NENF_MOUSE
ID NENF_MOUSE Reviewed; 171 AA.
AC Q9CQ45; Q5TM91;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Neudesin;
DE AltName: Full=Neuron-derived neurotrophic factor;
DE AltName: Full=Secreted protein of unknown function;
DE Short=SPUF protein;
DE Flags: Precursor;
GN Name=Nenf {ECO:0000312|MGI:MGI:1913458}; Synonyms=Spuf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=15605373; DOI=10.1002/jnr.20356;
RA Kimura I., Yoshioka M., Konishi M., Miyake A., Itoh N.;
RT "Neudesin, a novel secreted protein with a unique primary structure and
RT neurotrophic activity.";
RL J. Neurosci. Res. 79:287-294(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Dendritic cell, Embryo, Kidney, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=16547973; DOI=10.1002/jnr.20849;
RA Kimura I., Konishi M., Miyake A., Fujimoto M., Itoh N.;
RT "Neudesin, a secreted factor, promotes neural cell proliferation and
RT neuronal differentiation in mouse neural precursor cells.";
RL J. Neurosci. Res. 83:1415-1424(2006).
RN [5]
RP FUNCTION, HEME-BINDING, AND MUTAGENESIS OF 73-ASP--ASP-125.
RX PubMed=18056703; DOI=10.1074/jbc.m706679200;
RA Kimura I., Nakayama Y., Yamauchi H., Konishi M., Miyake A., Mori M.,
RA Ohta M., Itoh N., Fujimoto M.;
RT "Neurotrophic activity of neudesin, a novel extracellular heme-binding
RT protein, is dependent on the binding of heme to its cytochrome b5-like
RT heme/steroid-binding domain.";
RL J. Biol. Chem. 283:4323-4331(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23576617; DOI=10.1152/ajpregu.00368.2012;
RA Byerly M.S., Swanson R.D., Semsarzadeh N.N., McCulloh P.S., Kwon K.,
RA Aja S., Moran T.H., Wong G.W., Blackshaw S.;
RT "Identification of hypothalamic neuron-derived neurotrophic factor as a
RT novel factor modulating appetite.";
RL Am. J. Physiol. 304:R1085-1095(2013).
RN [8]
RP FUNCTION, INTERACTION WITH PINK1 AND PARK7, AND SUBCELLULAR LOCATION.
RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057;
RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A.,
RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J.,
RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G.,
RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y.,
RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.;
RT "Rewiring of the Human Mitochondrial Interactome during Neuronal
RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis.";
RL IScience 19:1114-1132(2019).
CC -!- FUNCTION: Acts as a neurotrophic factor in postnatal mature neurons,
CC enhancing neuronal survival (PubMed:15605373, PubMed:31536960).
CC Promotes cell proliferation and neurogenesis in undifferentiated neural
CC pro-genitor cells at the embryonic stage and inhibits differentiation
CC of astrocytes (PubMed:16547973). Its neurotrophic activity is exerted
CC via MAPK1/ERK2, MAPK3/ERK1 and AKT1/AKT pathways (PubMed:15605373,
CC PubMed:16547973). Neurotrophic activity is enhanced by binding to heme
CC (PubMed:18056703). Acts also as an anorexigenic neurotrophic factor
CC that contributes to energy balance (PubMed:23576617).
CC {ECO:0000269|PubMed:15605373, ECO:0000269|PubMed:16547973,
CC ECO:0000269|PubMed:18056703, ECO:0000269|PubMed:23576617,
CC ECO:0000269|PubMed:31536960}.
CC -!- SUBUNIT: Interacts with PINK1 and PARK7. {ECO:0000269|PubMed:31536960}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000269|PubMed:15605373}. Mitochondrion
CC {ECO:0000269|PubMed:31536960}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:31536960}. Note=Localized to mitochondria and
CC endoplasmic reticulum by PINK1 and PARK7.
CC {ECO:0000250|UniProtKB:Q9UMX5}.
CC -!- TISSUE SPECIFICITY: In the embryo, expressed most abundantly in brain
CC and spinal cord. Widely expressed in adult tissues including brain,
CC heart, lung and kidney. In brain, expressed in neurons but not in glial
CC cells (PubMed:15605373). In the hypothalamus is expressed primarily in
CC the paraventricular nucleus (PVN), with lower levels of expression in
CC the arcuate nucleus (ARC)(PubMed:23576617).
CC {ECO:0000269|PubMed:15605373, ECO:0000269|PubMed:23576617}.
CC -!- DEVELOPMENTAL STAGE: In embryonic cerebral cortex is first weakly
CC detected at 12.5 dpc, and thereafter gradually increased. At 13.5 dpc
CC expression is observed mostly in the preplate.
CC {ECO:0000269|PubMed:16547973}.
CC -!- DOMAIN: The cytochrome b5 heme-binding domain was proven to bind heme,
CC although it lacks the conserved iron-binding His residue at position
CC 81.
CC -!- MISCELLANEOUS: Non-classical progesterone receptors involved in
CC extranuclear signaling are classified in 2 groups: the class II
CC progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5,
CC PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding
CC protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).
CC {ECO:0000250|UniProtKB:Q9UMX5}.
CC -!- SIMILARITY: Belongs to the cytochrome b5 family. MAPR subfamily.
CC {ECO:0000305}.
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DR EMBL; AB126218; BAD72062.1; -; mRNA.
DR EMBL; AK002413; BAB22081.1; -; mRNA.
DR EMBL; AK004329; BAB23264.1; -; mRNA.
DR EMBL; AK009304; BAB26205.1; -; mRNA.
DR EMBL; AK020403; BAB32092.1; -; mRNA.
DR EMBL; AK155319; BAE33187.1; -; mRNA.
DR EMBL; BC048464; AAH48464.1; -; mRNA.
DR CCDS; CCDS15618.1; -.
DR RefSeq; NP_079700.1; NM_025424.2.
DR AlphaFoldDB; Q9CQ45; -.
DR SMR; Q9CQ45; -.
DR STRING; 10090.ENSMUSP00000046311; -.
DR PhosphoSitePlus; Q9CQ45; -.
DR EPD; Q9CQ45; -.
DR MaxQB; Q9CQ45; -.
DR PaxDb; Q9CQ45; -.
DR PeptideAtlas; Q9CQ45; -.
DR PRIDE; Q9CQ45; -.
DR ProteomicsDB; 252808; -.
DR Antibodypedia; 20714; 161 antibodies from 31 providers.
DR Ensembl; ENSMUST00000046770; ENSMUSP00000046311; ENSMUSG00000037499.
DR GeneID; 66208; -.
DR KEGG; mmu:66208; -.
DR UCSC; uc007ecg.1; mouse.
DR CTD; 29937; -.
DR MGI; MGI:1913458; Nenf.
DR VEuPathDB; HostDB:ENSMUSG00000037499; -.
DR eggNOG; KOG1110; Eukaryota.
DR GeneTree; ENSGT00940000162504; -.
DR HOGENOM; CLU_134788_0_0_1; -.
DR InParanoid; Q9CQ45; -.
DR OMA; FNIRDEF; -.
DR OrthoDB; 1532459at2759; -.
DR PhylomeDB; Q9CQ45; -.
DR TreeFam; TF332131; -.
DR BioGRID-ORCS; 66208; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Nenf; mouse.
DR PRO; PR:Q9CQ45; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9CQ45; protein.
DR Bgee; ENSMUSG00000037499; Expressed in interventricular septum and 243 other tissues.
DR Genevisible; Q9CQ45; MM.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000165; P:MAPK cascade; IDA:MGI.
DR GO; GO:0032099; P:negative regulation of appetite; IDA:UniProtKB.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR Gene3D; 3.10.120.10; -; 1.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR Pfam; PF00173; Cyt-b5; 1.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
PE 1: Evidence at protein level;
KW Acetylation; Endoplasmic reticulum; Heme; Iron; Metal-binding;
KW Mitochondrion; Reference proteome; Secreted; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..171
FT /note="Neudesin"
FT /id="PRO_0000018599"
FT DOMAIN 43..128
FT /note="Cytochrome b5 heme-binding"
FT MOD_RES 135
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UMX5"
FT MUTAGEN 73..125
FT /note="Missing: Does not bind heme."
FT /evidence="ECO:0000269|PubMed:18056703"
SQ SEQUENCE 171 AA; 18904 MW; C90C835FE2C7B3E2 CRC64;
MARPAPWWRL RLLAALVLAL ALVPVPSAWA GQTPRPAERG PPVRLFTEEE LARYGGEEED
QPIYLAVKGV VFDVTSGKEF YGRGAPYNAL AGKDSSRGVA KMSLDPADLT HDTTGLTAKE
LEALDDVFSK VYKAKYPIVG YTARRILNED GSPNLDFKPE DQPHFDIKDE F
