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 uredi

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 uredi

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 uredi

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 uredi

^ ^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 uredi

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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