SEC61/YLR378C Summary Help

Standard Name SEC61
Systematic Name YLR378C
Feature Type ORF, Verified
Description Conserved ER protein translocation channel; essential subunit of Sec61 complex (Sec61p, Sbh1p, and Sss1p); forms channel for SRP-dependent protein import; with Sec63 complex allows SRP-independent protein import into ER; involved in posttranslational soluble protein import into the ER, ERAD of soluble substrates, and misfolded soluble protein export from the ER (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description SECretory
Chromosomal Location
ChrXII:877178 to 875736 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All SEC61 GO evidence and references
  View Computational GO annotations for SEC61
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 8 genes
Classical genetics
reduction of function
Large-scale survey
reduction of function
257 total interaction(s) for 176 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 3
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 19
  • Co-fractionation: 9
  • Co-purification: 7
  • PCA: 33
  • Reconstituted Complex: 3

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 9
  • Negative Genetic: 125
  • Phenotypic Enhancement: 10
  • Phenotypic Suppression: 5
  • Positive Genetic: 22
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 2
  • Synthetic Rescue: 5

Expression Summary
Length (a.a.) 480
Molecular Weight (Da) 52,936
Isoelectric Point (pI) 10.18
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:877178 to 875736 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1443 877178..875736 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004370

Sec61p, an essential yeast protein, is the largest and major subunit of the heterotrimeric Sec61 complex, also referred to as the translocon (6; reviewed in 1). The Sec61 complex forms a channel in the endoplasmic reticulum (ER) membrane and mediates translocation of secretory and membrane proteins into the ER and also retrograde transport of misfolded proteins to the cytoplasm for degradation (reviewed in 7 and 1). The other subunits of the Sec61 complex are Sss1p, an essential protein thought to stabilize the complex, and Sbh1p (8, 9, 10).

Proteins that are transported into or across the ER membrane are directed there by signal sequences or by transmembrane segments that interact with the translocation apparatus. In S. cerevisiae the Sec61 complex mediates both co- and posttranslational translocation (while the mammalian Sec61 complex functions primarily with the cotranslational pathway; 11). During cotranslational translocation, ribosomes synthesizing signal sequence-containing proteins are targeted to the translocon via the signal recognition particle (SRP), and the ribosomes bind directly to Sec61p such that protein biosynthesis and translocation are synchronous (12). Posttranslational translocation requires Sec62p, Sec63p, Sec66p, and Sec72p (comprising the Sec63 complex), as well as Kar2p, in place of SRP to facilitate interaction of the full-length polypeptide with the translocon via the signal sequence (13, 14). S. cerevisiae contains a second Sec61-like complex involved in cotranslational translocation called the Ssh1p complex (containing Ssh1p, Sbh2p, and Sss1p; 15 and reviewed in 16).

Retrograde transport of misfolded proteins into the cytoplasm (also called dislocation) employs the Sec61 channel via interaction with the 19S proteasome regulatory particle (17). This interaction, which competes with the ribosome-Sec61p interaction, defines the Sec61 complex as the principal proteasome receptor in the ER membrane (17).

Sec61p contains 10 membrane spans separated by loops; the amino and carboxy termini and loops L2, L4, L6, and L8 face the cytoplasm (18). Structural studies of the conserved complex from Methanococcus jannaschii indicate that Sec61p forms two linked halves, transmembrane segments 1-5 and 6-10, that are clamped together by Sss1p; a side view of this structure reveals an hourglass shape with a hydrophilic conduit through the center (19). Transmembrane domain 2 (TM2) creates a channel 'plug' that is required to maintain a closed state (20). Interaction of Sec61p with Sss1p involves the region that includes TM6, TM7, and TM8 (9). Mutant analyses indicate that L6 and L8 are required for translocation of proteins that use the cotranslational pathway, with residues in L8 mediating normal affinity for 80S ribosomes but not required for proteasome binding (21, 22). TM3 and the fourth luminal loop are required for normal dislocation of a misfolded protein (23, 24).

Sec61p is widely conserved; the mammalian ortholog, Sec61alpha, and the archael ortholog SecY have been extensively studied and the mechanism of translocation is thought to be conserved among all species (reviewed in 25 and 26).

Last updated: 2007-10-03 Contact SGD

References cited on this page View Complete Literature Guide for SEC61
1) Romisch K  (1999) Surfing the Sec61 channel: bidirectional protein translocation across the ER membrane. J Cell Sci 112 ( Pt 23)():4185-91
2) Young BP, et al.  (2001) Sec63p and Kar2p are required for the translocation of SRP-dependent precursors into the yeast endoplasmic reticulum in vivo. EMBO J 20(1-2):262-71
3) Plath K, et al.  (2004) Interactions between Sec complex and prepro-alpha-factor during posttranslational protein transport into the endoplasmic reticulum. Mol Biol Cell 15(1):1-10
4) Trueman SF, et al.  (2012) A gating motif in the translocation channel sets the hydrophobicity threshold for signal sequence function. J Cell Biol 199(6):907-18
5) Tretter T, et al.  (2013) ERAD and protein import defects in a sec61 mutant lacking ER-lumenal loop 7. BMC Cell Biol 14(1):56
6) Deshaies RJ and Schekman R  (1987) A yeast mutant defective at an early stage in import of secretory protein precursors into the endoplasmic reticulum. J Cell Biol 105(2):633-45
7) Sommer T and Wolf DH  (1997) Endoplasmic reticulum degradation: reverse protein flow of no return. FASEB J 11(14):1227-33
8) Esnault Y, et al.  (1994) SSS1 encodes a stabilizing component of the Sec61 subcomplex of the yeast protein translocation apparatus. J Biol Chem 269(44):27478-85
9) Wilkinson BM, et al.  (1997) Molecular architecture of the ER translocase probed by chemical crosslinking of Sss1p to complementary fragments of Sec61p. EMBO J 16(15):4549-59
10) Feng D, et al.  (2007) The transmembrane domain is sufficient for Sbh1p function, its association with the Sec61 complex, and interaction with Rtn1p. J Biol Chem 282(42):30618-28
11) Ng DT, et al.  (1996) Signal sequences specify the targeting route to the endoplasmic reticulum membrane. J Cell Biol 134(2):269-78
12) Prinz A, et al.  (2000) Sec61p is the main ribosome receptor in the endoplasmic reticulum of Saccharomyces cerevisiae. Biol Chem 381(9-10):1025-9
13) Plath K, et al.  (1998) Signal sequence recognition in posttranslational protein transport across the yeast ER membrane. Cell 94(6):795-807
14) Panzner S, et al.  (1995) Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p. Cell 81(4):561-70
15) Finke K, et al.  (1996) A second trimeric complex containing homologs of the Sec61p complex functions in protein transport across the ER membrane of S. cerevisiae. EMBO J 15(7):1482-94
16) Robb A and Brown JD  (2001) Protein transport: two translocons are better than one. Mol Cell 8(3):484-6
17) Kalies KU, et al.  (2005) The protein translocation channel binds proteasomes to the endoplasmic reticulum membrane. EMBO J 24(13):2284-93
18) Wilkinson BM, et al.  (1996) Determination of the transmembrane topology of yeast Sec61p, an essential component of the endoplasmic reticulum translocation complex. J Biol Chem 271(41):25590-7
19) Van den Berg B, et al.  (2004) X-ray structure of a protein-conducting channel. Nature 427(6969):36-44
20) Li W, et al.  (2007) The plug domain of the SecY protein stabilizes the closed state of the translocation channel and maintains a membrane seal. Mol Cell 26(4):511-21
21) Cheng Z, et al.  (2005) Identification of cytoplasmic residues of Sec61p involved in ribosome binding and cotranslational translocation. J Cell Biol 168(1):67-77
22) Ng W, et al.  (2007) Characterization of the proteasome interaction with the Sec61 channel in the endoplasmic reticulum. J Cell Sci 120(Pt 4):682-91
23) Wilkinson BM, et al.  (2000) Distinct domains within yeast Sec61p involved in post-translational translocation and protein dislocation. J Biol Chem 275(1):521-9
24) Zhou M and Schekman R  (1999) The engagement of Sec61p in the ER dislocation process. Mol Cell 4(6):925-34
25) Jungnickel B, et al.  (1994) Protein translocation: common themes from bacteria to man. FEBS Lett 346(1):73-7
26) Osborne AR, et al.  (2005) Protein translocation by the Sec61/SecY channel. Annu Rev Cell Dev Biol 21():529-50