NMB_HUMAN
ID NMB_HUMAN Reviewed; 121 AA.
AC P08949; Q96A06; Q96HH5;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 4.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Neuromedin-B;
DE Contains:
DE RecName: Full=Neuromedin-B-32;
DE Contains:
DE RecName: Full=Neuromedin-B;
DE Flags: Precursor;
GN Name=NMB;
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] (ISOFORM 1).
RC TISSUE=Hypothalamus;
RX PubMed=2458345; DOI=10.1016/s0021-9258(18)37707-x;
RA Krane I.M., Naylor S.L., Helin-Davis D., Chin W.W., Spindel E.R.;
RT "Molecular cloning of cDNAs encoding the human bombesin-like peptide
RT neuromedin B. Chromosomal localization and comparison to cDNAs encoding its
RT amphibian homolog ranatensin.";
RL J. Biol. Chem. 263:13317-13323(1988).
RN [2]
RP ERRATUM OF PUBMED:2458345, AND SEQUENCE REVISION.
RA Krane I.M., Naylor S.L., Helin-Davis D., Chin W.W., Spindel E.R.;
RL J. Biol. Chem. 265:7091-7091(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP THR-73.
RC TISSUE=Brain, and Ovary;
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 FUNCTION, AND INDUCTION.
RX PubMed=31601264; DOI=10.1186/s13567-019-0695-2;
RA Yang G., Huang H., Tang M., Cai Z., Huang C., Qi B., Chen J.L.;
RT "Role of neuromedin B and its receptor in the innate immune responses
RT against influenza A virus infection in vitro and in vivo.";
RL Vet. Res. 50:80-80(2019).
RN [6]
RP STRUCTURE BY NMR OF 47-56.
RX PubMed=10544247; DOI=10.1016/s0014-5793(99)01346-0;
RA Lee S., Kim Y.;
RT "Solution structure of neuromedin B by (1)H nuclear magnetic resonance
RT spectroscopy.";
RL FEBS Lett. 460:263-269(1999).
CC -!- FUNCTION: Stimulates smooth muscle contraction (By similarity). Induces
CC sighing by acting directly on the pre-Botzinger complex, a cluster of
CC several thousand neurons in the ventrolateral medulla responsible for
CC inspiration during respiratory activity (By similarity). Contributes to
CC the induction of sneezing following exposure to chemical irritants or
CC allergens which causes release of NMB by nasal sensory neurons and
CC activation of NMBR-expressing neurons in the sneeze-evoking region of
CC the brainstem (By similarity). These in turn activate neurons of the
CC caudal ventral respiratory group, giving rise to the sneezing response
CC (By similarity). Contributes to induction of acute itch, possibly
CC through activation of the NMBR receptor on dorsal root ganglion neurons
CC (By similarity). Increases expression of NMBR and steroidogenic
CC mediators STAR, CYP11A1 and HSD3B1 in Leydig cells, induces secretion
CC of testosterone by Leydig cells and also promotes Leydig cell
CC proliferation (By similarity). Plays a role in the innate immune
CC response to influenza A virus infection by enhancing interferon alpha
CC expression and reducing expression of IL6 (PubMed:31601264). Plays a
CC role in CSF1-induced proliferation of osteoclast precursors by
CC contributing to the positive regulation of the expression of the CSF1
CC receptor CSF1R (By similarity). {ECO:0000250|UniProtKB:P01297,
CC ECO:0000250|UniProtKB:Q9CR53, ECO:0000269|PubMed:31601264}.
CC -!- INTERACTION:
CC P08949; Q13490: BIRC2; NbExp=3; IntAct=EBI-7964376, EBI-514538;
CC P08949-2; Q13490: BIRC2; NbExp=6; IntAct=EBI-12302085, EBI-514538;
CC P08949-2; O95257: GADD45G; NbExp=3; IntAct=EBI-12302085, EBI-448202;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9CR53}. Cell
CC projection, neuron projection {ECO:0000250|UniProtKB:Q9CR53}. Note=In
CC neurons of the retrotrapezoid nucleus//parafacial respiratory group,
CC expressed on neuron projections which project into the pre-Botzinger
CC complex. {ECO:0000250|UniProtKB:Q9CR53}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P08949-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08949-2; Sequence=VSP_000548;
CC -!- INDUCTION: Up-regulated in response to infection with influenza A
CC virus. {ECO:0000269|PubMed:31601264}.
CC -!- SIMILARITY: Belongs to the bombesin/neuromedin-B/ranatensin family.
CC {ECO:0000305}.
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DR EMBL; M21551; AAA59934.1; -; mRNA.
DR EMBL; AC048382; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007407; AAH07407.1; -; mRNA.
DR EMBL; BC007431; AAH07431.1; -; mRNA.
DR EMBL; BC008603; AAH08603.1; -; mRNA.
DR CCDS; CCDS10332.1; -. [P08949-1]
DR CCDS; CCDS42076.1; -. [P08949-2]
DR PIR; A28945; A28945.
DR RefSeq; NP_066563.2; NM_021077.3. [P08949-1]
DR RefSeq; NP_995580.1; NM_205858.1. [P08949-2]
DR PDB; 1C98; NMR; -; A=47-56.
DR PDB; 1C9A; NMR; -; A=47-56.
DR PDBsum; 1C98; -.
DR PDBsum; 1C9A; -.
DR AlphaFoldDB; P08949; -.
DR SMR; P08949; -.
DR BioGRID; 110892; 33.
DR IntAct; P08949; 4.
DR MINT; P08949; -.
DR STRING; 9606.ENSP00000378089; -.
DR iPTMnet; P08949; -.
DR PhosphoSitePlus; P08949; -.
DR BioMuta; NMB; -.
DR DMDM; 281185514; -.
DR MassIVE; P08949; -.
DR PaxDb; P08949; -.
DR PeptideAtlas; P08949; -.
DR PRIDE; P08949; -.
DR ProteomicsDB; 52178; -. [P08949-1]
DR ProteomicsDB; 52179; -. [P08949-2]
DR TopDownProteomics; P08949-2; -. [P08949-2]
DR Antibodypedia; 43613; 159 antibodies from 27 providers.
DR DNASU; 4828; -.
DR Ensembl; ENST00000360476.8; ENSP00000353664.3; ENSG00000197696.10. [P08949-1]
DR Ensembl; ENST00000394588.3; ENSP00000378089.3; ENSG00000197696.10. [P08949-2]
DR GeneID; 4828; -.
DR KEGG; hsa:4828; -.
DR MANE-Select; ENST00000360476.8; ENSP00000353664.3; NM_021077.4; NP_066563.2.
DR UCSC; uc002bkz.4; human. [P08949-1]
DR CTD; 4828; -.
DR DisGeNET; 4828; -.
DR GeneCards; NMB; -.
DR HGNC; HGNC:7842; NMB.
DR HPA; ENSG00000197696; Tissue enhanced (adipose tissue, brain).
DR MIM; 162340; gene.
DR neXtProt; NX_P08949; -.
DR OpenTargets; ENSG00000197696; -.
DR PharmGKB; PA31654; -.
DR VEuPathDB; HostDB:ENSG00000197696; -.
DR eggNOG; ENOG502S66V; Eukaryota.
DR GeneTree; ENSGT00940000154470; -.
DR HOGENOM; CLU_136527_0_0_1; -.
DR InParanoid; P08949; -.
DR OMA; NTAEMIP; -.
DR OrthoDB; 1517178at2759; -.
DR PhylomeDB; P08949; -.
DR TreeFam; TF336860; -.
DR PathwayCommons; P08949; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P08949; -.
DR SIGNOR; P08949; -.
DR BioGRID-ORCS; 4828; 8 hits in 1064 CRISPR screens.
DR ChiTaRS; NMB; human.
DR EvolutionaryTrace; P08949; -.
DR GenomeRNAi; 4828; -.
DR Pharos; P08949; Tbio.
DR PRO; PR:P08949; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P08949; protein.
DR Bgee; ENSG00000197696; Expressed in type B pancreatic cell and 149 other tissues.
DR Genevisible; P08949; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0005179; F:hormone activity; TAS:ProtInc.
DR GO; GO:0031710; F:neuromedin B receptor binding; IBA:GO_Central.
DR GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR GO; GO:0140374; P:antiviral innate immune response; ISS:UniProtKB.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0160024; P:Leydig cell proliferation; ISS:UniProtKB.
DR GO; GO:0046888; P:negative regulation of hormone secretion; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IEA:InterPro.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0046887; P:positive regulation of hormone secretion; IBA:GO_Central.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0090290; P:positive regulation of osteoclast proliferation; ISS:UniProtKB.
DR GO; GO:1903942; P:positive regulation of respiratory gaseous exchange; ISS:UniProtKB.
DR GO; GO:2000845; P:positive regulation of testosterone secretion; ISS:UniProtKB.
DR GO; GO:0160025; P:sensory perception of itch; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0160023; P:sneeze reflex; ISS:UniProtKB.
DR InterPro; IPR000874; Bombesin.
DR PANTHER; PTHR16866; PTHR16866; 1.
DR Pfam; PF02044; Bombesin; 1.
DR PROSITE; PS00257; BOMBESIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amidation; Cell projection;
KW Cleavage on pair of basic residues; Immunity; Innate immunity;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000250|UniProtKB:P01297"
FT PEPTIDE 25..56
FT /note="Neuromedin-B-32"
FT /evidence="ECO:0000250|UniProtKB:P01297"
FT /id="PRO_0000003017"
FT PEPTIDE 47..56
FT /note="Neuromedin-B"
FT /evidence="ECO:0000250|UniProtKB:P01297"
FT /id="PRO_0000003018"
FT PROPEP 60..121
FT /evidence="ECO:0000250|UniProtKB:P01297"
FT /id="PRO_0000003019"
FT MOD_RES 56
FT /note="Methionine amide"
FT /evidence="ECO:0000250|UniProtKB:P01297"
FT VAR_SEQ 111..121
FT /note="YRRLLVQILQK -> EAAGTNTAEMTPIMGQTQQRGLDCAHPGKVLNGTLLM
FT APSGCKS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000548"
FT VARIANT 73
FT /note="P -> T (in dbSNP:rs1051168)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060369"
FT CONFLICT 68..76
FT /note="PLGTAPHTS -> HWGQLPTPP (in Ref. 1; AAA59934)"
FT /evidence="ECO:0000305"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:1C98"
SQ SEQUENCE 121 AA; 13252 MW; 10E16BA4886F03FB CRC64;
MARRAGGARM FGSLLLFALL AAGVAPLSWD LPEPRSRASK IRVHSRGNLW ATGHFMGKKS
LEPSSPSPLG TAPHTSLRDQ RLQLSHDLLG ILLLKKALGV SLSRPAPQIQ YRRLLVQILQ
K
