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Identification
HMDB Protein ID HMDBP03981
Secondary Accession Numbers
  • 9569
Name Hematopoietic cell signal transducer
Synonyms
  1. DNAX-activation protein 10
  2. Membrane protein DAP10
  3. Transmembrane adapter protein KAP10
Gene Name HCST
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Transmembrane adapter protein which associates with NKG2D to form an activation receptor NKG2D-HCST in lymphoid and myeloid cells; this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain-related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands are up-regulated by stress conditions and pathological state such as viral infection and tumor transformation. Functions as docking site for PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with NKG2D-DAP10 triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK, and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required for full NKG2D-HCST-mediated activation and ultimate killing of target cells. In NK cells, NKG2D-HCST signaling directly induces cytotoxicity and enhances cytokine production initiated via DAP12/TYROBP-associated receptors. In T cells, it provides primarily costimulation for TCR-induced signals. NKG2D-HCST receptor plays a role in immune surveillance against tumors and is required for cytolysis of tumors cells; indeed, melanoma cells that do not express NKG2D ligands escape from immune surveillance mediated by NK cells
Pathways Not Available
Reactions Not Available
GO Classification Not Available
Cellular Location
  1. Membrane
  2. Single-pass type I membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 19q13.1
SNPs HCST
Gene Sequence
>282 bp
ATGATCCATCTGGGTCACATCCTCTTCCTGCTTTTGCTCCCAGTGGCTGCAGCTCAGACG
ACTCCAGGAGAGAGATCATCACTCCCTGCCTTTTACCCTGGCACTTCAGGCTCTTGTTCC
GGATGTGGGTCCCTCTCTCTGCCGCTCCTGGCAGGCCTCGTGGCTGCTGATGCGGTGGCA
TCGCTGCTCATCGTGGGGGCGGTGTTCCTGTGCGCACGCCCACGCCGCAGCCCCGCCCAA
GAAGATGGCAAAGTCTACATCAACATGCCAGGCAGGGGCTGA
Protein Properties
Number of Residues 93
Molecular Weight 9489.0
Theoretical pI 8.51
Pfam Domain Function
Signals
  • 1-18
Transmembrane Regions
  • 49-69
Protein Sequence
>Hematopoietic cell signal transducer
MIHLGHILFLLLLPVAAAQTTPGERSSLPAFYPGTSGSCSGCGSLSLPLLAGLVAADAVA
SLLIVGAVFLCARPRRSPAQEDGKVYINMPGRG
GenBank ID Protein 15826850
UniProtKB/Swiss-Prot ID Q9UBK5
UniProtKB/Swiss-Prot Entry Name HCST_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_014266.3
GeneCard ID HCST
GenAtlas ID HCST
HGNC ID HGNC:16977
References
General References
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  2. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  3. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed:12975309 ]
  4. Chang C, Dietrich J, Harpur AG, Lindquist JA, Haude A, Loke YW, King A, Colonna M, Trowsdale J, Wilson MJ: Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties. J Immunol. 1999 Nov 1;163(9):4651-4. [PubMed:10528161 ]
  5. Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, Phillips JH: An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999 Jul 30;285(5428):730-2. [PubMed:10426994 ]
  6. Yim D, Jie HB, Sotiriadis J, Kim YS, Kim KS, Rothschild MF, Lanier LL, Kim YB: Molecular cloning and characterization of pig immunoreceptor DAP10 and NKG2D. Immunogenetics. 2001 Apr;53(3):243-9. [PubMed:11398969 ]
  7. Wu J, Cherwinski H, Spies T, Phillips JH, Lanier LL: DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. J Exp Med. 2000 Oct 2;192(7):1059-68. [PubMed:11015446 ]
  8. Sutherland CL, Chalupny NJ, Schooley K, VandenBos T, Kubin M, Cosman D: UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. J Immunol. 2002 Jan 15;168(2):671-9. [PubMed:11777960 ]
  9. Billadeau DD, Upshaw JL, Schoon RA, Dick CJ, Leibson PJ: NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. Nat Immunol. 2003 Jun;4(6):557-64. Epub 2003 May 11. [PubMed:12740575 ]
  10. Zompi S, Hamerman JA, Ogasawara K, Schweighoffer E, Tybulewicz VL, Di Santo JP, Lanier LL, Colucci F: NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol. 2003 Jun;4(6):565-72. Epub 2003 May 11. [PubMed:12740576 ]
  11. Wiemann K, Mittrucker HW, Feger U, Welte SA, Yokoyama WM, Spies T, Rammensee HG, Steinle A: Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo. J Immunol. 2005 Jul 15;175(2):720-9. [PubMed:16002667 ]
  12. Karimi M, Cao TM, Baker JA, Verneris MR, Soares L, Negrin RS: Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells. J Immunol. 2005 Dec 15;175(12):7819-28. [PubMed:16339517 ]
  13. Burgess SJ, Marusina AI, Pathmanathan I, Borrego F, Coligan JE: IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells. J Immunol. 2006 Feb 1;176(3):1490-7. [PubMed:16424177 ]
  14. Upshaw JL, Arneson LN, Schoon RA, Dick CJ, Billadeau DD, Leibson PJ: NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nat Immunol. 2006 May;7(5):524-32. Epub 2006 Apr 2. [PubMed:16582911 ]
  15. Marusina AI, Burgess SJ, Pathmanathan I, Borrego F, Coligan JE: Regulation of human DAP10 gene expression in NK and T cells by Ap-1 transcription factors. J Immunol. 2008 Jan 1;180(1):409-17. [PubMed:18097042 ]