CARKD

Dostupne proteinske strukture:
Pfam	strukture / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	sažetak strukture
PDB	1kyh, 2ax3

Karbohidratna kinaza
Karbohidratna kinaza
	Kristalografska struktura navodne kinaze ugljikohidrata Bacillus subtilis (u boji duge, N-kraj = plava, C-kraj = crvena).
Identifikatori
Simbol	Carb_kinase
Pfam	PF01256
Pfam klan	CL0118
InterPro	IPR000631
PROSITE	PDOC00806
SCOP2	1kyh / SCOPe / SUPFAM
Pfam
Dostupne proteinske strukture:
Pfam	strukture / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	sažetak strukture
PDB	1kyh, 2ax3

CARKD
Identifikatori
Aliasi	NAXD
Vanjski ID-jevi	OMIM: 615910 MGI: 1913353 HomoloGene: 6333 GeneCards: NAXD
Lokacija gena (čovjek)
Hrom.	Hromosom 13 (čovjek)
Kraj	110,639,996 bp
Lokacija gena (miš)
Hrom.	Hromosom 8 (miš)
Kraj	11,564,960 bp
Ontologija gena
Molekularna funkcija	• nucleotide binding; • GO:0001948, GO:0016582 vezivanje za proteine; • ATP binding; • ADP-dependent NAD(P)H-hydrate dehydratase activity; • lyase activity; • ATP-dependent NAD(P)H-hydrate dehydratase activity; • molekularna funkcija;
Ćelijska komponenta	• mitohondrija; • mitochondrial matrix; • ćelijska komponenta;
Biološki proces	• NAD biosynthesis via nicotinamide riboside salvage pathway; • GO:0022610 biološki proces; • nicotinamide nucleotide metabolic process;
	Izvori:Amigo / QuickGO
Ortolozi
	55739
	69225
	ENSG00000213995
	ENSMUSG00000031505
	Q8IW45
	Q9CZ42
	NM_001242881; NM_001242882; NM_001242883; NM_018210
	NM_001190357; NM_001293661; NM_026995
	NP_001229810; NP_001229811; NP_001229812; NP_060680
	NP_001177286; NP_001280590; NP_081271; NP_001389565
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Domen ugljikohidratne kinaze koji sadrži protein (skraćeno CARKD), kodiran genom CARKD, je ljudski protein nepoznate funkcije. Gen CARKD kodira proteine s predviđenim mitohondrijskim propeptidom (mCARKD), signalnim peptidom (spCARKD) ili niti jednim od njih (cCARKD). Analiza konfokusne mikroskopije transficiranih CHO (jajnika kineskog hrčka) pokazala je da cCARKD ostaje u citosolu, dok su mCARKD i spCARKD usmjereni na mitohondrije i endoplazmatski retikulum.^[6] Protein je konzerviran u mnogim vrstama, sa predvđenim ortolozima do eukariota, bakterija i arheja.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 347 aminokiselina, a molekulska težina 36.576 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
MVTRAGAGTA	VAGAVVVALL	SAALALYGPP	LDAVLERAFS	LRKAHSIKDM
ENTLQLVRNI	IPPLSSTKHK	GQDGRIGVVG	GCQEYTGAPY	FAAISALKVG
ADLSHVFCAS	AAAPVIKAYS	PELIVHPVLD	SPNAVHEVEK	WLPRLHALVV
GPGLGRDDAL	LRNVQGILEV	SKARDIPVVI	DADGLWLVAQ	QPALIHGYRK
AVLTPNHVEF	SRLYDAVLRG	PMDSDDSHGS	VLRLSQALGN	VTVVQKGERD
ILSNGQQVLV	CSQEGSSRRC	GGQGDLLSGS	LGVLVHWALL	AGPQKTNGSS
PLLVAAFGAC	SLTRQCNHQA	FQKHGRSTTT	SDMIAEVGAA	FSKLFET

Simboli

Struktura

Gen

Ljudski gen CARKD ima 10 egzona i nalazi se na poziciji q34 hromosoma 13. Sljedeći geni su blizu CARKD -a na hromosomu:^[8]

COL4A2: za A2 podjedinicu kolagena tipa IV
RAB20: Potencijalni regulator prometa koneksina 43.
CARS2: za mitohondrijsku cistienil-tRNK sintetazu 2
ING1: za protein koji potiskuje tumore

Protein

Ovaj protein je dio natporodice fosfometilpirimidin-kinaza: ribokinaza / pfkB. Ovu porodicu karakterizira prisutnost domena koju dijeli porodica.^[9] CARKD sadrži domen karbohidratne kinaze porodice PF01256.^[9] Ova porodica je u srodstvu sa porodicama PF02210 i PF00294, što implicira da je to također ugljikohidrat-kinaza.

Predviđena svojstva

Pomoću bioinformatičkih analiza, predviđena su sljedeća svojstva CARKD-a:

Molekulska težina: 41,4 KDal^[10]
Izoelektrična tačka: 9,377^[11]
- Ortolozi CARKD-a imaju visoko varijabilnu izoelektrične tačke.^[11]
Posttranslacijske modifikacije: Predviđene su tri posttranslacijske modifikacije:
- Modificirani fosfotirozinski ostatak ^[12]
- Dva mjesta N-vezane glikozilacije ^[12]
Signalni peptid i mjesto cijepanja signalnog peptida.^[13]

Funkcija

Tkivna distribucija

Čini se da je CARKD sveprisutno eksprimiran na visokim nivoima. Podaci o ekspresiji u ljudskom proteinu i mišjeg ortologa ukazuju na njegovu ekspresiju u gotovo svim tkivima.^[14]^[15] Jedan osebujan obrazac ekspresije CARKD -a je različito ispoljavanje tokom razvoja oligodendrocita. Njegova ekspresija je niža u matičnim ćelijama oligodendrocita nego u zrelim oligodendrocitima.^[16]

Vezujući partneri

Predviđeno je da je partner za vezivanje za CARKD, prekursor apolipoproteina A-1 ljudskih proteina (APOA1BP).^[17] Ovo predviđanje temelji se na istovremenoj pojavi u genomima i koekspresiji. Osim ovih podataka, ortolozi CARKD -a u Escherichia coli sadrže domen sličan APOA1BP-u. Ovo ukazuje na to da su dva proteina vjerojatno nastala od zajedničkog evolucijskog pretka i, prema teoriji analize kamena rozeta,^[18] mogući su partneri u interakciji čak i kod vrsta poput ljudi, gdje se dva proteina ne proizvode kao jedan polipeptid.

Klinički značaj

Na osnovu alela specifične ekspresije CARKD-a, CARKD može imati ulogu u akutnoj limfoblastnoj leukemiji.^[19] Osim toga, mikročipni podaci pokazuju da je CARKD reguliran prema gore u tumorima glioblastoma multiforme.^[20]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000213995 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031505 - 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.
^ PDB 1kyh; Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, Joachimiak A (septembar 2002). "Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase". Journal of Structural Biology. 139 (3): 161–70. doi:10.1016/S1047-8477(02)00532-4. PMC 2793413. PMID 12457846.
^ Marbaix, AY; Tyteca, D; Niehaus, TD; Hanson, AD; Linster, CL; Van Schaftingen, E (15. 5. 2014). "Occurrence and subcellular distribution of the NADPHX repair system in mammals". The Biochemical Journal. 460 (1): 49–58. doi:10.1042/bj20131482. PMID 24611804.
^ "UniProt, Q8IW45". Pristupljeno 11. 9. 2017.
^ "UCSC Genome Browser: CARKD".
^ ^a ^b "CDD: Conserved Domain Database (NCBI)".
^ Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (mart 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6): 2002–6. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.
^ ^a ^b "PI Program (Isoelectric Point Prediction)". Arhivirano s originala, 26. 10. 2008.
^ ^a ^b "UniProt Database".
^ Bendtsen JD, Nielsen H, Gunnar vH (juli 2004). "Improved prediction of signal peptides: SignalP 3.0". Journal of Molecular Biology. 340 (4): 783–95. CiteSeerX 10.1.1.165.2784. doi:10.1016/j.jmb.2004.05.028. PMID 15223320. Zanemaren tekst "von Heijne G, Brunak S" (pomoć); Greška u vankuverskom stilu: initials u nazivu 3 (pomoć)
^ "Unigene (EST profile viewer) Human CARKD".
^ "Unigene (EST profile viewer) Mouse CARKD".
^ Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD (septembar 2006). "Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling". Journal of Neuroscience. 26 (39): 9881–91. doi:10.1523/JNEUROSCI.2246-06.2006. PMC 1613258. PMID 17005852.
^ "STRING: Known and Predicted Protein-Protein Interactions".
^ Date SV (2008). The Rosetta stone method. Methods Mol Biol. Methods in Molecular Biology™. 453. str. 169–80. doi:10.1007/978-1-60327-429-6_7. ISBN 978-1-60327-428-9. PMID 18712302.
^ Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, Kanerva J, Schmiegelow K, Gunderson KL, Lönnerholm G, Syvänen AC (januar 2009). "Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation". Genome Research. 19 (1): 1–11. doi:10.1101/gr.083931.108. PMC 2612957. PMID 18997001.
^ Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P, Meléndez B (2006). "Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling". Molecular Cancer. 5 (1): 39. doi:10.1186/1476-4598-5-39. PMC 1592108. PMID 17002787.

Vanjski linkovi

Lokacija ljudskog genoma CARKD i stranica sa detaljima o genu CARKD u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000213995 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000031505 - 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.

[pmid12457846-5] PDB 1kyh; Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, Joachimiak A (septembar 2002). "Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase". Journal of Structural Biology. 139 (3): 161–70. doi:10.1016/S1047-8477(02)00532-4. PMC 2793413. PMID 12457846.

[pmid24611804-6] Marbaix, AY; Tyteca, D; Niehaus, TD; Hanson, AD; Linster, CL; Van Schaftingen, E (15. 5. 2014). "Occurrence and subcellular distribution of the NADPHX repair system in mammals". The Biochemical Journal. 460 (1): 49–58. doi:10.1042/bj20131482. PMID 24611804.

[UniProt-7] "UniProt, Q8IW45". Pristupljeno 11. 9. 2017.

[UCSC-8] "UCSC Genome Browser: CARKD".

[CDD-9] "CDD: Conserved Domain Database (NCBI)".

[SAPS-10] Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (mart 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6): 2002–6. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.

[PI-11] "PI Program (Isoelectric Point Prediction)". Arhivirano s originala, 26. 10. 2008.

[Uniprot-12] "UniProt Database".

[SignalP-13] Bendtsen JD, Nielsen H, Gunnar vH (juli 2004). "Improved prediction of signal peptides: SignalP 3.0". Journal of Molecular Biology. 340 (4): 783–95. CiteSeerX 10.1.1.165.2784. doi:10.1016/j.jmb.2004.05.028. PMID 15223320. Zanemaren tekst "von Heijne G, Brunak S" (pomoć); Greška u vankuverskom stilu: initials u nazivu 3 (pomoć)

[ESTHuman-14] "Unigene (EST profile viewer) Human CARKD".

[CARKDmouse-15] "Unigene (EST profile viewer) Mouse CARKD".

[pmid17005852-16] Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD (septembar 2006). "Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling". Journal of Neuroscience. 26 (39): 9881–91. doi:10.1523/JNEUROSCI.2246-06.2006. PMC 1613258. PMID 17005852.

[String-17] "STRING: Known and Predicted Protein-Protein Interactions".

[18] Date SV (2008). The Rosetta stone method. Methods Mol Biol. Methods in Molecular Biology™. 453. str. 169–80. doi:10.1007/978-1-60327-429-6_7. ISBN 978-1-60327-428-9. PMID 18712302.

[pmid18997001-19] Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, Kanerva J, Schmiegelow K, Gunderson KL, Lönnerholm G, Syvänen AC (januar 2009). "Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation". Genome Research. 19 (1): 1–11. doi:10.1101/gr.083931.108. PMC 2612957. PMID 18997001.

[pmid17002787-20] Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P, Meléndez B (2006). "Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling". Molecular Cancer. 5 (1): 39. doi:10.1186/1476-4598-5-39. PMC 1592108. PMID 17002787.

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