NT2NB_HUMAN
ID NT2NB_HUMAN Reviewed; 275 AA.
AC P0DPK3;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Notch homolog 2 N-terminal-like protein B {ECO:0000303|PubMed:29856954, ECO:0000303|PubMed:29856955};
DE Flags: Precursor;
GN Name=NOTCH2NLB {ECO:0000303|PubMed:29856954, ECO:0000303|PubMed:29856955,
GN ECO:0000312|HGNC:HGNC:53923};
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=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NOTCH2, TISSUE
RP SPECIFICITY, AND INVOLVEMENT IN CHROMOSOME 1Q21.1 DELETION/DUPLICATION
RP SYNDROME.
RX PubMed=29856954; DOI=10.1016/j.cell.2018.03.051;
RA Fiddes I.T., Lodewijk G.A., Mooring M., Bosworth C.M., Ewing A.D.,
RA Mantalas G.L., Novak A.M., van den Bout A., Bishara A., Rosenkrantz J.L.,
RA Lorig-Roach R., Field A.R., Haeussler M., Russo L., Bhaduri A.,
RA Nowakowski T.J., Pollen A.A., Dougherty M.L., Nuttle X., Addor M.C.,
RA Zwolinski S., Katzman S., Kriegstein A., Eichler E.E., Salama S.R.,
RA Jacobs F.M.J., Haussler D.;
RT "Human-specific NOTCH2NL genes affect Notch signaling and cortical
RT neurogenesis.";
RL Cell 173:1356-1369(2018).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INTERACTION WITH
RP DLL1.
RX PubMed=29856955; DOI=10.1016/j.cell.2018.03.067;
RA Suzuki I.K., Gacquer D., Van Heurck R., Kumar D., Wojno M., Bilheu A.,
RA Herpoel A., Lambert N., Cheron J., Polleux F., Detours V.,
RA Vanderhaeghen P.;
RT "Human-specific NOTCH2NL genes expand cortical neurogenesis through
RT Delta/Notch regulation.";
RL Cell 173:1370-1384(2018).
RN [4]
RP FUNCTION.
RX PubMed=29561261; DOI=10.7554/elife.32332;
RA Florio M., Heide M., Pinson A., Brandl H., Albert M., Winkler S.,
RA Wimberger P., Huttner W.B., Hiller M.;
RT "Evolution and cell-type specificity of human-specific genes preferentially
RT expressed in progenitors of fetal neocortex.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Human-specific protein that promotes neural progenitor
CC proliferation and evolutionary expansion of the brain neocortex by
CC regulating the Notch signaling pathway (PubMed:29856954,
CC PubMed:29856955, PubMed:29561261). Able to promote neural progenitor
CC self-renewal, possibly by down-regulating neuronal differentiation
CC genes, thereby delaying the differentiation of neuronal progenitors and
CC leading to an overall final increase in neuronal production
CC (PubMed:29856954, PubMed:29856955). Acts by enhancing the Notch
CC signaling pathway via two different mechanisms that probably work in
CC parallel to reach the same effect (PubMed:29856954, PubMed:29856955).
CC Enhances Notch signaling pathway in a non-cell-autonomous manner via
CC direct interaction with NOTCH2 (PubMed:29856954). Also promotes Notch
CC signaling pathway in a cell-autonomous manner through inhibition of cis
CC DLL1-NOTCH2 interactions, which promotes neuronal differentiation
CC (PubMed:29856955). {ECO:0000269|PubMed:29561261,
CC ECO:0000269|PubMed:29856954, ECO:0000269|PubMed:29856955}.
CC -!- SUBUNIT: Interacts with NOTCH2 (PubMed:29856954). Interacts with DLL1;
CC the interaction is direct (PubMed:29856955).
CC {ECO:0000269|PubMed:29856954, ECO:0000269|PubMed:29856955}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29856954,
CC ECO:0000269|PubMed:29856955}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P0DPK3-1, A0A0B4J2B3-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P0DPK3-2, A0A0B4J2B3-2;
CC Sequence=VSP_059805;
CC -!- TISSUE SPECIFICITY: Expressed in radial glia neural stem cells during
CC cortical development. {ECO:0000269|PubMed:29856954}.
CC -!- DEVELOPMENTAL STAGE: Expressed at low levels at 7-9 gestational weeks
CC and then increases at later stages, including in the non-cortical plate
CC region at gestational week 21, containing the outer-subventricular
CC zone. {ECO:0000269|PubMed:29856955}.
CC -!- DISEASE: Note=Defects in NOTCH2NLB may be a cause of chromosome 1q21.1
CC deletion/duplication syndrome (PubMed:29856954). Deletions of NOTCH2NL
CC (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC) are present in patients
CC affected by microcephaly, whereas macrocephaly is observed in patients
CC with NOTCH2NL duplications (PubMed:29856954).
CC {ECO:0000269|PubMed:29856954}.
CC -!- MISCELLANEOUS: NOTCH2NLA, NOTCH2NLB and NOTCH2NLC paralogs arose
CC between 4 and 3 million years ago, after the separation of hominids
CC from the chimpanzee and during the early stages of the expansion of the
CC human cortex. {ECO:0000269|PubMed:29856954}.
CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
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DR EMBL; AC239811; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS86012.1; -. [P0DPK3-2]
DR AlphaFoldDB; P0DPK3; -.
DR SMR; P0DPK3; -.
DR STRING; 9606.ENSP00000464060; -.
DR GlyGen; P0DPK3; 2 sites.
DR jPOST; P0DPK3; -.
DR MassIVE; P0DPK3; -.
DR PeptideAtlas; P0DPK3; -.
DR Ensembl; ENST00000593495.3; ENSP00000472124.1; ENSG00000286019.1. [P0DPK3-2]
DR MANE-Select; ENST00000593495.4; ENSP00000472124.1; NM_001364008.2; NP_001350937.1. [P0DPK3-2]
DR GeneCards; NOTCH2NLB; -.
DR HGNC; HGNC:53923; NOTCH2NLB.
DR HPA; ENSG00000286019; Low tissue specificity.
DR neXtProt; NX_P0DPK3; -.
DR VEuPathDB; HostDB:ENSG00000286019; -.
DR GeneTree; ENSGT00940000167308; -.
DR OMA; VDPCHSD; -.
DR ChiTaRS; NOTCH2NLB; human.
DR Pharos; P0DPK3; Tbio.
DR PRO; PR:P0DPK3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR Bgee; ENSG00000286019; Expressed in stromal cell of endometrium and 92 other tissues.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR Pfam; PF00008; EGF; 3.
DR Pfam; PF07645; EGF_CA; 1.
DR SMART; SM00181; EGF; 6.
DR SMART; SM00179; EGF_CA; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 5.
DR PROSITE; PS01186; EGF_2; 5.
DR PROSITE; PS50026; EGF_3; 6.
DR PROSITE; PS01187; EGF_CA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Disulfide bond; EGF-like domain;
KW Glycoprotein; Notch signaling pathway; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..275
FT /note="Notch homolog 2 N-terminal-like protein B"
FT /evidence="ECO:0000255"
FT /id="PRO_0000445070"
FT DOMAIN 26..63
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 64..102
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 105..143
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 144..180
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 182..219
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 221..258
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..41
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 35..51
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 53..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 68..79
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 73..90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 92..101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 109..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 115..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 133..142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 148..159
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 153..168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 170..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 186..198
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 192..207
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 209..218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 225..236
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 230..246
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 1..27
FT /note="MPALRPALLWALLALWLCCATPAHALQ -> M (in isoform 2)"
FT /id="VSP_059805"
SQ SEQUENCE 275 AA; 30097 MW; 9166792CD8DEEFA6 CRC64;
MPALRPALLW ALLALWLCCA TPAHALQCRD GYEPCVNEGM CVTYHNGTGY CKCPEGFLGE
YCQHRDPCEK NRCQNGGTCV AQAMLGKATC RCASGFTGED CQYSTSHPCF VSRPCLNGGT
CHMLSRDTYE CTCQVGFTGK ECQWTDACLS HPCANGSTCT TVANQFSCKC LTGFTGQKCE
TDVNECDIPG HCQHGGICLN LPGSYQCQCL QGFTGQYCDS LYVPCAPSPC VNGGTCRQTG
DFTFECNCLP ETVRRGTELW ERDREVWNGK EHDEN
