ADAMTS13

ADAMTS13
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3GHM, 3GHN
Identifikatori
Aliasi	ADAMTS13
Vanjski ID-jevi	OMIM: 604134 MGI: 2685556 HomoloGene: 16372 GeneCards: ADAMTS13
Lokacija gena (čovjek)
Hrom.	Hromosom 9 (čovjek)
Kraj	133,459,402 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	26,899,640 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calcium ion binding; • endopeptidase activity; • vezivanje iona metala; • integrin binding; • GO:0070122 peptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • metalloendopeptidase activity; • hydrolase activity; • metallopeptidase activity; • vezivanje iona cinka;
Ćelijska komponenta	• endoplasmic reticulum lumen; • extracellular region; • cell surface; • Vanćelijsko; • GO:0005578 Vanćelijski matriks;
Biološki proces	• Hemostaza; • glycoprotein metabolic process; • response to interleukin-4; • response to interferon-gamma; • protein processing; • Koagulacija (krv); • Proteoliza; • platelet activation; • response to tumor necrosis factor; • integrin-mediated signaling pathway; • cell-matrix adhesion; • response to toxic substance; • peptide catabolic process; • response to potassium ion; • cellular response to interferon-gamma; • cellular response to lipopolysaccharide; • response to amine; • cellular response to interleukin-4; • cellular response to tumor necrosis factor;
	Izvori:Amigo / QuickGO
Ortolozi
	11093
	279028
	ENSG00000160323; ENSG00000281244
	ENSMUSG00000014852
	Q76LX8
	Q769J6
	NM_139025; NM_139026; NM_139027; NM_139028
	NM_001001322; NM_001290463; NM_001290464; NM_001290465
	NP_620594; NP_620595; NP_620596
	NP_001001322; NP_001277392; NP_001277393; NP_001277394
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

ADAMTS13 (eng. a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) — znan i kao von Willebrandov faktor cijepanja proteaze (VWFCP) — metaloproteazni enzim koji sadrži cink, a koja cijepa von Willebrandov factor (vWf), veliki protein uključen u zgrušavanje krvi. Izlučuje se u krv i razgrađuje velike multimere vWf, smanjujući njihovu aktivnost.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.427 aminokiselina, а molekulska težina 153.604 Da.^[6]

10	20	30	40	50
MHQRHPRARC	PPLCVAGILA	CGFLLGCWGP	SHFQQSCLQA	LEPQAVSSYL
SPGAPLKGRP	PSPGFQRQRQ	RQRRAAGGIL	HLELLVAVGP	DVFQAHQEDT
ERYVLTNLNI	GAELLRDPSL	GAQFRVHLVK	MVILTEPEGA	PNITANLTSS
LLSVCGWSQT	INPEDDTDPG	HADLVLYITR	FDLELPDGNR	QVRGVTQLGG
ACSPTWSCLI	TEDTGFDLGV	TIAHEIGHSF	GLEHDGAPGS	GCGPSGHVMA
SDGAAPRAGL	AWSPCSRRQL	LSLLSAGRAR	CVWDPPRPQP	GSAGHPPDAQ
PGLYYSANEQ	CRVAFGPKAV	ACTFAREHLD	MCQALSCHTD	PLDQSSCSRL
LVPLLDGTEC	GVEKWCSKGR	CRSLVELTPI	AAVHGRWSSW	GPRSPCSRSC
GGGVVTRRRQ	CNNPRPAFGG	RACVGADLQA	EMCNTQACEK	TQLEFMSQQC
ARTDGQPLRS	SPGGASFYHW	GAAVPHSQGD	ALCRHMCRAI	GESFIMKRGD
SFLDGTRCMP	SGPREDGTLS	LCVSGSCRTF	GCDGRMDSQQ	VWDRCQVCGG
DNSTCSPRKG	SFTAGRAREY	VTFLTVTPNL	TSVYIANHRP	LFTHLAVRIG
GRYVVAGKMS	ISPNTTYPSL	LEDGRVEYRV	ALTEDRLPRL	EEIRIWGPLQ
EDADIQVYRR	YGEEYGNLTR	PDITFTYFQP	KPRQAWVWAA	VRGPCSVSCG
AGLRWVNYSC	LDQARKELVE	TVQCQGSQQP	PAWPEACVLE	PCPPYWAVGD
FGPCSASCGG	GLRERPVRCV	EAQGSLLKTL	PPARCRAGAQ	QPAVALETCN
PQPCPARWEV	SEPSSCTSAG	GAGLALENET	CVPGADGLEA	PVTEGPGSVD
EKLPAPEPCV	GMSCPPGWGH	LDATSAGEKA	PSPWGSIRTG	AQAAHVWTPA
AGSCSVSCGR	GLMELRFLCM	DSALRVPVQE	ELCGLASKPG	SRREVCQAVP
CPARWQYKLA	ACSVSCGRGV	VRRILYCARA	HGEDDGEEIL	LDTQCQGLPR
PEPQEACSLE	PCPPRWKVMS	LGPCSASCGL	GTARRSVACV	QLDQGQDVEV
DEAACAALVR	PEASVPCLIA	DCTYRWHVGT	WMECSVSCGD	GIQRRRDTCL
GPQAQAPVPA	DFCQHLPKPV	TVRGCWAGPC	VGQGTPSLVP	HEEAAAPGRT
TATPAGASLE	WSQARGLLFS	PAPQPRRLLP	GPQENSVQSS	ACGRQHLEPT
GTIDMRGPGQ	ADCAVAIGRP	LGEVVTLRVL	ESSLNCSAGD	MLLLWGRLTW
RKMCRKLLDM	TFSSKTNTLV	VRQRCGRPGG	GVLLRYGSQL	APETFYRECD
MQLFGPWGEI	VSPSLSPATS	NAGGCRLFIN	VAPHARIAIH	ALATNMGAGT
EGANASYILI	RDTHSLRTTA	FHGQQVLYWE	SESSQAEMEF	SEGFLKAQAS
LRGQYWTLQS	WVPEMQDPQS	WKGKEGT

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

Genetika

Gen ADAMTS13 mapiran je na hromosomu 9, sekvenca 9q34.^[5]

Otkriće

Od 1982. godine bilo je poznato da je trombocita trombocitopenija purpura (TTP), jedna od mikroangiopatskih hemolitskih anemija (vidi dolje), u svom porodičnom obliku okarakterizirana prisustvom u plazmi neobično velikog multimernog von Willebrandov faktora (ULVWF).^[5]

Godine 1994. pokazano je da se vWF cijepa između tirozina na položaju 1.605 i metionina na 1.606 enzimnom metaloproteazom u plazmi kada je bio izložen visokim razinama smicanja. U 1996., dvije su istraživačke grupe neovisno dodatno okarakterizirale ovaj enzim. U sljedeće dvije godine, iste dvije grupe pokazale su da je urođeni nedostatak cijepanja vWF proteazama povezan s stvaranjem trombocitnih mikrotrombova u malim krvnim žilama. Osim toga, izvijestili su da su IgG antitijela usmjerena protiv istog enzima, izazivajući TTP u većini slučajeva koji nisu porodični.^[5]

Proteomika

Genomski, ADAMTS13 dijeli mnoga svojstva sa 19 članova porodice ADAMTS porodica, a sve njih karakterizira domen proteaze (dio koji obavla hidrolizu proteina), susjedni dezintegrinski domen i jedan ili više domena trombospondina. ADAMTS13 u stvari ima osam domena trombospondina. Nema hidrofobni transmembranski domen pa nije usidren u ćelijskoj membrani.^[5]

Klinički značaj

Nedostatak ADAMTS13 prvobitno je otkriven u Upshaw-Schulmanovom sindromu, ponavljajućem porodičnom obliku trombocitne trombocitopenije purpure. Do tada se već sumnjalo da se TTP javlja i u autoimunskom obliku, zbog odgovora na plazmaferezu i karakterizacije IgG inhibitora. Od otkrića ADAMTS13, pokazalo se da su specifični epitopi na njegovoj površini meta inhibitornih antitijela.^[5]^[7]^[8]

Nizak nivo ADAMTS13 je takođe povezan sa povećanim rizikom od arterijske tromboze,^[9] uključujući infarkt miokarda^[10] i cerebrovaskularnu bolest.^[11]^[12]= 6 | pages = e0179258 | date = 2017 | pmid = 28591212 | doi = 10.1371/journal.pone.0179258

Konačno, budući da je dokazano da je veza između stenoza aortnog zaliska i angiodisplazije posljedica visokog smicnog naprezanja (Heydeov sindrom), prihvaćeno je da povećana izloženost vWf do ADAMTS13 zbog različitih razloga koji bi predisponirali krvarenje, uzrokujući povećanu degradaciju vWf. Ovaj fenomen karakterizira oblik von Willebrandove bolesti (tip 2a).^[5]

Takpđer pogledajte

ADAMTS5

Reference

^ ^a ^b ^c ENSG00000281244 GRCh38: Ensembl release 89: ENSG00000160323, ENSG00000281244 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000014852 - 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.
^ ^a ^b ^c ^d ^e ^f ^g Levy GG, Motto DG, Ginsburg D (juli 2005). "ADAMTS13 turns 3". Blood. 106 (1): 11–7. doi:10.1182/blood-2004-10-4097. PMID 15774620.
^ "UniProt, Q76LX8". Pristupljeno 5. 9. 2021.
^ Tsai HM (april 2003). "Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura". Journal of the American Society of Nephrology. 14 (4): 1072–81. doi:10.1097/01.ASN.0000060805.04118.4C. PMID 12660343.
^ Furlan M, Lämmle B (juni 2001). "Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease". Best Practice & Research. Clinical Haematology. 14 (2): 437–54. doi:10.1053/beha.2001.0142. PMID 11686108.
^ Sonneveld MA, de Maat MP, Leebeek FW (juli 2014). "Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis". Blood Reviews. 28 (4): 167–78. doi:10.1016/j.blre.2014.04.003. PMID 24825749.
^ Maino A, Siegerink B, Lotta LA, Crawley JT, le Cessie S, Leebeek FW, Lane DA, Lowe GD, Peyvandi F, Rosendaal FR (august 2015). "Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis" (PDF). Journal of Thrombosis and Haemostasis. 13 (8): 1396–404. doi:10.1111/jth.13032. hdl:10044/1/26935. PMID 26073931. S2CID 324472.
^ Sonneveld MA, de Maat MP, Portegies ML, Kavousi M, Hofman A, Turecek PL, Rottensteiner H, Scheiflinger F, Koudstaal PJ, Ikram MA, Leebeek FW (decembar 2015). "Low ADAMTS13 activity is associated with an increased risk of ischemic stroke". Blood. 126 (25): 2739–46. doi:10.1182/blood-2015-05-643338. PMID 26511134.
^ Denorme F, Kraft P, Pareyn I, Drechsler C, Deckmyn H, Vanhoorelbeke K, Kleinschnitz C, De Meyer SF. "Reduced ADAMTS13 levels in patients with acute and chronic cerebrovascular disease". PLOS ONE. 12. Bibcode:2017PLoSO..1279258D. PMC 5462472. Zanemaren tekst "issue" (pomoć); |doi-access= zahtijeva |doi= (pomoć)

Dopunska literatura

Tang BL (januar 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.
Fujimura Y, Matsumoto M, Yagi H, Yoshioka A, Matsui T, Titani K (januar 2002). "Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome". International Journal of Hematology. 75 (1): 25–34. doi:10.1007/BF02981975. PMID 11843286. S2CID 19926816.
Zheng X, Majerus EM, Sadler JE (septembar 2002). "ADAMTS13 and TTP". Current Opinion in Hematology. 9 (5): 389–94. doi:10.1097/00062752-200209000-00001. PMID 12172456. S2CID 19457473.
Tsai HM (oktobar 2002). "Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura". Journal of Molecular Medicine. 80 (10): 639–47. doi:10.1007/s00109-002-0369-8. PMID 12395148. S2CID 24992893.
Tsai HM (mart 2003). "Platelet activation and the formation of the platelet plug: deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura". Arteriosclerosis, Thrombosis, and Vascular Biology. 23 (3): 388–96. doi:10.1161/01.ATV.0000058401.34021.D4. PMID 12615692.
Tsai HM (april 2003). "Is severe deficiency of ADAMTS-13 specific for thrombotic thrombocytopenic purpura? Yes". Journal of Thrombosis and Haemostasis. 1 (4): 625–31. doi:10.1046/j.1538-7836.2003.00169.x. PMID 12871390. S2CID 26485194.
Remuzzi G (april 2003). "Is ADAMTS-13 deficiency specific for thrombotic thrombocytopenic purpura? No". Journal of Thrombosis and Haemostasis. 1 (4): 632–4. doi:10.1046/j.1538-7836.2003.00170.x. PMID 12871391. S2CID 10742104.
Moake JL (januar 2004). "von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura". Seminars in Hematology. 41 (1): 4–14. doi:10.1053/j.seminhematol.2003.10.003. PMID 14727254.
López JA, Dong JF (januar 2004). "Cleavage of von Willebrand factor by ADAMTS-13 on endothelial cells". Seminars in Hematology. 41 (1): 15–23. doi:10.1053/j.seminhematol.2003.10.004. PMID 14727255.
Plaimauer B, Scheiflinger F (januar 2004). "Expression and characterization of recombinant human ADAMTS-13". Seminars in Hematology. 41 (1): 24–33. doi:10.1053/j.seminhematol.2003.10.006. PMID 14727256.
Kokame K, Miyata T (januar 2004). "Genetic defects leading to hereditary thrombotic thrombocytopenic purpura". Seminars in Hematology. 41 (1): 34–40. doi:10.1053/j.seminhematol.2003.10.002. PMID 14727257.
Schneppenheim R, Budde U, Hassenpflug W, Obser T (januar 2004). "Severe ADAMTS-13 deficiency in childhood". Seminars in Hematology. 41 (1): 83–9. doi:10.1053/j.seminhematol.2003.10.007. PMID 14727263.
Kremer Hovinga JA, Studt JD, Lämmle B (2005). "The von Willebrand factor-cleaving protease (ADAMTS-13) and the diagnosis of thrombotic thrombocytopenic purpura (TTP)". Pathophysiology of Haemostasis and Thrombosis. 33 (5–6): 417–21. doi:10.1159/000083839. PMID 15692254.
Levy GG, Motto DG, Ginsburg D (juli 2005). "ADAMTS13 turns 3". Blood. 106 (1): 11–7. doi:10.1182/blood-2004-10-4097. PMID 15774620.
George JN (maj 2005). "ADAMTS13, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome". Current Hematology Reports. 4 (3): 167–9. PMID 15865866.
Dong JF (august 2005). "Cleavage of ultra-large von Willebrand factor by ADAMTS-13 under flow conditions". Journal of Thrombosis and Haemostasis. 3 (8): 1710–6. doi:10.1111/j.1538-7836.2005.01360.x. PMID 16102037. S2CID 33464866.
Matsukawa M, Kaikita K, Soejima K, Fuchigami S, Nakamura Y, Honda T, Tsujita K, Nagayoshi Y, Kojima S, Shimomura H, Sugiyama S, Fujimoto K, Yoshimura M, Nakagaki T, Ogawa H (septembar 2007). "Serial changes in von Willebrand factor-cleaving protease (ADAMTS13) and prognosis after acute myocardial infarction". The American Journal of Cardiology. 100 (5): 758–63. doi:10.1016/j.amjcard.2007.03.095. PMID 17719316.

Vanjski linkovi

The MEROPS online database for peptidases and their inhibitors: M12.241^{[mrtav link]}
OMIM: 274150
Secreted protein database entry
Lokacija ljudskog genoma ADAMTS13 i stranica sa detaljima o genu ADAMTS13 u UCSC Genome Browseru.
Q76LX8

Portal Biologija

[refGRCh38Ensembl-1] ENSG00000281244 GRCh38: Ensembl release 89: ENSG00000160323, ENSG00000281244 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000014852 - 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.

[Levy2005-5] ^ ^a ^b ^c ^d ^e ^f ^g Levy GG, Motto DG, Ginsburg D (juli 2005). "ADAMTS13 turns 3". Blood. 106 (1): 11–7. doi:10.1182/blood-2004-10-4097. PMID 15774620.

[UniProt-6] "UniProt, Q76LX8". Pristupljeno 5. 9. 2021.

[7] Tsai HM (april 2003). "Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura". Journal of the American Society of Nephrology. 14 (4): 1072–81. doi:10.1097/01.ASN.0000060805.04118.4C. PMID 12660343.

[8] Furlan M, Lämmle B (juni 2001). "Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease". Best Practice & Research. Clinical Haematology. 14 (2): 437–54. doi:10.1053/beha.2001.0142. PMID 11686108.

[9] Sonneveld MA, de Maat MP, Leebeek FW (juli 2014). "Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis". Blood Reviews. 28 (4): 167–78. doi:10.1016/j.blre.2014.04.003. PMID 24825749.

[10] Maino A, Siegerink B, Lotta LA, Crawley JT, le Cessie S, Leebeek FW, Lane DA, Lowe GD, Peyvandi F, Rosendaal FR (august 2015). "Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis" (PDF). Journal of Thrombosis and Haemostasis. 13 (8): 1396–404. doi:10.1111/jth.13032. hdl:10044/1/26935. PMID 26073931. S2CID 324472.

[11] Sonneveld MA, de Maat MP, Portegies ML, Kavousi M, Hofman A, Turecek PL, Rottensteiner H, Scheiflinger F, Koudstaal PJ, Ikram MA, Leebeek FW (decembar 2015). "Low ADAMTS13 activity is associated with an increased risk of ischemic stroke". Blood. 126 (25): 2739–46. doi:10.1182/blood-2015-05-643338. PMID 26511134.

[12] Denorme F, Kraft P, Pareyn I, Drechsler C, Deckmyn H, Vanhoorelbeke K, Kleinschnitz C, De Meyer SF. "Reduced ADAMTS13 levels in patients with acute and chronic cerebrovascular disease". PLOS ONE. 12. Bibcode:2017PLoSO..1279258D. PMC 5462472. Zanemaren tekst "issue" (pomoć); |doi-access= zahtijeva |doi= (pomoć)

[1]

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