NEUFC_HUMAN
ID NEUFC_HUMAN Reviewed; 264 AA.
AC Q8WUJ1; B2R7R6; D3DTJ9; I3L1K2;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Neuferricin;
DE AltName: Full=Cytochrome b5 domain-containing protein 2;
DE Flags: Precursor;
GN Name=CYB5D2 {ECO:0000312|HGNC:HGNC:28471};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Rhabdomyosarcoma, and Skin;
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 [5]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-7 AND PRO-7.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [6]
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 [7]
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).
CC -!- FUNCTION: Heme-binding protein which promotes neuronal but not
CC astrocyte differentiation. {ECO:0000250}.
CC -!- INTERACTION:
CC Q8WUJ1; P08631-2: HCK; NbExp=3; IntAct=EBI-19113794, EBI-9834454;
CC Q8WUJ1; P17152: TMEM11; NbExp=3; IntAct=EBI-19113794, EBI-723946;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WUJ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WUJ1-3; Sequence=VSP_045028;
CC -!- DOMAIN: The cytochrome b5 heme-binding domain was proven to bind heme,
CC although it lacks the conserved iron-binding His residues at position
CC 73 and 106. {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; AK172844; BAD18808.1; -; mRNA.
DR EMBL; AK313088; BAG35913.1; -; mRNA.
DR EMBL; AC087292; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90452.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90453.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90454.1; -; Genomic_DNA.
DR EMBL; BC020263; AAH20263.1; -; mRNA.
DR EMBL; BC051697; AAH51697.1; -; mRNA.
DR CCDS; CCDS11044.1; -. [Q8WUJ1-1]
DR CCDS; CCDS58501.1; -. [Q8WUJ1-3]
DR RefSeq; NP_001241684.1; NM_001254755.1. [Q8WUJ1-3]
DR RefSeq; NP_001241685.1; NM_001254756.1. [Q8WUJ1-3]
DR RefSeq; NP_653212.1; NM_144611.3. [Q8WUJ1-1]
DR RefSeq; XP_011521951.1; XM_011523649.2. [Q8WUJ1-3]
DR RefSeq; XP_016879669.1; XM_017024180.1. [Q8WUJ1-3]
DR RefSeq; XP_016879670.1; XM_017024181.1.
DR RefSeq; XP_016879671.1; XM_017024182.1. [Q8WUJ1-3]
DR AlphaFoldDB; Q8WUJ1; -.
DR SMR; Q8WUJ1; -.
DR BioGRID; 125902; 40.
DR IntAct; Q8WUJ1; 17.
DR STRING; 9606.ENSP00000301391; -.
DR iPTMnet; Q8WUJ1; -.
DR PhosphoSitePlus; Q8WUJ1; -.
DR BioMuta; CYB5D2; -.
DR DMDM; 74730719; -.
DR EPD; Q8WUJ1; -.
DR MassIVE; Q8WUJ1; -.
DR MaxQB; Q8WUJ1; -.
DR PaxDb; Q8WUJ1; -.
DR PeptideAtlas; Q8WUJ1; -.
DR PRIDE; Q8WUJ1; -.
DR ProteomicsDB; 46668; -.
DR ProteomicsDB; 74689; -. [Q8WUJ1-1]
DR Antibodypedia; 23235; 73 antibodies from 15 providers.
DR DNASU; 124936; -.
DR Ensembl; ENST00000301391.8; ENSP00000301391.4; ENSG00000167740.10. [Q8WUJ1-1]
DR Ensembl; ENST00000575251.5; ENSP00000458903.1; ENSG00000167740.10. [Q8WUJ1-3]
DR Ensembl; ENST00000577075.6; ENSP00000458352.2; ENSG00000167740.10. [Q8WUJ1-3]
DR GeneID; 124936; -.
DR KEGG; hsa:124936; -.
DR MANE-Select; ENST00000301391.8; ENSP00000301391.4; NM_144611.4; NP_653212.1.
DR UCSC; uc002fxl.6; human. [Q8WUJ1-1]
DR CTD; 124936; -.
DR DisGeNET; 124936; -.
DR GeneCards; CYB5D2; -.
DR HGNC; HGNC:28471; CYB5D2.
DR HPA; ENSG00000167740; Low tissue specificity.
DR neXtProt; NX_Q8WUJ1; -.
DR OpenTargets; ENSG00000167740; -.
DR PharmGKB; PA142672059; -.
DR VEuPathDB; HostDB:ENSG00000167740; -.
DR eggNOG; KOG1108; Eukaryota.
DR GeneTree; ENSGT00940000160156; -.
DR HOGENOM; CLU_065455_2_0_1; -.
DR InParanoid; Q8WUJ1; -.
DR OMA; GHKHYGP; -.
DR OrthoDB; 1355837at2759; -.
DR PhylomeDB; Q8WUJ1; -.
DR TreeFam; TF313943; -.
DR PathwayCommons; Q8WUJ1; -.
DR SignaLink; Q8WUJ1; -.
DR BioGRID-ORCS; 124936; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; CYB5D2; human.
DR GenomeRNAi; 124936; -.
DR Pharos; Q8WUJ1; Tbio.
DR PRO; PR:Q8WUJ1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8WUJ1; protein.
DR Bgee; ENSG00000167740; Expressed in kidney epithelium and 136 other tissues.
DR ExpressionAtlas; Q8WUJ1; baseline and differential.
DR Genevisible; Q8WUJ1; HS.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; 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 Alternative splicing; Neurogenesis; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..264
FT /note="Neuferricin"
FT /id="PRO_0000312321"
FT DOMAIN 35..134
FT /note="Cytochrome b5 heme-binding"
FT VAR_SEQ 1..112
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_045028"
FT VARIANT 7
FT /note="R -> G (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs200936057)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_037487"
FT VARIANT 7
FT /note="R -> P (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_037488"
SQ SEQUENCE 264 AA; 28690 MW; D2AD67455D053882 CRC64;
MLRCGGRGLL LGLAVAAAAV MAARLMGWWG PRAGFRLFIP EELSRYRGGP GDPGLYLALL
GRVYDVSSGR RHYEPGSHYS GFAGRDASRA FVTGDCSEAG LVDDVSDLSA AEMLTLHNWL
SFYEKNYVCV GRVTGRFYGE DGLPTPALTQ VEAAITRGLE ANKLQLQEKQ TFPPCNAEWS
SARGSRLWCS QKSGGVSRDW IGVPRKLYKP GAKEPRCVCV RTTGPPSGQM PDNPPHRNRG
DLDHPNLAEY TGCPPLAITC SFPL
