NOBOX_HUMAN
ID NOBOX_HUMAN Reviewed; 691 AA.
AC O60393; A6NCD3; A8MZN5;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 4.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Homeobox protein NOBOX;
GN Name=NOBOX;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 99-458 (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=16597639; DOI=10.1093/molehr/gal035;
RA Huntriss J., Hinkins M., Picton H.M.;
RT "cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian
RT follicles.";
RL Mol. Hum. Reprod. 12:283-289(2006).
RN [3]
RP VARIANT POF5 HIS-355, AND VARIANTS GLN-360; ASN-452; SER-482 AND LEU-517.
RX PubMed=17701902; DOI=10.1086/519496;
RA Qin Y., Choi Y., Zhao H., Simpson J.L., Chen Z.-J., Rajkovic A.;
RT "NOBOX homeobox mutation causes premature ovarian failure.";
RL Am. J. Hum. Genet. 81:576-581(2007).
RN [4]
RP VARIANTS POF5 TRP-91; TRP-117; THR-342 AND LEU-350.
RX PubMed=21837770; DOI=10.1002/humu.21543;
RA Bouilly J., Bachelot A., Broutin I., Touraine P., Binart N.;
RT "Novel NOBOX loss-of-function mutations account for 6.2% of cases in a
RT large primary ovarian insufficiency cohort.";
RL Hum. Mutat. 32:1108-1113(2011).
RN [5]
RP VARIANTS POF5 TRP-91; ARG-111; TRP-117 AND THR-371, CHARACTERIZATION OF
RP VARIANTS POF5 TRP-91; ARG-111; TRP-117 AND THR-371, FUNCTION, DNA-BINDING,
RP VARIANTS LEU-44 AND LEU-619, AND CHARACTERIZATION OF VARIANTS LEU-44 AND
RP LEU-619.
RX PubMed=25514101; DOI=10.1210/jc.2014-2761;
RA Bouilly J., Roucher-Boulez F., Gompel A., Bry-Gauillard H., Azibi K.,
RA Beldjord C., Dode C., Bouligand J., Mantel A.G., Hecart A.C., Delemer B.,
RA Young J., Binart N.;
RT "New NOBOX mutations identified in a large cohort of women with primary
RT ovarian insufficiency decrease KIT-L expression.";
RL J. Clin. Endocrinol. Metab. 100:994-1001(2015).
RN [6]
RP VARIANT LEU-44, CHARACTERIZATION OF VARIANT LEU-44, VARIANTS POF5 TRP-91;
RP ARG-111; ARG-152; 449-ARG--PRO-691 DEL AND ASN-452, CHARACTERIZATION OF
RP VARIANTS POF5 TRP-91; ARG-111; ARG-152; 449-ARG--PRO-691 DEL AND ASN-452,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27798098; DOI=10.1093/hmg/ddw342;
RA Ferrari I., Bouilly J., Beau I., Guizzardi F., Ferlin A., Pollazzon M.,
RA Salerno M., Binart N., Persani L., Rossetti R.;
RT "Impaired protein stability and nuclear localization of NOBOX variants
RT associated with premature ovarian insufficiency.";
RL Hum. Mol. Genet. 25:5223-5233(2016).
CC -!- FUNCTION: Transcription factor which may play a role in oogenesis.
CC Binds preferentially to the DNA sequences 5'-TAATTG-3', 5'-TAGTTG-3'
CC and 5'-TAATTA-3'. {ECO:0000269|PubMed:25514101,
CC ECO:0000269|PubMed:27798098}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:27798098}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60393-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60393-2; Sequence=VSP_028796;
CC -!- TISSUE SPECIFICITY: Expressed in ovaries, testes and pancreas.
CC Expressed within all stages of the adult female germline, from
CC primordial follicles through to MII oocytes.
CC {ECO:0000269|PubMed:16597639}.
CC -!- DISEASE: Premature ovarian failure 5 (POF5) [MIM:611548]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:17701902, ECO:0000269|PubMed:21837770,
CC ECO:0000269|PubMed:25514101, ECO:0000269|PubMed:27798098}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC12957.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AC004534; AAC12957.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS47736.2; -. [O60393-1]
DR RefSeq; NP_001073882.3; NM_001080413.3. [O60393-1]
DR RefSeq; XP_016867231.1; XM_017011742.1. [O60393-2]
DR AlphaFoldDB; O60393; -.
DR BioGRID; 126440; 7.
DR IntAct; O60393; 1.
DR STRING; 9606.ENSP00000419457; -.
DR GlyGen; O60393; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O60393; -.
DR PhosphoSitePlus; O60393; -.
DR BioMuta; NOBOX; -.
DR jPOST; O60393; -.
DR MassIVE; O60393; -.
DR PaxDb; O60393; -.
DR PeptideAtlas; O60393; -.
DR PRIDE; O60393; -.
DR ProteomicsDB; 49389; -. [O60393-1]
DR ProteomicsDB; 49390; -. [O60393-2]
DR Antibodypedia; 32735; 143 antibodies from 19 providers.
DR DNASU; 135935; -.
DR Ensembl; ENST00000467773.1; ENSP00000419457.1; ENSG00000106410.15. [O60393-1]
DR Ensembl; ENST00000483238.5; ENSP00000419565.1; ENSG00000106410.15. [O60393-2]
DR GeneID; 135935; -.
DR KEGG; hsa:135935; -.
DR MANE-Select; ENST00000467773.1; ENSP00000419457.1; NM_001080413.3; NP_001073882.3.
DR UCSC; uc022aoj.1; human. [O60393-1]
DR CTD; 135935; -.
DR DisGeNET; 135935; -.
DR GeneCards; NOBOX; -.
DR HGNC; HGNC:22448; NOBOX.
DR HPA; ENSG00000106410; Not detected.
DR MalaCards; NOBOX; -.
DR MIM; 610934; gene.
DR MIM; 611548; phenotype.
DR neXtProt; NX_O60393; -.
DR OpenTargets; ENSG00000106410; -.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR VEuPathDB; HostDB:ENSG00000106410; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00650000093445; -.
DR HOGENOM; CLU_034811_2_0_1; -.
DR InParanoid; O60393; -.
DR OMA; PIYGVCG; -.
DR OrthoDB; 729946at2759; -.
DR PhylomeDB; O60393; -.
DR TreeFam; TF337576; -.
DR PathwayCommons; O60393; -.
DR BioGRID-ORCS; 135935; 3 hits in 276 CRISPR screens.
DR GeneWiki; NOBOX; -.
DR GenomeRNAi; 135935; -.
DR Pharos; O60393; Tbio.
DR PRO; PR:O60393; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O60393; protein.
DR Bgee; ENSG00000106410; Expressed in right testis and 3 other tissues.
DR ExpressionAtlas; O60393; baseline and differential.
DR Genevisible; O60393; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR042988; NOBOX.
DR PANTHER; PTHR47060; PTHR47060; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation;
KW Disease variant; DNA-binding; Homeobox; Nucleus; Oogenesis;
KW Premature ovarian failure; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..691
FT /note="Homeobox protein NOBOX"
FT /id="PRO_0000268865"
FT DNA_BIND 272..363
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 94..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 366..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 635..691
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..177
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..411
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..435
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 318..349
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16597639"
FT /id="VSP_028796"
FT VARIANT 44
FT /note="R -> L (no effect on transactivation activity; not
FT statistically significant decrease of nuclear location;
FT dbSNP:rs115206969)"
FT /evidence="ECO:0000269|PubMed:25514101,
FT ECO:0000269|PubMed:27798098"
FT /id="VAR_078291"
FT VARIANT 91
FT /note="G -> W (in POF5; unknown pathological significance;
FT decreased transactivation activity; decreased nuclear
FT location; intranuclear and cytosolic aggregates;
FT dbSNP:rs77587352)"
FT /evidence="ECO:0000269|PubMed:21837770,
FT ECO:0000269|PubMed:25514101, ECO:0000269|PubMed:27798098"
FT /id="VAR_066013"
FT VARIANT 111
FT /note="G -> R (in POF5; unknown pathological significance;
FT loss of transactivation activity; intranuclear and
FT cytosolic aggregates; not statistically significant
FT decrease of nuclear location; dbSNP:rs571490209)"
FT /evidence="ECO:0000269|PubMed:25514101,
FT ECO:0000269|PubMed:27798098"
FT /id="VAR_078292"
FT VARIANT 117
FT /note="R -> W (in POF5; unknown pathological significance;
FT decreased transactivation activity; dbSNP:rs7800847)"
FT /evidence="ECO:0000269|PubMed:21837770,
FT ECO:0000269|PubMed:25514101"
FT /id="VAR_061266"
FT VARIANT 152
FT /note="G -> R (in POF5; unknown pathological significance;
FT decreased nuclear location; intranuclear and cytosolic
FT aggregates; dbSNP:rs201806397)"
FT /evidence="ECO:0000269|PubMed:27798098"
FT /id="VAR_078293"
FT VARIANT 342
FT /note="S -> T (in POF5; dbSNP:rs193303103)"
FT /evidence="ECO:0000269|PubMed:21837770"
FT /id="VAR_066014"
FT VARIANT 350
FT /note="V -> L (in POF5; dbSNP:rs193303104)"
FT /evidence="ECO:0000269|PubMed:21837770"
FT /id="VAR_066015"
FT VARIANT 355
FT /note="R -> H (in POF5; dbSNP:rs201947677)"
FT /evidence="ECO:0000269|PubMed:17701902"
FT /id="VAR_036636"
FT VARIANT 360
FT /note="R -> Q (in dbSNP:rs199538689)"
FT /evidence="ECO:0000269|PubMed:17701902"
FT /id="VAR_036637"
FT VARIANT 371
FT /note="K -> T (in POF5; unknown pathological significance;
FT decreased transactivation activity; dbSNP:rs189306575)"
FT /evidence="ECO:0000269|PubMed:25514101"
FT /id="VAR_078294"
FT VARIANT 449..691
FT /note="Missing (in POF5; unknown pathological significance;
FT not statistically significant decrease of nuclear
FT location)"
FT /evidence="ECO:0000269|PubMed:27798098"
FT /id="VAR_078295"
FT VARIANT 452
FT /note="D -> N (in POF5; likely benign variant; decreased
FT nuclear location; intranuclear and cytosolic aggregates;
FT dbSNP:rs112190116)"
FT /evidence="ECO:0000269|PubMed:17701902,
FT ECO:0000269|PubMed:27798098"
FT /id="VAR_036638"
FT VARIANT 482
FT /note="G -> S (in dbSNP:rs2525702)"
FT /evidence="ECO:0000269|PubMed:17701902"
FT /id="VAR_036639"
FT VARIANT 517
FT /note="F -> L (in dbSNP:rs2699503)"
FT /evidence="ECO:0000269|PubMed:17701902"
FT /id="VAR_036640"
FT VARIANT 619
FT /note="P -> L (no effect on transactivation activity;
FT dbSNP:rs146227301)"
FT /evidence="ECO:0000269|PubMed:25514101"
FT /id="VAR_078296"
SQ SEQUENCE 691 AA; 73906 MW; 02ED17B02018A89C CRC64;
MALLLTLTSP DLEGTWDTRD KDGFKAQEGP PLAVPEFPVC GLYRIYGVCG SFSSFFIIRC
SLCALETLKS PQHDPLEIPE QSLKLIPLVS GKRELTRGQK AGEKPLAAGP GEEELLRGSA
PHAQDTQSEE LPPSCTISGE KKPPAVSGEA TGADAGRLCP PPRSRAPHKD RTLARSRPQT
QGEDCSLPVG EVKIGKRSYS PAPGKQKKPN AMGLAPTSSP GAPNSARATH NPVPCGSGRG
PCHLANLLST LAQSNQNRDH KQGPPEVTCQ IRKKTRTLYR SDQLEELEKI FQEDHYPDSD
KRREIAQTVG VTPQRIMVKG AGSLVAGWSG GGPTIETLEL QSERSAVAWV WFQNRRAKWR
KMEKLNGKES KDNPAAPGPA SSQCSSAAEI LPAVPMEPKP DPFPQESPLD TFPEPPMLLT
SDQTLAPTQP SEGAQRVVTP PLFSPPPVRR ADLPFPLGPV HTPQLMPLLM DVAGSDSSHK
DGPCGSWGTS ITLPPPCSYL EELEPQDYQQ SNQPGPFQFS QAPQPPLFQS PQPKLPYLPT
FPFSMPSSLT LPPPEDSLFM FPCGPSGGTS QGYCPGASSG QILMQPPAGN IGTASWSDPC
LPELPFPGPF CPQALGHPPG GDGYFPDLFP TPCPQALGRQ PSSALSWMPE GARPGTGPLL
SKAKEEPPAA SLDQPSALEE ARGDDKNSHV P
