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Protein

Choline transporter-like protein 4

Gene

SLC44A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Choline transporter that plays a role in the choline-acetylcholine system and is required to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury (By similarity) (PubMed:23651124, PubMed:28013291). Also described as a thiamine pyrophosphate transporter in colon, may mediate the absorption of microbiota-generated thiamine pyrophosphate and contribute to host thiamine (vitamin B1) homeostasis (PubMed:24379411).By similarity3 Publications
Isoform 3: Has also thiamine pyrophosphate transporter activity.1 Publication

Kineticsi

  1. KM=0.17 µM for thiamine pyrophosphate1 Publication
  1. Vmax=18.19 pmol/min/mg enzyme1 Publication

GO - Molecular functioni

  • choline transmembrane transporter activity Source: UniProtKB
  • thiamine pyrophosphate transporter activity Source: UniProtKB

GO - Biological processi

  • acetylcholine biosynthetic process Source: UniProtKB
  • acetylcholine secretion Source: UniProtKB
  • choline transport Source: UniProtKB
  • neuromast hair cell development Source: UniProtKB
  • otolith formation Source: UniProtKB
  • phosphatidylcholine biosynthetic process Source: Reactome
  • positive regulation of cell growth Source: UniProtKB
  • thiamine pyrophosphate transport Source: UniProtKB
  • transmembrane transport Source: Reactome

Enzyme and pathway databases

ReactomeiR-HSA-1483191. Synthesis of PC.
R-HSA-425366. Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds.

Protein family/group databases

TCDBi2.A.92.1.7. the choline transporter-like (ctl) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Choline transporter-like protein 41 Publication
Alternative name(s):
Solute carrier family 44 member 4Imported
Thiamine pyrophosphate transporter 11 Publication
Short name:
hTPPT11 Publication
Gene namesi
Name:SLC44A4Imported
Synonyms:C6orf29, CTL41 Publication, NG22, TPPT11 Publication
ORF Names:UNQ441/PRO874
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:13941. SLC44A4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 34CytoplasmicSequence analysisAdd BLAST34
Transmembranei35 – 55HelicalSequence analysisAdd BLAST21
Topological domaini56 – 229ExtracellularSequence analysisAdd BLAST174
Transmembranei230 – 250HelicalSequence analysisAdd BLAST21
Topological domaini251 – 252CytoplasmicSequence analysis2
Transmembranei253 – 273HelicalSequence analysisAdd BLAST21
Topological domaini274 – 309ExtracellularSequence analysisAdd BLAST36
Transmembranei310 – 330HelicalSequence analysisAdd BLAST21
Topological domaini331 – 358CytoplasmicSequence analysisAdd BLAST28
Transmembranei359 – 379HelicalSequence analysisAdd BLAST21
Topological domaini380 – 455ExtracellularSequence analysisAdd BLAST76
Transmembranei456 – 476HelicalSequence analysisAdd BLAST21
Topological domaini477 – 501CytoplasmicSequence analysisAdd BLAST25
Transmembranei502 – 522HelicalSequence analysisAdd BLAST21
Topological domaini523 – 560ExtracellularSequence analysisAdd BLAST38
Transmembranei561 – 581HelicalSequence analysisAdd BLAST21
Topological domaini582 – 597CytoplasmicSequence analysisAdd BLAST16
Transmembranei598 – 618HelicalSequence analysisAdd BLAST21
Topological domaini619 – 638ExtracellularSequence analysisAdd BLAST20
Transmembranei639 – 659HelicalSequence analysisAdd BLAST21
Topological domaini660 – 710CytoplasmicSequence analysisAdd BLAST51

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

An interstitial deletion causing the fusion of exon 10 of CTL4 with the 3'-UTR of NEU has been detected in two patients affected by sialidosis.
Mutations in this gene have been associated with autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi29N → D: No effect on glycosylation. 1 Publication1
Mutagenesisi69N → D: Decreases gylcosylation levels. Decreases thiamine pyrophosphate uptake. 1 Publication1
Mutagenesisi155N → D: Decreases gylcosylation levels. Decreases thiamine pyrophosphate uptake. 1 Publication1
Mutagenesisi197N → D: Decreases gylcosylation levels. No effect on thiamine pyrophosphate uptake. 1 Publication1
Mutagenesisi298N → D: No effect on glycosylation. 1 Publication1
Mutagenesisi393N → D: Decreases gylcosylation levels. Decreases thiamine pyrophosphate uptake. 1 Publication1
Mutagenesisi409N → D: No effect on glycosylation. 1 Publication1
Mutagenesisi416N → D: Decreases gylcosylation levels. No effect on thiamine pyrophosphate uptake. 1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei308Breakpoint for translocation with NEU11

Organism-specific databases

DisGeNETi80736.
OpenTargetsiENSG00000204385.
PharmGKBiPA25930.

Chemistry databases

DrugBankiDB00122. Choline.

Polymorphism and mutation databases

BioMutaiCTL4.
DMDMi311033368.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001917231 – 710Choline transporter-like protein 4Add BLAST710

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi69N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi155N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi197N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi298N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi393N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi405N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi416N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

N-glycosylated; N-glycosylation of Asn-69, Asn-155 and Asn-393 is required for a proper thiamine pyrophosphate uptake.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ53GD3.
PaxDbiQ53GD3.
PeptideAtlasiQ53GD3.
PRIDEiQ53GD3.

PTM databases

iPTMnetiQ53GD3.
PhosphoSitePlusiQ53GD3.

Expressioni

Tissue specificityi

Highly expressed in colon, also detected in prostate, trachea and lung (PubMed:24379411). Isoform 3 is also expressed in colon but a lower levels (PubMed:24379411).1 Publication

Gene expression databases

BgeeiENSG00000204385.
ExpressionAtlasiQ53GD3. baseline and differential.
GenevisibleiQ53GD3. HS.

Organism-specific databases

HPAiHPA046977.
HPA054176.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000229729.

Structurei

3D structure databases

ProteinModelPortaliQ53GD3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1362. Eukaryota.
ENOG410XS0P. LUCA.
GeneTreeiENSGT00550000074521.
HOGENOMiHOG000007110.
HOVERGENiHBG062155.
InParanoidiQ53GD3.
KOiK15377.
OMAiNYYWLPI.
OrthoDBiEOG091G04CQ.
PhylomeDBiQ53GD3.
TreeFamiTF313325.

Family and domain databases

InterProiView protein in InterPro
IPR007603. Choline_transptr-like.
PANTHERiPTHR12385. PTHR12385. 1 hit.
PfamiView protein in Pfam
PF04515. Choline_transpo. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q53GD3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGGKQRDEDD EAYGKPVKYD PSFRGPIKNR SCTDVICCVL FLLFILGYIV
60 70 80 90 100
VGIVAWLYGD PRQVLYPRNS TGAYCGMGEN KDKPYLLYFN IFSCILSSNI
110 120 130 140 150
ISVAENGLQC PTPQVCVSSC PEDPWTVGKN EFSQTVGEVF YTKNRNFCLP
160 170 180 190 200
GVPWNMTVIT SLQQELCPSF LLPSAPALGR CFPWTNVTPP ALPGITNDTT
210 220 230 240 250
IQQGISGLID SLNARDISVK IFEDFAQSWY WILVALGVAL VLSLLFILLL
260 270 280 290 300
RLVAGPLVLV LILGVLGVLA YGIYYCWEEY RVLRDKGASI SQLGFTTNLS
310 320 330 340 350
AYQSVQETWL AALIVLAVLE AILLLMLIFL RQRIRIAIAL LKEASKAVGQ
360 370 380 390 400
MMSTMFYPLV TFVLLLICIA YWAMTALYLA TSGQPQYVLW ASNISSPGCE
410 420 430 440 450
KVPINTSCNP TAHLVNSSCP GLMCVFQGYS SKGLIQRSVF NLQIYGVLGL
460 470 480 490 500
FWTLNWVLAL GQCVLAGAFA SFYWAFHKPQ DIPTFPLISA FIRTLRYHTG
510 520 530 540 550
SLAFGALILT LVQIARVILE YIDHKLRGVQ NPVARCIMCC FKCCLWCLEK
560 570 580 590 600
FIKFLNRNAY IMIAIYGKNF CVSAKNAFML LMRNIVRVVV LDKVTDLLLF
610 620 630 640 650
FGKLLVVGGV GVLSFFFFSG RIPGLGKDFK SPHLNYYWLP IMTSILGAYV
660 670 680 690 700
IASGFFSVFG MCVDTLFLCF LEDLERNNGS LDRPYYMSKS LLKILGKKNE
710
APPDNKKRKK
Length:710
Mass (Da):79,254
Last modified:November 2, 2010 - v2
Checksum:i4DE5B45574C408AD
GO
Isoform 2 (identifier: Q53GD3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-422: Missing.

Note: No experimental confirmation available.
Show »
Length:288
Mass (Da):32,729
Checksum:i6A1ACC9313FB9A3F
GO
Isoform 3 (identifier: Q53GD3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.

Note: No experimental confirmation available.
Show »
Length:634
Mass (Da):70,762
Checksum:iABBB965DD14DB114
GO
Isoform 4 (identifier: Q53GD3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     115-156: Missing.

Show »
Length:668
Mass (Da):74,504
Checksum:iBC10838F8AC3C6DE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti117 – 118Missing in CAH56275 (PubMed:17974005).Curated2
Sequence conflicti144 – 145NR → SS in BAB55083 (PubMed:14702039).Curated2
Sequence conflicti379 – 386LATSGQPQ → PLPTQPATLG in AAD21813 (PubMed:14656967).Curated8
Sequence conflicti379 – 386LATSGQPQ → PLPTQPATLG in BAB63296 (Ref. 5) Curated8
Sequence conflicti636Missing in AAH14659 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0234066R → L Polymorphism; no effect on thiamine pyrophosphate transporter activity. 1 PublicationCorresponds to variant dbSNP:rs2075798Ensembl.1
Natural variantiVAR_047020123D → V Polymorphism; no effect on thiamine pyrophosphate transporter activity. 1 PublicationCorresponds to variant dbSNP:rs12661281Ensembl.1
Natural variantiVAR_047021128G → E1 PublicationCorresponds to variant dbSNP:rs17856465Ensembl.1
Natural variantiVAR_078848156M → V Probable disease-associated mutation found in patients with autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss; decreases choline transmembrane transporter activity. 1 Publication1
Natural variantiVAR_023407187V → I9 PublicationsCorresponds to variant dbSNP:rs2242665Ensembl.1
Natural variantiVAR_023408326M → V8 PublicationsCorresponds to variant dbSNP:rs644827Ensembl.1
Natural variantiVAR_036210347A → T in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_078849397P → S Polymorphism; no effect on thiamine pyrophosphate transporter activity. 1 Publication1
Natural variantiVAR_036211411T → M in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs563426936Ensembl.1
Natural variantiVAR_023409493R → C. Corresponds to variant dbSNP:rs6915800Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0309981 – 422Missing in isoform 2. 1 PublicationAdd BLAST422
Alternative sequenceiVSP_0462361 – 76Missing in isoform 3. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_046821115 – 156Missing in isoform 4. 1 PublicationAdd BLAST42

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027397 mRNA. Translation: BAB55083.1.
AK300550 mRNA. Translation: BAG62256.1.
AK301596 mRNA. Translation: BAG63084.1.
AY358457 mRNA. Translation: AAQ88822.1.
AK222998 mRNA. Translation: BAD96718.1.
AF134726 Genomic DNA. Translation: AAD21813.1.
BA000025 Genomic DNA. Translation: BAB63296.1.
AL662834 Genomic DNA. Translation: CAI17744.1.
AL671762 Genomic DNA. Translation: CAI18223.2.
AL844853 Genomic DNA. Translation: CAI41851.1.
BX005460 Genomic DNA. Translation: CAM26148.1.
CR936237 Genomic DNA. Translation: CAQ09154.1.
CR759784 Genomic DNA. Translation: CAQ09306.1.
CR388202 Genomic DNA. Translation: CAQ09513.1.
CH471081 Genomic DNA. Translation: EAX03538.1.
BC014659 mRNA. Translation: AAH14659.1.
AF466766 mRNA. Translation: AAL75992.1.
AL833009 mRNA. Translation: CAH56275.1.
CCDSiCCDS4724.2. [Q53GD3-1]
CCDS54989.1. [Q53GD3-3]
CCDS54990.1. [Q53GD3-4]
RefSeqiNP_001171515.1. NM_001178044.1. [Q53GD3-4]
NP_001171516.1. NM_001178045.1. [Q53GD3-3]
NP_079533.2. NM_025257.2. [Q53GD3-1]
UniGeneiHs.335355.

Genome annotation databases

EnsembliENST00000229729; ENSP00000229729; ENSG00000204385. [Q53GD3-1]
ENST00000375562; ENSP00000364712; ENSG00000204385. [Q53GD3-4]
ENST00000383379; ENSP00000372870; ENSG00000206378. [Q53GD3-1]
ENST00000415517; ENSP00000414120; ENSG00000229077.
ENST00000417894; ENSP00000389244; ENSG00000235336.
ENST00000425238; ENSP00000399161; ENSG00000228263. [Q53GD3-1]
ENST00000442152; ENSP00000398852; ENSG00000232180.
ENST00000453831; ENSP00000393939; ENSG00000231479. [Q53GD3-1]
ENST00000544672; ENSP00000444109; ENSG00000204385. [Q53GD3-3]
ENST00000546461; ENSP00000449039; ENSG00000231479. [Q53GD3-3]
ENST00000547493; ENSP00000449232; ENSG00000229077.
ENST00000547684; ENSP00000449180; ENSG00000206378. [Q53GD3-3]
ENST00000548188; ENSP00000447560; ENSG00000228263. [Q53GD3-3]
ENST00000549663; ENSP00000449642; ENSG00000228263. [Q53GD3-4]
ENST00000549677; ENSP00000449518; ENSG00000206378. [Q53GD3-4]
ENST00000550401; ENSP00000448474; ENSG00000235336.
ENST00000551168; ENSP00000448088; ENSG00000231479. [Q53GD3-4]
ENST00000553121; ENSP00000447704; ENSG00000232180.
GeneIDi80736.
KEGGihsa:80736.
UCSCiuc010jti.4. human. [Q53GD3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCTL4_HUMAN
AccessioniPrimary (citable) accession number: Q53GD3
Secondary accession number(s): A2BED3
, B0UXX8, B0UZY8, B4DU94, B4DWM2, E9PEK7, Q5JP84, Q5JQ93, Q658S8, Q6UX89, Q8TEW4, Q96C58, Q96K59, Q9Y332
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: November 2, 2010
Last modified: August 30, 2017
This is version 118 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families