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Protein

Merlin

Gene

NF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex.2 Publications

GO - Biological processi

  • actin cytoskeleton organization Source: HGNC
  • cell-cell junction organization Source: Ensembl
  • ectoderm development Source: Ensembl
  • hippocampus development Source: Ensembl
  • lens fiber cell differentiation Source: Ensembl
  • mesoderm formation Source: Ensembl
  • negative regulation of cell-cell adhesion Source: HGNC
  • negative regulation of cell-matrix adhesion Source: HGNC
  • negative regulation of cell migration Source: HGNC
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of DNA replication Source: HGNC
  • negative regulation of JAK-STAT cascade Source: HGNC
  • negative regulation of MAPK cascade Source: Ensembl
  • negative regulation of protein kinase activity Source: Ensembl
  • negative regulation of tyrosine phosphorylation of Stat3 protein Source: HGNC
  • negative regulation of tyrosine phosphorylation of Stat5 protein Source: HGNC
  • odontogenesis of dentin-containing tooth Source: Ensembl
  • positive regulation of cell differentiation Source: Ensembl
  • positive regulation of stress fiber assembly Source: HGNC
  • regulation of gliogenesis Source: Ensembl
  • regulation of hippo signaling Source: UniProtKB
  • regulation of neural precursor cell proliferation Source: Ensembl
  • regulation of protein localization to nucleus Source: Ensembl
  • regulation of protein stability Source: Ensembl
  • regulation of stem cell proliferation Source: Ensembl
  • Schwann cell proliferation Source: HGNC
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100305-MONOMER.
ReactomeiR-HSA-5627123. RHO GTPases activate PAKs.
SignaLinkiP35240.
SIGNORiP35240.

Names & Taxonomyi

Protein namesi
Recommended name:
Merlin
Alternative name(s):
Moesin-ezrin-radixin-like protein
Neurofibromin-2
Schwannomerlin
Schwannomin
Gene namesi
Name:NF2
Synonyms:SCH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:7773. NF2.

Subcellular locationi

Isoform 1 :
Isoform 7 :
Isoform 9 :
Isoform 10 :

GO - Cellular componenti

  • adherens junction Source: Ensembl
  • apical part of cell Source: Ensembl
  • cell body Source: Ensembl
  • cleavage furrow Source: Ensembl
  • cortical actin cytoskeleton Source: Ensembl
  • cytoplasm Source: HGNC
  • cytoskeleton Source: ProtInc
  • early endosome Source: HGNC
  • extrinsic component of membrane Source: InterPro
  • filopodium membrane Source: UniProtKB-SubCell
  • lamellipodium Source: Ensembl
  • membrane Source: UniProtKB
  • neuron projection Source: Ensembl
  • nucleolus Source: HGNC
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: HGNC
  • plasma membrane Source: UniProtKB
  • ruffle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Neurofibromatosis 2 (NF2)12 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionGenetic disorder characterized by bilateral vestibular schwannomas (formerly called acoustic neuromas), schwannomas of other cranial and peripheral nerves, meningiomas, and ependymomas. It is inherited in an autosomal dominant fashion with full penetrance. Affected individuals generally develop symptoms of eighth-nerve dysfunction in early adulthood, including deafness and balance disorder. Although the tumors of NF2 are histologically benign, their anatomic location makes management difficult, and patients suffer great morbidity and mortality.
See also OMIM:101000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00081062F → S in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. 4 PublicationsCorresponds to variant rs121434261dbSNPEnsembl.1
Natural variantiVAR_04301177M → V in NF2. 1 Publication1
Natural variantiVAR_00081296Missing in NF2; also found in sporadic meningioma. 2 Publications1
Natural variantiVAR_000813106E → G in NF2. 2 Publications1
Natural variantiVAR_065227133C → R in NF2. 1 Publication1
Natural variantiVAR_043012141L → P in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. 2 Publications1
Natural variantiVAR_043013197G → C in NF2. 1 Publication1
Natural variantiVAR_000818220N → Y in NF2. 1 Publication1
Natural variantiVAR_009123234L → R in NF2; also found in retinal hamartoma; severe. 1 Publication1
Natural variantiVAR_000821352T → M in NF2. 2 PublicationsCorresponds to variant rs764441073dbSNPEnsembl.1
Natural variantiVAR_000822360L → P in NF2. Corresponds to variant rs74315492dbSNPEnsembl.1
Natural variantiVAR_043014413K → E in NF2. 2 PublicationsCorresponds to variant rs766974263dbSNPEnsembl.1
Natural variantiVAR_043015533K → T in NF2. 1 Publication1
Natural variantiVAR_000825535L → P in NF2; late onset. 3 PublicationsCorresponds to variant rs74315493dbSNPEnsembl.1
Natural variantiVAR_000826538Q → P in NF2; mild. 1 PublicationCorresponds to variant rs74315494dbSNPEnsembl.1
Natural variantiVAR_043016539L → H in NF2. 1 Publication1
Natural variantiVAR_043017579K → M in NF2. 1 Publication1
Schwannomatosis 1 (SWNTS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA cancer syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves.
See also OMIM:162091
Mesothelioma, malignant (MESOM)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionAn aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.
See also OMIM:156240

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi64L → P: Abolishes binding to AGAP2 and interaction with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. 2 Publications1
Mutagenesisi518S → A: Loss of phosphorylation. Significant accumulation in the nucleus and no effect on binding to VPRBP. 1 Publication1
Mutagenesisi518S → D: No effect on phosphorylation. Defective nuclear accumulation. Significant decrease in binding to VPRBP and in ability to inhibit cell proliferation. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi4771.
MalaCardsiNF2.
MIMi101000. phenotype.
156240. phenotype.
162091. phenotype.
OpenTargetsiENSG00000186575.
Orphaneti637. Neurofibromatosis type 2.
93921. Neurofibromatosis type 3.
PharmGKBiPA31580.

Polymorphism and mutation databases

BioMutaiNF2.
DMDMi462594.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002194121 – 595MerlinAdd BLAST595

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphoserineCombined sources1
Modified residuei518Phosphoserine; by PAKCombined sources1

Post-translational modificationi

Phosphorylation of Ser-518 inhibits nuclear localization by disrupting the intramolecular association of the FERM domain with the C-terminal tail.1 Publication
Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-protein ligase complex for ubiquitination and subsequent proteasome-dependent degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35240.
MaxQBiP35240.
PaxDbiP35240.
PeptideAtlasiP35240.
PRIDEiP35240.

PTM databases

iPTMnetiP35240.
PhosphoSitePlusiP35240.

Miscellaneous databases

PMAP-CutDBP35240.

Expressioni

Tissue specificityi

Widely expressed. Isoform 1 and isoform 3 are predominant. Isoform 4, isoform 5 and isoform 6 are expressed moderately. Isoform 8 is found at low frequency. Isoform 7, isoform 9 and isoform 10 are not expressed in adult tissues, with the exception of adult retina expressing isoform 10. Isoform 9 is faintly expressed in fetal brain, heart, lung, skeletal muscle and spleen. Fetal thymus expresses isoforms 1, 7, 9 and 10 at similar levels.

Gene expression databases

BgeeiENSG00000186575.
ExpressionAtlasiP35240. baseline and differential.
GenevisibleiP35240. HS.

Organism-specific databases

HPAiCAB005385.
HPA003097.

Interactioni

Subunit structurei

Interacts with SLC9A3R1, HGS and AGAP2. Interacts with LAYN (By similarity). Interacts with SGSM3. Interacts (via FERM domain) with MPP1. Interacts with WWC1. Interacts with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. The unphosphorylated form interacts (via FERM domain) with VPRBP/DCAF1.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AMOTQ4VCS58EBI-1014472,EBI-2511319
AMOTQ4VCS5-12EBI-1014472,EBI-3903812
AMOTQ4VCS5-26EBI-1014472,EBI-3891843
GTPBP4Q9BZE49EBI-1014472,EBI-1056249
INADLQ8NI352EBI-1014472,EBI-724390
LATS1O958354EBI-1014472,EBI-444209
MAP3K11Q165844EBI-1014472,EBI-49961
MED28Q9H2044EBI-1014472,EBI-514199
Ppp1r12aQ107282EBI-1014472,EBI-918263From a different organism.
Schip1Q3TI532EBI-1014472,EBI-1397475From a different organism.
SLC9A3R1O147454EBI-1014500,EBI-349787

Protein-protein interaction databases

BioGridi110844. 204 interactors.
DIPiDIP-35389N.
IntActiP35240. 34 interactors.
STRINGi9606.ENSP00000344666.

Structurei

Secondary structure

1595
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi21 – 27Combined sources7
Beta strandi32 – 38Combined sources7
Helixi43 – 54Combined sources12
Helixi59 – 61Combined sources3
Beta strandi62 – 68Combined sources7
Beta strandi71 – 74Combined sources4
Beta strandi77 – 80Combined sources4
Helixi81 – 83Combined sources3
Beta strandi84 – 86Combined sources3
Beta strandi89 – 100Combined sources12
Helixi105 – 108Combined sources4
Helixi112 – 127Combined sources16
Helixi135 – 150Combined sources16
Turni155 – 157Combined sources3
Turni160 – 165Combined sources6
Helixi171 – 174Combined sources4
Helixi181 – 193Combined sources13
Turni194 – 197Combined sources4
Helixi200 – 211Combined sources12
Turni215 – 218Combined sources4
Beta strandi220 – 226Combined sources7
Beta strandi231 – 236Combined sources6
Beta strandi238 – 244Combined sources7
Beta strandi249 – 251Combined sources3
Beta strandi253 – 257Combined sources5
Helixi258 – 260Combined sources3
Beta strandi261 – 267Combined sources7
Beta strandi270 – 277Combined sources8
Beta strandi283 – 286Combined sources4
Helixi290 – 310Combined sources21
Helixi513 – 547Combined sources35
Helixi552 – 554Combined sources3
Helixi557 – 562Combined sources6
Helixi573 – 581Combined sources9
Helixi585 – 594Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H4RX-ray1.80A/B1-313[»]
3U8ZX-ray2.64A/B/C/D18-312[»]
4ZRIX-ray2.70A/B1-320[»]
4ZRJX-ray2.30A1-320[»]
B506-595[»]
ProteinModelPortaliP35240.
SMRiP35240.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35240.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 311FERMPROSITE-ProRule annotationAdd BLAST290

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi327 – 465Glu-richAdd BLAST139

Sequence similaritiesi

Contains 1 FERM domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3529. Eukaryota.
ENOG410XQFP. LUCA.
GeneTreeiENSGT00860000133686.
HOVERGENiHBG002185.
InParanoidiP35240.
KOiK16684.
OMAiACYAEHR.
OrthoDBiEOG091G06UO.
PhylomeDBiP35240.
TreeFamiTF313935.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR011174. ERM.
IPR011259. ERM_C_dom.
IPR000798. Ez/rad/moesin-like.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR018979. FERM_N.
IPR018980. FERM_PH-like_C.
IPR008954. Moesin_tail.
IPR011993. PH_dom-like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00769. ERM. 1 hit.
PF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]
PIRSFiPIRSF002305. ERM. 1 hit.
PRINTSiPR00935. BAND41.
PR00661. ERMFAMILY.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF48678. SSF48678. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]

Sequences (10)i

Sequence statusi: Complete.

This entry describes 10 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35240-1) [UniParc]FASTAAdd to basket
Also known as: I

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
MAGAIASRMS FSSLKRKQPK TFTVRIVTMD AEMEFNCEMK WKGKDLFDLV
60 70 80 90 100
CRTLGLRETW FFGLQYTIKD TVAWLKMDKK VLDHDVSKEE PVTFHFLAKF
110 120 130 140 150
YPENAEEELV QEITQHLFFL QVKKQILDEK IYCPPEASVL LASYAVQAKY
160 170 180 190 200
GDYDPSVHKR GFLAQEELLP KRVINLYQMT PEMWEERITA WYAEHRGRAR
210 220 230 240 250
DEAEMEYLKI AQDLEMYGVN YFAIRNKKGT ELLLGVDALG LHIYDPENRL
260 270 280 290 300
TPKISFPWNE IRNISYSDKE FTIKPLDKKI DVFKFNSSKL RVNKLILQLC
310 320 330 340 350
IGNHDLFMRR RKADSLEVQQ MKAQAREEKA RKQMERQRLA REKQMREEAE
360 370 380 390 400
RTRDELERRL LQMKEEATMA NEALMRSEET ADLLAEKAQI TEEEAKLLAQ
410 420 430 440 450
KAAEAEQEMQ RIKATAIRTE EEKRLMEQKV LEAEVLALKM AEESERRAKE
460 470 480 490 500
ADQLKQDLQE AREAERRAKQ KLLEIATKPT YPPMNPIPAP LPPDIPSFNL
510 520 530 540 550
IGDSLSFDFK DTDMKRLSME IEKEKVEYME KSKHLQEQLN ELKTEIEALK
560 570 580 590
LKERETALDI LHNENSDRGG SSKHNTIKKL TLQSAKSRVA FFEEL
Length:595
Mass (Da):69,690
Last modified:February 1, 1994 - v1
Checksum:iB1A1BF2BD5DA561C
GO
Isoform 2 (identifier: P35240-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     580-595: LTLQSAKSRVAFFEEL → SSPRQKTYLHLSPQSRLFPGTLYVVMLYVVMVLPSVILTRA

Show »
Length:620
Mass (Da):72,514
Checksum:i6A462A3A113A6C28
GO
Isoform 3 (identifier: P35240-3) [UniParc]FASTAAdd to basket
Also known as: II

The sequence of this isoform differs from the canonical sequence as follows:
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.

Show »
Length:590
Mass (Da):69,090
Checksum:i99B732B48367D22A
GO
Isoform 4 (identifier: P35240-4) [UniParc]FASTAAdd to basket
Also known as: delE2/3

The sequence of this isoform differs from the canonical sequence as follows:
     39-121: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.

Show »
Length:507
Mass (Da):59,096
Checksum:iDD8162ABBC9EA4CA
GO
Isoform 5 (identifier: P35240-5) [UniParc]FASTAAdd to basket
Also known as: delE3

The sequence of this isoform differs from the canonical sequence as follows:
     81-121: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.

Show »
Length:549
Mass (Da):64,189
Checksum:i905559E6F72D3F4C
GO
Isoform 6 (identifier: P35240-6) [UniParc]FASTAAdd to basket
Also known as: delE2

The sequence of this isoform differs from the canonical sequence as follows:
     39-80: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.

Show »
Length:548
Mass (Da):63,996
Checksum:i58E15B35515C10EE
GO
Isoform 7 (identifier: P35240-7) [UniParc]FASTAAdd to basket
Also known as: MER150

The sequence of this isoform differs from the canonical sequence as follows:
     259-259: N → R
     260-595: Missing.

Show »
Length:259
Mass (Da):30,454
Checksum:i3C7B9CDBC884CDF6
GO
Isoform 8 (identifier: P35240-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     335-363: Missing.
     580-590: LTLQSAKSRVA → PQAQGRRPICI
     591-595: Missing.

Show »
Length:561
Mass (Da):65,350
Checksum:i371C417ABDB68D02
GO
Isoform 9 (identifier: P35240-9) [UniParc]FASTAAdd to basket
Also known as: MER162

The sequence of this isoform differs from the canonical sequence as follows:
     150-579: Missing.

Show »
Length:165
Mass (Da):19,215
Checksum:i01B92CD1AFEEB202
GO
Isoform 10 (identifier: P35240-10) [UniParc]FASTAAdd to basket
Also known as: MER151

The sequence of this isoform differs from the canonical sequence as follows:
     39-121: Missing.
     150-225: Missing.
     334-379: MERQRLAREK...ANEALMRSEE → GQRGRSAEAG...HEPNSSTVAS
     380-595: Missing.

Show »
Length:220
Mass (Da):24,515
Checksum:i05961D105F94276E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti77M → I in AAH20257 (PubMed:15489334).Curated1
Sequence conflicti581T → P in AAK54160 (PubMed:11827459).Curated1
Sequence conflicti581T → P in AAK54162 (PubMed:11827459).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00080946L → R in vestibular schwannoma; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. 2 Publications1
Natural variantiVAR_00081062F → S in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. 4 PublicationsCorresponds to variant rs121434261dbSNPEnsembl.1
Natural variantiVAR_04301177M → V in NF2. 1 Publication1
Natural variantiVAR_00081179K → E in vestibular schwannoma. 1 Publication1
Natural variantiVAR_00081296Missing in NF2; also found in sporadic meningioma. 2 Publications1
Natural variantiVAR_000813106E → G in NF2. 2 Publications1
Natural variantiVAR_000814117L → I in sporadic meningioma. 1 Publication1
Natural variantiVAR_000815119Missing in sporadic meningioma. 2 Publications1
Natural variantiVAR_000816122 – 129Missing in sporadic meningioma. 1 Publication8
Natural variantiVAR_065227133C → R in NF2. 1 Publication1
Natural variantiVAR_043012141L → P in NF2; loss of ability to interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. 2 Publications1
Natural variantiVAR_043013197G → C in NF2. 1 Publication1
Natural variantiVAR_000817219V → M in vestibular schwannoma. 1 Publication1
Natural variantiVAR_000818220N → Y in NF2. 1 Publication1
Natural variantiVAR_009123234L → R in NF2; also found in retinal hamartoma; severe. 1 Publication1
Natural variantiVAR_000819273I → F in breast ductal carcinoma. 1 Publication1
Natural variantiVAR_000820339L → F in sporadic meningioma. 1 Publication1
Natural variantiVAR_048358344Q → H.Corresponds to variant rs2229064dbSNPEnsembl.1
Natural variantiVAR_029041351R → H.1 PublicationCorresponds to variant rs771675702dbSNPEnsembl.1
Natural variantiVAR_000821352T → M in NF2. 2 PublicationsCorresponds to variant rs764441073dbSNPEnsembl.1
Natural variantiVAR_000822360L → P in NF2. Corresponds to variant rs74315492dbSNPEnsembl.1
Natural variantiVAR_000823364K → I in melanoma. 1 Publication1
Natural variantiVAR_043014413K → E in NF2. 2 PublicationsCorresponds to variant rs766974263dbSNPEnsembl.1
Natural variantiVAR_000824418R → C in vestibular schwannoma. 1 PublicationCorresponds to variant rs765540111dbSNPEnsembl.1
Natural variantiVAR_035848463E → K in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs74315503dbSNPEnsembl.1
Natural variantiVAR_043015533K → T in NF2. 1 Publication1
Natural variantiVAR_000825535L → P in NF2; late onset. 3 PublicationsCorresponds to variant rs74315493dbSNPEnsembl.1
Natural variantiVAR_000826538Q → P in NF2; mild. 1 PublicationCorresponds to variant rs74315494dbSNPEnsembl.1
Natural variantiVAR_043016539L → H in NF2. 1 Publication1
Natural variantiVAR_043017579K → M in NF2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00704139 – 121Missing in isoform 4 and isoform 10. 3 PublicationsAdd BLAST83
Alternative sequenceiVSP_00704039 – 80Missing in isoform 6. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_00704281 – 121Missing in isoform 5. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_007044150 – 579Missing in isoform 9. 1 PublicationAdd BLAST430
Alternative sequenceiVSP_007043150 – 225Missing in isoform 10. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_007045259N → R in isoform 7. 1 Publication1
Alternative sequenceiVSP_007046260 – 595Missing in isoform 7. 1 PublicationAdd BLAST336
Alternative sequenceiVSP_007047334 – 379MERQR…MRSEE → GQRGRSAEAGPAGSTRGGAK SQAEAPGDCHQAHVPAHEPN SSTVAS in isoform 10. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_007048335 – 363Missing in isoform 8. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_007049380 – 595Missing in isoform 10. 1 PublicationAdd BLAST216
Alternative sequenceiVSP_000492580 – 595LTLQS…FFEEL → SSPRQKTYLHLSPQSRLFPG TLYVVMLYVVMVLPSVILTR A in isoform 2. CuratedAdd BLAST16
Alternative sequenceiVSP_007050580 – 590LTLQSAKSRVA → PQAQGRRPICI in isoform 3, isoform 4, isoform 5, isoform 6 and isoform 8. 2 PublicationsAdd BLAST11
Alternative sequenceiVSP_007051591 – 595Missing in isoform 3, isoform 4, isoform 5, isoform 6 and isoform 8. 2 Publications5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11353 mRNA. Translation: AAA36212.1.
X72655
, X72656, X72657, X72658, X72659, X72660, X72661, X72662, X72663, X72664, X72665, X72666, X72667, X72668, X72669, X72670 Genomic DNA. Translation: CAA51220.1.
Z22664 mRNA. Translation: CAA80377.1.
Y18000 Genomic DNA. Translation: CAA76992.1.
Y18000 Genomic DNA. Translation: CAA76993.1.
AF122827 mRNA. Translation: AAD48752.1.
AF122828 mRNA. Translation: AAD48753.1.
AF123570 mRNA. Translation: AAD48754.1.
AF369657 mRNA. Translation: AAK54160.1.
AF369658 mRNA. Translation: AAK54161.1.
AF369661 mRNA. Translation: AAK54162.1.
AF369662 mRNA. Translation: AAK54163.1.
AF369663 mRNA. Translation: AAK54164.1.
AF369664 mRNA. Translation: AAK54165.1.
AF369665 mRNA. Translation: AAK54166.1.
AF369700 mRNA. Translation: AAK54195.1.
AF369701 mRNA. Translation: AAK54196.1.
CR456530 mRNA. Translation: CAG30416.1.
BC003112 mRNA. Translation: AAH03112.2.
BC020257 mRNA. Translation: AAH20257.1.
CCDSiCCDS13861.1. [P35240-1]
CCDS13862.1. [P35240-3]
CCDS13863.1. [P35240-6]
CCDS13864.1. [P35240-5]
CCDS13865.1. [P35240-4]
CCDS54516.1. [P35240-9]
PIRiS33809.
RefSeqiNP_000259.1. NM_000268.3. [P35240-1]
NP_057502.2. NM_016418.5. [P35240-3]
NP_861546.1. NM_181825.2. [P35240-3]
NP_861966.1. NM_181828.2. [P35240-6]
NP_861967.1. NM_181829.2. [P35240-5]
NP_861968.1. NM_181830.2. [P35240-4]
NP_861969.1. NM_181831.2. [P35240-4]
NP_861970.1. NM_181832.2. [P35240-3]
NP_861971.1. NM_181833.2. [P35240-9]
UniGeneiHs.187898.

Genome annotation databases

EnsembliENST00000334961; ENSP00000335652; ENSG00000186575. [P35240-4]
ENST00000338641; ENSP00000344666; ENSG00000186575. [P35240-1]
ENST00000353887; ENSP00000340626; ENSG00000186575. [P35240-4]
ENST00000361166; ENSP00000354529; ENSG00000186575. [P35240-3]
ENST00000361452; ENSP00000354897; ENSG00000186575. [P35240-5]
ENST00000361676; ENSP00000355183; ENSG00000186575. [P35240-6]
ENST00000397789; ENSP00000380891; ENSG00000186575. [P35240-3]
ENST00000403435; ENSP00000384029; ENSG00000186575. [P35240-8]
ENST00000403999; ENSP00000384797; ENSG00000186575. [P35240-3]
ENST00000413209; ENSP00000409921; ENSG00000186575. [P35240-9]
ENST00000432151; ENSP00000395885; ENSG00000186575. [P35240-10]
GeneIDi4771.
KEGGihsa:4771.
UCSCiuc003afy.5. human. [P35240-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11353 mRNA. Translation: AAA36212.1.
X72655
, X72656, X72657, X72658, X72659, X72660, X72661, X72662, X72663, X72664, X72665, X72666, X72667, X72668, X72669, X72670 Genomic DNA. Translation: CAA51220.1.
Z22664 mRNA. Translation: CAA80377.1.
Y18000 Genomic DNA. Translation: CAA76992.1.
Y18000 Genomic DNA. Translation: CAA76993.1.
AF122827 mRNA. Translation: AAD48752.1.
AF122828 mRNA. Translation: AAD48753.1.
AF123570 mRNA. Translation: AAD48754.1.
AF369657 mRNA. Translation: AAK54160.1.
AF369658 mRNA. Translation: AAK54161.1.
AF369661 mRNA. Translation: AAK54162.1.
AF369662 mRNA. Translation: AAK54163.1.
AF369663 mRNA. Translation: AAK54164.1.
AF369664 mRNA. Translation: AAK54165.1.
AF369665 mRNA. Translation: AAK54166.1.
AF369700 mRNA. Translation: AAK54195.1.
AF369701 mRNA. Translation: AAK54196.1.
CR456530 mRNA. Translation: CAG30416.1.
BC003112 mRNA. Translation: AAH03112.2.
BC020257 mRNA. Translation: AAH20257.1.
CCDSiCCDS13861.1. [P35240-1]
CCDS13862.1. [P35240-3]
CCDS13863.1. [P35240-6]
CCDS13864.1. [P35240-5]
CCDS13865.1. [P35240-4]
CCDS54516.1. [P35240-9]
PIRiS33809.
RefSeqiNP_000259.1. NM_000268.3. [P35240-1]
NP_057502.2. NM_016418.5. [P35240-3]
NP_861546.1. NM_181825.2. [P35240-3]
NP_861966.1. NM_181828.2. [P35240-6]
NP_861967.1. NM_181829.2. [P35240-5]
NP_861968.1. NM_181830.2. [P35240-4]
NP_861969.1. NM_181831.2. [P35240-4]
NP_861970.1. NM_181832.2. [P35240-3]
NP_861971.1. NM_181833.2. [P35240-9]
UniGeneiHs.187898.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H4RX-ray1.80A/B1-313[»]
3U8ZX-ray2.64A/B/C/D18-312[»]
4ZRIX-ray2.70A/B1-320[»]
4ZRJX-ray2.30A1-320[»]
B506-595[»]
ProteinModelPortaliP35240.
SMRiP35240.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110844. 204 interactors.
DIPiDIP-35389N.
IntActiP35240. 34 interactors.
STRINGi9606.ENSP00000344666.

PTM databases

iPTMnetiP35240.
PhosphoSitePlusiP35240.

Polymorphism and mutation databases

BioMutaiNF2.
DMDMi462594.

Proteomic databases

EPDiP35240.
MaxQBiP35240.
PaxDbiP35240.
PeptideAtlasiP35240.
PRIDEiP35240.

Protocols and materials databases

DNASUi4771.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000334961; ENSP00000335652; ENSG00000186575. [P35240-4]
ENST00000338641; ENSP00000344666; ENSG00000186575. [P35240-1]
ENST00000353887; ENSP00000340626; ENSG00000186575. [P35240-4]
ENST00000361166; ENSP00000354529; ENSG00000186575. [P35240-3]
ENST00000361452; ENSP00000354897; ENSG00000186575. [P35240-5]
ENST00000361676; ENSP00000355183; ENSG00000186575. [P35240-6]
ENST00000397789; ENSP00000380891; ENSG00000186575. [P35240-3]
ENST00000403435; ENSP00000384029; ENSG00000186575. [P35240-8]
ENST00000403999; ENSP00000384797; ENSG00000186575. [P35240-3]
ENST00000413209; ENSP00000409921; ENSG00000186575. [P35240-9]
ENST00000432151; ENSP00000395885; ENSG00000186575. [P35240-10]
GeneIDi4771.
KEGGihsa:4771.
UCSCiuc003afy.5. human. [P35240-1]

Organism-specific databases

CTDi4771.
DisGeNETi4771.
GeneCardsiNF2.
GeneReviewsiNF2.
HGNCiHGNC:7773. NF2.
HPAiCAB005385.
HPA003097.
MalaCardsiNF2.
MIMi101000. phenotype.
156240. phenotype.
162091. phenotype.
607379. gene.
neXtProtiNX_P35240.
OpenTargetsiENSG00000186575.
Orphaneti637. Neurofibromatosis type 2.
93921. Neurofibromatosis type 3.
PharmGKBiPA31580.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3529. Eukaryota.
ENOG410XQFP. LUCA.
GeneTreeiENSGT00860000133686.
HOVERGENiHBG002185.
InParanoidiP35240.
KOiK16684.
OMAiACYAEHR.
OrthoDBiEOG091G06UO.
PhylomeDBiP35240.
TreeFamiTF313935.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100305-MONOMER.
ReactomeiR-HSA-5627123. RHO GTPases activate PAKs.
SignaLinkiP35240.
SIGNORiP35240.

Miscellaneous databases

ChiTaRSiNF2. human.
EvolutionaryTraceiP35240.
GeneWikiiMerlin_(protein).
GenomeRNAii4771.
PMAP-CutDBP35240.
PROiP35240.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186575.
ExpressionAtlasiP35240. baseline and differential.
GenevisibleiP35240. HS.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR011174. ERM.
IPR011259. ERM_C_dom.
IPR000798. Ez/rad/moesin-like.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR018979. FERM_N.
IPR018980. FERM_PH-like_C.
IPR008954. Moesin_tail.
IPR011993. PH_dom-like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00769. ERM. 1 hit.
PF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]
PIRSFiPIRSF002305. ERM. 1 hit.
PRINTSiPR00935. BAND41.
PR00661. ERMFAMILY.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF48678. SSF48678. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS00660. FERM_1. 1 hit.
PS00661. FERM_2. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMERL_HUMAN
AccessioniPrimary (citable) accession number: P35240
Secondary accession number(s): O95683
, Q8WUJ2, Q969N0, Q969Q3, Q96T30, Q96T31, Q96T32, Q96T33, Q9BTW3, Q9UNG9, Q9UNH3, Q9UNH4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: November 30, 2016
This is version 198 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.