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Reviewed, UniProtKB/Swiss-Prot P20963 (CD3Z_HUMAN)

Last modified January 19, 2010. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length164 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

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. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17

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. Ref.19

Sequence similarities

Belongs to the CD3Z/FCER1G family.

Contains 3 ITAM domains.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-1165705,EBI-1165705
LCKP062391EBI-1165705,EBI-1348
PTPN22Q9Y2R22EBI-1165705,EBI-1211241

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P20963-1)

Also known as: CD-3-zeta;

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: P20963-2)

Also known as: CD-3-eta;

The sequence of this isoform is not available.
Isoform 3 (identifier: P20963-3)

The sequence of this isoform differs from the canonical sequence as follows:
     101-101: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Chain22 – 164143T-cell surface glycoprotein CD3 zeta chain
PRO_0000016493

Regions

Topological domain22 – 309Extracellular Potential
Transmembrane31 – 5121 Potential
Topological domain52 – 164113Cytoplasmic Potential
Domain61 – 8929ITAM 1
Domain100 – 12829ITAM 2
Domain131 – 15929ITAM 3

Amino acid modifications

Modified residue581Phosphoserine Ref.13
Modified residue641Phosphotyrosine Ref.13 Ref.14 Ref.15 Ref.17
Modified residue721Phosphotyrosine Ref.14 Ref.15 Ref.17
Modified residue831Phosphotyrosine Ref.12 Ref.14 Ref.15 Ref.17
Modified residue1111Phosphotyrosine Ref.12 Ref.14 Ref.15 Ref.16 Ref.17
Modified residue1231Phosphotyrosine Ref.12 Ref.15 Ref.17
Modified residue1421Phosphotyrosine Ref.12 Ref.14 Ref.15 Ref.17
Modified residue1531Phosphotyrosine Ref.15 Ref.17
Disulfide bond32Interchain Potential

Natural variations

Alternative sequence1011Missing in isoform 3.
VSP_036459

Experimental info

Sequence conflict60 – 612DA → EP in AAA60394. Ref.1

Secondary structure

1 ... 164
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CD-3-zeta) [UniParc].

Last modified October 10, 2002. Version 2.
Checksum: 9408260374856EE9

FASTA16418,696
        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

« Hide

Isoform 2 (CD-3-eta) (Sequence not available). FASTA––
Isoform 3.

Checksum: 34898620B67167C7
Show »

FASTA16318,568

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References

« Hide '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] (ISOFORM 3).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Skeletal muscle.
[3]NIEHS SNPs program
Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"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. expand/collapse author list , 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].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
Tissue: Pancreas.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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. expand/collapse author list , 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.
[17]"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-64; TYR-72; TYR-83; TYR-111; TYR-123; TYR-142 AND TYR-153, MASS SPECTROMETRY.
Tissue: T-cell.
[18]"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.
[19]"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.

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Web resources

CD247base

CD247 mutation db

NIEHS-SNPs

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		J04132 mRNA. Translation: AAA60394.1.
AK313946 mRNA. Translation: BAG36664.1.
DQ072717 Genomic DNA. Translation: AAY57330.1.
AL359962, AL031733 Genomic DNA. Translation: CAH69974.1.
AL359962, AL031733 Genomic DNA. Translation: CAH69975.1.
AL031733, AL359962 Genomic DNA. Translation: CAI21380.1.
AL031733, AL359962 Genomic DNA. Translation: CAI21381.1.
CH471067 Genomic DNA. Translation: EAW90792.1.
BC025703 mRNA. Translation: AAH25703.1.
IPIIPI00218634.
IPI00375504.
PIRA31768.
RefSeqNP_000725.1.
NP_932170.1.
UniGeneHs.156445

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TCENMR-B137-150[»]
1YGRX-ray2.90C/D80-85[»]
2HACNMR-A/B30-60[»]
2OQ1X-ray1.90B69-87[»]
DisProtDP00200.
ModBaseSearch...

Protein-protein interaction databases

IntActP20963. 3 interactions.
STRINGP20963.

PTM databases

PhosphoSiteP20963.

Proteomic databases

PRIDEP20963.

Genome annotation databases

EnsemblENST00000362089; ENSP00000354782; ENSG00000198821; Homo sapiens. [Genome view]
GeneID919.
KEGGhsa:919.
UCSCuc001gei.2. human.

Organism-specific databases

CTD919.
GeneCardsGC01M165666.
H-InvDBHIX0001296.
HGNCHGNC:1677. CD247.
HPACAB004651.
HPA008750.
MIM186780. gene.
610163. phenotype.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG20849.
HOVERGENP20963.
OMAHMQALPP.
OrthoDBEOG90KBJ4.

Enzyme and pathway databases

Pathway_Interaction_DBcd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
ReactomeREACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpressP20963.
BgeeP20963.
CleanExHS_CD247.
GenevestigatorP20963.
GermOnlineENSG00000198821. Homo sapiens.

Family and domain databases

InterProIPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]
PfamPF02189. ITAM. 3 hits.
[Graphical view]
SMARTSM00077. ITAM. 3 hits.
[Graphical view]
PROSITEPS51055. ITAM_1. 3 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio3800.
SOURCESearch...

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Entry information

Entry nameCD3Z_HUMAN
AccessionPrimary (citable) accession number: P20963
Secondary accession number(s): B1AK49, Q5VX13, Q8TAX4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: October 10, 2002
Last modified: January 19, 2010
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

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Relevant documents

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents