ADAMTS2

ADAMTS2
Identifikatori
Aliasi	ADAMTS2
Vanjski ID-jevi	OMIM: 604539 MGI: 1347356 HomoloGene: 8597 GeneCards: ADAMTS2
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	50,698,400 bp
Ontologija gena
Molekularna funkcija	• vezivanje iona cinka; • GO:0070122 peptidase activity; • metalloendopeptidase activity; • hydrolase activity; • metallopeptidase activity; • vezivanje iona metala;
Ćelijska komponenta	• extracellular region; • collagen-containing extracellular matrix; • GO:0005578 Vanćelijski matriks;
Biološki proces	• collagen catabolic process; • protein processing; • Spermatogeneza; • skin development; • collagen fibril organization; • lung development; • Proteoliza;
	Izvori:Amigo / QuickGO
Ortolozi
	9509
	216725
	n/a
	ENSMUSG00000036545
	O95450
	Q8C9W3
	NM_021599; NM_014244
	NM_001277305; NM_175643
	NP_055059; NP_067610
	NP_783574
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Disintegrin i metaloproteinaza sa trombospondinskim motivom 2 (ADAM-TS2), znana i kao prokolagenska I N-proteinaza (PC I-NP) je enzim^[4] koji je kod ljudi kodiran genom ADAMTS2.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.211 aminokiselina, а molekulska težina 134.755 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
MDPPAGAARR	LLCPALLLLL	LLLPPPLLPP	PPPPANARLA	AAADPPGGPL
GHGAERILAV	PVRTDAQGRL	VSHVVSAATS	RAGVRARRAA	PVRTPSFPGG
NEEEPGSHLF	YNVTVFGRDL	HLRLRPNARL	VAPGATMEWQ	GEKGTTRVEP
LLGSCLYVGD	VAGLAEASSV	ALSNCDGLAG	LIRMEEEEFF	IEPLEKGLAA
QEAEQGRVHV	VYRRPPTSPP	LGGPQALDTG	ASLDSLDSLS	RALGVLEEHA
NSSRRRARRH	AADDDYNIEV	LLGVDDSVVQ	FHGKEHVQKY	LLTLMNIVNE
IYHDESLGAH	INVVLVRIIL	LSYGKSMSLI	EIGNPSQSLE	NVCRWAYLQQ
KPDTGHDEYH	DHAIFLTRQD	FGPSGMQGYA	PVTGMCHPVR	SCTLNHEDGF
SSAFVVAHET	GHVLGMEHDG	QGNRCGDEVR	LGSIMAPLVQ	AAFHRFHWSR
CSQQELSRYL	HSYDCLLDDP	FAHDWPALPQ	LPGLHYSMNE	QCRFDFGLGY
MMCTAFRTFD	PCKQLWCSHP	DNPYFCKTKK	GPPLDGTMCA	PGKHCFKGHC
IWLTPDILKR	DGSWGAWSPF	GSCSRTCGTG	VKFRTRQCDN	PHPANGGRTC
SGLAYDFQLC	SRQDCPDSLA	DFREEQCRQW	DLYFEHGDAQ	HHWLPHEHRD
AKERCHLYCE	SRETGEVVSM	KRMVHDGTRC	SYKDAFSLCV	RGDCRKVGCD
GVIGSSKQED	KCGVCGGDNS	HCKVVKGTFT	RSPKKHGYIK	MFEIPAGARH
LLIQEVDATS	HHLAVKNLET	GKFILNEEND	VDASSKTFIA	MGVEWEYRDE
DGRETLQTMG	PLHGTITVLV	IPVGDTRVSL	TYKYMIHEDS	LNVDDNNVLE
EDSVVYEWAL	KKWSPCSKPC	GGGSQFTKYG	CRRRLDHKMV	HRGFCAALSK
PKAIRRACNP	QECSQPVWVT	GEWEPCSQTC	GRTGMQVRSV	RCIQPLHDNT
TRSVHAKHCN	DARPESRRAC	SRELCPGRWR	AGPWSQCSVT	CGNGTQERPV
LCRTADDSFG	ICQEERPETA	RTCRLGPCPR	NISDPSKKSY	VVQWLSRPDP
DSPIRKISSK	GHCQGDKSIF	CRMEVLSRYC	SIPGYNKLCC	KSCNLYNNLT
NVEGRIEPPP	GKHNDIDVFM	PTLPVPTVAM	EVRPSPSTPL	EVPLNASSTN
ATEDHPETNA	VDEPYKIHGL	EDEVQPPNLI	PRRPSPYEKT	RNQRIQELID
EMRKKEMLGK	F

Gen

Gen ADAMTS2 nalazi se na dugom (q) kraku hromosoma 5 na kraju kraka, između baznih parova 178,473.473 i 178,704.934.

Funkcija

ADAMTS2 je odgovoran za obradu nekoliko tipova prokolagenskih proteina. Prokolageni su prekursori kolagena, proteina koji dodaju snagu i podršku mnogim tjelesnim tkivima. Konkretno, ovaj enzim uklanja kratki lanac aminokiselina s jednog kraja prokolagena. Ovaj korak skraćivanja neophodan je za molekule kolagena za normalno funkcioniranje i sastavljanje u vlakna izvan ćelija.

Klinički značaj

Mutacijama u genu ADAMTS2 uzrokovan je Ehlers-Danlosov sindrom, dermatosparaksni tip.^[6] Nekoliko mutacija u genu ADAMTS2 identificirano je kod ljudi s ovim sindromom. Ove mutacije uveliko smanjuju proizvodnju enzima kojeg kodira gen ADAMTS2. Prokolagen se ne može pravilno preraditi bez ovog enzima. Kao rezultat toga, kolagenske fibrile nisu pravilno sastavljene; pod mikroskopom izgledaju poput vrpci i neorganizirano. Uspješne veze ili hemijske interakcije između kolagenih vlakana također su pogođene. Ovi nedostaci slabe vezivno tkivo (tkivo koje veže i podržava tjelesne mišiće, ligamente, organe i kožu), što uzrokuje znakove i simptome poremećaja.

Također pogledajte

Reference

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000036545 - 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.
^ Tang BL, Hong W (februar 1999). "ADAMTS: a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats". FEBS Lett. 445 (2–3): 223–5. doi:10.1016/S0014-5793(99)00119-2. PMID 10094461. S2CID 37955930.
^ "Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif".
^ ^a ^b Colige A, Nuytinck L, Hausser I, van Essen AJ, Thiry M, Herens C, Adès LC, Malfait F, Paepe AD, Franck P, Wolff G, Oosterwijk JC, Smitt JH, Lapière CM, Nusgens BV (oktobar 2004). "Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene". J. Invest. Dermatol. 123 (4): 656–63. doi:10.1111/j.0022-202X.2004.23406.x. PMID 15373769.^{[mrtav link]}
^ "UniProt, O95450" (jezik: engleski). Pristupljeno 12. 10. 2021.

Dopunska literatura

Wang WM, Lee S, Steiglitz BM, Scott IC, Lebares CC, Allen ML, Brenner MC, Takahara K, Greenspan DS (maj 2003). "Transforming growth factor-beta induces secretion of activated ADAMTS-2. A procollagen III N-proteinase". J. Biol. Chem. 278 (21): 19549–57. doi:10.1074/jbc.M300767200. PMID 12646579.
Reardon W, Winter RM, Smith LT, et al. (1995). "The natural history of human dermatosparaxis (Ehlers-Danlos syndrome type VIIC)". Clin. Dysmorphol. 4 (1): 1–11. doi:10.1097/00019605-199501000-00001. PMID 7735500. S2CID 2412884.
Colige A, Vandenberghe I, Thiry M, et al. (2002). "Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3". J. Biol. Chem. 277 (8): 5756–66. doi:10.1074/jbc.M105601200. PMID 11741898.
Kevorkian L, Young DA, Darrah C, et al. (2004). "Expression profiling of metalloproteinases and their inhibitors in cartilage". Arthritis Rheum. 50 (1): 131–41. doi:10.1002/art.11433. PMID 14730609.
Hurskainen TL, Hirohata S, Seldin MF, Apte SS (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". J. Biol. Chem. 274 (36): 25555–63. doi:10.1074/jbc.274.36.25555. PMID 10464288.
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Dubail J, Kesteloot F, Deroanne C, et al. (2010). "ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity" (PDF). Cellular and Molecular Life Sciences. 67 (24): 4213–32. doi:10.1007/s00018-010-0431-6. PMID 20574651. S2CID 20047628. Arhivirano s originala (PDF), 26. 2. 2022. Pristupljeno 12. 10. 2021.
Colige A, Sieron AL, Li SW, et al. (1999). "Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene". Am. J. Hum. Genet. 65 (2): 308–17. doi:10.1086/302504. PMC 1377929. PMID 10417273.
Hartley JL, Temple GF, Brasch MA (2000). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Tang BL (2001). "ADAMTS: a novel family of extracellular matrix proteases". Int. J. Biochem. Cell Biol. 33 (1): 33–44. doi:10.1016/S1357-2725(00)00061-3. PMID 11167130.
Lasky-Su J, Anney RJ, Neale BM, et al. (2008). "Genome-wide association scan of the time to onset of Attention Deficit Hyperactivity Disorder". Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B (8): 1355–8. doi:10.1002/ajmg.b.30869. PMC 2605611. PMID 18937294.
Colige A, Ruggiero F, Vandenberghe I, et al. (2005). "Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V". J. Biol. Chem. 280 (41): 34397–408. doi:10.1074/jbc.M506458200. PMID 16046392.
Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Brandenberger R, Wei H, Zhang S, et al. (2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197. S2CID 27764390.
Tomii Y, Kamochi J, Yamazaki H, et al. (2002). "Human thrombospondin 2 inhibits proliferation of microvascular endothelial cells". Int. J. Oncol. 20 (2): 339–42. doi:10.3892/ijo.20.2.339. PMID 11788898.

Vanjski linkovi

GeneCard
The MEROPS online database for peptidases and their inhibitors: M12.301^{[mrtav link]}
Lokacija ljudskog genoma ADAMTS2 i stranica sa detaljima o genu ADAMTS2 u UCSC Genome Browseru.

Portal Biologija

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000036545 - Ensembl, maj 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10094461-4] Tang BL, Hong W (februar 1999). "ADAMTS: a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats". FEBS Lett. 445 (2–3): 223–5. doi:10.1016/S0014-5793(99)00119-2. PMID 10094461. S2CID 37955930.

[entrez-5] "Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif".

[pmid15373769-6] Colige A, Nuytinck L, Hausser I, van Essen AJ, Thiry M, Herens C, Adès LC, Malfait F, Paepe AD, Franck P, Wolff G, Oosterwijk JC, Smitt JH, Lapière CM, Nusgens BV (oktobar 2004). "Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene". J. Invest. Dermatol. 123 (4): 656–63. doi:10.1111/j.0022-202X.2004.23406.x. PMID 15373769.^{[mrtav link]}

[UniProt-7] "UniProt, O95450" (jezik: engleski). Pristupljeno 12. 10. 2021.

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