• CD34 [HUGO gene name]
• gp105-120

MAJOR LINKS FOR CD34  

• NCBI LocusLink Record: 947
• Mendelian Inheritance in Man (OMIM): 142230
• SwissProt annotated protein record: P28906

CELLULAR FUNCTION OF CD34 Link to additional info in FORUM  

• Cell-cell adhesion
• Inhibition of hematopoietic differentiation?

DISEASE RELEVANCE OF CD34 AND FUNCTION OF CD34 IN INTACT ANIMAL  

• No abnormality in leukocyte trafficking was detected in the CD34 knock-out mice
• In 1 of 2 reports of CD34 knock-out mice, a decrease in hematopoietic progenitors was found in the knock-out mice
• Utilization of CD34 mAb to quantitate and purify lymphohematopoietic stem / progenitor cells for research and for clinical bone marrow transplantation

• Families in which CD34 is a member
  • CD34-->sialomucin-->Mucins

MOLECULAR STRUCTURE OF CD34  

• A heavily glycosylated type I transmembrane protein. There are two forms of the CD34 protein, resulting from alternative splicing
• The complete extracellular region is present in both forms of CD34
• There is a cysteine-rich repeat (Ig-like domain) in the extracellular region
• The full-length form of CD34 molecule has an intracellular domain, which contains consensus sites for protein kinase C (PKC) phosphorylation, serine and threonine phosphorylation by other kinases, and tyrosine phosphorylation (To date, only serine phosphorylation by has been actually demonstrated)
• The truncated form of CD34 lacks most of the intracellular domain, including many of the potential phosphorylation sites

  	Full-length form	Truncated form
  Full amino sequence	385	328
  Intracellular region	73	16
  Transmembrane	23	23
  Extracellular region	258	258
  Signal sequence	31	31

MOLECULAR MASS OF CD34  

POST-TRANSCRIPTIONAL MODIFICATION OF CD34  

• One species contains exons 1 through 8 and forms the full-length form of CD34
• An alternative splice variant results in the insertion of an additional exon (exon X, 194bp) between exon 7 and 8; this introduces a translational stop codon, which results in the truncated form of CD34 with a shorter cytoplasmic domain
• The transmembrane and extracellular regions of both forms of CD34 are identical

POST-TRANSLATIONAL MODIFICATION OF CD34  

• Beginning at the NH2 terminus, the extracellular domain is heavily N- and
• O-sialoglycosylated
• Serine phosphorylation of the intracellular domain has been demonstrated, and there are potential sites for serine, threonine, and tyrosine phosphorylation

SUBSTRATES FOR CD34   - No information

ENZYMES WHICH MODIFY CD34   - No information

LIGANDS FOR CD34 AND MOLECULES ASSOCIATED WITH CD34  

• Expressed on early lymphohematopoietic stem and progenitor cells, small-vessel endothelial cells, embryonic fibroblasts, and some cells in fetal and adult nervous tissue
• Also, expressed on hematopoietic progenitors derived from fetal yolk sac, embryonic liver, and extra-hepatic embryonic tissues including aorta-associated hematopoietic progenitors in the 5 week human embryo

SELECTION OF OTHER CD34-SPECIFIC REFERENCE MAB  

REVIEWS

1. Krause DS,Fackler MJ,Civin CI,May WS CD34: structure, biology, and clinical utility. Blood 1996 87:1 PubMed

2. Sutherland DR,Keating A The CD34 antigen: structure, biology, and potential clinical applications. J Hematother 1992 1:115 PubMed

PRIMARY CITATIONS

3. Baumheter S,Singer MS,Henzel W,Hemmerich S,Renz M,Rosen SD,Lasky LA Binding of L-selectin to the vascular sialomucin CD34. Science 1993 262:436 PubMed

4. Civin CI,Strauss LC,Brovall C,Fackler MJ,Schwartz JF,Shaper JH Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG- 1a cells. J Immunol 1984 133:157 PubMed

5. Fackler MJ,Krause DS,Smith OM,Civin CI,May WS Full-length but not truncated CD34 inhibits hematopoietic cell differentiation of M1 cells. Blood 1995 85:3040 PubMed

6. Gaudernack, G. and Egeland, T. Leucocyte typing (ed.Schlossman, S.F. et al), pp. 861-4. Oxford University Press, Oxford (1995)

7. Huyhn A,Dommergues M,Izac B,Croisille L,Katz A,Vainchenker W,Coulombel L Characterization of hematopoietic progenitors from human yolk sacs and embryos. Blood 1995 86:4474 PubMed

8. Lin G,Finger E,Gutierrez-Ramos JC Expression of CD34 in endothelial cells, hematopoietic progenitors and nervous cells in fetal and adult mouse tissues. Eur J Immunol 1995 25:1508 PubMed

9. Nakamura Y,Komano H,Nakauchi H Two alternative forms of cDNA encoding CD34. Exp Hematol 1993 21:236 PubMed

10. Perrotti D,Bellon T,Trotta R,Martinez R,Calabretta B A cell proliferation-dependent multiprotein complex NC-3A positively regulates the CD34 promoter via a TCATTT-containing element. Blood 1996 88:3336 PubMed

11. Sato N,Sawada K,Koizumi K,Tarumi T,Ieko M,Yasukouchi T,Yamaguchi M,Takahashi TA,Sekiguchi S,Koike T In vitro expansion of human peripheral blood CD34+ cells. Blood 1993 82:3600 PubMed

12. Satterthwaite AB,Burn TC,Le Beau MM,Tenen DG Structure of the gene encoding CD34, a human hematopoietic stem cell antigen. Genomics 1992 12:788 PubMed

13. Suda J,Sudo T,Ito M,Ohno N,Yamaguchi Y,Suda T Two types of murine CD34 mRNA generated by alternative splicing. Blood 1992 79:2288 PubMed

14. Sutherland DR,Abdullah KM,Cyopick P,Mellors A Cleavage of the cell-surface O-sialoglycoproteins CD34, CD43, CD44, and CD45 by a novel glycoprotease from Pasteurella haemolytica. J Immunol 1992 148:1458 PubMed

15. Tavian M,Coulombel L,Luton D,Clemente HS,Dieterlen-Lievre F,Peault B Aorta-associated CD34+ hematopoietic cells in the early human embryo. Blood 1996 87:67 PubMed

16. Tindle RW,Nichols RA,Chan L,Campana D,Catovsky D,Birnie GD A novel monoclonal antibody BI-3C5 recognises myeloblasts and non-B non- T lymphoblasts in acute leukaemias and CGL blast crises, and reacts with immature cells in normal bone marrow. Leuk Res 1985 9:1 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov