Xp22.22. View the map and BAC clones (data from UCSC genome browser).
GPR143/NM_000273: 9 exons, 40,464bp, ChrX: 9,104,959 - 9,145,422.
The figure below shows the structure of the GPR143 gene (data from UCSC genome browser).
Search the 5'UTR and 1kb upstream regions (human and mouse) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
Tissue specificity: Highly expressed in pigment cells. Maybe expressed in other tissues as shown below.
BMR: Bone marrow; SPL: Spleen; TMS: Thymus; BRN: Brain; SPC: Spinal cord; HRT: Heart; MSL: Skeletal muscle; LVR; Liver; PNC: Pancreas; PST: Prostate; KDN: Kidney; LNG: Lung. (data from GeneCards )
|Protein||NP_035081 (405aa)||XP_228848 (464aa)||NP_957116 (412aa)||XP_317232 (321aa)||NP_573140 (676aa)|
|Identities||77% /315aa||75% /279aa||60% /236aa||31% /71aa||19% /60aa|
View multiple sequence alignment (PDF files) by ClustalW and GeneDoc.
(1) Domains predicted by SMART:
a) low complexity: 5 - 18
b) Pfam:Ocular_alb: 21 - 424
(2) Transmembrane domains predicted by SOSUI: six transmembrane helices detected.
|No.||N terminal||transmembrane region||C terminal||type||length|
(1) Predicted results by ScanProsite:
a) Amidation site : [occurs frequently]
4 - 7: aGRR, 70 - 73: pGRR.
b) Protein kinase C phosphorylation site : [occurs frequently]
23 - 25: SpR, 87 - 89: SvR, 300 - 302: SlK, 342 - 344: SpR, 373 - 375: SgK.
c) N-myristoylation site : [occurs frequently]
58 - 63: GLrlAL, 78 - 83: GSpaTS, 207 - 212: GLdhAI, 335 - 340: GCslGF, 380 - 385: GGqtSD, 394 - 399: GSdaST.
d) Casein kinase II phosphorylation site : [occurs frequently]
121 - 124: SvsD, 202 - 205: SrcE, 252 - 255: TenE, 355 - 358: SaaE, 383 - 386: TsdE, 398 - 401: StiE, 404 - 407: TasE, 420 - 423: ThgD.
e) N-glycosylation site : [occurs frequently]
126 - 129: NHTE, 283 - 286: NESL.
Not that D106 is essential for N-glycosylation of the protein (Shen, et al (2001a)).
(2) Predicted results of subprograms by PSORT II:
a) Seems to no N-terminal signal peptide
b) KDEL ER retention motif in the C-terminus: none
c) ER Membrane Retention Signals: none
d) VAC possible vacuolar targeting motif: none
e) Actinin-type actin-binding motif: type 1: none; type 2: none
f) Prenylation motif: none
g) memYQRL transport motif from cell surface to Golgi: none
h) Tyrosines in the tail: none
i) Dileucine motif in the tail: none
(1)No ModBase entry found.
(2) 3D models predicted by SPARKS (fold recognition) below. View the models by PDB2MGIF.
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=46,051Da, pI=8.39 (NP_000264).
Two forms of the OA1 protein were identified by Western analysis, a 60-kDa glycoprotein and a doublet of 48 and 45 kDa probably corresponding to unglycosylated precursor polypeptides (Schiaffino, et al (1996)).
a) Biological process: eye pigment biosynthesis; visual perception
b) Biological process: G-protein coupled receptor protein signaling pathway
c) Integral to membrane
d) Belongs to family OA of G-protein coupled receptors.
OA1 protein is a conserved integral membrane protein with seven transmembrane domains that has weak similarities to G protein-coupled receptors (GPCRs), which participate in the most common signal transduction system at the plasma membrane. It binds heterotrimeric G proteins, which suggests that OA1 GPCR-mediated signal transduction systems also operate at the internal membranes in mammalian cells (Schiaffino, et al (1999) ). Two separate sorting signals that are both necessary and sufficient for intracellular retention, as well as lysosomal and melanosomal localization were identified. These sorting signals are an unconventional dileucine motif within the third cytosolic loop and a novel motif, characterized by a tryptophan-glutamic acid doublet, within the C-terminal tail (Piccirillo, et al). OA1 colocalizes and coprecipitates with arrestins, which downregulate the signaling of OA1 by specifically reducing its expression levels (Innamorati, et al). Oa1 is a target of MITF, and tissue-specific control of Oa1 transcription lies within a region of 617 bp that contains the E-box bound by Mitf (Vetrini, et al). L-DOPA is a ligand for OA1 (Lopez, et al).
The Drosophila homolog, CG4521, has no entries in the CuraGen Drosophila interaction database.
The OA1 gene product is a membrane glycoprotein that may play a role in controlling melanosome growth and maturation. OA1 protein functions in the late stage of melanosome development.
The distribution of 61 mutations and 3 polymorphisms is described in detail in Albinism Database. For cross-reference, view the distribution of mutations in the Retina International Mutation Database of OA1 Gene.
Except the 78 mutations deposited in HGMD, additional novel mutations are listed below:
(1) The S89F mutation was identified in a Chinese OA1 family by Liu, et al (2007).
(2) Eight novel mutations (W132R, E185K, R186P, R186W, c.616insC, c.737delG, c.780delC, and Y311X) were described by Roma, et al (2007).
(3) Two novel mutations, c.190delC and p.C116G, were reported in two United States OA1 family by Iannaccone, et al (2007).
(4) One novel mutation, c.222-258del37bp was reported in a Chinese OA1 family by Zhou, et al (2008), resulting in a truncated protein with 93 amino acids.
(5) Five novel mutations in GPR143 were identified in six Chinese OA1 families: c.849delT (p.Val284SerfsX15); c.238_240delCTC (p.Leu80del); c.658+1G>A, g.1103_7266del6164 (p.Gly84AlafsX65, deletion of exons 2 and 3); and g.25985_26546del562 (p.Gly296ValfsX26, deletion of exon 8) (Fang, et al (2008)).
(6) One novel nonsense mutation, G315X, was reported in a Chinese OA1 family by Wang, et al (2009).
(7) A previously unidentified 19 bp duplication (c.291_309) mutation in exon 1 was identified in a Chinese OA1 family by Peng, et al (2009).
(8)Micale, et al (2009) identified the c.564_565delCT and a novel intragenic deletion g.5360_6371del1012, encompassing exon 2, in two unrelated Italian families.
A number of mutations in the OA1 gene lead to at least in part the retention of the aberrant protein in the endoplasmic reticulum due to the protein misfolding (d'Addio, et al).
Defects in GPR143 are the cause of ocular albinism type 1 (OA1) (Bassi, et al (1995)) (OMIM 300500) ; also known as Nettleship-Falls type ocular albinism, or X-linked Nettleship-Falls ocular albinism (XLOA). OA1 is an X-linked disorder, mainly characterized by a severe reduction in visual acuity, foveal hypoplasia, nystagmus, hypopigmentation of the retina, the presence of macromelanosomes in the skin and eyes, and the misrouting of optic pathways, resulting in the loss of stereoscopic vision.
Defects in GPR143 are a cause of late-onset sensorineural deafness (OASD) (Bassi, et al (1999)) (OMIM 300650). OASD is an X-linked recessive disorder characterized by ocular albinism and progressive sensineural hearing loss in the fourth and fifth decades of life. OASD may be caused by deletion of both GPR143/OA1 and TBL1X adjacent genes; GPR143 defects probably causing the albinism phenotype.