Q9Y2G5 (OFUT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GDP-fucose protein O-fucosyltransferase 2
EC=2.4.1.221

Alternative name(s):
Peptide-O-fucosyltransferase 2
Short name=O-FucT-2

Gene names

Name:	POFUT2
Synonyms:	C21orf80, FUT13, KIAA0958

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	429 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	Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue in the consensus sequence C1-X(2,3)-S/T-C2-X(2)-G of thrombospondin type 1 repeats where C1 and C2 are the first and second cysteines, respectively. O-fucosylates members of several protein families including the ADAMTS family, the thrombosporin (TSP) and spondin families. The O-fucosylation of TSRs is also required for restricting epithelial to mesenchymal transition (EMT), maintaining the correct patterning of mesoderm and localization of the definite endoderm By similarity. Required for the proper secretion of ADAMTS family members such as ADAMSL1 and ADAMST13. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Catalytic activity	Transfers an alpha-L-fucosyl residue from GDP-beta-L-fucose to the serine hydroxy group of a protein acceptor. Ref.11
Enzyme regulation	Inhibited by EDTA and by Zn2+. Ref.11
Pathway	Protein modification; protein glycosylation.
Subcellular location	Endoplasmic reticulum. Golgi apparatus. Note: Mainly located in the endoplasmic reticulum. Ref.1
Tissue specificity	Isoform A is expressed in fetal liver and peripheral blood lymphocytes. Isoform B is expressed in spleen, lung, testis, bone marrow, thymus, pancreas, prostate, fetal brain, fetal liver and fetal kidney. Isoform C is expressed in brain, heart, spleen, liver, lung, stomach, testis, placenta, skin, thymus, pancreas, mammary gland, prostate, fetal brain, fetal liver and fetal heart. Ref.1
Sequence similarities	Belongs to the glycosyltransferase 68 family.
Biophysicochemical properties	Kinetic parameters: KM=9.8 µM for GDP-fucose Ref.11
Sequence caution	The sequence BAA76802.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAB90496.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Fucose metabolism
Cellular component	Endoplasmic reticulum Golgi apparatus
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW mesoderm formation Inferred from electronic annotation. Source: Compara regulation of epithelial to mesenchymal transition Inferred from electronic annotation. Source: Compara regulation of gene expression Inferred from electronic annotation. Source: Compara regulation of secretion Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay Ref.1. Source: UniProtKB endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	peptide-O-fucosyltransferase activity Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform C (identifier: Q9Y2G5-3)

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 A (identifier: Q9Y2G5-1)

The sequence of this isoform differs from the canonical sequence as follows:
     380-429: FFIGTSVSTF...EQPTHWKITY → CLPTSLSAES...GHFHTVCLLV

Isoform B (identifier: Q9Y2G5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     379-380: RF → SS
     381-429: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 429

408

GDP-fucose protein O-fucosyltransferase 2

PRO_0000012154

Regions

Region

53 – 56

4

Substrate binding

Region

388 – 389

2

Substrate binding

Sites

Active site

54

1

Proton donor/acceptor Probable

Binding site

294

1

Substrate

Site

396

1

Essential for catalytic activity

Amino acid modifications

Glycosylation

189

1

N-linked (GlcNAc...) Ref.11

Glycosylation

209

1

N-linked (GlcNAc...) Potential

Glycosylation

259

1

N-linked (GlcNAc...) Ref.11

Disulfide bond

161 ↔ 192

Ref.11

Disulfide bond

412 ↔ 419

Ref.11

Natural variations

Alternative sequence

379 – 380

2

RF → SS in isoform B.

VSP_003833

Alternative sequence

380 – 429

50

FFIGT…WKITY → CLPTSLSAESGSGGFQRFFC PKYSVSEQMVACVHSGHFHT VCLLV in isoform A.

VSP_003832

Alternative sequence

381 – 429

49

Missing in isoform B.

VSP_003834

Experimental info

Mutagenesis

54

1

E → A: Abolishes enzyme activity. Ref.11

Mutagenesis

92

1

W → A: Abolishes enzyme activity. Ref.11

Mutagenesis

152

1

W → A: Reduces enzyme activity. Ref.11

Mutagenesis

273

1

W → A: Reduces enzyme activity. Ref.11

Mutagenesis

294

1

R → A: Abolishes enzyme activity. Ref.11

Mutagenesis

297

1

D → A: Reduces enzyme activity. Ref.11

Mutagenesis

395

1

E → A: No enhanced secretion of ADASMTS13; when associated with A-396. Ref.9

Mutagenesis

396

1

E → A: Reduces enzyme activity. No enhanced secretion of ADASMTS13; when associated with A-396. Ref.9 Ref.11

Secondary structure

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429

Helix Strand Turn

Details...

Beta strand

44 – 48

5

Helix

56 – 74

19

Beta strand

79 – 83

5

Helix

91 – 93

3

Helix

104 – 106

3

Helix

110 – 114

5

Beta strand

119 – 121

3

Helix

122 – 128

7

Beta strand

129 – 141

13

Beta strand

156 – 159

4

Helix

179 – 181

3

Beta strand

186 – 195

10

Helix

199 – 202

4

Helix

203 – 208

6

Beta strand

213 – 219

7

Helix

220 – 222

3

Helix

231 – 238

8

Helix

244 – 258

15

Turn

262 – 266

5

Helix

273 – 275

3

Beta strand

286 – 293

8

Turn

296 – 302

7

Beta strand

304 – 306

3

Helix

309 – 323

15

Beta strand

328 – 332

5

Helix

336 – 345

10

Beta strand

349 – 351

3

Helix

356 – 376

21

Beta strand

378 – 383

6

Helix

388 – 400

13

Helix

404 – 406

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform C [UniParc]. Last modified February 15, 2005. Version 3. Checksum: 36A4213D905AFFD1	FASTA	429	49,976
	10 20 30 40 50 60 MATLSFVFLL LGAVSWPPAS ASGQEFWPGQ SAADILSGAA SRRRYLLYDV NPPEGFNLRR 70 80 90 100 110 120 DVYIRIASLL KTLLKTEEWV LVLPPWGRLY HWQSPDIHQV RIPWSEFFDL PSLNKNIPVI 130 140 150 160 170 180 EYEQFIAESG GPFIDQVYVL QSYAEGWKEG TWEEKVDERP CIDQLLYSQD KHEYYRGWFW 190 200 210 220 230 240 GYEETRGLNV SCLSVQGSAS IVAPLLLRNT SARSVMLDRA ENLLHDHYGG KEYWDTRRSM 250 260 270 280 290 300 VFARHLREVG DEFRSRHLNS TDDADRIPFQ EDWMKMKVKL GSALGGPYLG VHLRRKDFIW 310 320 330 340 350 360 GHRQDVPSLE GAVRKIRSLM KTHRLDKVFV ATDAVRKEYE ELKKLLPEMV RFEPTWEELE 370 380 390 400 410 420 LYKDGGVAII DQWICAHARF FIGTSVSTFS FRIHEEREIL GLDPKTTYNR FCGDQEKACE QPTHWKITY
	Isoform A [UniParc]. Checksum: 60BA687F0DFB8875	FASTA	424	48,896
	10 20 30 40 50 60 MATLSFVFLL LGAVSWPPAS ASGQEFWPGQ SAADILSGAA SRRRYLLYDV NPPEGFNLRR 70 80 90 100 110 120 DVYIRIASLL KTLLKTEEWV LVLPPWGRLY HWQSPDIHQV RIPWSEFFDL PSLNKNIPVI 130 140 150 160 170 180 EYEQFIAESG GPFIDQVYVL QSYAEGWKEG TWEEKVDERP CIDQLLYSQD KHEYYRGWFW 190 200 210 220 230 240 GYEETRGLNV SCLSVQGSAS IVAPLLLRNT SARSVMLDRA ENLLHDHYGG KEYWDTRRSM 250 260 270 280 290 300 VFARHLREVG DEFRSRHLNS TDDADRIPFQ EDWMKMKVKL GSALGGPYLG VHLRRKDFIW 310 320 330 340 350 360 GHRQDVPSLE GAVRKIRSLM KTHRLDKVFV ATDAVRKEYE ELKKLLPEMV RFEPTWEELE 370 380 390 400 410 420 LYKDGGVAII DQWICAHARC LPTSLSAESG SGGFQRFFCP KYSVSEQMVA CVHSGHFHTV CLLV
	Isoform B [UniParc]. Checksum: 7D640225C9A977C0	FASTA	380	44,083
	10 20 30 40 50 60 MATLSFVFLL LGAVSWPPAS ASGQEFWPGQ SAADILSGAA SRRRYLLYDV NPPEGFNLRR 70 80 90 100 110 120 DVYIRIASLL KTLLKTEEWV LVLPPWGRLY HWQSPDIHQV RIPWSEFFDL PSLNKNIPVI 130 140 150 160 170 180 EYEQFIAESG GPFIDQVYVL QSYAEGWKEG TWEEKVDERP CIDQLLYSQD KHEYYRGWFW 190 200 210 220 230 240 GYEETRGLNV SCLSVQGSAS IVAPLLLRNT SARSVMLDRA ENLLHDHYGG KEYWDTRRSM 250 260 270 280 290 300 VFARHLREVG DEFRSRHLNS TDDADRIPFQ EDWMKMKVKL GSALGGPYLG VHLRRKDFIW 310 320 330 340 350 360 GHRQDVPSLE GAVRKIRSLM KTHRLDKVFV ATDAVRKEYE ELKKLLPEMV RFEPTWEELE 370 380 LYKDGGVAII DQWICAHASS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Caenorhabditis elegans ortholog of C21orf80, a potential new protein O-fucosyltransferase, is required for normal development." Menzel O., Vellai T., Takacs-Vellai K., Reymond A., Mueller F., Antonarakis S.E., Guipponi M. Genomics 84:320-330(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"A new superfamily of protein-O-fucosyltransferases, alpha2-fucosyltransferases, and alpha6-fucosyltransferases: phylogeny and identification of conserved peptide motifs." Martinez-Duncker I., Mollicone R., Candelier J.-J., Breton C., Oriol R. Glycobiology 13:1C-5C(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
[3]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Tissue: Brain.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Tissue: Testis.
[5]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 B AND C). Tissue: Brain.
[7]	"C-mannosylation and O-fucosylation of the thrombospondin type 1 module." Hofsteenge J., Huwiler K.G., Macek B., Hess D., Lawler J., Mosher D.F., Peter-Katalinic J. J. Biol. Chem. 276:6485-6498(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Two distinct pathways for O-fucosylation of epidermal growth factor-like or thrombospondin type 1 repeats." Luo Y., Nita-Lazar A., Haltiwanger R.S. J. Biol. Chem. 281:9385-9392(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"O-fucosylation is required for ADAMTS13 secretion." Ricketts L.M., Dlugosz M., Luther K.B., Haltiwanger R.S., Majerus E.M. J. Biol. Chem. 282:17014-17023(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLU-395 AND GLU-396.
[10]	"O-fucosylation of thrombospondin type 1 repeats in ADAMTS-like-1/punctin-1 regulates secretion: implications for the ADAMTS superfamily." Wang L.W., Dlugosz M., Somerville R.P., Raed M., Haltiwanger R.S., Apte S.S. J. Biol. Chem. 282:17024-17031(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Structure of human POFUT2: insights into thrombospondin type 1 repeat fold and O-fucosylation." Chen C.I., Keusch J.J., Klein D., Hess D., Hofsteenge J., Gut H. EMBO J. 31:3183-3197(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 22-429 IN COMPLEX WITH GDP-FUCOSE, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-54; TRP-92; TRP-152; TRP-273; ARG-294; ASP-297 AND GLU-396, GLYCOSYLATION AT ASN-189 AND ASN-259, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Peptide-O-fucosyltransferase 2

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ302080 mRNA. Translation: CAC24557.1.
AJ302079 mRNA. Translation: CAC24556.1.
AY066015 mRNA. Translation: AAL47681.2.
AJ575591 mRNA. Translation: CAE01472.1.
AB023175 mRNA. Translation: BAA76802.1. Different initiation.
AL110285 mRNA. Translation: CAB53715.2.
AL163301 Genomic DNA. Translation: CAB90496.1. Different initiation.
BC011044 mRNA. Translation: AAH11044.1.
BC064623 mRNA. Translation: AAH64623.1.

IPI

IPI00032138.
IPI00218348.
IPI00218349.

RefSeq

NP_056042.1. NM_015227.4.
NP_598368.2. NM_133635.4.

UniGene

Hs.592164.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4AP5	X-ray	3.00	A/B	22-429	[»]
4AP6	X-ray	3.40	A/B/C/D	37-429	[»]

ProteinModelPortal

Q9Y2G5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y2G5. 3 interactions.

STRING

9606.ENSP00000339613.

Protein family/group databases

CAZy

GT68. Glycosyltransferase Family 68.

PTM databases

PhosphoSite

Q9Y2G5.

Polymorphism databases

DMDM

59803123.

Proteomic databases

PaxDb

Q9Y2G5.

PRIDE

Q9Y2G5.

Protocols and materials databases

DNASU

23275.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331343; ENSP00000329682; ENSG00000186866.
ENST00000334538; ENSP00000335427; ENSG00000186866.
ENST00000349485; ENSP00000339613; ENSG00000186866.

GeneID

23275.

KEGG

hsa:23275.

UCSC

uc002zhc.3. human.
uc002zhd.3. human.

Organism-specific databases

CTD

23275.

GeneCards

GC21M046683.

HGNC

HGNC:14683. POFUT2.

HPA

HPA044297.

MIM

610249. gene.

neXtProt

NX_Q9Y2G5.

PharmGKB

PA25867.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG77810.

HOVERGEN

HBG053367.

InParanoid

Q9Y2G5.

KO

K03691.

OMA

ICAHARF.

PhylomeDB

Q9Y2G5.

Enzyme and pathway databases

UniPathway

UPA00378.

Gene expression databases

ArrayExpress

Q9Y2G5.

Bgee

Q9Y2G5.

CleanEx

HS_POFUT2.

Genevestigator

Q9Y2G5.

GermOnline

ENSG00000186866. Homo sapiens.

Family and domain databases

InterPro

IPR019378. GDP-Fuc_O-FucTrfase.
[Graphical view]

Pfam

PF10250. O-FucT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

23275.

NextBio

45054.

SOURCE

Search...

Entry information

Entry name

OFUT2_HUMAN

Accession

Primary (citable) accession number: Q9Y2G5
Secondary accession number(s): Q6PJV1 , Q7Z4N0, Q8WWU6, Q9BQS4, Q9BQS5, Q9UFY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	February 15, 2005
Last modified:	May 1, 2013
This is version 96 of the entry and version 3 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.