SIGLEC14 (sialic acid binding Ig-like lectin 14)

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Human Uniqueness Compared to "Great Apes": 
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Siglec-14 is a sialic acid-recognizing activatory receptor found on certain immune cells types that is undergoing concerted evolution with the gene for Siglec-5 (an inhibitory receptor) via ongoing gene conversion of exons encoding amino-terminal V-set lg-like domains. The result is that the two molecules have similar binding properties for sialic acids. However surprisingly, a critical arginine residue required for sialic acid recognition has been mutated in the corresponding molecules from the chimpanzee, gorilla and orangutan. It appears that this may be the ancestral condition, and that the human molecules have restored the arginine residue required for sialic acid recognition. It is unclear what the evolutionary significance of this adjustment is, and further studies are needed. An unusual fusion event between SIGLEC14 and SIGLEC14 results in an allele that is functionally SIGLEC5, but under the control of the SIGLEC14 promoter.  This allele is unique to humans and polymorphic in all human populations studied to date.  Possible selection pressures include the interaction with sialic acid-expressing pathogens and general control of innate immune responses.


Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Possible Appearance (Lineage Separation Event): 
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Genetics Topic Attributes
Gene symbols follow the HUGO Gene Nomenclature Committee standard.
Gene Symbol Type of Human-Specific Changes
SIGLEC14 Pseudogenization, Amino Acid Change


  1. Deletion polymorphism of SIGLEC14 and its functional implications., Yamanaka, Masahiro, Kato Yukinari, Angata Takashi, and Narimatsu Hisashi , Glycobiology, 2009 Aug, Volume 19, Issue 8, p.841-6, (2009)
  2. Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5., Carlin, Aaron F., Chang Yung-Chi, Areschoug Thomas, Lindahl Gunnar, Hurtado-Ziola Nancy, King Charles C., Varki Ajit, and Nizet Victor , J Exp Med, 2009 Aug 3, Volume 206, Issue 8, p.1691-9, (2009)
  3. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates., Angata, Takashi, Hayakawa Toshiyuki, Yamanaka Masahiro, Varki Ajit, and Nakamura Mitsuru , FASEB J, 2006 Oct, Volume 20, Issue 12, p.1964-73, (2006)