Q8N697 (S15A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 15 member 4

Alternative name(s):
Peptide transporter 4
Peptide/histidine transporter 1
Short name=hPHT1

Gene names

Name:	SLC15A4
Synonyms:	PHT1, PTR4
ORF Names:	FP12591

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	577 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Proton oligopeptide cotransporter. Transports free histidine and certain di- and tripeptides. Ref.9
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Highly expressed in skeletal muscle. Moderately expressed in kidney, liver, and heart. Weakly expressed in colon and brain. Expressed in low levels throughout the gastrointestinal tract and in Caco-2 cells. Expressed in retinal fragment epithelium (RPE) and neural retina. Expressed in small intestine, stomach, duodenum, jejunum, ileum and colon. Ref.7 Ref.8 Ref.9
Sequence similarities	Belongs to the PTR2/POT transporter (TC 2.A.17) family. [View classification]
Sequence caution	The sequence AAI46804.1 differs from that shown. Reason: Frameshift at position 342. The sequence AAK95565.1 differs from that shown. Reason: Frameshift at position 572. The sequence AAQ04807.1 differs from that shown. Reason: Frameshift at position 497.

Ontologies

Keywords
Biological process	Peptide transport Protein transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ion transport Traceable author statement. Source: Reactome oligopeptide transport Inferred from electronic annotation. Source: InterPro protein transport Inferred from electronic annotation. Source: UniProtKB-KW transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosomal membrane Traceable author statement. Source: Reactome
Molecular_function	L-histidine transmembrane transporter activity Inferred from electronic annotation. Source: Compara symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N697-1)

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.

Isoform 2 (identifier: Q8N697-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-337: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 577	577	Solute carrier family 15 member 4		PRO_0000338599
Regions
	Transmembrane	49 – 69	21	Helical; Potential
	Transmembrane	76 – 96	21	Helical; Potential
	Transmembrane	105 – 125	21	Helical; Potential
	Transmembrane	158 – 178	21	Helical; Potential
	Transmembrane	194 – 214	21	Helical; Potential
	Transmembrane	222 – 242	21	Helical; Potential
	Transmembrane	318 – 338	21	Helical; Potential
	Transmembrane	363 – 383	21	Helical; Potential
	Transmembrane	405 – 425	21	Helical; Potential
	Transmembrane	459 – 479	21	Helical; Potential
	Transmembrane	490 – 510	21	Helical; Potential
	Transmembrane	535 – 555	21	Helical; Potential
	Compositional bias	8 – 39	32	Ala-rich
Amino acid modifications
	Modified residue	291	1	Phosphoserine By similarity
	Modified residue	298	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 337	337	Missing in isoform 2.		VSP_034052
	Natural variant	239	1	V → A. Corresponds to variant rs33990080 [ dbSNP | Ensembl ].		VAR_051611
Experimental info
	Sequence conflict	24	1	A → T in AAI46804. Ref.6
	Sequence conflict	34 – 35	2	RA → LL in AAK95565. Ref.1
	Sequence conflict	44	1	E → G in AAI46804. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 701111038C752E70	FASTA	577	62,034
	10 20 30 40 50 60 MEGSGGGAGE RAPLLGARRA AAAAAAAGAF AGRRAACGAV LLTELLERAA FYGITSNLVL 70 80 90 100 110 120 FLNGAPFCWE GAQASEALLL FMGLTYLGSP FGGWLADARL GRARAILLSL ALYLLGMLAF 130 140 150 160 170 180 PLLAAPATRA ALCGSARLLN CTAPGPDAAA RCCSPATFAG LVLVGLGVAT VKANITPFGA 190 200 210 220 230 240 DQVKDRGPEA TRRFFNWFYW SINLGAILSL GGIAYIQQNV SFVTGYAIPT VCVGLAFVVF 250 260 270 280 290 300 LCGQSVFITK PPDGSAFTDM FKILTYSCCS QKRSGERQSN GEGIGVFQQS SKQSLFDSCK 310 320 330 340 350 360 MSHGGPFTEE KVEDVKALVK IVPVFLALIP YWTVYFQMQT TYVLQSLHLR IPEISNITTT 370 380 390 400 410 420 PHTLPAAWLT MFDAVLILLL IPLKDKLVDP ILRRHGLLPS SLKRIAVGMF FVMCSAFAAG 430 440 450 460 470 480 ILESKRLNLV KEKTINQTIG NVVYHAADLS LWWQVPQYLL IGISEIFASI AGLEFAYSAA 490 500 510 520 530 540 PKSMQSAIMG LFFFFSGVGS FVGSGLLALV SIKAIGWMSS HTDFGNINGC YLNYYFFLLA 550 560 570 AIQGATLLLF LIISVKYDHH RDHQRSRANG VPTSRRA
	Isoform 2 [UniParc]. Checksum: 2896131C1AB96FB0	FASTA	240	26,606
	10 20 30 40 50 60 MQTTYVLQSL HLRIPEISNI TTTPHTLPAA WLTMFDAVLI LLLIPLKDKL VDPILRRHGL 70 80 90 100 110 120 LPSSLKRIAV GMFFVMCSAF AAGILESKRL NLVKEKTINQ TIGNVVYHAA DLSLWWQVPQ 130 140 150 160 170 180 YLLIGISEIF ASIAGLEFAY SAAPKSMQSA IMGLFFFFSG VGSFVGSGLL ALVSIKAIGW 190 200 210 220 230 240 MSSHTDFGNI NGCYLNYYFF LLAAIQGATL LLFLIISVKY DHHRDHQRSR ANGVPTSRRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a human novel gene with product of peptide/histidine." Guo J.H., Yu L. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Molecular cloning of a human brain peptide/histidine transporter, PTR4." Mondon P., Bouayadi K., Fournier J., Saubusse P., Lablie C. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Brain.
[7]	"Human proton/oligopeptide transporter (POT) genes: identification of putative human genes using bioinformatics." Botka C.W., Wittig T.W., Graul R.C., Nielsen C.U., Higaki K., Amidon G.L., Sadee W. AAPS PharmSci 2:E16-E16(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Spatial expression patterns of peptide transporters in the human and rat gastrointestinal tracts, Caco-2 in vitro cell culture model, and multiple human tissues." Herrera-Ruiz D., Wang Q., Gudmundsson O.S., Cook T.J., Smith R.L., Faria T.N., Knipp G.T. AAPS PharmSci 3:E9-E9(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in transiently transfected COS-7 cells." Bhardwaj R.K., Herrera-Ruiz D., Eltoukhy N., Saad M., Knipp G.T. Eur. J. Pharm. Sci. 27:533-542(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY050629 mRNA. Translation: AAK95565.1. Frameshift. AY038999 mRNA. Translation: AAK72099.1. AF461893 mRNA. Translation: AAQ04807.1. Frameshift. AK095717 mRNA. Translation: BAG53113.1. CH471054 Genomic DNA. Translation: EAW98494.1. BC028394 mRNA. Translation: AAH28394.2. BC146803 mRNA. Translation: AAI46804.1. Frameshift.
IPI	IPI00465259. IPI00883723.
RefSeq	NP_663623.1. NM_145648.3.
UniGene	Hs.507260.
3D structure databases
ProteinModelPortal	Q8N697.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N697. 1 interaction.
STRING	9606.ENSP00000266771.
PTM databases
PhosphoSite	Q8N697.
Polymorphism databases
DMDM	74751048.
Proteomic databases
PaxDb	Q8N697.
PRIDE	Q8N697.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000266771; ENSP00000266771; ENSG00000139370. ENST00000544112; ENSP00000439946; ENSG00000139370.
GeneID	121260.
KEGG	hsa:121260.
UCSC	uc001uhu.2. human.
Organism-specific databases
CTD	121260.
GeneCards	GC12M129277.
HGNC	HGNC:23090. SLC15A4.
HPA	HPA016713.
neXtProt	NX_Q8N697.
PharmGKB	PA134928948.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3104.
HOGENOM	HOG000143436.
HOVERGEN	HBG108431.
KO	K14638.
OMA	IQLMMDG.
PhylomeDB	Q8N697.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters.
Gene expression databases
ArrayExpress	Q8N697.
Bgee	Q8N697.
CleanEx	HS_SLC15A4.
Genevestigator	Q8N697.
Family and domain databases
InterPro	IPR016196. MFS_dom_general_subst_transpt. IPR000109. POT_fam. IPR018456. PTR2_symporter_CS. [Graphical view]
PANTHER	PTHR11654. PTHR11654. 1 hit.
Pfam	PF00854. PTR2. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS01023. PTR2_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC15A4. human.
GenomeRNAi	121260.
NextBio	80688.

Entry information

Entry name

S15A4_HUMAN

Accession

Primary (citable) accession number: Q8N697
Secondary accession number(s): A6H8Y9 , B3KTK1, Q71M34, Q7Z5F8, Q8TAH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 10, 2008
Last sequence update:	October 1, 2002
Last modified:	April 3, 2013
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.