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Protein

Transmembrane glycoprotein NMB

Gene

GPNMB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Could be a melanogenic enzyme.By similarity

GO - Molecular functioni

  • chemoattractant activity Source: ParkinsonsUK-UCL
  • heparin binding Source: ParkinsonsUK-UCL
  • integrin binding Source: GO_Central
  • receptor ligand activity Source: ParkinsonsUK-UCL
  • syndecan binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • bone mineralization Source: Ensembl
  • cell adhesion Source: Ensembl
  • cell-cell signaling Source: ParkinsonsUK-UCL
  • negative regulation of cell proliferation Source: ProtInc
  • negative regulation of cytokine production Source: ParkinsonsUK-UCL
  • negative regulation of G1/S transition of mitotic cell cycle Source: ParkinsonsUK-UCL
  • negative regulation of neuron death Source: ParkinsonsUK-UCL
  • negative regulation of T cell activation Source: ParkinsonsUK-UCL
  • negative regulation of T cell proliferation Source: ParkinsonsUK-UCL
  • negative regulation of tumor necrosis factor production Source: Ensembl
  • osteoblast differentiation Source: Ensembl
  • positive chemotaxis Source: ParkinsonsUK-UCL
  • positive regulation of cell migration Source: ParkinsonsUK-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: ParkinsonsUK-UCL
  • positive regulation of protein autophosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of protein phosphorylation Source: ParkinsonsUK-UCL
  • regulation of angiogenesis Source: ParkinsonsUK-UCL
  • regulation of tissue remodeling Source: ParkinsonsUK-UCL
  • signal transduction Source: ParkinsonsUK-UCL

Enzyme and pathway databases

ReactomeiR-HSA-8857538 PTK6 promotes HIF1A stabilization

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane glycoprotein NMB
Alternative name(s):
Transmembrane glycoprotein HGFIN
Gene namesi
Name:GPNMB
Synonyms:HGFIN, NMB
ORF Names:UNQ1725/PRO9925
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000136235.15
HGNCiHGNC:4462 GPNMB
MIMi604368 gene
neXtProtiNX_Q14956

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 486ExtracellularSequence analysisAdd BLAST465
Transmembranei487 – 507HelicalSequence analysisAdd BLAST21
Topological domaini508 – 572CytoplasmicSequence analysisAdd BLAST65

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Glioblastoma multiforme patients that exhibit increased mRNA and protein levels (>3-fold over normal brain) in biopsy samples have a significantly higher risk of death (PubMed:16609006). In the context of cancer immunotherapy, including that of melanoma, has been proposed to be used as a cell surface protein antigen targeted by antibodies coupled to cytotoxic drugs (PubMed:16489096).2 Publications

Organism-specific databases

DisGeNETi10457
OpenTargetsiENSG00000136235
PharmGKBiPA28845

Chemistry databases

ChEMBLiCHEMBL3712919

Polymorphism and mutation databases

BioMutaiGPNMB
DMDMi61252504

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000002470922 – 572Transmembrane glycoprotein NMBAdd BLAST551

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi93N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi134N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi146N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi200N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi249N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi275N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi296N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi300N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi306N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi312N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi459N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi467N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei542PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ14956
MaxQBiQ14956
PaxDbiQ14956
PeptideAtlasiQ14956
PRIDEiQ14956

PTM databases

iPTMnetiQ14956
PhosphoSitePlusiQ14956

Expressioni

Tissue specificityi

Up-regulated in various cancer cells, including in glioblastoma multiforme. Expressed in many melanoma cells, as well as in tissue macrophages, including liver Kuppfer cells and lung alveolar macrophages, in podocytes and in some cells of the ciliary body of the eye (at protein level). Hardly detectable in healthy brain.3 Publications

Gene expression databases

BgeeiENSG00000136235
CleanExiHS_GPNMB
HS_NMB
ExpressionAtlasiQ14956 baseline and differential
GenevisibleiQ14956 HS

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
EGFRP005333EBI-7250369,EBI-297353

GO - Molecular functioni

  • chemoattractant activity Source: ParkinsonsUK-UCL
  • integrin binding Source: GO_Central
  • receptor ligand activity Source: ParkinsonsUK-UCL
  • syndecan binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi115720, 7 interactors
DIPiDIP-57606N
IntActiQ14956, 4 interactors
MINTiQ14956
STRINGi9606.ENSP00000371420

Structurei

3D structure databases

ProteinModelPortaliQ14956
SMRiQ14956
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini240 – 327PKDPROSITE-ProRule annotationAdd BLAST88

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi64 – 66Cell attachment siteSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi320 – 332Poly-ProAdd BLAST13

Sequence similaritiesi

Belongs to the PMEL/NMB family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IE9P Eukaryota
ENOG4110Q2V LUCA
GeneTreeiENSGT00530000063573
HOGENOMiHOG000252941
HOVERGENiHBG051797
InParanoidiQ14956
KOiK20732
OMAiNFGDNTG
OrthoDBiEOG091G072N
PhylomeDBiQ14956
TreeFamiTF334865

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR013783 Ig-like_fold
IPR022409 PKD/Chitinase_dom
IPR000601 PKD_dom
IPR035986 PKD_dom_sf
PfamiView protein in Pfam
PF00801 PKD, 1 hit
SMARTiView protein in SMART
SM00089 PKD, 1 hit
SUPFAMiSSF49299 SSF49299, 1 hit
PROSITEiView protein in PROSITE
PS50093 PKD, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14956-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MECLYYFLGF LLLAARLPLD AAKRFHDVLG NERPSAYMRE HNQLNGWSSD
60 70 80 90 100
ENDWNEKLYP VWKRGDMRWK NSWKGGRVQA VLTSDSPALV GSNITFAVNL
110 120 130 140 150
IFPRCQKEDA NGNIVYEKNC RNEAGLSADP YVYNWTAWSE DSDGENGTGQ
160 170 180 190 200
SHHNVFPDGK PFPHHPGWRR WNFIYVFHTL GQYFQKLGRC SVRVSVNTAN
210 220 230 240 250
VTLGPQLMEV TVYRRHGRAY VPIAQVKDVY VVTDQIPVFV TMFQKNDRNS
260 270 280 290 300
SDETFLKDLP IMFDVLIHDP SHFLNYSTIN YKWSFGDNTG LFVSTNHTVN
310 320 330 340 350
HTYVLNGTFS LNLTVKAAAP GPCPPPPPPP RPSKPTPSLA TTLKSYDSNT
360 370 380 390 400
PGPAGDNPLE LSRIPDENCQ INRYGHFQAT ITIVEGILEV NIIQMTDVLM
410 420 430 440 450
PVPWPESSLI DFVVTCQGSI PTEVCTIISD PTCEITQNTV CSPVDVDEMC
460 470 480 490 500
LLTVRRTFNG SGTYCVNLTL GDDTSLALTS TLISVPDRDP ASPLRMANSA
510 520 530 540 550
LISVGCLAIF VTVISLLVYK KHKEYNPIEN SPGNVVRSKG LSVFLNRAKA
560 570
VFFPGNQEKD PLLKNQEFKG VS
Length:572
Mass (Da):63,923
Last modified:March 15, 2005 - v2
Checksum:i2465C12C2F0F3996
GO
Isoform 2 (identifier: Q14956-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     340-351: Missing.

Show »
Length:560
Mass (Da):62,643
Checksum:i570035B48CCE3ECC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti354A → T in AAQ89481 (PubMed:12975309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036262110A → D in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs755767733Ensembl.1
Natural variantiVAR_012076195S → C. Corresponds to variant dbSNP:rs530436Ensembl.1
Natural variantiVAR_012077197N → H. Corresponds to variant dbSNP:rs530413Ensembl.1
Natural variantiVAR_050603294S → F. Corresponds to variant dbSNP:rs35499907Ensembl.1
Natural variantiVAR_050604324P → L. Corresponds to variant dbSNP:rs35363287Ensembl.1
Natural variantiVAR_036263531S → I in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_050605538S → R. Corresponds to variant dbSNP:rs35878037Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013001340 – 351Missing in isoform 2. 2 PublicationsAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76534 mRNA Translation: CAA54044.1
AF322909 mRNA Translation: AAG42839.1
AY359124 mRNA Translation: AAQ89481.1
AC005082 Genomic DNA Translation: AAP22336.1
CH236948 Genomic DNA Translation: EAL24259.1
CH471073 Genomic DNA Translation: EAW93782.1
BC032783 mRNA Translation: AAH32783.1
CCDSiCCDS34610.1 [Q14956-1]
CCDS5380.1 [Q14956-2]
PIRiI38065
RefSeqiNP_001005340.1, NM_001005340.1 [Q14956-1]
NP_002501.1, NM_002510.2 [Q14956-2]
UniGeneiHs.190495

Genome annotation databases

EnsembliENST00000258733; ENSP00000258733; ENSG00000136235 [Q14956-2]
ENST00000381990; ENSP00000371420; ENSG00000136235 [Q14956-1]
GeneIDi10457
KEGGihsa:10457
UCSCiuc003swb.4 human [Q14956-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGPNMB_HUMAN
AccessioniPrimary (citable) accession number: Q14956
Secondary accession number(s): A4D155, Q6UVX1, Q8N1A1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 15, 2005
Last modified: March 28, 2018
This is version 148 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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