Reviewed, UniProtKB/Swiss-Prot Q14435 (GALT3_HUMAN)

Names and origin

Protein names

Recommended name:
    Polypeptide N-acetylgalactosaminyltransferase 3
    EC=2.4.1.41
Alternative name(s):
    Polypeptide GalNAc transferase 3
      Short name=pp-GaNTase 3
      Short name=GalNAc-T3
    Protein-UDP acetylgalactosaminyltransferase 3
    UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 3

Gene names

Name:

GALNT3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	633 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity toward HIV envelope glycoprotein gp120, EA2, Muc2 and Muc5. Probably glycosylates fibronectin in vivo. Glycosylates FGF23. Plays a central role in phosphate homeostasis. Ref.5 Ref.10
Catalytic activity	UDP-N-acetyl-D-galactosamine + polypeptide = UDP + N-acetyl-D-galactosaminyl-polypeptide. Ref.1
Cofactor	Manganese By similarity. Calcium By similarity.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Golgi apparatus › Golgi stack membrane; Single-pass type II membrane protein. Note: Resides preferentially in the trans and medial parts of the Golgi stack. Ref.6
Tissue specificity	Expressed in organs that contain secretory epithelial glands. Highly expressed in pancreas, skin, kidney and testis. Weakly expressed in prostate, ovary, intestine and colon. Also expressed in placenta and lung and fetal lung and fetal kidney. Ref.1 Ref.7
Domain	There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding By similarity. The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity By similarity.
Involvement in disease	Defects in GALNT3 are a cause of hyperphosphatemic familial tumoral calcinosis (HFTC) [MIM:211900]. HFTC is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Ref.8 Defects in GALNT3 are the cause of hyperostosis-hyperphosphatemia syndrome (HHS) [MIM:610233]; also known as hyperostosis with hyperphosphatemia. HHS is characterized by recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis. Serum phosphate is increased. The disorder shows similarities to HFTC, but can be distinguished by the presence of bone involvement and the absence of skin involvement. Ref.9
Miscellaneous	Overexpressed in many differentiated carcinomas, suggesting that it may serve as a marker of tumor differentiation.
Sequence similarities	Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily. Contains 1 ricin B-type lectin domain.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane
Ligand	Calcium Lectin Manganese
Molecular function	Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid O-linked glycosylation via serine Ref.5 Inferred from direct assay. Source: UniProtKB protein amino acid O-linked glycosylation via threonine Ref.5 Ref.10 Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA integral to membrane Ref.1 Traceable author statement. Source: ProtInc membrane fraction Ref.1 Traceable author statement. Source: ProtInc perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	calcium ion binding Ref.5 Inferred from direct assay. Source: UniProtKB manganese ion binding Ref.5 Inferred from direct assay. Source: UniProtKB polypeptide N-acetylgalactosaminyltransferase activity Ref.5 Inferred from direct assay. Source: UniProtKB sugar binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q14435-1)

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: Q14435-2)

The sequence of this isoform differs from the canonical sequence as follows:
     173-192: CIEQKFKRCPPLPTTSVIIV → YVEEYLLFILYHQALQGREG
     193-633: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 633	633	Polypeptide N-acetylgalactosaminyltransferase 3		PRO_0000059106
Regions
	Topological domain	1 – 19	19	Cytoplasmic Potential
	Transmembrane	20 – 37	18	Signal-anchor for type II membrane protein Potential
	Topological domain	38 – 633	596	Lumenal Potential
	Domain	504 – 630	127	Ricin B-type lectin
	Region	184 – 293	110	Catalytic subdomain A
	Region	356 – 418	63	Catalytic subdomain B
Amino acid modifications
	Glycosylation	132	1	N-linked (GlcNAc...) Potential
	Glycosylation	297	1	N-linked (GlcNAc...) Potential
	Glycosylation	484	1	N-linked (GlcNAc...) Potential
	Disulfide bond	517 ↔ 535		By similarity
	Disulfide bond	561 ↔ 574		By similarity
	Disulfide bond	605 ↔ 618		By similarity
Natural variations
	Alternative sequence	173 – 192	20	CIEQK…SVIIV → YVEEYLLFILYHQALQGREG in isoform 2.		VSP_011202
	Alternative sequence	193 – 633	441	Missing in isoform 2.		VSP_011203
Experimental info
	Sequence conflict	481	1	Q → R in CAA63371. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 3019B2DCCC19A584	FASTA	633	72,610
	10 20 30 40 50 60 MAHLKRLVKL HIKRHYHKKF WKLGAVIFFF IIVLVLMQRE VSVQYSKEES RMERNMKNKN 70 80 90 100 110 120 KMLDLMLEAV NNIKDAMPKM QIGAPVRQNI DAGERPCLQG YYTAAELKPV LDRPPQDSNA 130 140 150 160 170 180 PGASGKAFKT TNLSVEEQKE KERGEAKHCF NAFASDRISL HRDLGPDTRP PECIEQKFKR 190 200 210 220 230 240 CPPLPTTSVI IVFHNEAWST LLRTVHSVLY SSPAILLKEI ILVDDASVDE YLHDKLDEYV 250 260 270 280 290 300 KQFSIVKIVR QRERKGLITA RLLGATVATA ETLTFLDAHC ECFYGWLEPL LARIAENYTA 310 320 330 340 350 360 VVSPDIASID LNTFEFNKPS PYGSNHNRGN FDWSLSFGWE SLPDHEKQRR KDETYPIKTP 370 380 390 400 410 420 TFAGGLFSIS KEYFEYIGSY DEEMEIWGGE NIEMSFRVWQ CGGQLEIMPC SVVGHVFRSK 430 440 450 460 470 480 SPHSFPKGTQ VIARNQVRLA EVWMDEYKEI FYRRNTDAAK IVKQKAFGDL SKRFEIKHRL 490 500 510 520 530 540 QCKNFTWYLN NIYPEVYVPD LNPVISGYIK SVGQPLCLDV GENNQGGKPL IMYTCHGLGG 550 560 570 580 590 600 NQYFEYSAQH EIRHNIQKEL CLHAAQGLVQ LKACTYKGHK TVVTGEQIWE IQKDQLLYNP 610 620 630 FLKMCLSANG EHPSLVSCNP SDPLQKWILS QND
	Isoform 2. Checksum: 2EEE40B4D6537601	FASTA	192	22,212
	10 20 30 40 50 60 MAHLKRLVKL HIKRHYHKKF WKLGAVIFFF IIVLVLMQRE VSVQYSKEES RMERNMKNKN 70 80 90 100 110 120 KMLDLMLEAV NNIKDAMPKM QIGAPVRQNI DAGERPCLQG YYTAAELKPV LDRPPQDSNA 130 140 150 160 170 180 PGASGKAFKT TNLSVEEQKE KERGEAKHCF NAFASDRISL HRDLGPDTRP PEYVEEYLLF 190 ILYHQALQGR EG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and expression of a novel human UDP-N-acetyl-alpha-D-galactosamine polypeptide N-acetylgalactosaminyltransferase, GalNAc-T3." Bennett E.P., Hassan H., Clausen H. J. Biol. Chem. 271:17006-17012(1996) [PubMed: 8663203] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, TISSUE SPECIFICITY. Tissue: Salivary gland.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORMS 1 AND 2). Tissue: Lung.
[5]	"Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3." Wandall H.H., Hassan H., Mirgorodskaya E., Kristensen A.K., Roepstorff P., Bennett E.P., Nielsen P.A., Hollingsworth M.A., Burchell J., Taylor-Papadimitriou J., Clausen H. J. Biol. Chem. 272:23503-23514(1997) [PubMed: 9295285] [Abstract] Cited for: FUNCTION.
[6]	"Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus." Roettger S., White J., Wandall H.H., Olivo J.-C., Stark A., Bennett E.P., Whitehouse C., Berger E.G., Clausen H., Nilsson T. J. Cell Sci. 111:45-60(1998) [PubMed: 9394011] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"Prognostic significance of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-3 (GalNAc-T3) expression in patients with gastric carcinoma." Onitsuka K., Shibao K., Nakayama Y., Minagawa N., Hirata K., Izumi H., Matsuo K., Nagata N., Kitazato K., Kohno K., Itoh H. Cancer Sci. 94:32-36(2003) [PubMed: 12708471] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis." Topaz O., Shurman D.L., Bergman R., Indelman M., Ratajczak P., Mizrachi M., Khamaysi Z., Behar D., Petronius D., Friedman V., Zelikovic I., Raimer S., Metzker A., Richard G., Sprecher E. Nat. Genet. 36:579-581(2004) [PubMed: 15133511] [Abstract] Cited for: INVOLVEMENT IN HFTC.
[9]	"Identification of a recurrent mutation in GALNT3 demonstrates that hyperostosis-hyperphosphatemia syndrome and familial tumoral calcinosis are allelic disorders." Frishberg Y., Topaz O., Bergman R., Behar D., Fisher D., Gordon D., Richard G., Sprecher E. J. Mol. Med. 83:33-38(2005) [PubMed: 15599692] [Abstract] Cited for: INVOLVEMENT IN HHS.
[10]	"Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation." Kato K., Jeanneau C., Tarp M.A., Benet-Pages A., Lorenz-Depiereux B., Bennett E.P., Mandel U., Strom T.M., Clausen H. J. Biol. Chem. 281:18370-18377(2006) [PubMed: 16638743] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Polypeptide N-acetylgalactosaminyltransferase 3

Cross-references

Sequence databases
EMBL GenBank DDBJ	X92689 mRNA. Translation: CAA63371.1. AC009495 Genomic DNA. Translation: AAY14678.1. CH471058 Genomic DNA. Translation: EAX11324.1. BC056246 mRNA. Translation: AAH56246.1. Different initiation. BC113565 mRNA. Translation: AAI13566.1. BC113567 mRNA. Translation: AAI13568.1.
IPI	IPI00004670. IPI00456483.
RefSeq	NP_004473.2.
UniGene	Hs.170986
3D structure databases
SMR	Q14435. Positions 133-632.
ModBase	Search...
Protein-protein interaction databases
STRING	Q14435.
Protein family/group databases
CAZy	CBM13. Carbohydrate-Binding Module Family 13. GT27. Glycosyltransferase Family 27.
Proteomic databases
PRIDE	Q14435.
Genome annotation databases
Ensembl	ENST00000392701; ENSP00000376465; ENSG00000115339; Homo sapiens. [Genome view]
GeneID	2591.
KEGG	hsa:2591.
UCSC	uc002udi.2. human.
Organism-specific databases
CTD	2591.
GeneCards	GC02M166311.
H-InvDB	HIX0024214.
HGNC	HGNC:4125. GALNT3.
HPA	HPA007613.
MIM	211900. phenotype. 601756. gene. 610233. phenotype.
Orphanet	53715. Calcinosis, tumoral.
PharmGKB	PA142672564.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15002.
HOGENOM	HBG715048.
HOVERGEN	Q14435.
InParanoid	Q14435.
OMA	AGERPCL.
OrthoDB	EOG9G7FHX.
PhylomeDB	Q14435.
Enzyme and pathway databases
BRENDA	2.4.1.41. 247.
Gene expression databases
ArrayExpress	Q14435.
Bgee	Q14435.
CleanEx	HS_GALNT3.
Genevestigator	Q14435.
GermOnline	ENSG00000115339. Homo sapiens.
Family and domain databases
InterPro	IPR001173. Glyco_trans_2. IPR008997. Ricin_B-rel_lectin. IPR000772. Ricin_B_lectin. [Graphical view]
Pfam	PF00535. Glycos_transf_2. 1 hit. PF00652. Ricin_B_lectin. 1 hit. [Graphical view]
SMART	SM00458. RICIN. 1 hit. [Graphical view]
PROSITE	PS50231. RICIN_B_LECTIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

GALT3_HUMAN

Accession

Primary (citable) accession number: Q14435
Secondary accession number(s): Q53TG9, Q7Z476

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	October 14, 2008
Last modified:	January 19, 2010
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.