ACD_MOUSE
ID ACD_MOUSE Reviewed; 416 AA.
AC Q5EE38; Q3TBB1; Q3TUR7; Q3UKL6; Q3V3Y1; Q99KF8;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Adrenocortical dysplasia protein {ECO:0000305};
GN Name=Acd {ECO:0000312|MGI:MGI:87873};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1),
RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, FUNCTION, AND INVOLVEMENT IN ACD.
RC STRAIN=DW/J;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC STRAIN=C57BL/6J;
RC TISSUE=Adrenal gland, Cerebellum, Embryo, Pituitary, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25; SER-313 AND SER-317, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By
CC similarity). May play a role in organogenesis (PubMed:15537664).
CC {ECO:0000250|UniProtKB:Q96AP0, ECO:0000269|PubMed:15537664}.
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:0000250|UniProtKB:Q96AP0,
CC ECO:0000269|PubMed:19648609}.
CC -!- INTERACTION:
CC Q5EE38; Q8K2X3: Stn1; NbExp=2; IntAct=EBI-6258642, EBI-2553883;
CC Q5EE38-1; Q91WC1: Pot1; NbExp=2; IntAct=EBI-15647355, EBI-7051001;
CC Q5EE38-1; Q3TNS5: Pot1b; NbExp=2; IntAct=EBI-15647355, EBI-15647404;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96AP0}.
CC Chromosome, telomere {ECO:0000250|UniProtKB:Q96AP0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q5EE38-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5EE38-2; Sequence=VSP_019070, VSP_019071;
CC Name=3;
CC IsoId=Q5EE38-3; Sequence=VSP_019068, VSP_019073;
CC Name=4;
CC IsoId=Q5EE38-4; Sequence=VSP_019067;
CC Name=5;
CC IsoId=Q5EE38-5; Sequence=VSP_019069, VSP_019072, VSP_019074,
CC VSP_019075;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15537664}.
CC -!- DEVELOPMENTAL STAGE: Expressed from 7 dpc to 18 dpc throughout
CC development. {ECO:0000269|PubMed:15537664}.
CC -!- DISEASE: Note=Defects in Acd are the cause of adrenocortical dysplasia
CC (ACD). ACD is a spontaneous autosomal recessive mouse mutant resulting
CC from spontaneous splicing mutation of acd. ACD mice are characterized
CC by developmental defects in organs derived from the urogenital ridge,
CC reduced survival, poor growth, skin hyperpigmentation and adrenal
CC insufficiency. Forty percent of the mutants died within 24 hours.
CC Analysis of 14.5 dpc to 17.5 dpc embryos revealed reduced formation of
CC caudal structure as well as limb defects.
CC -!- MISCELLANEOUS: Adrenocortical dysplasia mouse was initially reported as
CC a model of human congenital adrenal hypoplasia (AHC).
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DR EMBL; AY902197; AAW82804.1; -; Genomic_DNA.
DR EMBL; AK030405; BAE20450.1; -; mRNA.
DR EMBL; AK032683; BAE43282.1; -; mRNA.
DR EMBL; AK145959; BAE26785.1; -; mRNA.
DR EMBL; AK160599; BAE35904.1; -; mRNA.
DR EMBL; AK171345; BAE42403.1; -; mRNA.
DR EMBL; BC004682; AAH04682.1; -; mRNA.
DR CCDS; CCDS22608.1; -. [Q5EE38-1]
DR RefSeq; NP_001012656.1; NM_001012638.2. [Q5EE38-1]
DR RefSeq; NP_001335278.1; NM_001348349.1. [Q5EE38-3]
DR RefSeq; XP_006531237.1; XM_006531174.3. [Q5EE38-3]
DR RefSeq; XP_006531238.1; XM_006531175.2. [Q5EE38-3]
DR RefSeq; XP_006531239.1; XM_006531176.2.
DR RefSeq; XP_011246737.1; XM_011248435.2. [Q5EE38-3]
DR RefSeq; XP_017168377.1; XM_017312888.1.
DR AlphaFoldDB; Q5EE38; -.
DR SMR; Q5EE38; -.
DR ComplexPortal; CPX-153; Shelterin complex.
DR DIP; DIP-29612N; -.
DR IntAct; Q5EE38; 9.
DR STRING; 10090.ENSMUSP00000048180; -.
DR iPTMnet; Q5EE38; -.
DR PhosphoSitePlus; Q5EE38; -.
DR EPD; Q5EE38; -.
DR jPOST; Q5EE38; -.
DR MaxQB; Q5EE38; -.
DR PaxDb; Q5EE38; -.
DR PeptideAtlas; Q5EE38; -.
DR PRIDE; Q5EE38; -.
DR ProteomicsDB; 285971; -. [Q5EE38-1]
DR ProteomicsDB; 285972; -. [Q5EE38-2]
DR ProteomicsDB; 285973; -. [Q5EE38-3]
DR ProteomicsDB; 285974; -. [Q5EE38-4]
DR ProteomicsDB; 285975; -. [Q5EE38-5]
DR Antibodypedia; 29595; 360 antibodies from 26 providers.
DR DNASU; 497652; -.
DR Ensembl; ENSMUST00000042608; ENSMUSP00000048180; ENSMUSG00000038000. [Q5EE38-1]
DR GeneID; 497652; -.
DR KEGG; mmu:497652; -.
DR UCSC; uc009ndq.1; mouse. [Q5EE38-1]
DR UCSC; uc009ndr.1; mouse. [Q5EE38-4]
DR UCSC; uc009ndt.1; mouse. [Q5EE38-3]
DR CTD; 65057; -.
DR MGI; MGI:87873; Acd.
DR VEuPathDB; HostDB:ENSMUSG00000038000; -.
DR eggNOG; ENOG502SAN8; Eukaryota.
DR GeneTree; ENSGT00390000004877; -.
DR HOGENOM; CLU_619569_0_0_1; -.
DR InParanoid; Q5EE38; -.
DR OMA; YEPPCAS; -.
DR PhylomeDB; Q5EE38; -.
DR TreeFam; TF338536; -.
DR Reactome; R-MMU-110330; Recognition and association of DNA glycosylase with site containing an affected purine.
DR Reactome; R-MMU-110331; Cleavage of the damaged purine.
DR Reactome; R-MMU-171319; Telomere Extension By Telomerase.
DR Reactome; R-MMU-174411; Polymerase switching on the C-strand of the telomere.
DR Reactome; R-MMU-174414; Processive synthesis on the C-strand of the telomere.
DR Reactome; R-MMU-174417; Telomere C-strand (Lagging Strand) Synthesis.
DR Reactome; R-MMU-174430; Telomere C-strand synthesis initiation.
DR Reactome; R-MMU-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-MMU-9670095; Inhibition of DNA recombination at telomere.
DR BioGRID-ORCS; 497652; 15 hits in 73 CRISPR screens.
DR ChiTaRS; Acd; mouse.
DR PRO; PR:Q5EE38; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q5EE38; protein.
DR Bgee; ENSMUSG00000038000; Expressed in animal zygote and 211 other tissues.
DR ExpressionAtlas; Q5EE38; baseline and differential.
DR Genevisible; Q5EE38; MM.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IEA:InterPro.
DR GO; GO:0070182; F:DNA polymerase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IMP:MGI.
DR GO; GO:0070200; P:establishment of protein localization to telomere; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0060381; P:positive regulation of single-stranded telomeric DNA binding; ISO:MGI.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IC:ComplexPortal.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0031848; P:protection from non-homologous end joining at telomere; IMP:BHF-UCL.
DR GO; GO:0070198; P:protein localization to chromosome, telomeric region; ISO:MGI.
DR GO; GO:0035282; P:segmentation; IMP:MGI.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR GO; GO:0032202; P:telomere assembly; ISO:MGI.
DR GO; GO:0016233; P:telomere capping; IMP:BHF-UCL.
DR GO; GO:0000723; P:telomere maintenance; ISO:MGI.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IEA:InterPro.
DR GO; GO:0001655; P:urogenital system development; IMP:MGI.
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 Alternative splicing; Chromosome; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Telomere; Ubl conjugation.
FT CHAIN 1..416
FT /note="Adrenocortical dysplasia protein"
FT /id="PRO_0000239020"
FT REGION 156..245
FT /note="Interaction with POT1"
FT /evidence="ECO:0000250"
FT REGION 234..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 11..13
FT /note="PWI"
FT COMPBIAS 234..257
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 345
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96AP0"
FT VAR_SEQ 1..253
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019067"
FT VAR_SEQ 1..191
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019068"
FT VAR_SEQ 1..158
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019069"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019070"
FT VAR_SEQ 101..136
FT /note="LRVQVAQDHAPAEFYLQVDRFNLLPTEQPRIQVTGC -> MKLPPFVSSRAL
FT GIDLQVRGMGINNPDHLPPSSSPS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019071"
FT VAR_SEQ 159..162
FT /note="SSSA -> MLAP (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019072"
FT VAR_SEQ 192..213
FT /note="VLKGPCTTTPLTDWITSGSQAL -> MCRENSMSVLRTTSQSLLLPVQ (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019073"
FT VAR_SEQ 214..232
FT /note="GKAVFTVSGSLLHIPEGEE -> VSAGLFLGGFRGRVRQLPC (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019074"
FT VAR_SEQ 233..416
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019075"
FT CONFLICT 158
FT /note="A -> T (in Ref. 2; BAE35904)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="R -> W (in Ref. 2; BAE20450)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 416 AA; 44713 MW; 357CB31A8C4639BF CRC64;
MSDSGLLALQ PWIRELILGS ETLSSPRTGQ LLKVLQDSET PGPSSAPDTP DTGAVLLVSD
GTHSVRCVVT RNAIDTSDWE EKELGFRGTE GRLLLLQACG LRVQVAQDHA PAEFYLQVDR
FNLLPTEQPR IQVTGCNQDS DVQRKLNECL EDHLSESASS SAGLTLSQLL DEVREDQDHR
GALVCLAKSC LVLKGPCTTT PLTDWITSGS QALGKAVFTV SGSLLHIPEG EEQILSSTGS
SQKARGTSAS PSHMPLEESG ASVSLLSALA TSDPGQMDSS QSPPAVGSTS PRAQAPTSPP
CNSTPSSLLL NCSPSLSPLH PAPRSHQSCE TRAQAPKLEF QCSFKKRQLL PRTSAQELCS
VWEPPERHRD TSAFQYKYET PSASLHTQVQ TARLSPQLVA WALNIVMESE SELTQV
