Reviewed, UniProtKB/Swiss-Prot P20963 (CD3Z_HUMAN)

Names and origin

Protein names

Recommended name:
    T-cell surface glycoprotein CD3 zeta chain
Alternative name(s):
    T-cell receptor T3 zeta chain
    CD_antigen=CD247

Gene names

Name:	CD247
Synonyms:	CD3Z, T3Z, TCRZ

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	164 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.
Subunit structure	The TCR/CD3 complex of T-lymphocytes consists of either a TCR alpha/beta or TCR gamma/delta heterodimer coexpressed at the cell surface with the invariant subunits of CD3 labeled gamma, delta, epsilon, zeta, and eta. CD3-zeta forms either homodimers or heterodimers with CD3-eta. Interacts with SLA and SLA2. Interacts with DOCK2 and TRAT1. Interacts with HIV-1 Nef protein. Interacts with SHB.
Subcellular location	Membrane; Single-pass type I membrane protein.
Domain	The ITAM domains mediate interaction with SHB.
Post-translational modification	Phosphorylated on Tyr residues after T-cell receptor triggering By similarity.
Involvement in disease	Defects in CD247 are a cause of primary T-cell immunodeficiency [MIM:610163]. Affected individuals suffer of recurrent infections. Patients T-cell counts are very low and B-cell counts are normal.
Sequence similarities	Belongs to the CD3Z/FCER1G family. Contains 3 ITAM domains.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Cellular component	T cell receptor complex Inferred from direct assay. Source: MGI cytoplasm Ref.8 Inferred from direct assay. Source: MGI
Molecular function	protein homodimerization activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-1165705,EBI-1165705
LCK	P06239	1	EBI-1165705,EBI-1348
PTPN22	Q9Y2R2	2	EBI-1165705,EBI-1211241

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]

Isoform CD-3-zeta (identifier: P20963-1)

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 CD-3-eta (identifier: P20963-2)

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 164

143

T-cell surface glycoprotein CD3 zeta chain

PRO_0000016493

Regions

Topological domain

22 – 30

9

Extracellular Potential

Transmembrane

31 – 51

21

Potential

Topological domain

52 – 164

113

Cytoplasmic Potential

Domain

61 – 89

29

ITAM 1

Domain

100 – 128

29

ITAM 2

Domain

131 – 159

29

ITAM 3

Amino acid modifications

Modified residue

58

1

Phosphoserine

Modified residue

64

1

Phosphotyrosine

Modified residue

72

1

Phosphotyrosine

Modified residue

83

1

Phosphotyrosine

Modified residue

111

1

Phosphotyrosine

Modified residue

123

1

Phosphotyrosine

Modified residue

142

1

Phosphotyrosine

Modified residue

153

1

Phosphotyrosine

Disulfide bond

32

Interchain Potential

Experimental info

Sequence conflict

60 – 61

2

DA → EP in AAA60394. Ref.1

Sequence conflict

101

1

Missing in AAA60394. Ref.1

Secondary structure

1

.

.

.

164

Helix Strand Turn

Details...

Helix

31 – 54

24

Sequences

	Sequence		Length	Mass (Da)
	Isoform CD-3-zeta [UniParc]. Last modified October 10, 2002. Version 2. Checksum: 9408260374856EE9	FASTA	164	18,696
	10 20 30 40 50 60 MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD 70 80 90 100 110 120 APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP QRRKNPQEGL YNELQKDKMA 130 140 150 160 EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR
	Isoform CD-3-eta (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex." Weissman A.M., Hou D., Orloff D.G., Modi W.S., Seuanez H., O'Brien S.J., Klausner R.D. Proc. Natl. Acad. Sci. U.S.A. 85:9709-9713(1988) [PubMed: 2974162] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A. Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [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]. Tissue: Pancreas.
[5]	"Stimulation through the T cell receptor leads to interactions between SHB and several signaling proteins." Welsh M., Songyang Z., Frantz J.D., Trueb T., Reedquist K.A., Karlsson T., Miyazaki M., Cantley L.C., Band H., Shoelson S.E. Oncogene 16:891-901(1998) [PubMed: 9484780] [Abstract] Cited for: INTERACTION WITH SHB.
[6]	"Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain." Xu X.-N., Laffert B., Screaton G.R., Kraft M., Wolf D., Kolanus W., Mongkolsapay J., McMichael A.J., Baur A.S. J. Exp. Med. 189:1489-1496(1999) [PubMed: 10224289] [Abstract] Cited for: INTERACTION WITH HIV-1 NEF.
[7]	"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 SLA.
[8]	"The transmembrane adaptor protein TRIM regulates T-cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain." Kirchgessner H., Dietrich J., Scherer J., Isomaeki P., Korinek V., Hilgert I., Bruyns E., Leo A., Cope A.P., Schraven B. J. Exp. Med. 193:1269-1284(2001) [PubMed: 11390434] [Abstract] Cited for: INTERACTION WITH TRAT1.
[9]	"DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription." Nishihara H., Maeda M., Tsuda M., Makino Y., Sawa H., Nagashima K., Tanaka S. Biochem. Biophys. Res. Commun. 296:716-720(2002) [PubMed: 12176041] [Abstract] Cited for: INTERACTION WITH DOCK2.
[10]	"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-83; TYR-111; TYR-123 AND TYR-142, MASS SPECTROMETRY.
[11]	"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-58 AND TYR-64, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"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-64; TYR-72; TYR-83; TYR-111 AND TYR-142, MASS SPECTROMETRY.
[13]	"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-64; TYR-72; TYR-83; TYR-111; TYR-123; TYR-142 AND TYR-153, MASS SPECTROMETRY. Tissue: T-cell.
[14]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-111, MASS SPECTROMETRY.
[15]	"Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: crystal structures of the complexed and peptide-free forms." Waksman G., Shoelson S.E., Pant N., Cowburn D., Kuriyan J. Cell 72:779-790(1993) [PubMed: 7680960] [Abstract] Cited for: STRUCTURE BY NMR OF 136-149.
[16]	"Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency." Rieux-Laucat F., Hivroz C., Lim A., Mateo V., Pellier I., Selz F., Fischer A., Le Deist F. N. Engl. J. Med. 354:1913-1921(2006) [PubMed: 16672702] [Abstract] Cited for: INVOLVEMENT IN PRIMARY T-CELL IMMUNODEFICIENCY.
+	Additional computationally mapped references.

Web resources

CD247base

CD247 mutation db

Cross-references

Sequence databases

EMBLGenBankDDBJ

J04132 mRNA. Translation: AAA60394.1.
DQ072717 Genomic DNA. Translation: AAY57330.1.
AL359962, AL031733 Genomic DNA. Translation: CAH69975.1.
AL031733, AL359962 Genomic DNA. Translation: CAI21381.1.
BC025703 mRNA. Translation: AAH25703.1.

PIR

A31768.

RefSeq

NP_932170.1.

UniGene

Hs.156445

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TCE	NMR	-	B	137-150	[»]
1YGR	X-ray	2.90	C/D	80-85	[»]
2HAC	NMR	-	A/B	28-60	[»]

DisProt

DP00200.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20963.

PTM databases

PhosphoSite

P20963.

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000198821. Homo sapiens. [Contig view]

GeneID

919.

Organism-specific databases

H-InvDB

HIX0001296.

HGNC

HGNC:1677. CD247.

HPA

CAB004651.
HPA008750.

MIM

186780. gene.
610163. phenotype.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P20963.

Enzyme and pathway databases

Reactome

REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune System.

Gene expression databases

ArrayExpress

P20963.

CleanEx

HS_CD247.

GermOnline

ENSG00000198821. Homo sapiens.

Family and domain databases

InterPro

IPR003110. Phos_rcpt_ITAM.
[Graphical view]

Pfam

PF02189. ITAM. 3 hits.
[Graphical view]

SMART

SM00077. ITAM. 3 hits.
[Graphical view]

PROSITE

PS51055. ITAM_1. 3 hits.
[Graphical view]

BLOCKS

Search...

ProtoNet

Search...

Other Resources

LinkHub

P20963.

NextBio

3800.

SOURCE

Search...

Entry information

Entry name

CD3Z_HUMAN

Accession

Primary (citable) accession number: P20963
Secondary accession number(s): Q5VX13, Q8TAX4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 10, 2002
Last modified:	November 4, 2008
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)