CAPN3

CAPN3
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4OKH
Identifikatori
Aliasi	CAPN3
Vanjski ID-jevi	OMIM: 114240 MGI: 107437 HomoloGene: 52 GeneCards: CAPN3
Lokacija gena (čovjek)
Hrom.	Hromosom 15 (čovjek)
Kraj	42,412,949 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	120,335,399 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calcium ion binding; • cysteine-type peptidase activity; • sodium ion binding; • titin binding; • signal transducer activity; • vezivanje iona metala; • calcium-dependent cysteine-type endopeptidase activity; • GO:0070122 peptidase activity; • catalytic activity; • GO:0001948, GO:0016582 vezivanje za proteine; • GO:0032947 molecular adaptor activity; • structural constituent of muscle; • hydrolase activity; • ligase regulator activity;
Ćelijska komponenta	• citoplazma; • citosol; • T-tubule; • ćelijska membrana; • intracellular anatomical structure; • Miofibril; • Z discdkac; • jedro; • GO:0009327 makromolekulani kompleks;
Biološki proces	• muscle structure development; • cellular response to calcium ion; • protein localization to membrane; • negative regulation of protein sumoylation; • positive regulation of satellite cell activation involved in skeletal muscle regeneration; • muscle cell cellular homeostasis; • muscle organ development; • self proteolysis; • negative regulation of apoptotic process; • positive regulation of release of sequestered calcium ion into cytosol; • Proteoliza; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • response to calcium ion; • negative regulation of skeletal muscle cell differentiation; • G1 to G0 transition involved in cell differentiation; • cellular response to salt stress; • myofibril assembly; • regulation of myoblast differentiation; • positive regulation of NF-kappaB transcription factor activity; • positive regulation of proteolysis; • GO:0048552 regulation of catalytic activity; • GO:0045996 negative regulation of transcription, DNA-templated; • sarcomere organization; • response to muscle activity; • regulation of I-kappaB kinase/NF-kappaB signaling; • GO:0097285 apoptoza; • GO:0072468 Transdukcija signala; • GO:0010703, GO:0010702 programirana ćelijska smrt; • GO:0034622 protein-containing complex assembly; • GO:0044257 protein catabolic process; • protein destabilization; • calcium-dependent self proteolysis;
	Izvori:Amigo / QuickGO
Ortolozi
	825
	12335
	ENSG00000092529
	ENSMUSG00000079110
	P20807
	Q64691
NM_000070; NM_024344; NM_173087; NM_173088; NM_173089;
	NM_173090; NM_212465
	NM_001109761; NM_001177799; NM_007601
NP_000061; NP_077320; NP_775110; NP_775111; NP_775112;
	NP_775113
	NP_001103231; NP_001171270; NP_031627
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Kalpain-3 je protein koji je kod ljudi kodirn genom CAPN3.^[5]^[6] Struktura gena Richard et al. (1995) pokazali su da gen CAPN3 sadrži 24 egzona i da se proteže preko 40 kb.

Ohno et al. (1990) mapirali su gen CAPN3 u hromosomu 15.

Hibridizacijom somatskih ćelija, Richard i Beckmann (1996) lokalizirali su mišji Capn3 ili na hromosomu 2 ili na hromosomu 4. Rezultati nisu omogućili razlikovanje između ova dva hromosoma, budući da svi hibridi koji nose mišji hromosom 2 nose i hromosom 4. Činjenica da izolirani mišji YAC pojačali su mjesto označeno sekvencom (STS) za gen TYRO3, koji je mapiran na ljudskom hromosomu 15, sugerirajući da su dva gena kod miša susjedna. Brojni primjeri dobro su utvrdili homologiju između mišjeg hromosoma 2 i ljudskog hromosoma 15; nije dokazana homologija sinteze između ljudskog 15 i mišjeg hromosoma 4.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 821 aminokiselina, a molekulska težina 94.254 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
MPTVISASVA	PRTAAEPRSP	GPVPHPAQSK	ATEAGGGNPS	GIYSAIISRN
FPIIGVKEKT	FEQLHKKCLE	KKVLYVDPEF	PPDETSLFYS	QKFPIQFVWK
RPPEICENPR	FIIDGANRTD	ICQGELGDCW	FLAAIACLTL	NQHLLFRVIP
HDQSFIENYA	GIFHFQFWRY	GEWVDVVIDD	CLPTYNNQLV	FTKSNHRNEF
WSALLEKAYA	KLHGSYEALK	GGNTTEAMED	FTGGVAEFFE	IRDAPSDMYK
IMKKAIERGS	LMGCSIDDGT	NMTYGTSPSG	LNMGELIARM	VRNMDNSLLQ
DSDLDPRGSD	ERPTRTIIPV	QYETRMACGL	VRGHAYSVTG	LDEVPFKGEK
VKLVRLRNPW	GQVEWNGSWS	DRWKDWSFVD	KDEKARLQHQ	VTEDGEFWMS
YEDFIYHFTK	LEICNLTADA	LQSDKLQTWT	VSVNEGRWVR	GCSAGGCRNF
PDTFWTNPQY	RLKLLEEDDD	PDDSEVICSF	LVALMQKNRR	KDRKLGASLF
TIGFAIYEVP	KEMHGNKQHL	QKDFFLYNAS	KARSKTYINM	REVSQRFRLP
PSEYVIVPST	YEPHQEGEFI	LRVFSEKRNL	SEEVENTISV	DRPVKKKKTK
PIIFVSDRAN	SNKELGVDQE	SEEGKGKTSP	DKQKQSPQPQ	PGSSDQESEE
QQQFRNIFKQ	IAGDDMEICA	DELKKVLNTV	VNKHKDLKTH	GFTLESCRSM
IALMDTDGSG	KLNLQEFHHL	WNKIKAWQKI	FKHYDTDQSG	TINSYEMRNA
VNDAGFHLNN	QLYDIITMRY	ADKHMNIDFD	SFICCFVRLE	GMFRAFHAFD
KDGDGIIKLN	VLEWLQLTMY	A

Funkcija

Kalpain, heterodimer koji se sastoji od velike i male podjedinice, glavna je unutarćelijska proteaza, iako njena funkcija nije dobro utvrđena. Ovaj gen kodira specifičnog člana za mišiće velike porodice podjedinica kalpaina koji se specifično veže za titin. Mutacije u ovom genu povezane su s mišićnom distrofijom udova i pojasa tipa 2A. Alternativni promotori i alternativna prerada rezultiraju u više varijanti transkripta koji kodiraju različite izoforme, a neke varijante su sveprisutno eksprimirane.^[8]

U melanocitnim ćelijama ekspresija gena CAPN3 može se regulirati pomoću MITF.^[9]

Interakcije

Pokazano je da CAPN3 komunicira sa titinom.^[10]^[11]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000092529 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000079110 - 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.
^ Sorimachi H, Imajoh-Ohmi S, Emori Y, Kawasaki H, Ohno S, Minami Y, Suzuki K (decembar 1989). "Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types. Specific expression of the mRNA in skeletal muscle". J. Biol. Chem. 264 (33): 20106–11. PMID 2555341.
^ Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C (maj 1995). "Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A". Cell. 81 (1): 27–40. doi:10.1016/0092-8674(95)90368-2. PMID 7720071.
^ "UniProt, P20807". Pristupljeno 12. 7. 2021.
^ "Entrez Gene: CAPN3 calpain 3, (p94)".
^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
^ Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K (juli 1998). "Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A". J. Biol. Chem. 273 (27): 17073–8. doi:10.1074/jbc.273.27.17073. PMID 9642272.
^ Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K (decembar 1995). "Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence". J. Biol. Chem. 270 (52): 31158–62. doi:10.1074/jbc.270.52.31158. PMID 8537379.

Dopunska literatura

Sorimachi H, Ishiura S, Suzuki K (1997). "Structure and physiological function of calpains". Biochem. J. 328 (3): 721–32. doi:10.1042/bj3280721. PMC 1218978. PMID 9396712.
Kinbara K, Sorimachi H, Ishiura S, Suzuki K (1998). "Skeletal muscle-specific calpain, p49: structure and physiological function". Biochem. Pharmacol. 56 (4): 415–20. doi:10.1016/S0006-2952(98)00095-1. PMID 9763216.
Sorimachi H, Ono Y, Suzuki K (2000). "Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions and relationship to limb-girdle muscular dystrophy type 2A". Adv. Exp. Med. Biol. 481: 383–95, discussion 395-7. doi:10.1007/978-1-4615-4267-4_23. PMID 10987085.
Baghdiguian S, Richard I, Martin M, Coopman P, Beckmann JS, Mangeat P, Lefranc G (2001). "Pathophysiology of limb girdle muscular dystrophy type 2A: hypothesis and new insights into the IkappaBalpha/NF-kappaB survival pathway in skeletal muscle". J. Mol. Med. 79 (5–6): 254–61. doi:10.1007/s001090100225. PMID 11485017.
Canki-Klain N, Milic A, Kovac B, Trlaja A, Grgicevic D, Zurak N, Fardeau M, Leturcq F, Kaplan JC, Urtizberea JA, Politano L, Piluso G, Feingold J (2004). "Prevalence of the 550delA mutation in calpainopathy (LGMD 2A) in Croatia". Am. J. Med. Genet. A. 125A (2): 152–6. doi:10.1002/ajmg.a.20408. PMID 14981715.
Kramerova I, Beckmann JS, Spencer MJ (2007). "Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A)" (PDF). Biochim. Biophys. Acta. 1772 (2): 128–44. doi:10.1016/j.bbadis.2006.07.002. PMID 16934440.
Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K (1990). "Four genes for the calpain family locate on four distinct human chromosomes". Cytogenet. Cell Genet. 53 (4): 225–9. doi:10.1159/000132937. PMID 2209092.
Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K (1995). "Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence". J. Biol. Chem. 270 (52): 31158–62. doi:10.1074/jbc.270.52.31158. PMID 8537379.
Fardeau M, Hillaire D, Mignard C, Feingold N, Feingold J, Mignard D, de Ubeda B, Collin H, Tome FM, Richard I, Beckmann J (1996). "Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island". Brain. 119 (1): 295–308. doi:10.1093/brain/119.1.295. PMID 8624690.
Corasaniti MT, Navarra M, Catani MV, Melino G, Nisticò G, Finazzi-Agrò A (1996). "NMDA and HIV-1 coat protein, GP120, produce necrotic but not apoptotic cell death in human CHP100 neuroblastoma cultures via a mechanism involving calpain". Biochem. Biophys. Res. Commun. 229 (1): 299–304. doi:10.1006/bbrc.1996.1796. PMID 8954122.
Richard I, Brenguier L, Dinçer P, Roudaut C, Bady B, Burgunder JM, Chemaly R, Garcia CA, Halaby G, Jackson CE, Kurnit DM, Lefranc G, Legum C, Loiselet J, Merlini L, Nivelon-Chevallier A, Ollagnon-Roman E, Restagno G, Topaloglu H, Beckmann JS (1997). "Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins". Am. J. Hum. Genet. 60 (5): 1128–38. PMC 1712426. PMID 9150160.
Kinbara K, Sorimachi H, Ishiura S, Suzuki K (1997). "Muscle-specific calpain, p94, interacts with the extreme C-terminal region of connectin, a unique region flanked by two immunoglobulin C2 motifs". Arch. Biochem. Biophys. 342 (1): 99–107. doi:10.1006/abbi.1997.0108. PMID 9185618.
Pratt VM, Jackson CE, Wallace DC, Gurley DS, Feit A, Feldman GL (1997). "DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a modifying mitochondrial gene and show no evidence for a modifying nuclear gene". Am. J. Hum. Genet. 61 (1): 231–3. doi:10.1016/S0002-9297(07)64296-7. PMC 1715865. PMID 9246005.
Dinçer P, Leturcq F, Richard I, Piccolo F, Yalnizoglu D, de Toma C, Akçören Z, Broux O, Deburgrave N, Brenguier L, Roudaut C, Urtizberea JA, Jung D, Tan E, Jeanpierre M, Campbell KP, Kaplan JC, Beckmann JS, Topaloglu H (1997). "A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey". Ann. Neurol. 42 (2): 222–9. doi:10.1002/ana.410420214. PMID 9266733.
Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K (1998). "Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A". J. Biol. Chem. 273 (27): 17073–8. doi:10.1074/jbc.273.27.17073. PMID 9642272.
Pénisson-Besnier I, Richard I, Dubas F, Beckmann JS, Fardeau M (1998). "Pseudometabolic expression and phenotypic variability of calpain deficiency in two siblings". Muscle Nerve. 21 (8): 1078–80. doi:10.1002/(SICI)1097-4598(199808)21:8<1078::AID-MUS15>3.0.CO;2-Q. PMID 9655129.
Urtasun M, Sáenz A, Roudaut C, Poza JJ, Urtizberea JA, Cobo AM, Richard I, García Bragado F, Leturcq F, Kaplan JC, Martí Massó JF, Beckmann JS, López de Munain A (1998). "Limb-girdle muscular dystrophy in Guipúzcoa (Basque Country, Spain)". Brain. 121 (9): 1735–47. doi:10.1093/brain/121.9.1735. PMID 9762961.
Huang Y, de Morrée A, van Remoortere A, Bushby K, Frants RR, den Dunnen JT, van der Maarel SM (2008). "Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle". Hum. Mol. Genet. 17 (12): 1855–66. doi:10.1093/hmg/ddn081. PMC 2900895. PMID 18334579.

Vanjski linkovi

The MEROPS online database for peptidases and their inhibitors: C02.004 Arhivirano 11. 4. 2008. na Wayback Machine
GeneReviews/NCBI/NIH/UW entry on Calpainopathy
LOVD mutation database: CAPN3
Lokacija ljudskog genoma CAPN3 i stranica sa detaljima o genu CAPN3 u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000092529 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000079110 - 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.

[pmid2555341-5] Sorimachi H, Imajoh-Ohmi S, Emori Y, Kawasaki H, Ohno S, Minami Y, Suzuki K (decembar 1989). "Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types. Specific expression of the mRNA in skeletal muscle". J. Biol. Chem. 264 (33): 20106–11. PMID 2555341.

[pmid7720071-6] Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C (maj 1995). "Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A". Cell. 81 (1): 27–40. doi:10.1016/0092-8674(95)90368-2. PMID 7720071.

[UniProt-7] "UniProt, P20807". Pristupljeno 12. 7. 2021.

[entrez-8] "Entrez Gene: CAPN3 calpain 3, (p94)".

[pmid19067971-9] Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

[pmid9642272-10] Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K (juli 1998). "Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A". J. Biol. Chem. 273 (27): 17073–8. doi:10.1074/jbc.273.27.17073. PMID 9642272.

[pmid8537379-11] Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K (decembar 1995). "Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence". J. Biol. Chem. 270 (52): 31158–62. doi:10.1074/jbc.270.52.31158. PMID 8537379.

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