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Protein

Transmembrane glycoprotein NMB

Gene

GPNMB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • syndecan binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • bone mineralization Source: Ensembl
  • cell adhesion Source: GO_Central
  • 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 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
Complete GO annotation...

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

HGNCiHGNC:4462. GPNMB.

Subcellular locationi

Topology

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

GO - Cellular componenti

Complete GO annotation...

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).

Organism-specific databases

DisGeNETi10457.
OpenTargetsiENSG00000136235.
PharmGKBiPA28845.

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...)Sequence analysis1
Glycosylationi134N-linked (GlcNAc...)Sequence analysis1
Glycosylationi146N-linked (GlcNAc...)Sequence analysis1
Glycosylationi200N-linked (GlcNAc...)1 Publication1
Glycosylationi249N-linked (GlcNAc...)1 Publication1
Glycosylationi275N-linked (GlcNAc...)1 Publication1
Glycosylationi296N-linked (GlcNAc...)1 Publication1
Glycosylationi300N-linked (GlcNAc...)1 Publication1
Glycosylationi306N-linked (GlcNAc...)1 Publication1
Glycosylationi312N-linked (GlcNAc...)Sequence analysis1
Glycosylationi459N-linked (GlcNAc...)Sequence analysis1
Glycosylationi467N-linked (GlcNAc...)Sequence 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.

Organism-specific databases

HPAiCAB026224.
HPA044969.

Interactioni

GO - Molecular functioni

  • integrin binding Source: GO_Central
  • syndecan binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi115720. 5 interactors.
DIPiDIP-57606N.
IntActiQ14956. 1 interactor.
MINTiMINT-1192048.
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
Contains 1 PKD domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.670. 1 hit.
InterProiIPR022409. PKD/Chitinase_dom.
IPR000601. PKD_dom.
[Graphical view]
PfamiPF00801. PKD. 1 hit.
[Graphical view]
SMARTiSM00089. PKD. 1 hit.
[Graphical view]
SUPFAMiSSF49299. SSF49299. 1 hit.
PROSITEiPS50093. PKD. 1 hit.
[Graphical view]

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 rs755767733dbSNPEnsembl.1
Natural variantiVAR_012076195S → C.Corresponds to variant rs530436dbSNPEnsembl.1
Natural variantiVAR_012077197N → H.Corresponds to variant rs530413dbSNPEnsembl.1
Natural variantiVAR_050603294S → F.Corresponds to variant rs35499907dbSNPEnsembl.1
Natural variantiVAR_050604324P → L.Corresponds to variant rs35363287dbSNPEnsembl.1
Natural variantiVAR_036263531S → I in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_050605538S → R.Corresponds to variant rs35878037dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

3D structure databases

ProteinModelPortaliQ14956.
SMRiQ14956.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115720. 5 interactors.
DIPiDIP-57606N.
IntActiQ14956. 1 interactor.
MINTiMINT-1192048.
STRINGi9606.ENSP00000371420.

PTM databases

iPTMnetiQ14956.
PhosphoSitePlusiQ14956.

Polymorphism and mutation databases

BioMutaiGPNMB.
DMDMi61252504.

Proteomic databases

EPDiQ14956.
MaxQBiQ14956.
PaxDbiQ14956.
PeptideAtlasiQ14956.
PRIDEiQ14956.

Protocols and materials databases

DNASUi10457.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10457.
DisGeNETi10457.
GeneCardsiGPNMB.
HGNCiHGNC:4462. GPNMB.
HPAiCAB026224.
HPA044969.
MIMi604368. gene.
neXtProtiNX_Q14956.
OpenTargetsiENSG00000136235.
PharmGKBiPA28845.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-8857538. PTK6 promotes HIF1A stabilization.

Miscellaneous databases

ChiTaRSiGPNMB. human.
GeneWikiiGPNMB.
GenomeRNAii10457.
PROiQ14956.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136235.
CleanExiHS_GPNMB.
HS_NMB.
ExpressionAtlasiQ14956. baseline and differential.
GenevisibleiQ14956. HS.

Family and domain databases

Gene3Di2.60.40.670. 1 hit.
InterProiIPR022409. PKD/Chitinase_dom.
IPR000601. PKD_dom.
[Graphical view]
PfamiPF00801. PKD. 1 hit.
[Graphical view]
SMARTiSM00089. PKD. 1 hit.
[Graphical view]
SUPFAMiSSF49299. SSF49299. 1 hit.
PROSITEiPS50093. PKD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGPNMB_HUMAN
AccessioniPrimary (citable) accession number: Q14956
Secondary accession number(s): A4D155, Q6UVX1, Q8N1A1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 15, 2005
Last modified: November 30, 2016
This is version 136 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.