Kalcineurin B homologni protein 1 je protein koji je kod ljudi kodiran genom CHP1 (ranija CHP).[5]
Kratke činjenice Dostupne strukture, PDB ...
Zatvori
Gen CHP1 kodira bitni kofaktor SLC9A1 (NHE1), izmjenjivača Na+/H+ koji regulira unutarćelijske ione i homeostazu pH. Međunarodni radijacijski konzorcij za hibridno mapiranje locirao je gen CHP na hromosom 15 (stSG38846).
Više signalnih puteva regulira Na+/H+ proteine koji se transportuju. Da bi identificirali regulatorne proteine, Lin i Barber (1996) koristili su C-terminalni citoplazmatski domen sveprisutno eksprimirane izoforme NHE1 za pregled biblioteke ekspresije ljudskih B-ćelija. Djelimična sekvenca dobijena s ovog snimka korištena je za kloniranje nove cDNK pune dužine, označene kao CHP, iz druge B-ćelijske biblioteke. Izvedeni protein od 195 aminokiselina sadrži dva različita i dva potencijalna motiva vezana za [kalcij|[Ca(2+) za EF-šaku i dijeli 43% i 33% identiteta s kalcineurinom B i kalmodulinom. Također ima 99% identiteta sekvence sa homologom pacova. Northern blot analiza pokazala je ekspresiju 4-kb CHP transkripta u svih osam ispitivanih fetush tkiva.
U mišjem malom mozgu, pronašli su ekspresiju gena Chp1 na presinapsnim terminalima Purkinjeovih ćelija, kao i na aksonskim terminalima drugih neurona.
Dužina polipeptidnog lanca je 195 aminokiselina, a molekulska težina 22.456 Da.[6].
- Simboli
10 | | 20 | | 30 | | 40 | | 50 |
MGSRASTLLR | | DEELEEIKKE | | TGFSHSQITR | | LYSRFTSLDK | | GENGTLSRED |
FQRIPELAIN | | PLGDRIINAF | | FPEGEDQVNF | | RGFMRTLAHF | | RPIEDNEKSK |
DVNGPEPLNS | | RSNKLHFAFR | | LYDLDKDEKI | | SRDELLQVLR | | MMVGVNISDE |
QLGSIADRTI | | QEADQDGDSA | | ISFTEFVKVL | | EKVDVEQKMS | | IRFLH |
Protein koji kodira ovaj gen je fosfoprotein koji se veže za izmjenjivače natrij-vodik (NHE). Ovaj protein služi kao esencijalni kofaktor koji podržava fiziološku aktivnost članova porodice NHE. Ima sličnost proteinske sekvence s kalcineurinom B, a poznato je i da je endogeni inhibitor aktivnosti kalcineurina.[5]
Pokazalo se da homologni protein 1 kalcineurina B ima interakcija sa
- natrij-vodik antiporterom 1,[7][8][9]
- natrij-vodik antiporterom 3,]],[7] i
- natrij-vodik antiporterom 9.[10]
- Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC (Sep 1994). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics. 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID 7829101.
- Barroso MR, Bernd KK, DeWitt ND, Chang A, Mills K, Sztul ES (Apr 1996). "A novel Ca2+-binding protein, p22, is required for constitutive membrane traffic". The Journal of Biological Chemistry. 271 (17): 10183–7. doi:10.1074/jbc.271.17.10183. PMID 8626580.
- Lin X, Barber DL (Oct 1996). "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange". Proceedings of the National Academy of Sciences of the United States of America. 93 (22): 12631–6. doi:10.1073/pnas.93.22.12631. PMC 38044. PMID 8901634.
- Lin X, Sikkink RA, Rusnak F, Barber DL (Dec 1999). "Inhibition of calcineurin phosphatase activity by a calcineurin B homologous protein". The Journal of Biological Chemistry. 274 (51): 36125–31. doi:10.1074/jbc.274.51.36125. PMID 10593895.
- Pang T, Su X, Wakabayashi S, Shigekawa M (maj 2001). "Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers". The Journal of Biological Chemistry. 276 (20): 17367–72. doi:10.1074/jbc.M100296200. PMID 11350981.
- Matsumoto M, Miyake Y, Nagita M, Inoue H, Shitakubo D, Takemoto K, Ohtsuka C, Murakami H, Nakamura N, Kanazawa H (Aug 2001). "A serine/threonine kinase which causes apoptosis-like cell death interacts with a calcineurin B-like protein capable of binding Na(+)/H(+) exchanger". Journal of Biochemistry. 130 (2): 217–25. doi:10.1093/oxfordjournals.jbchem.a002975. PMID 11481038.
- Nakamura N, Miyake Y, Matsushita M, Tanaka S, Inoue H, Kanazawa H (Sep 2002). "KIF1Bbeta2, capable of interacting with CHP, is localized to synaptic vesicles". Journal of Biochemistry. 132 (3): 483–91. doi:10.1093/oxfordjournals.jbchem.a003246. PMID 12204119.
- Pang T, Wakabayashi S, Shigekawa M (Nov 2002). "Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger". The Journal of Biological Chemistry. 277 (46): 43771–7. doi:10.1074/jbc.M208313200. PMID 12226101.
- Inoue H, Nakamura Y, Nagita M, Takai T, Masuda M, Nakamura N, Kanazawa H (Feb 2003). "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium". Biological & Pharmaceutical Bulletin. 26 (2): 148–55. doi:10.1248/bpb.26.148. PMID 12576672.
- Pang T, Hisamitsu T, Mori H, Shigekawa M, Wakabayashi S (Mar 2004). "Role of calcineurin B homologous protein in pH regulation by the Na+/H+ exchanger 1: tightly bound Ca2+ ions as important structural elements". Biochemistry. 43 (12): 3628–36. doi:10.1021/bi0360004. PMID 15035633.
- Andrade J, Pearce ST, Zhao H, Barroso M (Dec 2004). "Interactions among p22, glyceraldehyde-3-phosphate dehydrogenase and microtubules". The Biochemical Journal. 384 (Pt 2): 327–36. doi:10.1042/BJ20040622. PMC 1134116. PMID 15312048.
- Ben Ammar Y, Takeda S, Sugawara M, Miyano M, Mori H, Wakabayashi S (Oct 2005). "Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1". Acta Crystallographica Section F. 61 (Pt 10): 956–8. doi:10.1107/S1744309105030836. PMC 1991313. PMID 16511206.
- Mishima M, Wakabayashi S, Kojima C (Jan 2007). "Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1". The Journal of Biological Chemistry. 282 (4): 2741–51. doi:10.1074/jbc.M604092200. PMID 17050540.