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P55145

- MANF_HUMAN

UniProt

P55145 - MANF_HUMAN

Protein

Mesencephalic astrocyte-derived neurotrophic factor

Gene

MANF

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 3 (03 May 2011)
      Previous versions | rss
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    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

    1. poly(A) RNA binding Source: UniProtKB

    GO - Biological processi

    1. response to unfolded protein Source: UniProtKB-KW
    2. vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure Source: Ensembl

    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: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:15461. MANF.

    Subcellular locationi

    Secreted 2 Publications

    GO - Cellular componenti

    1. extracellular space Source: Ensembl
    2. nucleus Source: UniProt
    3. perinuclear region of cytoplasm Source: Ensembl

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti1333. Familial pancreatic carcinoma.
    PharmGKBiPA24993.

    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

    ArrayExpressiP55145.
    BgeeiP55145.
    CleanExiHS_ARMET.
    GenevestigatoriP55145.

    Organism-specific databases

    HPAiHPA011175.

    Interactioni

    Protein-protein interaction databases

    BioGridi113621. 2 interactions.
    IntActiP55145. 1 interaction.
    MINTiMINT-3020834.
    STRINGi9606.ENSP00000273628.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MRRMWATQGL AVALALSVLP GSRALRPGDC EVCISYLGRF YQDLKDRDVT    50
    FSPATIENEL IKFCREARGK ENRLCYYIGA TDDAATKIIN EVSKPLAHHI 100
    PVEKICEKLK KKDSQICELK YDKQIDLSTV DLKKLRVKEL KKILDDWGET 150
    CKGCAEKSDY IRKINELMPK YAPKAASART DL 182
    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.
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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

    EnsembliENST00000528157; ENSP00000432799; ENSG00000145050.
    GeneIDi7873.
    KEGGihsa:7873.
    UCSCiuc003dbc.3. human.

    Polymorphism databases

    DMDMi332278201.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    RefSeqi NP_006001.4. NM_006010.5.
    UniGenei Hs.436446.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2KVD NMR - A 25-182 [» ]
    2KVE NMR - A 120-182 [» ]
    2W51 X-ray 2.80 A 25-182 [» ]
    ProteinModelPortali P55145.
    SMRi P55145. Positions 25-161.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113621. 2 interactions.
    IntActi P55145. 1 interaction.
    MINTi MINT-3020834.
    STRINGi 9606.ENSP00000273628.

    PTM databases

    PhosphoSitei P55145.

    Polymorphism databases

    DMDMi 332278201.

    2D gel databases

    OGPi P55145.

    Proteomic databases

    MaxQBi P55145.
    PaxDbi P55145.
    PRIDEi P55145.

    Protocols and materials databases

    DNASUi 7873.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000528157 ; ENSP00000432799 ; ENSG00000145050 .
    GeneIDi 7873.
    KEGGi hsa:7873.
    UCSCi uc003dbc.3. human.

    Organism-specific databases

    CTDi 7873.
    GeneCardsi GC03P051399.
    HGNCi HGNC:15461. MANF.
    HPAi HPA011175.
    MIMi 601916. gene.
    neXtProti NX_P55145.
    Orphaneti 1333. Familial pancreatic carcinoma.
    PharmGKBi PA24993.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG301491.
    HOGENOMi HOG000264245.
    InParanoidi P55145.
    OMAi SCKGCAE.
    PhylomeDBi P55145.
    TreeFami TF314252.

    Miscellaneous databases

    EvolutionaryTracei P55145.
    GeneWikii ARMET.
    GenomeRNAii 7873.
    NextBioi 30328.
    PROi P55145.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P55145.
    Bgeei P55145.
    CleanExi HS_ARMET.
    Genevestigatori P55145.

    Family and domain databases

    Gene3Di 1.10.225.10. 1 hit.
    InterProi IPR019345. Armet_prot.
    IPR011001. Saposin-like.
    [Graphical view ]
    Pfami PF10208. Armet. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. "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. 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: October 1, 2014
    This is version 120 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