MFSD2

MFSD2
Identifikatori
Aliasi	MFSD2A
Vanjski ID-jevi	OMIM: 614397 MGI: 1923824 HomoloGene: 19229 GeneCards: MFSD2A
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	39,969,968 bp
Lokacija gena (miš)
Hrom.	Hromosom 4 (miš)
Kraj	122,854,981 bp
Ontologija gena
Molekularna funkcija	• symporter activity; • phospholipid transporter activity; • GO:0015246 fatty acid transmembrane transporter activity; • lysophospholipid:sodium symporter activity; • transporter activity;
Ćelijska komponenta	• integral component of membrane; • integral component of plasma membrane; • endoplasmic reticulum membrane; • Endoplazmatski retikulum; • membrana; • ćelijska membrana;
Biološki proces	• lipid transport; • fatty acid transport; • transcytosis; • lipid transport across blood-brain barrier; • transmembrane transport; • establishment of blood-brain barrier; • phosphatidylcholine biosynthetic process; • hippocampus development; • lysophospholipid transport; • GO:0006859 carbohydrate transport; • organic substance transport;
	Izvori:Amigo / QuickGO
Ortolozi
	84879
	76574
	ENSG00000168389
	ENSMUSG00000028655
	Q8NA29; Q5SSK0
	Q9DA75
NM_001136493; NM_001287808; NM_001287809; NM_032793; NM_001349821;
	NM_001349822; NM_001349823
	NM_029662
NP_001129965; NP_001274737; NP_001274738; NP_116182; NP_001336750;
	NP_001336751; NP_001336752
	NP_083938
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein sa glavnim modulatorom natporodičnog domena 2, MFSD2 ili MFSD2A – znan i kao natrij-ovisni lizofosfatidilholinski simporter 1 – jest protein koji je kod ljudi kodiran genom MFSD2A sa hromosoma 1.^[5]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 543 aminokiseline, a molekulska težina 60.170 Da.

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
MAKGEGAESG	SAAGLLPTSI	LQSTERPAQV	KKEPKKKKQQ	LSVCNKLCYA
LGGAPYQVTG	CALGFFLQIY	LLDVAQKDEE	VVFCFSSFQV	GPFSASIILF
VGRAWDAITD	PLVGLCISKS	PWTCLGRLMP	WIIFSTPLAV	IAYFLIWFVP
DFPHGQTYWY	LLFYCLFETM	VTCFHVPYSA	LTMFISTEQT	ERDSATAYRM
TVEVLGTVLG	TAIQGQIVGQ	ADTPCFQDLN	SSTVASQSAN	HTHGTTSHRE
TQKAYLLAAG	VIVCIYIICA	VILILGVREQ	REPYEAQQSE	PIAYFRGLRL
VMSHGPYIKL	ITGFLFTSLA	FMLVEGNFVL	FCTYTLGFRN	EFQNLLLAIM
LSATLTIPIW	QWFLTRFGKK	TAVYVGISSA	VPFLILVALM	ESNLIITYAV
AVAAGISVAA	AFLLPWSMLP	DVIDDFHLKQ	PHFHGTEPIF	FSFYVFFTKF
ASGVSLGIST	LSLDFAGYQT	RGCSQPERVK	FTLNMLVTMA	PIVLILLGLL
LFKMYPIDEE	RRRQNKKALQ	ALRDEASSSG	CSETDSTELA	SIL

Funkcija[uredi | uredi izvor]

MFSD2A je membranski transportni protein koji je izražen u endotelu krvno-moždane barijere (BBB) i ima esencijalnu ulogu u formiranju i funkciji BBB.^[5] Genetička ablacija MFSD2A dovodi do propuštanja BBB i povećava endotelne ćelije vezikulski transcitozu centralnog nervnog sistema, bez uticaja na čvrste spojeve.^[6] MFSD2A je atipski SLC,^[7] dakle predviđeni transporter peoretina porodice rastvornih nosača (SLC).^[8] Filogenetički grupira se u grupu AMTF8.^[8]

Pored transporta drugih lizofosfatidilholina kroz BBB, MSFD2A je primarni mehanizam za dokozaheksaensku kiselinu (DHA, omega-3 masna kiselina), unos i transport u mozak.< ref name="UniProt"/> Također može biti odgovoran za unos i transport tunikamicina (DHA, omega-3 masna kiselina) unos i transport u mozak.< ref name="UniProt" /> Također može biti odgovoran za unos i transport tunikamicina.^[9]^[10]^[11]

Potpuni gubitak MFSD2A kod ljudi dovodi do recesivnog smrtonosnog mikrocefalnog sindroma, koji se sastoji od uvećanih lateralnih komora i nerazvijenosti malog mozga i moždanog stabla. Ovo je vjerovatno zbog gubitka uzimanja esencijalnih polinezasićenih masnih kiselina u [[[endotel]]nim ćelijama mozga, koje koriste MFSD2A kao transporter za ove masti. Serum pacijenata pokazao je povišene nivoe esencijalnih polinezasićenih masnih kiselina, verovatno zbog nemogućnosti vaskularnih ćelija da preuzmu ove lipide u odsustvu proteinske funkcije. Bez mogućnosti preuzimanja ovih masti u endotelne ćelije, dolazi do raspada krvno-moždane barijere i gubitka volumena mozga. Ovo je pokazano na modelu zebrica, intrakardijalnom injekcijom boje, za koju je utvrđeno da ekstravazira u moždani parenhim nakon inaktivacije jednog od paraloga MSFD2A poznatog kao mfsd2aa.^[12]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000168389 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028655 - 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 "Sodium-dependent lysophosphatidylcholine symporter 1". UniProt. Pristupljeno 2 April 2016.
^ Ben-Zvi A, Lacoste B, Kur E, Andreone BJ, Mayshar Y, Yan H, Gu C (May 2014). "Mfsd2a is critical for the formation and function of the blood-brain barrier". Nature. 509 (7501): 507–11. Bibcode:2014Natur.509..507B. doi:10.1038/nature13324. PMC 4134871. PMID 24828040. Sažetak – Harvard Medical School.
^ Perland, Emelie; Fredriksson, Robert (March 2017). "Classification Systems of Secondary Active Transporters". Trends in Pharmacological Sciences. 38 (3): 305–315. doi:10.1016/j.tips.2016.11.008. ISSN 1873-3735. PMID 27939446.
^ ^a ^b Perland, Emelie; Bagchi, Sonchita; Klaesson, Axel; Fredriksson, Robert (September 2017). "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression". Open Biology. 7 (9): 170142. doi:10.1098/rsob.170142. ISSN 2046-2441. PMC 5627054. PMID 28878041.
^ Angers M, Uldry M, Kong D, Gimble JM, Jetten AM (November 2008). "Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis". Biochem J. 416 (3): 347–55. doi:10.1042/BJ20080165. PMC 2587516. PMID 18694395.
^ "Entrez Gene: MFSD2 major facilitator superfamily domain containing 2".
^ Reiling JH, Clish CB, Carette JE, Varadarajan M, Brummelkamp TR, Sabatini DM (July 2011). "A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin". Proc Natl Acad Sci U S A. 108 (29): 11756–65. Bibcode:2011PNAS..10811756R. doi:10.1073/pnas.1018098108. PMC 3141996. PMID 21677192.
^ Nat Genet. 2015 Jul;47(7):809-13

Dopunska literatura[uredi | uredi izvor]

Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A (2004). "Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas". Oncogene. 23 (35): 5901–11. doi:10.1038/sj.onc.1207782. PMID 15221005.
Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J (2004). "Large-scale cDNA transfection screening for genes related to cancer development and progression". Proc. Natl. Acad. Sci. U.S.A. 101 (44): 15724–9. Bibcode:2004PNAS..10115724W. doi:10.1073/pnas.0404089101. PMC 524842. PMID 15498874.
Spinola M, Falvella FS, Galvan A, Pignatiello C, Leoni VP, Pastorino U, Paroni R, Chen S, Skaug V, Haugen A, Dragani TA (2007). "Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients' survival" (PDF). Lung Cancer. 55 (3): 271–7. doi:10.1016/j.lungcan.2006.10.023. hdl:2434/25016. PMID 17145094.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000168389 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028655 - 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.

[UniProt-5] "Sodium-dependent lysophosphatidylcholine symporter 1". UniProt. Pristupljeno 2 April 2016.

[pmid24828040-6] Ben-Zvi A, Lacoste B, Kur E, Andreone BJ, Mayshar Y, Yan H, Gu C (May 2014). "Mfsd2a is critical for the formation and function of the blood-brain barrier". Nature. 509 (7501): 507–11. Bibcode:2014Natur.509..507B. doi:10.1038/nature13324. PMC 4134871. PMID 24828040. Sažetak – Harvard Medical School.

[7] Perland, Emelie; Fredriksson, Robert (March 2017). "Classification Systems of Secondary Active Transporters". Trends in Pharmacological Sciences. 38 (3): 305–315. doi:10.1016/j.tips.2016.11.008. ISSN 1873-3735. PMID 27939446.

[:0-8] Perland, Emelie; Bagchi, Sonchita; Klaesson, Axel; Fredriksson, Robert (September 2017). "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression". Open Biology. 7 (9): 170142. doi:10.1098/rsob.170142. ISSN 2046-2441. PMC 5627054. PMID 28878041.

[pmid18694395-9] Angers M, Uldry M, Kong D, Gimble JM, Jetten AM (November 2008). "Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis". Biochem J. 416 (3): 347–55. doi:10.1042/BJ20080165. PMC 2587516. PMID 18694395.

[entrez-10] "Entrez Gene: MFSD2 major facilitator superfamily domain containing 2".

[PMID21677192-11] Reiling JH, Clish CB, Carette JE, Varadarajan M, Brummelkamp TR, Sabatini DM (July 2011). "A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin". Proc Natl Acad Sci U S A. 108 (29): 11756–65. Bibcode:2011PNAS..10811756R. doi:10.1073/pnas.1018098108. PMC 3141996. PMID 21677192.

[12] Nat Genet. 2015 Jul;47(7):809-13

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