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)[1] Bend 15q15.1 Početak 42,359,498 bp[1] Kraj 42,412,949 bp[1]
Lokacija gena (miš) Hrom. Hromosom 2 (miš)[2] Bend 2 E5|2 60.31 cM Početak 120,294,053 bp[2] Kraj 120,335,399 bp[2]
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
Vrste	Čovjek	Miš
Entrez	825	12335
Ensembl	ENSG00000092529	ENSMUSG00000079110
UniProt	P20807	Q64691
RefSeq (mRNK)	NM_000070 NM_024344 NM_173087 NM_173088 NM_173089 NM_173090 NM_212465	NM_001109761 NM_001177799 NM_007601
RefSeq (bjelančevina)	NP_000061 NP_077320 NP_775110 NP_775111 NP_775112 NP_775113	NP_001103231 NP_001171270 NP_031627
Lokacija (UCSC)	Chr 15: 42.36 – 42.41 Mb	Chr 2: 120.29 – 120.34 Mb
PubMed pretraga	[3]	[4]
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

1. GRCh38: Ensembl release 89: ENSG00000092529 - Ensembl, maj 2017
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.
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.
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.
7. "UniProt, P20807". Pristupljeno 12. 7. 2021.
8. "Entrez Gene: CAPN3 calpain 3, (p94)".
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.
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.
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.

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.