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P55145 (MANF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mesencephalic astrocyte-derived neurotrophic factor
Alternative name(s):
Arginine-rich protein
Protein ARMET
Gene names
Name:MANF
Synonyms:ARMET, ARP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length182 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra. Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons By similarity. Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. Ref.6 Ref.8

Subcellular location

Secreted Ref.6 Ref.8.

Induction

By endoplasmic reticulum stress. Ref.8

Domain

The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response. Ref.10

Post-translational modification

May contain sialic acid residues.

Sequence similarities

Belongs to the ARMET family.

Caution

Was originally (Ref.1, Ref.11 and Ref.12) thought to be much longer and included an arginine-rich region thought to be the target of cancer-causing mutations. All these mutations are in what is now thought to be the 5'-UTR of the mRNA.

It is uncertain whether Met-1 or Met-4 is the initiator.

Sequence caution

The sequence AAB08753.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAI13589.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAI13591.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.5 Ref.6
Chain25 – 182158Mesencephalic astrocyte-derived neurotrophic factor
PRO_0000002305

Amino acid modifications

Modified residue761Phosphotyrosine By similarity
Disulfide bond30 ↔ 117 Ref.10
Disulfide bond33 ↔ 106 Ref.10
Disulfide bond64 ↔ 75 Ref.10
Disulfide bond151 ↔ 154 Ref.10

Experimental info

Sequence conflict13 – 142AL → RV in AAB08753. Ref.1
Sequence conflict1791R → P in AAB08753. Ref.1

Secondary structure

.......................... 182
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P55145 [UniParc].

Last modified May 3, 2011. Version 3.
Checksum: EE25A5D1A58D1AD7

FASTA18220,700
        10         20         30         40         50         60 
MRRMWATQGL AVALALSVLP GSRALRPGDC EVCISYLGRF YQDLKDRDVT FSPATIENEL 

        70         80         90        100        110        120 
IKFCREARGK ENRLCYYIGA TDDAATKIIN EVSKPLAHHI PVEKICEKLK KKDSQICELK 

       130        140        150        160        170        180 
YDKQIDLSTV DLKKLRVKEL KKILDDWGET CKGCAEKSDY IRKINELMPK YAPKAASART 


DL 

« Hide

References

« Hide 'large scale' references
[1]"A gene from human chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein and is mutated in renal cell carcinomas."
Shridhar V., Rivard S., Shridhar R., Mullins C., Bostick L., Sakr W., Grignon D., Miller O.J., Smith D.I.
Oncogene 12:1931-1939(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISCUSSION OF A PUTATIVE CANCER VARIANT.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon and Eye.
[4]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-39.
Tissue: Platelet.
[6]"MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons."
Petrova P., Raibekas A., Pevsner J., Vigo N., Anafi M., Moore M.K., Peaire A.E., Shridhar V., Smith D.I., Kelly J., Durocher Y., Commissiong J.W.
J. Mol. Neurosci. 20:173-188(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-29, FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION.
[7]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death."
Apostolou A., Shen Y., Liang Y., Luo J., Fang S.
Exp. Cell Res. 314:2454-2467(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional."
Parkash V., Lindholm P., Peranen J., Kalkkinen N., Oksanen E., Saarma M., Leppanen V.-M., Goldman A.
Protein Eng. Des. Sel. 22:233-241(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 25-182, DOMAIN, DISULFIDE BONDS.
[11]"Mutations in the arginine-rich protein gene, in lung, breast, and prostate cancers, and in squamous cell carcinoma of the head and neck."
Shridhar R., Shridhar V., Rivard S., Siegfried J.M., Pietraszkiewicz H., Ensley J., Pauley R., Grignon D., Sakr W., Miller O.J., Smith D.I.
Cancer Res. 56:5576-5578(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DISCUSSION OF A PUTATIVE CANCER VARIANT.
[12]"Mutations in the arginine-rich protein gene (ARP) in pancreatic cancer."
Shridhar V., Rivard S., Wang X., Shridhar R., Paisley C., Mullins C., Beirnat L., Dugan M., Sarkar F., Miller O.J., Vaitkevicius V.K., Smith D.I.
Oncogene 14:2213-2216(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: DISCUSSION OF PUTATIVE CANCER VARIANTS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M83751 mRNA. Translation: AAB08753.1. Different initiation.
BT007110 mRNA. Translation: AAP35774.1.
AC092037 Genomic DNA. No translation available.
BC007282 mRNA. Translation: AAH07282.1.
BC113588 mRNA. Translation: AAI13589.1. Different initiation.
BC113590 mRNA. Translation: AAI13591.1. Different initiation.
RefSeqNP_006001.3. NM_006010.4.
UniGeneHs.436446.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KVDNMR-A25-182[»]
2KVENMR-A120-182[»]
2W51X-ray2.80A25-181[»]
ProteinModelPortalP55145.
SMRP55145. Positions 25-161.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113621. 1 interaction.
MINTMINT-3020834.
STRING9606.ENSP00000273628.

PTM databases

PhosphoSiteP55145.

Polymorphism databases

DMDM332278201.

2D gel databases

OGPP55145.

Proteomic databases

PaxDbP55145.
PRIDEP55145.

Protocols and materials databases

DNASU7873.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000528157; ENSP00000432799; ENSG00000145050.
ENST00000566546; ENSP00000454660; ENSG00000259880.
GeneID7873.
KEGGhsa:7873.
UCSCuc003dbc.3. human.

Organism-specific databases

CTD7873.
GeneCardsGC03P051399.
HGNCHGNC:15461. MANF.
HPAHPA011175.
MIM601916. gene.
neXtProtNX_P55145.
Orphanet1333. Familial pancreatic carcinoma.
PharmGKBPA24993.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG301491.
HOGENOMHOG000264245.
InParanoidP55145.
OMASCKGCAE.
TreeFamTF314252.

Gene expression databases

ArrayExpressP55145.
BgeeP55145.
CleanExHS_ARMET.
GenevestigatorP55145.

Family and domain databases

Gene3D1.10.225.10. 1 hit.
InterProIPR019345. Armet_prot.
IPR011001. Saposin-like.
[Graphical view]
PfamPF10208. Armet. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP55145.
GeneWikiARMET.
GenomeRNAi7873.
NextBio30328.
PROP55145.
SOURCESearch...

Entry information

Entry nameMANF_HUMAN
AccessionPrimary (citable) accession number: P55145
Secondary accession number(s): Q14CX4, Q86U67, Q96IS4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 3, 2011
Last modified: April 16, 2014
This is version 115 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM