD. Ref.20

VAR_015538

Natural variant

518

1

S → R in STD. Ref.19

VAR_006351

Natural variant

523

1

W → L: dbSNP rs56189815. Ref.21

VAR_041849

Natural variant

541

1

K → KLEQ in STD.

VAR_038688

Experimental info

Mutagenesis

315

1

Y → F: No inhibition of activation. Ref.7

Mutagenesis

319

1

Y → F: Inhibition of activation. Ref.7

Secondary structure

1

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619

Helix Strand Turn

Details...

Turn

4 – 7

4

Helix

17 – 26

10

Beta strand

34 – 38

5

Beta strand

40 – 42

3

Beta strand

46 – 52

7

Beta strand

55 – 63

9

Beta strand

69 – 71

3

Beta strand

77 – 79

3

Helix

80 – 89

10

Beta strand

94 – 96

3

Helix

114 – 131

18

Helix

135 – 156

22

Helix

157 – 160

4

Helix

170 – 178

9

Beta strand

186 – 191

6

Beta strand

197 – 204

8

Beta strand

207 – 215

9

Beta strand

221 – 223

3

Beta strand

229 – 231

3

Helix

232 – 241

10

Beta strand

246 – 248

3

Beta strand

316 – 320

5

Helix

334 – 336

3

Beta strand

337 – 345

9

Beta strand

350 – 357

8

Beta strand

364 – 371

8

Helix

377 – 392

16

Beta strand

401 – 415

15

Helix

422 – 426

5

Turn

430 – 432

3

Helix

435 – 454

20

Helix

464 – 466

3

Beta strand

467 – 471

5

Beta strand

474 – 477

4

Helix

503 – 505

3

Helix

508 – 513

6

Helix

518 – 533

16

Turn

539 – 542

4

Helix

546 – 553

8

Helix

566 – 574

9

Helix

580 – 582

3

Helix

586 – 601

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: D1E1A8EC66FA116F	FASTA	619	69,872
	10 20 30 40 50 60 MPDPAAHLPF FYGSISRAEA EEHLKLAGMA DGLFLLRQCL RSLGGYVLSL VHDVRFHHFP 70 80 90 100 110 120 IERQLNGTYA IAGGKAHCGP AELCEFYSRD PDGLPCNLRK PCNRPSGLEP QPGVFDCLRD 130 140 150 160 170 180 AMVRDYVRQT WKLEGEALEQ AIISQAPQVE KLIATTAHER MPWYHSSLTR EEAERKLYSG 190 200 210 220 230 240 AQTDGKFLLR PRKEQGTYAL SLIYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK 250 260 270 280 290 300 LKADGLIYCL KEACPNSSAS NASGAAAPTL PAHPSTLTHP QRRIDTLNSD GYTPEPARIT 310 320 330 340 350 360 SPDKPRPMPM DTSVYESPYS DPEELKDKKL FLKRDNLLIA DIELGCGNFG SVRQGVYRMR 370 380 390 400 410 420 KKQIDVAIKV LKQGTEKADT EEMMREAQIM HQLDNPYIVR LIGVCQAEAL MLVMEMAGGG 430 440 450 460 470 480 PLHKFLVGKR EEIPVSNVAE LLHQVSMGMK YLEEKNFVHR DLAARNVLLV NRHYAKISDF 490 500 510 520 530 540 GLSKALGADD SYYTARSAGK WPLKWYAPEC INFRKFSSRS DVWSYGVTMW EALSYGQKPY 550 560 570 580 590 600 KKMKGPEVMA FIEQGKRMEC PPECPPELYA LMSDCWIYKW EDRPDFLTVE QRMRACYYSL 610 ASKVEGPPGS TQKAEAACA
	Isoform 2 (TZK). Checksum: B1D7A63A61D63215	FASTA	312	35,647
	10 20 30 40 50 60 MPMDTSVYES PYSDPEELKD KKLFLKRDNL LIADIELGCG NFGSVRQGVY RMRKKQIDVA 70 80 90 100 110 120 IKVLKQGTEK ADTEEMMREA QIMHQLDNPY IVRLIGVCQA EALMLVMEMA GGGPLHKFLV 130 140 150 160 170 180 GKREEIPVSN VAELLHQVSM GMKYLEEKNF VHRDLAARNV LLVNRHYAKI SDFGLSKALG 190 200 210 220 230 240 ADDSYYTARS AGKWPLKWYA PECINFRKFS SRSDVWSYGV TMWEALSYGQ KPYKKMKGPE 250 260 270 280 290 300 VMAFIEQGKR MECPPECPPE LYALMSDCWI YKWEDRPDFL TVEQRMRACY YSLASKVEGP 310 PGSTQKAEAA CA
	Isoform 3. Checksum: 14F1841C3F898EEF	FASTA	493	55,873
	10 20 30 40 50 60 MRLGPRWKGE ALEQAIISQA PQVEKLIATT AHERMPWYHS SLTREEAERK LYSGAQTDGK 70 80 90 100 110 120 FLLRPRKEQG TYALSLIYGK TVYHYLISQD KAGKYCIPEG TKFDTLWQLV EYLKLKADGL 130 140 150 160 170 180 IYCLKEACPN SSASNASGAA APTLPAHPST LTHPQRRIDT LNSDGYTPEP ARITSPDKPR 190 200 210 220 230 240 PMPMDTSVYE SPYSDPEELK DKKLFLKRDN LLIADIELGC GNFGSVRQGV YRMRKKQIDV 250 260 270 280 290 300 AIKVLKQGTE KADTEEMMRE AQIMHQLDNP YIVRLIGVCQ AEALMLVMEM AGGGPLHKFL 310 320 330 340 350 360 VGKREEIPVS NVAELLHQVS MGMKYLEEKN FVHRDLAARN VLLVNRHYAK ISDFGLSKAL 370 380 390 400 410 420 GADDSYYTAR SAGKWPLKWY APECINFRKF SSRSDVWSYG VTMWEALSYG QKPYKKMKGP 430 440 450 460 470 480 EVMAFIEQGK RMECPPECPP ELYALMSDCW IYKWEDRPDF LTVEQRMRAC YYSLASKVEG 490 PPGSTQKAEA ACA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain." Chan A.C., Iwashima M., Turck C.W., Weiss A. Cell 71:649-662(1992) [PubMed: 1423621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CD3Z, TISSUE SPECIFICITY, PHOSPHORYLATION.
[2]	"Identification of a novel isoform of ZAP-70, truncated ZAP kinase." Kuroyama H., Ikeda T., Kasai M., Yamasaki S., Tatsumi M., Utsuyama M., Saito T., Hirokawa K. Biochem. Biophys. Res. Commun. 315:935-941(2004) [PubMed: 14985102] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Leukocyte.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., 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 E.A., 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 S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Blood and Brain.
[5]	"Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase." Arpaia E., Shahar M., Dadi H., Cohen A., Roifman C.M. Cell 76:947-958(1994) [PubMed: 8124727] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 521-547, VARIANT STD LEU-GLU-GLN-541 INS, FUNCTION. Tissue: Lymphoid tissue.
[6]	"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." Isakov N., Wange R.L., Burgess W.H., Watts J.D., Aebersold R., Samelson L.E. J. Exp. Med. 181:375-380(1995) [PubMed: 7528772] [Abstract] Cited for: CHARACTERIZATION OF TAM-BINDING.
[7]	"Tyrosine 319, a newly identified phosphorylation site of ZAP-70, plays a critical role in T cell antigen receptor signaling." Di Bartolo V., Mege D., Germain V., Pelosi M., Dufour E., Michel F., Magistrelli G., Isacchi A., Acuto O. J. Biol. Chem. 274:6285-6294(1999) [PubMed: 10037717] [Abstract] Cited for: PHOSPHORYLATION AT TYR-315 AND TYR-319, MUTAGENESIS OF TYR-315 AND TYR-319.
[8]	"SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling." Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J. Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999) [PubMed: 10449770] [Abstract] Cited for: INTERACTION WITH CBL AND SLA.
[9]	"Molecular cloning and characterization of SPAP1, an inhibitory receptor." Xu M.-J., Zhao R., Zhao Z.J. Biochem. Biophys. Res. Commun. 280:768-775(2001) [PubMed: 11162587] [Abstract] Cited for: INTERACTION WITH FCRL3.
[10]	"Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells." Lindholm C.K., Henriksson M.L., Hallberg B., Welsh M. Eur. J. Biochem. 269:3279-3288(2002) [PubMed: 12084069] [Abstract] Cited for: INTERACTION WITH SHB.
[11]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed: 12522270] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292; TYR-315; TYR-319; TYR-492 AND TYR-493, MASS SPECTROMETRY.
[12]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289, MASS SPECTROMETRY. Tissue: T-cell.
[13]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-248; TYR-292; TYR-315; TYR-319; TYR-492 AND TYR-493, MASS SPECTROMETRY.
[14]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292; TYR-315; TYR-319; TYR-492 AND TYR-493, MASS SPECTROMETRY. Tissue: T-cell.
[15]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-248; TYR-292 AND TYR-492, MASS SPECTROMETRY.
[16]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND TYR-492, MASS SPECTROMETRY. Tissue: T-cell.
[17]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-603, MASS SPECTROMETRY.
[18]	"Crystal structure and NMR studies of the apo SH2 domains of ZAP-70: two bikes rather than a tandem." Folmer R.H., Geschwindner S., Xue Y. Biochemistry 41:14176-14184(2002) [PubMed: 12450381] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-256.
[19]	"ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency." Chan A.C., Kadlecek T.A., Elder M.E., Filipovich A.H., Kuo W.-L., Iwashima M., Parslow T.G., Weiss A. Science 264:1599-1601(1994) [PubMed: 8202713] [Abstract] Cited for: VARIANT STD ARG-518.
[20]	"Specific immunoglobulin E responses in ZAP-70-deficient patients are mediated by Syk-dependent T-cell receptor signalling." Toyabe S., Watanabe A., Harada W., Karasawa T., Uchiyama M. Immunology 103:164-171(2001) [PubMed: 11412303] [Abstract] Cited for: VARIANT STD HIS-465.
[21]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-175; LEU-191; GLU-448 AND LEU-523.
+	Additional computationally mapped references.

Web resources

ZAP70base

ZAP70 mutation db

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00329789.
IPI00410185.
IPI00885038.

PIR

A44266.
A49955.

RefSeq

NP_001070.2.
NP_997402.1.

UniGene

Hs.234569

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M61	X-ray	2.50	A	1-256	[»]
1U59	X-ray	2.30	A	327-606	[»]
2OQ1	X-ray	1.90	A	3-256	[»]
2OZO	X-ray	2.60	A	1-606	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P43403. 2 interactions.

STRING

P43403.

PTM databases

PhosphoSite

P43403.

Proteomic databases

PRIDE

P43403.

Genome annotation databases

Ensembl

ENST00000264972; ENSP00000264972; ENSG00000115085; Homo sapiens. [Genome view]

GeneID

7535.

KEGG

hsa:7535.

UCSC

uc002syd.1. human.
uc002sye.1. human.

Organism-specific databases

CTD

7535.

GeneCards

GC02P097788.

H-InvDB

HIX0002292.

HGNC

HGNC:12858. ZAP70.

HPA

CAB002625.
HPA003134.

MIM

176947. gene+phenotype.

Orphanet

911. Severe combined immunodeficiency due to ZAP70 deficiency.

PharmGKB

PA37447.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17394.

HOGENOM

HBG714705.

HOVERGEN

P43403.

InParanoid

P43403.

OMA

FIEQGKR.

OrthoDB

EOG908QT6.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P43403.

Bgee

P43403.

CleanEx

HS_ZAP70.

Genevestigator

P43403.

GermOnline

ENSG00000115085. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR012234. Tyr_kinase_non-rcpt_SYK/ZAP70.
IPR020686. Tyr_kinase_non-rcpt_ZAP-70.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 2 hits.

PANTHER

PTHR23256:SF98. Tyr_kinase_non-rcpt_ZAP-70. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

PF00017. SH2. 2 hits.
[Graphical view]

PIRSF

PIRSF000604. TyrPK_SYK. 1 hit.

PRINTS

PR00401. SH2DOMAIN.

SMART

SM00252. SH2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 2 hits.
[Graphical view]

ProtoNet

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Other Resources

NextBio

29481.

PMAP-CutDB

P43403.

SOURCE

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Entry information

Entry name

ZAP70_HUMAN

Accession

Primary (citable) accession number: P43403
Secondary accession number(s): A6NFP4 , Q6PIA4, Q8IXD6, Q9UBS6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	February 9, 2010
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.