Reviewed, UniProtKB/Swiss-Prot Q14956 (GPNMB_HUMAN)

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 proteinPotential. Melanosome. Note= Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
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-17/NMB family. Contains 1 PKD domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Ref.1 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	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
	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...) Potential
	Glycosylation	249	1	N-linked (GlcNAc...) Potential
	Glycosylation	275	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	300	1	N-linked (GlcNAc...) Potential
	Glycosylation	306	1	N-linked (GlcNAc...) Potential
	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.		VAR_036262
	Natural variant	195	1	S → C: dbSNP rs530436.		VAR_012076
	Natural variant	197	1	N → H: dbSNP rs530413.		VAR_012077
	Natural variant	531	1	S → I in a breast cancer sample; somatic mutation.		VAR_036263
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		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]	"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].
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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
EMBLGenBankDDBJ	X76534 mRNA. Translation: CAA54044.1. AF322909 mRNA. Translation: AAG42839.1. AY359124 mRNA. Translation: AAQ89481.1. AC005082 Genomic DNA. Translation: AAP22336.1. BC032783 mRNA. Translation: AAH32783.1.
PIR	I38065.
RefSeq	NP_001005340.1.
UniGene	Hs.190495
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000136235. Homo sapiens. [Contig view]
GeneID	10457.
KEGG	hsa:10457.
Organism-specific databases
H-InvDB	HIX0006519.
HGNC	HGNC:4462. GPNMB.
MIM	604368. gene.
PharmGKB	PA28845.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q14956.
HOVERGEN	Q14956.
Gene expression databases
ArrayExpress	Q14956.
CleanEx	HS_GPNMB. HS_NMB.
GermOnline	ENSG00000136235. Homo sapiens.
Family and domain databases
InterPro	IPR000601. PKD. [Graphical view]
Pfam	PF00801. PKD. 1 hit. [Graphical view]
SMART	SM00089. PKD. 1 hit. [Graphical view]
PROSITE	PS50093. PKD. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	39645.
SOURCE	Search...

Entry information

Entry name

GPNMB_HUMAN

Accession

Primary (citable) accession number: Q14956
Secondary accession number(s): Q6UVX1, Q8N1A1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	March 15, 2005
Last modified:	November 25, 2008
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)