NUMB_RAT
ID NUMB_RAT Reviewed; 652 AA.
AC Q2LC84; B2GVA9; F1MAI8;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 2.
DT 25-MAY-2022, entry version 91.
DE RecName: Full=Protein numb homolog;
GN Name=Numb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Lewis; TISSUE=Kidney;
RA Kwon S.H., Reichardt H.M.;
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Prostate;
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 [3]
RP INTERACTION WITH TFAP2A AND TFAP2B, PHOSPHORYLATION AT SER-275 AND SER-294,
RP AND MUTAGENESIS OF SER-275 AND SER-294.
RX PubMed=17022975; DOI=10.1016/j.febslet.2006.09.043;
RA Tokumitsu H., Hatano N., Yokokura S., Sueyoshi Y., Nozaki N., Kobayashi R.;
RT "Phosphorylation of Numb regulates its interaction with the clathrin-
RT associated adaptor AP-2.";
RL FEBS Lett. 580:5797-5801(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439 AND SER-635, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Regulates clathrin-mediated receptor endocytosis (By
CC similarity). Plays a role in the process of neurogenesis. Required
CC throughout embryonic neurogenesis to maintain neural progenitor cells,
CC also called radial glial cells (RGCs), by allowing their daughter cells
CC to choose progenitor over neuronal cell fate. Not required for the
CC proliferation of neural progenitor cells before the onset of
CC neurogenesis. Also involved postnatally in the subventricular zone
CC (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal
CC wall integrity. May also mediate local repair of brain ventricular wall
CC damage (By similarity). {ECO:0000250|UniProtKB:P49757,
CC ECO:0000250|UniProtKB:Q9QZS3}.
CC -!- SUBUNIT: Interacts with SIAH1 (By similarity). Interacts with LNX (By
CC similarity). Interacts with CDH1 (By similarity). Interacts with TFAP2A
CC and TFAP2B (PubMed:17022975). Interacts with RALBP1 in a complex also
CC containing EPN1 and TFAP2A during interphase and mitosis (By
CC similarity). Interacts with AAK1 (By similarity). May interact with
CC DUOXA1 (By similarity). {ECO:0000250|UniProtKB:P49757,
CC ECO:0000250|UniProtKB:Q9QZS3, ECO:0000269|PubMed:17022975}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P49757};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P49757}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:P49757}. Endosome membrane
CC {ECO:0000250|UniProtKB:P49757}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P49757}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P49757}. Note=Localizes to perinuclear endosomes
CC in an AAK1-dependent manner. {ECO:0000250|UniProtKB:P49757}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=i/i;
CC IsoId=Q2LC84-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2LC84-2; Sequence=VSP_041811;
CC -!- PTM: Phosphorylated on Ser-275 and Ser-294 by CaMK1.
CC {ECO:0000269|PubMed:17022975}.
CC -!- PTM: Isoform 1 and isoform 2 are ubiquitinated by LNX leading to their
CC subsequent proteasomal degradation. Ubiquitinated; mediated by SIAH1
CC and leading to its subsequent proteasomal degradation. {ECO:0000250}.
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DR EMBL; BC166596; AAI66596.1; -; mRNA.
DR EMBL; DQ336705; ABC69737.1; -; mRNA.
DR AlphaFoldDB; Q2LC84; -.
DR SMR; Q2LC84; -.
DR IntAct; Q2LC84; 20.
DR MINT; Q2LC84; -.
DR STRING; 10116.ENSRNOP00000048410; -.
DR iPTMnet; Q2LC84; -.
DR PhosphoSitePlus; Q2LC84; -.
DR PRIDE; Q2LC84; -.
DR RGD; 620107; Numb.
DR eggNOG; KOG3537; Eukaryota.
DR InParanoid; Q2LC84; -.
DR Reactome; R-RNO-437239; Recycling pathway of L1.
DR Reactome; R-RNO-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-RNO-5632684; Hedgehog 'on' state.
DR PRO; PR:Q2LC84; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0005905; C:clathrin-coated pit; ISO:RGD.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0045294; F:alpha-catenin binding; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0045296; F:cadherin binding; ISO:RGD.
DR GO; GO:0034332; P:adherens junction organization; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; NAS:RGD.
DR GO; GO:0008283; P:cell population proliferation; NAS:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0021670; P:lateral ventricle development; ISO:RGD.
DR GO; GO:0060487; P:lung epithelial cell differentiation; ISO:RGD.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISO:RGD.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0021849; P:neuroblast division in subventricular zone; ISO:RGD.
DR GO; GO:0007405; P:neuroblast proliferation; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:RGD.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISO:RGD.
DR GO; GO:0030862; P:positive regulation of polarized epithelial cell differentiation; ISO:RGD.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:RGD.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; ISO:RGD.
DR GO; GO:0099150; P:regulation of postsynaptic specialization assembly; IDA:SynGO.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016698; Numb/numb-like.
DR InterPro; IPR010449; Numb_domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR PANTHER; PTHR47368; PTHR47368; 1.
DR Pfam; PF06311; NumbF; 1.
DR Pfam; PF00640; PID; 1.
DR PIRSF; PIRSF017607; Numb/numb-like; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Developmental protein; Endosome;
KW Membrane; Neurogenesis; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..652
FT /note="Protein numb homolog"
FT /id="PRO_0000412901"
FT DOMAIN 37..173
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 213..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 624..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 547..580
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..644
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 102
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P49757"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49757"
FT MOD_RES 242
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZS3"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49757"
FT MOD_RES 275
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000269|PubMed:17022975"
FT MOD_RES 294
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000269|PubMed:17022975"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49757"
FT MOD_RES 437
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P49757"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 635
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 68..78
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041811"
FT MUTAGEN 275
FT /note="S->A: Loss of phosphorylation by CaMK1."
FT /evidence="ECO:0000269|PubMed:17022975"
FT MUTAGEN 294
FT /note="S->A: Loss of phosphorylation by CaMK1."
FT /evidence="ECO:0000269|PubMed:17022975"
FT CONFLICT 459
FT /note="A -> V (in Ref. 1; ABC69737)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 652 AA; 70596 MW; B4AD582D3A0CA45A CRC64;
MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD ESRGMHICED
AVKRLKAERK FFKGFFGKTG KKAVKAVLWV SADGLRVVDE KTKDLIVDQT IEKVSFCAPD
RNFDRAFSYI CRDGTTRRWI CHCFMAVKDT GERLSHAVGC AFAACLERKQ KREKECGVTA
TFDASRTTFT REGSFRVTTA TEQAEREEIM KQLQDAKKAE TDKTVGPSVA PGNSAPSPSS
PTSPTLDPTA SLEMNNPHAI PRRHAPIEQL ARQGSFRGFP ALSQKMSPFK RQLSLRINEL
PSTMQRKTDF PIKNTVPEVE GEAESISSLC SQITSAFSTP CEDPFSSAPM TKPVTLVAPQ
SPVLQANGTD SALHVLTAKP ASTALAPVAM PVRETNPWAH APDAANKEIA AIHSGTEWGQ
SSGAASPGLF QAGHRRTPSE ADRWLEEVSK SVRAQQPQAS AAPLQPVLQP PPPAAIAPPA
PPFQGHAFLT SQPVPVGVVP PLQPAFVSTQ SYPVANGMPY PASNVPVVGI TPSQMVANVF
GTAGHPQATH PHQSPSLAKQ QTFPQYETSS ATTSPFFKPS AQHLNGSAAF NGVDNSGLVS
GNRPAQVPPG TCPVDPFEAQ WAALESKPKQ RTNPSPTNPF SSDAQKAFEI EL
