NENF_HUMAN
ID NENF_HUMAN Reviewed; 172 AA.
AC Q9UMX5; A1KYQ8; Q53FZ6; Q5TM90;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Neudesin;
DE AltName: Full=Cell immortalization-related protein 2;
DE AltName: Full=Neuron-derived neurotrophic factor;
DE AltName: Full=Protein GIG47 {ECO:0000303|PubMed:22748190};
DE AltName: Full=Secreted protein of unknown function;
DE Short=SPUF protein;
DE Flags: Precursor;
GN Name=NENF {ECO:0000312|HGNC:HGNC:30384}; Synonyms=CIR2, SPUF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
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 [MRNA].
RA Rasheed Z.A., Haluska P., Saleem A., Rubin E.H.;
RT "Identification of a secreted protein of unknown function.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a cell growth-inhibiting gene.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastric carcinoma;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [7]
RP INDUCTION.
RX PubMed=9771976; DOI=10.1038/sj.onc.1202058;
RA Ma L., Broomfield S., Lavery C., Lin S.L., Xiao W., Bacchetti S.;
RT "Up-regulation of CIR1/CROC1 expression upon cell immortalization and in
RT tumor-derived human cell lines.";
RL Oncogene 17:1321-1326(1998).
RN [8]
RP INDUCTION.
RX PubMed=16645950; DOI=10.1002/elps.200500739;
RA Neubauer H., Clare S.E., Kurek R., Fehm T., Wallwiener D., Sotlar K.,
RA Nordheim A., Wozny W., Schwall G.P., Poznanovic S., Sastri C.,
RA Hunzinger C., Stegmann W., Schrattenholz A., Cahill M.A.;
RT "Breast cancer proteomics by laser capture microdissection, sample pooling,
RT 54-cm IPG IEF, and differential iodine radioisotope detection.";
RL Electrophoresis 27:1840-1852(2006).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-136, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
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., Buerckstuemmer T.,
RA 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 [11]
RP TISSUE SPECIFICITY, AND STRUCTURE BY NMR.
RX PubMed=22748190; DOI=10.1186/1471-2407-12-274;
RA Han K.H., Lee S.H., Ha S.A., Kim H.K., Lee C., Kim D.H., Gong K.H., Yoo J.,
RA Kim S., Kim J.W.;
RT "The functional and structural characterization of a novel oncogene GIG47
RT involved in the breast tumorigenesis.";
RL BMC Cancer 12:274-274(2012).
RN [12]
RP MISCELLANEOUS, AND REVIEW.
RX PubMed=23763432; DOI=10.1111/jne.12060;
RA Petersen S.L., Intlekofer K.A., Moura-Conlon P.J., Brewer D.N.,
RA Del Pino Sans J., Lopez J.A.;
RT "Nonclassical progesterone signalling molecules in the nervous system.";
RL J. Neuroendocrinol. 25:991-1001(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP REVIEW, AND MISCELLANEOUS.
RX PubMed=28396637; DOI=10.3389/fphar.2017.00159;
RA Ryu C.S., Klein K., Zanger U.M.;
RT "Membrane associated progesterone receptors: promiscuous proteins with
RT pleiotropic functions - focus on interactions with cytochromes P450.";
RL Front. Pharmacol. 8:159-159(2017).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH PINK1 AND
RP 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:31536960). Promotes cell
CC proliferation and neurogenesis in undifferentiated neural progenitor
CC cells at the embryonic stage and inhibits differentiation of astrocytes
CC (By similarity). Its neurotrophic activity is exerted via MAPK1/ERK2,
CC MAPK3/ERK1 and AKT1/AKT pathways (By similarity). Neurotrophic activity
CC is enhanced by binding to heme (By similarity). Acts also as an
CC anorexigenic neurotrophic factor that contributes to energy balance (By
CC similarity). {ECO:0000250|UniProtKB:Q9CQ45,
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:31536960}. 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:0000269|PubMed:31536960}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with high expression in
CC heart. Over-expressed in various tumors including carcinomas of the
CC uterine cervix, lymphoma, colon, lung, skin and leukemia, as well as
CC carcinoma of the breast. {ECO:0000269|PubMed:22748190}.
CC -!- INDUCTION: Up-regulated in immortal cells. Induced in estrogen receptor
CC positive breast cancer expressing progesterone receptor.
CC {ECO:0000269|PubMed:16645950, ECO:0000269|PubMed:9771976}.
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 82. {ECO:0000250}.
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:0000303|PubMed:23763432, ECO:0000303|PubMed:28396637}.
CC -!- SIMILARITY: Belongs to the cytochrome b5 family. MAPR subfamily.
CC {ECO:0000305}.
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DR EMBL; AB126219; BAD72063.1; -; mRNA.
DR EMBL; AF173937; AAD51419.1; -; mRNA.
DR EMBL; AY762102; AAX07829.1; -; mRNA.
DR EMBL; AK223135; BAD96855.1; -; mRNA.
DR EMBL; CH471100; EAW93389.1; -; Genomic_DNA.
DR EMBL; BC008823; AAH08823.1; -; mRNA.
DR CCDS; CCDS1505.1; -.
DR RefSeq; NP_037481.1; NM_013349.4.
DR AlphaFoldDB; Q9UMX5; -.
DR SMR; Q9UMX5; -.
DR BioGRID; 118976; 86.
DR IntAct; Q9UMX5; 6.
DR STRING; 9606.ENSP00000355955; -.
DR iPTMnet; Q9UMX5; -.
DR MetOSite; Q9UMX5; -.
DR PhosphoSitePlus; Q9UMX5; -.
DR BioMuta; NENF; -.
DR DMDM; 46577571; -.
DR EPD; Q9UMX5; -.
DR jPOST; Q9UMX5; -.
DR MassIVE; Q9UMX5; -.
DR MaxQB; Q9UMX5; -.
DR PaxDb; Q9UMX5; -.
DR PeptideAtlas; Q9UMX5; -.
DR PRIDE; Q9UMX5; -.
DR ProteomicsDB; 85222; -.
DR TopDownProteomics; Q9UMX5; -.
DR Antibodypedia; 20714; 161 antibodies from 31 providers.
DR DNASU; 29937; -.
DR Ensembl; ENST00000366988.5; ENSP00000355955.3; ENSG00000117691.10.
DR GeneID; 29937; -.
DR KEGG; hsa:29937; -.
DR MANE-Select; ENST00000366988.5; ENSP00000355955.3; NM_013349.5; NP_037481.1.
DR UCSC; uc001hjd.3; human.
DR CTD; 29937; -.
DR DisGeNET; 29937; -.
DR GeneCards; NENF; -.
DR HGNC; HGNC:30384; NENF.
DR HPA; ENSG00000117691; Low tissue specificity.
DR MIM; 611874; gene.
DR neXtProt; NX_Q9UMX5; -.
DR OpenTargets; ENSG00000117691; -.
DR PharmGKB; PA142671266; -.
DR VEuPathDB; HostDB:ENSG00000117691; -.
DR eggNOG; KOG1110; Eukaryota.
DR GeneTree; ENSGT00940000162504; -.
DR HOGENOM; CLU_134788_0_0_1; -.
DR InParanoid; Q9UMX5; -.
DR OMA; FNIRDEF; -.
DR OrthoDB; 1532459at2759; -.
DR PhylomeDB; Q9UMX5; -.
DR TreeFam; TF332131; -.
DR PathwayCommons; Q9UMX5; -.
DR SignaLink; Q9UMX5; -.
DR BioGRID-ORCS; 29937; 15 hits in 1084 CRISPR screens.
DR ChiTaRS; NENF; human.
DR GenomeRNAi; 29937; -.
DR Pharos; Q9UMX5; Tbio.
DR PRO; PR:Q9UMX5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UMX5; protein.
DR Bgee; ENSG00000117691; Expressed in tendon of biceps brachii and 198 other tissues.
DR Genevisible; Q9UMX5; HS.
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:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0032099; P:negative regulation of appetite; ISS:UniProtKB.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
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..31
FT /evidence="ECO:0000255"
FT CHAIN 32..172
FT /note="Neudesin"
FT /id="PRO_0000018598"
FT DOMAIN 44..129
FT /note="Cytochrome b5 heme-binding"
FT REGION 151..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 136
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CONFLICT 74
FT /note="D -> E (in Ref. 4; BAD96855)"
FT /evidence="ECO:0000305"
SQ 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
