SHC1

SHC1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1MIL, 1N3H, 1OY2, 1QG1, 1SHC, 1TCE, 2L1C, 4JMH, 4XWX, 5CZI
Identifikatori
Aliasi	SHC1
Vanjski ID-jevi	OMIM: 600560 MGI: 98296 HomoloGene: 7934 GeneCards: SHC1
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	154,974,395 bp
Lokacija gena (miš)
Hrom.	Hromosom 3 (miš)
Kraj	89,337,334 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• insulin-like growth factor receptor binding; • transmembrane receptor protein tyrosine kinase adaptor activity; • insulin receptor binding; • neurotrophin TRKA receptor binding; • ephrin receptor binding; • epidermal growth factor receptor binding; • receptor tyrosine kinase binding; • GO:0001948, GO:0016582 vezivanje za proteine; • phospholipid binding; • epidermal growth factor binding; • phosphotyrosine residue binding;
Ćelijska komponenta	• citoplazma; • citosol; • mitochondrial matrix; • mitohondrija; • Shc-EGFR complex; • ćelijska membrana;
Biološki proces	• actin cytoskeleton reorganization; • GO:1901047 insulin receptor signaling pathway; • GO:0007243 intracellular signal transduction; • epidermal growth factor receptor signaling pathway; • cellular response to growth factor stimulus; • MAPK cascade; • Fc-epsilon receptor signaling pathway; • heart development; • IRE1-mediated unfolded protein response; • regulation of cell population proliferation; • Angiogeneza; • regulation of epidermal growth factor-activated receptor activity; • regulation of growth; • Ras protein signal transduction; • GO:0022415 viral process; • leukocyte migration; • GO:0072468 Transdukcija signala; • ERBB2 signaling pathway; • axon guidance; • defense response to bacterium; • negative regulation of apoptotic process; • positive regulation of MAPK cascade; • GO:0045996 negative regulation of transcription, DNA-templated; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • positive regulation of ERK1 and ERK2 cascade; • cell-cell adhesion; • interleukin-15-mediated signaling pathway; • negative regulation of angiogenesis; • cytokine-mediated signaling pathway; • interleukin-2-mediated signaling pathway; • positive regulation of cell proliferation in bone marrow; • regulation of superoxide metabolic process; • positive regulation of cell population proliferation; • positive regulation of Ras protein signal transduction;
	Izvori:Amigo / QuickGO
Ortolozi
	6464
	20416
	ENSG00000160691
	ENSMUSG00000042626
	P29353
	P98083
	NM_001130040; NM_001130041; NM_001202859; NM_003029; NM_183001
	NM_001113331; NM_011368
	NP_001123512; NP_001123513; NP_001189788; NP_003020; NP_892113
	NP_001106802; NP_035498
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

SHC-transformirajući protein 1 jest protein koji je kod ljudi kodiran genom SHC1 sa hromosoma 1.^[5] Za SHC nađeno je da je u sisarskim ćelijama važan u regulaciji apoptoza i rezistenciji na lijekove.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 583 aminokiseline, a molekulska težina 62.822 Da.^[6]

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
MDLLPPKPKY	NPLRNESLSS	LEEGASGSTP	PEELPSPSAS	SLGPILPPLP
GDDSPTTLCS	FFPRMSNLRL	ANPAGGRPGS	KGEPGRAADD	GEGIVGAAMP
DSGPLPLLQD	MNKLSGGGGR	RTRVEGGQLG	GEEWTRHGSF	VNKPTRGWLH
PNDKVMGPGV	SYLVRYMGCV	EVLQSMRALD	FNTRTQVTRE	AISLVCEAVP
GAKGATRRRK	PCSRPLSSIL	GRSNLKFAGM	PITLTVSTSS	LNLMAADCKQ
IIANHHMQSI	SFASGGDPDT	AEYVAYVAKD	PVNQRACHIL	ECPEGLAQDV
ISTIGQAFEL	RFKQYLRNPP	KLVTPHDRMA	GFDGSAWDEE	EEEPPDHQYY
NDFPGKEPPL	GGVVDMRLRE	GAAPGAARPT	APNAQTPSHL	GATLPVGQPV
GGDPEVRKQM	PPPPPCPGRE	LFDDPSYVNV	QNLDKARQAV	GGAGPPNPAI
NGSAPRDLFD	MKPFEDALRV	PPPPQSVSMA	EQLRGEPWFH	GKLSRREAEA
LLQLNGDFLV	RESTTTPGQY	VLTGLQSGQP	KHLLLVDPEG	VVRTKDHRFE
SVSHLISYHM	DNHLPIISAG	SELCLQQPVE	RKL

SCOP klasifikuje 3D strukturu kao pripadnost porodici SH2-domena.

Gen i ekspresija

Gen SHC1 nalazi se na hromosomu 1 i kodira tri glavne izoforme proteina: p66SHC, p52SHC i p46SHC. Ovi proteini se razlikuju po aktivnosti i subćelijskoj lokaciji, p66 je najduži i dok p52 i p46 povezuju aktiviranu receptorsku tirozin kinazu na RAS putu.^[7] The protein SHC1 also acts as a scaffold protein which is used in cell surface receptors.^[8] The three proteins that SHC1 codes for have distinctly different molecular weights.^[9] All three SHC1 proteins share the same domain arrangement consisting of an N-terminal phosphotyrosine-binding(PTB) domain and a C-terminal Src-homology2(SH2) domain. Both of the domains for the three proteins can bind to tyrosine-phosphorylated proteins but they are different in their phosphopeptide-binding specificities.^[10] P66SHC is characterized by having an additional N-terminal CH2 domain.^[10]

Funkcija

Prekomjerna ekspresija SHC proteina povezana je sa mitogenezom raka, karcinogenezom i metastazama.^[9] SHC i njegovi adapterski proteini prenose signalizaciju receptora na površini ćelije kao što su EGFR, erbV-2 i insulinski receptori. p52SHC i p46SHC aktiviraju Ras-ERK put. p66SHC inhibira aktivnost ERK1/2 i antagonizira mitogenu sposobnost i sposobnost preživljavanja Jurkat ćelijskih linija T-limfoma.^[9] Porast p66SHC podstiče apoptoze izazvane stresom. Također je uključen u oksidativna i stresom izazvana apoptozom– posredovana djelovanja steroida, putem redoks signalnog puta. P52SHC i p66SHC pronađeni su u karcinomu i metastazama reguliranim steroidnim hormonima.

SHC-transformirajuči protein 1 ima raznolike funkcije u više područja,kao što su

EGFR put
Regulacija MCT-1
Oksidativni stres
Životni vijek
Metabolizam p66SHC

Klinički značaj

Aktivacija signala SHC-a uključena je u tumorigenost u ćelijama raka, a postoji potencijal da se SHC koristi kao prognostički marker kada se cilja na liječenje kancera.^[9] SHC1 interacts with SgK269 which is a member of the Src kinase signaling network that characterized basal breast cancer cells. When SgK269 is overexpressed in mammary epithelial cells it promotes the cell growth and might contribute to the progression of aggressive breast cancers.^[11] Čini se da kod raka prostate i jajnika povećana ekspresija p66Shc podstiče proliferaciju ćelija.^[12] i tumorigenost, posebno kod ksenotransplanta raka prostate ^[13] Ovaj tumorogeni efekat je povezan sa njegovom sposobnošću da poveća redoksni stres u ovim ćelijama raka.^[14]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000160691 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000042626 - 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.
^ Pelicci G, Lanfrancone L, Grignani F, McGlade J, Cavallo F, Forni G, Nicoletti I, Grignani F, Pawson T, Pelicci PG (Jul 1992). "A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction". Cell. 70 (1): 93–104. doi:10.1016/0092-8674(92)90536-L. PMID 1623525. S2CID 20390181.
^ "UniProt, P29353" (jezik: engleski). Pristupljeno 18. 12. 2021.
^ "Genes and Mapped Phenotypes". National Center for Biotechnology Information. US National Library of Medicine.
^ Zheng Y, Zhang C, Croucher DR, Soliman MA, St-Denis N, Pasculescu A, Taylor L, Tate SA, Hardy WR, Colwill K, Dai AY, Bagshaw R, Dennis JW, Gingras AC, Daly RJ, Pawson T (Jul 2013). "Temporal regulation of EGF signalling networks by the scaffold protein Shc1". Nature. 499 (7457): 166–71. Bibcode:2013Natur.499..166Z. doi:10.1038/nature12308. PMC 4931914. PMID 23846654.
^ ^a ^b ^c ^d Shih HJ, Chen HH, Chen YA, Wu MH, Liou GG, Chang WW, Chen L, Wang LH, Hsu HL (Nov 2012). "Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity". Oncotarget. 3 (11): 1401–15. doi:10.18632/oncotarget.688. PMC 3717801. PMID 23211466.
^ ^a ^b Neumann-Haefelin E, Qi W, Finkbeiner E, Walz G, Baumeister R, Hertweck M (Oct 2008). "SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans". Genes & Development. 22 (19): 2721–35. doi:10.1101/gad.478408. PMC 2559911. PMID 18832074.
^ Dikic I, Daly RJ (Mar 2012). "Signalling through the grapevine". EMBO Reports. 13 (3): 178–80. doi:10.1038/embor.2012.16. PMC 3323131. PMID 22354089.
^ Bhat SS, Anand D, Khanday FA (2015). "p66Shc as a switch in bringing about contrasting responses in cell growth: implications on cell proliferation and apoptosis". Molecular Cancer. 14: 76. doi:10.1186/s12943-015-0354-9. PMC 4421994. PMID 25890053.
^ Veeramani S, Chou YW, Lin FC, Muniyan S, Lin FF, Kumar S, Xie Y, Lele SM, Tu Y, Lin MF (juli 2012). "Reactive oxygen species induced by p66Shc longevity protein mediate nongenomic androgen action via tyrosine phosphorylation signaling to enhance tumorigenicity of prostate cancer cells". Free Radical Biology & Medicine. 53 (1): 95–108. doi:10.1016/j.freeradbiomed.2012.03.024. PMC 3384717. PMID 22561705.
^ Lebiedzinska-Arciszewska M, Oparka M, Vega-Naredo I, Karkucinska-Wieckowska A, Pinton P, Duszynski J, Wieckowski MR (2015). "The interplay between p66Shc, reactive oxygen species and cancer cell metabolism". European Journal of Clinical Investigation. 45 Suppl 1: 25–31. doi:10.1111/eci.12364. PMID 25524583. S2CID 18237773.

Dopunska literatura

Sasaoka T, Kobayashi M (Aug 2000). "The functional significance of Shc in insulin signaling as a substrate of the insulin receptor". Endocrine Journal. 47 (4): 373–81. doi:10.1507/endocrj.47.373. PMID 11075717.
Ravichandran KS (Oct 2001). "Signaling via Shc family adapter proteins". Oncogene. 20 (44): 6322–30. doi:10.1038/sj.onc.1204776. PMID 11607835.
van der Geer P (maj 2002). "Phosphorylation of LRP1: regulation of transport and signal transduction". Trends in Cardiovascular Medicine. 12 (4): 160–5. doi:10.1016/S1050-1738(02)00154-8. PMID 12069755.

Vanjski linkovi

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160691 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000042626 - 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.

[pmid1623525-5] Pelicci G, Lanfrancone L, Grignani F, McGlade J, Cavallo F, Forni G, Nicoletti I, Grignani F, Pawson T, Pelicci PG (Jul 1992). "A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction". Cell. 70 (1): 93–104. doi:10.1016/0092-8674(92)90536-L. PMID 1623525. S2CID 20390181.

[UniProt-6] "UniProt, P29353" (jezik: engleski). Pristupljeno 18. 12. 2021.

[A1-7] "Genes and Mapped Phenotypes". National Center for Biotechnology Information. US National Library of Medicine.

[pmid23846654-8] Zheng Y, Zhang C, Croucher DR, Soliman MA, St-Denis N, Pasculescu A, Taylor L, Tate SA, Hardy WR, Colwill K, Dai AY, Bagshaw R, Dennis JW, Gingras AC, Daly RJ, Pawson T (Jul 2013). "Temporal regulation of EGF signalling networks by the scaffold protein Shc1". Nature. 499 (7457): 166–71. Bibcode:2013Natur.499..166Z. doi:10.1038/nature12308. PMC 4931914. PMID 23846654.

[pmid23211466-9] Shih HJ, Chen HH, Chen YA, Wu MH, Liou GG, Chang WW, Chen L, Wang LH, Hsu HL (Nov 2012). "Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity". Oncotarget. 3 (11): 1401–15. doi:10.18632/oncotarget.688. PMC 3717801. PMID 23211466.

[pmid18832074-10] Neumann-Haefelin E, Qi W, Finkbeiner E, Walz G, Baumeister R, Hertweck M (Oct 2008). "SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans". Genes & Development. 22 (19): 2721–35. doi:10.1101/gad.478408. PMC 2559911. PMID 18832074.

[pmid22354089-11] Dikic I, Daly RJ (Mar 2012). "Signalling through the grapevine". EMBO Reports. 13 (3): 178–80. doi:10.1038/embor.2012.16. PMC 3323131. PMID 22354089.

[Bhat_2015-12] Bhat SS, Anand D, Khanday FA (2015). "p66Shc as a switch in bringing about contrasting responses in cell growth: implications on cell proliferation and apoptosis". Molecular Cancer. 14: 76. doi:10.1186/s12943-015-0354-9. PMC 4421994. PMID 25890053.

[13] Veeramani S, Chou YW, Lin FC, Muniyan S, Lin FF, Kumar S, Xie Y, Lele SM, Tu Y, Lin MF (juli 2012). "Reactive oxygen species induced by p66Shc longevity protein mediate nongenomic androgen action via tyrosine phosphorylation signaling to enhance tumorigenicity of prostate cancer cells". Free Radical Biology & Medicine. 53 (1): 95–108. doi:10.1016/j.freeradbiomed.2012.03.024. PMC 3384717. PMID 22561705.

[Lebiedzinska-Arciszewska_2015-14] Lebiedzinska-Arciszewska M, Oparka M, Vega-Naredo I, Karkucinska-Wieckowska A, Pinton P, Duszynski J, Wieckowski MR (2015). "The interplay between p66Shc, reactive oxygen species and cancer cell metabolism". European Journal of Clinical Investigation. 45 Suppl 1: 25–31. doi:10.1111/eci.12364. PMID 25524583. S2CID 18237773.

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