APCD1_HUMAN
ID APCD1_HUMAN Reviewed; 514 AA.
AC Q8J025; B4DUQ0; B4DZT0; Q71M25;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Protein APCDD1;
DE AltName: Full=Adenomatosis polyposis coli down-regulated 1 protein;
DE Flags: Precursor;
GN Name=APCDD1 {ECO:0000312|HGNC:HGNC:15718};
GN Synonyms=DRAPC1 {ECO:0000312|EMBL:BAC15563.1}; ORFNames=FP7019;
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] {ECO:0000305, ECO:0000312|EMBL:BAC15563.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Colon {ECO:0000269|PubMed:12384519, ECO:0000312|EMBL:BAC15563.1};
RX PubMed=12384519;
RA Takahashi M., Fujita M., Furukawa Y., Hamamoto R., Shimokawa T., Miwa N.,
RA Ogawa M., Nakamura Y.;
RT "Isolation of a novel human gene, APCDD1, as a direct target of the b-
RT catenin/T-cell factor 4 complex with probable involvement in colorectal
RT carcinogenesis.";
RL Cancer Res. 62:5651-5656(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neuroepithelioma, and Thymus;
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] {ECO:0000312|EMBL:AAH53324.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary {ECO:0000312|EMBL:AAH53324.1};
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 [LARGE SCALE MRNA] OF 18-514.
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [5]
RP VARIANT HYPT1 ARG-9, CHARACTERIZATION OF VARIANT HYPT1 ARG-9,
RP GLYCOSYLATION, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, SUBUNIT,
RP AND INTERACTION WITH LRP5 AND WNT3A.
RX PubMed=20393562; DOI=10.1038/nature08875;
RA Shimomura Y., Agalliu D., Vonica A., Luria V., Wajid M., Baumer A.,
RA Belli S., Petukhova L., Schinzel A., Brivanlou A.H., Barres B.A.,
RA Christiano A.M.;
RT "APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis
RT simplex.";
RL Nature 464:1043-1047(2010).
CC -!- FUNCTION: Negative regulator of the Wnt signaling pathway. Inhibits Wnt
CC signaling in a cell-autonomous manner and functions upstream of beta-
CC catenin. May act via its interaction with Wnt and LRP proteins. May
CC play a role in colorectal tumorigenesis. {ECO:0000269|PubMed:12384519,
CC ECO:0000269|PubMed:20393562}.
CC -!- SUBUNIT: Homodimer. Interacts with LRP5 and WNT3A.
CC {ECO:0000269|PubMed:20393562}.
CC -!- INTERACTION:
CC Q8J025; Q8J025: APCDD1; NbExp=2; IntAct=EBI-2683489, EBI-2683489;
CC Q8J025; O75197: LRP5; NbExp=3; IntAct=EBI-2683489, EBI-2466421;
CC Q8J025; P56704: WNT3A; NbExp=3; IntAct=EBI-2683489, EBI-6173037;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20393562};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:20393562}.
CC -!- TISSUE SPECIFICITY: Abundantly expressed in heart, pancreas, prostate
CC and ovary. Moderately expressed in lung, liver, kidney, spleen, thymus,
CC colon and peripheral lymphocytes. Abundantly expressed in both the
CC epidermal and dermal compartments of the hair follicle. Present in
CC scalp skin Highly expressed in the hair follicle dermal papilla, the
CC matrix, and the hair shaft (at protein level).
CC {ECO:0000269|PubMed:12384519, ECO:0000269|PubMed:20393562}.
CC -!- INDUCTION: Target gene of the Wnt/Beta-catenin pathway,
CC transcriptionally regulated by the CTNNB1/TF7L2 complex.
CC {ECO:0000269|PubMed:12384519}.
CC -!- PTM: N-Glycosylated. {ECO:0000269|PubMed:20393562}.
CC -!- DISEASE: Hypotrichosis 1 (HYPT1) [MIM:605389]: A rare form of non-
CC syndromic hereditary hypotrichosis without characteristic hair shaft
CC anomalies. Affected individuals typically show normal hair at birth,
CC but hair loss and thinning of the hair shaft start during early
CC childhood and progress with age. HYPT1 inheritance is autosomal
CC dominant. {ECO:0000269|PubMed:20393562}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the APCDD1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ04816.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAG62412.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG64192.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB056722; BAC15563.1; -; mRNA.
DR EMBL; AB104887; BAC65165.1; -; mRNA.
DR EMBL; AK300743; BAG62412.1; ALT_INIT; mRNA.
DR EMBL; AK303076; BAG64192.1; ALT_INIT; mRNA.
DR EMBL; BC053324; AAH53324.1; -; mRNA.
DR EMBL; AF461902; AAQ04816.1; ALT_FRAME; mRNA.
DR CCDS; CCDS11849.1; -.
DR RefSeq; NP_694545.1; NM_153000.4.
DR AlphaFoldDB; Q8J025; -.
DR BioGRID; 127063; 11.
DR DIP; DIP-56190N; -.
DR IntAct; Q8J025; 8.
DR STRING; 9606.ENSP00000347433; -.
DR GlyGen; Q8J025; 3 sites.
DR iPTMnet; Q8J025; -.
DR PhosphoSitePlus; Q8J025; -.
DR BioMuta; APCDD1; -.
DR DMDM; 74728445; -.
DR MassIVE; Q8J025; -.
DR PaxDb; Q8J025; -.
DR PeptideAtlas; Q8J025; -.
DR PRIDE; Q8J025; -.
DR ProteomicsDB; 71444; -.
DR Antibodypedia; 2521; 175 antibodies from 23 providers.
DR DNASU; 147495; -.
DR Ensembl; ENST00000355285.10; ENSP00000347433.4; ENSG00000154856.13.
DR GeneID; 147495; -.
DR KEGG; hsa:147495; -.
DR MANE-Select; ENST00000355285.10; ENSP00000347433.4; NM_153000.5; NP_694545.1.
DR UCSC; uc002kom.5; human.
DR CTD; 147495; -.
DR DisGeNET; 147495; -.
DR GeneCards; APCDD1; -.
DR HGNC; HGNC:15718; APCDD1.
DR HPA; ENSG00000154856; Tissue enhanced (skin).
DR MalaCards; APCDD1; -.
DR MIM; 605389; phenotype.
DR MIM; 607479; gene.
DR neXtProt; NX_Q8J025; -.
DR OpenTargets; ENSG00000154856; -.
DR Orphanet; 55654; Hypotrichosis simplex.
DR PharmGKB; PA24876; -.
DR VEuPathDB; HostDB:ENSG00000154856; -.
DR eggNOG; ENOG502QQ0C; Eukaryota.
DR GeneTree; ENSGT00640000091492; -.
DR HOGENOM; CLU_035648_0_0_1; -.
DR InParanoid; Q8J025; -.
DR OMA; GRHTWPL; -.
DR OrthoDB; 613671at2759; -.
DR PhylomeDB; Q8J025; -.
DR TreeFam; TF329491; -.
DR PathwayCommons; Q8J025; -.
DR SignaLink; Q8J025; -.
DR BioGRID-ORCS; 147495; 12 hits in 1059 CRISPR screens.
DR ChiTaRS; APCDD1; human.
DR GenomeRNAi; 147495; -.
DR Pharos; Q8J025; Tbio.
DR PRO; PR:Q8J025; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q8J025; protein.
DR Bgee; ENSG00000154856; Expressed in upper arm skin and 181 other tissues.
DR ExpressionAtlas; Q8J025; baseline and differential.
DR Genevisible; Q8J025; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0017147; F:Wnt-protein binding; IDA:UniProtKB.
DR GO; GO:0043615; P:astrocyte cell migration; IEA:Ensembl.
DR GO; GO:0001942; P:hair follicle development; IMP:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR042425; APCDD1.
DR InterPro; IPR029405; APCDD1_dom.
DR PANTHER; PTHR31021; PTHR31021; 1.
DR Pfam; PF14921; APCDDC; 2.
DR SMART; SM01352; APCDDC; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Glycoprotein; Hypotrichosis; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..514
FT /note="Protein APCDD1"
FT /id="PRO_0000227520"
FT TOPO_DOM 27..492
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 493..512
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 513..514
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 438..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 9
FT /note="L -> R (in HYPT1; dominant-negative mutant that
FT perturbs the translational processing from the endoplasmic
FT reticulum to the plasma membrane; dbSNP:rs267606659)"
FT /evidence="ECO:0000269|PubMed:20393562"
FT /id="VAR_063497"
FT VARIANT 150
FT /note="V -> I (in dbSNP:rs3748415)"
FT /id="VAR_050667"
SQ SEQUENCE 514 AA; 58797 MW; 75DA7B8B38E3FFE5 CRC64;
MSWPRRLLLR YLFPALLLHG LGEGSALLHP DSRSHPRSLE KSAWRAFKES QCHHMLKHLH
NGARITVQMP PTIEGHWVST GCEVRSGPEF ITRSYRFYHN NTFKAYQFYY GSNRCTNPTY
TLIIRGKIRL RQASWIIRGG TEADYQLHNV QVICHTEAVA EKLGQQVNRT CPGFLADGGP
WVQDVAYDLW REENGCECTK AVNFAMHELQ LIRVEKQYLH HNLDHLVEEL FLGDIHTDAT
QRMFYRPSSY QPPLQNAKNH DHACIACRII YRSDEHHPPI LPPKADLTIG LHGEWVSQRC
EVRPEVLFLT RHFIFHDNNN TWEGHYYHYS DPVCKHPTFS IYARGRYSRG VLSSRVMGGT
EFVFKVNHMK VTPMDAATAS LLNVFNGNEC GAEGSWQVGI QQDVTHTNGC VALGIKLPHT
EYEIFKMEQD ARGRYLLFNG QRPSDGSSPD RPEKRATSYQ MPLVQCASSS PRAEDLAEDS
GSSLYGRAPG RHTWSLLLAA LACLVPLLHW NIRR
