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Protein

Protein numb homolog

Gene

NUMB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a role in the process of neurogenesis. 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. 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. May also mediate local repair of brain ventricular wall damage.

GO - Molecular functioni

  • alpha-catenin binding Source: Ensembl
  • beta-catenin binding Source: Ensembl
  • cadherin binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processNeurogenesis

Enzyme and pathway databases

ReactomeiR-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
SignaLinkiP49757
SIGNORiP49757

Names & Taxonomyi

Protein namesi
Recommended name:
Protein numb homolog
Short name:
h-Numb
Alternative name(s):
Protein S171
Gene namesi
Name:NUMBImported
Synonyms:C14orf41Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000133961.19
HGNCiHGNC:8060 NUMB
MIMi603728 gene
neXtProtiNX_P49757

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8650
OpenTargetsiENSG00000133961
PharmGKBiPA31845

Polymorphism and mutation databases

BioMutaiNUMB
DMDMi14195675

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000580011 – 651Protein numb homologAdd BLAST651

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei194PhosphoserineCombined sources1
Modified residuei243PhosphothreonineBy similarity1
Modified residuei244PhosphoserineCombined sources1
Modified residuei276Phosphoserine; by CaMK1By similarity1
Modified residuei295Phosphoserine; by CaMK1By similarity1
Modified residuei425PhosphoserineCombined sources1
Modified residuei436PhosphothreonineCombined sources1
Modified residuei438PhosphoserineCombined sources1
Modified residuei634PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on Ser-276 and Ser-295 by CaMK1.By similarity
Isoform 1 and isoform 2 are ubiquitinated by LNX leading to their subsequent proteasomal degradation (By similarity). Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49757
MaxQBiP49757
PaxDbiP49757
PeptideAtlasiP49757
PRIDEiP49757

PTM databases

iPTMnetiP49757
PhosphoSitePlusiP49757

Expressioni

Gene expression databases

BgeeiENSG00000133961
ExpressionAtlasiP49757 baseline and differential
GenevisibleiP49757 HS

Organism-specific databases

HPAiCAB011478

Interactioni

Subunit structurei

Interacts with CDH1 and TFAP2B (By similarity). Interacts with EPS15, LNX and NOTCH1. May interact with DUOXA1. Interacts with RALBP1 in a complex also containing EPN1 and TFAP2A during interphase and mitosis.By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • alpha-catenin binding Source: Ensembl
  • beta-catenin binding Source: Ensembl
  • cadherin binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi114202, 62 interactors
CORUMiP49757
DIPiDIP-37981N
ELMiP49757
IntActiP49757, 47 interactors
MINTiP49757
STRINGi9606.ENSP00000347169

Structurei

Secondary structure

1651
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi28 – 33Combined sources6
Beta strandi38 – 48Combined sources11
Beta strandi50 – 53Combined sources4
Helixi55 – 71Combined sources17
Turni72 – 74Combined sources3
Helixi77 – 79Combined sources3
Beta strandi84 – 90Combined sources7
Beta strandi92 – 99Combined sources8
Turni100 – 102Combined sources3
Beta strandi105 – 110Combined sources6
Helixi111 – 113Combined sources3
Beta strandi114 – 119Combined sources6
Beta strandi126 – 133Combined sources8
Turni134 – 137Combined sources4
Beta strandi138 – 149Combined sources12
Helixi151 – 168Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5NJJX-ray2.70A/B/C/D20-175[»]
5NJKX-ray3.13A/B/C/D/E/F20-175[»]
ProteinModelPortaliP49757
SMRiP49757
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 193PIDPROSITE-ProRule annotationAdd BLAST161

Phylogenomic databases

eggNOGiKOG3537 Eukaryota
ENOG410XT15 LUCA
GeneTreeiENSGT00530000062937
HOGENOMiHOG000220819
HOVERGENiHBG006672
InParanoidiP49757
KOiK06057
OMAiETNPWAH
OrthoDBiEOG091G0FJH
PhylomeDBiP49757
TreeFamiTF314159

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR016698 Numb/numb-like
IPR010449 Numb_domain
IPR011993 PH-like_dom_sf
IPR006020 PTB/PI_dom
PfamiView protein in Pfam
PF06311 NumbF, 1 hit
PF00640 PID, 1 hit
PIRSFiPIRSF017607 Numb/numb-like, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit
PROSITEiView protein in PROSITE
PS01179 PID, 1 hit

Sequences (9)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49757-1) [UniParc]FASTAAdd to basket
Also known as: p72

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:651
Mass (Da):70,804
Last modified:June 1, 2001 - v2
Checksum:i5B590BE49A74FCF2
GO
Isoform 2 (identifier: P49757-2) [UniParc]FASTAAdd to basket
Also known as: p66

The sequence of this isoform differs from the canonical sequence as follows:
     366-413: Missing.

Show »
Length:603
Mass (Da):65,899
Checksum:iC7106FBD389F5E39
GO
Isoform 3 (identifier: P49757-3) [UniParc]FASTAAdd to basket
Also known as: p71

The sequence of this isoform differs from the canonical sequence as follows:
     68-78: Missing.

Show »
Length:640
Mass (Da):69,431
Checksum:i918C5B5DD5CD87B8
GO
Isoform 4 (identifier: P49757-4) [UniParc]FASTAAdd to basket
Also known as: p65

The sequence of this isoform differs from the canonical sequence as follows:
     68-78: Missing.
     366-413: Missing.

Show »
Length:592
Mass (Da):64,527
Checksum:i645599F01321222D
GO
Isoform 5 (identifier: P49757-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     219-316: Missing.
     366-413: Missing.

Show »
Length:505
Mass (Da):55,319
Checksum:i086027BD202D2782
GO
Isoform 6 (identifier: P49757-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     68-78: Missing.
     219-316: Missing.
     366-413: Missing.

Show »
Length:494
Mass (Da):53,947
Checksum:i7B90A93A1C41BEF7
GO
Isoform 7 (identifier: P49757-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     219-316: Missing.
     317-365: Missing.
     366-413: Missing.

Show »
Length:456
Mass (Da):50,198
Checksum:i6E557041549FBFB6
GO
Isoform 8 (identifier: P49757-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     68-78: Missing.
     219-316: Missing.
     317-365: Missing.
     366-413: Missing.

Show »
Length:445
Mass (Da):48,825
Checksum:iCF5A95DB5A1A91AE
GO
Isoform 9 (identifier: P49757-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-254: Missing.
     366-413: Missing.

Show »
Length:349
Mass (Da):37,396
Checksum:iC2238BAC87304A30
GO

Sequence cautioni

The sequence AAH20788 differs from that shown. Intron retention.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31G → S in AAD27959 (Ref. 4) Curated1
Sequence conflicti68E → Q in AAD27959 (Ref. 4) Curated1
Sequence conflicti193G → R in AAD27959 (Ref. 4) Curated1
Sequence conflicti450S → N in AAD27959 (Ref. 4) Curated1
Sequence conflicti533Q → K in AAH68476 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051249387V → I. Corresponds to variant dbSNP:rs17182272Ensembl.1
Natural variantiVAR_051250595G → D. Corresponds to variant dbSNP:rs17781919Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0537451 – 254Missing in isoform 9. 2 PublicationsAdd BLAST254
Alternative sequenceiVSP_00434868 – 78Missing in isoform 3, isoform 4, isoform 6 and isoform 8. 3 PublicationsAdd BLAST11
Alternative sequenceiVSP_047756219 – 316Missing in isoform 5, isoform 6, isoform 7 and isoform 8. 1 PublicationAdd BLAST98
Alternative sequenceiVSP_053763317 – 365Missing in isoform 7 and isoform 8. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_004349366 – 413Missing in isoform 2, isoform 4, isoform 5, isoform 6, isoform 7, isoform 8 and isoform 9. 6 PublicationsAdd BLAST48

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
CCDSiCCDS32115.1 [P49757-2]
CCDS32116.1 [P49757-1]
CCDS55927.1 [P49757-4]
CCDS9814.1 [P49757-3]
RefSeqiNP_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]
UniGeneiHs.525443
Hs.654609
Hs.714879

Genome annotation databases

EnsembliENST00000355058; ENSP00000347169; ENSG00000133961 [P49757-1]
ENST00000356296; ENSP00000348644; ENSG00000133961 [P49757-2]
ENST00000359560; ENSP00000352563; ENSG00000133961 [P49757-3]
ENST00000535282; ENSP00000441258; ENSG00000133961 [P49757-2]
ENST00000544991; ENSP00000446001; ENSG00000133961 [P49757-7]
ENST00000554521; ENSP00000450817; ENSG00000133961 [P49757-8]
ENST00000554546; ENSP00000452416; ENSG00000133961 [P49757-4]
ENST00000555238; ENSP00000451300; ENSG00000133961 [P49757-1]
ENST00000555394; ENSP00000451625; ENSG00000133961 [P49757-2]
ENST00000555738; ENSP00000452069; ENSG00000133961 [P49757-6]
ENST00000557597; ENSP00000451117; ENSG00000133961 [P49757-3]
ENST00000559312; ENSP00000452888; ENSG00000133961 [P49757-7]
ENST00000560335; ENSP00000453209; ENSG00000133961 [P49757-5]
GeneIDi8650
KEGGihsa:8650
UCSCiuc001xny.2 human [P49757-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNUMB_HUMAN
AccessioniPrimary (citable) accession number: P49757
Secondary accession number(s): B1P2N5
, B1P2N6, B1P2N7, B1P2N8, B1P2N9, B4E2B1, Q6NUQ7, Q86SY1, Q8WW73, Q9UBG1, Q9UEQ4, Q9UKE8, Q9UKE9, Q9UKF0, Q9UQJ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: June 1, 2001
Last modified: March 28, 2018
This is version 158 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health