PASD1_HUMAN
ID PASD1_HUMAN Reviewed; 773 AA.
AC Q8IV76; Q3MNE0; Q69HD7; Q8N7X9;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Circadian clock protein PASD1 {ECO:0000305};
DE AltName: Full=Cancer/testis antigen 63 {ECO:0000303|PubMed:16112646};
DE Short=CT63 {ECO:0000303|PubMed:16112646};
DE AltName: Full=OX-TES-1 {ECO:0000303|PubMed:15162151};
DE AltName: Full=PAS domain-containing protein 1 {ECO:0000303|PubMed:15162151, ECO:0000312|HGNC:HGNC:20686};
GN Name=PASD1 {ECO:0000312|HGNC:HGNC:20686};
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] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=15162151; DOI=10.1038/sj.bjc.6601875;
RA Liggins A.P., Brown P.J., Asker K., Pulford K., Banham A.H.;
RT "A novel diffuse large B-cell lymphoma-associated cancer testis antigen
RT encoding a PAS domain protein.";
RL Br. J. Cancer 91:141-149(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 469-773 (ISOFORM 1).
RX PubMed=16112646; DOI=10.1016/j.bbrc.2005.08.024;
RA Guinn B.-A., Bland E.A., Lodi U., Liggins A.P., Tobal K., Petters S.,
RA Wells J.W., Banham A.H., Mufti G.J.;
RT "Humoral detection of leukaemia-associated antigens in presentation acute
RT myeloid leukaemia.";
RL Biochem. Biophys. Res. Commun. 335:1293-1304(2005).
RN [5]
RP FUNCTION, INTERACTION WITH CLOCK-ARNTL/BMAL1, SUBCELLULAR LOCATION, DOMAIN,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF VAL-36 AND MET-45.
RX PubMed=25936801; DOI=10.1016/j.molcel.2015.03.031;
RA Michael A.K., Harvey S.L., Sammons P.J., Anderson A.P., Kopalle H.M.,
RA Banham A.H., Partch C.L.;
RT "Cancer/testis antigen PASD1 silences the circadian clock.";
RL Mol. Cell 58:743-754(2015).
CC -!- FUNCTION: Functions as a suppressor of the biological clock that drives
CC the daily circadian rhythms of cells throughout the body
CC (PubMed:25936801). Acts as a nuclear repressor of the CLOCK-ARNTL/BMAL1
CC heterodimer-mediated transcriptional activation of the core clock
CC components (PubMed:25936801). Inhibits circadian clock function in
CC cancer cells, when overexpressed (PubMed:25936801).
CC {ECO:0000269|PubMed:25936801}.
CC -!- SUBUNIT: Interacts with the CLOCK-ARNTL/BMAL1 heterodimer; this
CC interaction inhibits CLOCK-ARNTL/BMAL1 transcriptional activation and
CC suppress circadian timekeeping (PubMed:25936801). Interacts with
CC ARNTL/BMAL1 (PubMed:25936801). {ECO:0000269|PubMed:25936801}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:25936801}. Note=Associates preferentially at the
CC periphery of the nucleus with heterochromatin (PubMed:25936801).
CC {ECO:0000269|PubMed:25936801}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:25936801}. Note=Associates preferentially at the
CC periphery of the nucleus with heterochromatin (PubMed:25936801).
CC {ECO:0000269|PubMed:25936801}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PASD1_v2;
CC IsoId=Q8IV76-1; Sequence=Displayed;
CC Name=2; Synonyms=PASD1_v1;
CC IsoId=Q8IV76-2; Sequence=VSP_027663, VSP_027664;
CC -!- TISSUE SPECIFICITY: Testis-specific (PubMed:25936801). Expressed in a
CC broad range of cancer cells, including melanoma, lung cancer, and
CC breast cancer (at protein level). Testis-specific (PubMed:15162151).
CC Found in histologically normal tissues from patients with uterus, lung
CC and small intestine cancers. Widespread expression seen in solid tumors
CC and diffuse large B-cell lymphoma (DLBCL)-derived cell lines. Isoform 2
CC is expressed in all DLBCL-derived cell lines, while isoform 1 is
CC preferentially expressed in cell lines derived from non-germinal center
CC DLBCL (PubMed:15162151). {ECO:0000269|PubMed:15162151,
CC ECO:0000269|PubMed:25936801}.
CC -!- DOMAIN: C-termini of isoform 1 and isoform 2 are sufficient to interact
CC with and to repress the activity of CLOCK-ARNTL/BMAL1
CC (PubMed:25936801). {ECO:0000269|PubMed:25936801}.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron retention. {ECO:0000305}.
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DR EMBL; AY270020; AAQ01136.1; -; mRNA.
DR EMBL; AK097552; BAC05097.1; -; mRNA.
DR EMBL; BC040301; AAH40301.1; -; mRNA.
DR EMBL; AY623425; AAT49049.1; -; mRNA.
DR CCDS; CCDS35431.1; -. [Q8IV76-1]
DR RefSeq; NP_775764.2; NM_173493.2. [Q8IV76-1]
DR AlphaFoldDB; Q8IV76; -.
DR SMR; Q8IV76; -.
DR BioGRID; 126545; 3.
DR STRING; 9606.ENSP00000359382; -.
DR iPTMnet; Q8IV76; -.
DR PhosphoSitePlus; Q8IV76; -.
DR BioMuta; PASD1; -.
DR DMDM; 74728046; -.
DR MassIVE; Q8IV76; -.
DR PaxDb; Q8IV76; -.
DR PeptideAtlas; Q8IV76; -.
DR PRIDE; Q8IV76; -.
DR ProteomicsDB; 70670; -. [Q8IV76-1]
DR ProteomicsDB; 70671; -. [Q8IV76-2]
DR Antibodypedia; 17024; 279 antibodies from 20 providers.
DR DNASU; 139135; -.
DR Ensembl; ENST00000370357.5; ENSP00000359382.4; ENSG00000166049.11. [Q8IV76-1]
DR GeneID; 139135; -.
DR KEGG; hsa:139135; -.
DR MANE-Select; ENST00000370357.5; ENSP00000359382.4; NM_173493.3; NP_775764.2.
DR UCSC; uc004fev.5; human. [Q8IV76-1]
DR CTD; 139135; -.
DR DisGeNET; 139135; -.
DR GeneCards; PASD1; -.
DR HGNC; HGNC:20686; PASD1.
DR HPA; ENSG00000166049; Tissue enriched (testis).
DR MIM; 300993; gene.
DR neXtProt; NX_Q8IV76; -.
DR OpenTargets; ENSG00000166049; -.
DR PharmGKB; PA134909788; -.
DR VEuPathDB; HostDB:ENSG00000166049; -.
DR eggNOG; ENOG502SDT0; Eukaryota.
DR GeneTree; ENSGT00530000064765; -.
DR HOGENOM; CLU_441185_0_0_1; -.
DR InParanoid; Q8IV76; -.
DR OMA; DYIQLWQ; -.
DR OrthoDB; 647114at2759; -.
DR PhylomeDB; Q8IV76; -.
DR TreeFam; TF324568; -.
DR PathwayCommons; Q8IV76; -.
DR BioGRID-ORCS; 139135; 8 hits in 697 CRISPR screens.
DR ChiTaRS; PASD1; human.
DR GeneWiki; PASD1; -.
DR GenomeRNAi; 139135; -.
DR Pharos; Q8IV76; Tbio.
DR PRO; PR:Q8IV76; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q8IV76; protein.
DR Bgee; ENSG00000166049; Expressed in right testis and 13 other tissues.
DR Genevisible; Q8IV76; HS.
DR GO; GO:1990513; C:CLOCK-BMAL transcription complex; IBA:GO_Central.
DR GO; GO:1990512; C:Cry-Per complex; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:GO_Central.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IDA:GO_Central.
DR GO; GO:0032922; P:circadian regulation of gene expression; IBA:GO_Central.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00130; PAS; 1.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR SMART; SM00091; PAS; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Biological rhythms; Coiled coil; Nucleus;
KW Reference proteome.
FT CHAIN 1..773
FT /note="Circadian clock protein PASD1"
FT /id="PRO_0000299445"
FT DOMAIN 30..102
FT /note="PAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT REGION 313..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 365..412
FT /note="Necessary for transcriptional repression"
FT /evidence="ECO:0000269|PubMed:25936801"
FT REGION 427..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..773
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 365..412
FT /evidence="ECO:0000255"
FT COILED 475..553
FT /evidence="ECO:0000255"
FT COMPBIAS 506..533
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 547..567
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 639
FT /note="S -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15162151"
FT /id="VSP_027663"
FT VAR_SEQ 640..773
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15162151"
FT /id="VSP_027664"
FT VARIANT 213
FT /note="Q -> E (in dbSNP:rs5924658)"
FT /id="VAR_034819"
FT MUTAGEN 36
FT /note="V->E: Reduces inhibition of CLOCK-ARNTL/BMAL1
FT heterodimer activity; when associated with R-45."
FT /evidence="ECO:0000269|PubMed:25936801"
FT MUTAGEN 45
FT /note="M->R: Reduces inhibition of CLOCK-ARNTL/BMAL1
FT heterodimer activity; when associated with E-36."
FT /evidence="ECO:0000269|PubMed:25936801"
FT CONFLICT 107
FT /note="E -> K (in Ref. 2; BAC05097)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 773 AA; 87428 MW; 04DF5C10980CEE6F CRC64;
MKMRGEKRRD KVNPKSSQRK LNWIPSFPTY DYFNQVTLQL LDGFMITLST DGVIICVAEN
ISSLLGHLPA EIVGKKLLSL LPDEEKDEVY QKIILKFPLL NSETHIEFCC HLKRGNVEHG
DSSAYENVKF IVNVRDICNE FPVVFSGLFS SHLCADFAAC VPQEDRLYLV GNVCILRTQL
LQQLYTSKAV SDEAVLTQDS DEEPFVGELS SSQGQRGHTS MKAVYVEPAA AAAAAAISDD
QIDIAEVEQY GPQENVHMFV DSDSTYCSST VFLDTMPESP ALSLQDFRGE PEVNPLYRAD
PVDLEFSVDQ VDSVDQEGPM DQQDPENPVA PLDQAGLMDP VDPEDSVDLG AAGASAQPLQ
PSSPVAYDII SQELELMKKL KEQLEERTWL LHDAIQNQQN ALELMMDHLQ KQPNTLRHVV
IPDLQSSEAV PKKQQKQHAG QVKRPLPHPK DVKCFCGLSL SNSLKNTGEL QEPCVAFNQQ
QLVQQEQHLK EQQRQLREQL QQLREQRKVQ KQKKMQEKKK LQEQKMQEKK KLQEQRRQKK
KKLQERKKWQ GQMLQKEPEE EQQKQQLQEQ PLKHNVIVGN ERVQICLQNP RDVSVPLCNH
PVRFLQAQPI VPVQRAAEQQ PSGFYQDENC GQQEDESQSF YPEAYQGPPV NQLPLIDTSN
SEAISSSSIP QFPITSDSTI STLETPQDYI RLWQELSDSL GPVVQVNTWS CDEQGTLHGQ
PTYHQVQVSE VGVEGPPDPQ AFQGPAAYQP DQMRSAEQTR LMPAEQRDSN KPC
