CLCN7_HUMAN
ID CLCN7_HUMAN Reviewed; 805 AA.
AC P51798; A6NEJ7; A8K5T9; A8K7X1; B3KPN3; E9PDB9; Q9NYX5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=H(+)/Cl(-) exchange transporter 7;
DE AltName: Full=Chloride channel 7 alpha subunit;
DE AltName: Full=Chloride channel protein 7;
DE Short=ClC-7;
GN Name=CLCN7 {ECO:0000312|HGNC:HGNC:2025};
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=Lens epithelium;
RA Rae J.L.;
RT "Ion channels in lens epithelia.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Synovium;
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=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-805 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8543009; DOI=10.1016/0014-5793(95)01298-2;
RA Brandt S., Jentsch T.J.;
RT "ClC-6 and ClC-7 are two novel broadly expressed members of the CLC
RT chloride channel family.";
RL FEBS Lett. 377:15-20(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 275-432.
RX PubMed=9565675; DOI=10.1016/s0167-4781(98)00014-1;
RA Eggermont J.;
RT "The exon-intron architecture of human chloride channel genes is not
RT conserved.";
RL Biochim. Biophys. Acta 1397:156-160(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 744-805 (ISOFORM 1).
RC TISSUE=Mammary gland;
RA Schutte B.C., Malik M.I., Fingert J., Stone E., Lamb F.S.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=18449189; DOI=10.1038/nature06907;
RA Graves A.R., Curran P.K., Smith C.L., Mindell J.A.;
RT "The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in
RT lysosomes.";
RL Nature 453:788-792(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP FUNCTION, SUBUNIT, INTERACTION WITH OSTM1, AND SUBCELLULAR LOCATION.
RX PubMed=21527911; DOI=10.1038/emboj.2011.137;
RA Leisle L., Ludwig C.F., Wagner F.A., Jentsch T.J., Stauber T.;
RT "ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1
RT for transport activity.";
RL EMBO J. 30:2140-2152(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-801, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP VARIANT OPTB4 GLN-762.
RX PubMed=11207362; DOI=10.1016/s0092-8674(01)00206-9;
RA Kornak U., Kasper D., Boesl M.R., Kaiser E., Schweizer M., Schulz A.,
RA Friedrich W., Delling G., Jentsch T.J.;
RT "Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and
RT man.";
RL Cell 104:205-215(2001).
RN [18]
RP VARIANT OPTB4 PRO-766, AND VARIANT OPTA2 TRP-767.
RX PubMed=11741829; DOI=10.1093/hmg/10.25.2861;
RA Cleiren E., Benichou O., Van Hul E., Gram J., Bollerslav J., Singer F.R.,
RA Beaverson K., Aledo A., Whyte M.P., Yoneyama T., de Vernejoul M.-C.,
RA Van Hul W.;
RT "Albers-Schonberg disease (autosomal dominant osteopetrosis, type II)
RT results from mutations in the ClCN7 chloride channel gene.";
RL Hum. Mol. Genet. 10:2861-2867(2001).
RN [19]
RP VARIANTS OPTB4 ARG-240; ARG-249; VAL-332; TRP-526; PRO-614; PHE-744;
RP GLN-767 AND TRP-767, VARIANTS OPTA2 ARG-215; GLN-286; PHE-490 AND VAL-677,
RP AND VARIANT MET-418.
RX PubMed=14584882; DOI=10.1359/jbmr.2003.18.10.1740;
RA Frattini A., Pangrazio A., Susani L., Sobacchi C., Mirolo M., Abinun M.,
RA Andolina M., Flanagan A., Horwitz E.M., Mihci E., Notarangelo L.D.,
RA Ramenghi U., Teti A., Van Hove J., Vujic D., Young T., Albertini A.,
RA Orchard P.J., Vezzoni P., Villa A.;
RT "Chloride channel ClCN7 mutations are responsible for severe recessive,
RT dominant, and intermediate osteopetrosis.";
RL J. Bone Miner. Res. 18:1740-1747(2003).
RN [20]
RP VARIANT OPTB4 PHE-261.
RX PubMed=17033731; DOI=10.1007/s10038-006-0075-4;
RA Lam C.-W., Tong S.-F., Wong K., Luo Y.F., Tang H.-Y., Ha S.-Y.,
RA Chan M.H.-M.;
RT "DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using
RT a single-nucleotide polymorphism microarray: standardization of molecular
RT investigations of genetic diseases due to consanguinity.";
RL J. Hum. Genet. 52:98-101(2007).
RN [21]
RP VARIANT OPTA2 TRP-767.
RX PubMed=19288050; DOI=10.1007/s00774-009-0051-0;
RA Zhang Z.L., He J.W., Zhang H., Hu W.W., Fu W.Z., Gu J.M., Yu J.B., Gao G.,
RA Hu Y.Q., Li M., Liu Y.J.;
RT "Identification of the CLCN7 gene mutations in two Chinese families with
RT autosomal dominant osteopetrosis (type II).";
RL J. Bone Miner. Metab. 27:444-451(2009).
RN [22]
RP VARIANTS OPTB4 PRO-132; SER-214; LEU-227 DEL; ARG-240; GLN-403; ARG-521;
RP GLN-526; TRP-526; PRO-549; PRO-651; TRP-762 AND PRO-767, AND VARIANTS OPTA2
RP ARG-215; GLN-286; LEU-318; LEU-758; GLN-762 AND TRP-767.
RX PubMed=19953639; DOI=10.1002/humu.21167;
RA Pangrazio A., Pusch M., Caldana E., Frattini A., Lanino E., Tamhankar P.M.,
RA Phadke S., Lopez A.G., Orchard P., Mihci E., Abinun M., Wright M.,
RA Vettenranta K., Bariae I., Melis D., Tezcan I., Baumann C., Locatelli F.,
RA Zecca M., Horwitz E., Mansour L.S., Van Roij M., Vezzoni P., Villa A.,
RA Sobacchi C.;
RT "Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis:
RT report of 20 novel mutations.";
RL Hum. Mutat. 31:E1071-E1080(2010).
RN [23]
RP VARIANTS OPTA2 PHE-213; TRP-286; TYR-290; GLY-326; ARG-347; ASN-473 AND
RP PRO-564, AND VARIANT OPTB4 ARG-224.
RX PubMed=26395888; DOI=10.1007/s00198-015-3320-x;
RA Pang Q., Chi Y., Zhao Z., Xing X., Li M., Wang O., Jiang Y., Liao R.,
RA Sun Y., Dong J., Xia W.;
RT "Novel mutations of CLCN7 cause autosomal dominant osteopetrosis type II
RT (ADO-II) and intermediate autosomal recessive osteopetrosis (IARO) in
RT Chinese patients.";
RL Osteoporos. Int. 27:1047-1055(2016).
RN [24]
RP VARIANT OPTB4 VAL-299.
RX PubMed=26477479; DOI=10.1016/j.gene.2015.10.021;
RA Zeng B., Li R., Hu Y., Hu B., Zhao Q., Liu H., Yuan P., Wang Y.;
RT "A novel mutation and a known mutation in the CLCN7 gene associated with
RT relatively stable infantile malignant osteopetrosis in a Chinese patient.";
RL Gene 576:176-181(2016).
RN [25]
RP FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN HOD, VARIANT HOD CYS-715, AND
RP CHARACTERIZATION OF VARIANT HOD CYS-715.
RX PubMed=31155284; DOI=10.1016/j.ajhg.2019.04.008;
RG Undiagnosed Diseases Network;
RA Nicoli E.R., Weston M.R., Hackbarth M., Becerril A., Larson A., Zein W.M.,
RA Baker P.R. II, Burke J.D., Dorward H., Davids M., Huang Y., Adams D.R.,
RA Zerfas P.M., Chen D., Markello T.C., Toro C., Wood T., Elliott G., Vu M.,
RA Zheng W., Garrett L.J., Tifft C.J., Gahl W.A., Day-Salvatore D.L.,
RA Mindell J.A., Malicdan M.C.V.;
RT "Lysosomal Storage and Albinism Due to Effects of a De Novo CLCN7 Variant
RT on Lysosomal Acidification.";
RL Am. J. Hum. Genet. 104:1127-1138(2019).
CC -!- FUNCTION: Slowly voltage-gated channel mediating the exchange of
CC chloride ions against protons (PubMed:18449189, PubMed:21527911).
CC Functions as antiporter and contributes to the acidification of the
CC lysosome lumen and may be involved in maintaining lysosomal pH
CC (PubMed:18449189, PubMed:21527911, PubMed:31155284). The CLC channel
CC family contains both chloride channels and proton-coupled anion
CC transporters that exchange chloride or another anion for protons (By
CC similarity). The presence of conserved gating glutamate residues is
CC typical for family members that function as antiporters (By
CC similarity). {ECO:0000250|UniProtKB:P35523,
CC ECO:0000269|PubMed:18449189, ECO:0000269|PubMed:21527911,
CC ECO:0000269|PubMed:31155284}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 chloride(in) + H(+)(out) = 2 chloride(out) + H(+)(in);
CC Xref=Rhea:RHEA:29567, ChEBI:CHEBI:15378, ChEBI:CHEBI:17996;
CC Evidence={ECO:0000303|PubMed:18449189};
CC -!- SUBUNIT: Chloride channel 7 are heteromers of alpha (CLCN7) and beta
CC (OSTM1) subunits. {ECO:0000269|PubMed:21527911}.
CC -!- INTERACTION:
CC P51798; Q6P5T0: AQP7; NbExp=3; IntAct=EBI-4402346, EBI-10489564;
CC P51798; P19397: CD53; NbExp=3; IntAct=EBI-4402346, EBI-6657396;
CC P51798; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-4402346, EBI-11110431;
CC P51798; O00258: GET1; NbExp=3; IntAct=EBI-4402346, EBI-18908258;
CC P51798; Q53GS7: GLE1; NbExp=3; IntAct=EBI-4402346, EBI-1955541;
CC P51798; Q9UGI6-2: KCNN3; NbExp=3; IntAct=EBI-4402346, EBI-17888181;
CC P51798; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-4402346, EBI-2820517;
CC P51798; Q9Y5Y7: LYVE1; NbExp=3; IntAct=EBI-4402346, EBI-10329546;
CC P51798; P35372-10: OPRM1; NbExp=3; IntAct=EBI-4402346, EBI-12807478;
CC P51798; Q86WC4: OSTM1; NbExp=3; IntAct=EBI-4402346, EBI-11037160;
CC P51798; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-4402346, EBI-10314552;
CC P51798; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-4402346, EBI-3907610;
CC P51798; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-4402346, EBI-5235340;
CC P51798; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-4402346, EBI-12947623;
CC P51798; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-4402346, EBI-11724423;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:17897319,
CC ECO:0000269|PubMed:18449189, ECO:0000269|PubMed:21527911}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:17897319,
CC ECO:0000269|PubMed:18449189, ECO:0000269|PubMed:21527911}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P51798-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51798-2; Sequence=VSP_045698;
CC -!- TISSUE SPECIFICITY: Brain and kidney. {ECO:0000269|PubMed:31155284}.
CC -!- DISEASE: Osteopetrosis, autosomal recessive 4 (OPTB4) [MIM:611490]: A
CC rare genetic disease characterized by abnormally dense bone, due to
CC defective resorption of immature bone. Osteopetrosis occurs in two
CC forms: a severe autosomal recessive form occurring in utero, infancy,
CC or childhood, and a benign autosomal dominant form occurring in
CC adolescence or adulthood. Recessive osteopetrosis commonly manifests in
CC early infancy with macrocephaly, feeding difficulties, evolving
CC blindness and deafness, bone marrow failure, severe anemia, and
CC hepatosplenomegaly. Deafness and blindness are generally thought to
CC represent effects of pressure on nerves. {ECO:0000269|PubMed:11207362,
CC ECO:0000269|PubMed:11741829, ECO:0000269|PubMed:14584882,
CC ECO:0000269|PubMed:17033731, ECO:0000269|PubMed:19953639,
CC ECO:0000269|PubMed:26395888, ECO:0000269|PubMed:26477479}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Osteopetrosis, autosomal dominant 2 (OPTA2) [MIM:166600]: A
CC rare genetic disease characterized by abnormally dense bone, due to
CC defective resorption of immature bone. Osteopetrosis occurs in two
CC forms: a severe autosomal recessive form occurring in utero, infancy,
CC or childhood, and a benign autosomal dominant form occurring in
CC adolescence or adulthood. OPTA2 is the most common form of
CC osteopetrosis, occurring in adolescence or adulthood. It is
CC characterized by sclerosis, predominantly involving the spine, the
CC pelvis and the skull base. {ECO:0000269|PubMed:11741829,
CC ECO:0000269|PubMed:14584882, ECO:0000269|PubMed:19288050,
CC ECO:0000269|PubMed:19953639, ECO:0000269|PubMed:26395888}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hypopigmentation, organomegaly, and delayed myelination and
CC development (HOD) [MIM:618541]: An autosomal dominant pleiotropic
CC syndrome characterized by skin and hair hypopigmentation, growth and
CC developmental delay, organomegaly including enlarged liver, spleen and
CC kidneys, delayed brain myelination and developmental deficit in motor
CC skills. Skin and liver biopsies show cellular accumulation of large
CC intracellular vacuoles. {ECO:0000269|PubMed:31155284}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 7/CLCN7 subfamily. {ECO:0000305}.
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DR EMBL; AF224741; AAF34711.1; -; mRNA.
DR EMBL; AK056551; BAG51745.1; -; mRNA.
DR EMBL; AK291404; BAF84093.1; -; mRNA.
DR EMBL; AK292136; BAF84825.1; -; mRNA.
DR EMBL; AL031600; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012737; AAH12737.1; -; mRNA.
DR EMBL; Z67743; CAA91556.1; -; mRNA.
DR EMBL; AJ001910; CAA05083.1; -; Genomic_DNA.
DR EMBL; U88844; AAB48530.1; -; mRNA.
DR CCDS; CCDS32361.1; -. [P51798-1]
DR CCDS; CCDS45378.1; -. [P51798-2]
DR PIR; S68427; S68427.
DR RefSeq; NP_001107803.1; NM_001114331.2. [P51798-2]
DR RefSeq; NP_001278.1; NM_001287.5. [P51798-1]
DR PDB; 7BXU; EM; 3.70 A; A/B=1-805.
DR PDB; 7CQ5; EM; 2.60 A; C/D=1-805.
DR PDB; 7CQ6; EM; 3.00 A; C/D=1-805.
DR PDB; 7CQ7; EM; 3.55 A; C/D=1-805.
DR PDB; 7JM7; EM; 2.82 A; A/C=1-805.
DR PDBsum; 7BXU; -.
DR PDBsum; 7CQ5; -.
DR PDBsum; 7CQ6; -.
DR PDBsum; 7CQ7; -.
DR PDBsum; 7JM7; -.
DR AlphaFoldDB; P51798; -.
DR SMR; P51798; -.
DR BioGRID; 107600; 149.
DR ComplexPortal; CPX-6321; CLCN7-OSTM1 chloride channel complex.
DR IntAct; P51798; 65.
DR MINT; P51798; -.
DR STRING; 9606.ENSP00000372193; -.
DR GuidetoPHARMACOLOGY; 706; -.
DR TCDB; 2.A.49.3.3; the chloride carrier/channel (clc) family.
DR iPTMnet; P51798; -.
DR PhosphoSitePlus; P51798; -.
DR SwissPalm; P51798; -.
DR BioMuta; CLCN7; -.
DR DMDM; 12644301; -.
DR EPD; P51798; -.
DR jPOST; P51798; -.
DR MassIVE; P51798; -.
DR MaxQB; P51798; -.
DR PaxDb; P51798; -.
DR PeptideAtlas; P51798; -.
DR PRIDE; P51798; -.
DR ProteomicsDB; 19628; -.
DR ProteomicsDB; 56398; -. [P51798-1]
DR Antibodypedia; 23121; 200 antibodies from 27 providers.
DR DNASU; 1186; -.
DR Ensembl; ENST00000382745.9; ENSP00000372193.4; ENSG00000103249.18. [P51798-1]
DR Ensembl; ENST00000448525.5; ENSP00000410907.1; ENSG00000103249.18. [P51798-2]
DR GeneID; 1186; -.
DR KEGG; hsa:1186; -.
DR MANE-Select; ENST00000382745.9; ENSP00000372193.4; NM_001287.6; NP_001278.1.
DR UCSC; uc002clv.4; human. [P51798-1]
DR CTD; 1186; -.
DR DisGeNET; 1186; -.
DR GeneCards; CLCN7; -.
DR GeneReviews; CLCN7; -.
DR HGNC; HGNC:2025; CLCN7.
DR HPA; ENSG00000103249; Low tissue specificity.
DR MalaCards; CLCN7; -.
DR MIM; 166600; phenotype.
DR MIM; 602727; gene.
DR MIM; 611490; phenotype.
DR MIM; 618541; phenotype.
DR neXtProt; NX_P51798; -.
DR OpenTargets; ENSG00000103249; -.
DR Orphanet; 53; Albers-Schoenberg osteopetrosis.
DR Orphanet; 667; Autosomal recessive malignant osteopetrosis.
DR Orphanet; 210110; Intermediate osteopetrosis.
DR PharmGKB; PA26552; -.
DR VEuPathDB; HostDB:ENSG00000103249; -.
DR eggNOG; KOG0474; Eukaryota.
DR GeneTree; ENSGT00940000158458; -.
DR HOGENOM; CLU_003181_4_1_1; -.
DR InParanoid; P51798; -.
DR OMA; DYDVCEN; -.
DR OrthoDB; 410280at2759; -.
DR PhylomeDB; P51798; -.
DR TreeFam; TF313867; -.
DR PathwayCommons; P51798; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; P51798; -.
DR BioGRID-ORCS; 1186; 6 hits in 1077 CRISPR screens.
DR ChiTaRS; CLCN7; human.
DR GeneWiki; CLCN7; -.
DR GenomeRNAi; 1186; -.
DR Pharos; P51798; Tchem.
DR PRO; PR:P51798; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P51798; protein.
DR Bgee; ENSG00000103249; Expressed in metanephros cortex and 201 other tissues.
DR ExpressionAtlas; P51798; baseline and differential.
DR Genevisible; P51798; HS.
DR GO; GO:0034707; C:chloride channel complex; IPI:ComplexPortal.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IDA:ComplexPortal.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005254; F:chloride channel activity; TAS:ProtInc.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IEA:InterPro.
DR GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR GO; GO:0030321; P:transepithelial chloride transport; IDA:ComplexPortal.
DR Gene3D; 3.10.580.10; -; 1.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR014743; Cl-channel_core.
DR InterPro; IPR001807; Cl-channel_volt-gated.
DR InterPro; IPR002249; Cl_channel-7.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01118; CLCHANNEL7.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antiport; ATP-binding; CBS domain;
KW Chloride; Disease variant; Ion transport; Lysosome; Membrane;
KW Nucleotide-binding; Osteopetrosis; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..805
FT /note="H(+)/Cl(-) exchange transporter 7"
FT /id="PRO_0000094452"
FT TOPO_DOM 1..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 127..159
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 174..197
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 206..213
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 223..241
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 247..264
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 288..300
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 304..312
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 322..341
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 375..405
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 410..432
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 487..507
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 512..535
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 545..559
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 560..562
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT INTRAMEM 563..574
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 575..578
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT TRANSMEM 579..597
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 598..805
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 631..695
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 741..799
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 203..207
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 245..249
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 512..516
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT COMPBIAS 9..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 204
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 514
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 602
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 658..660
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 783..786
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 247
FT /note="Mediates proton transfer from the outer aqueous
FT phase to the interior of the protein; involved in linking
FT H(+) and Cl(-) transport"
FT /evidence="ECO:0000250"
FT SITE 314
FT /note="Mediates proton transfer from the protein to the
FT inner aqueous phase"
FT /evidence="ECO:0000250"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70496"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 801
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 48..71
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045698"
FT VARIANT 132
FT /note="L -> P (in OPTB4)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064637"
FT VARIANT 213
FT /note="L -> F (in OPTA2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075576"
FT VARIANT 214
FT /note="N -> S (in OPTB4; dbSNP:rs367567630)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064638"
FT VARIANT 215
FT /note="G -> R (in OPTA2; dbSNP:rs397515539)"
FT /evidence="ECO:0000269|PubMed:14584882,
FT ECO:0000269|PubMed:19953639"
FT /id="VAR_020997"
FT VARIANT 224
FT /note="L -> R (in OPTB4; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075577"
FT VARIANT 227
FT /note="Missing (in OPTB4; dbSNP:rs760209068)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064639"
FT VARIANT 240
FT /note="G -> R (in OPTB4; dbSNP:rs1360480518)"
FT /evidence="ECO:0000269|PubMed:14584882,
FT ECO:0000269|PubMed:19953639"
FT /id="VAR_020998"
FT VARIANT 249
FT /note="P -> R (in OPTB4)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_020999"
FT VARIANT 261
FT /note="I -> F (in OPTB4; dbSNP:rs121434436)"
FT /evidence="ECO:0000269|PubMed:17033731"
FT /id="VAR_037427"
FT VARIANT 286
FT /note="R -> Q (in OPTA2; dbSNP:rs760956030)"
FT /evidence="ECO:0000269|PubMed:14584882,
FT ECO:0000269|PubMed:19953639"
FT /id="VAR_021000"
FT VARIANT 286
FT /note="R -> W (in OPTA2; unknown pathological significance;
FT dbSNP:rs1291061962)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075578"
FT VARIANT 290
FT /note="S -> Y (in OPTA2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075579"
FT VARIANT 299
FT /note="A -> V (in OPTB4; unknown pathological significance;
FT dbSNP:rs977932714)"
FT /evidence="ECO:0000269|PubMed:26477479"
FT /id="VAR_075580"
FT VARIANT 318
FT /note="F -> L (in OPTA2)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064640"
FT VARIANT 326
FT /note="R -> G (in OPTA2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075581"
FT VARIANT 332
FT /note="M -> V (in OPTB4)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_021001"
FT VARIANT 347
FT /note="G -> R (in OPTA2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075582"
FT VARIANT 403
FT /note="R -> Q (in OPTB4; dbSNP:rs765444328)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064641"
FT VARIANT 418
FT /note="V -> M (in dbSNP:rs12926089)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_021002"
FT VARIANT 473
FT /note="S -> N (in OPTA2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075583"
FT VARIANT 490
FT /note="L -> F (in OPTA2)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_021003"
FT VARIANT 521
FT /note="G -> R (in OPTB4; dbSNP:rs368190250)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064642"
FT VARIANT 526
FT /note="R -> Q (in OPTB4; dbSNP:rs139329533)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064643"
FT VARIANT 526
FT /note="R -> W (in OPTB4; dbSNP:rs1233085260)"
FT /evidence="ECO:0000269|PubMed:14584882,
FT ECO:0000269|PubMed:19953639"
FT /id="VAR_021004"
FT VARIANT 549
FT /note="L -> P (in OPTB4)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064644"
FT VARIANT 564
FT /note="L -> P (in OPTA2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26395888"
FT /id="VAR_075584"
FT VARIANT 614
FT /note="L -> P (in OPTB4; dbSNP:rs1064794323)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_021005"
FT VARIANT 651
FT /note="L -> P (in OPTB4)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064645"
FT VARIANT 677
FT /note="G -> V (in OPTA2)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_021006"
FT VARIANT 715
FT /note="Y -> C (in HOD; increased voltage-gated chloride
FT channel activity; increased lysosomal lumen acidification;
FT increased cytoplasmic vacuole size; dbSNP:rs1057517718)"
FT /evidence="ECO:0000269|PubMed:31155284"
FT /id="VAR_083175"
FT VARIANT 744
FT /note="S -> F (in OPTB4; dbSNP:rs1320932332)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_021007"
FT VARIANT 758
FT /note="F -> L (in OPTA2; dbSNP:rs760740877)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064646"
FT VARIANT 762
FT /note="R -> Q (in OPTA2 and OPTB4; not detected in the
FT fibroblasts from the patient; dbSNP:rs121434433)"
FT /evidence="ECO:0000269|PubMed:11207362,
FT ECO:0000269|PubMed:19953639"
FT /id="VAR_017838"
FT VARIANT 762
FT /note="R -> W (in OPTB4; dbSNP:rs1490598538)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064647"
FT VARIANT 766
FT /note="L -> P (in OPTB4; dbSNP:rs121434434)"
FT /evidence="ECO:0000269|PubMed:11741829"
FT /id="VAR_017839"
FT VARIANT 767
FT /note="R -> P (in OPTB4)"
FT /evidence="ECO:0000269|PubMed:19953639"
FT /id="VAR_064648"
FT VARIANT 767
FT /note="R -> Q (in OPTB4; dbSNP:rs772579858)"
FT /evidence="ECO:0000269|PubMed:14584882"
FT /id="VAR_021008"
FT VARIANT 767
FT /note="R -> W (in OPTA2 and OPTB4; dbSNP:rs121434435)"
FT /evidence="ECO:0000269|PubMed:11741829,
FT ECO:0000269|PubMed:14584882, ECO:0000269|PubMed:19288050,
FT ECO:0000269|PubMed:19953639"
FT /id="VAR_017840"
FT CONFLICT 74
FT /note="D -> V (in Ref. 2; BAF84825)"
FT /evidence="ECO:0000305"
FT CONFLICT 267
FT /note="T -> S (in Ref. 5; CAA91556)"
FT /evidence="ECO:0000305"
FT CONFLICT 279
FT /note="F -> L (in Ref. 5; CAA91556 and 6; CAA05083)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="T -> A (in Ref. 2; BAF84825)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="N -> S (in Ref. 2; BAG51745)"
FT /evidence="ECO:0000305"
FT CONFLICT 415
FT /note="I -> V (in Ref. 2; BAG51745)"
FT /evidence="ECO:0000305"
FT CONFLICT 710
FT /note="D -> G (in Ref. 2; BAG51745)"
FT /evidence="ECO:0000305"
FT HELIX 105..114
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 122..169
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 172..195
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 206..214
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 224..239
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 251..261
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:7CQ5"
FT TURN 267..270
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 283..301
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 304..313
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 321..345
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 355..358
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 365..368
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:7JM7"
FT HELIX 375..405
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 410..433
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:7JM7"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 452..454
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 462..465
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 470..479
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 487..504
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 507..510
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 514..535
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 544..559
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 566..573
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 580..595
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 601..607
FT /evidence="ECO:0007829|PDB:7CQ5"
FT TURN 608..610
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 623..626
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 627..629
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 631..634
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 638..643
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 644..651
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 654..656
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 660..664
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 674..680
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 681..689
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 708..710
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 721..723
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 730..732
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 733..736
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 738..744
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 747..749
FT /evidence="ECO:0007829|PDB:7CQ5"
FT HELIX 754..764
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 769..772
FT /evidence="ECO:0007829|PDB:7CQ5"
FT STRAND 774..782
FT /evidence="ECO:0007829|PDB:7CQ5"
FT TURN 786..788
FT /evidence="ECO:0007829|PDB:7CQ5"
SQ SEQUENCE 805 AA; 88679 MW; E56BC0B4ADE1C695 CRC64;
MANVSKKVSW SGRDRDDEEA APLLRRTARP GGGTPLLNGA GPGAARQSPR SALFRVGHMS
SVELDDELLD PDMDPPHPFP KEIPHNEKLL SLKYESLDYD NSENQLFLEE ERRINHTAFR
TVEIKRWVIC ALIGILTGLV ACFIDIVVEN LAGLKYRVIK GNIDKFTEKG GLSFSLLLWA
TLNAAFVLVG SVIVAFIEPV AAGSGIPQIK CFLNGVKIPH VVRLKTLVIK VSGVILSVVG
GLAVGKEGPM IHSGSVIAAG ISQGRSTSLK RDFKIFEYFR RDTEKRDFVS AGAAAGVSAA
FGAPVGGVLF SLEEGASFWN QFLTWRIFFA SMISTFTLNF VLSIYHGNMW DLSSPGLINF
GRFDSEKMAY TIHEIPVFIA MGVVGGVLGA VFNALNYWLT MFRIRYIHRP CLQVIEAVLV
AAVTATVAFV LIYSSRDCQP LQGGSMSYPL QLFCADGEYN SMAAAFFNTP EKSVVSLFHD
PPGSYNPLTL GLFTLVYFFL ACWTYGLTVS AGVFIPSLLI GAAWGRLFGI SLSYLTGAAI
WADPGKYALM GAAAQLGGIV RMTLSLTVIM MEATSNVTYG FPIMLVLMTA KIVGDVFIEG
LYDMHIQLQS VPFLHWEAPV TSHSLTAREV MSTPVTCLRR REKVGVIVDV LSDTASNHNG
FPVVEHADDT QPARLQGLIL RSQLIVLLKH KVFVERSNLG LVQRRLRLKD FRDAYPRFPP
IQSIHVSQDE RECTMDLSEF MNPSPYTVPQ EASLPRVFKL FRALGLRHLV VVDNRNQVVG
LVTRKDLARY RLGKRGLEEL SLAQT
