GPHB5
Glikoproteinski hormon beta-5 je protein koji je kod ljudi kodiran genom GPHB5.[5]
Analizom genomske sekvence, Hsu et al. (2002) mapirali su gen GPHB5 u hromosomu14. Utvrdili su da gen GPHB5 sadrži dva egzona.[6]
GPHB5 je polipeptid koji formira cistinski čvor i podjedinicu iz porodice dimernih glikoproteinskih hormona (Hsu et al., 2002, prema OMIM][5]
Aminokiselinska sekvenca
Dužina polipeptidnog lanca je 130 aminokiselina, a molekulska težina 14.232 Da.[7]
- 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
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MKLAFLFLGP | MALLLLAGYG | CVLGASSGNL | RTFVGCAVRE | FTFLAKKPGC | ||||
| RGLRITTDAC | WGRCETWEKP | ILEPPYIEAH | HRVCTYNETK | QVTVKLPNCA | ||||
| PGVDPFYTYP | VAIRCDCGAC | STATTECETI |
Kloniranje i ekspresija
Traženjem gena sličnih podjedinicama glikoproteinskih hormona, nakon čega slijede EST analiza baze podataka i PCR ljudskog mozga, i hipofizne cDNK, Hsu et al. (2002) klonirani GPB5. Izvedeni proteinski prekursor od 130 aminokiselina sadrži signalni peptid od 24 aminokiseline na N-kraju, a zreli protein ima navodno mjesto N-glikozilacije. GPB5 ima 10 od 12 konzerviranih cisteina u klasičnim beta-podjedinicama. Prema tome, GPB5 ima tri disulfidna mosta unutar strukture cistinskog čvora, ali nedostaje mu jedan od tri dodatna mosta nađena u klasičnim beta-podjedinicama. Zbog krnjeg C-kraja i odsustva trećeg disulfidnog mosta, GPB5 nema strukturu sigurnosnog pojasa pronađenu u drugim beta podjedinicama. Međutim, sadrži dva pretpostavljena područja ukosnice ispod cistinskog čvora i dugačku petlju iznad. PCR analiza nekoliko ljudskih tkiva otkrila je GPB5 pretežno u mozgu i hipofizi. Transfekcija GPD5 cDNK u ljudskim embrionskim ćelijama bubrega rezultirala je izlučenim proteinom od oko 16 kD.
Koristeći Western blot analizu, Nakabayashi et al. (2002) pokazali su da se glikoproteini A2 (GPHA2) i B5 izlučuju u medij kotransficiranih ćelija embrionskog ljudskog bubrega. Prividna molekulska masa B5 iznosila je 20 kD, a tretman glikozidazom ukazao je da je B5 glikoprotein. Imunohistohemijska analiza otkrila je A2 i B5 koeksprimirane u prednjem režnju hipofize pacova, ali proteini nisu koekspricirani u pacovskom mozgu, štitnjači ili jajnicima.
Funkcija gena
Analizom 2-hibridnog kvasca, Nakabayashi et al. (2002) pronašli su snažne interakcije između A2 i B5. Frakcionacijom ljudskih embrionskih ćelija bubrega kotransficiranim sa A2 i B5, otkriven je A2-B5 dimer od oko 43 kD. Dimer, koji su autori odredili kao tirostimulin, stimulirao je proizvodnju cAMP-a u ćelijama koje eksprimiraju rekombinantne ljudske TSH receptore. Tirostimulin je takođe stimulirao proizvodnju cAMP i ugradnju timidina u ćelijsku liniju štitne žlijezde pacova, a povećao je nivo T4 kod odraslih. Tirostimulin je bio neučinkovit u aktiviranju bilo LH (LHCGR), bilo FSH receptora (FSHR).[8]
Reference
- ^ a b c GRCh38: Ensembl release 89: ENSG00000179600 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048982 - 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.
- ^ a b "Entrez Gene: GPHB5 glycoprotein hormone beta 5".
- ^ Hsu, S. Y., Nakabayashi, K., Bhalla, A. Evolution of glycoprotein hormone subunit genes in bilateral metazoa: identification of two novel human glycoprotein hormone subunit family genes, GPA2 and GPB5. Molec. Endocr. 16: 1538-1551, 2002. PubMed: 12089349
- ^ "UniProt, Q86YW7". Pristupljeno 25. 7. 2021.
- ^ Nakabayashi, K., Matsumi, H., Bhalla, A., Bae, J., Mosselman, S., Hsu, S. Y., Hsueh, A. J. W. Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor. J. Clin. Invest. 109: 1445-1452, 2002. PubMed: 12045258
Dopunska literatura
- Okada SL, Ellsworth JL, Durnam DM, et al. (2006). "A glycoprotein hormone expressed in corticotrophs exhibits unique binding properties on thyroid-stimulating hormone receptor". Mol. Endocrinol. 20 (2): 414–25. doi:10.1210/me.2005-0270. PMID 16210345.
- Sudo S, Kuwabara Y, Park JI, et al. (2005). "Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5". Endocrinology. 146 (8): 3596–604. doi:10.1210/en.2005-0317. PMID 15890769.
- 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.
- Heilig R, Eckenberg R, Petit JL, et al. (2003). "The DNA sequence and analysis of human chromosome 14". Nature. 421 (6923): 601–7. Bibcode:2003Natur.421..601H. doi:10.1038/nature01348. PMID 12508121.
- 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Hsu SY, Nakabayashi K, Bhalla A (2003). "Evolution of glycoprotein hormone subunit genes in bilateral metazoa: identification of two novel human glycoprotein hormone subunit family genes, GPA2 and GPB5". Mol. Endocrinol. 16 (7): 1538–51. doi:10.1210/me.16.7.1538. PMID 12089349.
- Nakabayashi K, Matsumi H, Bhalla A, et al. (2002). "Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor". J. Clin. Invest. 109 (11): 1445–52. doi:10.1172/JCI14340. PMC 150994. PMID 12045258.
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