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 28-JAN-2026, entry version 233. 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=6; IntAct=EBI-4402346, EBI-11037160; CC P51798; Q8N697: SLC15A4; NbExp=2; IntAct=EBI-4402346, EBI-4319594; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PIR; S68427; S68427. DR RefSeq; NP_001107803.1; NM_001114331.3. [P51798-2] DR RefSeq; NP_001278.1; NM_001287.6. [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 PDB; 8HVT; EM; 3.60 A; A/C=1-805. DR PDB; 9G6C; EM; 1.80 A; A/C=1-805. DR PDB; 9G6D; EM; 2.70 A; A/C=1-805. DR PDB; 9G6E; EM; 2.60 A; A/C=1-805. DR PDBsum; 7BXU; -. DR PDBsum; 7CQ5; -. DR PDBsum; 7CQ6; -. DR PDBsum; 7CQ7; -. DR PDBsum; 7JM7; -. DR PDBsum; 8HVT; -. DR PDBsum; 9G6C; -. DR PDBsum; 9G6D; -. DR PDBsum; 9G6E; -. DR AlphaFoldDB; P51798; -. DR EMDB; EMD-22389; -. DR EMDB; EMD-30238; -. DR EMDB; EMD-30436; -. DR EMDB; EMD-30437; -. DR EMDB; EMD-30438; -. DR EMDB; EMD-35048; -. DR EMDB; EMD-51097; -. DR EMDB; EMD-51098; -. DR EMDB; EMD-51099; -. DR SMR; P51798; -. DR BioGRID; 107600; 180. DR ComplexPortal; CPX-6321; CLCN7-OSTM1 chloride channel complex. DR FunCoup; P51798; 1524. DR IntAct; P51798; 102. 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 jPOST; P51798; -. DR MassIVE; P51798; -. DR PaxDb; 9606-ENSP00000372193; -. DR PeptideAtlas; P51798; -. DR ProteomicsDB; 19628; -. DR ProteomicsDB; 56398; -. [P51798-1] DR Pumba; P51798; -. DR Antibodypedia; 23121; 209 antibodies from 27 providers. DR DNASU; 1186; -. DR Ensembl; ENST00000382745.9; ENSP00000372193.4; ENSG00000103249.20. [P51798-1] 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 AGR; HGNC:2025; -. DR ClinPGx; PA26552; -. 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 OpenTargets; ENSG00000103249; -. DR Orphanet; 53; Albers-Schoenberg osteopetrosis. DR Orphanet; 667; Autosomal recessive malignant osteopetrosis. DR Orphanet; 210110; Intermediate osteopetrosis. DR VEuPathDB; HostDB:ENSG00000103249; -. DR eggNOG; KOG0474; Eukaryota. DR GeneTree; ENSGT00940000158458; -. DR HOGENOM; CLU_003181_4_1_1; -. DR InParanoid; P51798; -. DR OMA; KCDHNGF; -. DR OrthoDB; 428525at2759; -. DR PAN-GO; P51798; 3 GO annotations based on evolutionary models. DR PhylomeDB; P51798; -. DR PathwayCommons; P51798; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR SignaLink; P51798; -. DR SIGNOR; P51798; -. DR Agora; ENSG00000103249; -. DR BioGRID-ORCS; 1186; 8 hits in 1157 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 203 other cell types or tissues. DR ExpressionAtlas; P51798; baseline and differential. DR GO; GO:0034707; C:chloride channel complex; IPI:ComplexPortal. DR GO; GO:0005765; C:lysosomal membrane; IDA:ComplexPortal. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005254; F:chloride channel activity; TAS:ProtInc. DR GO; GO:0062158; F:chloride:proton antiporter activity; IBA:GO_Central. DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central. DR GO; GO:0009268; P:response to pH; IEA:Ensembl. DR GO; GO:0030321; P:transepithelial chloride transport; IDA:ComplexPortal. DR CDD; cd04591; CBS_pair_voltage-gated_CLC_euk_bac; 1. DR CDD; cd03685; ClC_6_like; 1. DR FunFam; 3.10.580.10:FF:000076; Chloride channel protein; 1. DR Gene3D; 3.10.580.10; CBS-domain; 1. DR Gene3D; 1.10.3080.10; Clc chloride channel; 1. DR InterPro; IPR000644; CBS_dom. DR InterPro; IPR046342; CBS_dom_sf. DR InterPro; IPR002249; CIC-7. DR InterPro; IPR051280; Cl-channel/antiporter. DR InterPro; IPR014743; Cl-channel_core. DR InterPro; IPR001807; ClC. DR PANTHER; PTHR11689; CHLORIDE CHANNEL PROTEIN CLC FAMILY MEMBER; 1. DR PANTHER; PTHR11689:SF136; H(+)_CL(-) EXCHANGE TRANSPORTER 7; 1. DR Pfam; PF00571; CBS; 1. DR Pfam; PF00654; Voltage_CLC; 1. DR PRINTS; PR00762; CLCHANNEL. DR PRINTS; PR01118; CLCHANNEL7. DR SMART; SM00116; CBS; 2. DR SUPFAM; SSF54631; CBS-domain pair; 1. DR SUPFAM; SSF81340; Clc chloride channel; 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; KW Proteomics identification; Reference proteome; Repeat; Transmembrane; KW 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 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; uncertain 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; uncertain 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; uncertain significance; FT dbSNP:rs1291061962)" FT /evidence="ECO:0000269|PubMed:26395888" FT /id="VAR_075578" FT VARIANT 290 FT /note="S -> Y (in OPTA2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26395888" FT /id="VAR_075579" FT VARIANT 299 FT /note="A -> V (in OPTB4; uncertain significance; FT dbSNP:rs977932714)" FT /evidence="ECO:0000269|PubMed:26477479" FT /id="VAR_075580" FT VARIANT 318 FT /note="F -> L (in OPTA2; dbSNP:rs2038825509)" FT /evidence="ECO:0000269|PubMed:19953639" FT /id="VAR_064640" FT VARIANT 326 FT /note="R -> G (in OPTA2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26395888" FT /id="VAR_075581" FT VARIANT 332 FT /note="M -> V (in OPTB4; dbSNP:rs2142378539)" FT /evidence="ECO:0000269|PubMed:14584882" FT /id="VAR_021001" FT VARIANT 347 FT /note="G -> R (in OPTA2; uncertain 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; uncertain 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; uncertain 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; dbSNP:rs2142366157)" 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 //