O35899 (SC6A4_CAVPO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium-dependent serotonin transporter

Alternative name(s):
5HT transporter
Short name=5HTT
Solute carrier family 6 member 4

Gene names

Name:

SLC6A4

Organism

Cavia porcellus (Guinea pig) [Reference proteome]

Taxonomic identifier

10141 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Hystricognathi › Caviidae › Cavia

Protein attributes

Sequence length	630 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner By similarity.
Subunit structure	Monomer or homooligomer By similarity. Interacts with TGFB1I1. Interacts (via C-terminus) with VIM. Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly. Interacts with RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly. Interacts (via sialylated form) with MYH9. Interacts with SEC23A, SEC24C and INADL. Interacts with NOS1; the interaction may diminish the cell surface localization of SERT in the brain and, correspondingly, reduce serotonin reuptake. Interacts with filamentous actin and STX1A By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Endomembrane system By similarity; Multi-pass membrane protein. Endosome membrane; Multi-pass membrane protein By similarity. Note: Translocates from intracellular locations to the plasma membrane. Density of transporter molecules on the plasma membrane is itself regulated by serotonin By similarity.
Post-translational modification	Glycosylated; modification with sialylated N-glycans is a requirement for transporters to associate with each other and to function as homooligomeric forms By similarity. Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity By similarity. Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation By similarity.
Miscellaneous	This protein is the target of psychomotor stimulants such as amphetamines or cocaine.
Sequence similarities	Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily. [View classification]

Ontologies

Keywords
Biological process	Neurotransmitter transport Symport Transport
Cellular component	Cell membrane Endosome Membrane
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain morphogenesis Inferred from electronic annotation. Source: Compara cellular response to organic substance Inferred from electronic annotation. Source: Compara negative regulation of organ growth Inferred from electronic annotation. Source: Compara positive regulation of cell cycle Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara protein oligomerization Inferred from sequence or structural similarity. Source: UniProtKB response to toxin Inferred from electronic annotation. Source: Compara serotonin uptake Inferred from sequence or structural similarity. Source: UniProtKB social behavior Inferred from electronic annotation. Source: Compara thalamus development Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara endomembrane system Inferred from sequence or structural similarity. Source: UniProtKB endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from electronic annotation. Source: InterPro membrane raft Inferred from electronic annotation. Source: Compara plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	actin filament binding Inferred from sequence or structural similarity. Source: UniProtKB serotonin transmembrane transporter activity Inferred from sequence or structural similarity. Source: UniProtKB serotonin:sodium symporter activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 630	630	Sodium-dependent serotonin transporter		PRO_0000214756
Regions
	Topological domain	1 – 87	87	Cytoplasmic Potential
	Transmembrane	88 – 108	21	Helical; Name=1; Potential
	Transmembrane	116 – 135	20	Helical; Name=2; Potential
	Transmembrane	160 – 180	21	Helical; Name=3; Potential
	Topological domain	181 – 252	72	Extracellular Potential
	Transmembrane	253 – 271	19	Helical; Name=4; Potential
	Transmembrane	280 – 297	18	Helical; Name=5; Potential
	Transmembrane	333 – 350	18	Helical; Name=6; Potential
	Transmembrane	362 – 383	22	Helical; Name=7; Potential
	Transmembrane	417 – 436	20	Helical; Name=8; Potential
	Transmembrane	464 – 482	19	Helical; Name=9; Potential
	Transmembrane	498 – 518	21	Helical; Name=10; Potential
	Transmembrane	539 – 558	20	Helical; Name=11; Potential
	Transmembrane	577 – 595	19	Helical; Name=12; Potential
	Topological domain	596 – 630	35	Cytoplasmic Potential
	Region	611 – 630	20	Required for serotonin uptake activity By similarity
	Region	616 – 624	9	Interaction with RAB4A By similarity
Amino acid modifications
	Modified residue	47	1	Phosphotyrosine By similarity
	Modified residue	142	1	Phosphotyrosine By similarity
	Modified residue	276	1	Phosphothreonine By similarity
	Modified residue	611	1	Phosphoserine By similarity
	Modified residue	613	1	Phosphothreonine By similarity
	Modified residue	616	1	Phosphothreonine By similarity
	Glycosylation	208	1	N-linked (GlcNAc...) Potential
	Glycosylation	217	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	O35899 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: EE2A717DD9926D2F	FASTA	630	70,114
	10 20 30 40 50 60 METTALNSQK APSVCKDRED CQENSILQKS GPTSAGGVES GQIFNGYSSV PSTGMGDDAE 70 80 90 100 110 120 HSVPTATTTL VAEVHHGERE TWGKKVDFLL SVIGYAVDLG NIWRFPYVCY QNGGGAFLLP 130 140 150 160 170 180 YIIMAIFGGI PLFYMELALG QYHRNGCISI WRKICPIFKG IGYTICIIAF YIASYYNTII 190 200 210 220 230 240 AWALYYLISS FTDRLPWTSC RNSWNTANCT NYFSEDNITW TLHSTSPAEE FYIRHILQIH 250 260 270 280 290 300 RSKGLQDVGG VSWQLTLCIM LIFTIIYFSI WKGVKTSGKV VWVTATFPYI VLSVLLVRGA 310 320 330 340 350 360 TLPGAWKGVL FYLKPNWQKL LETGVWIDAA AQIFFSLGPG FGVLLAFASY NKFNNNCYQD 370 380 390 400 410 420 ALVTSAVNCM TSFVSGFVIF TVLGYMAEMR SEDVSEVAKD AGPSLLFITY AEAIANMPAS 430 440 450 460 470 480 TFFAIIFFLM LITLGLDSTF AGLEGVITAV LDEFPHIWAK HREWFVLAVV ITCFFGSLTT 490 500 510 520 530 540 LTFGGAYVVK LLEEYATGPA VLTVVFIEAI AVSWFYGVTQ FCSDVKEMLG FSPGWFWRIC 550 560 570 580 590 600 WVAVSPVFLL FIICSFLMSP PQLRLFQYSY PHWSVILGYC IGTSSVICIP TYITYRLVTT 610 620 630 PGTLKERIIK SITPETPTEI PCGDICLNAV

References

[1]	"Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract." Wade P.R., Chen J., Jaffe B., Kassem I.S., Blakely R.D., Gershon M.D. J. Neurosci. 16:2352-2364(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Intestinal mucosa.
[2]	Chen J., Wade P.R., Rothman T.P., Gershon M.D. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Intestinal mucosa.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U84498 mRNA. Translation: AAB82737.1.
RefSeq	NP_001166489.1. NM_001173018.1.
3D structure databases
ProteinModelPortal	O35899.
ModBase	Search...
Protein-protein interaction databases
STRING	10141.ENSCPOP00000009515.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100135619.
Organism-specific databases
CTD	6532.
Phylogenomic databases
eggNOG	COG0733.
HOGENOM	HOG000116406.
HOVERGEN	HBG071421.
InParanoid	O35899.
OrthoDB	EOG447FSX.
Family and domain databases
InterPro	IPR000175. Na/ntran_symport. IPR013086. Na/ntran_symport_serotonin_N. [Graphical view]
PANTHER	PTHR11616. PTHR11616. 1 hit.
Pfam	PF03491. 5HT_transporter. 1 hit. PF00209. SNF. 1 hit. [Graphical view]
PRINTS	PR01203. 5HTTRANSPORT. PR00176. NANEUSMPORT.
PROSITE	PS00610. NA_NEUROTRAN_SYMP_1. 1 hit. PS00754. NA_NEUROTRAN_SYMP_2. 1 hit. PS50267. NA_NEUROTRAN_SYMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O35899.

Entry information

Entry name

SC6A4_CAVPO

Accession

Primary (citable) accession number: O35899

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program