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Q8IXK2 (GLT12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Polypeptide N-acetylgalactosaminyltransferase 12

EC=2.4.1.41
Alternative name(s):
Polypeptide GalNAc transferase 12
Short name=GalNAc-T12
Short name=pp-GaNTase 12
Protein-UDP acetylgalactosaminyltransferase 12
UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 12
Gene names
Name:GALNT12
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length581 AA.
Sequence statusComplete.
Protein existenceEvidence 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 non-glycosylated peptides such as Muc5AC, Muc1a and EA2, and no detectable activity with Muc2 and Muc7. Displays enzymatic activity toward the Gal-NAc-Muc5AC glycopeptide, but no detectable activity to mono-GalNAc-glycosylated Muc1a, Muc2, Muc7 and EA2. May play an important role in the initial step of mucin-type oligosaccharide biosynthesis in digestive organs.

Catalytic activity

UDP-N-acetyl-alpha-D-galactosamine + polypeptide = UDP + N-acetyl-alpha-D-galactosaminyl-polypeptide. Ref.1

Cofactor

Manganese By similarity.

Pathway

Protein modification; protein glycosylation.

Subcellular location

Golgi apparatus membrane; Single-pass type II membrane protein By similarity.

Tissue specificity

Widely expressed at different levels of expression. Highly expressed in digestive organs such as small intestine, stomach, pancreas and colon. Expressed at intermediate level in testis, thyroid gland and spleen. Weakly expressed in whole brain, cerebral cortex, cerebellum, fetal brain, bone marrow, thymus, leukocytes, heart, skeletal muscle, liver, lung, esophagus, kidney, adrenal gland, mammary gland, uterus, placenta, ovary and prostate. Ref.1

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

Colorectal cancer 1 (CRCS1) [MIM:608812]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. The role of GALNT12 in colon cancer susceptibility is however subject to discussion: studies on 103 probants with colorectal cancer 1 (CRCS1) suggest that it does not act as a major contributor of CRCS1 (Ref.8). Ref.6 Ref.7 Ref.8

Sequence similarities

Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.

Contains 1 ricin B-type lectin domain.

Sequence caution

The sequence BAB15027.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IXK2-1)

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: Q8IXK2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-309: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 581581Polypeptide N-acetylgalactosaminyltransferase 12
PRO_0000059128

Regions

Topological domain1 – 1919Cytoplasmic Potential
Transmembrane20 – 3718Helical; Signal-anchor for type II membrane protein; Potential
Topological domain38 – 581544Lumenal Potential
Domain445 – 577133Ricin B-type lectin
Region135 – 244110Catalytic subdomain A
Region304 – 36663Catalytic subdomain B

Sites

Metal binding2281Manganese By similarity
Metal binding2301Manganese By similarity
Metal binding3631Manganese By similarity
Binding site1761Substrate By similarity
Binding site2051Substrate By similarity
Binding site3351Substrate By similarity
Binding site3711Substrate By similarity

Amino acid modifications

Disulfide bond125 ↔ 358 By similarity
Disulfide bond349 ↔ 422 By similarity
Disulfide bond458 ↔ 479 By similarity
Disulfide bond506 ↔ 521 By similarity
Disulfide bond547 ↔ 566 By similarity

Natural variations

Alternative sequence1 – 309309Missing in isoform 2.
VSP_011217
Natural variant31G → E. Ref.6
VAR_064352
Natural variant461G → R. Ref.6
Corresponds to variant rs10987768 [ dbSNP | Ensembl ].
VAR_064353
Natural variant1191E → V. Ref.1 Ref.6
Corresponds to variant rs1137654 [ dbSNP | Ensembl ].
VAR_064354
Natural variant2611D → N. Ref.6
Corresponds to variant rs41306504 [ dbSNP | Ensembl ].
VAR_064355
Natural variant2721G → R. Ref.6
VAR_064356
Natural variant2971R → W in CRCS1; germline mutation; partial loss of activity. Ref.6
VAR_064357
Natural variant3031D → N in CRCS1; germline mutation; reduction of activity. Ref.6 Ref.7
Corresponds to variant rs145236923 [ dbSNP | Ensembl ].
VAR_064358
Natural variant3411E → D in CRCS1; somatic mutation; loss of activity. Ref.6
VAR_064359
Natural variant3731R → H in CRCS1; germline mutation; partial loss of activity. Ref.6
VAR_064360
Natural variant3821R → H in CRCS1; germline mutation; loss of activity. Ref.6
VAR_064361
Natural variant3961Y → C in CRCS1. Ref.7
VAR_068509
Natural variant4791C → F in CRCS1; somatic mutation; loss of activity. Ref.6
VAR_064362
Natural variant4911T → M in CRCS1; germline mutation; loss of activity. Ref.6
VAR_064363
Natural variant5521R → K. Ref.6
VAR_064364

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 20, 2005. Version 3.
Checksum: 8C001D58E103A523

FASTA58166,938
        10         20         30         40         50         60 
MWGRTARRRC PRELRRGREA LLVLLALLAL AGLGSVLRAQ RGAGAGAAEP GPPRTPRPGR 

        70         80         90        100        110        120 
REPVMPRPPV PANALGARGE AVRLQLQGEE LRLQEESVRL HQINIYLSDR ISLHRRLPER 

       130        140        150        160        170        180 
WNPLCKEKKY DYDNLPRTSV IIAFYNEAWS TLLRTVYSVL ETSPDILLEE VILVDDYSDR 

       190        200        210        220        230        240 
EHLKERLANE LSGLPKVRLI RANKREGLVR ARLLGASAAR GDVLTFLDCH CECHEGWLEP 

       250        260        270        280        290        300 
LLQRIHEEES AVVCPVIDVI DWNTFEYLGN SGEPQIGGFD WRLVFTWHTV PERERIRMQS 

       310        320        330        340        350        360 
PVDVIRSPTM AGGLFAVSKK YFEYLGSYDT GMEVWGGENL EFSFRIWQCG GVLETHPCSH 

       370        380        390        400        410        420 
VGHVFPKQAP YSRNKALANS VRAAEVWMDE FKELYYHRNP RARLEPFGDV TERKQLRDKL 

       430        440        450        460        470        480 
QCKDFKWFLE TVYPELHVPE DRPGFFGMLQ NKGLTDYCFD YNPPDENQIV GHQVILYLCH 

       490        500        510        520        530        540 
GMGQNQFFEY TSQKEIRYNT HQPEGCIAVE AGMDTLIMHL CEETAPENQK FILQEDGSLF 

       550        560        570        580 
HEQSKKCVQA ARKESSDSFV PLLRDCTNSD HQKWFFKERM L 

« Hide

Isoform 2 [UniParc].

Checksum: 6E78ADD3FC84390F
Show »

FASTA27231,726

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a novel member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, pp-GalNAc-T12(1)."
Guo J.-M., Zhang Y., Cheng L., Iwasaki H., Wang H., Kubota T., Tachibana K., Narimatsu H.
FEBS Lett. 524:211-218(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, TISSUE SPECIFICITY, VARIANT VAL-119.
Tissue: Lung.
[2]Bennett E.P.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
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] (ISOFORM 2).
Tissue: Bone marrow.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-581 (ISOFORM 1).
Tissue: Colon.
[6]"Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers."
Guda K., Moinova H., He J., Jamison O., Ravi L., Natale L., Lutterbaugh J., Lawrence E., Lewis S., Willson J.K., Lowe J.B., Wiesner G.L., Parmigiani G., Barnholtz-Sloan J., Dawson D.W., Velculescu V.E., Kinzler K.W., Papadopoulos N. expand/collapse author list , Vogelstein B., Willis J., Gerken T.A., Markowitz S.D.
Proc. Natl. Acad. Sci. U.S.A. 106:12921-12925(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CRCS1 TRP-297; ASN-303; ASP-341; HIS-373; HIS-382; PHE-479 AND MET-491, CHARACTERIZATION OF VARIANTS CRCS1 TRP-297; ASN-303; ASP-341; HIS-373; HIS-382; PHE-479 AND MET-491, VARIANTS GLU-3; ARG-46; VAL-119; ASN-261; ARG-272 AND LYS-552.
[7]"Inherited deleterious variants in GALNT12 are associated with CRC susceptibility."
Clarke E., Green R.C., Green J.S., Mahoney K., Parfrey P.S., Younghusband H.B., Woods M.O.
Hum. Mutat. 33:1056-1058(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CRCS1 ASN-303 AND CYS-396.
[8]"GALNT12 is not a major contributor of familial colorectal cancer type X."
Segui N., Pineda M., Navarro M., Lazaro C., Brunet J., Infante M., Duran M., Soto J.L., Blanco I., Capella G., Valle L.
Hum. Mutat. 35:50-52(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CRCS1.
+Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Polypeptide N-acetylgalactosaminyltransferase 12

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB078146 mRNA. Translation: BAC07181.1.
AJ132365 mRNA. Translation: CAC80100.2.
AL136084 Genomic DNA. Translation: CAI17042.1.
BC013945 mRNA. Translation: AAH13945.1.
AK024865 mRNA. Translation: BAB15027.1. Different initiation.
CCDSCCDS6737.1. [Q8IXK2-1]
RefSeqNP_078918.3. NM_024642.4. [Q8IXK2-1]
XP_006717350.1. XM_006717287.1.
UniGeneHs.47099.

3D structure databases

ProteinModelPortalQ8IXK2.
SMRQ8IXK2. Positions 117-350.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122816. 3 interactions.
STRING9606.ENSP00000364150.

Protein family/group databases

CAZyCBM13. Carbohydrate-Binding Module Family 13.
GT27. Glycosyltransferase Family 27.

PTM databases

PhosphoSiteQ8IXK2.

Polymorphism databases

DMDM84028209.

Proteomic databases

MaxQBQ8IXK2.
PaxDbQ8IXK2.
PRIDEQ8IXK2.

Protocols and materials databases

DNASU79695.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375011; ENSP00000364150; ENSG00000119514. [Q8IXK2-1]
GeneID79695.
KEGGhsa:79695.
UCSCuc004ayz.3. human. [Q8IXK2-1]

Organism-specific databases

CTD79695.
GeneCardsGC09P101569.
H-InvDBHIX0008226.
HGNCHGNC:19877. GALNT12.
HPAHPA048292.
MIM608812. phenotype.
610290. gene.
neXtProtNX_Q8IXK2.
PharmGKBPA134929192.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG239675.
HOGENOMHOG000038227.
HOVERGENHBG051699.
InParanoidQ8IXK2.
KOK00710.
OMAKELYYHR.
OrthoDBEOG7J9VP2.
PhylomeDBQ8IXK2.
TreeFamTF352660.

Enzyme and pathway databases

BRENDA2.4.1.41. 2681.
ReactomeREACT_17015. Metabolism of proteins.
UniPathwayUPA00378.

Gene expression databases

BgeeQ8IXK2.
CleanExHS_GALNT12.
GenevestigatorQ8IXK2.

Family and domain databases

Gene3D3.90.550.10. 1 hit.
InterProIPR001173. Glyco_trans_2-like.
IPR029044. Nucleotide-diphossugar_trans.
IPR000772. Ricin_B_lectin.
[Graphical view]
PfamPF00535. Glycos_transf_2. 1 hit.
PF00652. Ricin_B_lectin. 1 hit.
[Graphical view]
SMARTSM00458. RICIN. 1 hit.
[Graphical view]
SUPFAMSSF50370. SSF50370. 1 hit.
SSF53448. SSF53448. 1 hit.
PROSITEPS50231. RICIN_B_LECTIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi79695.
NextBio68982.
PROQ8IXK2.
SOURCESearch...

Entry information

Entry nameGLT12_HUMAN
AccessionPrimary (citable) accession number: Q8IXK2
Secondary accession number(s): Q5TCF7 expand/collapse secondary AC list , Q8NG54, Q96CT9, Q9H771
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: December 20, 2005
Last modified: July 9, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM