Inhibicijski faktor migracije makrofaga

S Wikipedije, slobodne enciklopedije
Inhibicijski faktor migracije makrofaga
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1CA7, 1CGQ, 1GCZ, 1GD0, 1GIF, 1LJT, 1MIF, 1P1G, 2OOH, 2OOW, 2OOZ, 3B9S, 3CE4, 3DJH, 3DJI, 3HOF, 3IJG, 3IJJ, 3JSF, 3JSG, 3JTU, 3L5P, 3L5R, 3L5S, 3L5T, 3L5U, 3L5V, 3SMB, 3SMC, 3U18, 4ETG, 4EUI, 4EVG, 4F2K, 4GRN, 4GRO, 4GRP, 4GRQ, 4GRR, 4GRU, 3WNR, 3WNS, 3WNT, 4K9G, 4OSF, 4OYQ, 4P01, 4P0H, 4WR8, 4WRB, 4PKZ, 4PLU, 4TRF, 4TRU, 4XX7, 4XX8, 5BS9, 5BSC, 5BSI, 5EIZ, 5HVV, 5CG4, 5J7Q, 5BSJ, 5HVT, 4PKK, 5B4O, 5HVS, 5J7P

Identifikatori
AliasiMIF
Vanjski ID-jeviOMIM: 153620 MGI: 96982 HomoloGene: 55655 GeneCards: MIF
EC broj5.3.3.12
Lokacija gena (čovjek)
Hromosom 22 (čovjek)
Hrom.Hromosom 22 (čovjek)[1]
Hromosom 22 (čovjek)
Genomska lokacija za Inhibicijski faktor migracije makrofaga
Genomska lokacija za Inhibicijski faktor migracije makrofaga
Bend22q11.23Početak23,894,383 bp[1]
Kraj23,895,227 bp[1]
Lokacija gena (miš)
Hromosom 10 (miš)
Hrom.Hromosom 10 (miš)[2]
Hromosom 10 (miš)
Genomska lokacija za Inhibicijski faktor migracije makrofaga
Genomska lokacija za Inhibicijski faktor migracije makrofaga
Bend10 38.59 cM|10 C1Početak75,695,187 bp[2]
Kraj75,696,074 bp[2]
Ontologija gena
Molekularna funkcija• cytokine activity
• isomerase activity
• GO:0001948, GO:0016582 vezivanje za proteine
• chemoattractant activity
• phenylpyruvate tautomerase activity
• signaling receptor binding
• dopachrome isomerase activity
• protease binding
• GO:0005145 cytokine receptor binding
• vezivanje identičnih proteina
Ćelijska komponenta• Vezikula
• myelin sheath
• nukleoplazma
• extracellular region
• cell surface
• Egzosom
• citoplazma
• citosol
• secretory granule lumen
• ficolin-1-rich granule lumen
• Vanćelijsko
Biološki proces• positive regulation of protein phosphorylation
• negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
• positive regulation of MAP kinase activity
• carboxylic acid metabolic process
• positive regulation of chemokine (C-X-C motif) ligand 2 production
• immune system process
• positive regulation of fibroblast proliferation
• DNA damage response, signal transduction by p53 class mediator
• negative regulation of apoptotic process
• negative regulation of mature B cell apoptotic process
• negative regulation of gene expression
• positive regulation of peptidyl-serine phosphorylation
• protein homotrimerization
• positive regulation of lipopolysaccharide-mediated signaling pathway
• cell surface receptor signaling pathway
• negative regulation of DNA damage response, signal transduction by p53 class mediator
• regulation of cell population proliferation
• positive regulation of arachidonic acid secretion
• positive regulation of B cell proliferation
• positive regulation of peptidyl-tyrosine phosphorylation
• positive regulation of prostaglandin secretion involved in immune response
• prostaglandin biosynthetic process
• Urođeni imunski sistem
• negative regulation of myeloid cell apoptotic process
• inflammatory response
• Ćelijska proliferacija
• positive regulation of phosphorylation
• positive regulation of myeloid leukocyte cytokine production involved in immune response
• leukocyte migration
• regulation of macrophage activation
• positive regulation of protein kinase A signaling
• positive chemotaxis
• neutrophil degranulation
• interleukin-12-mediated signaling pathway
• negative regulation of macrophage chemotaxis
• positive regulation of tumor necrosis factor production
• positive regulation of ERK1 and ERK2 cascade
• regulation of signaling receptor activity
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

4282

17319

Ensembl

ENSG00000276701
ENSG00000240972

ENSMUSG00000033307

UniProt

P14174

P34884

RefSeq (mRNK)

NM_002415

NM_010798

RefSeq (bjelančevina)

NP_002406
NP_002406.1

NP_034928

Lokacija (UCSC)Chr 22: 23.89 – 23.9 MbChr 10: 75.7 – 75.7 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš
Inhibitorni faktor migracije makrofaga (MIF)
Makrofag
Identifikatori
SimbolMIF

Inhibitorni faktor migracije makrofaga (MIF), znan i kao inhibitorni faktor glikozilacije (GIF), L-dopahrom-izomeraza ili fenilpiruvat-tautomeraza jest protein/enzim koji je kod ljudi kodiran genom MIF sa hromosoma 22.[5][6] MIF je važan regulator urođene imunosti.[7] Natporodica proteina MIF također uključuje drugog člana s funkcionalno srodnim svojstvima, D-dopahrom-tautomerazu (D-DT).[8]Površinski receptor za MIF je CD74.[9]

Bakterijski antigeni stimuliraju bijela krvna zrnca da otpuste MIF u krvotok.[10] Cirkulirajući MIF se vezuje za CD74 na drugim imunskim ćelijama, kako bi pokrenuo akutni imunski odgovor. Stoga je MIF klasifikovan kao upalni citokin. Štaviše, glukokortikoidi također stimulišu bijela krvna zrnca da oslobađaju MIF i stoga on delimično suprotstavlja inhibitorne efekte koje glukokortikoidi imaju na imunski sistem. Konačno trauma aktivira prednji režanj hipofize da oslobodi MIF.[11]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 115 aminokiseline, a molekulska težina 12 476 Da.[11]

1020304050
MPMFIVNTNVPRASVPDGFLSELTQQLAQATGKPPQYIAVHVVPDQLMAF
GGSSEPCALCSLHSIGKIGGAQNRSYSKLLCGLLAERLRISPDRVYINYY
DMNAANVGWNNSTFA

Struktura[uredi | uredi izvor]

Inhibicijski faktor migracije makrofaga sastavlja se u trimer od tri identične podjedinice. Svaki od ovih monomera sadrži dva antiparalelna alfa heliksa i četvorolančani beta-list. Monomere okružuju centralni kanal sa trostrukom rotacijskom simetrijom.[12][13]

Odgovor na povredu[uredi | uredi izvor]

Citokini imaju važnu ulogu u podsticanju zacjeljivanja rana i obnavljanja tkiva. Povreda ćelije dovodi do oslobađanja MIF-a koji zatim stupa u interakciju sa CD74. MIF-CD74 signalizacija aktivira proopstanak i proliferativne puteve koji štite domaćina tokom ozljede.[14]

Enzimska aktivnost[uredi | uredi izvor]

MIF sadrži dva motiva sa katalitskom aktivnošću. Prvi je motiv od 27 aminokiselina koji se nalazi na N-terminalu funkcioniše kao fenilpiruvat-tautomeraza koja može katalizirati konverziju 2-karboksi-2,3-dihidroindol-5,6-kinona (dopahrom) u 5,6-dihidroksiindol-2-karboksilnu kiselinu (DHICA).[15][16] MIF također sadrži Cys-Ala-Leu-Cys katalitsko mjesto između ostataka 57 i 60 koje funkcionira kao disulfid- reduktaza.[17]

Funkcija[uredi | uredi izvor]

Ovaj gen kodira limfokin uključen u ćelijski posredovanu imunost, imunoregulaciju i upale.[18][19][20] MIF ima ulogu u regulaciji funkcije makrofaga u odbrani domaćina kroz supresiju protivupalnih efekata glukokortikoida.[20][21][22] Ovaj limfokin i JAB1 protein formiraju kompleks u citosolu blizu periferne plazmamembrane, što može ukazivati na ulogu u integrinskim signalnim putevima.[23]

Mehanizam djelovanja[uredi | uredi izvor]

MIF se vezuje za CD74,[24] izazivajući njegove fosforilacije i regrutacije CD44 koji zatim aktivira nereceptorske tirozin kinaze, što u konačnici dovodi do fosforilacije kinaza reguliranih vanćelijskim signalom.[25] Osim ERK-a, stimulacija CD74 aktivira i druge signalne puteve kao što su PI3K-Akt, NF-κB i AMP-aktivirani putevi protein kinaze (AMPK).[26]

Interakcije[uredi | uredi izvor]

Zabilježeno je da inhibitorni faktor migracije makrofaga ima interakcije sa:

Klinički značaj[uredi | uredi izvor]

MIF je potencijalni cilj lijeka za sepsu, reumatoidni artritis i rak.[40][41]

Parazitno-proitvedeni homolozi MIF-a[uredi | uredi izvor]

MIF citokin proizveden parazitima u imunskoj evaziji, invaziji i patogenezi

Višestruki protozojski paraziti proizvode homologe MIF-a koji imaju slične upalne funkcije kao i ljudski MIF i imaju ulogu u njihovoj patogenezi, invaziji i imunskoj evaziji.[42][43] Pretklinička studija je pokazala da blokiranje parazitskog MIF poboljšava ishod kod teških infekcija protozoaama.[44] Prijavljeni primjeri protozoa sa homolozima MIF-a:

Reference[uredi | uredi izvor]

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Vanjski linkovi[uredi | uredi izvor]

Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=Inhibicijski_faktor_migracije_makrofaga&oldid=3396828"