Glukosa-6-fosfat isomerase

Kawasan terminal C fosfoglukosa isomerase bakteria
Kawasan terminal C fosfoglukosa isomerase bakteria
	Struktur hablur isomerase Pyrobaculum aerophilum dalam kompleks dengan fruktosa 6-fosfat
Pengenal pasti
Simbol	bact-PGI_C
Pfam	PF10432
InterPro	IPR019490
CDD	cd05016
Pfam
Struktur protein yang tersedia:
Pfam	struktur
PDB	RCSB PDB; PDBe; PDBj
PDBsum	ringkasan struktur

Gelintar
PMC	Rencana
PubMed	Rencana
NCBI	Protein

Glukosa-6-fosfat isomerase
Glukosa-6-fosfat isomerase
	Dimer glukosa-6-fosfat isomerase, arnab
Pengenal pasti
Nombor EC	5.3.1.9
Nombor CAS	9001-41-6
Pangkalan data
IntEnz	Lihat IntEnz
BRENDA	Entri BRENDA
ExPASy	Lihat NiceZyme
KEGG	Entri KEGG
MetaCyc	Laluan metabolik
PRIAM	Profil
Struktur PDB	RCSB PDB; PDBj; PDBe; PDBsum
Ontologi gen	AmiGO / EGO
PMC
Gelintar
PMC	Rencana
PubMed	Rencana
NCBI	Protein

Fosfoglukosa isomerase

Pengenal pasti

Simbol

PGI

Struktur protein yang tersedia:
Pfam	struktur
PDB	RCSB PDB; PDBe; PDBj
PDBsum	ringkasan struktur

GPI

Struktur sedia ada

PDB

Pencarian ortolog: data%20or%20P06744%20or%20A0A0J9YYH3 PDBe data,P06744,A0A0J9YYH3 RCSB

Senarai kod PDB
1NUH, 1IAT, 1IRI, 1JIQ, 1JLH

Pengecam

Alias

GPI, AMF, GNPI, NLK, PGI, PHI, SA-36, SA36, glucose-6-phosphate isomerase

Pengecam-pengecam luaran

OMIM: 172400 HomoloGene: 145 GeneCards: GPI

Kedudukan gen (Manusia)

Kr.	Kromosom 19^[1]

Jalur	19q13.11	Mula	34,359,480 bp^[1]
Jalur	19q13.11	Tamat	34,402,413 bp^[1]

Corak ekspresi RNA

Bgee

Human

Mouse (ortholog)

Top expressed in

apex of heart

right adrenal gland

right adrenal cortex

right frontal lobe

left adrenal gland

right hemisphere of cerebellum

Ventrikel kiri

left adrenal cortex

right auricle

prefrontal cortex

tiada data

More reference expression data

BioGPS

tiada data

Ontologi gen
Fungsi molekul	cytokine activity monosaccharide binding intramolecular transferase activity glucose-6-phosphate isomerase activity isomerase activity growth factor activity ubiquitin protein ligase binding
Komponen sel	membran myelin sheath Membran plasma nucleoplasm ciliary membrane neuron projection extracellular exosome extracellular region Ekstrasel Sitoplasma cytosol secretory granule lumen ficolin-1-rich granule lumen
Proses biologi	negative regulation of neuron apoptotic process Hemostasis Glukoneogenesis negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Glikolisis glucose homeostasis canonical glycolysis mesoderm formation aldehyde catabolic process in utero embryonic development erythrocyte homeostasis humoral immune response methylglyoxal biosynthetic process Angiogenesi learning or memory glucose 6-phosphate metabolic process response to progesterone response to morphine response to immobilization stress response to estradiol response to testosterone response to cadmium ion response to muscle stretch neutrophil degranulation proses metabolisme karbohidrat regulation of signaling receptor activity positive regulation of endothelial cell migration Transduksi isyarat
Sumber:Amigo / QuickGO

Ortolog

Spesies

Manusia

Mencit

Entrez


2821


14751

Ensembl


ENSG00000282019 ENSG00000105220


ENSMUSG00000036427

UniProt


P06744


tiada data

RefSeq (mRNA)

NM_000175 NM_001184722 NM_001289789 NM_001289790 NM_001329909
NM_001329910 NM_001329911


NM_008155

RefSeq (protein)

NP_000166 NP_001171651 NP_001276718 NP_001276719 NP_001316838
NP_001316839 NP_001316840


tiada data

Kedudukan (UCSC)

Chr 19: 34.36 – 34.4 Mb

tiada data

Carian PubMed

^[2]

^[3]

Wikidata

Papar/Sunting data manusia

Papar/Sunting data mencit

Glukosa-6-fosfat isomerase (GPI), secara alternatif dikenali sebagai fosfoglukosa isomerase/fosfoglukoisomerase (PGI) atau fosfoheksosa isomerase (PHI), ialah enzim (EC 5.3.1.9) pada dikodkan badan manusia oleh gen GPI pada kromosom 19.^[4] Gen ini mengekod ahli keluarga protein isomerase glukosa berfosfat. Protein yang dikodkan telah dikenal pasti sebagai protein "cahaya bulan" berdasarkan keupayaannya untuk melaksanakan fungsi yang berbeza secara mekanikal. Dalam sitoplasma, produk gen berfungsi sebagai enzim glikolisis (langkah kedua) yang saling menukar molekul glukosa 6-fosfat (G6P) dan fruktosa-6-fosfat (F6P). Di luar sel, protein dikodkan (juga dirujuk sebagai neuroleukin) berfungsi sebagai faktor neurotropik yang menggalakkan kemandirian neuron motor rangka dan neuron deria, dan sebagai limfokin yang mendorong rembesan imunoglobulin (antibodi). Protein yang dikodkan juga dirujuk sebagai faktor motiliti autokrin (AMF) berdasarkan fungsi tambahan sebagai sitokin dan faktor angiogenik yang dirembeskan tumor. Kecacatan gen ini adalah punca anemia hemolitik tak sferositik, dan kekurangan enzim yang teruk boleh dikaitkan dengan hidrops fetalis, kematian neonatal serta-merta dan kerosakan saraf. Penyambungan alternatif menghasilkan berbilang variasi transkrip. [disediakan oleh RefSeq, Jan 2014]^[5]

Mekanisme

D-Glukosa	Fosfoglukosa isomerase	D-Fruktosa





	Fosfoglukosa isomerase

α-D-Glukosa 6-fosfat	Fosfoglukosa isomerase	α-D-Fruktosa 6-fosfat





	Fosfoglukosa isomerase

Mekanisme yang digunakan GPI untuk menukar glukosa 6-fosfat dan fruktosa 6-fosfat (aldosa kepada ketosa) terdiri daripada tiga langkah utama: membuka gelang glukosa, mengisomerikan glukosa kepada fruktosa melalui perantaraan enediol, dan menutup gelang fruktosa.^[6]

Pengisomeran glukosa

Glukosa 6-fosfat mengikat GPI dalam bentuk piranosa. Cincin dibuka dalam mekanisme "tolak-tarik" oleh His388, yang memprotonasi oksigen C5, dan Lys518, yang menyahproton kumpulan hidroksil C1. Ini mewujudkan aldosa rantai terbuka. Kemudian, substrat diputarkan di ikatan C3-C4 bagi pengisomeran. Pada ketika ini, Glu357 menyahproton C2 untuk mencipta perantaraan cis-enediolat yang distabilkan oleh Arg272. Untuk melengkapkan pengisomeran, Glu357 mendermakan protonnya kepada C1, kumpulan hidroksil C2 kehilangan protonnya, dan fruktosa 6-fosfat ketosa rantai terbuka terbentuk. Akhirnya, cincin ditutup dengan memutarkan substrat mengenai ikatan C3-C4 sekali lagi dan menyahprotonasi hidroksil C5 dengan Lys518.^[7]

Fungsi

Gen ini tergolong dalam keluarga GPI.^[5] Protein yang dikodkan oleh gen ini ialah enzim dimerik yang memangkinkan pengisomeran boleh balik G6P dan F6P.^[8]^[9] Oleh kerana tindak balas boleh diterbalikkan, arahnya ditentukan oleh kepekatan G6P dan F6P.^[10]

glukosa 6-fosfat ↔ fruktosa 6-fosfat

Protein mempunyai fungsi yang berbeza di dalam dan di luar sel. Dalam sitoplasma, protein ini terlibat dalam glikolisis dan glukoneogenesis, serta laluan pentosa fosfat.^[10] Di luar sel, ia berfungsi sebagai faktor neurotropik bagi neuron tulang belakang dan deria, dipanggil neuroleukin.^[9] Protein yang sama juga dirembeskan oleh sel-sel kanser, di mana ia dipanggil faktor motiliti autokrin^[11] dan merangsang metastasis.^[12] GPI ekstraselular juga diketahui berfungsi sebagai faktor pematangan.^[10]^[9]

Kepentingan klinikal

Kekurangan GPI bertanggungjawab untuk 4% daripada kes-kes anemia hemolisis disebabkan oleh kekurangan enzim glikolisis.^[8]^[9]^[13]^[14] Beberapa kes kekurangan GPI telah dikenal pasti baru-baru ini.^[15]

Aplikasi

GPI manusia mampu mendorong arthritis pada tikus dengan latar belakang genetik yang berbeza-beza melalui suntikan intradermis.^[16]^[17]

Rujukan

^ ^a ^b ^c ENSG00000105220 GRCh38: Ensembl release 89: ENSG00000282019, ENSG00000105220 - Ensembl, May 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.
^ "UniProtKB: P06744 (G6PI_HUMAN)".
^ ^a ^b "Entrez Gene: GPI glucose phosphate isomerase".
^ "The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia". Journal of Molecular Biology. 309 (2): 447–463. June 2001. doi:10.1006/jmbi.2001.4680. PMID 11371164.
^ "The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening". Journal of Molecular Biology. 342 (3): 847–860. September 2004. doi:10.1016/j.jmb.2004.07.085. PMID 15342241. Unknown parameter |displayauthors= ignored (bantuan)
^ ^a ^b "Glucose-6-phosphate isomerase deficiency". Bailliere's Best Practice & Research. Clinical Haematology. 13 (1): 89–101. March 2000. doi:10.1053/beha.1999.0059. PMID 10916680.
^ ^a ^b ^c ^d "A tale of two isomerases: compact versus extended active sites in ketosteroid isomerase and phosphoglucose isomerase". Biochemistry. 50 (43): 9283–9295. November 2011. doi:10.1021/bi201089v. PMID 21970785.
^ ^a ^b ^c "Crystal structure of human phosphoglucose isomerase and analysis of the initial catalytic steps". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1645 (2): 117–122. February 2003. doi:10.1016/s1570-9639(02)00464-8. PMID 12573240.
^ "Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas". The Journal of Pathology. 210 (4): 431–440. December 2006. doi:10.1002/path.2069. PMID 17029220.
^ "Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide". Cancer Research. 56 (13): 2960–2963. July 1996. PMID 8674049.
^ "DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency". Human Molecular Genetics. 2 (3): 327–329. March 1993. doi:10.1093/hmg/2.3.327. PMID 8499925.
^ "Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia". Blood. 88 (6): 2321–2325. September 1996. doi:10.1182/blood.V88.6.2321.bloodjournal8862321. PMID 8822954. Unknown parameter |displayauthors= ignored (bantuan)
^ "GPI Deficiency".
^ "A glucose-6-phosphate isomerase peptide induces T and B cell-dependent chronic arthritis in C57BL/10 mice: arthritis without reactive oxygen species and complement". The American Journal of Pathology. 183 (4): 1144–1155. October 2013. doi:10.1016/j.ajpath.2013.06.019. PMID 23911657.
^ "Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis". Arthritis Research & Therapy. 11 (4): R118. 2009. doi:10.1186/ar2779. PMC 2745801. PMID 19660107. Unknown parameter |displayauthors= ignored (bantuan)

[refGRCh38Ensembl-1] ENSG00000105220 GRCh38: Ensembl release 89: ENSG00000282019, ENSG00000105220 - Ensembl, May 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.

[uniprot-4] "UniProtKB: P06744 (G6PI_HUMAN)".

[entrez-5] "Entrez Gene: GPI glucose phosphate isomerase".

[pmid11371164-6] "The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia". Journal of Molecular Biology. 309 (2): 447–463. June 2001. doi:10.1006/jmbi.2001.4680. PMID 11371164.

[pmid15342241-7] "The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening". Journal of Molecular Biology. 342 (3): 847–860. September 2004. doi:10.1016/j.jmb.2004.07.085. PMID 15342241. Unknown parameter |displayauthors= ignored (bantuan)

[pmid10916680-8] "Glucose-6-phosphate isomerase deficiency". Bailliere's Best Practice & Research. Clinical Haematology. 13 (1): 89–101. March 2000. doi:10.1053/beha.1999.0059. PMID 10916680.

[pmid21970785-9] "A tale of two isomerases: compact versus extended active sites in ketosteroid isomerase and phosphoglucose isomerase". Biochemistry. 50 (43): 9283–9295. November 2011. doi:10.1021/bi201089v. PMID 21970785.

[pmid12573240-10] "Crystal structure of human phosphoglucose isomerase and analysis of the initial catalytic steps". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1645 (2): 117–122. February 2003. doi:10.1016/s1570-9639(02)00464-8. PMID 12573240.

[pmid17029220-11] "Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas". The Journal of Pathology. 210 (4): 431–440. December 2006. doi:10.1002/path.2069. PMID 17029220.

[12] "Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide". Cancer Research. 56 (13): 2960–2963. July 1996. PMID 8674049.

[pmid8499925-13] "DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency". Human Molecular Genetics. 2 (3): 327–329. March 1993. doi:10.1093/hmg/2.3.327. PMID 8499925.

[pmid8822954-14] "Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia". Blood. 88 (6): 2321–2325. September 1996. doi:10.1182/blood.V88.6.2321.bloodjournal8862321. PMID 8822954. Unknown parameter |displayauthors= ignored (bantuan)

[15] "GPI Deficiency".

[pmid23911657-16] "A glucose-6-phosphate isomerase peptide induces T and B cell-dependent chronic arthritis in C57BL/10 mice: arthritis without reactive oxygen species and complement". The American Journal of Pathology. 183 (4): 1144–1155. October 2013. doi:10.1016/j.ajpath.2013.06.019. PMID 23911657.

[pmid19660107-17] "Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis". Arthritis Research & Therapy. 11 (4): R118. 2009. doi:10.1186/ar2779. PMC 2745801. PMID 19660107. Unknown parameter |displayauthors= ignored (bantuan)

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]