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Q14956 (GPNMB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane glycoprotein NMB
Alternative name(s):
Transmembrane glycoprotein HGFIN
Gene names
Name:GPNMB
Synonyms:HGFIN, NMB
ORF Names:UNQ1725/PRO9925
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length572 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Could be a melanogenic enzyme By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Detected at the cell surface in different types of cancers cells, including glioblastoma multiforme cells and most melanoma cell lines. Ref.8 Ref.9 Ref.10 Ref.11

Tissue specificity

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. Ref.1 Ref.9 Ref.10

Involvement in disease

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 (Ref.10). 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 (Ref.9). Ref.9 Ref.10

Sequence similarities

Belongs to the PMEL/NMB family.

Contains 1 PKD domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14956-1)

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.
Isoform 2 (identifier: Q14956-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 572551Transmembrane glycoprotein NMB
PRO_0000024709

Regions

Topological domain22 – 486465Extracellular Potential
Transmembrane487 – 50721Helical; Potential
Topological domain508 – 57265Cytoplasmic Potential
Domain240 – 32788PKD
Motif64 – 663Cell attachment site Potential
Compositional bias320 – 33213Poly-Pro

Amino acid modifications

Modified residue5421Phosphoserine By similarity
Glycosylation931N-linked (GlcNAc...) Potential
Glycosylation1341N-linked (GlcNAc...) Potential
Glycosylation1461N-linked (GlcNAc...) Potential
Glycosylation2001N-linked (GlcNAc...) Ref.12
Glycosylation2491N-linked (GlcNAc...) Ref.12
Glycosylation2751N-linked (GlcNAc...) Ref.12
Glycosylation2961N-linked (GlcNAc...) Ref.12
Glycosylation3001N-linked (GlcNAc...) Ref.12
Glycosylation3061N-linked (GlcNAc...) Ref.12
Glycosylation3121N-linked (GlcNAc...) Potential
Glycosylation4591N-linked (GlcNAc...) Potential
Glycosylation4671N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence340 – 35112Missing in isoform 2.
VSP_013001
Natural variant1101A → D in a breast cancer sample; somatic mutation. Ref.13
VAR_036262
Natural variant1951S → C.
Corresponds to variant rs530436 [ dbSNP | Ensembl ].
VAR_012076
Natural variant1971N → H.
Corresponds to variant rs530413 [ dbSNP | Ensembl ].
VAR_012077
Natural variant2941S → F.
Corresponds to variant rs35499907 [ dbSNP | Ensembl ].
VAR_050603
Natural variant3241P → L.
Corresponds to variant rs35363287 [ dbSNP | Ensembl ].
VAR_050604
Natural variant5311S → I in a breast cancer sample; somatic mutation. Ref.13
VAR_036263
Natural variant5381S → R.
Corresponds to variant rs35878037 [ dbSNP | Ensembl ].
VAR_050605

Experimental info

Sequence conflict3541A → T in AAQ89481. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 15, 2005. Version 2.
Checksum: 2465C12C2F0F3996

FASTA57263,923
        10         20         30         40         50         60 
MECLYYFLGF LLLAARLPLD AAKRFHDVLG NERPSAYMRE HNQLNGWSSD ENDWNEKLYP 

        70         80         90        100        110        120 
VWKRGDMRWK NSWKGGRVQA VLTSDSPALV GSNITFAVNL IFPRCQKEDA NGNIVYEKNC 

       130        140        150        160        170        180 
RNEAGLSADP YVYNWTAWSE DSDGENGTGQ SHHNVFPDGK PFPHHPGWRR WNFIYVFHTL 

       190        200        210        220        230        240 
GQYFQKLGRC SVRVSVNTAN VTLGPQLMEV TVYRRHGRAY VPIAQVKDVY VVTDQIPVFV 

       250        260        270        280        290        300 
TMFQKNDRNS SDETFLKDLP IMFDVLIHDP SHFLNYSTIN YKWSFGDNTG LFVSTNHTVN 

       310        320        330        340        350        360 
HTYVLNGTFS LNLTVKAAAP GPCPPPPPPP RPSKPTPSLA TTLKSYDSNT PGPAGDNPLE 

       370        380        390        400        410        420 
LSRIPDENCQ INRYGHFQAT ITIVEGILEV NIIQMTDVLM PVPWPESSLI DFVVTCQGSI 

       430        440        450        460        470        480 
PTEVCTIISD PTCEITQNTV CSPVDVDEMC LLTVRRTFNG SGTYCVNLTL GDDTSLALTS 

       490        500        510        520        530        540 
TLISVPDRDP ASPLRMANSA LISVGCLAIF VTVISLLVYK KHKEYNPIEN SPGNVVRSKG 

       550        560        570 
LSVFLNRAKA VFFPGNQEKD PLLKNQEFKG VS 

« Hide

Isoform 2 [UniParc].

Checksum: 570035B48CCE3ECC
Show »

FASTA56062,643

References

« Hide 'large scale' references
[1]"NMB, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts."
Weterman M.A.J., Ajubi N., van Dinter I.M.R., Degen W.G.J., van Muijen G.N.P., Ruiter D.J., Bloemers H.P.J.
Int. J. Cancer 60:73-81(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Tissue: Melanoma.
[2]"Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane protein that is similar to neurokinin 1 interacts with substance P."
Bandari P.S., Qian J., Yehia G., Joshi D.D., Maloof P.B., Potian J., Oh H.S., Gascon P., Harrison J.S., Rameshwar P.
Regul. Pept. 111:169-178(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Peripheral blood.
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[8]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[9]"CR011, a fully human monoclonal antibody-auristatin E conjugate, for the treatment of melanoma."
Tse K.F., Jeffers M., Pollack V.A., McCabe D.A., Shadish M.L., Khramtsov N.V., Hackett C.S., Shenoy S.G., Kuang B., Boldog F.L., MacDougall J.R., Rastelli L., Herrmann J., Gallo M., Gazit-Bornstein G., Senter P.D., Meyer D.L., Lichenstein H.S., LaRochelle W.J.
Clin. Cancer Res. 12:1373-1382(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, ALTERNATIVE SPLICING, POTENTIAL TUMOR-ASSOCIATED ANTIGEN FOR IMMUNOTHERAPY, DISEASE.
[10]"Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme."
Kuan C.T., Wakiya K., Dowell J.M., Herndon J.E. II, Reardon D.A., Graner M.W., Riggins G.J., Wikstrand C.J., Bigner D.D.
Clin. Cancer Res. 12:1970-1982(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING, DISEASE.
[11]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[12]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-200; ASN-249; ASN-275; ASN-296; ASN-300 AND ASN-306.
Tissue: Liver.
[13]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-110 AND ILE-531.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS34610.1. [Q14956-1]
CCDS5380.1. [Q14956-2]
PIRI38065.
RefSeqNP_001005340.1. NM_001005340.1. [Q14956-1]
NP_002501.1. NM_002510.2. [Q14956-2]
UniGeneHs.190495.

3D structure databases

ProteinModelPortalQ14956.
SMRQ14956. Positions 260-321.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115720. 3 interactions.
IntActQ14956. 1 interaction.
MINTMINT-1192048.
STRING9606.ENSP00000371420.

PTM databases

PhosphoSiteQ14956.

Polymorphism databases

DMDM61252504.

Proteomic databases

MaxQBQ14956.
PaxDbQ14956.
PRIDEQ14956.

Protocols and materials databases

DNASU10457.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258733; ENSP00000258733; ENSG00000136235. [Q14956-2]
ENST00000381990; ENSP00000371420; ENSG00000136235. [Q14956-1]
GeneID10457.
KEGGhsa:10457.
UCSCuc003swb.3. human. [Q14956-2]
uc003swc.3. human. [Q14956-1]

Organism-specific databases

CTD10457.
GeneCardsGC07P023252.
HGNCHGNC:4462. GPNMB.
HPACAB026224.
HPA044969.
MIM604368. gene.
neXtProtNX_Q14956.
PharmGKBPA28845.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40272.
HOGENOMHOG000252941.
HOVERGENHBG051797.
InParanoidQ14956.
OMAHTYVLNG.
OrthoDBEOG7GXPB9.
PhylomeDBQ14956.
TreeFamTF334865.

Gene expression databases

ArrayExpressQ14956.
BgeeQ14956.
CleanExHS_GPNMB.
HS_NMB.
GenevestigatorQ14956.

Family and domain databases

Gene3D2.60.40.670. 1 hit.
InterProIPR022409. PKD/Chitinase_dom.
IPR000601. PKD_dom.
[Graphical view]
PfamPF00801. PKD. 1 hit.
[Graphical view]
SMARTSM00089. PKD. 1 hit.
[Graphical view]
SUPFAMSSF49299. SSF49299. 1 hit.
PROSITEPS50093. PKD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGPNMB. human.
GeneWikiGPNMB.
GenomeRNAi10457.
NextBio39645.
PROQ14956.
SOURCESearch...

Entry information

Entry nameGPNMB_HUMAN
AccessionPrimary (citable) accession number: Q14956
Secondary accession number(s): A4D155, Q6UVX1, Q8N1A1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 15, 2005
Last modified: July 9, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM