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CIB1

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CIB1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCIB1, CIB, CIBP, KIP1, PRKDCIP, SIP2-28, calcium and integrin binding 1
External IDsOMIM: 602293; MGI: 1344418; HomoloGene: 4654; GeneCards: CIB1; OMA:CIB1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10519

23991

Ensembl

ENSG00000185043

ENSMUSG00000030538

UniProt

Q99828

Q9Z0F4

RefSeq (mRNA)

NM_001277764
NM_006384

NM_001291275
NM_001291276
NM_011870

RefSeq (protein)

NP_001264693
NP_006375

NP_001278204
NP_001278205
NP_036000

Location (UCSC)Chr 15: 90.23 – 90.23 MbChr 7: 79.88 – 79.88 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Calcium and integrin-binding protein 1 is a protein that in humans is encoded by the CIB1 gene and is located in Chromosome 15.[5][6][7] The protein encoded by this gene is a member of the calcium-binding protein family. The specific function of this protein has not yet been determined; however this protein is known to interact with DNA-dependent protein kinase and may play a role in kinase-phosphatase regulation of DNA end-joining. This protein also interacts with integrin alpha(IIb)beta(3), which may implicate this protein as a regulatory molecule for alpha(IIb)beta(3).[7]

Structure and function

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CIB1 is a small protein with a molecular weight of approximately 22 kDa. It has a conserved calcium-binding EF hand domain, which consists of two alpha-helices connected by a loop.[8][9] CIB1 also has an integrin-binding domain, located near the N-terminus of the protein. In addition, CIB1 has a coiled-coil domain and a C-terminal domain.[8][10][11] CIB1 is involved in regulating cell adhesion, migration, and differentiation, as well as other cellular processes. It interacts with integrins, which are transmembrane receptors that play a key role in cell signaling and adhesion to the extracellular matrix. CIB1 has also been shown to regulate other signaling pathways that are important for cell survival and proliferation.[8] Upregulation of CIB1 expression has been observed in several types of cancer, and it has been implicated in cancer development and progression.[8] CIB1 is involved in several cellular processes that are important for cancer progression, including cell adhesion, migration, and invasion. It has been shown to interact with integrins, which are transmembrane receptors that play a key role in these processes.[8] The structure and function of CIB1 make it an important protein in regulating various cellular processes, including those involved in cancer progression, and targeting it may offer potential therapeutic benefits.

Cancer

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CIB1 expression has been observed in several types of cancer, including breast, lung, prostate, ovarian, and pancreatic cancer. In breast cancer, CIB1 expression has been shown to be higher in invasive ductal carcinoma compared to normal breast tissue.[12] High levels of CIB1 expression have also been associated with poor prognosis in breast cancer patients.[12] CIB1 has been implicated in cancer development and progression. In breast cancer, CIB1 has been shown to promote cell proliferation, migration, invasion, and metastasis.[13] CIB1 has also been shown to promote the growth of prostate cancer cells and the invasion of ovarian cancer cells.[13] Targeting CIB1 has been explored as a potential therapeutic strategy for cancer. Small molecule inhibitors of CIB1 have shown promise in preclinical models of breast cancer. Silencing CIB1 expression has also been shown to sensitize cancer cells to chemotherapy and radiation therapy.[14][13]

Male infertility

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CIB1 has been implicated in male fertility, specifically in sperm function and motility.[15] CIB1 expression has been detected in human sperm, and its levels have been correlated with sperm motility. CIB1 has also been shown to be present in the acrosome region of the sperm, which plays a critical role in fertilization. Studies in mice have shown that CIB1 deficiency leads to impaired sperm motility and reduced fertility.[8][15] Male mice lacking CIB1 exhibited decreased sperm count and decreased sperm motility, resulting in reduced fertility. CIB1 was also found to be required for the proper formation of the sperm tail, which is critical for sperm motility.[8] In addition, CIB1 has been shown to regulate calcium signaling in sperm, which is important for sperm motility and fertilization. CIB1 interacts with the sperm-specific calcium channel CatSper, which is important for regulating intracellular calcium levels in sperm.[8]

Spermatogenesis

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Spermatogenesis is the process of producing mature spermatozoa from spermatogonia, the precursor cells in the testes. This process involves several stages, including mitotic division, meiotic division, and differentiation, which results in the production of four haploid sperm cells from one diploid spermatogonium. CIB1 has been shown to play a critical role in spermatogenesis by regulating the differentiation of spermatogonia into spermatocytes. Studies have shown that CIB1 is expressed in spermatogonia, spermatocytes, and spermatids, indicating its role throughout the entire process of spermatogenesis.[8][15] In mice, CIB1 deficiency has been shown to lead to decreased spermatogonia proliferation and impaired differentiation into spermatocytes, resulting in reduced sperm production and male infertility.[15] In addition, CIB1 has been shown to regulate the expression of genes involved in spermatogenesis, including genes involved in cell proliferation and differentiation.[8][15]

Interactions

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CIB1 has been shown to interact with RAC3,[16] PSEN2,[17] DNA-PKcs,[18] UBR5[19] and CD61.[5]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000185043 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030538 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Naik UP, Patel PM, Parise LV (Apr 1997). "Identification of a novel calcium-binding protein that interacts with the integrin alphaIIb cytoplasmic domain". J Biol Chem. 272 (8): 4651–4. doi:10.1074/jbc.272.8.4651. PMID 9030514.
  6. ^ Hattori A, Seki N, Hayashi A, Kozuma S, Saito T (Aug 2000). "Genomic structure of mouse and human genes for DNA-PKcs interacting protein (KIP)". DNA Seq. 10 (6): 415–8. doi:10.3109/10425170009015612. PMID 10826701. S2CID 21570442.
  7. ^ a b "Entrez Gene: CIB1 calcium and integrin binding 1 (calmyrin)".
  8. ^ a b c d e f g h i j Leisner TM, Freeman TC, Black JL, Parise LV (August 2016). "CIB1: a small protein with big ambitions". The FASEB Journal. 30 (8): 2640–2650. doi:10.1096/fj.201500073R. ISSN 0892-6638. PMC 4970603. PMID 27118676.
  9. ^ Kretsinger RH, Nockolds CE (1973-05-10). "Carp muscle calcium-binding protein. II. Structure determination and general description". The Journal of Biological Chemistry. 248 (9): 3313–3326. doi:10.1016/S0021-9258(19)44043-X. ISSN 0021-9258. PMID 4700463.
  10. ^ Blamey CJ, Ceccarelli C, Naik UP, Bahnson BJ (May 2005). "The crystal structure of calcium- and integrin-binding protein 1: Insights into redox regulated functions". Protein Science. 14 (5): 1214–1221. doi:10.1110/ps.041270805. ISSN 0961-8368. PMC 2253279. PMID 15840829.
  11. ^ Huang H, Ishida H, Yamniuk AP, Vogel HJ (May 2011). "Solution Structures of Ca2+-CIB1 and Mg2+-CIB1 and Their Interactions with the Platelet Integrin αIIb Cytoplasmic Domain". Journal of Biological Chemistry. 286 (19): 17181–17192. doi:10.1074/jbc.m110.179028. ISSN 0021-9258. PMC 3089561. PMID 21388953.
  12. ^ a b Black JL, Harrell JC, Leisner TM, Fellmeth MJ, George SD, Reinhold D, Baker NM, Jones CD, Der CJ, Perou CM, Parise LV (2015-06-24). "CIB1 depletion impairs cell survival and tumor growth in triple-negative breast cancer". Breast Cancer Research and Treatment. 152 (2): 337–346. doi:10.1007/s10549-015-3458-4. ISSN 0167-6806. PMC 4516161. PMID 26105795.
  13. ^ a b c Liu Y, Zhou Y, Zhang P, Li X, Duan C, Zhang C (March 2021). "CHIP-mediated CIB1 ubiquitination regulated epithelial–mesenchymal transition and tumor metastasis in lung adenocarcinoma". Cell Death & Differentiation. 28 (3): 1026–1040. doi:10.1038/s41418-020-00635-5. ISSN 1476-5403. PMC 7937682. PMID 33082516.
  14. ^ Qin X, Sun L, Wang J (2017-08-17). "Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway". Cell Biology International. 41 (10): 1110–1118. doi:10.1002/cbin.10819. ISSN 1065-6995. PMID 28685895. S2CID 4124914.
  15. ^ a b c d e Yuan W, Leisner TM, McFadden AW, Clark S, Hiller S, Maeda N, O'Brien DA, Parise LV (2006-11-01). "CIB1 Is Essential for Mouse Spermatogenesis". Molecular and Cellular Biology. 26 (22): 8507–8514. doi:10.1128/mcb.01488-06. ISSN 1098-5549. PMC 1636792. PMID 16982698.
  16. ^ Haataja L, Kaartinen Vesa, Groffen John, Heisterkamp Nora (Mar 2002). "The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading". J. Biol. Chem. 277 (10): 8321–8. doi:10.1074/jbc.M105363200. ISSN 0021-9258. PMID 11756406.
  17. ^ Stabler SM, Ostrowski L L, Janicki S M, Monteiro M J (Jun 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. 145 (6): 1277–92. doi:10.1083/jcb.145.6.1277. ISSN 0021-9525. PMC 2133148. PMID 10366599.
  18. ^ Wu X, Lieber M R (Oct 1997). "Interaction between DNA-dependent protein kinase and a novel protein, KIP". Mutat. Res. 385 (1): 13–20. doi:10.1016/s0921-8777(97)00035-9. ISSN 0027-5107. PMID 9372844.
  19. ^ Henderson MJ, Russell Amanda J, Hird Samantha, Muñoz Marcia, Clancy Jennifer L, Lehrbach Gillian M, Calanni Sophina T, Jans David A, Sutherland Robert L, Watts Colin K W (Jul 2002). "EDD, the human hyperplastic discs protein, has a role in progesterone receptor coactivation and potential involvement in DNA damage response". J. Biol. Chem. 277 (29): 26468–78. doi:10.1074/jbc.M203527200. hdl:1885/64590. ISSN 0021-9258. PMID 12011095.

Further reading

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