Q14435 (GALT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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=GalNAc-T3
Short name=pp-GaNTase 3
Protein-UDP acetylgalactosaminyltransferase 3
UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 3

Gene names

Name:

GALNT3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	633 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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-alpha-D-galactosamine + polypeptide = UDP + N-acetyl-alpha-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	Tumoral calcinosis, hyperphosphatemic, familial (HFTC) [MIM:211900]: A severe metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients manifest recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 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.
Sequence caution	The sequence AAH56246.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Calcium Lectin Manganese
Molecular function	Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	O-glycan processing Traceable author statement. Source: Reactome post-translational protein modification Traceable author statement. Source: Reactome protein O-linked glycosylation via serine Inferred from direct assay Ref.5. Source: BHF-UCL protein O-linked glycosylation via threonine Inferred from direct assay Ref.10. Source: UniProtKB
Cellular_component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell Golgi membrane Traceable author statement. Source: Reactome integral to membrane Traceable author statement Ref.1. Source: ProtInc nucleus Inferred from direct assay. Source: HPA perinuclear region of cytoplasm Inferred from direct assay PubMed 12506059. Source: BHF-UCL
Molecular_function	calcium ion binding Inferred from direct assay Ref.5. Source: BHF-UCL manganese ion binding Inferred from direct assay Ref.5. Source: BHF-UCL polypeptide N-acetylgalactosaminyltransferase activity Inferred from direct assay Ref.5. Source: BHF-UCL
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	Helical; 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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HFTC.
[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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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. NM_004482.3.
UniGene	Hs.170986.
3D structure databases
ProteinModelPortal	Q14435.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000376465.
Protein family/group databases
CAZy	CBM13. Carbohydrate-Binding Module Family 13. GT27. Glycosyltransferase Family 27.
PTM databases
PhosphoSite	Q14435.
Polymorphism databases
DMDM	209572629.
Proteomic databases
PaxDb	Q14435.
PRIDE	Q14435.
Protocols and materials databases
DNASU	2591.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000392701; ENSP00000376465; ENSG00000115339.
GeneID	2591.
KEGG	hsa:2591.
UCSC	uc002udi.2. human. uc010fph.1. human.
Organism-specific databases
CTD	2591.
GeneCards	GC02M166567.
H-InvDB	HIX0024214.
HGNC	HGNC:4125. GALNT3.
HPA	HPA007613.
MIM	211900. phenotype. 601756. gene.
neXtProt	NX_Q14435.
Orphanet	53715. Tumoral calcinosis.
PharmGKB	PA28538.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG239675.
HOGENOM	HOG000038227.
HOVERGEN	HBG051699.
InParanoid	Q14435.
KO	K00710.
OMA	QYFEYSA.
OrthoDB	EOG4GB75S.
PhylomeDB	Q14435.
Enzyme and pathway databases
BRENDA	2.4.1.41. 2681.
Reactome	REACT_17015. Metabolism of proteins.
UniPathway	UPA00378.
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. 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]
SUPFAM	SSF50370. RicinB_like. 1 hit.
PROSITE	PS50231. RICIN_B_LECTIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GALNT3. human.
GenomeRNAi	2591.
NextBio	10249.
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:	May 1, 2013
This is version 121 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.