Protein numb homolog - Homo sapiens (Human)

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Names and origin

Protein names

Recommended name:
    Protein numb homolog
      Short name=h-Numb
Alternative name(s):
    Protein S171

Gene names

Name:

NUMB

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	651 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Implicated in the control of cell fate decisions during development.
Subunit structure	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. Ref.8 Ref.9 Ref.10
Subcellular location	Membrane; Peripheral membrane protein.
Post-translational modification	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.
Sequence similarities	Contains 1 PID domain.
Sequence caution	The sequence AAH20788.1 differs from that shown. Reason: Miscellaneous discrepancy. Intron retention.

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Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Cellular component	integral to plasma membrane Ref.7 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
LNX1	Q8TBB1	1	EBI-915016,EBI-739832

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Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P49757-1) 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.

Isoform 2 (identifier: P49757-2) Also known as: p66; The sequence of this isoform differs from the canonical sequence as follows: 366-413: Missing.

Isoform 3 (identifier: P49757-3) Also known as: p71; The sequence of this isoform differs from the canonical sequence as follows: 68-78: Missing.

Isoform 4 (identifier: P49757-4) Also known as: p65; The sequence of this isoform differs from the canonical sequence as follows: 68-78: Missing. 366-413: Missing.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 651

651

Protein numb homolog

PRO_0000058001

Regions

Domain

33 – 193

161

PID

Amino acid modifications

Modified residue

240

1

Phosphoserine Ref.13

Modified residue

241

1

Phosphoserine Ref.13

Modified residue

244

1

Phosphoserine Ref.13

Modified residue

276

1

Phosphoserine Ref.11

Modified residue

295

1

Phosphoserine Ref.11

Modified residue

631

1

Phosphothreonine By similarity

Modified residue

634

1

Phosphoserine Ref.12

Natural variations

Alternative sequence

68 – 78

11

Missing in isoform 3 and isoform 4.

VSP_004348

Alternative sequence

366 – 413

48

Missing in isoform 2 and isoform 4.

VSP_004349

Natural variant

387

1

V → I: dbSNP rs17182272.

VAR_051249

Natural variant

595

1

G → D: dbSNP rs17781919.

VAR_051250

Experimental info

Sequence conflict

31

1

G → S in AAD27959. Ref.3

Sequence conflict

68

1

E → Q in AAD27959. Ref.3

Sequence conflict

193

1

G → R in AAD27959. Ref.3

Sequence conflict

450

1

S → N in AAD27959. Ref.3

Sequence conflict

533

1

Q → K in AAH68476. Ref.4

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (p72) [UniParc]. Last modified June 1, 2001. Version 2. Checksum: 5B590BE49A74FCF2 Show »	FASTA	651	70,804
10 20 30 40 50 60 MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD ESRGMHICED 70 80 90 100 110 120 AVKRLKAERK FFKGFFGKTG KKAVKAVLWV SADGLRVVDE KTKDLIVDQT IEKVSFCAPD 130 140 150 160 170 180 RNFDRAFSYI CRDGTTRRWI CHCFMAVKDT GERLSHAVGC AFAACLERKQ KREKECGVTA 190 200 210 220 230 240 TFDASRTTFT REGSFRVTTA TEQAEREEIM KQMQDAKKAE TDKIVVGSSV APGNTAPSPS 250 260 270 280 290 300 SPTSPTSDAT TSLEMNNPHA IPRRHAPIEQ LARQGSFRGF PALSQKMSPF KRQLSLRINE 310 320 330 340 350 360 LPSTMQRKTD FPIKNAVPEV EGEAESISSL CSQITNAFST PEDPFSSAPM TKPVTVVAPQ 370 380 390 400 410 420 SPTFQANGTD SAFHVLAKPA HTALAPVAMP VRETNPWAHA PDAANKEIAA TCSGTEWGQS 430 440 450 460 470 480 SGAASPGLFQ AGHRRTPSEA DRWLEEVSKS VRAQQPQASA APLQPVLQPP PPTAISQPAS 490 500 510 520 530 540 PFQGNAFLTS QPVPVGVVPA LQPAFVPAQS YPVANGMPYP APNVPVVGIT PSQMVANVFG 550 560 570 580 590 600 TAGHPQAAHP HQSPSLVRQQ TFPHYEASSA TTSPFFKPPA QHLNGSAAFN GVDDGRLASA 610 620 630 640 650 DRHTEVPTGT CPVDPFEAQW AALENKSKQR TNPSPTNPFS SDLQKTFEIE L « Hide
Isoform 2 (p66). Checksum: C7106FBD389F5E39 Show »	FASTA	603	65,899
10 20 30 40 50 60 MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD ESRGMHICED 70 80 90 100 110 120 AVKRLKAERK FFKGFFGKTG KKAVKAVLWV SADGLRVVDE KTKDLIVDQT IEKVSFCAPD 130 140 150 160 170 180 RNFDRAFSYI CRDGTTRRWI CHCFMAVKDT GERLSHAVGC AFAACLERKQ KREKECGVTA 190 200 210 220 230 240 TFDASRTTFT REGSFRVTTA TEQAEREEIM KQMQDAKKAE TDKIVVGSSV APGNTAPSPS 250 260 270 280 290 300 SPTSPTSDAT TSLEMNNPHA IPRRHAPIEQ LARQGSFRGF PALSQKMSPF KRQLSLRINE 310 320 330 340 350 360 LPSTMQRKTD FPIKNAVPEV EGEAESISSL CSQITNAFST PEDPFSSAPM TKPVTVVAPQ 370 380 390 400 410 420 SPTFQGTEWG QSSGAASPGL FQAGHRRTPS EADRWLEEVS KSVRAQQPQA SAAPLQPVLQ 430 440 450 460 470 480 PPPPTAISQP ASPFQGNAFL TSQPVPVGVV PALQPAFVPA QSYPVANGMP YPAPNVPVVG 490 500 510 520 530 540 ITPSQMVANV FGTAGHPQAA HPHQSPSLVR QQTFPHYEAS SATTSPFFKP PAQHLNGSAA 550 560 570 580 590 600 FNGVDDGRLA SADRHTEVPT GTCPVDPFEA QWAALENKSK QRTNPSPTNP FSSDLQKTFE IEL « Hide
Isoform 3 (p71). Checksum: 918C5B5DD5CD87B8 Show »	FASTA	640	69,431
10 20 30 40 50 60 MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD ESRGMHICED 70 80 90 100 110 120 AVKRLKATGK KAVKAVLWVS ADGLRVVDEK TKDLIVDQTI EKVSFCAPDR NFDRAFSYIC 130 140 150 160 170 180 RDGTTRRWIC HCFMAVKDTG ERLSHAVGCA FAACLERKQK REKECGVTAT FDASRTTFTR 190 200 210 220 230 240 EGSFRVTTAT EQAEREEIMK QMQDAKKAET DKIVVGSSVA PGNTAPSPSS PTSPTSDATT 250 260 270 280 290 300 SLEMNNPHAI PRRHAPIEQL ARQGSFRGFP ALSQKMSPFK RQLSLRINEL PSTMQRKTDF 310 320 330 340 350 360 PIKNAVPEVE GEAESISSLC SQITNAFSTP EDPFSSAPMT KPVTVVAPQS PTFQANGTDS 370 380 390 400 410 420 AFHVLAKPAH TALAPVAMPV RETNPWAHAP DAANKEIAAT CSGTEWGQSS GAASPGLFQA 430 440 450 460 470 480 GHRRTPSEAD RWLEEVSKSV RAQQPQASAA PLQPVLQPPP PTAISQPASP FQGNAFLTSQ 490 500 510 520 530 540 PVPVGVVPAL QPAFVPAQSY PVANGMPYPA PNVPVVGITP SQMVANVFGT AGHPQAAHPH 550 560 570 580 590 600 QSPSLVRQQT FPHYEASSAT TSPFFKPPAQ HLNGSAAFNG VDDGRLASAD RHTEVPTGTC 610 620 630 640 PVDPFEAQWA ALENKSKQRT NPSPTNPFSS DLQKTFEIEL « Hide
Isoform 4 (p65). Checksum: 645599F01321222D Show »	FASTA	592	64,527
10 20 30 40 50 60 MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD ESRGMHICED 70 80 90 100 110 120 AVKRLKATGK KAVKAVLWVS ADGLRVVDEK TKDLIVDQTI EKVSFCAPDR NFDRAFSYIC 130 140 150 160 170 180 RDGTTRRWIC HCFMAVKDTG ERLSHAVGCA FAACLERKQK REKECGVTAT FDASRTTFTR 190 200 210 220 230 240 EGSFRVTTAT EQAEREEIMK QMQDAKKAET DKIVVGSSVA PGNTAPSPSS PTSPTSDATT 250 260 270 280 290 300 SLEMNNPHAI PRRHAPIEQL ARQGSFRGFP ALSQKMSPFK RQLSLRINEL PSTMQRKTDF 310 320 330 340 350 360 PIKNAVPEVE GEAESISSLC SQITNAFSTP EDPFSSAPMT KPVTVVAPQS PTFQGTEWGQ 370 380 390 400 410 420 SSGAASPGLF QAGHRRTPSE ADRWLEEVSK SVRAQQPQAS AAPLQPVLQP PPPTAISQPA 430 440 450 460 470 480 SPFQGNAFLT SQPVPVGVVP ALQPAFVPAQ SYPVANGMPY PAPNVPVVGI TPSQMVANVF 490 500 510 520 530 540 GTAGHPQAAH PHQSPSLVRQ QTFPHYEASS ATTSPFFKPP AQHLNGSAAF NGVDDGRLAS 550 560 570 580 590 ADRHTEVPTG TCPVDPFEAQ WAALENKSKQ RTNPSPTNPF SSDLQKTFEI EL « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module." Salcini A.E., Confalonieri S., Doria M., Santolini E., Tassi E., Minenkova O., Cesareni G., Pelicci P.G., Di Fiore P.P. Genes Dev. 11:2239-2249(1997) [PubMed: 9303539] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage." Verdi J.M., Bashirullah A., Goldhawk D.E., Kubu C.J., Jamali M., Meakin S.O., Lipshitz H.D. Proc. Natl. Acad. Sci. U.S.A. 96:10472-10476(1999) [PubMed: 10468633] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4). Tissue: Neuron.
[3]	Ye Q., Jiang K., Han W., Moore M.A.S. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-256 (ISOFORMS 3/4). Tissue: Liver and Testis.
[5]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-529 (ISOFORM 1). Tissue: Cervix carcinoma.
[6]	"Complete sequence of the gene for presenilin 1." Rowen L., Madan A., Qin S., Abbasi N., Dors M., Ratcliffe A., Madan A., Dickhoff R., Shaffer T., James R., Lasky S., Hood L. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 79-651 (ISOFORMS 2/4). Tissue: Fetal brain.
[7]	"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease." Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L. St George-Hyslop P.H. Nature 375:754-760(1995) [PubMed: 7596406] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 517-651. Tissue: Brain.
[8]	"Siah-1 binds and regulates the function of Numb." Susini L., Passer B.J., Amzallag-Elbaz N., Juven-Gershon T., Prieur S., Privat N., Tuynder M., Gendron M.-C., Israeel A., Amson R., Oren M., Telerman A. Proc. Natl. Acad. Sci. U.S.A. 98:15067-15072(2001) [PubMed: 11752454] [Abstract] Cited for: INTERACTION WITH SIAH1, DEGRADATION.
[9]	"RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis." Rosse C., L'Hoste S., Offner N., Picard A., Camonis J. J. Biol. Chem. 278:30597-30604(2003) [PubMed: 12775724] [Abstract] Cited for: INTERACTION WITH RALBP1.
[10]	"A novel transmembrane protein recruits numb to the plasma membrane during asymmetric cell division." Qin H., Percival-Smith A., Li C., Jia C.Y.H., Gloor G., Li S.S.-C. J. Biol. Chem. 279:11304-11312(2004) [PubMed: 14670962] [Abstract] Cited for: INTERACTION WITH DUOXA1.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-276 AND SER-295, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-634, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-240; SER-241 AND SER-244, MASS SPECTROMETRY.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	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. AF108092 mRNA. Translation: AAD27959.1. 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.
IPI	IPI00028059. IPI00180634. IPI00180920. IPI00216241.
RefSeq	NP_001005743.1. NP_001005744.1. NP_001005745.1. NP_003735.3.
UniGene	Hs.654609 Hs.714879
3D structure databases
SMR	P49757. Positions 21-172.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49757. 1 interaction.
STRING	P49757.
PTM databases
PhosphoSite	P49757.
Proteomic databases
PRIDE	P49757.
Genome annotation databases
Ensembl	ENST00000355058; ENSP00000347169; ENSG00000133961; Homo sapiens. [Genome view]
GeneID	8650.
KEGG	hsa:8650.
UCSC	uc001xny.1. human. uc001xnz.1. human.
Organism-specific databases
CTD	8650.
GeneCards	GC14M072811.
H-InvDB	HIX0011792.
HGNC	HGNC:8060. NUMB.
HPA	CAB011478.
MIM	603728. gene.
PharmGKB	PA31845.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P49757.
OMA	VDPFEAQ
OrthoDB	EOG9BK7PT
Enzyme and pathway databases
BioCyc	CATTLE:ENSBTAG00000011683-MON.
Gene expression databases
ArrayExpress	P49757.
Bgee	P49757.
Genevestigator	P49757.
GermOnline	ENSG00000133961. Homo sapiens.
Family and domain databases
InterPro	IPR016698. Numb/numb-like. IPR010449. Numb_domain. IPR011993. PH_type. IPR006020. PTB_PID. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
Pfam	PF06311. NumbF. 1 hit. PF00640. PID. 1 hit. [Graphical view]
PIRSF	PIRSF017607. Numb/numb-like. 1 hit.
SMART	SM00462. PTB. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	32435.
SOURCE	Search...

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Entry information

Entry name

NUMB_HUMAN

Accession

Primary (citable) accession number: P49757
Secondary accession number(s): Q6NUQ7

Q9UQJ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	June 1, 2001
Last modified:	November 24, 2009
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

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Index of human polymorphisms and disease mutations

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SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents