ADAMTS5

ADAMTS5
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2RJQ, 3B8Z, 3HY7, 3HY9, 3HYG, 3LJT
Identifikatori
Aliasi	ADAMTS5
Vanjski ID-jevi	OMIM: 605007 MGI: 1346321 HomoloGene: 5109 GeneCards: ADAMTS5
Lokacija gena (čovjek)
Hrom.	Hromosom 21 (čovjek)
Kraj	26,967,088 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	85,698,716 bp
Ontologija gena
Molekularna funkcija	• heparin binding; • vezivanje iona cinka; • extracellular matrix binding; • vezivanje iona metala; • integrin binding; • GO:0070122 peptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • hydrolase activity; • metallopeptidase activity; • metalloendopeptidase activity;
Ćelijska komponenta	• endoplasmic reticulum lumen; • extracellular region; • Vanćelijsko; • GO:0005578 Vanćelijski matriks; • collagen-containing extracellular matrix;
Biološki proces	• extracellular matrix disassembly; • Proteoliza; • defense response to bacterium; • tooth eruption; • negative regulation of cold-induced thermogenesis;
	Izvori:Amigo / QuickGO
Ortolozi
	11096
	23794
	ENSG00000154736
	ENSMUSG00000022894
	Q9UNA0
	Q9R001
	NM_007038
	NM_011782
	NP_008969
	NP_035912
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Disintegrin i metaloproteinaza sa trombospondinskim motivima 5 jest enzim koji je kod ljudi kodiran genom ADAMTS5 sa hromosoma 21.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 930 aminokiselina, a molekulska težina 101.718 Da.^[7]

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
MLLGWASLLL	CAFRLPLAAV	GPAATPAQDK	AGQPPTAAAA	AQPRRRQGEE
VQERAEPPGH	PHPLAQRRRS	KGLVQNIDQL	YSGGGKVGYL	VYAGGRRFLL
DLERDGSVGI	AGFVPAGGGT	SAPWRHRSHC	FYRGTVDGSP	RSLAVFDLCG
GLDGFFAVKH	ARYTLKPLLR	GPWAEEEKGR	VYGDGSARIL	HVYTREGFSF
EALPPRASCE	TPASTPEAHE	HAPAHSNPSG	RAALASQLLD	QSALSPAGGS
GPQTWWRRRR	RSISRARQVE	LLLVADASMA	RLYGRGLQHY	LLTLASIANR
LYSHASIENH	IRLAVVKVVV	LGDKDKSLEV	SKNAATTLKN	FCKWQHQHNQ
LGDDHEEHYD	AAILFTREDL	CGHHSCDTLG	MADVGTICSP	ERSCAVIEDD
GLHAAFTVAH	EIGHLLGLSH	DDSKFCEETF	GSTEDKRLMS	SILTSIDASK
PWSKCTSATI	TEFLDDGHGN	CLLDLPRKQI	LGPEELPGQT	YDATQQCNLT
FGPEYSVCPG	MDVCARLWCA	VVRQGQMVCL	TKKLPAVEGT	PCGKGRICLQ
GKCVDKTKKK	YYSTSSHGNW	GSWGSWGQCS	RSCGGGVQFA	YRHCNNPAPR
NNGRYCTGKR	AIYRSCSLMP	CPPNGKSFRH	EQCEAKNGYQ	SDAKGVKTFV
EWVPKYAGVL	PADVCKLTCR	AKGTGYYVVF	SPKVTDGTEC	RLYSNSVCVR
GKCVRTGCDG	IIGSKLQYDK	CGVCGGDNSS	CTKIVGTFNK	KSKGYTDVVR
IPEGATHIKV	RQFKAKDQTR	FTAYLALKKK	NGEYLINGKY	MISTSETIID
INGTVMNYSG	WSHRDDFLHG	MGYSATKEIL	IVQILATDPT	KPLDVRYSFF
VPKKSTPKVN	SVTSHGSNKV	GSHTSQPQWV	TGPWLACSRT	CDTGWHTRTV
QCQDGNRKLA	KGCPLSQRPS	AFKQCLLKKC

Funkcija

ADAMTS5 je član porodice proteina ADAMTS (dezintegrin i metaloproteinaza sa motivima trombospondina). Članovi porodice dijele nekoliko različitih proteinskih modula, uključujući propeptidnu regiju, metaloproteinazni domen, disintegrinski domen i trombospondinski tip 1 (TS) motiva. Pojedini članovi ove porodice razlikuju se po broju C-terminalnih TS motiva, a neki imaju jedinstvene ove motive. Enzim kodiran ovim genom sadrži dva C-terminalna TS motiva i funkcionira kao agrekanaza za cijepanje agrekana, glavnog hrskavičnog proteoglikana.^[7] ADAMTS5 također može imati ulogu u patogenezi ljudskog osteoartritisa.^[8]

Studije na životinjama

Genetički modificirani miševi kod kojih je deletirana katalitsk domen ADAMTS5 otporni su na destrukciju hrskavice u eksperimentalnom modelu osteoartritisa.^[9] ADAMTS5 je glavna agrekanaza u mišjoj hrskavici u mišjem modelu upalnog artritisa.^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000154736 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022894 - 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.
^ Abbaszade I, Liu RQ, Yang F, Rosenfeld SA, Ross OH, Link JR, Ellis DM, Tortorella MD, Pratta MA, Hollis JM, Wynn R, Duke JL, George HJ, Hillman MC, Murphy K, Wiswall BH, Copeland RA, Decicco CP, Bruckner R, Nagase H, Itoh Y, Newton RC, Magolda RL, Trzaskos JM, Burn TC (Aug 1999). "Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family". The Journal of Biological Chemistry. 274 (33): 23443–50. doi:10.1074/jbc.274.33.23443. PMID 10438522.
^ Hurskainen TL, Hirohata S, Seldin MF, Apte SS (Sep 1999). "ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family". The Journal of Biological Chemistry. 274 (36): 25555–63. doi:10.1074/jbc.274.36.25555. PMID 10464288.
^ ^a ^b "Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif".
^ Verma P, Dalal K (Dec 2011). "ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis". Journal of Cellular Biochemistry. 112 (12): 3507–14. doi:10.1002/jcb.23298. PMID 21815191. S2CID 30611107.
^ Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA (Mar 2005). "Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis". Nature. 434 (7033): 644–8. Bibcode:2005Natur.434..644G. doi:10.1038/nature03369. PMID 15800624. S2CID 4339874.
^ Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, Fosang AJ (Mar 2005). "ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro". Nature. 434 (7033): 648–52. Bibcode:2005Natur.434..648S. doi:10.1038/nature03417. PMID 15800625. S2CID 4366441.

Dopunska literatira

Mosyak L, Georgiadis K, Shane T, Svenson K, Hebert T, McDonagh T, Mackie S, Olland S, Lin L, Zhong X, Kriz R, Reifenberg EL, Collins-Racie LA, Corcoran C, Freeman B, Zollner R, Marvell T, Vera M, Sum PE, Lavallie ER, Stahl M, Somers W (Jan 2008). "Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5". Protein Science. 17 (1): 16–21. doi:10.1110/ps.073287008. PMC 2144589. PMID 18042673.
Malfait AM, Arner EC, Song RH, Alston JT, Markosyan S, Staten N, Yang Z, Griggs DW, Tortorella MD (Oct 2008). "Proprotein convertase activation of aggrecanases in cartilage in situ". Archives of Biochemistry and Biophysics. 478 (1): 43–51. doi:10.1016/j.abb.2008.07.012. PMID 18671934.
Matsumoto T, Tojyo I, Kiga N, Hiraishi Y, Fujita S (Dec 2008). "Expression of ADAMTS-5 in deformed human temporomandibular joint discs". Histology and Histopathology. 23 (12): 1485–93. PMID 18830934.
Thirunavukkarasu K, Pei Y, Wei T (Dec 2007). "Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter". Molecular Biology Reports. 34 (4): 225–31. doi:10.1007/s11033-006-9037-3. PMID 17211519. S2CID 20729185.
Patel KP, Sandy JD, Akeda K, Miyamoto K, Chujo T, An HS, Masuda K (Nov 2007). "Aggrecanases and aggrecanase-generated fragments in the human intervertebral disc at early and advanced stages of disc degeneration". Spine. 32 (23): 2596–603. doi:10.1097/BRS.0b013e318158cb85. PMID 17978660. S2CID 6965994.
Wheeler HE, Metter EJ, Tanaka T, Absher D, Higgins J, Zahn JM, Wilhelmy J, Davis RW, Singleton A, Myers RM, Ferrucci L, Kim SK (Oct 2009). Gibson G (ured.). "Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging". PLOS Genetics. 5 (10): e1000685. doi:10.1371/journal.pgen.1000685. PMC 2752811. PMID 19834535.
Shieh HS, Mathis KJ, Williams JM, Hills RL, Wiese JF, Benson TE, Kiefer JR, Marino MH, Carroll JN, Leone JW, Malfait AM, Arner EC, Tortorella MD, Tomasselli A (Jan 2008). "High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2)". The Journal of Biological Chemistry. 283 (3): 1501–7. doi:10.1074/jbc.M705879200. PMID 17991750.
Grogan SP, Barbero A, Diaz-Romero J, Cleton-Jansen AM, Soeder S, Whiteside R, Hogendoorn PC, Farhadi J, Aigner T, Martin I, Mainil-Varlet P (Feb 2007). "Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity" (PDF). Arthritis and Rheumatism. 56 (2): 586–95. doi:10.1002/art.22408. PMID 17265493.
Nakada M, Miyamori H, Kita D, Takahashi T, Yamashita J, Sato H, Miura R, Yamaguchi Y, Okada Y (Sep 2005). "Human glioblastomas overexpress ADAMTS-5 that degrades brevican". Acta Neuropathologica. 110 (3): 239–46. doi:10.1007/s00401-005-1032-6. PMID 16133547. S2CID 25744956.
Gendron C, Kashiwagi M, Lim NH, Enghild JJ, Thøgersen IB, Hughes C, Caterson B, Nagase H (Jun 2007). "Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4". The Journal of Biological Chemistry. 282 (25): 18294–306. doi:10.1074/jbc.M701523200. PMID 17430884.
Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H (Mar 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics. 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
Rodriguez-Lopez J, Mustafa Z, Pombo-Suarez M, Malizos KN, Rego I, Blanco FJ, Tsezou A, Loughlin J, Gomez-Reino JJ, Gonzalez A (Feb 2008). "Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis". Arthritis and Rheumatism. 58 (2): 435–41. doi:10.1002/art.23201. PMID 18240210.
Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA, Flannery CR (Mar 2006). "Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18". Biochimica et Biophysica Acta (BBA) - General Subjects. 1760 (3): 517–24. doi:10.1016/j.bbagen.2006.01.013. PMID 16507336.
Zhu H, Leung PC, MacCalman CD (Jan 2007). "Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines". Human Reproduction. 22 (1): 63–74. doi:10.1093/humrep/del356. PMID 17067994.
Hirohata S (Nov 2001). "[ADAMTS family--new extracellular matrix degrading enzyme]". Seikagaku. The Journal of Japanese Biochemical Society. 73 (11): 1333–7. PMID 11831030.
Fushimi K, Troeberg L, Nakamura H, Lim NH, Nagase H (Mar 2008). "Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity". The Journal of Biological Chemistry. 283 (11): 6706–16. doi:10.1074/jbc.M708647200. PMID 18156631.
Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G, Pap T (Sep 2009). "Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis". Nature Medicine. 15 (9): 1072–6. doi:10.1038/nm.1998. PMID 19684582. S2CID 10914435.
Tang BL (Jan 2001). "ADAMTS: a novel family of extracellular matrix proteases". The International Journal of Biochemistry & Cell Biology. 33 (1): 33–44. doi:10.1016/S1357-2725(00)00061-3. PMID 11167130.
Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW (Feb 2007). "Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5". Arthritis and Rheumatism. 56 (2): 575–85. doi:10.1002/art.22334. PMID 17265492.
Barthel KK, Liu X (2008). Abraham E (ured.). "A transcriptional enhancer from the coding region of ADAMTS5". PLOS ONE. 3 (5): e2184. Bibcode:2008PLoSO...3.2184B. doi:10.1371/journal.pone.0002184. PMC 2364661. PMID 18478108.

Vanjski linkovi

The MEROPS online database for peptidases and their inhibitors: M12.225^{[mrtav link]}
Rat Genome Database
Lokacija ljudskog genoma ADAMTS5 i stranica sa detaljima o genu ADAMTS5 u UCSC Genome Browseru.

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000154736 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022894 - 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.

[pmid10438522-5] Abbaszade I, Liu RQ, Yang F, Rosenfeld SA, Ross OH, Link JR, Ellis DM, Tortorella MD, Pratta MA, Hollis JM, Wynn R, Duke JL, George HJ, Hillman MC, Murphy K, Wiswall BH, Copeland RA, Decicco CP, Bruckner R, Nagase H, Itoh Y, Newton RC, Magolda RL, Trzaskos JM, Burn TC (Aug 1999). "Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family". The Journal of Biological Chemistry. 274 (33): 23443–50. doi:10.1074/jbc.274.33.23443. PMID 10438522.

[pmid10464288-6] Hurskainen TL, Hirohata S, Seldin MF, Apte SS (Sep 1999). "ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family". The Journal of Biological Chemistry. 274 (36): 25555–63. doi:10.1074/jbc.274.36.25555. PMID 10464288.

[entrez-7] "Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif".

[8] Verma P, Dalal K (Dec 2011). "ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis". Journal of Cellular Biochemistry. 112 (12): 3507–14. doi:10.1002/jcb.23298. PMID 21815191. S2CID 30611107.

[pmid15800624-9] Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA (Mar 2005). "Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis". Nature. 434 (7033): 644–8. Bibcode:2005Natur.434..644G. doi:10.1038/nature03369. PMID 15800624. S2CID 4339874.

[pmid15800625-10] Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, Fosang AJ (Mar 2005). "ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro". Nature. 434 (7033): 648–52. Bibcode:2005Natur.434..648S. doi:10.1038/nature03417. PMID 15800625. S2CID 4366441.

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p r u Proteaze: metaloendopeptidaze (EC 3.4.24)
ADAM proteins	Alpha secretases ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
Matrix metalloproteinases	Collagenases MMP1 MMP8 Gelatinases MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23A MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
Ostali	Neprilysin Procollagen peptidase Thermolysin Pregnancy-associated plasma protein A Bone morphogenetic protein 1 Lysostaphin Insulin-degrading enzyme ZMPSTE24

p r u Enzimi
Teme	Aktivno mjesto Alosterna regulacija Difuzijski limitirani enzim EC broj Enzimska kataliza Inhibicija enzimskih reakcija Kinetika enzima Koenzim Kooperativnost Lineweaver–Burkov dijagram Michaelis–Mentenova kinetika Mjesto vezanja Spisak enzima
Tipovi	EC1 Oksidoreduktaze/spisak EC2 Transferaze/spisak EC3 Hidrolaze/spisak EC4 Lijaze/spisak EC5 Izomeraze/spisak EC6 Ligaze/spisak