CC115_HUMAN
ID CC115_HUMAN Reviewed; 180 AA.
AC Q96NT0; B4DJ47; Q9BR88;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Coiled-coil domain-containing protein 115 {ECO:0000303|PubMed:26833332};
GN Name=CCDC115 {ECO:0000303|PubMed:26833332, ECO:0000312|HGNC:HGNC:28178};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum, and Substantia nigra;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=16378758; DOI=10.1016/j.modgep.2005.07.004;
RA Pellicano F., Inglis-Broadgate S.L., Pante G., Ansorge W., Iwata T.;
RT "Expression of coiled-coil protein 1, a novel gene downstream of FGF2, in
RT the developing brain.";
RL Gene Expr. Patterns 6:285-293(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [6]
RP SUBCELLULAR LOCATION, VARIANTS CDG2O TYR-11 AND SER-31, FUNCTION, AND
RP INVOLVEMENT IN CDG2O.
RX PubMed=26833332; DOI=10.1016/j.ajhg.2015.12.010;
RA Jansen J.C., Cirak S., van Scherpenzeel M., Timal S., Reunert J., Rust S.,
RA Perez B., Vicogne D., Krawitz P., Wada Y., Ashikov A., Perez-Cerda C.,
RA Medrano C., Arnoldy A., Hoischen A., Huijben K., Steenbergen G.,
RA Quelhas D., Diogo L., Rymen D., Jaeken J., Guffon N., Cheillan D.,
RA van den Heuvel L.P., Maeda Y., Kaiser O., Schara U., Gerner P.,
RA van den Boogert M.A., Holleboom A.G., Nassogne M.C., Sokal E., Salomon J.,
RA van den Bogaart G., Drenth J.P., Huynen M.A., Veltman J.A., Wevers R.A.,
RA Morava E., Matthijs G., Foulquier F., Marquardt T., Lefeber D.J.;
RT "CCDC115 deficiency causes a disorder of Golgi homeostasis with abnormal
RT protein glycosylation.";
RL Am. J. Hum. Genet. 98:310-321(2016).
RN [7]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=28296633; DOI=10.7554/elife.22693;
RA Miles A.L., Burr S.P., Grice G.L., Nathan J.A.;
RT "The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115,
RT control HIF1alpha prolyl hydroxylation by regulating cellular iron
RT levels.";
RL Elife 6:E22693-E22693(2017).
CC -!- FUNCTION: Accessory component of the proton-transporting vacuolar (V)-
CC ATPase protein pump involved in intracellular iron homeostasis. In
CC aerobic conditions, required for intracellular iron homeostasis, thus
CC triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and
CC leading to HIF1A hydroxylation and subsequent proteasomal degradation.
CC Necessary for endolysosomal acidification and lysosomal degradation
CC (PubMed:28296633). May be involved in Golgi homeostasis
CC (PubMed:26833332). {ECO:0000269|PubMed:26833332,
CC ECO:0000269|PubMed:28296633}.
CC -!- SUBUNIT: Accessory component of the multisubunit proton-transporting
CC vacuolar (V)-ATPase protein pump. {ECO:0000269|PubMed:28296633}.
CC -!- INTERACTION:
CC Q96NT0; Q9NYB9-2: ABI2; NbExp=5; IntAct=EBI-2810325, EBI-11096309;
CC Q96NT0; O15296: ALOX15B; NbExp=3; IntAct=EBI-2810325, EBI-12150557;
CC Q96NT0; Q9NYP9: MIS18A; NbExp=3; IntAct=EBI-2810325, EBI-1104552;
CC Q96NT0; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-2810325, EBI-741158;
CC Q96NT0; P54136: RARS1; NbExp=3; IntAct=EBI-2810325, EBI-355482;
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000250|UniProtKB:Q8VE99}. Lysosome
CC {ECO:0000250|UniProtKB:Q8VE99}. Endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000269|PubMed:26833332}. Cytoplasmic
CC vesicle, COPI-coated vesicle {ECO:0000269|PubMed:26833332}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:28296633}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96NT0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96NT0-2; Sequence=VSP_056115, VSP_056116;
CC -!- TISSUE SPECIFICITY: Expressed throughout the brain.
CC {ECO:0000269|PubMed:16378758}.
CC -!- DISEASE: Congenital disorder of glycosylation 2O (CDG2O) [MIM:616828]:
CC A form of congenital disorder of glycosylation, a genetically
CC heterogeneous group of autosomal recessive, multisystem disorders
CC caused by a defect in glycoprotein biosynthesis and characterized by
CC under-glycosylated serum glycoproteins. Congenital disorders of
CC glycosylation result in a wide variety of clinical features, such as
CC defects in the nervous system development, psychomotor retardation,
CC dysmorphic features, hypotonia, coagulation disorders, and
CC immunodeficiency. The broad spectrum of features reflects the critical
CC role of N-glycoproteins during embryonic development, differentiation,
CC and maintenance of cell functions. CDG2O is characterized by
CC hepatosplenomegaly, liver failure, hypotonia, and psychomotor
CC disability. {ECO:0000269|PubMed:26833332}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
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DR EMBL; AK054693; BAB70794.1; -; mRNA.
DR EMBL; AK295922; BAG58709.1; -; mRNA.
DR EMBL; AC132479; AAY24075.1; -; Genomic_DNA.
DR EMBL; BC006429; AAH06429.2; -; mRNA.
DR CCDS; CCDS2159.1; -. [Q96NT0-1]
DR RefSeq; NP_001308047.1; NM_001321118.1.
DR RefSeq; NP_001308048.1; NM_001321119.1.
DR RefSeq; NP_115733.2; NM_032357.3. [Q96NT0-1]
DR AlphaFoldDB; Q96NT0; -.
DR SMR; Q96NT0; -.
DR BioGRID; 124043; 101.
DR IntAct; Q96NT0; 44.
DR MINT; Q96NT0; -.
DR STRING; 9606.ENSP00000259229; -.
DR iPTMnet; Q96NT0; -.
DR PhosphoSitePlus; Q96NT0; -.
DR BioMuta; CCDC115; -.
DR DMDM; 74732634; -.
DR EPD; Q96NT0; -.
DR jPOST; Q96NT0; -.
DR MassIVE; Q96NT0; -.
DR MaxQB; Q96NT0; -.
DR PaxDb; Q96NT0; -.
DR PeptideAtlas; Q96NT0; -.
DR PRIDE; Q96NT0; -.
DR ProteomicsDB; 4345; -.
DR ProteomicsDB; 77553; -. [Q96NT0-1]
DR TopDownProteomics; Q96NT0-1; -. [Q96NT0-1]
DR Antibodypedia; 33494; 67 antibodies from 20 providers.
DR DNASU; 84317; -.
DR Ensembl; ENST00000259229.7; ENSP00000259229.2; ENSG00000136710.10. [Q96NT0-1]
DR Ensembl; ENST00000651709.1; ENSP00000499101.1; ENSG00000136710.10. [Q96NT0-2]
DR GeneID; 84317; -.
DR KEGG; hsa:84317; -.
DR MANE-Select; ENST00000259229.7; ENSP00000259229.2; NM_032357.4; NP_115733.2.
DR UCSC; uc002tqy.3; human. [Q96NT0-1]
DR CTD; 84317; -.
DR DisGeNET; 84317; -.
DR GeneCards; CCDC115; -.
DR HGNC; HGNC:28178; CCDC115.
DR HPA; ENSG00000136710; Low tissue specificity.
DR MalaCards; CCDC115; -.
DR MIM; 613734; gene.
DR MIM; 616828; phenotype.
DR neXtProt; NX_Q96NT0; -.
DR OpenTargets; ENSG00000136710; -.
DR Orphanet; 468684; CCDC115-CDG.
DR PharmGKB; PA145149287; -.
DR VEuPathDB; HostDB:ENSG00000136710; -.
DR eggNOG; ENOG502S392; Eukaryota.
DR GeneTree; ENSGT00390000012929; -.
DR HOGENOM; CLU_107415_0_0_1; -.
DR InParanoid; Q96NT0; -.
DR OMA; RMEPRVC; -.
DR PhylomeDB; Q96NT0; -.
DR TreeFam; TF324647; -.
DR PathwayCommons; Q96NT0; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR SignaLink; Q96NT0; -.
DR BioGRID-ORCS; 84317; 525 hits in 1101 CRISPR screens.
DR GenomeRNAi; 84317; -.
DR Pharos; Q96NT0; Tbio.
DR PRO; PR:Q96NT0; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96NT0; protein.
DR Bgee; ENSG00000136710; Expressed in kidney epithelium and 179 other tissues.
DR ExpressionAtlas; Q96NT0; baseline and differential.
DR Genevisible; Q96NT0; HS.
DR GO; GO:0030137; C:COPI-coated vesicle; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IDA:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:UniProtKB.
DR GO; GO:0036295; P:cellular response to increased oxygen levels; IMP:UniProtKB.
DR GO; GO:0007042; P:lysosomal lumen acidification; IMP:UniProtKB.
DR GO; GO:1905146; P:lysosomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070072; P:vacuolar proton-transporting V-type ATPase complex assembly; IEA:InterPro.
DR InterPro; IPR040357; Vma22/CCDC115.
DR PANTHER; PTHR31996; PTHR31996; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Congenital disorder of glycosylation;
KW Cytoplasmic vesicle; Disease variant; Endoplasmic reticulum; Endosome;
KW Lysosome; Reference proteome.
FT CHAIN 1..180
FT /note="Coiled-coil domain-containing protein 115"
FT /id="PRO_0000279403"
FT REGION 92..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 16..37
FT /evidence="ECO:0000255"
FT COILED 153..176
FT /evidence="ECO:0000255"
FT COMPBIAS 92..111
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..36
FT /note="MAALDLRAELDSLVLQLLGDLEELEGKRTVLNARVE -> MGTPLDGGSRVP
FT IGCPAKLRRVTRKKVAPDL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056115"
FT VAR_SEQ 145..180
FT /note="LQLAADIASLQNRIDWGRSQLRGLQEKLKQLEPGAA -> VLEAKKRKCFLE
FT RVIQCVVSPAAEQEAEDESCPEDWAAAVPAETSAKAI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056116"
FT VARIANT 11
FT /note="D -> Y (in CDG2O; dbSNP:rs869025583)"
FT /evidence="ECO:0000269|PubMed:26833332"
FT /id="VAR_075752"
FT VARIANT 31
FT /note="L -> S (in CDG2O; dbSNP:rs751325113)"
FT /evidence="ECO:0000269|PubMed:26833332"
FT /id="VAR_075753"
SQ SEQUENCE 180 AA; 19761 MW; 45DEB6AF24F59452 CRC64;
MAALDLRAEL DSLVLQLLGD LEELEGKRTV LNARVEEGWL SLAKARYAMG AKSVGPLQYA
SHMEPQVCLH ASEAQEGLQK FKVVRAGVHA PEEVGPREAG LRRRKGPTKT PEPESSEAPQ
DPLNWFGILV PHSLRQAQAS FRDGLQLAAD IASLQNRIDW GRSQLRGLQE KLKQLEPGAA
