5jzv

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The structure of D77G hCINAP-ADP

Structural highlights

5jzv is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.07Å
Ligands:ADP
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAD6_HUMAN Broad-specificity nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. AMP and dAMP are the preferred substrates, but CMP and dCMP are also good substrates. IMP is phosphorylated to a much lesser extent. All nucleoside triphosphates ATP, GTP, UTP, CTP, dATP, dCTP, dGTP, and TTP are accepted as phosphate donors. CTP is the best phosphate donor, followed by UTP, ATP, GTP and dCTP. May have a role in nuclear energy homeostasis. Has also ATPase activity. May be involved in regulation of Cajal body (CB) formation.[1]

Publication Abstract from PubMed

Dysfunctions in ribosome biogenesis cause developmental defects and increased cancer susceptibility; however, the connection between ribosome assembly and tumorigenesis remains unestablished. Here we show that hCINAP (also named AK6) is required for human 18S rRNA processing and 40S subunit assembly. Homozygous CINAP(-/-) mice show embryonic lethality. The heterozygotes are viable and show defects in 18S rRNA processing, whereas no delayed cell growth is observed. However, during rapid growth, CINAP haploinsufficiency impairs protein synthesis. Consistently, hCINAP depletion in fast-growing cancer cells inhibits ribosome assembly and abolishes tumorigenesis. These data demonstrate that hCINAP reduction is a specific rate-limiting controller during rapid growth. Notably, hCINAP is highly expressed in cancers and correlated with a worse prognosis. Genome-wide polysome profiling shows that hCINAP selectively modulates cancer-associated translatome to promote malignancy. Our results connect the role of hCINAP in ribosome assembly with tumorigenesis. Modulation of hCINAP expression may be a promising target for cancer therapy.

The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth.,Bai D, Zhang J, Li T, Hang R, Liu Y, Tian Y, Huang D, Qu L, Cao X, Ji J, Zheng X Nat Commun. 2016 Aug 1;7:12310. doi: 10.1038/ncomms12310. PMID:27477389[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
8 reviews cite this structure
Uncovering the assembly pathway of human ribosomes and its emerging links to disease.
Bohnsack et al. (2019)
7 more
21 other articles
No citations found

See Also

References

  1. ↑ Ren H, Wang L, Bennett M, Liang Y, Zheng X, Lu F, Li L, Nan J, Luo M, Eriksson S, Zhang C, Su XD. The crystal structure of human adenylate kinase 6: An adenylate kinase localized to the cell nucleus. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):303-8. Epub 2005 Jan 3. PMID:15630091
  2. ↑ Bai D, Zhang J, Li T, Hang R, Liu Y, Tian Y, Huang D, Qu L, Cao X, Ji J, Zheng X. The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth. Nat Commun. 2016 Aug 1;7:12310. doi: 10.1038/ncomms12310. PMID:27477389 doi:http://dx.doi.org/10.1038/ncomms12310

Contents


PDB ID 5jzv

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OCA

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