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)[1] Bend 9q34.2 Početak 133,414,358 bp[1] Kraj 133,459,402 bp[1]
Lokacija gena (miš) Hrom. Hromosom 2 (miš)[2] Bend 2|2 A3 Početak 26,863,428 bp[2] Kraj 26,899,640 bp[2]
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
Vrste	Čovjek	Miš
Entrez	11093	279028
Ensembl	ENSG00000160323 ENSG00000281244	ENSMUSG00000014852
UniProt	Q76LX8	Q769J6
RefSeq (mRNK)	NM_139025 NM_139026 NM_139027 NM_139028	NM_001001322 NM_001290463 NM_001290464 NM_001290465
RefSeq (bjelančevina)	NP_620594 NP_620595 NP_620596	NP_001001322 NP_001277392 NP_001277393 NP_001277394
Lokacija (UCSC)	Chr 9: 133.41 – 133.46 Mb	Chr 2: 26.86 – 26.9 Mb
PubMed pretraga	[3]	[4]
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

1. ENSG00000281244 GRCh38: Ensembl release 89: ENSG00000160323, ENSG00000281244 - Ensembl, maj 2017
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.
5. 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.
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)

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

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