Full text data of MANF
MANF
(ARMET, ARP)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Mesencephalic astrocyte-derived neurotrophic factor (Arginine-rich protein; Protein ARMET; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Mesencephalic astrocyte-derived neurotrophic factor (Arginine-rich protein; Protein ARMET; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P55145
ID MANF_HUMAN Reviewed; 182 AA.
AC P55145; Q14CX4; Q86U67; Q96IS4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-MAY-2011, sequence version 3.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Mesencephalic astrocyte-derived neurotrophic factor;
DE AltName: Full=Arginine-rich protein;
DE AltName: Full=Protein ARMET;
DE Flags: Precursor;
GN Name=MANF; Synonyms=ARMET, ARP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DISCUSSION OF A PUTATIVE CANCER
RP VARIANT.
RX PubMed=8649854;
RA Shridhar V., Rivard S., Shridhar R., Mullins C., Bostick L., Sakr W.,
RA Grignon D., Miller O.J., Smith D.I.;
RT "A gene from human chromosomal band 3p21.1 encodes a highly conserved
RT arginine-rich protein and is mutated in renal cell carcinomas.";
RL Oncogene 12:1931-1939(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP PROTEIN SEQUENCE OF 25-39.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP PROTEIN SEQUENCE OF 25-29, FUNCTION, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=12794311; DOI=10.1385/JMN:20:2:173;
RA Petrova P., Raibekas A., Pevsner J., Vigo N., Anafi M., Moore M.K.,
RA Peaire A.E., Shridhar V., Smith D.I., Kelly J., Durocher Y.,
RA Commissiong J.W.;
RT "MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with
RT selectivity for dopaminergic neurons.";
RL J. Mol. Neurosci. 20:173-188(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18561914; DOI=10.1016/j.yexcr.2008.05.001;
RA Apostolou A., Shen Y., Liang Y., Luo J., Fang S.;
RT "Armet, a UPR-upregulated protein, inhibits cell proliferation and ER
RT stress-induced cell death.";
RL Exp. Cell Res. 314:2454-2467(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 25-182, DOMAIN, AND
RP DISULFIDE BONDS.
RX PubMed=19258449; DOI=10.1093/protein/gzn080;
RA Parkash V., Lindholm P., Peranen J., Kalkkinen N., Oksanen E.,
RA Saarma M., Leppanen V.-M., Goldman A.;
RT "The structure of the conserved neurotrophic factors MANF and CDNF
RT explains why they are bifunctional.";
RL Protein Eng. Des. Sel. 22:233-241(2009).
RN [11]
RP DISCUSSION OF A PUTATIVE CANCER VARIANT.
RX PubMed=8971156;
RA Shridhar R., Shridhar V., Rivard S., Siegfried J.M.,
RA Pietraszkiewicz H., Ensley J., Pauley R., Grignon D., Sakr W.,
RA Miller O.J., Smith D.I.;
RT "Mutations in the arginine-rich protein gene, in lung, breast, and
RT prostate cancers, and in squamous cell carcinoma of the head and
RT neck.";
RL Cancer Res. 56:5576-5578(1996).
RN [12]
RP DISCUSSION OF PUTATIVE CANCER VARIANTS.
RX PubMed=9174057; DOI=10.1038/sj.onc.1201054;
RA Shridhar V., Rivard S., Wang X., Shridhar R., Paisley C., Mullins C.,
RA Beirnat L., Dugan M., Sarkar F., Miller O.J., Vaitkevicius V.K.,
RA Smith D.I.;
RT "Mutations in the arginine-rich protein gene (ARP) in pancreatic
RT cancer.";
RL Oncogene 14:2213-2216(1997).
CC -!- FUNCTION: Selectively promotes the survival of dopaminergic
CC neurons of the ventral mid-brain. Modulates GABAergic transmission
CC to the dopaminergic neurons of the substantia nigra. Enhances
CC spontaneous, as well as evoked, GABAergic inhibitory postsynaptic
CC currents in dopaminergic neurons (By similarity). Inhibits cell
CC proliferation and endoplasmic reticulum (ER) stress-induced cell
CC death.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- INDUCTION: By endoplasmic reticulum stress.
CC -!- DOMAIN: The N-terminal region may be responsible for neurotrophic
CC activity while the C-terminal region may play a role in the ER
CC stress response.
CC -!- PTM: May contain sialic acid residues.
CC -!- SIMILARITY: Belongs to the ARMET family.
CC -!- CAUTION: Was originally (PubMed:8649854, PubMed:8971156 and
CC PubMed:9174057) thought to be much longer and included an
CC arginine-rich region thought to be the target of cancer-causing
CC mutations. All these mutations are in what is now thought to be
CC the 5'-UTR of the mRNA.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB08753.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAI13589.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAI13591.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M83751; AAB08753.1; ALT_INIT; mRNA.
DR EMBL; BT007110; AAP35774.1; -; mRNA.
DR EMBL; AC092037; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007282; AAH07282.1; -; mRNA.
DR EMBL; BC113588; AAI13589.1; ALT_INIT; mRNA.
DR EMBL; BC113590; AAI13591.1; ALT_INIT; mRNA.
DR RefSeq; NP_006001.3; NM_006010.4.
DR UniGene; Hs.436446; -.
DR PDB; 2KVD; NMR; -; A=25-182.
DR PDB; 2KVE; NMR; -; A=120-182.
DR PDB; 2W51; X-ray; 2.80 A; A=25-181.
DR PDBsum; 2KVD; -.
DR PDBsum; 2KVE; -.
DR PDBsum; 2W51; -.
DR ProteinModelPortal; P55145; -.
DR SMR; P55145; 25-161.
DR MINT; MINT-3020834; -.
DR STRING; 9606.ENSP00000273628; -.
DR PhosphoSite; P55145; -.
DR DMDM; 23503040; -.
DR OGP; P55145; -.
DR PaxDb; P55145; -.
DR PRIDE; P55145; -.
DR DNASU; 7873; -.
DR Ensembl; ENST00000528157; ENSP00000432799; ENSG00000145050.
DR Ensembl; ENST00000566546; ENSP00000454660; ENSG00000259880.
DR GeneID; 7873; -.
DR KEGG; hsa:7873; -.
DR UCSC; uc003dbc.3; human.
DR CTD; 7873; -.
DR GeneCards; GC03P051399; -.
DR HGNC; HGNC:15461; MANF.
DR HPA; HPA011175; -.
DR MIM; 601916; gene.
DR neXtProt; NX_P55145; -.
DR Orphanet; 1333; Familial pancreatic carcinoma.
DR PharmGKB; PA24993; -.
DR eggNOG; NOG301491; -.
DR HOGENOM; HOG000264245; -.
DR InParanoid; P55145; -.
DR OMA; SCKGCAE; -.
DR EvolutionaryTrace; P55145; -.
DR GeneWiki; ARMET; -.
DR GenomeRNAi; 7873; -.
DR NextBio; 30328; -.
DR PRO; PR:P55145; -.
DR ArrayExpress; P55145; -.
DR Bgee; P55145; -.
DR CleanEx; HS_ARMET; -.
DR Genevestigator; P55145; -.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0002014; P:vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure; IEA:Ensembl.
DR Gene3D; 1.10.225.10; -; 1.
DR InterPro; IPR019345; Armet_prot.
DR InterPro; IPR011001; Saposin-like.
DR Pfam; PF10208; Armet; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Growth factor; Phosphoprotein;
KW Reference proteome; Secreted; Sialic acid; Signal;
KW Unfolded protein response.
FT SIGNAL 1 24
FT CHAIN 25 182 Mesencephalic astrocyte-derived
FT neurotrophic factor.
FT /FTId=PRO_0000002305.
FT MOD_RES 76 76 Phosphotyrosine (By similarity).
FT DISULFID 30 117
FT DISULFID 33 106
FT DISULFID 64 75
FT DISULFID 151 154
FT CONFLICT 13 14 AL -> RV (in Ref. 1; AAB08753).
FT CONFLICT 179 179 R -> P (in Ref. 1; AAB08753).
FT HELIX 31 46
FT HELIX 53 64
FT HELIX 69 77
FT STRAND 81 83
FT HELIX 87 89
FT HELIX 90 97
FT HELIX 102 112
FT TURN 115 118
FT HELIX 127 129
FT TURN 132 134
FT HELIX 136 143
FT HELIX 155 158
FT TURN 166 173
SQ SEQUENCE 182 AA; 20700 MW; EE25A5D1A58D1AD7 CRC64;
MRRMWATQGL AVALALSVLP GSRALRPGDC EVCISYLGRF YQDLKDRDVT FSPATIENEL
IKFCREARGK ENRLCYYIGA TDDAATKIIN EVSKPLAHHI PVEKICEKLK KKDSQICELK
YDKQIDLSTV DLKKLRVKEL KKILDDWGET CKGCAEKSDY IRKINELMPK YAPKAASART
DL
//
ID MANF_HUMAN Reviewed; 182 AA.
AC P55145; Q14CX4; Q86U67; Q96IS4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-MAY-2011, sequence version 3.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Mesencephalic astrocyte-derived neurotrophic factor;
DE AltName: Full=Arginine-rich protein;
DE AltName: Full=Protein ARMET;
DE Flags: Precursor;
GN Name=MANF; Synonyms=ARMET, ARP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DISCUSSION OF A PUTATIVE CANCER
RP VARIANT.
RX PubMed=8649854;
RA Shridhar V., Rivard S., Shridhar R., Mullins C., Bostick L., Sakr W.,
RA Grignon D., Miller O.J., Smith D.I.;
RT "A gene from human chromosomal band 3p21.1 encodes a highly conserved
RT arginine-rich protein and is mutated in renal cell carcinomas.";
RL Oncogene 12:1931-1939(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP PROTEIN SEQUENCE OF 25-39.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP PROTEIN SEQUENCE OF 25-29, FUNCTION, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=12794311; DOI=10.1385/JMN:20:2:173;
RA Petrova P., Raibekas A., Pevsner J., Vigo N., Anafi M., Moore M.K.,
RA Peaire A.E., Shridhar V., Smith D.I., Kelly J., Durocher Y.,
RA Commissiong J.W.;
RT "MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with
RT selectivity for dopaminergic neurons.";
RL J. Mol. Neurosci. 20:173-188(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18561914; DOI=10.1016/j.yexcr.2008.05.001;
RA Apostolou A., Shen Y., Liang Y., Luo J., Fang S.;
RT "Armet, a UPR-upregulated protein, inhibits cell proliferation and ER
RT stress-induced cell death.";
RL Exp. Cell Res. 314:2454-2467(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 25-182, DOMAIN, AND
RP DISULFIDE BONDS.
RX PubMed=19258449; DOI=10.1093/protein/gzn080;
RA Parkash V., Lindholm P., Peranen J., Kalkkinen N., Oksanen E.,
RA Saarma M., Leppanen V.-M., Goldman A.;
RT "The structure of the conserved neurotrophic factors MANF and CDNF
RT explains why they are bifunctional.";
RL Protein Eng. Des. Sel. 22:233-241(2009).
RN [11]
RP DISCUSSION OF A PUTATIVE CANCER VARIANT.
RX PubMed=8971156;
RA Shridhar R., Shridhar V., Rivard S., Siegfried J.M.,
RA Pietraszkiewicz H., Ensley J., Pauley R., Grignon D., Sakr W.,
RA Miller O.J., Smith D.I.;
RT "Mutations in the arginine-rich protein gene, in lung, breast, and
RT prostate cancers, and in squamous cell carcinoma of the head and
RT neck.";
RL Cancer Res. 56:5576-5578(1996).
RN [12]
RP DISCUSSION OF PUTATIVE CANCER VARIANTS.
RX PubMed=9174057; DOI=10.1038/sj.onc.1201054;
RA Shridhar V., Rivard S., Wang X., Shridhar R., Paisley C., Mullins C.,
RA Beirnat L., Dugan M., Sarkar F., Miller O.J., Vaitkevicius V.K.,
RA Smith D.I.;
RT "Mutations in the arginine-rich protein gene (ARP) in pancreatic
RT cancer.";
RL Oncogene 14:2213-2216(1997).
CC -!- FUNCTION: Selectively promotes the survival of dopaminergic
CC neurons of the ventral mid-brain. Modulates GABAergic transmission
CC to the dopaminergic neurons of the substantia nigra. Enhances
CC spontaneous, as well as evoked, GABAergic inhibitory postsynaptic
CC currents in dopaminergic neurons (By similarity). Inhibits cell
CC proliferation and endoplasmic reticulum (ER) stress-induced cell
CC death.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- INDUCTION: By endoplasmic reticulum stress.
CC -!- DOMAIN: The N-terminal region may be responsible for neurotrophic
CC activity while the C-terminal region may play a role in the ER
CC stress response.
CC -!- PTM: May contain sialic acid residues.
CC -!- SIMILARITY: Belongs to the ARMET family.
CC -!- CAUTION: Was originally (PubMed:8649854, PubMed:8971156 and
CC PubMed:9174057) thought to be much longer and included an
CC arginine-rich region thought to be the target of cancer-causing
CC mutations. All these mutations are in what is now thought to be
CC the 5'-UTR of the mRNA.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB08753.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAI13589.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAI13591.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M83751; AAB08753.1; ALT_INIT; mRNA.
DR EMBL; BT007110; AAP35774.1; -; mRNA.
DR EMBL; AC092037; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007282; AAH07282.1; -; mRNA.
DR EMBL; BC113588; AAI13589.1; ALT_INIT; mRNA.
DR EMBL; BC113590; AAI13591.1; ALT_INIT; mRNA.
DR RefSeq; NP_006001.3; NM_006010.4.
DR UniGene; Hs.436446; -.
DR PDB; 2KVD; NMR; -; A=25-182.
DR PDB; 2KVE; NMR; -; A=120-182.
DR PDB; 2W51; X-ray; 2.80 A; A=25-181.
DR PDBsum; 2KVD; -.
DR PDBsum; 2KVE; -.
DR PDBsum; 2W51; -.
DR ProteinModelPortal; P55145; -.
DR SMR; P55145; 25-161.
DR MINT; MINT-3020834; -.
DR STRING; 9606.ENSP00000273628; -.
DR PhosphoSite; P55145; -.
DR DMDM; 23503040; -.
DR OGP; P55145; -.
DR PaxDb; P55145; -.
DR PRIDE; P55145; -.
DR DNASU; 7873; -.
DR Ensembl; ENST00000528157; ENSP00000432799; ENSG00000145050.
DR Ensembl; ENST00000566546; ENSP00000454660; ENSG00000259880.
DR GeneID; 7873; -.
DR KEGG; hsa:7873; -.
DR UCSC; uc003dbc.3; human.
DR CTD; 7873; -.
DR GeneCards; GC03P051399; -.
DR HGNC; HGNC:15461; MANF.
DR HPA; HPA011175; -.
DR MIM; 601916; gene.
DR neXtProt; NX_P55145; -.
DR Orphanet; 1333; Familial pancreatic carcinoma.
DR PharmGKB; PA24993; -.
DR eggNOG; NOG301491; -.
DR HOGENOM; HOG000264245; -.
DR InParanoid; P55145; -.
DR OMA; SCKGCAE; -.
DR EvolutionaryTrace; P55145; -.
DR GeneWiki; ARMET; -.
DR GenomeRNAi; 7873; -.
DR NextBio; 30328; -.
DR PRO; PR:P55145; -.
DR ArrayExpress; P55145; -.
DR Bgee; P55145; -.
DR CleanEx; HS_ARMET; -.
DR Genevestigator; P55145; -.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0002014; P:vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure; IEA:Ensembl.
DR Gene3D; 1.10.225.10; -; 1.
DR InterPro; IPR019345; Armet_prot.
DR InterPro; IPR011001; Saposin-like.
DR Pfam; PF10208; Armet; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Growth factor; Phosphoprotein;
KW Reference proteome; Secreted; Sialic acid; Signal;
KW Unfolded protein response.
FT SIGNAL 1 24
FT CHAIN 25 182 Mesencephalic astrocyte-derived
FT neurotrophic factor.
FT /FTId=PRO_0000002305.
FT MOD_RES 76 76 Phosphotyrosine (By similarity).
FT DISULFID 30 117
FT DISULFID 33 106
FT DISULFID 64 75
FT DISULFID 151 154
FT CONFLICT 13 14 AL -> RV (in Ref. 1; AAB08753).
FT CONFLICT 179 179 R -> P (in Ref. 1; AAB08753).
FT HELIX 31 46
FT HELIX 53 64
FT HELIX 69 77
FT STRAND 81 83
FT HELIX 87 89
FT HELIX 90 97
FT HELIX 102 112
FT TURN 115 118
FT HELIX 127 129
FT TURN 132 134
FT HELIX 136 143
FT HELIX 155 158
FT TURN 166 173
SQ SEQUENCE 182 AA; 20700 MW; EE25A5D1A58D1AD7 CRC64;
MRRMWATQGL AVALALSVLP GSRALRPGDC EVCISYLGRF YQDLKDRDVT FSPATIENEL
IKFCREARGK ENRLCYYIGA TDDAATKIIN EVSKPLAHHI PVEKICEKLK KKDSQICELK
YDKQIDLSTV DLKKLRVKEL KKILDDWGET CKGCAEKSDY IRKINELMPK YAPKAASART
DL
//
MIM
601916
*RECORD*
*FIELD* NO
601916
*FIELD* TI
*601916 ARGININE-RICH PROTEIN MUTATED IN EARLY STAGE TUMORS; ARMET
;;ARGININE-RICH PROTEIN; ARP;;
read moreMESENCEPHALIC ASTROCYTE-DERIVED NEUROTROPHIC FACTOR; MANF
*FIELD* TX
CLONING
Shridhar et al. (1996) isolated a novel cDNA, which they designated ARP,
from a gastric adenocarcinoma cDNA library. ARP encodes a deduced
234-amino acid that is arginine-rich. The ubiquitously expressed protein
is highly conserved in evolution.
GENE STRUCTURE
Shridhar et al. (1996) determined that the ARP gene contains 4 exons.
The nucleotide sequence at the 5-prime end of the mature transcript has
an imperfect trinucleotide repeat (AGG/CGG) coding for arginine in 15 of
18 residues between amino acids 38 and 55.
MAPPING
Shridhar et al. (1996) identified the ARP gene on chromosome 3p21.1, a
region that is frequently deleted in a variety of solid tumors.
MOLECULAR GENETICS
Shridhar et al. (1996, 1996) reported an ATG-to-AGG transversion in
codon 50 of the ARP gene or deletion of codon 50 of the ARP gene in
different tumor types including 10 of 21 sporadic renal cell carcinomas.
Shridhar et al. (1997) observed the same mutations in 11 of 37
pancreatic tumors. Either of the changes abolishes a methionine residue
and gives rise to an uninterrupted string of AGG trinucleotides in the
ARP gene and arginines in its predicted protein product. The finding of
4 other nucleotide substitutions in codon 50 that replaced methionine
with 4 different amino acids other than arginine suggested that loss of
this methionine residue is critical to a carcinogenic role of this gene.
Their finding of an AGG-to-AAG (arg-to-lys) mutation in the adjacent
codon 51 in 2 tumors emphasized further the importance of this region.
Other evidence (Shridhar et al., 1996) suggested that only a single copy
of the ARP gene is mutated in the cancer cells, indicating its possible
causal role as an oncogene.
*FIELD* RF
1. 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.: Mutations in the arginine-rich protein gene, in lung,
breast, and prostate cancers, and in squamous cell carcinoma of the
head and neck. Cancer Res. 56: 5576-5578, 1996.
2. Shridhar, V.; Rivard, S.; Shridhar, R.; Mullins, C.; Bostick, L.;
Sakr, W.; Grignon, D.; Miller, O. J.; Smith, D. I.: A gene from human
chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein
and is mutated in renal cell carcinomas. Oncogene 12: 1931-1939,
1996.
3. 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.: Mutations in the arginine-rich protein gene
(ARP) in pancreatic cancer. Oncogene 14: 2213-2216, 1997.
*FIELD* CN
Joanna S. Amberger - updated: 07/17/2009
*FIELD* CD
Victor A. McKusick: 7/1/1997
*FIELD* ED
carol: 07/17/2009
joanna: 7/16/2009
carol: 6/1/2009
alopez: 7/20/2007
cwells: 11/10/2003
carol: 4/3/2001
alopez: 7/22/1997
mark: 7/2/1997
jenny: 7/1/1997
*RECORD*
*FIELD* NO
601916
*FIELD* TI
*601916 ARGININE-RICH PROTEIN MUTATED IN EARLY STAGE TUMORS; ARMET
;;ARGININE-RICH PROTEIN; ARP;;
read moreMESENCEPHALIC ASTROCYTE-DERIVED NEUROTROPHIC FACTOR; MANF
*FIELD* TX
CLONING
Shridhar et al. (1996) isolated a novel cDNA, which they designated ARP,
from a gastric adenocarcinoma cDNA library. ARP encodes a deduced
234-amino acid that is arginine-rich. The ubiquitously expressed protein
is highly conserved in evolution.
GENE STRUCTURE
Shridhar et al. (1996) determined that the ARP gene contains 4 exons.
The nucleotide sequence at the 5-prime end of the mature transcript has
an imperfect trinucleotide repeat (AGG/CGG) coding for arginine in 15 of
18 residues between amino acids 38 and 55.
MAPPING
Shridhar et al. (1996) identified the ARP gene on chromosome 3p21.1, a
region that is frequently deleted in a variety of solid tumors.
MOLECULAR GENETICS
Shridhar et al. (1996, 1996) reported an ATG-to-AGG transversion in
codon 50 of the ARP gene or deletion of codon 50 of the ARP gene in
different tumor types including 10 of 21 sporadic renal cell carcinomas.
Shridhar et al. (1997) observed the same mutations in 11 of 37
pancreatic tumors. Either of the changes abolishes a methionine residue
and gives rise to an uninterrupted string of AGG trinucleotides in the
ARP gene and arginines in its predicted protein product. The finding of
4 other nucleotide substitutions in codon 50 that replaced methionine
with 4 different amino acids other than arginine suggested that loss of
this methionine residue is critical to a carcinogenic role of this gene.
Their finding of an AGG-to-AAG (arg-to-lys) mutation in the adjacent
codon 51 in 2 tumors emphasized further the importance of this region.
Other evidence (Shridhar et al., 1996) suggested that only a single copy
of the ARP gene is mutated in the cancer cells, indicating its possible
causal role as an oncogene.
*FIELD* RF
1. 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.: Mutations in the arginine-rich protein gene, in lung,
breast, and prostate cancers, and in squamous cell carcinoma of the
head and neck. Cancer Res. 56: 5576-5578, 1996.
2. Shridhar, V.; Rivard, S.; Shridhar, R.; Mullins, C.; Bostick, L.;
Sakr, W.; Grignon, D.; Miller, O. J.; Smith, D. I.: A gene from human
chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein
and is mutated in renal cell carcinomas. Oncogene 12: 1931-1939,
1996.
3. 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.: Mutations in the arginine-rich protein gene
(ARP) in pancreatic cancer. Oncogene 14: 2213-2216, 1997.
*FIELD* CN
Joanna S. Amberger - updated: 07/17/2009
*FIELD* CD
Victor A. McKusick: 7/1/1997
*FIELD* ED
carol: 07/17/2009
joanna: 7/16/2009
carol: 6/1/2009
alopez: 7/20/2007
cwells: 11/10/2003
carol: 4/3/2001
alopez: 7/22/1997
mark: 7/2/1997
jenny: 7/1/1997