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Protein

Mesencephalic astrocyte-derived neurotrophic factor

Gene

MANF

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

Functioni

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.By similarity2 Publications

GO - Molecular functioni

  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Keywords - Biological processi

Unfolded protein response

Keywords - Ligandi

Sialic acid

Names & Taxonomyi

Protein namesi
Recommended name:
Mesencephalic astrocyte-derived neurotrophic factor
Alternative name(s):
Arginine-rich protein
Protein ARMET
Gene namesi
Name:MANF
Synonyms:ARMET, ARP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:15461. MANF.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: Ensembl
  • extracellular space Source: Ensembl
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti1333. Familial pancreatic carcinoma.
PharmGKBiPA24993.

Polymorphism and mutation databases

BioMutaiMANF.
DMDMi332278201.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 24242 PublicationsAdd
BLAST
Chaini25 – 182158Mesencephalic astrocyte-derived neurotrophic factorPRO_0000002305Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 1171 Publication
Disulfide bondi33 ↔ 1061 Publication
Disulfide bondi64 ↔ 751 Publication
Modified residuei76 – 761PhosphotyrosineBy similarity
Disulfide bondi151 ↔ 1541 Publication

Post-translational modificationi

May contain sialic acid residues.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP55145.
PaxDbiP55145.
PRIDEiP55145.

2D gel databases

OGPiP55145.

PTM databases

PhosphoSiteiP55145.

Expressioni

Inductioni

By endoplasmic reticulum stress.1 Publication

Gene expression databases

BgeeiP55145.
CleanExiHS_ARMET.
ExpressionAtlasiP55145. baseline and differential.
GenevisibleiP55145. HS.

Organism-specific databases

HPAiHPA011175.

Interactioni

Protein-protein interaction databases

BioGridi113621. 4 interactions.
IntActiP55145. 1 interaction.
MINTiMINT-3020834.

Structurei

Secondary structure

1
182
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi31 – 4616Combined sources
Helixi53 – 6412Combined sources
Helixi69 – 779Combined sources
Beta strandi81 – 833Combined sources
Helixi87 – 893Combined sources
Helixi90 – 978Combined sources
Helixi102 – 11211Combined sources
Turni115 – 1184Combined sources
Helixi127 – 1293Combined sources
Turni132 – 1343Combined sources
Helixi136 – 1438Combined sources
Helixi155 – 1584Combined sources
Turni166 – 1738Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KVDNMR-A25-182[»]
2KVENMR-A120-182[»]
2W51X-ray2.80A25-182[»]
ProteinModelPortaliP55145.
SMRiP55145. Positions 25-161.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55145.

Family & Domainsi

Domaini

The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response.1 Publication

Sequence similaritiesi

Belongs to the ARMET family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG301491.
GeneTreeiENSGT00390000007160.
HOGENOMiHOG000264245.
InParanoidiP55145.
OMAiSCKGCAE.
PhylomeDBiP55145.
TreeFamiTF314252.

Family and domain databases

Gene3Di1.10.225.10. 1 hit.
InterProiIPR019345. Armet_prot.
IPR011001. Saposin-like.
[Graphical view]
PfamiPF10208. Armet. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P55145-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRRMWATQGL AVALALSVLP GSRALRPGDC EVCISYLGRF YQDLKDRDVT
60 70 80 90 100
FSPATIENEL IKFCREARGK ENRLCYYIGA TDDAATKIIN EVSKPLAHHI
110 120 130 140 150
PVEKICEKLK KKDSQICELK YDKQIDLSTV DLKKLRVKEL KKILDDWGET
160 170 180
CKGCAEKSDY IRKINELMPK YAPKAASART DL
Length:182
Mass (Da):20,700
Last modified:May 3, 2011 - v3
Checksum:iEE25A5D1A58D1AD7
GO

Sequence cautioni

The sequence AAB08753.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAI13589.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAI13591.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 142AL → RV in AAB08753 (PubMed:8649854).Curated
Sequence conflicti179 – 1791R → P in AAB08753 (PubMed:8649854).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_006001.4. NM_006010.5.
UniGeneiHs.436446.

Genome annotation databases

EnsembliENST00000627526; ENSP00000487450; ENSG00000145050.
GeneIDi7873.
KEGGihsa:7873.
UCSCiuc003dbc.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_006001.4. NM_006010.5.
UniGeneiHs.436446.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KVDNMR-A25-182[»]
2KVENMR-A120-182[»]
2W51X-ray2.80A25-182[»]
ProteinModelPortaliP55145.
SMRiP55145. Positions 25-161.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113621. 4 interactions.
IntActiP55145. 1 interaction.
MINTiMINT-3020834.

PTM databases

PhosphoSiteiP55145.

Polymorphism and mutation databases

BioMutaiMANF.
DMDMi332278201.

2D gel databases

OGPiP55145.

Proteomic databases

MaxQBiP55145.
PaxDbiP55145.
PRIDEiP55145.

Protocols and materials databases

DNASUi7873.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000627526; ENSP00000487450; ENSG00000145050.
GeneIDi7873.
KEGGihsa:7873.
UCSCiuc003dbc.3. human.

Organism-specific databases

CTDi7873.
GeneCardsiGC03P051399.
HGNCiHGNC:15461. MANF.
HPAiHPA011175.
MIMi601916. gene.
neXtProtiNX_P55145.
Orphaneti1333. Familial pancreatic carcinoma.
PharmGKBiPA24993.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG301491.
GeneTreeiENSGT00390000007160.
HOGENOMiHOG000264245.
InParanoidiP55145.
OMAiSCKGCAE.
PhylomeDBiP55145.
TreeFamiTF314252.

Miscellaneous databases

EvolutionaryTraceiP55145.
GeneWikiiARMET.
GenomeRNAii7873.
NextBioi30328.
PROiP55145.
SOURCEiSearch...

Gene expression databases

BgeeiP55145.
CleanExiHS_ARMET.
ExpressionAtlasiP55145. baseline and differential.
GenevisibleiP55145. HS.

Family and domain databases

Gene3Di1.10.225.10. 1 hit.
InterProiIPR019345. Armet_prot.
IPR011001. Saposin-like.
[Graphical view]
PfamiPF10208. Armet. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. "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.
  12. "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.
  13. Cited for: DISCUSSION OF PUTATIVE CANCER VARIANTS.

Entry informationi

Entry nameiMANF_HUMAN
AccessioniPrimary (citable) accession number: P55145
Secondary accession number(s): Q14CX4, Q86U67, Q96IS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 3, 2011
Last modified: June 24, 2015
This is version 126 of the entry and version 3 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

Caution

Was originally (PubMed:8649854, PubMed:8971156 and PubMed:9174057) 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.Curated
It is uncertain whether Met-1 or Met-4 is the initiator.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

External Data

Dasty 3

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 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.