Koštanomorfogenetski protein 1

BMP1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3EDG, 3EDH
Identifikatori
Aliasi	BMP1
Vanjski ID-jevi	OMIM: 112264 MGI: 88176 HomoloGene: 55955 GeneCards: BMP1
Lokacija gena (čovjek)
Hrom.	Hromosom 8 (čovjek)
Kraj	22,212,326 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	70,520,234 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calcium ion binding; • vezivanje iona cinka; • vezivanje iona metala; • GO:0070122 peptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • metalloendopeptidase activity; • growth factor activity; • hydrolase activity; • metallopeptidase activity; • serine-type endopeptidase activity; • cytokine activity; • vezivanje identičnih proteina;
Ćelijska komponenta	• Golđijev aparat; • extracellular region; • Vezikula; • Vanćelijsko;
Biološki proces	• skeletal system development; • Ćelijska diferencijacija; • ossification; • extracellular matrix disassembly; • Proteoliza; • multicellular organism development; • cartilage development; • positive regulation of cartilage development; • cartilage condensation; • high-density lipoprotein particle assembly; • regulation of signaling receptor activity; • GO:0072468 Transdukcija signala;
	Izvori:Amigo / QuickGO
Ortolozi
	649
	12153
	ENSG00000168487
	ENSMUSG00000022098
	P13497
	P98063
NM_001199; NM_006128; NM_006129; NM_006130; NM_006131;
	NM_006132
	NM_009755; NM_001360021
	NP_001190; NP_006120
	NP_033885; NP_001346950
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Koštanomorfogenetski protein 1, poznat i kao BMP1, jest protein koji je kod ljudi kodiran genom BMP1 sa kratkog krka hromosoma 8, p21.3.^[5]^[6] Postoji sedam izoformi proteina, varijanti transkripta stvorenih alternativnim preradom.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 986 aminokiselina, a molekulska težina 111.249 Da.^[5]

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
MPGVARLPLL	LGLLLLPRPG	RPLDLADYTY	DLAEEDDSEP	LNYKDPCKAA
AFLGDIALDE	EDLRAFQVQQ	AVDLRRHTAR	KSSIKAAVPG	NTSTPSCQST
NGQPQRGACG	RWRGRSRSRR	AATSRPERVW	PDGVIPFVIG	GNFTGSQRAV
FRQAMRHWEK	HTCVTFLERT	DEDSYIVFTY	RPCGCCSYVG	RRGGGPQAIS
IGKNCDKFGI	VVHELGHVVG	FWHEHTRPDR	DRHVSIVREN	IQPGQEYNFL
KMEPQEVESL	GETYDFDSIM	HYARNTFSRG	IFLDTIVPKY	EVNGVKPPIG
QRTRLSKGDI	AQARKLYKCP	ACGETLQDST	GNFSSPEYPN	GYSAHMHCVW
RISVTPGEKI	ILNFTSLDLY	RSRLCWYDYV	EVRDGFWRKA	PLRGRFCGSK
LPEPIVSTDS	RLWVEFRSSS	NWVGKGFFAV	YEAICGGDVK	KDYGHIQSPN
YPDDYRPSKV	CIWRIQVSEG	FHVGLTFQSF	EIERHDSCAY	DYLEVRDGHS
ESSTLIGRYC	GYEKPDDIKS	TSSRLWLKFV	SDGSINKAGF	AVNFFKEVDE
CSRPNRGGCE	QRCLNTLGSY	KCSCDPGYEL	APDKRRCEAA	CGGFLTKLNG
SITSPGWPKE	YPPNKNCIWQ	LVAPTQYRIS	LQFDFFETEG	NDVCKYDFVE
VRSGLTADSK	LHGKFCGSEK	PEVITSQYNN	MRVEFKSDNT	VSKKGFKAHF
FSDKDECSKD	NGGCQQDCVN	TFGSYECQCR	SGFVLHDNKH	DCKEAGCDHK
VTSTSGTITS	PNWPDKYPSK	KECTWAISST	PGHRVKLTFM	EMDIESQPEC
AYDHLEVFDG	RDAKAPVLGR	FCGSKKPEPV	LATGSRMFLR	FYSDNSVQRK
GFQASHATEC	GGQVRADVKT	KDLYSHAQFG	DNNYPGGVDC	EWVIVAEEGY
GVELVFQTFE	VEEETDCGYD	YMELFDGYDS	TAPRLGRYCG	SGPPEEVYSA
GDSVLVKFHS	DDTITKKGFH	LRYTSTKFQD	TLHSRK

Struktura[uredi | uredi izvor]

Struktura BMP1 je određena pomoću rengenske difrakcije sa rezolucijom od 1,27 Å.^[7] Kristalografski eksperimenti rađeni su difuzijom pare pri pH od 7,5. Ovo je važno jer je blizu pH vrijednosti ljudskog tijela, gdje se BMP1 nalazi in vivo. BMP1 ima dužinu od 202 aminokiselionska ostatka. Njegova sekundarna struktura sastoji se od 30% , ili 10 alfa-heliksa, 61 ostatka dužine i 15% beta-listova, ili 11 niti, dužine 32 ostatka. Sadrži ligande acetilne grupe i ion cinka.

Za BMP izgrađen je Ramachandranov prikaz.^[8] Ovaj dijagram pokazuje da BMP1 najviše preferira Phi i Psi uglove (Phi, Psi) od oko (–60°,–45°) i (–60°, 140°). Ovi preferirani uglovi su procjena najgrupisanijih podataka Ramachandranove grafike. Preferirana regija je mnogo većeg dometa. Oko 97% ostataka je bilo u preferiranim regionima, a 100% u dozvoljenom regionu, bez odstupanja.

Funkcija[uredi | uredi izvor]

BMP1 pripada porodici peptidaza M12A koštanomorfogenetskih proteina (BMP). Podstiče razvoj kostiju i hrskavice. Za razliku od drugih BMP, ne pripada natporodici TGFβ. U početku je otkriveno da djeluje kao i drugi BMP, tako što podstiče razvoj kostiju i hrskavice. Međutim, to je metaloproteaza koja cijepa C-terminal prokolagena I, II i III. Ima domen astacinu sličnih proteaza.

Pokazalo se da cijepa laminin 5 i da se nalazi u baznom epitelnom sloju goveđe kože. Ovaj dijagram pokazuje da BMP1 najviše preferira Phi i Psi uglove (Phi, Psi) od oko (-60°,-45°) i (-60°, 140°). Ovi preferirani uglovi su procjena najgrupisanijih podataka Ramachandran grafike. Preferirana regija je mnogo većeg dometa. 97% ostataka je bilo u preferiranim regionima, a 100% ostataka je bilo u dozvoljenom regionu, bez odstupanja.

Funkcija[uredi | uredi izvor]

BMP1 pripada porodici peptidaza M12A koštanomorfogenetskih proteina (BMP). Podstiče razvoj kostiju i hrskavice. Za razliku od drugih BMP, ne pripada natporodici TGFβ. U početku je otkriveno da djeluje kao i drugi BMP tako što podstiče razvoj kostiju i hrskavice. Međutim, to je metaloproteaza koja cijepa C-terminal prokolagena I, II i III. Ima astacinu sličan domen proteaza.

BMP1 lokus kodira protein koji je sposoban inducirati stvaranje hrskavice in vivo. Iako su drugi koštani morfogenetski proteini članovi natporodice TGF-beta, BMP1 kodira protein koji nije blisko povezan s drugim poznatim faktorima rasta. BMP1 protein i prokolagen C-proteinaza (PCP), izlučena metaloproteaza kojoj je potreban kalcij za formiranje hrskavice i kostiju. PCP ili BMP1 protein cijepa C-terminalne propeptide prokolagena I, II i III i njegovu aktivnost povećava protein pojačivača prokolagenske C-endopeptidaze. BMP1 gen eksprimira se kao alternativno prerađene varijante transkripta, koje dijele N-terminalni domen proteaze, ali se razlikuju u svojoj C-terminalnoj regiji^[5]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000168487 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022098 - 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 "Entrez Gene: BMP1 bone morphogenetic protein 1".
^ Tabas JA, Zasloff M, Wasmuth JJ, Emanuel BS, Altherr MR, McPherson JD, Wozney JM, Kaplan FS (februar 1991). "Bone morphogenetic protein: chromosomal localization of human genes for BMP1, BMP2A, and BMP3". Genomics. 9 (2): 283–9. doi:10.1016/0888-7543(91)90254-C. PMID 2004778.
^ PDB 3EDG; Mac Sweeney A, Gil-Parrado S, Vinzenz D, Bernardi A, Hein A, Bodendorf U, Erbel P, Logel C, Gerhartz B (decembar 2008). "Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases". J. Mol. Biol. 384 (1): 228–39. doi:10.1016/j.jmb.2008.09.029. PMID 18824173.
^ "MolProbity Ramachandran analysis of 3EDG, model 1" (PDF). www.rcsb.org. Arhivirano s originala (PDF), 12. 10. 2012.

Dopunska literatura[uredi | uredi izvor]

Tabas JA, Zasloff M, Wasmuth JJ, et al. (1991). "Bone morphogenetic protein: chromosomal localization of human genes for BMP1, BMP2A, and BMP3". Genomics. 9 (2): 283–9. doi:10.1016/0888-7543(91)90254-C. PMID 2004778.
Wozney JM, Rosen V, Celeste AJ, et al. (1989). "Novel regulators of bone formation: molecular clones and activities". Science. 242 (4885): 1528–34. doi:10.1126/science.3201241. PMID 3201241.
Takahara K, Lyons GE, Greenspan DS (1995). "Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues". J. Biol. Chem. 269 (51): 32572–8. doi:10.1016/S0021-9258(18)31672-7. PMID 7798260.
Yoshiura K, Tamura T, Hong HS, et al. (1993). "Mapping of the bone morphogenetic protein 1 gene (BMP1) to 8p21: removal of BMP1 from candidacy for the bone disorder in Langer-Giedion syndrome". Cytogenet. Cell Genet. 64 (3–4): 208–9. doi:10.1159/000133577. PMID 8404039.
Takahara K, Lee S, Wood S, Greenspan DS (1996). "Structural organization and genetic localization of the human bone morphogenetic protein 1/mammalian tolloid gene". Genomics. 29 (1): 9–15. doi:10.1006/geno.1995.1209. PMID 8530106.
Kessler E, Takahara K, Biniaminov L, et al. (1996). "Bone morphogenetic protein-1: the type I procollagen C-proteinase". Science. 271 (5247): 360–2. Bibcode:1996Sci...271..360K. doi:10.1126/science.271.5247.360. PMID 8553073. S2CID 26378870.
Li SW, Sieron AL, Fertala A, et al. (1996). "The C-proteinase that processes procollagens to fibrillar collagens is identical to the protein previously identified as bone morphogenic protein-1". Proc. Natl. Acad. Sci. U.S.A. 93 (10): 5127–30. Bibcode:1996PNAS...93.5127L. doi:10.1073/pnas.93.10.5127. PMC 39418. PMID 8643539.
Janitz M, Heiser V, Böttcher U, et al. (1998). "Three alternatively spliced variants of the gene coding for the human bone morphogenetic protein-1". J. Mol. Med. 76 (2): 141–6. doi:10.1007/s001090050202. PMID 9500680. S2CID 26374071.
Scott IC, Blitz IL, Pappano WN, et al. (1999). "Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis". Dev. Biol. 213 (2): 283–300. doi:10.1006/dbio.1999.9383. PMID 10479448.
Amano S, Scott IC, Takahara K, et al. (2000). "Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain". J. Biol. Chem. 275 (30): 22728–35. doi:10.1074/jbc.M002345200. PMID 10806203.
Scott IC, Blitz IL, Pappano WN, et al. (2001). "Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling". Nature. 410 (6827): 475–8. Bibcode:2001Natur.410..475S. doi:10.1038/35068572. PMID 11260715. S2CID 4392365.
Garrigue-Antar L, Barker C, Kadler KE (2001). "Identification of amino acid residues in bone morphogenetic protein-1 important for procollagen C-proteinase activity". J. Biol. Chem. 276 (28): 26237–42. doi:10.1074/jbc.M010814200. PMID 11283002.
Unsöld C, Pappano WN, Imamura Y, et al. (2002). "Biosynthetic processing of the pro-alpha 1(V)2pro-alpha 2(V) collagen heterotrimer by bone morphogenetic protein-1 and furin-like proprotein convertases". J. Biol. Chem. 277 (7): 5596–602. doi:10.1074/jbc.M110003200. PMID 11741999.
Rattenholl A, Pappano WN, Koch M, et al. (2002). "Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen". J. Biol. Chem. 277 (29): 26372–8. doi:10.1074/jbc.M203247200. PMID 11986329.
Garrigue-Antar L, Hartigan N, Kadler KE (2003). "Post-translational modification of bone morphogenetic protein-1 is required for secretion and stability of the protein". J. Biol. Chem. 277 (45): 43327–34. doi:10.1074/jbc.M207342200. PMID 12218058.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Hartigan N, Garrigue-Antar L, Kadler KE (2003). "Bone morphogenetic protein-1 (BMP-1). Identification of the minimal domain structure for procollagen C-proteinase activity". J. Biol. Chem. 278 (20): 18045–9. doi:10.1074/jbc.M211448200. PMID 12637537.
Leighton M, Kadler KE (2003). "Paired basic/Furin-like proprotein convertase cleavage of Pro-BMP-1 in the trans-Golgi network". J. Biol. Chem. 278 (20): 18478–84. doi:10.1074/jbc.M213021200. PMID 12637569.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance". Genome Biol. 5 (2): R8. doi:10.1186/gb-2004-5-2-r8. PMC 395752. PMID 14759258.

Vanjski linkovi[uredi | uredi izvor]

bone morphogenetic protein 1 na US National Library of Medicine Medical Subject Headings (MeSH)
Lokacija ljudskog genoma BMP1 i stranica sa detaljima o genu BMP1 u UCSC Genome Browseru.
Lokacija ljudskog genoma PCP2 i stranica sa detaljima o genu PCP2 u UCSC Genome Browseru.
The MEROPS online database for peptidases and their inhibitors: M12.005^{[mrtav link]}

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000168487 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022098 - 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.

[entrez-5] "Entrez Gene: BMP1 bone morphogenetic protein 1".

[pmid2004778-6] Tabas JA, Zasloff M, Wasmuth JJ, Emanuel BS, Altherr MR, McPherson JD, Wozney JM, Kaplan FS (februar 1991). "Bone morphogenetic protein: chromosomal localization of human genes for BMP1, BMP2A, and BMP3". Genomics. 9 (2): 283–9. doi:10.1016/0888-7543(91)90254-C. PMID 2004778.

[pmid18824173-7] PDB 3EDG; Mac Sweeney A, Gil-Parrado S, Vinzenz D, Bernardi A, Hein A, Bodendorf U, Erbel P, Logel C, Gerhartz B (decembar 2008). "Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases". J. Mol. Biol. 384 (1): 228–39. doi:10.1016/j.jmb.2008.09.029. PMID 18824173.

[urlwww.rcsb.org-8] "MolProbity Ramachandran analysis of 3EDG, model 1" (PDF). www.rcsb.org. Arhivirano s originala (PDF), 12. 10. 2012.

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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