S4A11_HUMAN
ID S4A11_HUMAN Reviewed; 875 AA.
AC Q8NBS3; B4DKC8; B4DKX9; G3V1M3; Q2TB62; Q2TB63; Q9BXF4; Q9NTW9;
DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Solute carrier family 4 member 11;
DE AltName: Full=Sodium borate cotransporter 1 {ECO:0000303|PubMed:15525507};
DE Short=NaBC1 {ECO:0000303|PubMed:15525507};
GN Name=SLC4A11; Synonyms=BTR1;
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), TISSUE SPECIFICITY, AND VARIANTS
RP HIS-392; ASN-393; THR-467 AND ALA-692.
RC TISSUE=Kidney;
RX PubMed=11302728; DOI=10.1006/bbrc.2001.4692;
RA Parker M.D., Ourmozdi E.P., Tanner M.J.A.;
RT "Human BTR1, a new bicarbonate transporter superfamily member and human AE4
RT from kidney.";
RL Biochem. Biophys. Res. Commun. 282:1103-1109(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 211-875 (ISOFORM 1).
RC TISSUE=Retinoblastoma, Thalamus, and Tongue;
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 GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=15525507; DOI=10.1016/j.molcel.2004.09.030;
RA Park M., Li Q., Shcheynikov N., Zeng W., Muallem S.;
RT "NaBC1 is a ubiquitous electrogenic Na+-coupled borate transporter
RT essential for cellular boron homeostasis and cell growth and
RT proliferation.";
RL Mol. Cell 16:331-341(2004).
RN [7]
RP TOPOLOGY, AND CHARACTERIZATION OF VARIANTS CHED HIS-109; LYS-127; VAL-253;
RP ARG-370; ASP-448; LEU-473; GLN-739; TRP-739 AND CYS-853.
RX PubMed=21288032; DOI=10.1021/bi101887z;
RA Vilas G.L., Morgan P.E., Loganathan S.K., Quon A., Casey J.R.;
RT "A biochemical framework for SLC4A11, the plasma membrane protein defective
RT in corneal dystrophies.";
RL Biochemistry 50:2157-2169(2011).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT CHED HIS-109,
RP AND MUTAGENESIS OF ASN-623.
RX PubMed=23813972; DOI=10.1093/hmg/ddt307;
RA Vilas G.L., Loganathan S.K., Liu J., Riau A.K., Young J.D., Mehta J.S.,
RA Vithana E.N., Casey J.R.;
RT "Transmembrane water-flux through SLC4A11: a route defective in genetic
RT corneal diseases.";
RL Hum. Mol. Genet. 22:4579-4590(2013).
RN [9]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT CHED HIS-109.
RX PubMed=27581649; DOI=10.1152/ajpcell.00233.2016;
RA Kao L., Azimov R., Shao X.M., Frausto R.F., Abuladze N., Newman D.,
RA Aldave A.J., Kurtz I.;
RT "Multifunctional ion transport properties of human SLC4A11: comparison of
RT the SLC4A11-B and SLC4A11-C variants.";
RL Am. J. Physiol. 311:C820-C830(2016).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=28642546; DOI=10.1038/s41598-017-03654-4;
RA Guha S., Chaurasia S., Ramachandran C., Roy S.;
RT "SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and
RT increases reactive oxygen species in human corneal endothelial cells during
RT oxidative stress.";
RL Sci. Rep. 7:4074-4074(2017).
RN [11]
RP FUNCTION, TISSUE SPECIFICITY (ISOFORMS 3 AND 5), AND TRANSLATION INITIATION
RP SITE (ISOFORM 5).
RX PubMed=31273259; DOI=10.1038/s41598-019-46094-y;
RA Malhotra D., Loganathan S.K., Chiu A.M., Lukowski C.M., Casey J.R.;
RT "Human Corneal Expression of SLC4A11, a Gene Mutated in Endothelial Corneal
RT Dystrophies.";
RL Sci. Rep. 9:9681-9681(2019).
RN [12]
RP VARIANTS CHED ASP-448; LEU-473; GLN-739 AND CYS-853, CHARACTERIZATION OF
RP VARIANTS CHED ASP-448; LEU-473; GLN-739 AND CYS-853, AND TISSUE
RP SPECIFICITY.
RX PubMed=16767101; DOI=10.1038/ng1824;
RA Vithana E.N., Morgan P., Sundaresan P., Ebenezer N.D., Tan D.T.H.,
RA Mohamed M.D., Anand S., Khine K.O., Venkataraman D., Yong V.H.K.,
RA Salto-Tellez M., Venkatraman A., Guo K., Hemadevi B., Srinivasan M.,
RA Prajna V., Khine M., Casey J.R., Inglehearn C.F., Aung T.;
RT "Mutations in sodium-borate cotransporter SLC4A11 cause recessive
RT congenital hereditary endothelial dystrophy (CHED2).";
RL Nat. Genet. 38:755-757(2006).
RN [13]
RP VARIANTS CHED LYS-127; ARG-370; TRP-739; GLN-739 AND CYS-853.
RX PubMed=17397048; DOI=10.1002/humu.9487;
RA Ramprasad V.L., Ebenezer N.D., Aung T., Rajagopal R., Yong V.H., Tuft S.J.,
RA Viswanathan D., El-Ashry M.F., Liskova P., Tan D.T., Bhattacharya S.S.,
RA Kumaramanickavel G., Vithana E.N.;
RT "Novel SLC4A11 mutations in patients with recessive congenital hereditary
RT endothelial dystrophy (CHED2). Mutation in brief #958. Online.";
RL Hum. Mutat. 28:522-523(2007).
RN [14]
RP VARIANTS CHED GLN-739; HIS-788; MET-817 AND HIS-853, AND VARIANT THR-144.
RX PubMed=16825429; DOI=10.1136/jmg.2006.044644;
RA Jiao X., Sultana A., Garg P., Ramamurthy B., Vemuganti G.K.,
RA Gangopadhyay N., Hejtmancik J.F., Kannabiran C.;
RT "Autosomal recessive corneal endothelial dystrophy (CHED2) is associated
RT with mutations in SLC4A11.";
RL J. Med. Genet. 44:64-68(2007).
RN [15]
RP VARIANTS CDPD PRO-197; LYS-472; PRO-827 AND VAL-840, AND VARIANT CHED
RP MET-808.
RX PubMed=17220209; DOI=10.1136/jmg.2006.046904;
RA Desir J., Moya G., Reish O., Van Regemorter N., Deconinck H., David K.L.,
RA Meire F.M., Abramowicz M.J.;
RT "Borate transporter SLC4A11 mutations cause both Harboyan syndrome and non-
RT syndromic corneal endothelial dystrophy.";
RL J. Med. Genet. 44:322-326(2007).
RN [16]
RP VARIANTS CHED TRP-193; LEU-197; CYS-217; LYS-385; ASP-402; ARG-457;
RP LEU-473; LYS-568; TRP-739; GLN-739; LEU-757; MET-808 AND CYS-853.
RX PubMed=17679935;
RA Sultana A., Garg P., Ramamurthy B., Vemuganti G.K., Kannabiran C.;
RT "Mutational spectrum of the SLC4A11 gene in autosomal recessive congenital
RT hereditary endothelial dystrophy.";
RL Mol. Vis. 13:1327-1332(2007).
RN [17]
RP VARIANTS CHED HIS-109; THR-144; VAL-253; ARG-370; TRP-739; LEU-757 AND
RP PRO-857.
RX PubMed=18474783; DOI=10.1001/archopht.126.5.700;
RA Hemadevi B., Veitia R.A., Srinivasan M., Arunkumar J., Prajna N.V.,
RA Lesaffre C., Sundaresan P.;
RT "Identification of mutations in the SLC4A11 gene in patients with recessive
RT congenital hereditary endothelial dystrophy.";
RL Arch. Ophthalmol. 126:700-708(2008).
RN [18]
RP VARIANTS FECD4 LYS-383; GLU-693 AND MET-738, VARIANTS THR-56; VAL-75;
RP VAL-311; MET-545 AND LEU-549, CHARACTERIZATION OF VARIANTS FECD4 LYS-383;
RP GLU-693 AND MET-738, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=18024964; DOI=10.1093/hmg/ddm337;
RA Vithana E.N., Morgan P.E., Ramprasad V., Tan D.T.H., Yong V.H.K.,
RA Venkataraman D., Venkatraman A., Yam G.H.F., Nagasamy S., Law R.W.K.,
RA Rajagopal R., Pang C.P., Kumaramanickevel G., Casey J.R., Aung T.;
RT "SLC4A11 mutations in Fuchs endothelial corneal dystrophy.";
RL Hum. Mol. Genet. 17:656-666(2008).
RN [19]
RP VARIANTS CHED ARG-378 AND ASP-402.
RX PubMed=19369245; DOI=10.1167/iovs.08-3006;
RA Aldahmesh M.A., Khan A.O., Meyer B.F., Alkuraya F.S.;
RT "Mutational spectrum of SLC4A11 in autosomal recessive CHED in Saudi
RT Arabia.";
RL Invest. Ophthalmol. Vis. Sci. 50:4142-4145(2009).
RN [20]
RP VARIANT CHED ARG-378.
RX PubMed=20108384;
RA Chai S.M., Vithana E.N., Venkataraman D., Saleh H.,
RA Chekkalichintavida N.P., al-Sayyed F., Aung T.;
RT "Novel human pathological mutations. Gene symbol: SLC4A11. Disease: Corneal
RT endothelial dystrophy 2.";
RL Hum. Genet. 127:110-110(2010).
RN [21]
RP VARIANTS FECD4 ASP-151; PRO-266; CYS-510; MET-559; ASP-567; ARG-726 AND
RP SER-818, AND CHARACTERIZATION OF VARIANTS FECD4 ASP-151; PRO-266; CYS-510;
RP MET-559; ASP-567; ARG-726 AND SER-818.
RX PubMed=20848555; DOI=10.1002/humu.21356;
RA Riazuddin S.A., Vithana E.N., Seet L.F., Liu Y., Al-Saif A., Koh L.W.,
RA Heng Y.M., Aung T., Meadows D.N., Eghrari A.O., Gottsch J.D., Katsanis N.;
RT "Missense mutations in the sodium borate cotransporter SLC4A11 cause late-
RT onset Fuchs corneal dystrophya.";
RL Hum. Mutat. 31:1261-1268(2010).
RN [22]
RP CHARACTERIZATION OF VARIANT CHED VAL-253.
RX PubMed=20185830; DOI=10.1074/jbc.m109.094680;
RA Groger N., Frohlich H., Maier H., Olbrich A., Kostin S., Braun T.,
RA Boettger T.;
RT "SLC4A11 prevents osmotic imbalance leading to corneal endothelial
RT dystrophy, deafness, and polyuria.";
RL J. Biol. Chem. 285:14467-14474(2010).
RN [23]
RP VARIANTS CHED ARG-370 AND MET-808.
RX PubMed=21203343;
RA Paliwal P., Sharma A., Tandon R., Sharma N., Titiyal J.S., Sen S.,
RA Nag T.C., Vajpayee R.B.;
RT "Congenital hereditary endothelial dystrophy - mutation analysis of SLC4A11
RT and genotype-phenotype correlation in a North Indian patient cohort.";
RL Mol. Vis. 16:2955-2963(2010).
RN [24]
RP CHARACTERIZATION OF VARIANTS CHED LYS-127; ARG-370 AND TRP-739,
RP CHARACTERIZATION OF VARIANTS FECD4 LYS-383; GLU-693 AND MET-738, AND
RP HOMODIMERIZATION.
RX PubMed=22072594; DOI=10.1002/humu.21655;
RA Vilas G.L., Loganathan S.K., Quon A., Sundaresan P., Vithana E.N.,
RA Casey J.;
RT "Oligomerization of SLC4A11 protein and the severity of FECD and CHED2
RT corneal dystrophies caused by SLC4A11 mutations.";
RL Hum. Mutat. 33:419-428(2012).
RN [25]
RP VARIANTS FECD4 SER-224; LYS-383; ILE-418 AND ILE-491, CHARACTERIZATION OF
RP VARIANTS FECD4 SER-224; ILE-418 AND ILE-491, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=25007886; DOI=10.1038/jhg.2014.55;
RA Soumittra N., Loganathan S.K., Madhavan D., Ramprasad V.L., Arokiasamy T.,
RA Sumathi S., Karthiyayini T., Rachapalli S.R., Kumaramanickavel G.,
RA Casey J.R., Rajagopal R.;
RT "Biosynthetic and functional defects in newly identified SLC4A11 mutants
RT and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy.";
RL J. Hum. Genet. 59:444-453(2014).
RN [26]
RP VARIANT CHED ALA-659.
RX PubMed=26286922; DOI=10.1111/cxo.12276;
RA Kaul H., Suman M., Khan Z., Ullah M.I., Ashfaq U.A., Idrees S.;
RT "Missense mutation in SLC4A11 in two Pakistani families affected with
RT congenital hereditary endothelial dystrophy (CHED2).";
RL Clin. Exp. Optom. 99:73-77(2016).
CC -!- FUNCTION: Multifunctional transporter with an impact in cell morphology
CC and differentiation. In the presence of borate B(OH)4(-), acts as a
CC voltage-dependent electrogenic Na(+)-coupled B(OH)4(-) cotransporter
CC controlling boron homeostasis (PubMed:15525507). At early stages of
CC stem cell differentiation, participates in synergy with ITGA5-ITGB1 and
CC ITGAV-ITGB3 integrins and BMPR1A to promote cell adhesion and
CC contractility that drives differentiation toward osteogenic commitment
CC while inhibiting adipogenesis (By similarity). In the absence of
CC B(OH)4(-), acts as a Na(+)-coupled OH(-) or H(+) permeable channel with
CC implications in cellular redox balance (PubMed:15525507,
CC PubMed:28642546). Regulates the oxidative stress response in corneal
CC endothelium by enhancing antioxidant defenses and protecting cells from
CC reactive oxygen species (PubMed:28642546). In response to hypo-osmotic
CC challenge, also acts as water permeable channel at the basolateral cell
CC membrane of corneal endothelial cells and facilitates transendothelial
CC fluid reabsorption in the aqueous humor (PubMed:31273259,
CC PubMed:25007886, PubMed:23813972). In the presence of ammonia, acts as
CC an electrogenic NH3/H(+) cotransporter and may play a role in ammonia
CC transport and reabsorption in renal Henle's loop epithelium
CC (PubMed:27581649). {ECO:0000250|UniProtKB:A2AJN7,
CC ECO:0000269|PubMed:15525507, ECO:0000269|PubMed:23813972,
CC ECO:0000269|PubMed:25007886, ECO:0000269|PubMed:27581649,
CC ECO:0000269|PubMed:28642546, ECO:0000269|PubMed:31273259}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Na(+)(in) + tetrahydroxoborate(in) = 2 Na(+)(out) +
CC tetrahydroxoborate(out); Xref=Rhea:RHEA:66816, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:41132; Evidence={ECO:0000269|PubMed:15525507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66817;
CC Evidence={ECO:0000305|PubMed:15525507};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22072594}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18024964,
CC ECO:0000269|PubMed:25007886}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:23813972};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=5;
CC Name=3; Synonyms=SLC4A11-C {ECO:0000303|PubMed:31273259};
CC IsoId=Q8NBS3-3; Sequence=Displayed;
CC Name=1; Synonyms=SLC4A11-B {ECO:0000303|PubMed:31273259};
CC IsoId=Q8NBS3-1; Sequence=VSP_061109;
CC Name=2;
CC IsoId=Q8NBS3-2; Sequence=VSP_061106;
CC Name=4; Synonyms=SLC4A11-A {ECO:0000303|PubMed:31273259};
CC IsoId=Q8NBS3-4; Sequence=VSP_061108;
CC Name=5;
CC IsoId=Q8NBS3-5; Sequence=VSP_061107;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in kidney,
CC testis, salivary gland, thyroid, trachea and corneal endothelium. Not
CC detected in retina and lymphocytes. {ECO:0000269|PubMed:11302728,
CC ECO:0000269|PubMed:16767101}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in corneal endothelium (at
CC protein level). {ECO:0000269|PubMed:31273259}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: The predominant isoform in corneal
CC endothelium (at protein level). {ECO:0000269|PubMed:31273259}.
CC -!- INDUCTION: Up-regulated upon oxidative stress, as it occurs in cells
CC exposed to tert-butyl hydroperoxide. {ECO:0000269|PubMed:28642546}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:18024964}.
CC -!- DISEASE: Corneal dystrophy and perceptive deafness (CDPD) [MIM:217400]:
CC An ocular disease characterized by the association of corneal clouding
CC with progressive perceptive hearing loss.
CC {ECO:0000269|PubMed:17220209}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Corneal endothelial dystrophy (CHED) [MIM:217700]: A
CC congenital corneal dystrophy characterized by thickening and
CC opacification of the cornea, altered morphology of the endothelium, and
CC secretion of an abnormal collagenous layer at the Descemet membrane.
CC {ECO:0000269|PubMed:16767101, ECO:0000269|PubMed:16825429,
CC ECO:0000269|PubMed:17220209, ECO:0000269|PubMed:17397048,
CC ECO:0000269|PubMed:17679935, ECO:0000269|PubMed:18474783,
CC ECO:0000269|PubMed:19369245, ECO:0000269|PubMed:20108384,
CC ECO:0000269|PubMed:20185830, ECO:0000269|PubMed:21203343,
CC ECO:0000269|PubMed:21288032, ECO:0000269|PubMed:22072594,
CC ECO:0000269|PubMed:23813972, ECO:0000269|PubMed:26286922,
CC ECO:0000269|PubMed:27581649}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Corneal dystrophy, Fuchs endothelial, 4 (FECD4) [MIM:613268]:
CC A corneal disease caused by loss of endothelium of the central cornea.
CC It is characterized by focal wart-like guttata that arise from Descemet
CC membrane and develop in the central cornea, epithelial blisters,
CC reduced vision and pain. Descemet membrane is thickened by abnormal
CC collagenous deposition. {ECO:0000269|PubMed:18024964,
CC ECO:0000269|PubMed:20848555, ECO:0000269|PubMed:22072594,
CC ECO:0000269|PubMed:25007886}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Isoforms 1 and 5 correspond to alternative translation
CC start site of the same transcript. There is no evidence that isoform 1
CC is expressed in primary tissues. It is shown that it is not expressed
CC in cornea, however it is strongly expressed upon transfection into HEK-
CC 293 cells. {ECO:0000269|PubMed:31273259}.
CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11536.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF336127; AAK16734.1; -; mRNA.
DR EMBL; AK075303; BAC11536.1; ALT_INIT; mRNA.
DR EMBL; AK296508; BAG59140.1; -; mRNA.
DR EMBL; AK296760; BAG59341.1; -; mRNA.
DR EMBL; AL109976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10536.1; -; Genomic_DNA.
DR EMBL; BC110540; AAI10541.1; -; mRNA.
DR EMBL; BC110541; AAI10542.1; -; mRNA.
DR CCDS; CCDS13052.1; -. [Q8NBS3-1]
DR CCDS; CCDS54445.1; -. [Q8NBS3-4]
DR CCDS; CCDS54446.1; -. [Q8NBS3-3]
DR RefSeq; NP_001167560.1; NM_001174089.1. [Q8NBS3-3]
DR RefSeq; NP_001167561.1; NM_001174090.1. [Q8NBS3-4]
DR RefSeq; NP_114423.1; NM_032034.3. [Q8NBS3-1]
DR RefSeq; XP_005260914.1; XM_005260857.1. [Q8NBS3-5]
DR RefSeq; XP_011527686.1; XM_011529384.1. [Q8NBS3-5]
DR RefSeq; XP_011527687.1; XM_011529385.1. [Q8NBS3-5]
DR RefSeq; XP_016883583.1; XM_017028094.1. [Q8NBS3-5]
DR RefSeq; XP_016883585.1; XM_017028096.1. [Q8NBS3-5]
DR AlphaFoldDB; Q8NBS3; -.
DR SMR; Q8NBS3; -.
DR BioGRID; 123832; 2.
DR IntAct; Q8NBS3; 1.
DR STRING; 9606.ENSP00000369399; -.
DR TCDB; 2.A.31.4.1; the anion exchanger (ae) family.
DR GlyGen; Q8NBS3; 2 sites.
DR iPTMnet; Q8NBS3; -.
DR PhosphoSitePlus; Q8NBS3; -.
DR BioMuta; SLC4A11; -.
DR DMDM; 29611858; -.
DR EPD; Q8NBS3; -.
DR MassIVE; Q8NBS3; -.
DR MaxQB; Q8NBS3; -.
DR PaxDb; Q8NBS3; -.
DR PeptideAtlas; Q8NBS3; -.
DR PRIDE; Q8NBS3; -.
DR ProteomicsDB; 32378; -.
DR ProteomicsDB; 72815; -. [Q8NBS3-1]
DR ProteomicsDB; 72816; -. [Q8NBS3-2]
DR Antibodypedia; 7351; 111 antibodies from 27 providers.
DR DNASU; 83959; -.
DR Ensembl; ENST00000380056.7; ENSP00000369396.3; ENSG00000088836.14. [Q8NBS3-1]
DR Ensembl; ENST00000380059.7; ENSP00000369399.3; ENSG00000088836.14. [Q8NBS3-4]
DR Ensembl; ENST00000642402.1; ENSP00000493503.1; ENSG00000088836.14. [Q8NBS3-3]
DR GeneID; 83959; -.
DR KEGG; hsa:83959; -.
DR MANE-Select; ENST00000642402.1; ENSP00000493503.1; NM_001174089.2; NP_001167560.1.
DR UCSC; uc002wig.3; human. [Q8NBS3-3]
DR CTD; 83959; -.
DR DisGeNET; 83959; -.
DR GeneCards; SLC4A11; -.
DR HGNC; HGNC:16438; SLC4A11.
DR HPA; ENSG00000088836; Tissue enhanced (salivary gland, thyroid gland).
DR MalaCards; SLC4A11; -.
DR MIM; 217400; phenotype.
DR MIM; 217700; phenotype.
DR MIM; 610206; gene.
DR MIM; 613268; phenotype.
DR neXtProt; NX_Q8NBS3; -.
DR OpenTargets; ENSG00000088836; -.
DR Orphanet; 293603; Congenital hereditary endothelial dystrophy type II.
DR Orphanet; 1490; Corneal dystrophy-perceptive deafness syndrome.
DR Orphanet; 98974; Fuchs endothelial corneal dystrophy.
DR PharmGKB; PA38139; -.
DR VEuPathDB; HostDB:ENSG00000088836; -.
DR eggNOG; KOG1172; Eukaryota.
DR GeneTree; ENSGT00940000154894; -.
DR HOGENOM; CLU_002289_6_0_1; -.
DR InParanoid; Q8NBS3; -.
DR OMA; YDHNVSS; -.
DR OrthoDB; 265068at2759; -.
DR PhylomeDB; Q8NBS3; -.
DR TreeFam; TF313630; -.
DR PathwayCommons; Q8NBS3; -.
DR SignaLink; Q8NBS3; -.
DR BioGRID-ORCS; 83959; 20 hits in 1074 CRISPR screens.
DR ChiTaRS; SLC4A11; human.
DR GeneWiki; SLC4A11; -.
DR GenomeRNAi; 83959; -.
DR Pharos; Q8NBS3; Tbio.
DR PRO; PR:Q8NBS3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8NBS3; protein.
DR Bgee; ENSG00000088836; Expressed in nasal cavity epithelium and 136 other tissues.
DR ExpressionAtlas; Q8NBS3; baseline and differential.
DR Genevisible; Q8NBS3; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0012506; C:vesicle membrane; ISS:ARUK-UCL.
DR GO; GO:0046715; F:active borate transmembrane transporter activity; IDA:HGNC-UCL.
DR GO; GO:0015301; F:anion:anion antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; IDA:HGNC-UCL.
DR GO; GO:0005452; F:inorganic anion exchanger activity; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0015252; F:proton channel activity; IDA:HGNC-UCL.
DR GO; GO:0015078; F:proton transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005272; F:sodium channel activity; IDA:HGNC-UCL.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005372; F:water transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; IDA:HGNC-UCL.
DR GO; GO:0046713; P:borate transport; IDA:HGNC-UCL.
DR GO; GO:0030003; P:cellular cation homeostasis; IDA:HGNC-UCL.
DR GO; GO:0071476; P:cellular hypotonic response; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0042044; P:fluid transport; ISS:UniProtKB.
DR GO; GO:0050801; P:ion homeostasis; IBA:GO_Central.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:HGNC-UCL.
DR GO; GO:2000739; P:regulation of mesenchymal stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; IDA:HGNC-UCL.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 3.40.930.10; -; 1.
DR InterPro; IPR011531; HCO3_transpt-like_TM_dom.
DR InterPro; IPR003020; HCO3_transpt_euk.
DR InterPro; IPR016152; PTrfase/Anion_transptr.
DR PANTHER; PTHR11453; PTHR11453; 1.
DR Pfam; PF00955; HCO3_cotransp; 1.
DR PRINTS; PR01231; HCO3TRNSPORT.
DR SUPFAM; SSF55804; SSF55804; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Alternative splicing; Anion exchange;
KW Cell membrane; Corneal dystrophy; Deafness; Disease variant; Glycoprotein;
KW Ion transport; Membrane; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..875
FT /note="Solute carrier family 4 member 11"
FT /id="PRO_0000079236"
FT TOPO_DOM 1..358
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 359..381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..394
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 395..408
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 414..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..443
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 444..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 468..475
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 476..496
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 497..555
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 556..577
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 578..590
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 591..612
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 613..640
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 641..658
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 659..683
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 684..704
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 705..734
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 735..759
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 760..765
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 766..783
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 784..787
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 788..810
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 811..815
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 816..832
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 833..836
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:21288032"
FT TRANSMEM 837..857
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 858..875
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:21288032"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 537
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..466
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_061106"
FT VAR_SEQ 1..19
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305|PubMed:31273259"
FT /id="VSP_061107"
FT VAR_SEQ 1..14
FT /note="MAAATRRVFHLQPC -> MGVYGPQDRSESEKRDVQRDPPPWHPRREGERPA
FT RARSLPLAAAGQGFLRKTWISEH (in isoform 4)"
FT /id="VSP_061108"
FT VAR_SEQ 2..14
FT /note="AAATRRVFHLQPC -> SQVGGRGDRCTQEVQGLVHGAGDLSASLA (in
FT isoform 1)"
FT /id="VSP_061109"
FT VARIANT 56
FT /note="N -> T (in dbSNP:rs778688114)"
FT /evidence="ECO:0000269|PubMed:18024964"
FT /id="VAR_047806"
FT VARIANT 75
FT /note="M -> V (in dbSNP:rs200940928)"
FT /evidence="ECO:0000269|PubMed:18024964"
FT /id="VAR_047807"
FT VARIANT 109
FT /note="R -> H (in CHED; does not facilitate water flux
FT across the plasma membrane; decreases proton flux with or
FT without cotransport of ammonia; does not affect protein
FT processing; dbSNP:rs1276051624)"
FT /evidence="ECO:0000269|PubMed:18474783,
FT ECO:0000269|PubMed:21288032, ECO:0000269|PubMed:23813972,
FT ECO:0000269|PubMed:27581649"
FT /id="VAR_063713"
FT VARIANT 127
FT /note="E -> K (in CHED; affects protein processing; the
FT mutant protein is retained intracellularly; coexpression
FT with wild-type protein partially rescues the cell surface
FT trafficking of CHED2 mutant; dbSNP:rs1482631297)"
FT /evidence="ECO:0000269|PubMed:17397048,
FT ECO:0000269|PubMed:21288032, ECO:0000269|PubMed:22072594"
FT /id="VAR_067272"
FT VARIANT 134
FT /note="N -> S (in dbSNP:rs34520315)"
FT /id="VAR_034944"
FT VARIANT 144
FT /note="A -> T (in CHED; dbSNP:rs752287261)"
FT /evidence="ECO:0000269|PubMed:16825429,
FT ECO:0000269|PubMed:18474783"
FT /id="VAR_034945"
FT VARIANT 151
FT /note="E -> D (in FECD4; interferes with post-translational
FT processing; the mutant protein localizes to the cytoplasm;
FT dbSNP:rs141836046)"
FT /evidence="ECO:0000269|PubMed:20848555"
FT /id="VAR_064422"
FT VARIANT 193
FT /note="R -> W (in CHED; dbSNP:rs566507872)"
FT /evidence="ECO:0000269|PubMed:17679935"
FT /id="VAR_064978"
FT VARIANT 197
FT /note="S -> L (in CHED; dbSNP:rs759667344)"
FT /evidence="ECO:0000269|PubMed:17679935"
FT /id="VAR_064979"
FT VARIANT 197
FT /note="S -> P (in CDPD; dbSNP:rs121909395)"
FT /evidence="ECO:0000269|PubMed:17220209"
FT /id="VAR_034946"
FT VARIANT 217
FT /note="R -> C (in CHED; dbSNP:rs762942751)"
FT /evidence="ECO:0000269|PubMed:17679935"
FT /id="VAR_064980"
FT VARIANT 224
FT /note="W -> S (in FECD4; decreases cell surface expression;
FT abolishes functional activity; dbSNP:rs746532062)"
FT /evidence="ECO:0000269|PubMed:25007886"
FT /id="VAR_075537"
FT VARIANT 253
FT /note="A -> V (in CHED; affects protein processing and
FT transport to the cell surface; dbSNP:rs1298347142)"
FT /evidence="ECO:0000269|PubMed:18474783,
FT ECO:0000269|PubMed:20185830, ECO:0000269|PubMed:21288032"
FT /id="VAR_063714"
FT VARIANT 266
FT /note="R -> P (in FECD4; interferes with post-translational
FT processing; the mutant protein localizes to the cytoplasm)"
FT /evidence="ECO:0000269|PubMed:20848555"
FT /id="VAR_064423"
FT VARIANT 311
FT /note="A -> V (in dbSNP:rs760889152)"
FT /evidence="ECO:0000269|PubMed:18024964"
FT /id="VAR_047808"
FT VARIANT 370
FT /note="C -> R (in CHED; affects protein processing; the
FT mutant protein is retained intracellularly; coexpression
FT with wild-type protein partially rescues the cell surface
FT trafficking of CHED2 mutant)"
FT /evidence="ECO:0000269|PubMed:17397048,
FT ECO:0000269|PubMed:18474783, ECO:0000269|PubMed:21203343,
FT ECO:0000269|PubMed:21288032, ECO:0000269|PubMed:22072594"
FT /id="VAR_063715"
FT VARIANT 378
FT /note="G -> R (in CHED; dbSNP:rs780171125)"
FT /evidence="ECO:0000269|PubMed:19369245,
FT ECO:0000269|PubMed:20108384"
FT /id="VAR_064981"
FT VARIANT 383
FT /note="E -> K (in FECD4; affects protein processing and
FT transport to the cell surface; the mutant protein is
FT retained intracellularly; coexpression with wild-type
FT protein does not rescue the cell surface trafficking of
FT FECD4 mutant; dbSNP:rs267607065)"
FT /evidence="ECO:0000269|PubMed:18024964,
FT ECO:0000269|PubMed:22072594, ECO:0000269|PubMed:25007886"
FT /id="VAR_047809"
FT VARIANT 385
FT /note="T -> K (in CHED)"
FT /evidence="ECO:0000269|PubMed:17679935"
FT /id="VAR_064982"
FT VARIANT 392
FT /note="Q -> H"
FT /evidence="ECO:0000269|PubMed:11302728"
FT /id="VAR_015521"
FT VARIANT 393
FT /note="K -> N"
FT /evidence="ECO:0000269|PubMed:11302728"
FT /id="VAR_015522"
FT VARIANT 402
FT /note="G -> D (in CHED)"
FT /evidence="ECO:0000269|PubMed:17679935,
FT ECO:0000269|PubMed:19369245"
FT /id="VAR_064983"
FT VARIANT 418
FT /note="T -> I (in FECD4; decreases cell surface expression;
FT highly reduces functional activity)"
FT /evidence="ECO:0000269|PubMed:25007886"
FT /id="VAR_075538"
FT VARIANT 448
FT /note="G -> D (in CHED; affects protein processing and
FT transport to the cell surface; dbSNP:rs121909389)"
FT /evidence="ECO:0000269|PubMed:16767101,
FT ECO:0000269|PubMed:21288032"
FT /id="VAR_030662"
FT VARIANT 457
FT /note="L -> R (in CHED)"
FT /evidence="ECO:0000269|PubMed:17679935"
FT /id="VAR_064984"
FT VARIANT 467
FT /note="M -> T"
FT /evidence="ECO:0000269|PubMed:11302728"
FT /id="VAR_015523"
FT VARIANT 472
FT /note="R -> K (in CDPD; dbSNP:rs121909393)"
FT /evidence="ECO:0000269|PubMed:17220209"
FT /id="VAR_034947"
FT VARIANT 473
FT /note="S -> L (in CHED; affects protein processing and
FT transport to the cell surface; dbSNP:rs121909388)"
FT /evidence="ECO:0000269|PubMed:16767101,
FT ECO:0000269|PubMed:17679935, ECO:0000269|PubMed:21288032"
FT /id="VAR_030663"
FT VARIANT 491
FT /note="V -> I (in FECD4; slightly decreases cell surface
FT expression; reduces; dbSNP:rs532728316)"
FT /evidence="ECO:0000269|PubMed:25007886"
FT /id="VAR_075539"
FT VARIANT 510
FT /note="Y -> C (in FECD4; does not interferes with post-
FT translational processing; the mutant protein partially
FT localizes to the cytoplasm; dbSNP:rs150571742)"
FT /evidence="ECO:0000269|PubMed:20848555"
FT /id="VAR_064424"
FT VARIANT 545
FT /note="T -> M (in dbSNP:rs755379986)"
FT /evidence="ECO:0000269|PubMed:18024964"
FT /id="VAR_047810"
FT VARIANT 549
FT /note="S -> L (in dbSNP:rs754745672)"
FT /evidence="ECO:0000269|PubMed:18024964"
FT /id="VAR_047811"
FT VARIANT 559
FT /note="V -> M (in FECD4; does not interferes with post-
FT translational processing; the mutant protein partially
FT localizes to the cytoplasm; dbSNP:rs144734280)"
FT /evidence="ECO:0000269|PubMed:20848555"
FT /id="VAR_064425"
FT VARIANT 567
FT /note="G -> D (in FECD4; interferes with post-translational
FT processing; the mutant protein localizes to the cytoplasm;
FT dbSNP:rs139078082)"
FT /evidence="ECO:0000269|PubMed:20848555"
FT /id="VAR_064426"
FT VARIANT 568
FT /note="T -> K (in CHED)"
FT /evidence="ECO:0000269|PubMed:17679935"
FT /id="VAR_064985"
FT VARIANT 659
FT /note="E -> A (in CHED; dbSNP:rs749826950)"
FT /evidence="ECO:0000269|PubMed:26286922"
FT /id="VAR_074015"
FT VARIANT 692
FT /note="T -> A (in dbSNP:rs1180556979)"
FT /evidence="ECO:0000269|PubMed:11302728"
FT /id="VAR_015524"
FT VARIANT 693
FT /note="G -> E (in FECD4; affects protein processing and
FT transport to the cell surface; the mutant protein is
FT retained intracellularly; coexpression with wild-type
FT protein does not rescue the cell surface trafficking of
FT FECD4 mutant; dbSNP:rs267607064)"
FT /evidence="ECO:0000269|PubMed:18024964,
FT ECO:0000269|PubMed:22072594"
FT /id="VAR_047812"
FT VARIANT 726
FT /note="G -> R (in FECD4; interferes with post-translational
FT processing; the mutant protein partially localizes to the
FT cytoplasm; dbSNP:rs143965185)"
FT /evidence="ECO:0000269|PubMed:20848555"
FT /id="VAR_064427"
FT VARIANT 738
FT /note="T -> M (in FECD4; affects protein processing and
FT transport to the cell surface; the mutant protein is
FT retained intracellularly; coexpression with wild-type
FT protein does not rescue the cell surface trafficking of
FT FECD4 mutant; dbSNP:rs267607066)"
FT /evidence="ECO:0000269|PubMed:18024964,
FT ECO:0000269|PubMed:22072594"
FT /id="VAR_047813"
FT VARIANT 739
FT /note="R -> Q (in CHED; affects protein processing and
FT transport to the cell surface; the mutant protein is
FT retained intracellularly; coexpression with wild-type
FT protein partially rescues the cell surface trafficking of
FT CHED mutant; dbSNP:rs121909387)"
FT /evidence="ECO:0000269|PubMed:16767101,
FT ECO:0000269|PubMed:16825429, ECO:0000269|PubMed:17397048,
FT ECO:0000269|PubMed:17679935, ECO:0000269|PubMed:21288032"
FT /id="VAR_030664"
FT VARIANT 739
FT /note="R -> W (in CHED; affects protein processing and
FT folding; dbSNP:rs757553189)"
FT /evidence="ECO:0000269|PubMed:17397048,
FT ECO:0000269|PubMed:17679935, ECO:0000269|PubMed:18474783,
FT ECO:0000269|PubMed:21288032, ECO:0000269|PubMed:22072594"
FT /id="VAR_063716"
FT VARIANT 757
FT /note="P -> L (in CHED; dbSNP:rs1465111896)"
FT /evidence="ECO:0000269|PubMed:17679935,
FT ECO:0000269|PubMed:18474783"
FT /id="VAR_063717"
FT VARIANT 788
FT /note="R -> H (in CHED; dbSNP:rs766567944)"
FT /evidence="ECO:0000269|PubMed:16825429"
FT /id="VAR_034948"
FT VARIANT 808
FT /note="V -> M (in CHED; deafness not assessed;
FT dbSNP:rs757244518)"
FT /evidence="ECO:0000269|PubMed:17220209,
FT ECO:0000269|PubMed:17679935, ECO:0000269|PubMed:21203343"
FT /id="VAR_034949"
FT VARIANT 817
FT /note="T -> M (in CHED; dbSNP:rs1422526172)"
FT /evidence="ECO:0000269|PubMed:16825429"
FT /id="VAR_034950"
FT VARIANT 818
FT /note="G -> S (in FECD4; does not interferes with post-
FT translational processing; the mutant protein partially
FT localizes to the cytoplasm; dbSNP:rs144586846)"
FT /evidence="ECO:0000269|PubMed:20848555"
FT /id="VAR_064428"
FT VARIANT 827
FT /note="L -> P (in CDPD; dbSNP:rs121909394)"
FT /evidence="ECO:0000269|PubMed:17220209"
FT /id="VAR_034951"
FT VARIANT 832
FT /note="M -> I (in dbSNP:rs34224785)"
FT /id="VAR_034952"
FT VARIANT 840
FT /note="M -> V (in CDPD; dbSNP:rs121909396)"
FT /evidence="ECO:0000269|PubMed:17220209"
FT /id="VAR_034953"
FT VARIANT 853
FT /note="R -> C (in CHED; affects protein processing and
FT transport to the cell surface; dbSNP:rs121909391)"
FT /evidence="ECO:0000269|PubMed:16767101,
FT ECO:0000269|PubMed:17397048, ECO:0000269|PubMed:17679935,
FT ECO:0000269|PubMed:21288032"
FT /id="VAR_030665"
FT VARIANT 853
FT /note="R -> H (in CHED; dbSNP:rs121909392)"
FT /evidence="ECO:0000269|PubMed:16825429"
FT /id="VAR_034954"
FT VARIANT 857
FT /note="L -> P (in CHED)"
FT /evidence="ECO:0000269|PubMed:18474783"
FT /id="VAR_063718"
FT MUTAGEN 623
FT /note="N->A: Decreases the water flux across the plasma
FT membrane."
FT /evidence="ECO:0000269|PubMed:23813972"
FT CONFLICT 308
FT /note="S -> P (in Ref. 2; BAC11536)"
FT /evidence="ECO:0000305"
FT CONFLICT 560
FT /note="L -> P (in Ref. 2; BAG59341)"
FT /evidence="ECO:0000305"
FT CONFLICT 668
FT /note="N -> S (in Ref. 2; BAG59140)"
FT /evidence="ECO:0000305"
FT CONFLICT 768
FT /note="L -> R (in Ref. 5; AAI10541)"
FT /evidence="ECO:0000305"
FT CONFLICT 818
FT /note="G -> D (in Ref. 2; BAG59341)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 875 AA; 98181 MW; 6BEDDC9939BADF10 CRC64;
MAAATRRVFH LQPCENSPTM SQNGYFEDSS YYKCDTDDTF EAREEILGDE AFDTANSSIV
SGESIRFFVN VNLEMQATNT ENEATSGGCV LLHTSRKYLK LKNFKEEIRA HRDLDGFLAQ
ASIVLNETAT SLDNVLRTML RRFARDPDNN EPNCNLDLLM AMLFTDAGAP MRGKVHLLSD
TIQGVTATVT GVRYQQSWLC IICTMKALQK RHVCISRLVR PQNWGENSCE VRFVILVLAP
PKMKSTKTAM EVARTFATMF SDIAFRQKLL ETRTEEEFKE ALVHQRQLLT MVSHGPVAPR
TKERSTVSLP AHRHPEPPKC KDFVPFGKGI REDIARRFPL YPLDFTDGII GKNKAVGKYI
TTTLFLYFAC LLPTIAFGSL NDENTDGAID VQKTIAGQSI GGLLYALFSG QPLVILLTTA
PLALYIQVIR VICDDYDLDF NSFYAWTGLW NSFFLALYAF FNLSLVMSLF KRSTEEIIAL
FISITFVLDA VKGTVKIFWK YYYGHYLDDY HTKRTSSLVS LSGLGASLNA SLHTALNASF
LASPTELPSA THSGQATAVL SLLIMLGTLW LGYTLYQFKK SPYLHPCVRE ILSDCALPIA
VLAFSLISSH GFREIEMSKF RYNPSESPFA MAQIQSLSLR AVSGAMGLGF LLSMLFFIEQ
NLVAALVNAP ENRLVKGTAY HWDLLLLAII NTGLSLFGLP WIHAAYPHSP LHVRALALVE
ERVENGHIYD TIVNVKETRL TSLGASVLVG LSLLLLPVPL QWIPKPVLYG LFLYIALTSL
DGNQLVQRVA LLLKEQTAYP PTHYIRRVPQ RKIHYFTGLQ VLQLLLLCAF GMSSLPYMKM
IFPLIMIAMI PIRYILLPRI IEAKYLDVMD AEHRP
