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Neudesin (Cell immortalization-related protein 2) (Neuron-derived neurotrophic factor) (Protein GIG47) (Secreted protein of unknown function) (SPUF protein)

 NENF_HUMAN              Reviewed;         172 AA.
Q9UMX5; A1KYQ8; Q53FZ6; Q5TM90;
26-APR-2004, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
28-FEB-2018, entry version 121.
RecName: Full=Neudesin;
AltName: Full=Cell immortalization-related protein 2;
AltName: Full=Neuron-derived neurotrophic factor;
AltName: Full=Protein GIG47 {ECO:0000303|PubMed:22748190};
AltName: Full=Secreted protein of unknown function;
Short=SPUF protein;
Flags: Precursor;
Name=NENF {ECO:0000312|HGNC:HGNC:30384}; Synonyms=CIR2, SPUF;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Brain;
PubMed=15605373; DOI=10.1002/jnr.20356;
Kimura I., Yoshioka M., Konishi M., Miyake A., Itoh N.;
"Neudesin, a novel secreted protein with a unique primary structure
and neurotrophic activity.";
J. Neurosci. Res. 79:287-294(2005).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
Rasheed Z.A., Haluska P., Saleem A., Rubin E.H.;
"Identification of a secreted protein of unknown function.";
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kim J.W.;
"Identification of a cell growth-inhibiting gene.";
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Gastric carcinoma;
Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
Tanaka A., Yokoyama S.;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Uterus;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
INDUCTION.
PubMed=9771976; DOI=10.1038/sj.onc.1202058;
Ma L., Broomfield S., Lavery C., Lin S.L., Xiao W., Bacchetti S.;
"Up-regulation of CIR1/CROC1 expression upon cell immortalization and
in tumor-derived human cell lines.";
Oncogene 17:1321-1326(1998).
[8]
INDUCTION.
PubMed=16645950; DOI=10.1002/elps.200500739;
Neubauer H., Clare S.E., Kurek R., Fehm T., Wallwiener D., Sotlar K.,
Nordheim A., Wozny W., Schwall G.P., Poznanovic S., Sastri C.,
Hunzinger C., Stegmann W., Schrattenholz A., Cahill M.A.;
"Breast cancer proteomics by laser capture microdissection, sample
pooling, 54-cm IPG IEF, and differential iodine radioisotope
detection.";
Electrophoresis 27:1840-1852(2006).
[9]
ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-136, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19608861; DOI=10.1126/science.1175371;
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
Walther T.C., Olsen J.V., Mann M.;
"Lysine acetylation targets protein complexes and co-regulates major
cellular functions.";
Science 325:834-840(2009).
[10]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[11]
TISSUE SPECIFICITY, FUNCTION, AND STRUCTURE BY NMR.
PubMed=22748190; DOI=10.1186/1471-2407-12-274;
Han K.H., Lee S.H., Ha S.A., Kim H.K., Lee C., Kim D.H., Gong K.H.,
Yoo J., Kim S., Kim J.W.;
"The functional and structural characterization of a novel oncogene
GIG47 involved in the breast tumorigenesis.";
BMC Cancer 12:274-274(2012).
[12]
MISCELLANEOUS, AND REVIEW.
PubMed=23763432; DOI=10.1111/jne.12060;
Petersen S.L., Intlekofer K.A., Moura-Conlon P.J., Brewer D.N.,
Del Pino Sans J., Lopez J.A.;
"Nonclassical progesterone signalling molecules in the nervous
system.";
J. Neuroendocrinol. 25:991-1001(2013).
[13]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[14]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=25944712; DOI=10.1002/pmic.201400617;
Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M.,
Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
"N-terminome analysis of the human mitochondrial proteome.";
Proteomics 15:2519-2524(2015).
[15]
REVIEW, AND MISCELLANEOUS.
PubMed=28396637; DOI=10.3389/fphar.2017.00159;
Ryu C.S., Klein K., Zanger U.M.;
"Membrane associated progesterone receptors: promiscuous proteins with
pleiotropic functions - focus on interactions with cytochromes P450.";
Front. Pharmacol. 8:159-159(2017).
-!- FUNCTION: Acts as a neurotrophic factor in postnatal mature
neurons enhancing neuronal survival. Promotes cell proliferation
and neurogenesis in undifferentiated neural pro-genitor cells at
the embryonic stage and inhibits differentiation of astrocyte. Its
neurotrophic activity is exerted via MAPK1/ERK2, MAPK3/ERK1 and
AKT1/AKT pathways. Neurotrophic activity is enhanced by binding to
heme. Acts also as an anorexigenic neurotrophic factor that
contributes to energy balance (By similarity). Plays a role in the
human tumorigenesis (PubMed:22748190).
{ECO:0000250|UniProtKB:Q9CQ45, ECO:0000269|PubMed:22748190}.
-!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}.
-!- TISSUE SPECIFICITY: Ubiquitously expressed with high expression in
heart. Over-expressed in various tumors including carcinomas of
the uterine cervix, lymphoma, colon, lung, skin and leukemia, as
well as carcinoma of the breast. {ECO:0000269|PubMed:22748190}.
-!- INDUCTION: Up-regulated in immortal cells. Induced in estrogen
receptor positive breast cancer expressing progesterone receptor.
{ECO:0000269|PubMed:16645950, ECO:0000269|PubMed:9771976}.
-!- DOMAIN: The cytochrome b5 heme-binding domain was proven to bind
heme, although it lacks the conserved iron-binding His residue at
position 82. {ECO:0000250}.
-!- MISCELLANEOUS: Non-classical progesterone receptors involved in
extranuclear signaling are classified in 2 groups: the class II
progestin and adipoQ receptor (PAQR) family (also called mPRs)
(PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like
heme/steroid-binding protein family (also called MAPRs) (PGRMC1,
PGRMC2, NENF and CYB5D2). {ECO:0000303|PubMed:23763432,
ECO:0000303|PubMed:28396637}.
-!- SIMILARITY: Belongs to the cytochrome b5 family. MAPR subfamily.
{ECO:0000305}.
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EMBL; AB126219; BAD72063.1; -; mRNA.
EMBL; AF173937; AAD51419.1; -; mRNA.
EMBL; AY762102; AAX07829.1; -; mRNA.
EMBL; AK223135; BAD96855.1; -; mRNA.
EMBL; CH471100; EAW93389.1; -; Genomic_DNA.
EMBL; BC008823; AAH08823.1; -; mRNA.
CCDS; CCDS1505.1; -.
RefSeq; NP_037481.1; NM_013349.4.
UniGene; Hs.461787; -.
ProteinModelPortal; Q9UMX5; -.
SMR; Q9UMX5; -.
BioGrid; 118976; 35.
IntAct; Q9UMX5; 1.
STRING; 9606.ENSP00000355955; -.
iPTMnet; Q9UMX5; -.
PhosphoSitePlus; Q9UMX5; -.
BioMuta; NENF; -.
DMDM; 46577571; -.
EPD; Q9UMX5; -.
MaxQB; Q9UMX5; -.
PaxDb; Q9UMX5; -.
PeptideAtlas; Q9UMX5; -.
PRIDE; Q9UMX5; -.
TopDownProteomics; Q9UMX5; -.
Ensembl; ENST00000366988; ENSP00000355955; ENSG00000117691.
GeneID; 29937; -.
KEGG; hsa:29937; -.
UCSC; uc001hjd.3; human.
CTD; 29937; -.
DisGeNET; 29937; -.
EuPathDB; HostDB:ENSG00000117691.9; -.
GeneCards; NENF; -.
HGNC; HGNC:30384; NENF.
HPA; HPA026763; -.
HPA; HPA028488; -.
MIM; 611874; gene.
neXtProt; NX_Q9UMX5; -.
OpenTargets; ENSG00000117691; -.
PharmGKB; PA142671266; -.
eggNOG; KOG1110; Eukaryota.
eggNOG; ENOG4111UG0; LUCA.
GeneTree; ENSGT00730000110948; -.
HOGENOM; HOG000187840; -.
HOVERGEN; HBG059971; -.
InParanoid; Q9UMX5; -.
OMA; GKGAPYN; -.
OrthoDB; EOG091G0QKM; -.
PhylomeDB; Q9UMX5; -.
TreeFam; TF332131; -.
ChiTaRS; NENF; human.
GenomeRNAi; 29937; -.
PRO; PR:Q9UMX5; -.
Proteomes; UP000005640; Chromosome 1.
Bgee; ENSG00000117691; -.
CleanEx; HS_NENF; -.
Genevisible; Q9UMX5; HS.
GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
GO; GO:0016020; C:membrane; IBA:GO_Central.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005634; C:nucleus; IDA:HPA.
GO; GO:0008083; F:growth factor activity; IEA:Ensembl.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0032099; P:negative regulation of appetite; ISS:UniProtKB.
GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
Gene3D; 3.10.120.10; -; 1.
InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
Pfam; PF00173; Cyt-b5; 1.
SMART; SM01117; Cyt-b5; 1.
SUPFAM; SSF55856; SSF55856; 1.
1: Evidence at protein level;
Acetylation; Complete proteome; Heme; Iron; Metal-binding;
Reference proteome; Secreted; Signal.
SIGNAL 1 31 {ECO:0000255}.
CHAIN 32 172 Neudesin.
/FTId=PRO_0000018598.
DOMAIN 44 129 Cytochrome b5 heme-binding.
MOD_RES 136 136 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
CONFLICT 74 74 D -> E (in Ref. 4; BAD96855).
{ECO:0000305}.
SEQUENCE 172 AA; 18856 MW; 24527D540B000F2E CRC64;
MVGPAPRRRL RPLAALALVL ALAPGLPTAR AGQTPRPAER GPPVRLFTEE ELARYGGEEE
DQPIYLAVKG VVFDVTSGKE FYGRGAPYNA LTGKDSTRGV AKMSLDPADL THDTTGLTAK
ELEALDEVFT KVYKAKYPIV GYTARRILNE DGSPNLDFKP EDQPHFDIKD EF


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