Q6PEM8 (PCFT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proton-coupled folate transporter

Alternative name(s):
Heme carrier protein 1
PCFT/HCP1
Solute carrier family 46 member 1

Gene names

Name:	Slc46a1
Synonyms:	D11Ertd18e, Hcp1, Pcft

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	459 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. The iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron. Shows a higher affinity for folate than heme. Ref.5
Subcellular location	Apical cell membrane; Multi-pass membrane protein. Cytoplasm. Note: Localizes to the apical membrane of intestinal cells in iron-deficient cells, while it resides in internal cellular compartments in iron-replete cells. Ref.5
Tissue specificity	Highly expressed in duodenum, especially in duodenal mucosa, the main site of intestinal heme absorption. Weakly expressed in the kidney. Not expressed in duodenum before weaning or in placenta. Weakly or not expressed in brain, heart, lung, skeletal muscle, testis and neonatal liver. Ref.5
Induction	Up-regulated in response to hypoxia, it is however unclear whether such up-regulation is direct or not. Not induced in the duodenum of iron-deficient mice. Ref.5
Sequence similarities	Belongs to the major facilitator superfamily. SLC46A family.
Sequence caution	The sequence BAD90126.1 differs from that shown. Reason: Erroneous initiation. The sequence CAI25543.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Cytoplasm Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Folate-binding
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	transmembrane transport Inferred from electronic annotation. Source: InterPro
Cellular_component	apical plasma membrane Inferred from direct assay Ref.5. Source: UniProtKB cytoplasm Inferred from direct assay Ref.5. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	folic acid binding Inferred from electronic annotation. Source: UniProtKB-KW folic acid transporter activity Inferred from sequence or structural similarity. Source: UniProtKB heme transporter activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 459	459	Proton-coupled folate transporter		PRO_0000084852
Regions
	Transmembrane	28 – 48	21	Helical; Potential
	Transmembrane	87 – 107	21	Helical; Potential
	Transmembrane	115 – 135	21	Helical; Potential
	Transmembrane	149 – 169	21	Helical; Potential
	Transmembrane	183 – 203	21	Helical; Potential
	Transmembrane	211 – 231	21	Helical; Potential
	Transmembrane	267 – 287	21	Helical; Potential
	Transmembrane	303 – 325	23	Helical; Potential
	Transmembrane	337 – 357	21	Helical; Potential
	Transmembrane	390 – 410	21	Helical; Potential
	Transmembrane	423 – 443	21	Helical; Potential
Amino acid modifications
	Modified residue	458	1	Phosphoserine Ref.6
	Glycosylation	58	1	N-linked (GlcNAc...) Ref.7
Experimental info
	Sequence conflict	402	1	A → V in BAB22685. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q6PEM8 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: A251124B3B9846AF	FASTA	459	50,089
	10 20 30 40 50 60 MEGRVSSVGS PHSFLNAPVL FRGPVEPLVF LANFALVLQG PLTTQYLWHR FSTELGYNGT 70 80 90 100 110 120 RHRENCGNQS ADPLMKEVET LTSHWTLYMN VGGFLVGLFW STLLGAWSDR VGRRPLLVLA 130 140 150 160 170 180 SLGLLLQAVV SIFVVQLELH VGFFVLGRAL CALLGDFNGL LAASFASVAD VSSNHSRTFR 190 200 210 220 230 240 MALLEACIGV AGTLASLLGG HWLRAQGYAN PFWLALALLI VMALYAAFCF GETVKEPKST 250 260 270 280 290 300 RLFTLRHHRS IARLYVVPAP EKSRMHLALY SLAIFVVVTV HFGAQDILTL YELSAPLCWD 310 320 330 340 350 360 SKLIGYGSAA QHLPYLTSLL GLRLLQFCLA DTWVAEIGLA FNILGMVVFA FATITPLMFT 370 380 390 400 410 420 GYGLLFLSLV TTPVIRAKLS KLVSESEQGA LFSAVACVNS LAMLMASGIF NSIYPATLNF 430 440 450 MKGFPFLLGA GLLFIPAILI GVLEKVNPHP EFQQFPQSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD.
[2]	Okazaki N., Kikuno F.R., Nagase T., Ohara O., Koga H. Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Colon and Liver.
[5]	"Identification of an intestinal heme transporter." Shayeghi M., Latunde-Dada G.O., Oakhill J.S., Laftah A.H., Takeuchi K., Halliday N., Khan Y., Warley A., McCann F.E., Hider R.C., Frazer D.M., Anderson G.J., Vulpe C.D., Simpson R.J., McKie A.T. Cell 122:789-801(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, MASS SPECTROMETRY. Tissue: Macrophage.
[7]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-58, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK003278 mRNA. Translation: BAB22685.1. AK170505 mRNA. Translation: BAE41843.1. AK220201 mRNA. Translation: BAD90126.1. Different initiation. AL591177 Genomic DNA. Translation: CAI25542.1. AL591177 Genomic DNA. Translation: CAI25543.1. Sequence problems. BC024522 mRNA. Translation: AAH24522.1. BC057976 mRNA. Translation: AAH57976.1.
IPI	IPI00134013.
RefSeq	NP_081016.2. NM_026740.2.
UniGene	Mm.131618.
3D structure databases
ProteinModelPortal	Q6PEM8.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000001126.
PTM databases
PhosphoSite	Q6PEM8.
Proteomic databases
PRIDE	Q6PEM8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000001126; ENSMUSP00000001126; ENSMUSG00000020829.
GeneID	52466.
KEGG	mmu:52466.
UCSC	uc007kjg.2. mouse.
Organism-specific databases
CTD	113235.
MGI	MGI:1098733. Slc46a1.
Phylogenomic databases
eggNOG	NOG306680.
GeneTree	ENSGT00530000063076.
HOGENOM	HOG000054191.
HOVERGEN	HBG055334.
InParanoid	Q6PEM8.
KO	K14613.
OMA	TRDRGSC.
OrthoDB	EOG4W6NWF.
Gene expression databases
Bgee	Q6PEM8.
CleanEx	MM_SLC46A1.
Genevestigator	Q6PEM8.
GermOnline	ENSMUSG00000020829. Mus musculus.
Family and domain databases
InterPro	IPR011701. MFS. IPR016196. MFS_dom_general_subst_transpt. IPR005829. Sugar_transporter_CS. [Graphical view]
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC46A1. mouse.
NextBio	308995.
SOURCE	Search...

Entry information

Entry name

PCFT_MOUSE

Accession

Primary (citable) accession number: Q6PEM8
Secondary accession number(s): Q571I8 , Q5SYG0, Q8R1H7, Q9D1P1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program