S36A4_HUMAN
ID S36A4_HUMAN Reviewed; 504 AA.
AC Q6YBV0; Q86X30; Q8IVM5; Q8N8S6;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Proton-coupled amino acid transporter 4;
DE Short=Proton/amino acid transporter 4;
DE AltName: Full=Solute carrier family 36 member 4;
GN Name=SLC36A4; Synonyms=PAT4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Boll M., Foltz M., Rubio-Aliaga I., Kolmeder D., Daniel H.;
RT "A cluster of proton/amino acid transporter (PAT) genes in the human and
RT murine genome.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-209
RP AND HIS-376 AND ILE-429.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 162-504.
RC TISSUE=Skeletal muscle;
RA Ievolella C., Zara I., Millino C., Faulkner G., Lanfranchi G.;
RT "Full length sequencing of some human and murine muscular transcripts
RT (Telethon Italy project B41).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21097500; DOI=10.1074/jbc.m110.172403;
RA Pillai S.M., Meredith D.;
RT "SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed
RT in Xenopus laevis oocytes.";
RL J. Biol. Chem. 286:2455-2460(2011).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Functions as a sodium-independent electroneutral transporter
CC for tryptophan, proline and alanine. Inhibited by sarcosine.
CC {ECO:0000269|PubMed:21097500}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.1 uM for L-proline {ECO:0000269|PubMed:21097500};
CC KM=1.7 uM for L-tryptophan {ECO:0000269|PubMed:21097500};
CC pH dependence:
CC Optimum pH is 7.4 (for proline transport).
CC {ECO:0000269|PubMed:21097500};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6YBV0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6YBV0-2; Sequence=VSP_028959;
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAC82496.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY162216; AAO11790.1; -; mRNA.
DR EMBL; AK096251; BAC04737.1; -; mRNA.
DR EMBL; BC047374; AAH47374.1; -; mRNA.
DR EMBL; AJ295983; CAC82496.1; ALT_FRAME; mRNA.
DR CCDS; CCDS66202.1; -. [Q6YBV0-2]
DR CCDS; CCDS8291.1; -. [Q6YBV0-1]
DR RefSeq; NP_001273068.1; NM_001286139.1. [Q6YBV0-2]
DR RefSeq; NP_689526.2; NM_152313.3. [Q6YBV0-1]
DR RefSeq; XP_016872665.1; XM_017017176.1. [Q6YBV0-2]
DR AlphaFoldDB; Q6YBV0; -.
DR IntAct; Q6YBV0; 1.
DR STRING; 9606.ENSP00000317382; -.
DR TCDB; 2.A.18.8.5; the amino acid/auxin permease (aaap) family.
DR GlyGen; Q6YBV0; 2 sites.
DR iPTMnet; Q6YBV0; -.
DR PhosphoSitePlus; Q6YBV0; -.
DR BioMuta; SLC36A4; -.
DR DMDM; 74749514; -.
DR EPD; Q6YBV0; -.
DR jPOST; Q6YBV0; -.
DR MassIVE; Q6YBV0; -.
DR MaxQB; Q6YBV0; -.
DR PaxDb; Q6YBV0; -.
DR PeptideAtlas; Q6YBV0; -.
DR PRIDE; Q6YBV0; -.
DR ProteomicsDB; 67839; -. [Q6YBV0-1]
DR Antibodypedia; 17800; 128 antibodies from 15 providers.
DR DNASU; 120103; -.
DR Ensembl; ENST00000326402.9; ENSP00000317382.4; ENSG00000180773.15. [Q6YBV0-1]
DR Ensembl; ENST00000529184.5; ENSP00000436570.1; ENSG00000180773.15. [Q6YBV0-2]
DR GeneID; 120103; -.
DR KEGG; hsa:120103; -.
DR MANE-Select; ENST00000326402.9; ENSP00000317382.4; NM_152313.4; NP_689526.2.
DR UCSC; uc001pdl.3; human. [Q6YBV0-1]
DR CTD; 120103; -.
DR DisGeNET; 120103; -.
DR GeneCards; SLC36A4; -.
DR HGNC; HGNC:19660; SLC36A4.
DR HPA; ENSG00000180773; Low tissue specificity.
DR MIM; 613760; gene.
DR neXtProt; NX_Q6YBV0; -.
DR OpenTargets; ENSG00000180773; -.
DR PharmGKB; PA134908925; -.
DR VEuPathDB; HostDB:ENSG00000180773; -.
DR eggNOG; KOG1304; Eukaryota.
DR GeneTree; ENSGT00940000160117; -.
DR HOGENOM; CLU_009646_0_0_1; -.
DR InParanoid; Q6YBV0; -.
DR OMA; HELCRRY; -.
DR OrthoDB; 697331at2759; -.
DR PhylomeDB; Q6YBV0; -.
DR TreeFam; TF314873; -.
DR PathwayCommons; Q6YBV0; -.
DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane.
DR Reactome; R-HSA-71240; Tryptophan catabolism.
DR SignaLink; Q6YBV0; -.
DR SIGNOR; Q6YBV0; -.
DR BioGRID-ORCS; 120103; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; SLC36A4; human.
DR GenomeRNAi; 120103; -.
DR Pharos; Q6YBV0; Tbio.
DR PRO; PR:Q6YBV0; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6YBV0; protein.
DR Bgee; ENSG00000180773; Expressed in islet of Langerhans and 160 other tissues.
DR ExpressionAtlas; Q6YBV0; baseline and differential.
DR Genevisible; Q6YBV0; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015180; F:L-alanine transmembrane transporter activity; IDA:WormBase.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015193; F:L-proline transmembrane transporter activity; IDA:WormBase.
DR GO; GO:0015196; F:L-tryptophan transmembrane transporter activity; IDA:WormBase.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR GO; GO:0015808; P:L-alanine transport; IDA:UniProtKB.
DR GO; GO:1904271; P:L-proline import across plasma membrane; TAS:Reactome.
DR GO; GO:1904556; P:L-tryptophan transmembrane transport; TAS:Reactome.
DR GO; GO:0015824; P:proline transport; IDA:UniProtKB.
DR GO; GO:0015827; P:tryptophan transport; IDA:UniProtKB.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Amino-acid transport; Glycoprotein;
KW Membrane; Reference proteome; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..504
FT /note="Proton-coupled amino acid transporter 4"
FT /id="PRO_0000308318"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..251
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 273..293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 309..329
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 358..378
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 456..476
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..135
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_028959"
FT VARIANT 209
FT /note="L -> I (in dbSNP:rs17854446)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036791"
FT VARIANT 376
FT /note="P -> H (in dbSNP:rs17854445)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036792"
FT VARIANT 429
FT /note="L -> I (in dbSNP:rs17854443)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036793"
FT CONFLICT 330
FT /note="H -> R (in Ref. 2; BAC04737)"
FT /evidence="ECO:0000305"
FT CONFLICT 387
FT /note="K -> E (in Ref. 4; CAC82496)"
FT /evidence="ECO:0000305"
FT CONFLICT 391..392
FT /note="EF -> GI (in Ref. 4; CAC82496)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 56157 MW; 066CCC585EB2F170 CRC64;
MEAAATPAAA GAARREELDM DVMRPLINEQ NFDGTSDEEH EQELLPVQKH YQLDDQEGIS
FVQTLMHLLK GNIGTGLLGL PLAIKNAGIV LGPISLVFIG IISVHCMHIL VRCSHFLCLR
FKKSTLGYSD TVSFAMEVSP WSCLQKQAAW GRSVVDFFLV ITQLGFCSVY IVFLAENVKQ
VHEGFLESKV FISNSTNSSN PCERRSVDLR IYMLCFLPFI ILLVFIRELK NLFVLSFLAN
VSMAVSLVII YQYVVRNMPD PHNLPIVAGW KKYPLFFGTA VFAFEGIGVV LPLENQMKES
KRFPQALNIG MGIVTTLYVT LATLGYMCFH DEIKGSITLN LPQDVWLYQS VKILYSFGIF
VTYSIQFYVP AEIIIPGITS KFHTKWKQIC EFGIRSFLVS ITCAGAILIP RLDIVISFVG
AVSSSTLALI LPPLVEILTF SKEHYNIWMV LKNISIAFTG VVGFLLGTYI TVEEIIYPTP
KVVAGTPQSP FLNLNSTCLT SGLK
