Sandwalk: Human Genes Involved in the Signal Hypothesis Pathway

Thursday, September 27, 2007

Human Genes Involved in the Signal Hypothesis Pathway

The Signal Hypothesis describes the mechanism whereby proteins that are destined to cross a membrane are synthesized. One of the key components of this pathway is Signal Recognition Particle or SRP. The structure of SRP is shown below from a paper by Maity and Weeks (2007)

Most of SRP is composed of an RNA molecule called 7SL RNA. It is shown as red and yellow helices in the bottom figure. The secondary structure is depicted in the top right-hand corner of the figure. There are six different proteins in SRP. All of them are bound to the RNA in one way or another. The six proteins are SRP9, SRP14, SRP54, SRP68, and SRP72. The numbers refer to the molecular mass in kilodaltons.

There are three genes for 7SL RNA. They are all found on chromosome 14 (above). Two of them are closely linked and the third one is somewhat farther away.

RN7SL1: Entrez Gene 6029. Chromosome 14q22.1
RN7SL2: Entrez Gene 378706. Chromosome 14
RN7SL3: Entrez Gene 378707. Chromosome 14

The genes for the protein components are:

SRP9: Entrez Gene 6726. Chromosome 1q42.12
SRP14: Entreez Gene 6727. Chromosome 15q22
SRP54: Entrez Gene 6729. Chromosome 14q13.2
SRP68: Entrez Gene 6730. Chromosome 17q25.1
SRP72: Entrez Gene 6731. Chromosome 4q11

The three membrane components are the SRP receptor, the translocon (formerly known as ribophorin), and the signal peptidase. There are two subunits in the SRP receptor, α (docking protein) and β. The human genome contains a single gene for SRP receptor α subunit called SSPR (SSPRα). The genome has two separate genes for the β subunit called SSRB and SSR2.

SSPR (Docking protein) (SSRα): Entrez Gene 6734. Chromosome 11q24.3
SRPRB: Entrez Gene 58447. Chromosome 3q22.1
SSR2: Entrez Gene 6746. Chromosome 1q21-q23

The translocon is composed of three proteins; SEC61, SEC62, and SEC63. The SEC61 protein has three subunits; α (genes SEC61A1 and SEC61A2), β (gene SEC61B), and γ (gene SEC61G).

SEC61A1: Entrez Gene 29927. Chromosome 3q21.3
SEC61A2: Entrez Gene 55176. Chromosome 10p14
SEC61B: Entrez Gene 10952. Chromosome 9q22.32-q31.3
SEC61G: Entrez Gene 23480. Chromosome 7p11.2
TLOC1 (SEC62): Entrez Gene 7095. Chromosome 3q26.2
SEC63: Entrez Gene 11231. Chromosome 6q21

Finally, there are three subunits of the signal peptidase complex encoded by SPCS1 (signal peptidase complex, subunit 1), SPCS2, and SPCS3.

SPCS1: Entrez Gene 28972. Chromosome 3q22.1
SPCS2: Entrez Gene 9789. Chromosome 1q21-q23
SPCS3: Entrez Gene 60559. Chromosome 11q24.3

There are 20 genes required for effective translocation of proteins with a signal sequence (only the SRP are shown on the chromosome maps). Additional proteins are required to assist in the translocation (chaperones) and in glycosylation of the protein once it enters the lumen of the endoplasmic reticulum.

Maity, T.S. and Weeks, K.M. (2007) A threefold RNA-protein interface in the signal recognition particle gates native complex assembly. J. Mol. Biol. 369:512-24 [PubMed]

2 comments :

Anonymous said...: Please, correct the citation.; Monday, October 08, 2007 2:44:00 PM
Larry Moran said...: Done. Thanks.; Monday, October 08, 2007 5:37:00 PM

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The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)

Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)

Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Peter Atkins

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The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake. Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory. Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change. Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance. Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change. Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat. Stephen Jay Gould (1999) p.84

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My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is True

I once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000

It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

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There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner

An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins

Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod

The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.

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Thursday, September 27, 2007

Human Genes Involved in the Signal Hypothesis Pathway

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