COCH

COCH
Identifikatori
Aliasi
Vanjski ID-jevi	GeneCards: [1]
Ortolozi
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	n; a
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	Wikipodaci
Pogledaj/uredi – čovjek

Kohlin je protein koji je kod ljudi kodiran genom COCH.^[1]^[2] To je o protein vanćelijskog matriksa (ECM) koji je vrlo bogato eksprimiran u pužnici i predvorju unutrašnjeg uha, čineći njegovu glavnu ne-kolagenu komponentu ECM-a.^[3]^[4] Protein je visoko konzerviran u ljudi, miša i kokoši, pokazujući 94% i 79% aminokiselinskih identiteta sekvenci čovjeka i miša, odnosno kokoši.^[2]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 550 aminokiselina, a molekulska težina 59.483 Da.^[5].

10	20	30	40	50
MSAAWIPALG	LGVCLLLLPG	PAGSEGAAPI	AITCFTRGLD	IRKEKADVLC
PGGCPLEEFS	VYGNIVYASV	SSICGAAVHR	GVISNSGGPV	RVYSLPGREN
YSSVDANGIQ	SQMLSRWSAS	FTVTKGKSST	QEATGQAVST	AHPPTGKRLK
KTPEKKTGNK	DCKADIAFLI	DGSFNIGQRR	FNLQKNFVGK	VALMLGIGTE
GPHVGLVQAS	EHPKIEFYLK	NFTSAKDVLF	AIKEVGFRGG	NSNTGKALKH
TAQKFFTVDA	GVRKGIPKVV	VVFIDGWPSD	DIEEAGIVAR	EFGVNVFIVS
VAKPIPEELG	MVQDVTFVDK	AVCRNNGFFS	YHMPNWFGTT	KYVKPLVQKL
CTHEQMMCSK	TCYNSVNIAF	LIDGSSSVGD	SNFRLMLEFV	SNIAKTFEIS
DIGAKIAAVQ	FTYDQRTEFS	FTDYSTKENV	LAVIRNIRYM	SGGTATGDAI
SFTVRNVFGP	IRESPNKNFL	VIVTDGQSYD	DVQGPAAAAH	DAGITIFSVG
VAWAPLDDLK	DMASKPKESH	AFFTREFTGL	EPIVSDVIRG	ICRDFLESQQ

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

Struktura

Kohlin sadrži tri proteinska domena: N-terminalni LCCL domen i dvije kopije Von Willebrandovog domenskog faktora tipa A.^[6]

Funkcija

Gen je eksprimiran u vretenastim čeliojamama duž nervnih vlakana između slušnoe ganglije i njušnog epitela. Te ćelije prate neurita na habenula perforata, otvor kroz koji se neuriti protežu kako bi inervirali trepljaste ćelije. Ovo i obrazac ekspresije ovog gena u unutrašnjem uhu kokoši paralelni su sa histološkim nalazima acidofilnih naslaga, u skladu sa mukopolisaharidnom zrnastom supstancom, u sljepoočnim kostima kod pacijenata sa DFNA9 (autosomno dominantna nesindromska senzorineuralna gluhoća 9) pacijenti. U ovom su genu zabilježene mutacije koje uzrokuju DFNA9.^[2]

Kohlin je identificiran kod trabekulske mreže (TM) pacijenata sa glaukomom, ali ne i kod zdravih kontrola. TM je područje tkiva na oku poput filtera; kohlin može imati ulogu u adheziji ćelija, mehanoosjetljivosti i modulaciji TM filtra.^[7]^[8]

Takođe se eksprimiraa u folikulskim dendritskim ćelijama u slezeni i limfnim čvorovima . Ovdje se kohlin cijepa enzimom agrekanaza i izlučuje u krvotok tokom upala, doprinoseći antibakterijskom urođenom imunskom odgovoru.^[9]

Reference

^ Robertson NG, Lu L, Heller S, Merchant SN, Eavey RD, McKenna M, Nadol JB, Miyamoto RT, Linthicum FH, Lubianca Neto JF, Hudspeth AJ, Seidman CE, Morton CC, Seidman JG (novembar 1998). "Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction". Nature Genetics. 20 (3): 299–303. doi:10.1038/3118. PMID 9806553.
^ ^a ^b ^c "Entrez Gene: COCH coagulation factor C homolog, cochlin (Limulus polyphemus)".
^ Robertson NG, Skvorak AB, Yin Y, Weremowicz S, Johnson KR, Kovatch KA, Battey JF, Bieber FR, Morton CC (decembar 1997). "Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9". Genomics. 46 (3): 345–54. doi:10.1006/geno.1997.5067. PMID 9441737.
^ Ikezono T, Omori A, Ichinose S, Pawankar R, Watanabe A, Yagi T (mart 2001). "Identification of the protein product of the Coch gene (hereditary deafness gene) as the major component of bovine inner ear protein". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1535 (3): 258–65. doi:10.1016/s0925-4439(00)00101-0. PMID 11278165.
^ "UniProt, O43405". Pristupljeno 22. 7. 2021.
^ "Cochlin (O43405)". InterPro < EMBL-EBI.
^ Goel M, Sienkiewicz AE, Picciani R, Lee RK, Bhattacharya SK (2011). "Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility". PLOS ONE. 6 (8): e23070. doi:10.1371/journal.pone.0023070. PMC 3160293. PMID 21886777.
^ Picciani R, Desai K, Guduric-Fuchs J, Cogliati T, Morton CC, Bhattacharya SK (septembar 2007). "Cochlin in the eye: functional implications". Progress in Retinal and Eye Research. 26 (5): 453–69. doi:10.1016/j.preteyeres.2007.06.002. PMC 2064858. PMID 17662637.
^ Py BF, Gonzalez SF, Long K, Kim MS, Kim YA, Zhu H, Yao J, Degauque N, Villet R, Ymele-Leki P, Gadjeva M, Pier GB, Carroll MC, Yuan J (maj 2013). "Cochlin produced by follicular dendritic cells promotes antibacterial innate immunity". Immunity. 38 (5): 1063–72. doi:10.1016/j.immuni.2013.01.015. PMC 3758559. PMID 23684986.

Dopunska literatura

Khetarpal U, Schuknecht HF, Gacek RR, Holmes LB (septembar 1991). "Autosomal dominant sensorineural hearing loss. Pedigrees, audiologic findings, and temporal bone findings in two kindreds". Archives of Otolaryngology–Head & Neck Surgery. 117 (9): 1032–42. doi:10.1001/archotol.1991.01870210104022. PMID 1910721.
Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC (septembar 1994). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics. 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID 7829101.
Khetarpal U (januar 1993). "Autosomal dominant sensorineural hearing loss. Further temporal bone findings". Archives of Otolaryngology–Head & Neck Surgery. 119 (1): 106–8. doi:10.1001/archotol.1993.01880130108016. PMID 8417734.
Manolis EN, Yandavi N, Nadol JB, Eavey RD, McKenna M, Rosenbaum S, Khetarpal U, Halpin C, Merchant SN, Duyk GM, MacRae C, Seidman CE, Seidman JG (juli 1996). "A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13". Human Molecular Genetics. 5 (7): 1047–50. doi:10.1093/hmg/5.7.1047. PMID 8817345.
de Kok YJ, Bom SJ, Brunt TM, Kemperman MH, van Beusekom E, van der Velde-Visser SD, Robertson NG, Morton CC, Huygen PL, Verhagen WI, Brunner HG, Cremers CW, Cremers FP (februar 1999). "A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects". Human Molecular Genetics. 8 (2): 361–6. doi:10.1093/hmg/8.2.361. PMID 9931344.
Fransen E, Verstreken M, Verhagen WI, Wuyts FL, Huygen PL, D'Haese P, Robertson NG, Morton CC, McGuirt WT, Smith RJ, Declau F, Van de Heyning PH, Van Camp G (august 1999). "High prevalence of symptoms of Menière's disease in three families with a mutation in the COCH gene". Human Molecular Genetics. 8 (8): 1425–9. doi:10.1093/hmg/8.8.1425. PMID 10400989.
Kamarinos M, McGill J, Lynch M, Dahl H (april 2001). "Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families". Human Mutation. 17 (4): 351. doi:10.1002/humu.37. PMID 11295836.
Boulassel MR, Tomasi JP, Deggouj N, Gersdorff M (septembar 2001). "COCH5B2 is a target antigen of anti-inner ear antibodies in autoimmune inner ear diseases". Otology & Neurotology. 22 (5): 614–8. doi:10.1097/00129492-200109000-00009. PMID 11568667.
Liepinsh E, Trexler M, Kaikkonen A, Weigelt J, Bányai L, Patthy L, Otting G (oktobar 2001). "NMR structure of the LCCL domain and implications for DFNA9 deafness disorder". The EMBO Journal. 20 (19): 5347–53. doi:10.1093/emboj/20.19.5347. PMC 125649. PMID 11574466.
Robertson NG, Resendes BL, Lin JS, Lee C, Aster JC, Adams JC, Morton CC (oktobar 2001). "Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9". Human Molecular Genetics. 10 (22): 2493–500. doi:10.1093/hmg/10.22.2493. PMID 11709536.
Robertson NG, Hamaker SA, Patriub V, Aster JC, Morton CC (juli 2003). "Subcellular localisation, secretion, and post-translational processing of normal cochlin, and of mutants causing the sensorineural deafness and vestibular disorder, DFNA9". Journal of Medical Genetics. 40 (7): 479–86. doi:10.1136/jmg.40.7.479. PMC 1735525. PMID 12843317.
Grabski R, Szul T, Sasaki T, Timpl R, Mayne R, Hicks B, Sztul E (oktobar 2003). "Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin". Human Genetics. 113 (5): 406–16. doi:10.1007/s00439-003-0992-7. PMID 12928864.
Lemaire FX, Feenstra L, Huygen PL, Fransen E, Devriendt K, Van Camp G, Vantrappen G, Cremers CW, Wackym PA, Koss JC (septembar 2003). "Progressive late-onset sensorineural hearing loss and vestibular impairment with vertigo (DFNA9/COCH): longitudinal analyses in a belgian family". Otology & Neurotology. 24 (5): 743–8. doi:10.1097/00129492-200309000-00009. PMID 14501450.
Usami S, Takahashi K, Yuge I, Ohtsuka A, Namba A, Abe S, Fransen E, Patthy L, Otting G, Van Camp G (oktobar 2003). "Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease". European Journal of Human Genetics. 11 (10): 744–8. doi:10.1038/sj.ejhg.5201043. PMID 14512963.
Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A (april 2004). "The human plasma proteome: a nonredundant list developed by combination of four separate sources". Molecular & Cellular Proteomics. 3 (4): 311–26. doi:10.1074/mcp.M300127-MCP200. PMID 14718574.

[pmid9806553-1] Robertson NG, Lu L, Heller S, Merchant SN, Eavey RD, McKenna M, Nadol JB, Miyamoto RT, Linthicum FH, Lubianca Neto JF, Hudspeth AJ, Seidman CE, Morton CC, Seidman JG (novembar 1998). "Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction". Nature Genetics. 20 (3): 299–303. doi:10.1038/3118. PMID 9806553.

[entrez-2] "Entrez Gene: COCH coagulation factor C homolog, cochlin (Limulus polyphemus)".

[pmid9441737-3] Robertson NG, Skvorak AB, Yin Y, Weremowicz S, Johnson KR, Kovatch KA, Battey JF, Bieber FR, Morton CC (decembar 1997). "Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9". Genomics. 46 (3): 345–54. doi:10.1006/geno.1997.5067. PMID 9441737.

[pmid11278165-4] Ikezono T, Omori A, Ichinose S, Pawankar R, Watanabe A, Yagi T (mart 2001). "Identification of the protein product of the Coch gene (hereditary deafness gene) as the major component of bovine inner ear protein". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1535 (3): 258–65. doi:10.1016/s0925-4439(00)00101-0. PMID 11278165.

[UniProt-5] "UniProt, O43405". Pristupljeno 22. 7. 2021.

[6] "Cochlin (O43405)". InterPro < EMBL-EBI.

[7] Goel M, Sienkiewicz AE, Picciani R, Lee RK, Bhattacharya SK (2011). "Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility". PLOS ONE. 6 (8): e23070. doi:10.1371/journal.pone.0023070. PMC 3160293. PMID 21886777.

[pmid17662637-8] Picciani R, Desai K, Guduric-Fuchs J, Cogliati T, Morton CC, Bhattacharya SK (septembar 2007). "Cochlin in the eye: functional implications". Progress in Retinal and Eye Research. 26 (5): 453–69. doi:10.1016/j.preteyeres.2007.06.002. PMC 2064858. PMID 17662637.

[9] Py BF, Gonzalez SF, Long K, Kim MS, Kim YA, Zhu H, Yao J, Degauque N, Villet R, Ymele-Leki P, Gadjeva M, Pier GB, Carroll MC, Yuan J (maj 2013). "Cochlin produced by follicular dendritic cells promotes antibacterial innate immunity". Immunity. 38 (5): 1063–72. doi:10.1016/j.immuni.2013.01.015. PMC 3758559. PMID 23684986.

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