NECD_HUMAN
ID NECD_HUMAN Reviewed; 321 AA.
AC Q99608; B2R6Z5;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Necdin;
GN Name=NDN;
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].
RC TISSUE=Embryo;
RX PubMed=9354807; DOI=10.1038/ng1197-357;
RA Jay P., Rougeulle C., Massacrier A., Moncla A., Mattei M.-G., Malzac P.,
RA Roeckel N., Taviaux S., Lefranc J.-L.B., Cau P., Berta P., Lalande M.,
RA Muscatelli F.;
RT "The human necdin gene, NDN, is maternally imprinted and located in the
RT Prader-Willi syndrome chromosomal region.";
RL Nat. Genet. 17:357-360(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9630521; DOI=10.1016/s0378-1119(98)00206-6;
RA Nakada Y., Taniura H., Uetsuki T., Inazawa J., Yoshikawa K.;
RT "The human chromosomal gene for necdin, a neuronal growth suppressor, in
RT the Prader-Willi syndrome deletion region.";
RL Gene 213:65-72(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [5]
RP VARIANT ALA-318.
RX PubMed=21543378; DOI=10.1530/eje-11-0199;
RA Beneduzzi D., Iyer A.K., Trarbach E.B., Silveira-Neto A.P., Silveira L.G.,
RA Tusset C., Yip K., Mendonca B.B., Mellon P.L., Latronico A.C.;
RT "Mutational analysis of the necdin gene in patients with congenital
RT isolated hypogonadotropic hypogonadism.";
RL Eur. J. Endocrinol. 165:145-150(2011).
CC -!- FUNCTION: Growth suppressor that facilitates the entry of the cell into
CC cell cycle arrest. Functionally similar to the retinoblastoma protein
CC it binds to and represses the activity of cell-cycle-promoting proteins
CC such as SV40 large T antigen, adenovirus E1A, and the transcription
CC factor E2F. Necdin also interacts with p53 and works in an additive
CC manner to inhibit cell growth. Also functions as a transcription factor
CC and directly binds to specific guanosine-rich DNA sequences (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds to the transactivation domains of E2F1 and p53. Binds
CC also SV40 large T antigen and adenovirus E1A. Interacts with
CC nucleobindin 1 and 2 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q99608; Q9Y6B2: EID1; NbExp=3; IntAct=EBI-718177, EBI-1049975;
CC Q99608; P28799: GRN; NbExp=3; IntAct=EBI-718177, EBI-747754;
CC Q99608; P04792: HSPB1; NbExp=3; IntAct=EBI-718177, EBI-352682;
CC Q99608; P42858: HTT; NbExp=6; IntAct=EBI-718177, EBI-466029;
CC Q99608; I6L9F6: NEFL; NbExp=3; IntAct=EBI-718177, EBI-10178578;
CC Q99608; P07196: NEFL; NbExp=4; IntAct=EBI-718177, EBI-475646;
CC Q99608; Q9BPZ3: PAIP2; NbExp=6; IntAct=EBI-718177, EBI-2957445;
CC Q99608; Q96A49: SYAP1; NbExp=6; IntAct=EBI-718177, EBI-10770179;
CC Q99608; O76024: WFS1; NbExp=3; IntAct=EBI-718177, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Perikaryon. Nucleus. Note=Neural perikarya,
CC translocates to the nucleus of postmitotic neurons and interacts with
CC the nuclear matrix.
CC -!- TISSUE SPECIFICITY: Almost ubiquitous. Detected in fetal brain, lung,
CC liver and kidney; in adult heart, brain, placenta, lung, liver,
CC skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis,
CC ovary, small intestine and colon. Not detected in peripheral blood
CC leukocytes. In brain, restricted to post-mitotic neurons.
CC -!- MISCELLANEOUS: Located in the Prader-Willi syndrome (PWS) chromosome
CC region. Prader-Willi syndrome is a contiguous gene syndrome resulting
CC from deletion of the paternal copies of the imprinted SNRPN gene, the
CC necdin gene, and possibly other genes within the chromosome region
CC 15q11-q13.
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DR EMBL; U35139; AAB39469.1; -; mRNA.
DR EMBL; AB007828; BAA22660.1; -; Genomic_DNA.
DR EMBL; AK312779; BAG35642.1; -; mRNA.
DR EMBL; BC008750; AAH08750.1; -; mRNA.
DR CCDS; CCDS10014.1; -.
DR RefSeq; NP_002478.1; NM_002487.2.
DR AlphaFoldDB; Q99608; -.
DR SMR; Q99608; -.
DR BioGRID; 110772; 384.
DR IntAct; Q99608; 273.
DR MINT; Q99608; -.
DR STRING; 9606.ENSP00000332643; -.
DR iPTMnet; Q99608; -.
DR PhosphoSitePlus; Q99608; -.
DR BioMuta; NDN; -.
DR DMDM; 17380142; -.
DR EPD; Q99608; -.
DR jPOST; Q99608; -.
DR MassIVE; Q99608; -.
DR PaxDb; Q99608; -.
DR PeptideAtlas; Q99608; -.
DR PRIDE; Q99608; -.
DR ProteomicsDB; 78353; -.
DR Antibodypedia; 22276; 368 antibodies from 26 providers.
DR DNASU; 4692; -.
DR Ensembl; ENST00000649030.2; ENSP00000497916.1; ENSG00000182636.8.
DR GeneID; 4692; -.
DR KEGG; hsa:4692; -.
DR MANE-Select; ENST00000649030.2; ENSP00000497916.1; NM_002487.3; NP_002478.1.
DR CTD; 4692; -.
DR DisGeNET; 4692; -.
DR GeneCards; NDN; -.
DR GeneReviews; NDN; -.
DR HGNC; HGNC:7675; NDN.
DR HPA; ENSG00000182636; Low tissue specificity.
DR MalaCards; NDN; -.
DR MIM; 176270; phenotype.
DR MIM; 602117; gene.
DR neXtProt; NX_Q99608; -.
DR OpenTargets; ENSG00000182636; -.
DR Orphanet; 177910; Prader-Willi syndrome due to imprinting mutation.
DR Orphanet; 98754; Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15.
DR Orphanet; 177901; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1.
DR Orphanet; 177904; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2.
DR PharmGKB; PA31479; -.
DR VEuPathDB; HostDB:ENSG00000182636; -.
DR eggNOG; KOG4562; Eukaryota.
DR GeneTree; ENSGT00940000163084; -.
DR HOGENOM; CLU_039582_1_1_1; -.
DR InParanoid; Q99608; -.
DR OMA; EQSKDVC; -.
DR OrthoDB; 1195799at2759; -.
DR PhylomeDB; Q99608; -.
DR TreeFam; TF328505; -.
DR PathwayCommons; Q99608; -.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR SignaLink; Q99608; -.
DR SIGNOR; Q99608; -.
DR BioGRID-ORCS; 4692; 11 hits in 1081 CRISPR screens.
DR ChiTaRS; NDN; human.
DR GeneWiki; NDN_(gene); -.
DR GenomeRNAi; 4692; -.
DR Pharos; Q99608; Tbio.
DR PRO; PR:Q99608; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q99608; protein.
DR Bgee; ENSG00000182636; Expressed in endothelial cell and 199 other tissues.
DR ExpressionAtlas; Q99608; baseline and differential.
DR Genevisible; Q99608; HS.
DR GO; GO:0042995; C:cell projection; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0043015; F:gamma-tubulin binding; IEA:Ensembl.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0048675; P:axon extension; IEA:Ensembl.
DR GO; GO:0007413; P:axonal fasciculation; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
DR GO; GO:0071514; P:genomic imprinting; IEA:Ensembl.
DR GO; GO:0008347; P:glial cell migration; IEA:Ensembl.
DR GO; GO:0048871; P:multicellular organismal homeostasis; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:InterPro.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0090312; P:positive regulation of protein deacetylation; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0003016; P:respiratory system process; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR Gene3D; 1.10.10.1200; -; 1.
DR Gene3D; 1.10.10.1210; -; 1.
DR InterPro; IPR037445; MAGE.
DR InterPro; IPR041898; MAGE_WH1.
DR InterPro; IPR041899; MAGE_WH2.
DR InterPro; IPR002190; MHD_dom.
DR InterPro; IPR030086; Necdin.
DR PANTHER; PTHR11736; PTHR11736; 1.
DR PANTHER; PTHR11736:SF10; PTHR11736:SF10; 1.
DR Pfam; PF01454; MAGE; 1.
DR SMART; SM01373; MAGE; 1.
DR PROSITE; PS50838; MAGE; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Growth regulation; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..321
FT /note="Necdin"
FT /id="PRO_0000156740"
FT DOMAIN 98..297
FT /note="MAGE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00127"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..63
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 318
FT /note="V -> A (in dbSNP:rs114077338)"
FT /evidence="ECO:0000269|PubMed:21543378"
FT /id="VAR_065889"
SQ SEQUENCE 321 AA; 36086 MW; 5068FE121308BFAF CRC64;
MSEQSKDLSD PNFAAEAPNS EVHSSPGVSE GVPPSATLAE PQSPPLGPTA APQAAPPPQA
PNDEGDPKAL QQAAEEGRAH QAPSAAQPGP APPAPAQLVQ KAHELMWYVL VKDQKKMIIW
FPDMVKDVIG SYKKWCRSIL RRTSLILARV FGLHLRLTSL HTMEFALVKA LEPEELDRVA
LSNRMPMTGL LLMILSLIYV KGRGARESAV WNVLRILGLR PWKKHSTFGD VRKLITEEFV
QMNYLKYQRV PYVEPPEYEF FWGSRASREI TKMQIMEFLA RVFKKDPQAW PSRYREALEE
ARALREANPT AHYPRSSVSE D
