ACD_HUMAN
ID ACD_HUMAN Reviewed; 458 AA.
AC Q96AP0; A0A0C4DGT6; Q562H5; Q9H8F9;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 4.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Adrenocortical dysplasia protein homolog {ECO:0000305};
DE AltName: Full=POT1 and TIN2-interacting protein;
GN Name=ACD {ECO:0000312|HGNC:HGNC:25070};
GN Synonyms=PIP1 {ECO:0000303|PubMed:15231715},
GN PTOP {ECO:0000303|PubMed:15181449}, TINT1, TPP1;
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 3), MOTIF, SUBCELLULAR LOCATION,
RP INTERACTION WITH POT1 AND TINF2, FUNCTION, AND VARIANT ALA-432.
RX PubMed=15181449; DOI=10.1038/ncb1142;
RA Liu D., Safari A., O'Connor M.S., Chan D.W., Laegeler A., Qin J.,
RA Songyang Z.;
RT "PTOP interacts with POT1 and regulates its localization to telomeres.";
RL Nat. Cell Biol. 6:673-680(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
RX PubMed=15537664; DOI=10.1093/hmg/ddi011;
RA Keegan C.E., Hutz J.E., Else T., Adamska M., Shah S.P., Kent A.E.,
RA Howes J.M., Beamer W.G., Hammer G.D.;
RT "Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is
RT caused by a splicing mutation in a novel telomeric regulator.";
RL Hum. Mol. Genet. 14:113-123(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ALA-432.
RC TISSUE=Duodenum;
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 INTERACTION WITH POT1 AND TINF2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15231715; DOI=10.1101/gad.1215404;
RA Ye J.Z.-S., Hockemeyer D., Krutchinsky A.N., Loayza D., Hooper S.M.,
RA Chait B.T., de Lange T.;
RT "POT1-interacting protein PIP1: a telomere length regulator that recruits
RT POT1 to the TIN2/TRF1 complex.";
RL Genes Dev. 18:1649-1654(2004).
RN [7]
RP IDENTIFICATION IN THE SHELTERIN COMPLEX.
RX PubMed=15316005; DOI=10.1074/jbc.m409047200;
RA Ye J.Z.-S., Donigian J.R., van Overbeek M., Loayza D., Luo Y.,
RA Krutchinsky A.N., Chait B.T., de Lange T.;
RT "TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on
RT telomeres.";
RL J. Biol. Chem. 279:47264-47271(2004).
RN [8]
RP IDENTIFICATION IN THE SHELTERIN COMPLEX.
RX PubMed=15383534; DOI=10.1074/jbc.m409293200;
RA Liu D., O'Connor M.S., Qin J., Songyang Z.;
RT "Telosome, a mammalian telomere-associated complex formed by multiple
RT telomeric proteins.";
RL J. Biol. Chem. 279:51338-51342(2004).
RN [9]
RP FUNCTION OF THE SHELTERIN COMPLEX.
RX PubMed=16166375; DOI=10.1101/gad.1346005;
RA de Lange T.;
RT "Shelterin: the protein complex that shapes and safeguards human
RT telomeres.";
RL Genes Dev. 19:2100-2110(2005).
RN [10]
RP FUNCTION IN SHELTERIN COMPLEX ASSEMBLY.
RX PubMed=16880378; DOI=10.1073/pnas.0605303103;
RA O'Connor M.S., Safari A., Xin H., Liu D., Songyang Z.;
RT "A critical role for TPP1 and TIN2 interaction in high-order telomeric
RT complex assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11874-11879(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP INTERACTION WITH STN1.
RX PubMed=19648609; DOI=10.1074/jbc.m109.021105;
RA Wan M., Qin J., Songyang Z., Liu D.;
RT "OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1,
RT associates with TPP1 and is implicated in telomere length regulation.";
RL J. Biol. Chem. 284:26725-26731(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, AND IDENTIFICATION BY
RP 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 [16]
RP FUNCTION.
RX PubMed=20231318; DOI=10.1101/gad.1881810;
RA Zaug A.J., Podell E.R., Nandakumar J., Cech T.R.;
RT "Functional interaction between telomere protein TPP1 and telomerase.";
RL Genes Dev. 24:613-622(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, 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 [19]
RP INVOLVEMENT IN DKCA6, VARIANT DKCA6 LYS-84 DEL, CHARACTERIZATION OF VARIANT
RP DKCA6 LYS-84 DEL, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25205116; DOI=10.1182/blood-2014-08-596445;
RA Guo Y., Kartawinata M., Li J., Pickett H.A., Teo J., Kilo T., Barbaro P.M.,
RA Keating B., Chen Y., Tian L., Al-Odaib A., Reddel R.R., Christodoulou J.,
RA Xu X., Hakonarson H., Bryan T.M.;
RT "Inherited bone marrow failure associated with germline mutation of ACD,
RT the gene encoding telomere protein TPP1.";
RL Blood 124:2767-2774(2014).
RN [20]
RP INVOLVEMENT IN DKCB7, VARIANTS DKCB7 LYS-84 DEL AND THR-405,
RP CHARACTERIZATION OF VARIANTS DKCB7 LYS-84 DEL AND THR-405, FUNCTION,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TINF2.
RX PubMed=25233904; DOI=10.1101/gad.248567.114;
RG NCI DCEG Cancer Genomics Research Laboratory;
RG NCI DCEG Cancer Sequencing Working Group;
RA Kocak H., Ballew B.J., Bisht K., Eggebeen R., Hicks B.D., Suman S.,
RA O'Neil A., Giri N., Maillard I., Alter B.P., Keegan C.E., Nandakumar J.,
RA Savage S.A.;
RT "Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL
RT patch of the telomere protein TPP1.";
RL Genes Dev. 28:2090-2102(2014).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, 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 [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-381, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 4-164, FUNCTION, SUBUNIT, AND
RP IDENTIFICATION IN A COMPLEX WITH POT1 AND SINGLE-STRANDED TELOMERIC DNA.
RX PubMed=17237768; DOI=10.1038/nature05454;
RA Wang F., Podell E.R., Zaug A.J., Yang Y., Baciu P., Cech T.R., Lei M.;
RT "The POT1-TPP1 telomere complex is a telomerase processivity factor.";
RL Nature 445:506-510(2007).
CC -!- FUNCTION: Component of the shelterin complex (telosome) that is
CC involved in the regulation of telomere length and protection. Shelterin
CC associates with arrays of double-stranded TTAGGG repeats added by
CC telomerase and protects chromosome ends. Without its protective
CC activity, telomeres are no longer hidden from the DNA damage
CC surveillance and chromosome ends are inappropriately processed by DNA
CC repair pathways. Promotes binding of POT1 to single-stranded telomeric
CC DNA. Modulates the inhibitory effects of POT1 on telomere elongation.
CC The ACD-POT1 heterodimer enhances telomere elongation by recruiting
CC telomerase to telomeres and increasing its processivity. May play a
CC role in organogenesis. {ECO:0000269|PubMed:15181449,
CC ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:16880378,
CC ECO:0000269|PubMed:17237768, ECO:0000269|PubMed:20231318,
CC ECO:0000269|PubMed:25205116, ECO:0000269|PubMed:25233904}.
CC -!- SUBUNIT: Component of the shelterin complex (telosome) composed of
CC TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Forms heterodimers with
CC POT1. Identified in a complex with POT1 and single-stranded telomeric
CC DNA. Interacts with STN1 and TINF2. {ECO:0000269|PubMed:15181449,
CC ECO:0000269|PubMed:15231715, ECO:0000269|PubMed:15316005,
CC ECO:0000269|PubMed:15383534, ECO:0000269|PubMed:17237768,
CC ECO:0000269|PubMed:19648609, ECO:0000269|PubMed:25233904}.
CC -!- INTERACTION:
CC Q96AP0; Q9UJU6: DBNL; NbExp=2; IntAct=EBI-717666, EBI-751783;
CC Q96AP0; Q14195: DPYSL3; NbExp=2; IntAct=EBI-717666, EBI-1104726;
CC Q96AP0; O75821: EIF3G; NbExp=2; IntAct=EBI-717666, EBI-366632;
CC Q96AP0; O43768: ENSA; NbExp=2; IntAct=EBI-717666, EBI-714511;
CC Q96AP0; O00410: IPO5; NbExp=2; IntAct=EBI-717666, EBI-356424;
CC Q96AP0; P07476: IVL; NbExp=2; IntAct=EBI-717666, EBI-11307220;
CC Q96AP0; Q8N386: LRRC25; NbExp=2; IntAct=EBI-717666, EBI-11304917;
CC Q96AP0; Q96JY6: PDLIM2; NbExp=2; IntAct=EBI-717666, EBI-9057264;
CC Q96AP0; Q9NUX5: POT1; NbExp=9; IntAct=EBI-717666, EBI-752420;
CC Q96AP0; Q9NUX5-1: POT1; NbExp=4; IntAct=EBI-717666, EBI-15593881;
CC Q96AP0; Q9NUX5-2: POT1; NbExp=3; IntAct=EBI-717666, EBI-752435;
CC Q96AP0; Q9H477: RBKS; NbExp=2; IntAct=EBI-717666, EBI-10982959;
CC Q96AP0; P49796: RGS3; NbExp=2; IntAct=EBI-717666, EBI-2107809;
CC Q96AP0; Q9Y3A5: SBDS; NbExp=2; IntAct=EBI-717666, EBI-1046471;
CC Q96AP0; P31948: STIP1; NbExp=2; IntAct=EBI-717666, EBI-1054052;
CC Q96AP0; Q9H668: STN1; NbExp=4; IntAct=EBI-717666, EBI-746930;
CC Q96AP0; Q9UNE7: STUB1; NbExp=2; IntAct=EBI-717666, EBI-357085;
CC Q96AP0; Q9BXI6: TBC1D10A; NbExp=2; IntAct=EBI-717666, EBI-7815040;
CC Q96AP0; Q9BTW9: TBCD; NbExp=2; IntAct=EBI-717666, EBI-356005;
CC Q96AP0; Q9BSI4: TINF2; NbExp=15; IntAct=EBI-717666, EBI-717399;
CC Q96AP0; Q9BSI4-3: TINF2; NbExp=5; IntAct=EBI-717666, EBI-717418;
CC Q96AP0; Q13885: TUBB2A; NbExp=2; IntAct=EBI-717666, EBI-711595;
CC Q96AP0; Q92900: UPF1; NbExp=3; IntAct=EBI-717666, EBI-373471;
CC Q96AP0; P62258: YWHAE; NbExp=2; IntAct=EBI-717666, EBI-356498;
CC Q96AP0; Q91WC1: Pot1; Xeno; NbExp=3; IntAct=EBI-717666, EBI-7051001;
CC Q96AP0; Q8VC56: Rnf8; Xeno; NbExp=2; IntAct=EBI-717666, EBI-15954293;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15181449,
CC ECO:0000269|PubMed:25205116, ECO:0000269|PubMed:25233904}. Chromosome,
CC telomere {ECO:0000269|PubMed:15181449, ECO:0000269|PubMed:25205116,
CC ECO:0000269|PubMed:25233904}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=3;
CC IsoId=Q96AP0-3; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96AP0-2; Sequence=VSP_060243;
CC -!- DISEASE: Dyskeratosis congenita, autosomal dominant, 6 (DKCA6)
CC [MIM:616553]: A form of dyskeratosis congenita, a rare multisystem
CC disorder caused by defective telomere maintenance. It is characterized
CC by progressive bone marrow failure, and the clinical triad of
CC reticulated skin hyperpigmentation, nail dystrophy, and mucosal
CC leukoplakia. Common but variable features include premature graying,
CC aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and
CC liver fibrosis among others. Early mortality is often associated with
CC bone marrow failure, infections, fatal pulmonary complications, or
CC malignancy. {ECO:0000269|PubMed:25205116}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- DISEASE: Dyskeratosis congenita, autosomal recessive, 7 (DKCB7)
CC [MIM:616553]: A form of dyskeratosis congenita, a rare multisystem
CC disorder caused by defective telomere maintenance. It is characterized
CC by progressive bone marrow failure, and the clinical triad of
CC reticulated skin hyperpigmentation, nail dystrophy, and mucosal
CC leukoplakia. Common but variable features include premature graying,
CC aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and
CC liver fibrosis among others. Early mortality is often associated with
CC bone marrow failure, infections, fatal pulmonary complications, or
CC malignancy. {ECO:0000269|PubMed:25233904}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH16904.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAS80318.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14658.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY502940; AAS80318.1; ALT_INIT; mRNA.
DR EMBL; AY971883; AAX82621.1; -; Genomic_DNA.
DR EMBL; AK023726; BAB14658.1; ALT_INIT; mRNA.
DR EMBL; AC010530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016904; AAH16904.1; ALT_INIT; mRNA.
DR CCDS; CCDS10842.1; -. [Q96AP0-2]
DR CCDS; CCDS42181.1; -. [Q96AP0-3]
DR RefSeq; NP_001075955.1; NM_001082486.1. [Q96AP0-3]
DR RefSeq; NP_001075956.1; NM_001082487.1.
DR RefSeq; NP_075065.2; NM_022914.2. [Q96AP0-2]
DR PDB; 2I46; X-ray; 2.70 A; A/B=4-164.
DR PDB; 5H65; X-ray; 2.10 A; B=180-230.
DR PDB; 5I2X; X-ray; 3.00 A; A/B=4-164.
DR PDB; 5I2Y; X-ray; 3.00 A; A/B=4-164.
DR PDB; 5UN7; X-ray; 2.10 A; B=169-251.
DR PDB; 5XYF; X-ray; 2.20 A; B=424-458.
DR PDB; 7S1T; X-ray; 2.90 A; B/E/H/K=159-251.
DR PDBsum; 2I46; -.
DR PDBsum; 5H65; -.
DR PDBsum; 5I2X; -.
DR PDBsum; 5I2Y; -.
DR PDBsum; 5UN7; -.
DR PDBsum; 5XYF; -.
DR PDBsum; 7S1T; -.
DR AlphaFoldDB; Q96AP0; -.
DR SMR; Q96AP0; -.
DR BioGRID; 122379; 81.
DR ComplexPortal; CPX-152; Shelterin complex.
DR CORUM; Q96AP0; -.
DR DIP; DIP-29611N; -.
DR IntAct; Q96AP0; 81.
DR MINT; Q96AP0; -.
DR STRING; 9606.ENSP00000483117; -.
DR MoonDB; Q96AP0; Predicted.
DR iPTMnet; Q96AP0; -.
DR PhosphoSitePlus; Q96AP0; -.
DR SwissPalm; Q96AP0; -.
DR BioMuta; ACD; -.
DR DMDM; 296439451; -.
DR EPD; Q96AP0; -.
DR jPOST; Q96AP0; -.
DR MassIVE; Q96AP0; -.
DR MaxQB; Q96AP0; -.
DR PaxDb; Q96AP0; -.
DR PeptideAtlas; Q96AP0; -.
DR PRIDE; Q96AP0; -.
DR ProteomicsDB; 75980; -. [Q96AP0-2]
DR Antibodypedia; 29595; 360 antibodies from 26 providers.
DR DNASU; 65057; -.
DR Ensembl; ENST00000219251.13; ENSP00000219251.8; ENSG00000102977.17. [Q96AP0-2]
DR Ensembl; ENST00000620761.6; ENSP00000478084.1; ENSG00000102977.17. [Q96AP0-3]
DR GeneID; 65057; -.
DR KEGG; hsa:65057; -.
DR MANE-Select; ENST00000620761.6; ENSP00000478084.1; NM_001082486.2; NP_001075955.2.
DR UCSC; uc002etp.5; human. [Q96AP0-3]
DR CTD; 65057; -.
DR DisGeNET; 65057; -.
DR GeneCards; ACD; -.
DR GeneReviews; ACD; -.
DR HGNC; HGNC:25070; ACD.
DR HPA; ENSG00000102977; Low tissue specificity.
DR MalaCards; ACD; -.
DR MIM; 609377; gene.
DR MIM; 616553; phenotype.
DR neXtProt; NX_Q96AP0; -.
DR OpenTargets; ENSG00000102977; -.
DR Orphanet; 618; Familial melanoma.
DR Orphanet; 397692; Hereditary isolated aplastic anemia.
DR Orphanet; 3322; Hoyeraal-Hreidarsson syndrome.
DR PharmGKB; PA134882431; -.
DR VEuPathDB; HostDB:ENSG00000102977; -.
DR eggNOG; ENOG502SAN8; Eukaryota.
DR GeneTree; ENSGT00390000004877; -.
DR HOGENOM; CLU_619569_0_0_1; -.
DR InParanoid; Q96AP0; -.
DR OMA; YEPPCAS; -.
DR OrthoDB; 841353at2759; -.
DR PhylomeDB; Q96AP0; -.
DR TreeFam; TF338536; -.
DR PathwayCommons; Q96AP0; -.
DR Reactome; R-HSA-110328; Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
DR Reactome; R-HSA-110329; Cleavage of the damaged pyrimidine.
DR Reactome; R-HSA-110330; Recognition and association of DNA glycosylase with site containing an affected purine.
DR Reactome; R-HSA-110331; Cleavage of the damaged purine.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR Reactome; R-HSA-171306; Packaging Of Telomere Ends.
DR Reactome; R-HSA-171319; Telomere Extension By Telomerase.
DR Reactome; R-HSA-174411; Polymerase switching on the C-strand of the telomere.
DR Reactome; R-HSA-174414; Processive synthesis on the C-strand of the telomere.
DR Reactome; R-HSA-174417; Telomere C-strand (Lagging Strand) Synthesis.
DR Reactome; R-HSA-174430; Telomere C-strand synthesis initiation.
DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-9670095; Inhibition of DNA recombination at telomere.
DR SignaLink; Q96AP0; -.
DR SIGNOR; Q96AP0; -.
DR BioGRID-ORCS; 65057; 129 hits in 1081 CRISPR screens.
DR ChiTaRS; ACD; human.
DR EvolutionaryTrace; Q96AP0; -.
DR GeneWiki; ACD_(gene); -.
DR GenomeRNAi; 65057; -.
DR Pharos; Q96AP0; Tbio.
DR PRO; PR:Q96AP0; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96AP0; protein.
DR Bgee; ENSG00000102977; Expressed in right hemisphere of cerebellum and 191 other tissues.
DR ExpressionAtlas; Q96AP0; baseline and differential.
DR Genevisible; Q96AP0; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0000783; C:nuclear telomere cap complex; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0070187; C:shelterin complex; IDA:BHF-UCL.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IEA:InterPro.
DR GO; GO:0070182; F:DNA polymerase binding; IPI:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:BHF-UCL.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IEA:Ensembl.
DR GO; GO:0070200; P:establishment of protein localization to telomere; IMP:BHF-UCL.
DR GO; GO:0006886; P:intracellular protein transport; IMP:BHF-UCL.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:0060381; P:positive regulation of single-stranded telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:BHF-UCL.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IC:ComplexPortal.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IDA:BHF-UCL.
DR GO; GO:0031848; P:protection from non-homologous end joining at telomere; ISS:BHF-UCL.
DR GO; GO:0070198; P:protein localization to chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0035282; P:segmentation; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0032202; P:telomere assembly; IMP:BHF-UCL.
DR GO; GO:0016233; P:telomere capping; IDA:BHF-UCL.
DR GO; GO:0000723; P:telomere maintenance; IDA:MGI.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IEA:InterPro.
DR GO; GO:0001655; P:urogenital system development; IEA:Ensembl.
DR InterPro; IPR028631; ACD.
DR InterPro; IPR019437; TPP1/Est3.
DR PANTHER; PTHR14487; PTHR14487; 1.
DR Pfam; PF10341; TPP1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Disease variant;
KW DNA-binding; Dyskeratosis congenita; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Telomere; Ubl conjugation.
FT CHAIN 1..458
FT /note="Adrenocortical dysplasia protein homolog"
FT /id="PRO_0000239019"
FT REGION 158..251
FT /note="Interaction with POT1"
FT REGION 265..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 11..13
FT /note="PWI"
FT COMPBIAS 265..297
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 381
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 34..36
FT /note="Missing (in isoform 2)"
FT /id="VSP_060243"
FT VARIANT 84
FT /note="Missing (in DKCA6 and DKCB7; localizes properly on
FT telomeres; unable to recruit telomerase to the telomeres;
FT dbSNP:rs797045144)"
FT /evidence="ECO:0000269|PubMed:25205116,
FT ECO:0000269|PubMed:25233904"
FT /id="VAR_075693"
FT VARIANT 215
FT /note="T -> M (in dbSNP:rs72547495)"
FT /id="VAR_060224"
FT VARIANT 405
FT /note="P -> T (in DKCB7; localizes properly on telomeres;
FT decreased interaction with TINF2; dbSNP:rs201441120)"
FT /evidence="ECO:0000269|PubMed:25233904"
FT /id="VAR_075694"
FT VARIANT 432
FT /note="V -> A (in dbSNP:rs6979)"
FT /evidence="ECO:0000269|PubMed:15181449,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_060225"
FT CONFLICT 138
FT /note="C -> R (in Ref. 3; BAB14658)"
FT /evidence="ECO:0000305"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:5I2X"
FT HELIX 13..18
FT /evidence="ECO:0007829|PDB:2I46"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:2I46"
FT STRAND 27..36
FT /evidence="ECO:0007829|PDB:2I46"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:2I46"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:2I46"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:2I46"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:5I2X"
FT STRAND 94..106
FT /evidence="ECO:0007829|PDB:2I46"
FT STRAND 115..129
FT /evidence="ECO:0007829|PDB:2I46"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:2I46"
FT HELIX 142..152
FT /evidence="ECO:0007829|PDB:2I46"
FT HELIX 168..173
FT /evidence="ECO:0007829|PDB:7S1T"
FT HELIX 180..192
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:5UN7"
FT HELIX 206..213
FT /evidence="ECO:0007829|PDB:5H65"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 231..238
FT /evidence="ECO:0007829|PDB:5UN7"
FT HELIX 425..430
FT /evidence="ECO:0007829|PDB:5XYF"
FT HELIX 436..446
FT /evidence="ECO:0007829|PDB:5XYF"
SQ SEQUENCE 458 AA; 48967 MW; 6EA98FFC753E9A10 CRC64;
MAGSGRLVLR PWIRELILGS ETPSSPRAGQ LLEVLQDAEA AVAGPSHAPD TSDVGATLLV
SDGTHSVRCL VTREALDTSD WEEKEFGFRG TEGRLLLLQD CGVHVQVAEG GAPAEFYLQV
DRFSLLPTEQ PRLRVPGCNQ DLDVQKKLYD CLEEHLSEST SSNAGLSLSQ LLDEMREDQE
HQGALVCLAE SCLTLEGPCT APPVTHWAAS RCKATGEAVY TVPSSMLCIS ENDQLILSSL
GPCQRTQGPE LPPPDPALQD LSLTLIASPP SSPSSSGTPA LPGHMSSEES GTSISLLPAL
SLAAPDPGQR SSSQPSPAIC SAPATLTPRS PHASRTPSSP LQSCTPSLSP RSHVPSPHQA
LVTRPQKPSL EFKEFVGLPC KNRPPFPRTG ATRGAQEPCS VWEPPKRHRD GSAFQYEYEP
PCTSLCARVQ AVRLPPQLMA WALHFLMDAQ PGSEPTPM
