5-HTT (Serotonin Transporter/SERT)

The serotonin transport protein 5-HTT (another name for serotonin is 5-hydroxy- tryptamine) has been implicated in depression and some other human mental disorders. Serotonin is an important neurotransmitter -- one of the short-range signaling molecules with which one neuron communicates with another. Serotonin seems to be involved in reducing the level of stress hormones in stress-provoking situations. The job of 5-HTT is to transport serotonin back into the cell after its message has been delivered. (This is sort of like hanging up the telephone, so that somebody else can call you.) 5-HTT also appears to be a target of stimulants like "ecstasy" and cocaine, and of antidepressants. The protein is a large membrane protein with 12 transmembrane domains.

In a long-range study that followed a single group of people from the age of 3 to 26 years, investigators observed that people who had inherited one of two forms of the 5-HTT gene seemed to be more susceptible to depression following stressful conditions like changes in their relationships, jobs, or financial situations. However, the difference is not in the part of the gene that encodes the structure of the protein, which is the same in both forms of the gene. The difference lies in the structure of the promoter -- the regulatory region that turns the gene on and off. One promoter region is longer than the other. The gene is less active in individuals with shorter promoter.

The 5-HTT gene is located on the long arm of human chromosome 17 (17q11.2). The short allele is found in about half of Caucasians. Even a single copy of the shortened 5-HTT gene seems to make its carriers more likely to experience stress-induced depression. The short form of the disease does not directly cause depression, but lower levels of the transporter may lead to less efficient management of stress-related hormone levels. The possible role of the gene in other disorders, like alcoholism, anxiety, obsessive-compulsive disorder and sudden-infant-death-syndrome has also been studied.

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The 5-Hydroxytryptamine Transporter
(5-HTT)

( ) = cytoplasmic domain
[ ] = Transmembrane domain
{ } = extracellular domain

(METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQI
SNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQGERETWGKKVD)
[FLLSVIGYAVDLGNVWRFPYI]
CYQNGGG
[AFLLPYTIMAIFGGIPLFYM]
ELALGQYHRNGCISIWRKICPIFK
[GIGYAICIIAFYIASYYNTIM]
{AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSED
NITWTLHSTSPAEEFYTRHVLQIHRSKGLQDLGGIS}
[WQLALCIMLIFTVIYFSIW]
KGVKTSGK
[VVWVTATFPYIILSVLLV]
RGATLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQ
[IFFSLGPGFGVLLAFASY]
NKFNNNCYQDA
[LVTSVVNCMTSFVSGFVIFTVL]
GYMAEMRNEDVSEVAKDAGPSLLFITYAEAIAN
[MPASTFFAIIFFLMLITLGL]
DSTFAGLEGVITAVLDEFPHVWAKRRE
[RFVLAVVITCFFGSLVTLT]
FGGAYVVKLLEEYAT
[GPAVLTVALIEAVAVSWFYGI]
TQFCRDVKEMLGFSPGWFWR
[ICWVAISPLFLLFIICSFLM]
SPPQLRLFQYNYPYWSII
[LGYCIGTSSFICIPTYIAY]
(RLIITPGTFKERIIKSITPETPTEIPCGDIRLNAV)

LINK TO THE MUSIC

Notes on the Music:

This piece has been set as a pensive meditation. Like the other two transmembrane proteins (the PTC receptor and the Mosquito odorant receptor) in this set of pieces, 5-HTT is played with three overlapping voices representing the low (bass pizzicato), midrange (muted horns) and high (oboe) solubility amino acids of the protein. One additional voice (strings) identifies the 12 transmembrane domains of the protein. The piece plays through the sequence once, then ends quietly.

This piece was composed using ArtWonk algorithmic music software from Algorithmic Arts.

References: