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3.A.5.8.1
The general secretory pathway (Sec-SRP) complex. The Yet1 and Yet3 proteins interact directly with the Sec translocon (Wilson & Barlowe et al., 2010). The Sss1/Sec61γ protein (80aas) has two domains. The cytosolic domain is required for Sec61p interaction while the transmembrane clamp domain is required to complete activation of the translocon after precursor targeting to Sec61p (Wilkinson et al., 2010). However, the apolar surfrace area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum (Öjemalm et al., 2011). The essential Sec62, Sec63 and non-essential Sec66 and Sec72 proteins may comprise an SRP-independent tetrameric translocon enlisting the lumenal chaperone, BiP/Kar2 to ""ratchet"" its substrates into the ER (Feldheim and Schekman 1994; Ast et al. 2013). Cytosolic segments of the Sec61 complex important for promoting the structural transition between the closed and open conformations of the complex have been identified (Mandon et al. 2018). Positively charged residues in multiple cytosolic segments, as well as bulky hydrophobic residues in the L6/7-TMS7 junction may be required for cotranslational translocation or integration of membrane proteins by the Sec61 complex (Mandon et al. 2018). The structure of the yeast post-translational Sec complex (Sec61-Sec63-Sec71-Sec72) by cryo-EM shows that Sec63 tightly associates with Sec61 through interactions in cytosolic, transmembrane, and ER-luminal domains, prying open Sec61's lateral gate and translocation pore, and thus activating the channel for substrate engagement.  Sec63 optimally positions binding sites for cytosolic and luminal chaperones in the complex to enable efficient polypeptide translocation (Itskanov and Park 2019). Further, post-translational translocation is mediated by the association of the Sec61 channel with the membrane protein complex, the Sec62-Sec63 complex, and substrates move through the channel by the luminal BiP ATPase. Wu et al. 2019 determined the cryoEM structure of the S. cerevisiae Sec complex, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins. Sec63 causes wide opening of the lateral gate of the Sec61 channel, priming it for the passage of low-hydrophobicity signal sequences into the lipid phase, without displacing the channel's plug domain. Lateral channel opening is triggered by Sec63 interacting both with cytosolic loops in the C-terminal half of Sec61 and transmembrane segments in the N-terminal half of the Sec61 channel. The cytosolic Brl domain of Sec63 blocks ribosome binding to the channel and recruits Sec71 and Sec72, positioning them for the capture of polypeptides associated with cytosolic Hsp70. The structure thus shows how the Sec61 channel is activated for post-translational protein translocation (Wu et al. 2019).

Accession Number:P14906
Protein Name:Sec63 aka NPL1 aka PTL1 aka YOR254C
Length:663
Molecular Weight:75345.00
Species:Saccharomyces cerevisiae (Baker's yeast) [4932]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate protein

Cross database links:

DIP: DIP-2396N
RefSeq: NP_014897.1   
Entrez Gene ID: 854428   
Pfam: PF00226    PF02889   
KEGG: sce:YOR254C   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005739 C:mitochondrion
GO:0005637 C:nuclear inner membrane
GO:0031207 C:Sec62/Sec63 complex
GO:0031072 F:heat shock protein binding
GO:0008565 F:protein transporter activity
GO:0046967 P:cytosol to ER transport
GO:0031204 P:posttranslational protein targeting to memb...
GO:0006614 P:SRP-dependent cotranslational protein targe...

References (16)

[1] “A yeast gene important for protein assembly into the endoplasmic reticulum and the nucleus has homology to DnaJ, an Escherichia coli heat shock protein.”  Sadler I.et.al.   2556404
[2] “Sequencing analysis of a 36.8 kb fragment of yeast chromosome XV reveals 26 open reading frames including SEC63, CDC31, SUG2, GCD1, RBL2, PNT1, PAC1 and VPH1.”  Poirey R.et.al.   9153759
[3] “The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.”  Dujon B.et.al.   9169874
[4] “Assembly of yeast Sec proteins involved in translocation into the endoplasmic reticulum into a membrane-bound multisubunit complex.”  Deshaies R.J.et.al.   2000150
[5] “Topology and functional domains of Sec63p, an endoplasmic reticulum membrane protein required for secretory protein translocation.”  Feldheim D.et.al.   1620130
[6] “Extragenic suppressors of mutations in the cytoplasmic C-terminus of SEC63 define five genes in Saccharomyces cerevisiae.”  Nelson M.K.et.al.   8514125
[7] “A Sec63p-BiP complex from yeast is required for protein translocation in a reconstituted proteoliposome.”  Brodsky J.L.et.al.   8253836
[8] “Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p.”  Panzner S.et.al.   7758110
[9] “Sec63p and Kar2p are required for the translocation of SRP-dependent precursors into the yeast endoplasmic reticulum in vivo.”  Young B.P.et.al.   11226176
[10] “Global analysis of protein expression in yeast.”  Ghaemmaghami S.et.al.   14562106
[11] “Identification of novel protein-protein interactions at the cytosolic surface of the Sec63 complex in the yeast ER membrane.”  Willer M.et.al.   12518317
[12] “Protein kinase CK2 phosphorylates Sec63p to stimulate the assembly of the endoplasmic reticulum protein translocation apparatus.”  Wang X.et.al.   15671059
[13] “A global topology map of the Saccharomyces cerevisiae membrane proteome.”  Kim H.et.al.   16847258
[14] “Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae.”  Li X.et.al.   17330950
[15] “Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry.”  Chi A.et.al.   17287358
[16] “A multidimensional chromatography technology for in-depth phosphoproteome analysis.”  Albuquerque C.P.et.al.   18407956
Structure:
6N3Q   6ND1     

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FASTA formatted sequence
1:	MPTNYEYDEA SETWPSFILT GLLMVVGPMT LLQIYQIFFG ANAEDGNSGK SKEFNEEVFK 
61:	NLNEEYTSDE IKQFRRKFDK NSNKKSKIWS RRNIIIIVGW ILVAILLQRI NSNDAIKDAA 
121:	TKLFDPYEIL GISTSASDRD IKSAYRKLSV KFHPDKLAKG LTPDEKSVME ETYVQITKAY 
181:	ESLTDELVRQ NYLKYGHPDG PQSTSHGIAL PRFLVDGSAS PLLVVCYVAL LGLILPYFVS 
241:	RWWARTQSYT KKGIHNVTAS NFVSNLVNYK PSEIVTTDLI LHWLSFAHEF KQFFPDLQPT 
301:	DFEKLLQDHI NRRDSGKLNN AKFRIVAKCH SLLHGLLDIA CGFRNLDIAL GAINTFKCIV 
361:	QAVPLTPNCQ ILQLPNVDKE HFITKTGDIH TLGKLFTLED AKIGEVLGIK DQAKLNETLR 
421:	VASHIPNLKI IKADFLVPGE NQVTPSSTPY ISLKVLVRSA KQPLIPTSLI PEENLTEPQD 
481:	FESQRDPFAM MSKQPLVPYS FAPFFPTKRR GSWCCLVSSQ KDGKILQTPI IIEKLSYKNL 
541:	NDDKDFFDKR IKMDLTKHEK FDINDWEIGT IKIPLGQPAP ETVGDFFFRV IVKSTDYFTT 
601:	DLDITMNMKV RDSPAVEQVE VYSEEDDEYS TDDDETESDD ESDASDYTDI DTDTEAEDDE 
661:	SPE