UniProtKB - Q14956 (GPNMB_HUMAN)
Protein
Transmembrane glycoprotein NMB
Gene
GPNMB
Organism
Homo sapiens (Human)
Status
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
- cell adhesion Source: GO_Central
- cell-cell signaling Source: ParkinsonsUK-UCL
- negative regulation of cell population 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
- 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
PathwayCommonsi | Q14956 |
Reactomei | R-HSA-8857538, PTK6 promotes HIF1A stabilization |
Names & Taxonomyi
Protein namesi | Recommended name: Transmembrane glycoprotein NMBAlternative name(s): Hematopoietic growth factor inducible neurokinin-1 type1 Publication |
Gene namesi | Name:GPNMB Synonyms:HGFIN1 Publication, NMB ORF Names:UNQ1725/PRO9925 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4462, GPNMB |
MIMi | 604368, gene |
neXtProti | NX_Q14956 |
VEuPathDBi | HostDB:ENSG00000136235.15 |
Subcellular locationi
Plasma membrane
- Cell membrane ; Single-pass type I membrane protein 2 Publications
Endosome
- Early endosome membrane 1 Publication; Single-pass type I membrane protein Curated
Other locations
- Melanosome membrane 2 Publications; Single-pass type I membrane protein Curated
Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV.1 Publication
Endosome
- early endosome membrane Source: UniProtKB-SubCell
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
- integral component of membrane Source: ParkinsonsUK-UCL
- melanosome membrane Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 23 – 498 | ExtracellularSequence analysisAdd BLAST | 476 | |
Transmembranei | 499 – 519 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 520 – 572 | CytoplasmicSequence analysisAdd BLAST | 53 |
Keywords - Cellular componenti
Cell membrane, Endosome, MembranePathology & Biotechi
Involvement in diseasei
Increased expression levels in glioblastoma multiforme biopsy samples correlate with poor patient survival prognosis (PubMed:16609006). Has been proposed as a potential target for antibodies coupled to cytotoxic drugs in the context of cancer immunotherapy, including that of melanoma (PubMed:16489096).2 Publications
Amyloidosis, primary localized cutaneous, 3 (PLCA3)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins. PLCA3 inheritance is autosomal recessive.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080643 | 189 – 572 | Missing in PLCA3; may be expressed at much lower levels than wild-type protein; mislocalized to the endoplasmic reticulum and nuclear envelope. 1 PublicationAdd BLAST | 384 | |
Natural variantiVAR_080644 | 220 – 572 | Missing in PLCA3. 1 PublicationAdd BLAST | 353 |
Keywords - Diseasei
Amyloidosis, Disease variantOrganism-specific databases
DisGeNETi | 10457 |
MalaCardsi | GPNMB |
MIMi | 617920, phenotype |
OpenTargetsi | ENSG00000136235 |
Orphaneti | 319635, Amyloidosis cutis dyschromia |
PharmGKBi | PA28845 |
Miscellaneous databases
Pharosi | Q14956, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3712919 |
DrugBanki | DB05996, Glembatumumab vedotin |
Genetic variation databases
BioMutai | GPNMB |
DMDMi | 61252504 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
ChainiPRO_0000024709 | 23 – 572 | Transmembrane glycoprotein NMBAdd BLAST | 550 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 93 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 134 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 146 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 200 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 249 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 275 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 296 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 300 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 306 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 312 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 459 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 467 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 542 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
EPDi | Q14956 |
jPOSTi | Q14956 |
MassIVEi | Q14956 |
MaxQBi | Q14956 |
PaxDbi | Q14956 |
PeptideAtlasi | Q14956 |
PRIDEi | Q14956 |
ProteomicsDBi | 60258 [Q14956-1] 60259 [Q14956-2] |
PTM databases
GlyConnecti | 1847, 27 N-Linked glycans (4 sites) |
GlyGeni | Q14956, 13 sites, 1 O-linked glycan (1 site) |
iPTMneti | Q14956 |
PhosphoSitePlusi | Q14956 |
Expressioni
Tissue specificityi
Widely expressed, but very low expression, if any, in the brain (PubMed:12609765, PubMed:16609006). Expressed in the epidermis with higher levels in melanocytes compared with keratinocytes and Langerhans cells (at protein level) (PubMed:29336782). Expressed in peripheral blood, but not bone marrow mononuclear cells (PubMed:12609765). Expressed 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) (PubMed:16489096). May be overexpressed in various cancers, including melanoma and glioblastoma multiforme (PubMed:7814155, PubMed:16489096, PubMed:16609006).5 Publications
Inductioni
Up-regulated by G-CSF/CSF3 and M-CSF/CSF1 in bone marrow mononuclear cells, hence up-regulation may be linked to differentiation.1 Publication
Gene expression databases
Bgeei | ENSG00000136235, Expressed in visceral pleura and 240 other tissues |
ExpressionAtlasi | Q14956, baseline and differential |
Genevisiblei | Q14956, HS |
Organism-specific databases
HPAi | ENSG00000136235, Tissue enhanced (adipose) |
Interactioni
Binary interactionsi
Hide detailsQ14956
With | #Exp. | IntAct |
---|---|---|
EGFR [P00533] | 3 | EBI-7250369,EBI-297353 |
Isoform 1 [Q14956-1]
With | #Exp. | IntAct |
---|---|---|
EGFR [P00533] | 2 | EBI-16191078,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
BioGRIDi | 115720, 12 interactors |
DIPi | DIP-57606N |
IntActi | Q14956, 6 interactors |
MINTi | Q14956 |
STRINGi | 9606.ENSP00000371420 |
Miscellaneous databases
RNActi | Q14956, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 240 – 327 | PKDPROSITE-ProRule annotationAdd BLAST | 88 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 64 – 66 | Cell attachment siteSequence analysis | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 320 – 332 | Poly-ProAdd BLAST | 13 |
Sequence similaritiesi
Belongs to the PMEL/NMB family.Curated
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QVWX, Eukaryota |
GeneTreei | ENSGT00950000183188 |
HOGENOMi | CLU_017264_1_0_1 |
InParanoidi | Q14956 |
OMAi | CWKGGRV |
OrthoDBi | 833491at2759 |
PhylomeDBi | Q14956 |
TreeFami | TF334865 |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR013783, Ig-like_fold IPR022409, PKD/Chitinase_dom IPR000601, PKD_dom IPR035986, PKD_dom_sf |
Pfami | View protein in Pfam PF00801, PKD, 1 hit |
SMARTi | View protein in SMART SM00089, PKD, 1 hit |
SUPFAMi | SSF49299, SSF49299, 1 hit |
PROSITEi | View protein in PROSITE PS50093, PKD, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q14956-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A3B3ISS6 | A0A3B3ISS6_HUMAN | Transmembrane glycoprotein NMB | GPNMB | 588 | Annotation score: | ||
Q96F58 | Q96F58_HUMAN | GPNMB protein | GPNMB hCG_37976 | 206 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 354 | A → T in AAQ89481 (PubMed:12975309).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_036262 | 110 | A → D in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs755767733Ensembl. | 1 | |
Natural variantiVAR_080643 | 189 – 572 | Missing in PLCA3; may be expressed at much lower levels than wild-type protein; mislocalized to the endoplasmic reticulum and nuclear envelope. 1 PublicationAdd BLAST | 384 | |
Natural variantiVAR_012076 | 195 | S → C. Corresponds to variant dbSNP:rs530436Ensembl. | 1 | |
Natural variantiVAR_012077 | 197 | N → H. Corresponds to variant dbSNP:rs530413Ensembl. | 1 | |
Natural variantiVAR_080644 | 220 – 572 | Missing in PLCA3. 1 PublicationAdd BLAST | 353 | |
Natural variantiVAR_050603 | 294 | S → F1 PublicationCorresponds to variant dbSNP:rs35499907Ensembl. | 1 | |
Natural variantiVAR_050604 | 324 | P → L. Corresponds to variant dbSNP:rs35363287EnsemblClinVar. | 1 | |
Natural variantiVAR_036263 | 531 | S → I in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_050605 | 538 | S → R. Corresponds to variant dbSNP:rs35878037Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013001 | 340 – 351 | Missing in isoform 2. 2 PublicationsAdd BLAST | 12 |
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 |
CCDSi | CCDS34610.1 [Q14956-1] CCDS5380.1 [Q14956-2] |
PIRi | I38065 |
RefSeqi | NP_001005340.1, NM_001005340.1 [Q14956-1] NP_002501.1, NM_002510.2 [Q14956-2] |
Genome annotation databases
Ensembli | ENST00000258733; ENSP00000258733; ENSG00000136235 [Q14956-2] ENST00000381990; ENSP00000371420; ENSG00000136235 [Q14956-1] |
GeneIDi | 10457 |
KEGGi | hsa:10457 |
UCSCi | uc003swb.4, human [Q14956-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS34610.1 [Q14956-1] CCDS5380.1 [Q14956-2] |
PIRi | I38065 |
RefSeqi | NP_001005340.1, NM_001005340.1 [Q14956-1] NP_002501.1, NM_002510.2 [Q14956-2] |
3D structure databases
SMRi | Q14956 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 115720, 12 interactors |
DIPi | DIP-57606N |
IntActi | Q14956, 6 interactors |
MINTi | Q14956 |
STRINGi | 9606.ENSP00000371420 |
Chemistry databases
ChEMBLi | CHEMBL3712919 |
DrugBanki | DB05996, Glembatumumab vedotin |
PTM databases
GlyConnecti | 1847, 27 N-Linked glycans (4 sites) |
GlyGeni | Q14956, 13 sites, 1 O-linked glycan (1 site) |
iPTMneti | Q14956 |
PhosphoSitePlusi | Q14956 |
Genetic variation databases
BioMutai | GPNMB |
DMDMi | 61252504 |
Proteomic databases
EPDi | Q14956 |
jPOSTi | Q14956 |
MassIVEi | Q14956 |
MaxQBi | Q14956 |
PaxDbi | Q14956 |
PeptideAtlasi | Q14956 |
PRIDEi | Q14956 |
ProteomicsDBi | 60258 [Q14956-1] 60259 [Q14956-2] |
Protocols and materials databases
ABCDi | Q14956, 1 sequenced antibody |
Antibodypediai | 12086, 430 antibodies |
DNASUi | 10457 |
Genome annotation databases
Ensembli | ENST00000258733; ENSP00000258733; ENSG00000136235 [Q14956-2] ENST00000381990; ENSP00000371420; ENSG00000136235 [Q14956-1] |
GeneIDi | 10457 |
KEGGi | hsa:10457 |
UCSCi | uc003swb.4, human [Q14956-1] |
Organism-specific databases
CTDi | 10457 |
DisGeNETi | 10457 |
GeneCardsi | GPNMB |
HGNCi | HGNC:4462, GPNMB |
HPAi | ENSG00000136235, Tissue enhanced (adipose) |
MalaCardsi | GPNMB |
MIMi | 604368, gene 617920, phenotype |
neXtProti | NX_Q14956 |
OpenTargetsi | ENSG00000136235 |
Orphaneti | 319635, Amyloidosis cutis dyschromia |
PharmGKBi | PA28845 |
VEuPathDBi | HostDB:ENSG00000136235.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QVWX, Eukaryota |
GeneTreei | ENSGT00950000183188 |
HOGENOMi | CLU_017264_1_0_1 |
InParanoidi | Q14956 |
OMAi | CWKGGRV |
OrthoDBi | 833491at2759 |
PhylomeDBi | Q14956 |
TreeFami | TF334865 |
Enzyme and pathway databases
PathwayCommonsi | Q14956 |
Reactomei | R-HSA-8857538, PTK6 promotes HIF1A stabilization |
Miscellaneous databases
BioGRID-ORCSi | 10457, 7 hits in 987 CRISPR screens |
ChiTaRSi | GPNMB, human |
GeneWikii | GPNMB |
GenomeRNAii | 10457 |
Pharosi | Q14956, Tbio |
PROi | PR:Q14956 |
RNActi | Q14956, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136235, Expressed in visceral pleura and 240 other tissues |
ExpressionAtlasi | Q14956, baseline and differential |
Genevisiblei | Q14956, HS |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR013783, Ig-like_fold IPR022409, PKD/Chitinase_dom IPR000601, PKD_dom IPR035986, PKD_dom_sf |
Pfami | View protein in Pfam PF00801, PKD, 1 hit |
SMARTi | View protein in SMART SM00089, PKD, 1 hit |
SUPFAMi | SSF49299, SSF49299, 1 hit |
PROSITEi | View protein in PROSITE PS50093, PKD, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GPNMB_HUMAN | |
Accessioni | Q14956Primary (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: | April 7, 2021 | |
This is version 169 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families