PAM18/YLR008C Summary Help

Standard Name PAM18 1
Systematic Name YLR008C
Alias TIM14 2
Feature Type ORF, Verified
Description Subunit of the import motor (PAM complex); the PAM complex is a component of the Translocase of the Inner Mitochondrial membrane (TIM23 complex); essential J-protein cochaperone that stimulates Ssc1p ATPase activity to drive import; inhibited by Pam16p (1, 2, 3, 4 and see Summary Paragraph)
Name Description Presequence translocase-Associated Motor 1
Chromosomal Location
ChrXII:166083 to 165577 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All PAM18 GO evidence and references
  View Computational GO annotations for PAM18
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
reduction of function
Large-scale survey
reduction of function
120 total interaction(s) for 63 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 41
  • Biochemical Activity: 3
  • Co-crystal Structure: 1
  • Co-purification: 5
  • Reconstituted Complex: 9

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 2
  • Negative Genetic: 40
  • Phenotypic Enhancement: 2
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 7

Expression Summary
Length (a.a.) 168
Molecular Weight (Da) 17,910
Isoelectric Point (pI) 10.31
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:166083 to 165577 | 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..507 166083..165577 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 SGDIDS000003998

Hsp40/DnaJ is a family of proteins, established by bacterial DnaJ, that regulates Hsp70 chaperone activity. Hsp40s stimulate the intrinsically weak ATPase activity of Hsp70 proteins and facilitate Hsp70 interaction with polypeptide substrates. Hsp70 family members often have multiple Hsp40 partners, and these specific pairings govern Hsp70 chaperone involvement in particular processes (reviewed in 5, 6, and 7). All Hsp40s contain a highly conserved 75-amino acid J domain, which interacts with the ATPase domain of Hsp70 to stimulate ATP hydrolysis. However, there are also other conserved structural domains, and based on the presence or absence of these regions, the Hsp40 family can be divided into three subtypes: type I, type II and type III (a comprehensive overview of the structural features of the different HSP40 subtypes can be found in 7). Sequence analysis of the S. cerevisiae genome has revealed 22 proteins in the Hsp40/DnaJ family: YDJ1, XDJ1, APJ1, SIS1, DJP1, ZUO1, SWA2, JJJ1, JJJ2, JJJ3, CAJ1, CWC23, MDJ1, MDJ2, PAM18, JAC1, JID1, SCJ1, HLJ1, JEM1, SEC63, and ERJ5 (7).

About mitochondrial import

While the mitochondrial genome encodes a handful of proteins, most of the hundreds of proteins that reside in the mitochondrion are encoded by nuclear genes, translated in the cytoplasm, and imported into mitochondria via a series of complex molecular machines (see 8, 9 for review). Many of the proteins imported into mitochondria are involved in respiration, which is not an essential process: S. cerevisiae is able to carry out either fermentative growth on carbon sources such as glucose, or respiratory growth on nonfermentable carbon sources such as glycerol and ethanol. However, since maintenance of the mitochondrial compartment is essential to life, mutations that completely disrupt mitochondrial import are lethal.

About the TIM23 complex

The Translocase of the Inner Mitochondrial membrane (TIM23 complex) receives proteins from the Translocase of the Outer Mitochondrial membrane (TOM complex) and either directs them into the mitochondrial matrix or facilitates their integration into the mitochondrial inner membrane (reviewed in 10, 9, 11). The membrane-embedded core of the complex is composed of three essential proteins: Tim23p, Tim17p, and Tim50p. Tim23p and Tim17p, which share sequence similarity, comprise the twin-pore structure through which precursor proteins translocate. Tim23p alone has the ability to form a voltage-sensitive channel (12), but Tim17p is required in vivo for maintenance of the twin-pore architecture and for normal function of the pore (13). Tim17p also has a role in sorting incoming proteins to the mitochondrial matrix or the inner membrane (14). Tim50p interacts with precursor proteins and with Tim23p to guide precursors from the TOM complex to the TIM23 complex (15, 16). Two additional non-essential components, Tim21p and Pam17p, interact with the core of the TIM23 complex and may modulate its activity (14, 17, 18).

Proteins destined for the mitochondrial matrix require the action of a sub-complex of the TIM23 complex, known as the import motor or presequence translocase-associated motor (PAM) complex. Its catalytic component is Ssc1p, a member of the heat shock 70 protein family commonly referred to as mtHsp70, which undergoes cycles of binding and release of the precursor, hydrolyzing ATP and changing conformation in the process. The nucleotide release factor Mge1p promotes this cycle by facilitating the dissociation of ADP from Ssc1p (19, 20). Other components include Tim44p, an essential subunit that mediates the association of the core TIM23 complex with the PAM complex (21, 18); Pam18p (Tim14p), a J-protein cochaperone that stimulates the ATPase activity of Ssc1p; and Pam16p (Tim16p), a J-like protein that binds to Pam18p and regulates its activity (4). Pam17p mediates the association between Pam16p and Pam18p (22). Once imported proteins reach the mitochondrial matrix, their correct folding is facilitated by a soluble complex consisting of Ssc1p and its cochaperones Mdj1p and Mge1p (23).

A subset of proteins destined for insertion into the mitochondrial inner membrane is translocated via the TIM23 complex but then inserted laterally into the inner membrane rather than entering the mitochondrial matrix. This mechanism is currently not understood in detail. The TIM23 complex adopts different conformations during the two kinds of import, but it is unclear whether this inner membrane import is accomplished by the core complex alone (Tim23p, Tim17p, and Tim50p), or by the entire TIM23 complex including the import motor subunits (10, 17).

About PAM16, PAM17, and PAM18

Pam16p and Pam18p are both related to J-proteins, which act as cochaperones for chaperone proteins belonging to the Hsp70 family. Pam18p is considered a J-protein because it has all of the characteristic sequence elements, while Pam16p is "J-like" because it lacks the conserved HPD motif (24, 25, 1). Both proteins are constituents of the import motor (PAM) complex, and interact with each other to form a heterodimer (26, 4). Pam18p stimulates the ATPase activity of Ssc1p, which is the catalytic component of the import motor, while Pam16p inhibits the stimulatory activity of Pam18p (27, 26).

The localization and role of Pam17p are currently unclear. It is a conserved protein that was identified as a component of the import motor complex (22), but other studies have detected interactions between Pam17p and components of the TIM23 core complex, and not between Pam17p and the import motor subunits (17). It has been proposed that Pam17p mediates association of the Pam16p-Pam18p heterodimer with the TIM23 complex, and alternatively that its role is to modulate the function of the core complex by affecting its conformation (17, 22).

In keeping with their proposed roles in the import motor, mutations in all three of the PAM genes affect the ability of the TIM23 complex to import proteins into the mitochondrial matrix, but not its ability to insert proteins into the inner membrane (24, 25, 28, 22). PAM16 and PAM18 are essential genes (26, 4), while a pam17 null mutant is viable but displays a slow respiratory growth phenotype (22).

Last updated: 2006-12-19 Contact SGD

References cited on this page View Complete Literature Guide for PAM18
1) Truscott KN, et al.  (2003) A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria. J Cell Biol 163(4):707-13
2) Mokranjac D, et al.  (2003) Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria. EMBO J 22(19):4945-56
3) D'Silva PD, et al.  (2003) J protein cochaperone of the mitochondrial inner membrane required for protein import into the mitochondrial matrix. Proc Natl Acad Sci U S A 100(24):13839-44
4) Mokranjac D, et al.  (2006) Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor. EMBO J 25(19):4675-85
5) Qiu XB, et al.  (2006) The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci 63(22):2560-2570
6) Cyr DM, et al.  (1994) DnaJ-like proteins: molecular chaperones and specific regulators of Hsp70. Trends Biochem Sci 19(4):176-81
7) Walsh P, et al.  (2004) The J-protein family: modulating protein assembly, disassembly and translocation. EMBO Rep 5(6):567-71
8) Neupert W and Herrmann JM  (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723-49
9) Mokranjac D and Neupert W  (2009) Thirty years of protein translocation into mitochondria: unexpectedly complex and still puzzling. Biochim Biophys Acta 1793(1):33-41
10) Wagner K, et al.  (2009) Protein transport machineries for precursor translocation across the inner mitochondrial membrane. Biochim Biophys Acta 1793(1):52-9
11) Bolender N, et al.  (2008) Multiple pathways for sorting mitochondrial precursor proteins. EMBO Rep 9(1):42-9
12) Truscott KN, et al.  (2001) A presequence- and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23. Nat Struct Biol 8(12):1074-82
13) Martinez-Caballero S, et al.  (2007) Tim17p regulates the twin pore structure and voltage gating of the mitochondrial protein import complex TIM23. J Biol Chem 282(6):3584-93
14) Chacinska A, et al.  (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120(6):817-29
15) Mokranjac D, et al.  (2009) Role of Tim50 in the transfer of precursor proteins from the outer to the inner membrane of mitochondria. Mol Biol Cell 20(5):1400-7
16) Gevorkyan-Airapetov L, et al.  (2009) Interaction of Tim23 with Tim50 Is Essential for Protein Translocation by the Mitochondrial TIM23 Complex. J Biol Chem 284(8):4865-72
17) Popov-Celeketic D, et al.  (2008) Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria. EMBO J 27(10):1469-80
18) Hutu DP, et al.  (2008) Mitochondrial protein import motor: differential role of tim44 in the recruitment of pam17 and j-complex to the presequence translocase. Mol Biol Cell 19(6):2642-9
19) Schneider HC, et al.  (1996) The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import. EMBO J 15(21):5796-803
20) Liu Q, et al.  (2003) Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science 300(5616):139-41
21) D'Silva P, et al.  (2004) Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane. Nat Struct Mol Biol 11(11):1084-91
22) Van Der Laan M, et al.  (2005) Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor. Mol Cell Biol 25(17):7449-58
23) Kubo Y, et al.  (1999) Two distinct mechanisms operate in the reactivation of heat-denatured proteins by the mitochondrial Hsp70/Mdj1p/Yge1p chaperone system. J Mol Biol 286(2):447-64
24) Frazier AE, et al.  (2004) Pam16 has an essential role in the mitochondrial protein import motor. Nat Struct Mol Biol 11(3):226-33
25) Kozany C, et al.  (2004) The J domain-related cochaperone Tim16 is a constituent of the mitochondrial TIM23 preprotein translocase. Nat Struct Mol Biol 11(3):234-41
26) D'Silva PR, et al.  (2005) Role of Pam16's degenerate J domain in protein import across the mitochondrial inner membrane. Proc Natl Acad Sci U S A 102(35):12419-24
27) Li Y, et al.  (2004) The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18. J Biol Chem 279(36):38047-54
28) Mokranjac D, et al.  (2007) Association of the Tim14.Tim16 subcomplex with the TIM23 translocase is crucial for function of the mitochondrial protein import motor. J Biol Chem 282(25):18037-45