PCDH15

PCDH15
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4APX, 4AQ8, 4AQA, 4AQE, 4AXW
Identifikatori
Aliasi	PCDH15
Vanjski ID-jevi	OMIM: 605514 MGI: 1891428 HomoloGene: 23401 GeneCards: PCDH15
Lokacija gena (čovjek)
Hrom.	Hromosom 10 (čovjek)
Kraj	55,627,942 bp
Lokacija gena (miš)
Hrom.	Hromosom 10 (miš)
Kraj	74,649,737 bp
Ontologija gena
Molekularna funkcija	• calcium ion binding;
Ćelijska komponenta	• integral component of membrane; • extracellular region; • ćelijska membrana; • photoreceptor outer segment; • sinapsa; • membrana; • stereocilium; • Vanćelijsko; • integral component of plasma membrane;
Biološki proces	• inner ear development; • photoreceptor cell maintenance; • sensory perception of light stimulus; • sluh; • Čulo ravnoteže; • homophilic cell adhesion via plasma membrane adhesion molecules; • Ćelijska adhezija; • cell-cell signaling; • nervous system development;
	Izvori:Amigo / QuickGO
Ortolozi
	65217
	11994
	ENSG00000150275
	ENSMUSG00000052613
	Q96QU1
	Q99PJ1
NM_033056; NM_001142763; NM_001142764; NM_001142765; NM_001142766;
	NM_001142767; NM_001142768; NM_001142769; NM_001142770; NM_001142771; NM_001142772; NM_001142773; NM_001354404; NM_001354411; NM_001354420; NM_001354429; NM_001354430; NM_001384140
NM_001142735; NM_001142736; NM_001142737; NM_001142738; NM_001142739;
	NM_001142740; NM_001142741; NM_001142742; NM_001142743; NM_001142746; NM_001142747; NM_001142748; NM_001142760; NM_023115
NP_001136235; NP_001136236; NP_001136237; NP_001136238; NP_001136239;
	NP_001136240; NP_001136241; NP_001136242; NP_001136243; NP_001136244; NP_001136245; NP_149045; NP_001341333; NP_001341340; NP_001341349; NP_001341358; NP_001341359; NP_001371069
NP_001136207; NP_001136208; NP_001136209; NP_001136210; NP_001136211;
	NP_001136212; NP_001136213; NP_001136214; NP_001136215; NP_001136218; NP_001136219; NP_001136220; NP_001136232; NP_075604
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protokadherin-15 je protein koji je kod ljudi kodiran genom PCDH15.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.955 aminokiselina, а molekulska težina 216.069 Da.^[8]

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
MFRQFYLWTC	LASGIILGSL	FEICLGQYDD	DCKLARGGPP	ATIVAIDEES
RNGTILVDNM	LIKGTAGGPD	PTIELSLKDN	VDYWVLMDPV	KQMLFLNSTG
RVLDRDPPMN	IHSIVVQVQC	INKKVGTIIY	HEVRIVVRDR	NDNSPTFKHE
SYYATVNELT	PVGTTIFTGF	SGDNGATDID	DGPNGQIEYV	IQYNPDDPTS
NDTFEIPLML	TGNIVLRKRL	NYEDKTRYFV	IIQANDRAQN	LNERRTTTTT
LTVDVLDGDD	LGPMFLPCVL	VPNTRDCRPL	TYQAAIPELR	TPEELNPIIV
TPPIQAIDQD	RNIQPPSDRP	GILYSILVGT	PEDYPRFFHM	HPRTAELSLL
EPVNRDFHQK	FDLVIKAEQD	NGHPLPAFAG	LHIEILDENN	QSPYFTMPSY
QGYILESAPV	GATISDSLNL	TSPLRIVALD	KDIEDTKDPE	LHLFLNDYTS
VFTVTQTGIT	RYLTLLQPVD	REEQQTYTFS	ITAFDGVQES	EPVIVNIQVM
DANDNTPTFP	EISYDVYVYT	DMRPGDSVIQ	LTAVDADEGS	NGEITYEILV
GAQGDFIINK	TTGLITIAPG	VEMIVGRTYA	LTVQAADNAP	PAERRNSICT
VYIEVLPPNN	QSPPRFPQLM	YSLEISEAMR	VGAVLLNLQA	TDREGDSITY
AIENGDPQRV	FNLSETTGIL	TLGKALDRES	TDRYILIITA	SDGRPDGTST
ATVNIVVTDV	NDNAPVFDPY	LPRNLSVVEE	EANAFVGQVK	ATDPDAGING
QVHYSLGNFN	NLFRITSNGS	IYTAVKLNRE	VRDYYELVVV	ATDGAVHPRH
STLTLAIKVL	DIDDNSPVFT	NSTYTVLVEE	NLPAGTTILQ	IEAKDVDLGA
NVSYRIRSPE	VKHFFALHPF	TGELSLLRSL	DYEAFPDQEA	SITFLVEAFD
IYGTMPPGIA	TVTVIVKDMN	DYPPVFSKRI	YKGMVAPDAV	KGTPITTVYA
EDADPPGLPA	SRVRYRVDDV	QFPYPASIFE	VEEDSGRVIT	RVNLNEEPTT
IFKLVVVAFD	DGEPVMSSSA	TVKILVLHPG	EIPRFTQEEY	RPPPVSELAT
KGTMVGVISA	AAINQSIVYS	IVSGNEEDTF	GINNITGVIY	VNGPLDYETR
TSYVLRVQAD	SLEVVLANLR	VPSKSNTAKV	YIEIQDENNH	PPVFQKKFYI
GGVSEDARMF	TSVLRVKATD	KDTGNYSVMA	YRLIIPPIKE	GKEGFVVETY
TGLIKTAMLF	HNMRRSYFKF	QVIATDDYGK	GLSGKADVLV	SVVNQLDMQV
IVSNVPPTLV	EKKIEDLTEI	LDRYVQEQIP	GAKVVVESIG	ARRHGDAFSL
EDYTKCDLTV	YAIDPQTNRA	IDRNELFKFL	DGKLLDINKD	FQPYYGEGGR
ILEIRTPEAV	TSIKKRGESL	GYTEGALLAL	AFIIILCCIP	AILVVLVSYR
QFKVRQAECT	KTARIQAALP	AAKPAVPAPA	PVAAPPPPPP	PPPGAHLYEE
LGDSSILFLL	YHFQQSRGNN	SVSEDRKHQQ	VVMPFSSNTI	EAHKSAHVDG
SLKSNKLKSA	RKFTFLSDED	DLSAHNPLYK	ENISQVSTNS	DISQRTDFVD
PFSPKIQAKS	KSLRGPREKI	QRLWSQSVSL	PRRLMRKVPN	RPEIIDLQQW
QGTRQKAENE	NTGICTNKRG	SSNPLLTTEE	ANLTEKEEIR	QGETLMIEGT
EQLKSLSSDS	SFCFPRPHFS	FSTLPTVSRT	VELKSEPNVI	SSPAECSLEL
SPSRPCVLHS	SLSRRETPIC	MLPIETERNI	FENFAHPPNI	SPSACPLPPP
PPISPPSPPP	APAPLAPPPD	ISPFSLFCPP	PSPPSIPLPL	PPPTFFPLSV
STSGPPTPPL	LPPFPTPLPP	PPPSIPCPPP	PSASFLSTEC	VCITGVKCTT
NLMPAEKIKS	SMTQLSTTTV	CKTDPQREPK	GILRHVKNLA	ELEKSVANMY
SQIEKNYLRT	NVSELQTMCP	SEVTNMEITS	EQNKGSLNNI	VEGTEKQSHS
QSTSL

Funkcija

Ovaj gen je član nadporodice kadherina. Članovi porodice kodiraju proteine integralne membrane koji posreduju kalcij-ovisnoj adheziji. Proteinski proizvod ovog gena sastoji se od signalog peptida, 11 vanćelijskih domena koji vezuju kalcij, transmembranskog domena i jedinstvenog citoplazmatskog domena. Ima bitnu ulogu u održavanju normalnih funkcija mrežnjače l i pužnice.^[7] Smatra se da je u interakciji s CDH23, kako bi formirao vrh-linkovane filamente.^[9]

Klinički znčaj

Mutacije u ovom genu povezane su s gubitkom sluha, što je u skladu s njegovom lokacijom u Usherovom sindromu tip 1F (USH1F), kritičnoj regiji na hromosomu 10.^[7] Utvrđeno je da su varijacije unutar njega povezane s normalnim razlikama u izgledu ljudskog lica.^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000150275 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000052613 - 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.
^ Ahmed ZM, Riazuddin S, Bernstein SL, Ahmed Z, Khan S, Griffith AJ, et al. (juli 2001). "Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F". American Journal of Human Genetics. 69 (1): 25–34. doi:10.1086/321277. PMC 1226045. PMID 11398101.
^ Ahmed ZM, Riazuddin S, Ahmad J, Bernstein SL, Guo Y, Sabar MF, et al. (decembar 2003). "PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23". Human Molecular Genetics. 12 (24): 3215–23. doi:10.1093/hmg/ddg358. PMID 14570705. S2CID 14028314.
^ ^a ^b ^c "Entrez Gene: PCDH15 protocadherin 15".
^ "UniProt, Q96QU1". Pristupljeno 3. 9. 2021.
^ Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek EM, Milligan RA, Müller U, Kachar B (septembar 2007). "Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells". Nature. 449 (7158): 87–91. Bibcode:2007Natur.449...87K. doi:10.1038/nature06091. PMID 17805295. S2CID 4414814.
^ Crouch DJ, Winney B, Koppen WP, Christmas WJ, Hutnik K, Day T, et al. (januar 2018). "Genetics of the human face: Identification of large-effect single gene variants". Proceedings of the National Academy of Sciences of the United States of America. 115 (4): E676–E685. doi:10.1073/pnas.1708207114. PMC 5789906. PMID 29301965.

Dopunska literatura

Alagramam KN, Murcia CL, Kwon HY, Pawlowski KS, Wright CG, Woychik RP (januar 2001). "The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene". Nature Genetics. 27 (1): 99–102. doi:10.1038/83837. PMID 11138007. S2CID 32444699.
Alagramam KN, Yuan H, Kuehn MH, Murcia CL, Wayne S, Srisailpathy CR, et al. (august 2001). "Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F". Human Molecular Genetics. 10 (16): 1709–18. doi:10.1093/hmg/10.16.1709. PMID 11487575.
Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, et al. (april 2003). "A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome". The New England Journal of Medicine. 348 (17): 1664–70. doi:10.1056/NEJMoa021502. PMID 12711741.
Zheng QY, Yan D, Ouyang XM, Du LL, Yu H, Chang B, et al. (januar 2005). "Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans". Human Molecular Genetics. 14 (1): 103–11. doi:10.1093/hmg/ddi010. PMC 2858222. PMID 15537665.
Ouyang XM, Yan D, Du LL, Hejtmancik JF, Jacobson SG, Nance WE, et al. (mart 2005). "Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population". Human Genetics. 116 (4): 292–9. doi:10.1007/s00439-004-1227-2. PMID 15660226. S2CID 22812718.
Roux AF, Faugère V, Le Guédard S, Pallares-Ruiz N, Vielle A, Chambert S, et al. (septembar 2006). "Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%". Journal of Medical Genetics. 43 (9): 763–8. doi:10.1136/jmg.2006.041954. PMC 2564578. PMID 16679490.
Zheng QY, Yu H, Washington JL, Kisley LB, Kikkawa YS, Pawlowski KS, et al. (septembar 2006). "A new spontaneous mutation in the mouse protocadherin 15 gene". Hearing Research. 219 (1–2): 110–20. doi:10.1016/j.heares.2006.06.010. PMC 2855306. PMID 16887306.
Le Guédard S, Faugère V, Malcolm S, Claustres M, Roux AF (januar 2007). "Large genomic rearrangements within the PCDH15 gene are a significant cause of USH1F syndrome". Molecular Vision. 13: 102–7. PMC 2533038. PMID 17277737.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Usher Syndrome Type I
PDBe-KB provides an overview of all the structure information available in the PDB for Human Protocadherin-15 (PCDH15)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000150275 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000052613 - 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.

[pmid11398101-5] Ahmed ZM, Riazuddin S, Bernstein SL, Ahmed Z, Khan S, Griffith AJ, et al. (juli 2001). "Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F". American Journal of Human Genetics. 69 (1): 25–34. doi:10.1086/321277. PMC 1226045. PMID 11398101.

[pmid14570705-6] Ahmed ZM, Riazuddin S, Ahmad J, Bernstein SL, Guo Y, Sabar MF, et al. (decembar 2003). "PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23". Human Molecular Genetics. 12 (24): 3215–23. doi:10.1093/hmg/ddg358. PMID 14570705. S2CID 14028314.

[entrez-7] "Entrez Gene: PCDH15 protocadherin 15".

[UniProt-8] "UniProt, Q96QU1". Pristupljeno 3. 9. 2021.

[9] Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek EM, Milligan RA, Müller U, Kachar B (septembar 2007). "Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells". Nature. 449 (7158): 87–91. Bibcode:2007Natur.449...87K. doi:10.1038/nature06091. PMID 17805295. S2CID 4414814.

[10] Crouch DJ, Winney B, Koppen WP, Christmas WJ, Hutnik K, Day T, et al. (januar 2018). "Genetics of the human face: Identification of large-effect single gene variants". Proceedings of the National Academy of Sciences of the United States of America. 115 (4): E676–E685. doi:10.1073/pnas.1708207114. PMC 5789906. PMID 29301965.

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