ID GPNMB_HUMAN Reviewed; 572 AA. AC Q14956; A4D155; Q6UVX1; Q8N1A1; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2005, sequence version 2. DT 28-JAN-2026, entry version 190. DE RecName: Full=Transmembrane glycoprotein NMB; DE AltName: Full=Hematopoietic growth factor inducible neurokinin-1 type {ECO:0000303|PubMed:12609765}; DE Flags: Precursor; GN Name=GPNMB; Synonyms=HGFIN {ECO:0000303|PubMed:12609765}, NMB; GN ORFNames=UNQ1725/PRO9925; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY. RC TISSUE=Melanoma; RX PubMed=7814155; DOI=10.1002/ijc.2910600111; RA Weterman M.A.J., Ajubi N., van Dinter I.M.R., Degen W.G.J., RA van Muijen G.N.P., Ruiter D.J., Bloemers H.P.J.; RT "NMB, a novel gene, is expressed in low-metastatic human melanoma cell RT lines and xenografts."; RL Int. J. Cancer 60:73-81(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND INDUCTION RP BY G-CSF AND M-CSF. RC TISSUE=Peripheral blood; RX PubMed=12609765; DOI=10.1016/s0167-0115(02)00288-4; RA Bandari P.S., Qian J., Yehia G., Joshi D.D., Maloof P.B., Potian J., RA Oh H.S., Gascon P., Harrison J.S., Rameshwar P.; RT "Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane RT protein that is similar to neurokinin 1 interacts with substance P."; RL Regul. Pept. 111:169-178(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=12643545; DOI=10.1021/pr025562r; RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., RA Appella E.; RT "Proteomic analysis of early melanosomes: identification of novel RT melanosomal proteins."; RL J. Proteome Res. 2:69-79(2003). RN [9] RP SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, GLYCOSYLATION, RP ALTERNATIVE SPLICING, POTENTIAL TUMOR-ASSOCIATED ANTIGEN FOR IMMUNOTHERAPY, RP AND DISEASE. RX PubMed=16489096; DOI=10.1158/1078-0432.ccr-05-2018; RA Tse K.F., Jeffers M., Pollack V.A., McCabe D.A., Shadish M.L., RA Khramtsov N.V., Hackett C.S., Shenoy S.G., Kuang B., Boldog F.L., RA MacDougall J.R., Rastelli L., Herrmann J., Gallo M., Gazit-Bornstein G., RA Senter P.D., Meyer D.L., Lichenstein H.S., LaRochelle W.J.; RT "CR011, a fully human monoclonal antibody-auristatin E conjugate, for the RT treatment of melanoma."; RL Clin. Cancer Res. 12:1373-1382(2006). RN [10] RP SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, ALTERNATIVE SPLICING, RP AND DISEASE. RX PubMed=16609006; DOI=10.1158/1078-0432.ccr-05-2797; RA Kuan C.T., Wakiya K., Dowell J.M., Herndon J.E. II, Reardon D.A., RA Graner M.W., Riggins G.J., Wikstrand C.J., Bigner D.D.; RT "Glycoprotein nonmetastatic melanoma protein B, a potential molecular RT therapeutic target in patients with glioblastoma multiforme."; RL Clin. Cancer Res. 12:1970-1982(2006). RN [11] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [12] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-200; ASN-249; ASN-275; ASN-296; RP ASN-300 AND ASN-306. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [14] RP VARIANTS [LARGE SCALE ANALYSIS] ASP-110 AND ILE-531. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [15] RP INVOLVEMENT IN PLCA3, VARIANTS PLCA3 189-ARG--SER-572 DEL AND RP 220-TYR--SER-572 DEL, CHARACTERIZATION OF VARIANT PLCA3 189-ARG--SER-572 RP DEL, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT PHE-294. RX PubMed=29336782; DOI=10.1016/j.ajhg.2017.12.012; RA Yang C.F., Lin S.P., Chiang C.P., Wu Y.H., H'ng W.S., Chang C.P., RA Chen Y.T., Wu J.Y.; RT "Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in RT Humans."; RL Am. J. Hum. Genet. 102:219-232(2018). CC -!- FUNCTION: Could be a melanogenic enzyme. {ECO:0000250}. CC -!- INTERACTION: CC Q14956; P00533: EGFR; NbExp=3; IntAct=EBI-7250369, EBI-297353; CC Q14956-1; P00533: EGFR; NbExp=2; IntAct=EBI-16191078, EBI-297353; CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein {ECO:0000269|PubMed:16489096, ECO:0000269|PubMed:16609006}. CC Melanosome membrane {ECO:0000269|PubMed:12643545, CC ECO:0000269|PubMed:17081065}; Single-pass type I membrane protein CC {ECO:0000305}. Early endosome membrane {ECO:0000269|PubMed:29336782}; CC Single-pass type I membrane protein {ECO:0000305}. Note=Identified by CC mass spectrometry in melanosome fractions from stage I to stage IV. CC {ECO:0000269|PubMed:17081065}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q14956-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14956-2; Sequence=VSP_013001; CC -!- TISSUE SPECIFICITY: Widely expressed, but very low expression, if any, CC in the brain (PubMed:12609765, PubMed:16609006). Expressed in the CC epidermis with higher levels in melanocytes compared with keratinocytes CC and Langerhans cells (at protein level) (PubMed:29336782). Expressed in CC peripheral blood, but not bone marrow mononuclear cells CC (PubMed:12609765). Expressed in tissue macrophages, including liver CC Kuppfer cells and lung alveolar macrophages, in podocytes and in some CC cells of the ciliary body of the eye (at protein level) CC (PubMed:16489096). May be overexpressed in various cancers, including CC melanoma and glioblastoma multiforme (PubMed:16489096, PubMed:16609006, CC PubMed:7814155). {ECO:0000269|PubMed:12609765, CC ECO:0000269|PubMed:16489096, ECO:0000269|PubMed:16609006, CC ECO:0000269|PubMed:29336782, ECO:0000269|PubMed:7814155}. CC -!- INDUCTION: Up-regulated by G-CSF/CSF3 and M-CSF/CSF1 in bone marrow CC mononuclear cells, hence up-regulation may be linked to CC differentiation. {ECO:0000269|PubMed:12609765}. CC -!- DISEASE: Note=Increased expression levels in glioblastoma multiforme CC biopsy samples correlate with poor patient survival prognosis CC (PubMed:16609006). Has been proposed as a potential target for CC antibodies coupled to cytotoxic drugs in the context of cancer CC immunotherapy, including that of melanoma (PubMed:16489096). CC {ECO:0000269|PubMed:16489096, ECO:0000269|PubMed:16609006}. CC -!- DISEASE: Amyloidosis, primary localized cutaneous, 3 (PLCA3) CC [MIM:617920]: A primary amyloidosis characterized by localized CC cutaneous amyloid deposition. This condition usually presents with CC itching (especially on the lower legs) and visible changes of skin CC hyperpigmentation and thickening that may be exacerbated by chronic CC scratching and rubbing. Primary localized cutaneous amyloidosis is CC often divided into macular and lichen subtypes although many affected CC individuals often show both variants coexisting. Lichen amyloidosis CC characteristically presents as a pruritic eruption of grouped CC hyperkeratotic papules with a predilection for the shins, calves, CC ankles and dorsa of feet and thighs. Papules may coalesce to form CC hyperkeratotic plaques that can resemble lichen planus, lichen simplex CC or nodular prurigo. Macular amyloidosis is characterized by small CC pigmented macules that may merge to produce macular hyperpigmentation, CC sometimes with a reticulate or rippled pattern. In macular and lichen CC amyloidosis, amyloid is deposited in the papillary dermis in CC association with grouped colloid bodies, thought to represent CC degenerate basal keratinocytes. The amyloid deposits probably reflect a CC combination of degenerate keratin filaments, serum amyloid P component, CC and deposition of immunoglobulins. PLCA3 inheritance is autosomal CC recessive. {ECO:0000269|PubMed:29336782}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the PMEL/NMB family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40739/GPNMB"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X76534; CAA54044.1; -; mRNA. DR EMBL; AF322909; AAG42839.1; -; mRNA. DR EMBL; AY359124; AAQ89481.1; -; mRNA. DR EMBL; AC005082; AAP22336.1; -; Genomic_DNA. DR EMBL; CH236948; EAL24259.1; -; Genomic_DNA. DR EMBL; CH471073; EAW93782.1; -; Genomic_DNA. DR EMBL; BC032783; AAH32783.1; -; mRNA. DR CCDS; CCDS34610.1; -. [Q14956-1] DR CCDS; CCDS5380.1; -. [Q14956-2] DR PIR; I38065; I38065. DR RefSeq; NP_001005340.1; NM_001005340.2. [Q14956-1] DR RefSeq; NP_002501.1; NM_002510.3. [Q14956-2] DR RefSeq; XP_047275732.1; XM_047419776.1. [Q14956-1] DR AlphaFoldDB; Q14956; -. DR BioGRID; 115720; 23. DR DIP; DIP-57606N; -. DR FunCoup; Q14956; 704. DR IntAct; Q14956; 9. DR MINT; Q14956; -. DR STRING; 9606.ENSP00000371420; -. DR ChEMBL; CHEMBL3712919; -. DR DrugBank; DB05996; Glembatumumab vedotin. DR GlyConnect; 1847; 27 N-Linked glycans (4 sites). DR GlyCosmos; Q14956; 13 sites, 27 glycans. DR GlyGen; Q14956; 15 sites, 209 N-linked glycans (4 sites), 2 O-linked glycans (2 sites). DR iPTMnet; Q14956; -. DR PhosphoSitePlus; Q14956; -. DR BioMuta; GPNMB; -. DR DMDM; 61252504; -. DR jPOST; Q14956; -. DR MassIVE; Q14956; -. DR PaxDb; 9606-ENSP00000371420; -. DR PeptideAtlas; Q14956; -. DR ProteomicsDB; 60258; -. [Q14956-1] DR ProteomicsDB; 60259; -. [Q14956-2] DR Pumba; Q14956; -. DR ABCD; Q14956; 1 sequenced antibody. DR Antibodypedia; 12086; 497 antibodies from 37 providers. DR DNASU; 10457; -. DR Ensembl; ENST00000258733.9; ENSP00000258733.5; ENSG00000136235.18. [Q14956-2] DR Ensembl; ENST00000381990.6; ENSP00000371420.2; ENSG00000136235.18. [Q14956-1] DR GeneID; 10457; -. DR KEGG; hsa:10457; -. DR MANE-Select; ENST00000258733.9; ENSP00000258733.5; NM_002510.3; NP_002501.1. [Q14956-2] DR UCSC; uc003swb.4; human. [Q14956-1] DR AGR; HGNC:4462; -. DR ClinPGx; PA28845; -. DR CTD; 10457; -. DR DisGeNET; 10457; -. DR GeneCards; GPNMB; -. DR HGNC; HGNC:4462; GPNMB. DR HPA; ENSG00000136235; Tissue enhanced (skin). DR MalaCards; GPNMB; -. DR MIM; 604368; gene. DR MIM; 617920; phenotype. DR OpenTargets; ENSG00000136235; -. DR Orphanet; 319635; Amyloidosis cutis dyschromia. DR VEuPathDB; HostDB:ENSG00000136235; -. DR eggNOG; ENOG502QVWX; Eukaryota. DR GeneTree; ENSGT00950000183188; -. DR HOGENOM; CLU_017264_1_0_1; -. DR InParanoid; Q14956; -. DR OrthoDB; 9940970at2759; -. DR PAN-GO; Q14956; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q14956; -. DR PathwayCommons; Q14956; -. DR Reactome; R-HSA-8857538; PTK6 promotes HIF1A stabilization. DR SignaLink; Q14956; -. DR Agora; ENSG00000136235; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 10457; 11 hits in 1153 CRISPR screens. DR ChiTaRS; GPNMB; human. DR GeneWiki; GPNMB; -. DR GenomeRNAi; 10457; -. DR Pharos; Q14956; Tbio. DR PRO; PR:Q14956; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q14956; protein. DR Bgee; ENSG00000136235; Expressed in upper leg skin and 204 other cell types or tissues. DR ExpressionAtlas; Q14956; baseline and differential. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0042056; F:chemoattractant activity; NAS:ParkinsonsUK-UCL. DR GO; GO:0008201; F:heparin binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0005178; F:integrin binding; IBA:GO_Central. DR GO; GO:0048018; F:receptor ligand activity; IMP:ParkinsonsUK-UCL. DR GO; GO:0045545; F:syndecan binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0007267; P:cell-cell signaling; IMP:ParkinsonsUK-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0001818; P:negative regulation of cytokine production; IDA:ParkinsonsUK-UCL. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IDA:ParkinsonsUK-UCL. DR GO; GO:0050868; P:negative regulation of T cell activation; IMP:ParkinsonsUK-UCL. DR GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:ParkinsonsUK-UCL. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0050918; P:positive chemotaxis; NAS:ParkinsonsUK-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:ParkinsonsUK-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; TAS:ParkinsonsUK-UCL. DR GO; GO:0045765; P:regulation of angiogenesis; NAS:ParkinsonsUK-UCL. DR GO; GO:0034103; P:regulation of tissue remodeling; IDA:ParkinsonsUK-UCL. DR GO; GO:0007165; P:signal transduction; IMP:ParkinsonsUK-UCL. DR CDD; cd00146; PKD; 1. DR FunFam; 2.60.40.10:FF:000893; Transmembrane glycoprotein NMB; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR045219; PKAT. DR InterPro; IPR046846; PKAT_KLD. DR InterPro; IPR022409; PKD/Chitinase_dom. DR InterPro; IPR000601; PKD_dom. DR InterPro; IPR035986; PKD_dom_sf. DR InterPro; IPR059017; PMEL_NMB_N. DR PANTHER; PTHR11861; MELANOCYTE PROTEIN PMEL 17-RELATED; 1. DR PANTHER; PTHR11861:SF11; TRANSMEMBRANE GLYCOPROTEIN NMB; 1. DR Pfam; PF20433; PKAT_KLD; 1. DR Pfam; PF18911; PKD_4; 1. DR Pfam; PF26141; PMEL_NMB_N; 1. DR SMART; SM00089; PKD; 1. DR SUPFAM; SSF49299; PKD domain; 1. DR PROSITE; PS50093; PKD; 1. PE 1: Evidence at protein level; KW Alternative splicing; Amyloidosis; Cell membrane; Disease variant; KW Endosome; Glycoprotein; Membrane; Phosphoprotein; KW Proteomics identification; Reference proteome; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..572 FT /note="Transmembrane glycoprotein NMB" FT /id="PRO_0000024709" FT TOPO_DOM 23..498 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 499..519 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 520..572 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 240..327 FT /note="PKD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151" FT REGION 320..362 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 64..66 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT COMPBIAS 321..335 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 338..351 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 542 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99P91" FT CARBOHYD 93 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 146 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 200 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 249 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 275 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 300 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 306 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 312 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 459 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 467 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 340..351 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12609765, FT ECO:0000303|PubMed:7814155" FT /id="VSP_013001" FT VARIANT 110 FT /note="A -> D (in a breast cancer sample; somatic mutation; FT dbSNP:rs755767733)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036262" FT VARIANT 189..572 FT /note="Missing (in PLCA3; may be expressed at much lower FT levels than wild-type protein; mislocalized to the FT endoplasmic reticulum and nuclear envelope)" FT /evidence="ECO:0000269|PubMed:29336782" FT /id="VAR_080643" FT VARIANT 195 FT /note="S -> C (in dbSNP:rs530436)" FT /id="VAR_012076" FT VARIANT 197 FT /note="N -> H (in dbSNP:rs530413)" FT /id="VAR_012077" FT VARIANT 220..572 FT /note="Missing (in PLCA3)" FT /evidence="ECO:0000269|PubMed:29336782" FT /id="VAR_080644" FT VARIANT 294 FT /note="S -> F (in dbSNP:rs35499907)" FT /evidence="ECO:0000269|PubMed:29336782" FT /id="VAR_050603" FT VARIANT 324 FT /note="P -> L (in dbSNP:rs35363287)" FT /id="VAR_050604" FT VARIANT 531 FT /note="S -> I (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036263" FT VARIANT 538 FT /note="S -> R (in dbSNP:rs35878037)" FT /id="VAR_050605" FT CONFLICT 354 FT /note="A -> T (in Ref. 3; AAQ89481)" FT /evidence="ECO:0000305" SQ SEQUENCE 572 AA; 63923 MW; 2465C12C2F0F3996 CRC64; MECLYYFLGF LLLAARLPLD AAKRFHDVLG NERPSAYMRE HNQLNGWSSD ENDWNEKLYP VWKRGDMRWK NSWKGGRVQA VLTSDSPALV GSNITFAVNL IFPRCQKEDA NGNIVYEKNC RNEAGLSADP YVYNWTAWSE DSDGENGTGQ SHHNVFPDGK PFPHHPGWRR WNFIYVFHTL GQYFQKLGRC SVRVSVNTAN VTLGPQLMEV TVYRRHGRAY VPIAQVKDVY VVTDQIPVFV TMFQKNDRNS SDETFLKDLP IMFDVLIHDP SHFLNYSTIN YKWSFGDNTG LFVSTNHTVN HTYVLNGTFS LNLTVKAAAP GPCPPPPPPP RPSKPTPSLA TTLKSYDSNT PGPAGDNPLE LSRIPDENCQ INRYGHFQAT ITIVEGILEV NIIQMTDVLM PVPWPESSLI DFVVTCQGSI PTEVCTIISD PTCEITQNTV CSPVDVDEMC LLTVRRTFNG SGTYCVNLTL GDDTSLALTS TLISVPDRDP ASPLRMANSA LISVGCLAIF VTVISLLVYK KHKEYNPIEN SPGNVVRSKG LSVFLNRAKA VFFPGNQEKD PLLKNQEFKG VS //