UniProtKB - P49757 (NUMB_HUMAN)
Protein numb homolog
NUMB
Functioni
Regulates clathrin-mediated receptor endocytosis (PubMed:18657069).
Plays a role in the process of neurogenesis (By similarity).
Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate (By similarity).
Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity (By similarity).
May also mediate local repair of brain ventricular wall damage (By similarity).
By similarity1 PublicationGO - Molecular functioni
- alpha-catenin binding Source: Ensembl
- beta-catenin binding Source: Ensembl
- cadherin binding Source: BHF-UCL
GO - Biological processi
- adherens junction organization Source: Ensembl
- axonogenesis Source: Ensembl
- lateral ventricle development Source: UniProtKB
- negative regulation of protein localization to plasma membrane Source: UniProtKB
- neuroblast division in subventricular zone Source: UniProtKB
- positive regulation of cell migration Source: UniProtKB
- positive regulation of neurogenesis Source: UniProtKB
- regulation of postsynaptic neurotransmitter receptor internalization Source: Ensembl
Keywordsi
Molecular function | Developmental protein |
Biological process | Neurogenesis |
Enzyme and pathway databases
PathwayCommonsi | P49757 |
Reactomei | R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-437239, Recycling pathway of L1 R-HSA-5610780, Degradation of GLI1 by the proteasome R-HSA-5632684, Hedgehog 'on' state |
SignaLinki | P49757 |
SIGNORi | P49757 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein numb homologShort name: h-Numb Alternative name(s): Protein S171 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:8060, NUMB |
MIMi | 603728, gene |
neXtProti | NX_P49757 |
VEuPathDBi | HostDB:ENSG00000133961 |
Subcellular locationi
Endosome
- Endosome membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
Plasma membrane
- Cell membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
Note: Localizes to perinuclear endosomes in an AAK1-dependent manner.1 Publication
Endosome
- early endosome Source: Ensembl
- endosome membrane Source: UniProtKB-SubCell
Nucleus
- nucleus Source: Ensembl
Plasma Membrane
- basolateral plasma membrane Source: Ensembl
- clathrin-coated pit Source: Ensembl
- extrinsic component of plasma membrane Source: Ensembl
- plasma membrane Source: Reactome
Other locations
- apical part of cell Source: Ensembl
- clathrin-coated vesicle Source: UniProtKB
- cytoplasm Source: GO_Central
- focal adhesion Source: UniProtKB
- glutamatergic synapse Source: Ensembl
Keywords - Cellular componenti
Cell membrane, Endosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 102 | T → A: Loss of AAK1-mediated phosphorylation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8650 |
OpenTargetsi | ENSG00000133961 |
PharmGKBi | PA31845 |
Miscellaneous databases
Pharosi | P49757, Tbio |
Genetic variation databases
BioMutai | NUMB |
DMDMi | 14195675 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000058001 | 1 – 651 | Protein numb homologAdd BLAST | 651 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 102 | Phosphothreonine; by AAK11 Publication | 1 | |
Modified residuei | 194 | PhosphoserineCombined sources | 1 | |
Modified residuei | 243 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 244 | PhosphoserineCombined sources | 1 | |
Modified residuei | 276 | Phosphoserine; by CaMK1By similarity | 1 | |
Modified residuei | 295 | Phosphoserine; by CaMK1By similarity | 1 | |
Modified residuei | 425 | PhosphoserineCombined sources | 1 | |
Modified residuei | 436 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 438 | PhosphoserineCombined sources | 1 | |
Modified residuei | 634 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P49757 |
jPOSTi | P49757 |
MassIVEi | P49757 |
MaxQBi | P49757 |
PaxDbi | P49757 |
PeptideAtlasi | P49757 |
PRIDEi | P49757 |
ProteomicsDBi | 3393 3394 3395 3396 56075 [P49757-1] 56076 [P49757-2] 56077 [P49757-3] 56078 [P49757-4] |
PTM databases
GlyGeni | P49757, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P49757 |
MetOSitei | P49757 |
PhosphoSitePlusi | P49757 |
SwissPalmi | P49757 |
Expressioni
Gene expression databases
Bgeei | ENSG00000133961, Expressed in monocyte and 239 other tissues |
ExpressionAtlasi | P49757, baseline and differential |
Genevisiblei | P49757, HS |
Organism-specific databases
HPAi | ENSG00000133961, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with SIAH1 (PubMed:11752454).
Interacts with LNX (By similarity).
Interacts with CDH1 (By similarity).
Interacts with TFAP2A and TFAP2B (By similarity).
Interacts with RALBP1 in a complex also containing EPN1 and TFAP2A during interphase and mitosis (PubMed:12775724).
Interacts with AAK1 (PubMed:18657069). May interact with DUOXA1 (PubMed:14670962).
By similarity4 PublicationsBinary interactionsi
P49757
With | #Exp. | IntAct |
---|---|---|
CTNNB1 [P35222] | 2 | EBI-915016,EBI-491549 |
EPS15 [P42566] | 4 | EBI-915016,EBI-396684 |
MDM2 [Q00987] | 9 | EBI-915016,EBI-389668 |
REPS1 [Q96D71] | 3 | EBI-915016,EBI-1171195 |
TP53 [P04637] | 5 | EBI-915016,EBI-366083 |
Isoform 1 [P49757-1]
With | #Exp. | IntAct |
---|---|---|
PRKCZ [Q05513] | 4 | EBI-7199607,EBI-295351 |
Isoform 3 [P49757-3]
With | #Exp. | IntAct |
---|---|---|
CTNNB1 [P35222] | 3 | EBI-10692196,EBI-491549 |
Isoform 8 [P49757-8]
With | #Exp. | IntAct |
---|---|---|
APP [P05067] | 3 | EBI-25937715,EBI-77613 |
GO - Molecular functioni
- alpha-catenin binding Source: Ensembl
- beta-catenin binding Source: Ensembl
- cadherin binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 114202, 158 interactors |
CORUMi | P49757 |
DIPi | DIP-37981N |
ELMi | P49757 |
IntActi | P49757, 66 interactors |
MINTi | P49757 |
STRINGi | 9606.ENSP00000451300 |
Miscellaneous databases
RNActi | P49757, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P49757 |
SMRi | P49757 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 33 – 193 | PIDPROSITE-ProRule annotationAdd BLAST | 161 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 228 – 257 | DisorderedSequence analysisAdd BLAST | 30 | |
Regioni | 419 – 483 | DisorderedSequence analysisAdd BLAST | 65 | |
Regioni | 623 – 651 | DisorderedSequence analysisAdd BLAST | 29 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 231 – 257 | Polar residuesSequence analysisAdd BLAST | 27 | |
Compositional biasi | 463 – 477 | Pro residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 624 – 644 | Polar residuesSequence analysisAdd BLAST | 21 |
Phylogenomic databases
eggNOGi | KOG3537, Eukaryota |
GeneTreei | ENSGT00940000156005 |
HOGENOMi | CLU_031797_1_1_1 |
InParanoidi | P49757 |
OMAi | CSFPVKX |
PhylomeDBi | P49757 |
TreeFami | TF314159 |
Family and domain databases
DisProti | DP01130 |
Gene3Di | 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR016698, Numb/numb-like IPR010449, Numb_domain IPR011993, PH-like_dom_sf IPR006020, PTB/PI_dom |
PANTHERi | PTHR47368, PTHR47368, 1 hit |
Pfami | View protein in Pfam PF06311, NumbF, 1 hit PF00640, PID, 1 hit |
PIRSFi | PIRSF017607, Numb/numb-like, 1 hit |
SMARTi | View protein in SMART SM00462, PTB, 1 hit |
PROSITEi | View protein in PROSITE PS01179, PID, 1 hit |
s (9+)i Sequence
Sequence statusi: Complete.
This entry describes 9 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 9 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD
60 70 80 90 100
ESRGMHICED AVKRLKAERK FFKGFFGKTG KKAVKAVLWV SADGLRVVDE
110 120 130 140 150
KTKDLIVDQT IEKVSFCAPD RNFDRAFSYI CRDGTTRRWI CHCFMAVKDT
160 170 180 190 200
GERLSHAVGC AFAACLERKQ KREKECGVTA TFDASRTTFT REGSFRVTTA
210 220 230 240 250
TEQAEREEIM KQMQDAKKAE TDKIVVGSSV APGNTAPSPS SPTSPTSDAT
260 270 280 290 300
TSLEMNNPHA IPRRHAPIEQ LARQGSFRGF PALSQKMSPF KRQLSLRINE
310 320 330 340 350
LPSTMQRKTD FPIKNAVPEV EGEAESISSL CSQITNAFST PEDPFSSAPM
360 370 380 390 400
TKPVTVVAPQ SPTFQANGTD SAFHVLAKPA HTALAPVAMP VRETNPWAHA
410 420 430 440 450
PDAANKEIAA TCSGTEWGQS SGAASPGLFQ AGHRRTPSEA DRWLEEVSKS
460 470 480 490 500
VRAQQPQASA APLQPVLQPP PPTAISQPAS PFQGNAFLTS QPVPVGVVPA
510 520 530 540 550
LQPAFVPAQS YPVANGMPYP APNVPVVGIT PSQMVANVFG TAGHPQAAHP
560 570 580 590 600
HQSPSLVRQQ TFPHYEASSA TTSPFFKPPA QHLNGSAAFN GVDDGRLASA
610 620 630 640 650
DRHTEVPTGT CPVDPFEAQW AALENKSKQR TNPSPTNPFS SDLQKTFEIE
L
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3V3M5 | G3V3M5_HUMAN | Protein numb homolog | NUMB | 223 | Annotation score: | ||
G3V3Z8 | G3V3Z8_HUMAN | Protein numb homolog | NUMB | 507 | Annotation score: | ||
G3V3R1 | G3V3R1_HUMAN | Protein numb homolog | NUMB | 258 | Annotation score: | ||
G3V433 | G3V433_HUMAN | Protein numb homolog | NUMB | 80 | Annotation score: | ||
G3V4S6 | G3V4S6_HUMAN | Protein numb homolog | NUMB | 67 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 31 | G → S in AAD27959 (Ref. 4) Curated | 1 | |
Sequence conflicti | 68 | E → Q in AAD27959 (Ref. 4) Curated | 1 | |
Sequence conflicti | 193 | G → R in AAD27959 (Ref. 4) Curated | 1 | |
Sequence conflicti | 450 | S → N in AAD27959 (Ref. 4) Curated | 1 | |
Sequence conflicti | 533 | Q → K in AAH68476 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051249 | 387 | V → I. Corresponds to variant dbSNP:rs17182272Ensembl. | 1 | |
Natural variantiVAR_051250 | 595 | G → D. Corresponds to variant dbSNP:rs17781919Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053745 | 1 – 254 | Missing in isoform 9. 2 PublicationsAdd BLAST | 254 | |
Alternative sequenceiVSP_004348 | 68 – 78 | Missing in isoform 3, isoform 4, isoform 6 and isoform 8. 3 PublicationsAdd BLAST | 11 | |
Alternative sequenceiVSP_047756 | 219 – 316 | Missing in isoform 5, isoform 6, isoform 7 and isoform 8. 1 PublicationAdd BLAST | 98 | |
Alternative sequenceiVSP_053763 | 317 – 365 | Missing in isoform 7 and isoform 8. 1 PublicationAdd BLAST | 49 | |
Alternative sequenceiVSP_004349 | 366 – 413 | Missing in isoform 2, isoform 4, isoform 5, isoform 6, isoform 7, isoform 8 and isoform 9. 6 PublicationsAdd BLAST | 48 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF015040 mRNA Translation: AAD01548.1 AF171938 mRNA Translation: AAD54279.1 AF171939 mRNA Translation: AAD54280.1 AF171940 mRNA Translation: AAD54281.1 AF171941 mRNA Translation: AAD54282.1 EU265734 mRNA Translation: ABY89090.1 EU265735 mRNA Translation: ABY89091.1 EU265736 mRNA Translation: ABY89092.1 EU265737 mRNA Translation: ABY89093.1 EU265738 mRNA Translation: ABY89094.1 AF108092 mRNA Translation: AAD27959.1 AK294591 mRNA Translation: BAG57779.1 AK304193 mRNA Translation: BAG65073.1 AC004846 Genomic DNA No translation available. AC005280 Genomic DNA No translation available. AL391733 Genomic DNA No translation available. CH471061 Genomic DNA Translation: EAW81106.1 BC020788 mRNA Translation: AAH20788.1 Sequence problems. BC068476 mRNA Translation: AAH68476.1 BX248073 mRNA Translation: CAD62362.1 AF109907 Genomic DNA Translation: AAC97962.1 L40393 mRNA Translation: AAC42000.1 |
CCDSi | CCDS32115.1 [P49757-2] CCDS32116.1 [P49757-1] CCDS55927.1 [P49757-4] CCDS9814.1 [P49757-3] |
RefSeqi | NP_001005743.1, NM_001005743.1 [P49757-1] NP_001005744.1, NM_001005744.1 [P49757-2] NP_001005745.1, NM_001005745.1 [P49757-4] NP_001307043.1, NM_001320114.1 [P49757-2] NP_003735.3, NM_003744.5 [P49757-3] |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF015040 mRNA Translation: AAD01548.1 AF171938 mRNA Translation: AAD54279.1 AF171939 mRNA Translation: AAD54280.1 AF171940 mRNA Translation: AAD54281.1 AF171941 mRNA Translation: AAD54282.1 EU265734 mRNA Translation: ABY89090.1 EU265735 mRNA Translation: ABY89091.1 EU265736 mRNA Translation: ABY89092.1 EU265737 mRNA Translation: ABY89093.1 EU265738 mRNA Translation: ABY89094.1 AF108092 mRNA Translation: AAD27959.1 AK294591 mRNA Translation: BAG57779.1 AK304193 mRNA Translation: BAG65073.1 AC004846 Genomic DNA No translation available. AC005280 Genomic DNA No translation available. AL391733 Genomic DNA No translation available. CH471061 Genomic DNA Translation: EAW81106.1 BC020788 mRNA Translation: AAH20788.1 Sequence problems. BC068476 mRNA Translation: AAH68476.1 BX248073 mRNA Translation: CAD62362.1 AF109907 Genomic DNA Translation: AAC97962.1 L40393 mRNA Translation: AAC42000.1 |
CCDSi | CCDS32115.1 [P49757-2] CCDS32116.1 [P49757-1] CCDS55927.1 [P49757-4] CCDS9814.1 [P49757-3] |
RefSeqi | NP_001005743.1, NM_001005743.1 [P49757-1] NP_001005744.1, NM_001005744.1 [P49757-2] NP_001005745.1, NM_001005745.1 [P49757-4] NP_001307043.1, NM_001320114.1 [P49757-2] NP_003735.3, NM_003744.5 [P49757-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5NJJ | X-ray | 2.70 | A/B/C/D | 20-175 | [»] | |
5NJK | X-ray | 3.13 | A/B/C/D/E/F | 20-175 | [»] | |
AlphaFoldDBi | P49757 | |||||
SMRi | P49757 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114202, 158 interactors |
CORUMi | P49757 |
DIPi | DIP-37981N |
ELMi | P49757 |
IntActi | P49757, 66 interactors |
MINTi | P49757 |
STRINGi | 9606.ENSP00000451300 |
PTM databases
GlyGeni | P49757, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P49757 |
MetOSitei | P49757 |
PhosphoSitePlusi | P49757 |
SwissPalmi | P49757 |
Genetic variation databases
BioMutai | NUMB |
DMDMi | 14195675 |
Proteomic databases
EPDi | P49757 |
jPOSTi | P49757 |
MassIVEi | P49757 |
MaxQBi | P49757 |
PaxDbi | P49757 |
PeptideAtlasi | P49757 |
PRIDEi | P49757 |
ProteomicsDBi | 3393 3394 3395 3396 56075 [P49757-1] 56076 [P49757-2] 56077 [P49757-3] 56078 [P49757-4] |
Protocols and materials databases
Antibodypediai | 131, 846 antibodies from 43 providers |
DNASUi | 8650 |
Genome annotation databases
Organism-specific databases
CTDi | 8650 |
DisGeNETi | 8650 |
GeneCardsi | NUMB |
HGNCi | HGNC:8060, NUMB |
HPAi | ENSG00000133961, Low tissue specificity |
MIMi | 603728, gene |
neXtProti | NX_P49757 |
OpenTargetsi | ENSG00000133961 |
PharmGKBi | PA31845 |
VEuPathDBi | HostDB:ENSG00000133961 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3537, Eukaryota |
GeneTreei | ENSGT00940000156005 |
HOGENOMi | CLU_031797_1_1_1 |
InParanoidi | P49757 |
OMAi | CSFPVKX |
PhylomeDBi | P49757 |
TreeFami | TF314159 |
Enzyme and pathway databases
PathwayCommonsi | P49757 |
Reactomei | R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-437239, Recycling pathway of L1 R-HSA-5610780, Degradation of GLI1 by the proteasome R-HSA-5632684, Hedgehog 'on' state |
SignaLinki | P49757 |
SIGNORi | P49757 |
Miscellaneous databases
BioGRID-ORCSi | 8650, 15 hits in 1078 CRISPR screens |
ChiTaRSi | NUMB, human |
GeneWikii | NUMB_(gene) |
GenomeRNAii | 8650 |
Pharosi | P49757, Tbio |
PROi | PR:P49757 |
RNActi | P49757, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000133961, Expressed in monocyte and 239 other tissues |
ExpressionAtlasi | P49757, baseline and differential |
Genevisiblei | P49757, HS |
Family and domain databases
DisProti | DP01130 |
Gene3Di | 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR016698, Numb/numb-like IPR010449, Numb_domain IPR011993, PH-like_dom_sf IPR006020, PTB/PI_dom |
PANTHERi | PTHR47368, PTHR47368, 1 hit |
Pfami | View protein in Pfam PF06311, NumbF, 1 hit PF00640, PID, 1 hit |
PIRSFi | PIRSF017607, Numb/numb-like, 1 hit |
SMARTi | View protein in SMART SM00462, PTB, 1 hit |
PROSITEi | View protein in PROSITE PS01179, PID, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NUMB_HUMAN | |
Accessioni | P49757Primary (citable) accession number: P49757 Secondary accession number(s): B1P2N5 Q9UQJ4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | June 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 187 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references