ID   CCD62_HUMAN             Reviewed;         684 AA.
AC   Q6P9F0; A8K8V1; B3KUP3; Q6ZVF2; Q86VJ0; Q9BYZ5;
DT   13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   13-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 140.
DE   RecName: Full=Coiled-coil domain-containing protein 62;
DE   AltName: Full=Protein TSP-NY;
DE   AltName: Full=Protein aaa;
GN   Name=CCDC62;
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 2), AND TISSUE SPECIFICITY.
RA   Shan Y.X., Yu L.;
RT   "Cloning and characterization of a novel gene highly expressed in testis.";
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC   TISSUE=Cerebellum, and 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), AND VARIANT LYS-394.
RC   TISSUE=Brain;
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 176-684 (ISOFORM 2), AND TISSUE SPECIFICITY.
RC   TISSUE=Testis;
RA   Li J.M., Chen R.H., Chen Q., Zhu H., Lin M., Zhou Z.M., Wang L.R.,
RA   Zhou Y.D., Cheng L.J., Ying L.L., Zhu H., Sha J.H.;
RT   "A novel testis specific protein (TSP-NY) gene from adult testis.";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   INTERACTION WITH ESR1, AND MUTAGENESIS OF 637-LEU-LEU-638 AND
RP   653-LEU-LEU-654.
RX   PubMed=18563714; DOI=10.1002/pros.20774;
RA   Chen M., Ni J., Zhang Y., Muyan M., Yeh S.;
RT   "ERAP75 functions as a coactivator to enhance estrogen receptor alpha
RT   transactivation in prostate stromal cells.";
RL   Prostate 68:1273-1282(2008).
RN   [6]
RP   FUNCTION, INTERACTION WITH ESR2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   AND MUTAGENESIS OF 637-LEU-LEU-638 AND 653-LEU-LEU-654.
RX   PubMed=19126643; DOI=10.1093/carcin/bgn288;
RA   Chen M., Ni J., Chang H.C., Lin C.Y., Muyan M., Yeh S.;
RT   "CCDC62/ERAP75 functions as a coactivator to enhance estrogen receptor
RT   beta-mediated transactivation and target gene expression in prostate cancer
RT   cells.";
RL   Carcinogenesis 30:841-850(2009).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=19165854; DOI=10.1002/ijc.24220;
RA   Domae S., Nakamura Y., Nakamura Y., Uenaka A., Wada H., Nakata M., Oka M.,
RA   Kishimoto K., Tsukamoto G., Yoshihama Y., Matsuoka J., Gochi A., Kohno S.,
RA   Saika T., Sasaki A., Nakayama E., Ono T.;
RT   "Identification of CCDC62-2 as a novel cancer/testis antigen and its
RT   immunogenicity.";
RL   Int. J. Cancer 124:2347-2352(2009).
RN   [8]
RP   SUBCELLULAR LOCATION.
RX   PubMed=28339613; DOI=10.1095/biolreprod.116.141408;
RA   Li Y., Li C., Lin S., Yang B., Huang W., Wu H., Chen Y., Yang L., Luo M.,
RA   Guo H., Chen J., Wang T., Ma Q., Gu Y., Mou L., Jiang Z., Xia J., Gui Y.;
RT   "A nonsense mutation in Ccdc62 gene is responsible for spermiogenesis
RT   defects and male infertility in repro29/repro29 mice.";
RL   Biol. Reprod. 96:587-597(2017).
RN   [9]
RP   VARIANT [LARGE SCALE ANALYSIS] GLU-31.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [10]
RP   VARIANTS SPGF67 148-GLN--TYR-684 DEL AND TYR-283, AND INVOLVEMENT IN
RP   SPGF67.
RX   PubMed=31985809; DOI=10.1093/humrep/dez246;
RA   Oud M.S., Okutman O., Hendricks L.A.J., de Vries P.F., Houston B.J.,
RA   Vissers L.E.L.M., O'Bryan M.K., Ramos L., Chemes H.E., Viville S.,
RA   Veltman J.A.;
RT   "Exome sequencing reveals novel causes as well as new candidate genes for
RT   human globozoospermia.";
RL   Hum. Reprod. 35:240-252(2020).
CC   -!- FUNCTION: Nuclear receptor coactivator that can enhance preferentially
CC       estrogen receptors ESR1 and ESR2 transactivation. Modulates also
CC       progesterone/PGR, glucocorticoid/NR3C1 and androgen/AR receptors
CC       transactivation, although at lower level; little effect on vitamin D
CC       receptor/VDR. Required for normal spermiogenesis. It probably plays a
CC       role in acrosome formation (By similarity).
CC       {ECO:0000250|UniProtKB:E9PVD1, ECO:0000269|PubMed:19126643}.
CC   -!- SUBUNIT: Interacts with ESR1 and ESR2 in the presence of estradiol/E2.
CC       The interaction with ESR2 recruits CCDC62 to ER target genes, including
CC       cyclin-D1/CCND1 AP-1 promoter. Interacts with GOPC (By similarity).
CC       {ECO:0000250|UniProtKB:E9PVD1, ECO:0000269|PubMed:18563714,
CC       ECO:0000269|PubMed:19126643}.
CC   -!- INTERACTION:
CC       Q6P9F0; Q92731-1: ESR2; NbExp=6; IntAct=EBI-11176612, EBI-11176604;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19126643}. Nucleus
CC       {ECO:0000269|PubMed:19126643}. Cytoplasmic vesicle, secretory vesicle,
CC       acrosome {ECO:0000269|PubMed:28339613}. Note=Mainly nuclear.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q6P9F0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6P9F0-2; Sequence=VSP_019329;
CC       Name=3;
CC         IsoId=Q6P9F0-3; Sequence=VSP_019327, VSP_019328;
CC   -!- TISSUE SPECIFICITY: Highly expressed in adult testis. Expressed in both
CC       prostate epithelial and stromal cells, with predominant expression in
CC       epithelial cells (at protein level) (PubMed:19126643). Not detected in
CC       prostate by RT-PCR (PubMed:19165854). Overexpressed in various cancers.
CC       {ECO:0000269|PubMed:19126643, ECO:0000269|PubMed:19165854,
CC       ECO:0000269|Ref.1, ECO:0000269|Ref.4}.
CC   -!- DOMAIN: Contains 2 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The first one is
CC       essential for the association with ESR1 and ESR2.
CC   -!- DISEASE: Spermatogenic failure 67 (SPGF67) [MIM:619803]: An autosomal
CC       recessive male infertility disorder characterized by globozoospermia.
CC       Affected individuals have a normal sperm count, but spermatozoa are
CC       round-headed and lack the acrosome. In addition to pure
CC       globozoospermia, some patients have a mixture of acrosomeless
CC       spermatozoa and spermatozoa with small or detached acrosomes, which is
CC       defined as acrosomal hypoplasia. {ECO:0000269|PubMed:31985809}.
CC       Note=The disease may be caused by variants affecting the gene
CC       represented in this entry.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAG49396.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY254201; AAP13075.1; -; mRNA.
DR   EMBL; AK097663; BAG53505.1; -; mRNA.
DR   EMBL; AK124633; BAC85909.1; -; mRNA.
DR   EMBL; AK292466; BAF85155.1; -; mRNA.
DR   EMBL; BC060796; AAH60796.1; -; mRNA.
DR   EMBL; AY009105; AAG49396.1; ALT_INIT; mRNA.
DR   CCDS; CCDS9238.1; -. [Q6P9F0-1]
DR   RefSeq; NP_958843.2; NM_201435.4. [Q6P9F0-1]
DR   RefSeq; XP_006719706.1; XM_006719643.1. [Q6P9F0-1]
DR   RefSeq; XP_006719707.1; XM_006719644.1. [Q6P9F0-2]
DR   AlphaFoldDB; Q6P9F0; -.
DR   SMR; Q6P9F0; -.
DR   BioGRID; 124180; 4.
DR   IntAct; Q6P9F0; 4.
DR   STRING; 9606.ENSP00000253079; -.
DR   iPTMnet; Q6P9F0; -.
DR   PhosphoSitePlus; Q6P9F0; -.
DR   BioMuta; CCDC62; -.
DR   DMDM; 108935965; -.
DR   EPD; Q6P9F0; -.
DR   jPOST; Q6P9F0; -.
DR   MassIVE; Q6P9F0; -.
DR   PaxDb; 9606-ENSP00000253079; -.
DR   PeptideAtlas; Q6P9F0; -.
DR   ProteomicsDB; 67037; -. [Q6P9F0-1]
DR   ProteomicsDB; 67038; -. [Q6P9F0-2]
DR   ProteomicsDB; 67039; -. [Q6P9F0-3]
DR   Antibodypedia; 52252; 86 antibodies from 17 providers.
DR   DNASU; 84660; -.
DR   Ensembl; ENST00000253079.11; ENSP00000253079.6; ENSG00000130783.14. [Q6P9F0-1]
DR   Ensembl; ENST00000341952.8; ENSP00000341471.4; ENSG00000130783.14. [Q6P9F0-2]
DR   Ensembl; ENST00000392441.8; ENSP00000376236.4; ENSG00000130783.14. [Q6P9F0-2]
DR   Ensembl; ENST00000537566.5; ENSP00000445045.1; ENSG00000130783.14. [Q6P9F0-3]
DR   GeneID; 84660; -.
DR   KEGG; hsa:84660; -.
DR   MANE-Select; ENST00000253079.11; ENSP00000253079.6; NM_201435.5; NP_958843.2.
DR   UCSC; uc001udc.4; human. [Q6P9F0-1]
DR   AGR; HGNC:30723; -.
DR   CTD; 84660; -.
DR   DisGeNET; 84660; -.
DR   GeneCards; CCDC62; -.
DR   HGNC; HGNC:30723; CCDC62.
DR   HPA; ENSG00000130783; Tissue enriched (testis).
DR   MalaCards; CCDC62; -.
DR   MIM; 613481; gene.
DR   MIM; 619803; phenotype.
DR   neXtProt; NX_Q6P9F0; -.
DR   OpenTargets; ENSG00000130783; -.
DR   PharmGKB; PA143485414; -.
DR   VEuPathDB; HostDB:ENSG00000130783; -.
DR   eggNOG; ENOG502RHSF; Eukaryota.
DR   GeneTree; ENSGT00400000022269; -.
DR   HOGENOM; CLU_025504_0_0_1; -.
DR   InParanoid; Q6P9F0; -.
DR   OMA; SSYDVCK; -.
DR   OrthoDB; 2906280at2759; -.
DR   PhylomeDB; Q6P9F0; -.
DR   TreeFam; TF329149; -.
DR   PathwayCommons; Q6P9F0; -.
DR   SignaLink; Q6P9F0; -.
DR   BioGRID-ORCS; 84660; 33 hits in 1153 CRISPR screens.
DR   ChiTaRS; CCDC62; human.
DR   GenomeRNAi; 84660; -.
DR   Pharos; Q6P9F0; Tbio.
DR   PRO; PR:Q6P9F0; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q6P9F0; Protein.
DR   Bgee; ENSG00000130783; Expressed in sperm and 107 other cell types or tissues.
DR   ExpressionAtlas; Q6P9F0; baseline and differential.
DR   GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0030374; F:nuclear receptor coactivator activity; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl.
DR   GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR   Genevisible; Q6P9F0; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW   Disease variant; Nucleus; Reference proteome; Repeat.
FT   CHAIN           1..684
FT                   /note="Coiled-coil domain-containing protein 62"
FT                   /id="PRO_0000240247"
FT   REGION          579..603
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          657..684
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          11..160
FT                   /evidence="ECO:0000255"
FT   COILED          199..322
FT                   /evidence="ECO:0000255"
FT   MOTIF           634..638
FT                   /note="LXXLL motif 1"
FT   MOTIF           650..654
FT                   /note="LXXLL motif 2"
FT   VAR_SEQ         1..239
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_019327"
FT   VAR_SEQ         240..257
FT                   /note="IIRLKQEKSCLHDELLFT -> MPNSSPKDPTTASGNGSK (in isoform
FT                   3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_019328"
FT   VAR_SEQ         668..684
FT                   /note="KSEVPEESAQKNTFVSY -> ISHLCGRQKADTNTE (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.1,
FT                   ECO:0000303|Ref.4"
FT                   /id="VSP_019329"
FT   VARIANT         31
FT                   /note="Q -> E (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035498"
FT   VARIANT         141
FT                   /note="T -> M (in dbSNP:rs58131754)"
FT                   /id="VAR_061585"
FT   VARIANT         148..684
FT                   /note="Missing (in SPGF67)"
FT                   /evidence="ECO:0000269|PubMed:31985809"
FT                   /id="VAR_086975"
FT   VARIANT         283
FT                   /note="H -> Y (in SPGF67; uncertain significance;
FT                   dbSNP:rs139198472)"
FT                   /evidence="ECO:0000269|PubMed:31985809"
FT                   /id="VAR_086976"
FT   VARIANT         394
FT                   /note="T -> K (in dbSNP:rs17855031)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_026715"
FT   MUTAGEN         637..638
FT                   /note="LL->AA: Abrogates interaction with ESR1 and ESR2."
FT                   /evidence="ECO:0000269|PubMed:18563714,
FT                   ECO:0000269|PubMed:19126643"
FT   MUTAGEN         653..654
FT                   /note="LL->AA: No effect on interaction with ESR1 or ESR2."
FT                   /evidence="ECO:0000269|PubMed:18563714,
FT                   ECO:0000269|PubMed:19126643"
FT   CONFLICT        486
FT                   /note="C -> R (in Ref. 2; BAF85155)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        651
FT                   /note="S -> N (in Ref. 4; AAG49396)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   684 AA;  77748 MW;  071DCEC789E4DF60 CRC64;
     MNPPAAFLAG RQNIGSEVEI STIEKQRKEL QLLIGELKDR DKELNDMVAV HQQQLLSWEE
     DRQKVLTLEE RCSKLEGELH KRTEIIRSLT KKVKALESNQ MECQTALQKT QLQLQEMAQK
     ATHSSLLSED LEARNETLSN TLVELSAQVG QLQAREQALT TMIKLKDKDI IEAVNHIADC
     SGKFKMLEHA LRDAKMAETC IVKEKQDYKQ KLKALKIEVN KLKEDLNEKT TENNEQREEI
     IRLKQEKSCL HDELLFTVER EKRKDELLNI AKSKQERTNS ELHNLRQIYV KQQSDLQFLN
     FNVENSQELI QMYDSKMEES KALDSSRDMC LSDLENNHPK VDIKREKNQK SLFKDQKFEA
     MLVQQNRSDK SSCDECKEKK QQIDTVFGEK SVITLSSIFT KDLVEKHNLP WSLGGKTQIE
     PENKITLCKI HTKSPKCHGT GVQNEGKQPS ETPTLSDEKQ WHDVSVYLGL TNCPSSKHPE
     KLDVECQDQM ERSEISCCQK NEACLGESGM CDSKCCHPSN FIIEAPGHMS DVEWMSIFKP
     SKMQRIVRLK SGCTCSESIC GTQHDSPASE LIAIQDSHSL GSSKSALRED ETESSSNKKN
     SPTSLLIYKD APAFNEKASI VLPSQDDFSP TSKLQRLLAE SRQMVTDLEL STLLPISHEN
     LTGSATNKSE VPEESAQKNT FVSY
//