1152:, and a compromised blood supply, human epithelial cancers grow within an acidic milieu, as lactate is produced during anaerobic glycolysis. Because PCFT activity is optimal at low pH, and its expression and a prominent low-pH transport activity are present in human cancers, there is interest in exploiting these properties by the development of antifolates that have a high affinity for this transporter and a very low affinity for the reduced folate carrier which delivers antifolates to normal tissues and thereby mediates the toxicity of these agents. A novel class of inhibitors of one carbon incorporation into purines is being developed with these properties. Pemetrexed, an antifolate inhibitor primarily of thymidylate synthase, is a good substrate for PCFT even at neutral pH as compared to other antifolates and folates.
1100:
of folate in the cerebrospinal fluid (CSF) in PCFT-null humans, PCFT must play a role in transport of folates across the choroid plexus into the CSF; however, the underlying mechanism for this has not been established. PCFT is expressed at the sinusoidal (basolateral) membrane of the hepatocyte, the apical brush-border membrane of the proximal tubule of the kidney, the basolateral membrane of the retinal pigment epithelium and the placenta. There is a prominent low-pH folate transport activity in the cells and/or membrane vesicles derived from these tissues which, in some cases, has been shown to be indicative of a proton-coupled folate transport process. However, it is unclear as to the extent that PCFT contributes to folate transport across these epithelia.
1091:. The transporter is specific for the monoglutamyl forms of folates. A variety of organic anions inhibit PCFT-mediated transport at extremely high ratio of inhibitor to folate, the most potent are sulfobromophthalein, p-aminobenzylglutamate, and sulfathalazine. This may have pharmacological relevance in terms of the inhibitory effect of these agents on the intestinal absorption of folates. The PCFT minimal promoter has been defined and contains an NRF1 response element. There is also evidence for a role of vitamin D in the regulation of PCFT with a VDR response element upstream of the minimal promoter. PCFT mRNA was reported to be increased in folate-deficient mice.
253:
230:
127:
152:
1087:(optimal activity at pH 7.4, very low affinity for folic acid and very high affinity for PT523), another member (SLC19A1) of the superfamily of solute transporters. Influx mediated by PCFT is electrogenic and can be assessed by current, cellular acidification, and radiotracer uptake. Influx has a Km range of 0.5 to 3 ΞΌM for most folates and antifolates at pH 5.5. The influx Km rises and the influx Vmax falls as the pH is increased, least so for the antifolate,
504:
259:
158:
1128:, always accompanies the folate deficiency. Sometimes there is pancytopenia and/or hypogammaglobulinemia and/or T-cell dysfunction which can result in infections such as Pneumocystis jirovecii pneumonia. There can be GI signs including diarrhea and mucositis. The CNS folate deficiency is associated with a variety of neurological findings including developmental delays and seizures. The phenotype of the PCFT-
1099:
PCFT is expressed in the proximal jejunum with a lower level of expression elsewhere in the intestine. Expression is localized to the apical membrane of intestinal and polarized MDCK dog kidney cells. PCFT is also expressed at the basolateral membrane of the choroid plexus. In view of the low levels
1069:
connecting residues C66, in the 1st and C298 in the 4th, external loop. Neither glycosylation nor the disulfide bond are essential for function. Residues have been identified that play a role in proton-coupling, proton binding, folate binding and oscillation of the carrier between its conformational
1060:
PCFT is located on chromosome 17q11.2 and consists of five exons encoding a protein with 459 amino acids and a MW of ~50kDa. PCFT is highly conserved, sharing 87% identity to the mouse and rat PCFT and retaining more than 50% amino acid identity to the frog (XP415815) and zebrafish (AAH77859)
1082:
PCFT-mediated transport into cells is optimal at pH 5.5. The low-pH activity and the structural specificity of PCFT (high affinity for folic acid, and low affinity for PT523 - a non-polyglutamable analog of aminopterin) distinguishes this transporter functionally from the other major folate
1885:
Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, et al. (August 2007). "Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter".
1787:
Qiu A, Min SH, Jansen M, Malhotra U, Tsai E, Cabelof DC, et al. (November 2007). "Rodent intestinal folate transporters (SLC46A1): secondary structure, functional properties, and response to dietary folate restriction".
2159:
Eloranta JJ, ZaΓ―r ZM, Hiller C, HΓ€usler S, Stieger B, Kullak-Ublick GA (November 2009). "Vitamin D3 and its nuclear receptor increase the expression and activity of the human proton-coupled folate transporter".
2783:
Salojin KV, Cabrera RM, Sun W, Chang WC, Lin C, Duncan L, et al. (May 2011). "A mouse model of hereditary folate malabsorption: deletion of the PCFT gene leads to systemic folate deficiency".
2869:"A prominent low-pH methotrexate transport activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier"
1981:
Urquhart BL, Gregor JC, Chande N, Knauer MJ, Tirona RG, Kim RB (February 2010). "The human proton-coupled folate transporter (hPCFT): modulation of intestinal expression and function by drugs".
2820:"Therapeutic targeting of a novel 6-substituted pyrrolo [2,3-d]pyrimidine thienoyl antifolate to human solid tumors based on selective uptake by the proton-coupled folate transporter"
1061:
proteins. Structurally, there are twelve transmembrane helices with the N- and C- termini directed to the cytoplasm and a large internal loop that divides the molecule in half. There are two
1667:"Structural determinants of human proton-coupled folate transporter oligomerization: role of GXXXG motifs and identification of oligomeric interfaces at transmembrane domains 3 and 6"
1140:
or heme deficient and the anemia, and all other systemic consequences of the loss of this transporter, are completely corrected with high-dose oral, or low-dose, parenteral folate.
2628:
Keating E, Lemos C, Azevedo I, Martel F (February 2006). "Comparison of folic acid uptake characteristics by human placental choriocarcinoma cells at acidic and physiological pH".
1310:
Sharma S, Dimasi D, BrΓΆer S, Kumar R, Della NG (April 2007). "Heme carrier protein 1 (HCP1) expression and functional analysis in the retina and retinal pigment epithelium".
266:
165:
1108:
The physiological role of PCFT is known based upon the phenotype of subjects with loss-of-function mutations of this gene β the rare autosomal hereditary disorder,
1136:
transporter. However, a role for PCFT in heme and iron homeostasis is excluded by the observation that humans or mice with loss-of-function PCFT mutations are not
2726:"CSF 5-Methyltetrahydrofolate Serial Monitoring to Guide Treatment of Congenital Folate Malabsorption Due to Proton-Coupled Folate Transporter (PCFT) Deficiency"
2257:
Subramanian VS, Marchant JS, Said HM (January 2008). "Apical membrane targeting and trafficking of the human proton-coupled transporter in polarized epithelia".
2061:"Hypermethylation of the human proton-coupled folate transporter (SLC46A1) minimal transcriptional regulatory region in an antifolate-resistant HeLa cell line"
2462:
Williams PJ, Mistry HD, Morgan L (April 2012). "Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia".
743:
762:
88:
2540:"Expression and differential polarization of the reduced-folate transporter-1 and the folate receptor alpha in mammalian retinal pigment epithelium"
1833:"Cloning and functional characterization of the proton-coupled electrogenic folate transporter and analysis of its expression in retinal cell types"
1934:"The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier"
1211:
2966:
2749:
1229:
1518:"N-linked glycosylation and its impact on the electrophoretic mobility and function of the human proton-coupled folate transporter (HsPCFT)"
2024:
Stark M, Gonen N, Assaraf YG (October 2009). "Functional elements in the minimal promoter of the human proton-coupled folate transporter".
252:
1410:"Membrane topological analysis of the proton-coupled folate transporter (PCFT-SLC46A1) by the substituted cysteine accessibility method"
970:
2701:
Goldman ID (1993). Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.). "Hereditary Folate
Malabsorption".
977:
229:
1742:
1247:
2663:
Bhandari SD, Joshi SK, McMartin KE (January 1988). "Folate binding and transport by rat kidney brush-border membrane vesicles".
1198:
1177:
1109:
2971:
151:
126:
1194:
1173:
68:
265:
164:
258:
157:
1121:
1567:"Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors"
1149:
1356:"Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption"
1132:
has been reported and mirrors many of the findings in humans. PCFT was initially reported to be a low-affinity
807:
76:
788:
2208:
Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, et al. (September 2005).
2110:"The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1"
1261:
Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, et al. (September 2005).
1084:
1049:
140:
1616:"Identification and functional impact of homo-oligomers of the human proton-coupled folate transporter"
2367:
1470:
55:
1831:
Umapathy NS, Gnana-Prakasam JP, Martin PM, Mysona B, Dun Y, Smith SB, et al. (November 2007).
928:
877:
2724:
Torres A, Newton SA, Crompton B, Borzutzky A, Neufeld EJ, Notarangelo L, Berry GT (26 May 2015).
2415:"Molecular and biochemical characterization of folate transport proteins in retinal MΓΌller cells"
2336:
2282:
2239:
2185:
2006:
1911:
1813:
1459:"Delineating the extracellular water-accessible surface of the proton-coupled folate transporter"
1385:
1292:
100:
953:
932:
902:
881:
1614:
Hou Z, Kugel
Desmoulin S, Etnyre E, Olive M, Hsiung B, Cherian C, et al. (February 2012).
503:
2942:
2890:
2849:
2818:
Kugel
Desmoulin S, Wang L, Hales E, Polin L, White K, Kushner J, et al. (December 2011).
2800:
2765:
2745:
2706:
2680:
2645:
2610:
2561:
2520:
2479:
2444:
2395:
2328:
2274:
2231:
2177:
2141:
2090:
2041:
1998:
1963:
1903:
1862:
1805:
1758:
1738:
1696:
1647:
1596:
1547:
1498:
1439:
1377:
1327:
1284:
1125:
1113:
48:
2913:"The human proton-coupled folate transporter: Biology and therapeutic applications to cancer"
96:
2932:
2924:
2880:
2839:
2831:
2792:
2755:
2737:
2672:
2637:
2600:
2592:
2551:
2510:
2471:
2434:
2426:
2385:
2375:
2318:
2266:
2221:
2169:
2131:
2121:
2080:
2072:
2033:
1990:
1953:
1945:
1895:
1852:
1844:
1797:
1748:
1730:
1686:
1678:
1637:
1627:
1586:
1578:
1537:
1529:
1488:
1478:
1429:
1421:
1367:
1319:
1274:
345:
276:
220:
175:
2538:
Chancy CD, Kekuda R, Huang W, Prasad PD, Kuhnel JM, Sirotnak FM, et al. (July 2000).
2390:
1354:
Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, et al. (December 2006).
320:
2413:
Bozard BR, Ganapathy PS, Duplantier J, Mysona B, Ha Y, Roon P, et al. (June 2010).
2371:
2356:"Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma"
1665:
Wilson MR, Kugel S, Huang J, Wilson LJ, Wloszczynski PA, Ye J, et al. (July 2015).
1474:
2937:
2912:
2844:
2819:
2760:
2725:
2605:
2596:
2580:
2439:
2414:
2136:
2109:
2085:
2060:
1958:
1933:
1857:
1832:
1753:
1734:
1718:
1691:
1666:
1642:
1615:
1591:
1566:
1542:
1517:
1493:
1458:
1434:
1409:
1122:
very low CSF folate levels even when the blood folate level is corrected or supranormal
1117:
1066:
1044:. The major physiological roles of PCFTs are in mediating the intestinal absorption of
2499:"5-Methyltetrahydrofolate transport in basolateral membrane vesicles from human liver"
677:
672:
667:
662:
657:
652:
647:
642:
637:
632:
616:
611:
606:
601:
596:
591:
586:
570:
565:
560:
555:
550:
545:
2960:
2676:
2323:
2306:
1062:
532:
2340:
2189:
2010:
1915:
80:
2286:
2243:
1817:
1389:
1296:
338:
117:
2885:
2868:
2354:
Grapp M, Wrede A, Schweizer M, HΓΌwel S, Galla HJ, Snaidero N, et al. (2013).
2076:
2796:
2475:
1533:
1483:
104:
1323:
1234:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1216:
National Center for
Biotechnology Information, U.S. National Library of Medicine
2270:
2226:
2209:
2037:
1801:
1372:
1355:
1279:
1262:
421:
1582:
1129:
1088:
237:
134:
84:
2581:"Mechanisms of membrane transport of folates into cells and across epithelia"
2307:"Hereditary folate malabsorption: family report and review of the literature"
1994:
2126:
1899:
1632:
1071:
707:
481:
359:
304:
291:
203:
190:
92:
2946:
2894:
2853:
2835:
2804:
2769:
2710:
2649:
2614:
2565:
2556:
2539:
2515:
2498:
2483:
2448:
2399:
2332:
2278:
2235:
2181:
2173:
2145:
2094:
2045:
2002:
1967:
1949:
1907:
1866:
1809:
1762:
1719:"Biology of the major facilitative folate transporters SLC19A1 and SLC46A1"
1700:
1651:
1600:
1551:
1502:
1443:
1381:
1331:
1288:
2741:
2684:
2524:
1017:
1012:
2430:
1932:
Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, Goldman ID (September 2008).
1848:
1001:
852:
833:
1112:(HFM). These subjects have two major abnormalities: (i) severe systemic
2380:
2355:
1682:
1034:
819:
774:
17:
2928:
1425:
1983:
American
Journal of Physiology. Gastrointestinal and Liver Physiology
1045:
985:
729:
2641:
1116:
and (ii) a defect in the transport of folates from blood across the
1927:
1925:
692:
688:
512:
2906:
2904:
2059:
Diop-Bove NK, Wu J, Zhao R, Locker J, Goldman ID (August 2009).
1137:
1133:
1041:
72:
2911:
Desmoulin SK, Hou Z, Gangjee A, Matherly LH (December 2012).
2579:
Zhao R, Diop-Bove N, Visentin M, Goldman ID (August 2011).
2305:
Geller J, Kronn D, Jayabose S, Sandoval C (January 2002).
1880:
1878:
1876:
1888:
The
Journal of Pharmacology and Experimental Therapeutics
1403:
1401:
1399:
328:
2300:
2298:
2296:
1074:
and some of the linking residues have been identified.
1782:
1780:
1778:
1776:
1774:
1772:
2867:
Zhao R, Gao F, Hanscom M, Goldman ID (January 2004).
2203:
2201:
2199:
1248:"Entrez Gene: PCFT proton-coupled folate transporter"
493:
59:, G21, HCP1, PCFT, solute carrier family 46 member 1
2705:. Seattle (WA): University of Washington, Seattle.
2026:
1408:Zhao R, Unal ES, Shin DS, Goldman ID (April 2010).
946:
921:
895:
870:
2665:Biochimica et Biophysica Acta (BBA) - Biomembranes
2210:"Identification of an intestinal heme transporter"
1522:Biochimica et Biophysica Acta (BBA) - Biomembranes
1457:Duddempudi PK, Goyal R, Date SS, Jansen M (2013).
1263:"Identification of an intestinal heme transporter"
1190:
1188:
1186:
1169:
1167:
1165:
2497:Horne DW, Reed KA, Hoefs J, Said HM (July 1993).
275:
174:
2419:Investigative Ophthalmology & Visual Science
1837:Investigative Ophthalmology & Visual Science
1712:
1710:
1516:Unal ES, Zhao R, Qiu A, Goldman ID (June 2008).
2630:Canadian Journal of Physiology and Pharmacology
2259:American Journal of Physiology. Cell Physiology
1790:American Journal of Physiology. Cell Physiology
1349:
1347:
1345:
1343:
1341:
561:methotrexate transmembrane transporter activity
1195:GRCm38: Ensembl release 89: ENSMUSG00000020829
566:folic acid transmembrane transporter activity
8:
2696:
2694:
1174:GRCh38: Ensembl release 89: ENSG00000076351
2503:The American Journal of Clinical Nutrition
703:
528:
316:
215:
112:
2936:
2884:
2843:
2759:
2604:
2555:
2514:
2438:
2389:
2379:
2322:
2225:
2135:
2125:
2084:
1957:
1856:
1752:
1690:
1641:
1631:
1590:
1541:
1492:
1482:
1433:
1371:
1278:
556:proton transmembrane transporter activity
1161:
571:heme transmembrane transporter activity
27:Mammalian protein found in Homo sapiens
1048:(Vitamin B9), and its delivery to the
29:
280:
241:
236:
179:
138:
133:
7:
2108:Gonen N, Assaraf YG (October 2010).
633:folate import across plasma membrane
2544:The Journal of Biological Chemistry
2114:The Journal of Biological Chemistry
1620:The Journal of Biological Chemistry
2597:10.1146/annurev-nutr-072610-145133
1735:10.1016/B978-0-12-800223-0.00004-9
943:
918:
892:
867:
843:
824:
798:
779:
753:
734:
498:
448:choroid plexus of fourth ventricle
416:
354:
333:
25:
1037:that in humans is encoded by the
1031:proton-coupled folate transporter
2324:10.1097/00005792-200201000-00004
502:
264:
257:
251:
228:
163:
156:
150:
125:
1110:hereditary folate malabsorption
2391:11858/00-001M-0000-0014-164F-1
638:proton transmembrane transport
592:integral component of membrane
513:More reference expression data
482:More reference expression data
1:
2886:10.1158/1078-0432.ccr-1066-03
2077:10.1158/1535-7163.mct-08-0938
2065:Molecular Cancer Therapeutics
1571:Molecular Aspects of Medicine
658:cellular iron ion homeostasis
249:
148:
2967:Genes on human chromosome 17
2917:Cancer Biology & Therapy
2797:10.1182/blood-2010-04-279653
2677:10.1016/0005-2736(88)90243-x
2476:10.1016/j.preghy.2011.12.001
1534:10.1016/j.bbamem.2008.03.009
1484:10.1371/journal.pone.0078301
653:intestinal folate absorption
648:folic acid metabolic process
1723:Current Topics in Membranes
1717:Hou Z, Matherly LH (2014).
1565:Zhao R, Goldman ID (2013).
1324:10.1016/j.yexcr.2007.01.019
2988:
2585:Annual Review of Nutrition
2271:10.1152/ajpcell.00468.2007
2227:10.1016/j.cell.2005.06.025
2038:10.1016/j.bbrc.2009.07.116
1802:10.1152/ajpcell.00202.2007
1373:10.1016/j.cell.2006.09.041
1312:Experimental Cell Research
1280:10.1016/j.cell.2005.06.025
1124:. Severe anemia, usually
1583:10.1016/j.mam.2012.07.006
1230:"Mouse PubMed Reference:"
1212:"Human PubMed Reference:"
1016:
1011:
1007:
1000:
984:
965:
950:
925:
914:
899:
874:
863:
850:
846:
831:
827:
818:
805:
801:
786:
782:
773:
760:
756:
741:
737:
728:
713:
706:
702:
686:
531:
527:
510:
501:
492:
479:
428:
419:
366:
357:
327:
319:
315:
298:
285:
248:
227:
218:
214:
197:
184:
147:
124:
115:
111:
66:
63:
53:
46:
41:
37:
32:
2873:Clinical Cancer Research
1995:10.1152/ajpgi.00224.2009
978:Chr 11: 78.36 β 78.36 Mb
971:Chr 17: 28.39 β 28.41 Mb
2127:10.1074/jbc.m110.135640
1900:10.1124/jpet.107.122606
1671:The Biochemical Journal
1633:10.1074/jbc.m111.306860
1065:sites (N58, N68) and a
673:transmembrane transport
2836:10.1124/mol.111.073833
2824:Molecular Pharmacology
2557:10.1074/jbc.m002328200
2464:Pregnancy Hypertension
2174:10.1124/mol.109.055392
2162:Molecular Pharmacology
1950:10.1124/mol.108.045443
1938:Molecular Pharmacology
1085:reduced folate carrier
1050:central nervous system
668:methotrexate transport
612:apical plasma membrane
452:neural layer of retina
282:11 B5|11 46.74 cM
2972:Solute carrier family
2742:10.1007/8904_2015_445
2360:Nature Communications
607:brush border membrane
243:Chromosome 11 (mouse)
141:Chromosome 17 (human)
2516:10.1093/ajcn/58.1.80
2431:10.1167/iovs.09-4833
1849:10.1167/iovs.07-0288
1070:states. PCFT forms
663:folic acid transport
546:transporter activity
382:right adrenal cortex
2550:(27): 20676β20684.
2372:2013NatCo...4.2123G
2120:(44): 33602β33613.
1475:2013PLoSO...878301D
1095:Tissue distribution
406:islet of Langerhans
390:right lobe of liver
386:left adrenal cortex
378:right adrenal gland
105:SLC46A1 - orthologs
2381:10.1038/ncomms3123
1796:(5): C1669βC1678.
1683:10.1042/bj20150169
1120:into the CSF with
808:ENSMUSG00000020829
626:Biological process
580:Cellular component
551:folic acid binding
539:Molecular function
460:left lobe of liver
402:anterior pituitary
394:right uterine tube
2929:10.4161/cbt.22020
2923:(14): 1355β1373.
2791:(18): 4895β4904.
2751:978-3-662-48226-1
1843:(11): 5299β5305.
1426:10.1021/bi9021439
1420:(13): 2925β2931.
1114:folate deficiency
1083:transporter, the
1027:
1026:
1023:
1022:
996:
995:
961:
960:
940:
939:
910:
909:
889:
888:
859:
858:
840:
839:
814:
813:
795:
794:
769:
768:
750:
749:
698:
697:
523:
522:
519:
518:
488:
487:
475:
474:
413:
412:
311:
310:
210:
209:
16:(Redirected from
2979:
2951:
2950:
2940:
2908:
2899:
2898:
2888:
2864:
2858:
2857:
2847:
2830:(6): 1096β1107.
2815:
2809:
2808:
2780:
2774:
2773:
2763:
2721:
2715:
2714:
2698:
2689:
2688:
2660:
2654:
2653:
2625:
2619:
2618:
2608:
2576:
2570:
2569:
2559:
2535:
2529:
2528:
2518:
2494:
2488:
2487:
2459:
2453:
2452:
2442:
2425:(6): 3226β3235.
2410:
2404:
2403:
2393:
2383:
2351:
2345:
2344:
2326:
2302:
2291:
2290:
2265:(1): C233βC240.
2254:
2248:
2247:
2229:
2205:
2194:
2193:
2168:(5): 1062β1071.
2156:
2150:
2149:
2139:
2129:
2105:
2099:
2098:
2088:
2071:(8): 2424β2431.
2056:
2050:
2049:
2021:
2015:
2014:
1989:(2): G248βG254.
1978:
1972:
1971:
1961:
1929:
1920:
1919:
1882:
1871:
1870:
1860:
1828:
1822:
1821:
1784:
1767:
1766:
1756:
1714:
1705:
1704:
1694:
1662:
1656:
1655:
1645:
1635:
1626:(7): 4982β4995.
1611:
1605:
1604:
1594:
1577:(2β3): 373β385.
1562:
1556:
1555:
1545:
1528:(6): 1407β1414.
1513:
1507:
1506:
1496:
1486:
1454:
1448:
1447:
1437:
1405:
1394:
1393:
1375:
1351:
1336:
1335:
1318:(6): 1251β1259.
1307:
1301:
1300:
1282:
1258:
1252:
1251:
1244:
1238:
1237:
1226:
1220:
1219:
1208:
1202:
1192:
1181:
1171:
1144:As a drug target
1104:Loss-of-function
1009:
1008:
980:
973:
956:
944:
935:
919:
915:RefSeq (protein)
905:
893:
884:
868:
844:
825:
799:
780:
754:
735:
704:
529:
515:
506:
499:
484:
424:
422:Top expressed in
417:
398:body of pancreas
362:
360:Top expressed in
355:
334:
317:
307:
294:
283:
268:
261:
255:
244:
232:
216:
206:
193:
182:
167:
160:
154:
143:
129:
113:
107:
58:
51:
30:
21:
2987:
2986:
2982:
2981:
2980:
2978:
2977:
2976:
2957:
2956:
2955:
2954:
2910:
2909:
2902:
2866:
2865:
2861:
2817:
2816:
2812:
2782:
2781:
2777:
2752:
2723:
2722:
2718:
2700:
2699:
2692:
2662:
2661:
2657:
2642:10.1139/y05-129
2627:
2626:
2622:
2578:
2577:
2573:
2537:
2536:
2532:
2496:
2495:
2491:
2461:
2460:
2456:
2412:
2411:
2407:
2353:
2352:
2348:
2304:
2303:
2294:
2256:
2255:
2251:
2207:
2206:
2197:
2158:
2157:
2153:
2107:
2106:
2102:
2058:
2057:
2053:
2023:
2022:
2018:
1980:
1979:
1975:
1931:
1930:
1923:
1884:
1883:
1874:
1830:
1829:
1825:
1786:
1785:
1770:
1745:
1716:
1715:
1708:
1664:
1663:
1659:
1613:
1612:
1608:
1564:
1563:
1559:
1515:
1514:
1510:
1456:
1455:
1451:
1407:
1406:
1397:
1353:
1352:
1339:
1309:
1308:
1304:
1260:
1259:
1255:
1246:
1245:
1241:
1228:
1227:
1223:
1210:
1209:
1205:
1193:
1184:
1172:
1163:
1158:
1148:Because of the
1146:
1106:
1097:
1080:
1058:
1018:View/Edit Mouse
1013:View/Edit Human
976:
969:
966:Location (UCSC)
952:
931:
927:
901:
880:
876:
789:ENSG00000076351
682:
621:
617:plasma membrane
575:
511:
480:
471:
468:proximal tubule
466:
462:
458:
454:
450:
446:
442:
438:
434:
420:
409:
404:
400:
396:
392:
388:
384:
380:
376:
372:
358:
302:
289:
281:
271:
270:
269:
262:
242:
219:Gene location (
201:
188:
180:
170:
169:
168:
161:
139:
116:Gene location (
67:
54:
47:
28:
23:
22:
15:
12:
11:
5:
2985:
2983:
2975:
2974:
2969:
2959:
2958:
2953:
2952:
2900:
2879:(2): 718β727.
2859:
2810:
2775:
2750:
2716:
2690:
2671:(2): 211β218.
2655:
2636:(2): 247β255.
2620:
2571:
2530:
2489:
2470:(2): 123β131.
2454:
2405:
2346:
2292:
2249:
2220:(5): 789β801.
2195:
2151:
2100:
2051:
2016:
1973:
1944:(3): 854β862.
1921:
1894:(2): 469β476.
1872:
1823:
1768:
1743:
1706:
1657:
1606:
1557:
1508:
1469:(10): e78301.
1449:
1395:
1366:(5): 917β928.
1337:
1302:
1273:(5): 789β801.
1253:
1239:
1221:
1203:
1182:
1160:
1159:
1157:
1154:
1150:Warburg effect
1145:
1142:
1118:choroid plexus
1105:
1102:
1096:
1093:
1079:
1076:
1067:disulfide bond
1057:
1054:
1025:
1024:
1021:
1020:
1015:
1005:
1004:
998:
997:
994:
993:
991:
989:
982:
981:
974:
967:
963:
962:
959:
958:
948:
947:
941:
938:
937:
923:
922:
916:
912:
911:
908:
907:
897:
896:
890:
887:
886:
872:
871:
865:
861:
860:
857:
856:
848:
847:
841:
838:
837:
829:
828:
822:
816:
815:
812:
811:
803:
802:
796:
793:
792:
784:
783:
777:
771:
770:
767:
766:
758:
757:
751:
748:
747:
739:
738:
732:
726:
725:
720:
715:
711:
710:
700:
699:
696:
695:
684:
683:
681:
680:
675:
670:
665:
660:
655:
650:
645:
643:heme transport
640:
635:
629:
627:
623:
622:
620:
619:
614:
609:
604:
599:
594:
589:
583:
581:
577:
576:
574:
573:
568:
563:
558:
553:
548:
542:
540:
536:
535:
525:
524:
521:
520:
517:
516:
508:
507:
496:
490:
489:
486:
485:
477:
476:
473:
472:
470:
469:
465:
461:
457:
453:
449:
445:
441:
437:
433:
429:
426:
425:
414:
411:
410:
408:
407:
403:
399:
395:
391:
387:
383:
379:
375:
371:
370:jejunal mucosa
367:
364:
363:
351:
350:
342:
331:
325:
324:
321:RNA expression
313:
312:
309:
308:
300:
296:
295:
287:
284:
279:
273:
272:
263:
256:
250:
246:
245:
240:
234:
233:
225:
224:
212:
211:
208:
207:
199:
195:
194:
186:
183:
178:
172:
171:
162:
155:
149:
145:
144:
137:
131:
130:
122:
121:
109:
108:
65:
61:
60:
52:
44:
43:
39:
38:
35:
34:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
2984:
2973:
2970:
2968:
2965:
2964:
2962:
2948:
2944:
2939:
2934:
2930:
2926:
2922:
2918:
2914:
2907:
2905:
2901:
2896:
2892:
2887:
2882:
2878:
2874:
2870:
2863:
2860:
2855:
2851:
2846:
2841:
2837:
2833:
2829:
2825:
2821:
2814:
2811:
2806:
2802:
2798:
2794:
2790:
2786:
2779:
2776:
2771:
2767:
2762:
2757:
2753:
2747:
2743:
2739:
2735:
2731:
2727:
2720:
2717:
2712:
2708:
2704:
2697:
2695:
2691:
2686:
2682:
2678:
2674:
2670:
2666:
2659:
2656:
2651:
2647:
2643:
2639:
2635:
2631:
2624:
2621:
2616:
2612:
2607:
2602:
2598:
2594:
2590:
2586:
2582:
2575:
2572:
2567:
2563:
2558:
2553:
2549:
2545:
2541:
2534:
2531:
2526:
2522:
2517:
2512:
2508:
2504:
2500:
2493:
2490:
2485:
2481:
2477:
2473:
2469:
2465:
2458:
2455:
2450:
2446:
2441:
2436:
2432:
2428:
2424:
2420:
2416:
2409:
2406:
2401:
2397:
2392:
2387:
2382:
2377:
2373:
2369:
2365:
2361:
2357:
2350:
2347:
2342:
2338:
2334:
2330:
2325:
2320:
2316:
2312:
2308:
2301:
2299:
2297:
2293:
2288:
2284:
2280:
2276:
2272:
2268:
2264:
2260:
2253:
2250:
2245:
2241:
2237:
2233:
2228:
2223:
2219:
2215:
2211:
2204:
2202:
2200:
2196:
2191:
2187:
2183:
2179:
2175:
2171:
2167:
2163:
2155:
2152:
2147:
2143:
2138:
2133:
2128:
2123:
2119:
2115:
2111:
2104:
2101:
2096:
2092:
2087:
2082:
2078:
2074:
2070:
2066:
2062:
2055:
2052:
2047:
2043:
2039:
2035:
2031:
2027:
2020:
2017:
2012:
2008:
2004:
2000:
1996:
1992:
1988:
1984:
1977:
1974:
1969:
1965:
1960:
1955:
1951:
1947:
1943:
1939:
1935:
1928:
1926:
1922:
1917:
1913:
1909:
1905:
1901:
1897:
1893:
1889:
1881:
1879:
1877:
1873:
1868:
1864:
1859:
1854:
1850:
1846:
1842:
1838:
1834:
1827:
1824:
1819:
1815:
1811:
1807:
1803:
1799:
1795:
1791:
1783:
1781:
1779:
1777:
1775:
1773:
1769:
1764:
1760:
1755:
1750:
1746:
1744:9780128002230
1740:
1736:
1732:
1728:
1724:
1720:
1713:
1711:
1707:
1702:
1698:
1693:
1688:
1684:
1680:
1676:
1672:
1668:
1661:
1658:
1653:
1649:
1644:
1639:
1634:
1629:
1625:
1621:
1617:
1610:
1607:
1602:
1598:
1593:
1588:
1584:
1580:
1576:
1572:
1568:
1561:
1558:
1553:
1549:
1544:
1539:
1535:
1531:
1527:
1523:
1519:
1512:
1509:
1504:
1500:
1495:
1490:
1485:
1480:
1476:
1472:
1468:
1464:
1460:
1453:
1450:
1445:
1441:
1436:
1431:
1427:
1423:
1419:
1415:
1411:
1404:
1402:
1400:
1396:
1391:
1387:
1383:
1379:
1374:
1369:
1365:
1361:
1357:
1350:
1348:
1346:
1344:
1342:
1338:
1333:
1329:
1325:
1321:
1317:
1313:
1306:
1303:
1298:
1294:
1290:
1286:
1281:
1276:
1272:
1268:
1264:
1257:
1254:
1249:
1243:
1240:
1235:
1231:
1225:
1222:
1217:
1213:
1207:
1204:
1200:
1196:
1191:
1189:
1187:
1183:
1179:
1175:
1170:
1168:
1166:
1162:
1155:
1153:
1151:
1143:
1141:
1139:
1135:
1131:
1127:
1123:
1119:
1115:
1111:
1103:
1101:
1094:
1092:
1090:
1086:
1077:
1075:
1073:
1068:
1064:
1063:glycosylation
1055:
1053:
1051:
1047:
1043:
1040:
1036:
1032:
1019:
1014:
1010:
1006:
1003:
999:
992:
990:
987:
983:
979:
975:
972:
968:
964:
957:
955:
949:
945:
942:
936:
934:
930:
924:
920:
917:
913:
906:
904:
898:
894:
891:
885:
883:
879:
873:
869:
866:
864:RefSeq (mRNA)
862:
855:
854:
849:
845:
842:
836:
835:
830:
826:
823:
821:
817:
810:
809:
804:
800:
797:
791:
790:
785:
781:
778:
776:
772:
765:
764:
759:
755:
752:
746:
745:
740:
736:
733:
731:
727:
724:
721:
719:
716:
712:
709:
705:
701:
694:
690:
685:
679:
676:
674:
671:
669:
666:
664:
661:
659:
656:
654:
651:
649:
646:
644:
641:
639:
636:
634:
631:
630:
628:
625:
624:
618:
615:
613:
610:
608:
605:
603:
600:
598:
595:
593:
590:
588:
585:
584:
582:
579:
578:
572:
569:
567:
564:
562:
559:
557:
554:
552:
549:
547:
544:
543:
541:
538:
537:
534:
533:Gene ontology
530:
526:
514:
509:
505:
500:
497:
495:
491:
483:
478:
467:
463:
459:
456:parotid gland
455:
451:
447:
443:
439:
435:
431:
430:
427:
423:
418:
415:
405:
401:
397:
393:
389:
385:
381:
377:
373:
369:
368:
365:
361:
356:
353:
352:
349:
347:
343:
341:
340:
336:
335:
332:
330:
326:
322:
318:
314:
306:
301:
297:
293:
288:
278:
274:
267:
260:
254:
247:
239:
235:
231:
226:
222:
217:
213:
205:
200:
196:
192:
187:
177:
173:
166:
159:
153:
146:
142:
136:
132:
128:
123:
119:
114:
110:
106:
102:
98:
94:
90:
86:
82:
78:
74:
70:
62:
57:
50:
45:
40:
36:
31:
19:
2920:
2916:
2876:
2872:
2862:
2827:
2823:
2813:
2788:
2784:
2778:
2733:
2730:JIMD Reports
2729:
2719:
2702:
2668:
2664:
2658:
2633:
2629:
2623:
2588:
2584:
2574:
2547:
2543:
2533:
2509:(1): 80β84.
2506:
2502:
2492:
2467:
2463:
2457:
2422:
2418:
2408:
2363:
2359:
2349:
2317:(1): 51β68.
2314:
2310:
2262:
2258:
2252:
2217:
2213:
2165:
2161:
2154:
2117:
2113:
2103:
2068:
2064:
2054:
2032:(1): 79β85.
2029:
2025:
2019:
1986:
1982:
1976:
1941:
1937:
1891:
1887:
1840:
1836:
1826:
1793:
1789:
1726:
1722:
1677:(1): 33β44.
1674:
1670:
1660:
1623:
1619:
1609:
1574:
1570:
1560:
1525:
1521:
1511:
1466:
1462:
1452:
1417:
1414:Biochemistry
1413:
1363:
1359:
1315:
1311:
1305:
1270:
1266:
1256:
1242:
1233:
1224:
1215:
1206:
1147:
1107:
1098:
1081:
1059:
1038:
1030:
1028:
951:
929:NP_001229295
926:
900:
878:NM_001242366
875:
851:
832:
806:
787:
761:
742:
722:
717:
602:cell surface
444:right kidney
344:
337:
64:External IDs
2703:GeneReviews
2591:: 177β201.
1729:: 175β204.
303:78,362,885
290:78,356,523
202:28,407,197
189:28,394,642
42:Identifiers
2961:Categories
1201:, May 2017
1180:, May 2017
1156:References
1130:null mouse
1126:macrocytic
1089:pemetrexed
1078:Regulation
440:blastocyst
348:(ortholog)
85:HomoloGene
2736:: 91β96.
1072:oligomers
1056:Structure
954:NP_081016
933:NP_542400
903:NM_026740
882:NM_080669
708:Orthologs
678:transport
587:cytoplasm
93:GeneCards
2947:22954694
2895:14760095
2854:21940787
2805:21346251
2770:26006721
2711:20301716
2650:16900951
2615:21568705
2566:10787414
2484:26105097
2449:20053979
2400:23828504
2366:: 2123.
2341:27156694
2333:11807405
2311:Medicine
2279:18003745
2236:16143108
2190:11155598
2182:19666701
2146:20724482
2095:19671745
2046:19643086
2011:12974427
2003:19762432
1968:18524888
1916:23277839
1908:17475902
1867:17962486
1810:17898134
1763:24745983
1701:25877470
1652:22179615
1601:23506878
1552:18405659
1503:24205192
1463:PLOS ONE
1444:20225891
1382:17129779
1332:17335806
1289:16143108
1197:–
1176:–
1002:Wikidata
687:Sources:
597:membrane
432:duodenum
374:duodenum
2938:3542225
2845:3228537
2761:4582027
2685:2892531
2606:3885234
2525:8317394
2440:2891475
2368:Bibcode
2287:7730829
2244:9130882
2137:2962458
2086:2735101
1959:2716086
1858:3850295
1818:7250544
1754:4185403
1692:4713120
1643:3281668
1592:3831518
1543:2762823
1494:3799626
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