CARHSP1

CARHSP1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3AQQ
Identifikatori
Aliasi	CARHSP1
Vanjski ID-jevi	OMIM: 616885 MGI: 1196368 HomoloGene: 8632 GeneCards: CARHSP1
Lokacija gena (čovjek)
Hrom.	Hromosom 16 (čovjek)
Kraj	8,869,012 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	8,490,019 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• mRNA 3'-UTR binding; • vezivanje sa DNK; • phosphatase binding; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje sa RNK; • nucleic acid binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Ćelijska komponenta	• cytoplasmic exosome (RNase complex); • citosol; • P-tijelo; • P granule; • citoplazma;
Biološki proces	• GO:0007243 intracellular signal transduction; • GO:0009373 regulation of transcription, DNA-templated; • regulation of mRNA stability; • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II;
	Izvori:Amigo / QuickGO
Ortolozi
	23589
	52502
	ENSG00000153048
	ENSMUSG00000008393
	Q9Y2V2
	Q9CR86
NM_001042476; NM_001278260; NM_001278261; NM_001278262; NM_001278263;
	NM_001278264; NM_001278265; NM_001278266; NM_014316
	NM_025821
NP_001035941; NP_001265189; NP_001265190; NP_001265191; NP_001265192;
	NP_001265193; NP_001265194; NP_001265195; NP_055131
	NP_080097
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Kalcijem regulirani toplotno stabilni protein 1 (CARHSP1), znan i kao kalcij-regulirani toplotno-stabilni protein od 24 kDa (CRHSP-24), jest protein koji je kod ljudi kodiran genom CARHSP1.^[5]^[6]

CARHSP1 sadrži domen hladnog šoka sa dva motiva koji vežu RNK. Proteini koji sadrže domene hladnog šoka vežu polipirimidinske regije jednolančane RNK i DNK i reguliraju translaciju ribosoma, razgradnju iRNK i brzinu završetka transkripcije. CARHSP1 ima ulogu u stabilizaciji iRNK TNF.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 147 aminokiselina, a molekulska težina 15.892 Da.^[7]

10	20	30	40	50
MSSEPPPPPQ	PPTHQASVGL	LDTPRSRERS	PSPLRGNVVP	SPLPTRRTRT
FSATVRASQG	PVYKGVCKCF	CRSKGHGFIT	PADGGPDIFL	HISDVEGEYV
PVEGDEVTYK	MCSIPPKNEK	LQAVEVVITH	LAPGTKHETW	SGHVISS

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Kloniranje i ekspresija

Korištenjem pacovskog Crhsp24 za ispitivanje EST baze podataka, Groblewski et al. (1998) identificirali su ljudski CARHSP1, kojeg su nazvali CRHSP24. Izvedeni hljudskii protein sa 147 aminokiselina sadrži gotovo 14% prolina i razlikuje se od pacovskog ortologa po samo pet ostataka. Northern blot analizom otkriveni su transkripti Crhsp24 od približno 2,9 i 0,7 kb u svim ispitivanim tkivima pacova, s najvećom ekspresijom u gušterači, sjemenicima, jetri i plućima. Western blot analiza tkiva pacova otkrila je očigledni protein od 24 kD sa sličnim profilom ekspresije. Imunohistokemijska analiza pankreasnog acinusa pacova pokazala je difuzno bojenje Crhsp24 u citoplazmi, sa malo ili nimalo bojenja u jedrima ili sekretornim granulama.

Pfeiffer et al. (2011) izvijestili su da mišji i ljudski CARHSP1 proteini dijele oko 97% identiteta aminokiselina i da oba sadrže domen hladnog šoka sa dva motiva koji vežu RNK. U RAW264.7 mišjeg makrofaga, Carhsp1 lokaliziran je u tijelima za obradu citoplazme koja sadrže translacijski potisnutu iRNK. Čini se da se Carhsp1 lokalizirao na egzosome, koji razgrađuju iRNK, ali se nije lokalizirao tanslacijom iRNK.^[8]

Funkcija gena

Groblewski et al. (1998) otkrili su da je aktivator kalcineurina specifično defosforilirani Crhsp24 u acinarnim ćelijama pankreasa pacova. U baznom stanju izgledalo je da je Crhsp24 fosforiliran na četiri serina, od kojih je najmanje tri defosforilirano kalcineurinom, kao odgovor na mobilizaciju kalcija. Inhibicija kalcineurina sprečila je kalcij-ovisnu defosforilaciju Crhsp24. Schafer et al. (2003) otkrili su da ester forbol i sekretin (SCT) induciraju defosforilaciju Chrosp24 nezavisnu od kalcija u acinarnim ćelijama pacova. Studije inhibitora otkrile su da su esteri forbola i sekretina izazvali defosforilaciju Crhsp24 na najmanje dva serina, vjerovatno preko Pp2a ili Pp4 (PPP4C ^[9]

Koristeći analizu zadržavanja RNK, Pfeiffer et al. (2011) otkrili su da se CARHSP1 vezao za 3-primarni UTR TNF iRNK. Studije prekomkerne ekspresije i nokdaunskim u RAW264.7 mišjim makrofazima sugeriraju da je miš Carhsp1 stabilizirao Tnf i u mirovanju i u ćelijama stimuliranim lipopolisaharidima.

Hartz (2016) mapirala je gen CARHSP1 na hromosom 16, sekvenca p13.2, a na osnovu poravnanja sekvence CARHSP1 (GenBank AF115345) sa genomskom sekvencom (GRCh38).^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000153048 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000008393 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Groblewski GE, Yoshida M, Bragado MJ, Ernst SA, Leykam J, Williams JA (Sep 1998). "Purification and characterization of a novel physiological substrate for calcineurin in mammalian cells". J Biol Chem. 273 (35): 22738–44. doi:10.1074/jbc.273.35.22738. PMID 9712905.
^ "Entrez Gene: CARHSP1 calcium regulated heat stable protein 1, 24kDa".
^ "UniProt, Q9Y2V2". Pristupljeno 2. 7. 2021.
^ Pfeiffer, J. R., McAvoy, B. L., Fecteau, R. E., Deleault, K. M., Brooks, S. A. CARHSP1 is required for effective tumor necrosis factor alpha mRNA stabilization and localizes to processing bodies and exosomes. Molec. Cell. Biol. 31: 277-286, 2011. PubMed: 21078874.
^ Schafer, C., Steffen, H., Krzykowski, K. J., Goke, B., Groblewski, G. E. CRHSP-24 phosphorylation is regulated by multiple signaling pathways in pancreatic acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G726-G734, 2003. [PubMed: 12801884
^ Groblewski, G. E., Yoshida, M., Bragado, M. J., Ernst, S. A., Leykam, J., Williams, J. A. Purification and characterization of a novel physiological substrate for calcineurin in mammalian cells. J. Biol. Chem. 273: 22738-22744, 1998. PubMed: 9712905

Dopunska literatura

Wishart MJ, Dixon JE (2002). "The archetype STYX/dead-phosphatase complexes with a spermatid mRNA-binding protein and is essential for normal sperm production". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 2112–7. doi:10.1073/pnas.251686198. PMC 122327. PMID 11842224.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Schäfer C, Steffen H, Krzykowski KJ, et al. (2003). "CRHSP-24 phosphorylation is regulated by multiple signaling pathways in pancreatic acinar cells". Am. J. Physiol. Gastrointest. Liver Physiol. 285 (4): G726–34. doi:10.1152/ajpgi.00111.2003. PMID 12801884.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Kim JE, Tannenbaum SR, White FM (2005). "Global phosphoproteome of HT-29 human colon adenocarcinoma cells". J. Proteome Res. 4 (4): 1339–46. doi:10.1021/pr050048h. PMID 16083285.
Beausoleil SA, Villén J, Gerber SA, et al. (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000153048 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000008393 - Ensembl, maj 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.

[pmid9712905-5] Groblewski GE, Yoshida M, Bragado MJ, Ernst SA, Leykam J, Williams JA (Sep 1998). "Purification and characterization of a novel physiological substrate for calcineurin in mammalian cells". J Biol Chem. 273 (35): 22738–44. doi:10.1074/jbc.273.35.22738. PMID 9712905.

[entrez-6] "Entrez Gene: CARHSP1 calcium regulated heat stable protein 1, 24kDa".

[UniProt-7] "UniProt, Q9Y2V2". Pristupljeno 2. 7. 2021.

[8] Pfeiffer, J. R., McAvoy, B. L., Fecteau, R. E., Deleault, K. M., Brooks, S. A. CARHSP1 is required for effective tumor necrosis factor alpha mRNA stabilization and localizes to processing bodies and exosomes. Molec. Cell. Biol. 31: 277-286, 2011. PubMed: 21078874.

[9] Schafer, C., Steffen, H., Krzykowski, K. J., Goke, B., Groblewski, G. E. CRHSP-24 phosphorylation is regulated by multiple signaling pathways in pancreatic acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G726-G734, 2003. [PubMed: 12801884

[10] Groblewski, G. E., Yoshida, M., Bragado, M. J., Ernst, S. A., Leykam, J., Williams, J. A. Purification and characterization of a novel physiological substrate for calcineurin in mammalian cells. J. Biol. Chem. 273: 22738-22744, 1998. PubMed: 9712905

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