GPHB5

GPHB5
Identifikatori
Aliasi	GPHB5
Vanjski ID-jevi	OMIM: 609652 MGI: 2156540 HomoloGene: 18476 GeneCards: GPHB5
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	63,318,935 bp
Lokacija gena (miš)
Hrom.	Hromosom 12 (miš)
Kraj	75,463,555 bp
Ontologija gena
Molekularna funkcija	• hormone activity; • thyrotropin-releasing hormone receptor binding; • protein heterodimerization activity; • GO:0001948, GO:0016582 vezivanje za proteine;
Ćelijska komponenta	• extracellular region; • Vanćelijsko; • citoplazma;
Biološki proces	• regulation of thyroid hormone mediated signaling pathway; • cell-cell signaling; • hormone-mediated signaling pathway; • cell surface receptor signaling pathway; • regulation of signaling receptor activity; • G protein-coupled receptor signaling pathway; • adenylate cyclase-activating G protein-coupled receptor signaling pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	122876
	217674
	ENSG00000179600
	ENSMUSG00000048982
	Q86YW7
	Q812B2
	NM_145171
	NM_175644
	NP_660154
	NP_783575
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000179600 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000048982 - 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.

[entrez-5] "Entrez Gene: GPHB5 glycoprotein hormone beta 5".

[6] 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-7] "UniProt, Q86YW7". Pristupljeno 25. 7. 2021.

[8] 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

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