Q14956 (GPNMB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane glycoprotein NMB

Alternative name(s):
Transmembrane glycoprotein HGFIN

Gene names

Name:	GPNMB
Synonyms:	HGFIN, NMB
ORF Names:	UNQ1725/PRO9925

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	572 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Could be a melanogenic enzyme By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Potential. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.8 Ref.9
Tissue specificity	Not restricted to the melanocytic lineage.
Developmental stage	Expression in poorly metastatic melanoma cell lines; no expression in highly metastatic melanoma cell lines.
Sequence similarities	Belongs to the PMEL/NMB family. Contains 1 PKD domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Traceable author statement. Source: ProtInc
Cellular component	melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 572	551	Transmembrane glycoprotein NMB		PRO_0000024709
Regions
	Topological domain	22 – 486	465	Extracellular Potential
	Transmembrane	487 – 507	21	Helical; Potential
	Topological domain	508 – 572	65	Cytoplasmic Potential
	Domain	240 – 327	88	PKD
	Motif	64 – 66	3	Cell attachment site Potential
	Compositional bias	320 – 332	13	Poly-Pro
Amino acid modifications
	Modified residue	542	1	Phosphoserine By similarity
	Glycosylation	93	1	N-linked (GlcNAc...) Potential
	Glycosylation	134	1	N-linked (GlcNAc...) Potential
	Glycosylation	146	1	N-linked (GlcNAc...) Potential
	Glycosylation	200	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	249	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	275	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	296	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	300	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	306	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
	Glycosylation	459	1	N-linked (GlcNAc...) Potential
	Glycosylation	467	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	340 – 351	12	Missing in isoform 2.		VSP_013001
	Natural variant	110	1	A → D in a breast cancer sample; somatic mutation. Ref.11		VAR_036262
	Natural variant	195	1	S → C. Corresponds to variant rs530436 [ dbSNP | Ensembl ].		VAR_012076
	Natural variant	197	1	N → H. Corresponds to variant rs530413 [ dbSNP | Ensembl ].		VAR_012077
	Natural variant	294	1	S → F. Corresponds to variant rs35499907 [ dbSNP | Ensembl ].		VAR_050603
	Natural variant	324	1	P → L. Corresponds to variant rs35363287 [ dbSNP | Ensembl ].		VAR_050604
	Natural variant	531	1	S → I in a breast cancer sample; somatic mutation. Ref.11		VAR_036263
	Natural variant	538	1	S → R. Corresponds to variant rs35878037 [ dbSNP | Ensembl ].		VAR_050605
Experimental info
	Sequence conflict	354	1	A → T in AAQ89481. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: 2465C12C2F0F3996	FASTA	572	63,923
	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
	Isoform 2 [UniParc]. Checksum: 570035B48CCE3ECC	FASTA	560	62,643
	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 RPSKPTPSLG PAGDNPLELS RIPDENCQIN 370 380 390 400 410 420 RYGHFQATIT IVEGILEVNI IQMTDVLMPV PWPESSLIDF VVTCQGSIPT EVCTIISDPT 430 440 450 460 470 480 CEITQNTVCS PVDVDEMCLL TVRRTFNGSG TYCVNLTLGD DTSLALTSTL ISVPDRDPAS 490 500 510 520 530 540 PLRMANSALI SVGCLAIFVT VISLLVYKKH KEYNPIENSP GNVVRSKGLS VFLNRAKAVF 550 560 FPGNQEKDPL LKNQEFKGVS

References

	« Hide 'large scale' referencesShow '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: 7814155] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). 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: 12609765] [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. , 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: 12975309] [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. , 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: 12690205] [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. , 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. , 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: 12853948] [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: 15489334] [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: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[9]	"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: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[10]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-200; ASN-249; ASN-275; ASN-296; ASN-300 AND ASN-306, MASS SPECTROMETRY. Tissue: Liver.
[11]	"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. , 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: 16959974] [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.
IPI	IPI00001592. IPI00940949.
PIR	I38065.
RefSeq	NP_001005340.1. NM_001005340.1. NP_002501.1. NM_002510.2.
UniGene	Hs.190495.
3D structure databases
ProteinModelPortal	Q14956.
SMR	Q14956. Positions 260-320, 430-485.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1192048.
STRING	Q14956.
PTM databases
PhosphoSite	Q14956.
Polymorphism databases
DMDM	61252504.
Proteomic databases
PRIDE	Q14956.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000381990; ENSP00000371420; ENSG00000136235. ENST00000435486; ENSP00000409199; ENSG00000136235.
GeneID	10457.
KEGG	hsa:10457.
UCSC	uc003swb.1. human. uc003swc.1. human.
Organism-specific databases
CTD	10457.
GeneCards	GC07P023252.
HGNC	HGNC:4462. GPNMB.
HPA	CAB026224.
MIM	604368. gene.
neXtProt	NX_Q14956.
PharmGKB	PA28845.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000063573.
HOVERGEN	HBG051797.
InParanoid	Q14956.
Gene expression databases
ArrayExpress	Q14956.
Bgee	Q14956.
CleanEx	HS_GPNMB. HS_NMB.
Genevestigator	Q14956.
GermOnline	ENSG00000136235. Homo sapiens.
Family and domain databases
InterPro	IPR022409. PKD/Chitinase_dom. IPR000601. PKD_dom. [Graphical view]
Gene3D	G3DSA:2.60.40.670. PKD. 1 hit.
Pfam	PF00801. PKD. 1 hit. [Graphical view]
SMART	SM00089. PKD. 1 hit. [Graphical view]
SUPFAM	SSF49299. PKD. 1 hit.
PROSITE	PS50093. PKD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	39645.
SOURCE	Search...

Entry information

Entry name

GPNMB_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.