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UniProtKB - P46977 (STT3A_HUMAN)

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Protein

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A

Gene

STT3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic subunit of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). SST3A seems to be involved in complex substrate specificity. STT3A is present in the majority of OST complexes and mediates cotranslational N-glycosylation of most sites on target proteins, while STT3B-containing complexes are required for efficient post-translational glycosylation and mediate glycosylation of sites that have been skipped by STT3A.By similarityCurated1 Publication

Catalytic activityi

Dolichyl diphosphooligosaccharide + [protein]-L-asparagine = dolichyl diphosphate + a glycoprotein with the oligosaccharide chain attached by N-beta-D-glycosyl linkage to a protein L-asparagine.

Pathwayi: protein glycosylation

This protein is involved in the pathway protein glycosylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.

GO - Molecular functioni

  • dolichyl-diphosphooligosaccharide-protein glycotransferase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
Complete GO annotation...

GO - Biological processi

  • co-translational protein modification Source: UniProtKB
  • post-translational protein modification Source: GO_Central
  • protein N-linked glycosylation via asparagine Source: UniProtKB
Complete GO annotation...

Keywordsi

Molecular functionGlycosyltransferase, Transferase
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-446203. Asparagine N-linked glycosylation.
SignaLinkiP46977.
UniPathwayiUPA00378.

Protein family/group databases

CAZyiGT66. Glycosyltransferase Family 66.
TCDBi9.B.142.3.4. the integral membrane glycosyltransferase family 39 (gt39) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A (EC:2.4.99.18)
Short name:
Oligosaccharyl transferase subunit STT3A
Short name:
STT3-A
Alternative name(s):
B5
Integral membrane protein 1
Transmembrane protein TMC
Gene namesi
Name:STT3A
Synonyms:ITM1, TMC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6172. STT3A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 17CytoplasmicSequence analysisAdd BLAST17
Transmembranei18 – 38HelicalSequence analysisAdd BLAST21
Topological domaini39 – 114LumenalSequence analysisAdd BLAST76
Transmembranei115 – 135HelicalSequence analysisAdd BLAST21
Topological domaini136 – 169CytoplasmicSequence analysisAdd BLAST34
Transmembranei170 – 190HelicalSequence analysisAdd BLAST21
Topological domaini191 – 208LumenalSequence analysisAdd BLAST18
Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
Topological domaini230 – 235CytoplasmicSequence analysis6
Transmembranei236 – 259HelicalSequence analysisAdd BLAST24
Topological domaini260 – 265LumenalSequence analysis6
Transmembranei266 – 286HelicalSequence analysisAdd BLAST21
Topological domaini287 – 300CytoplasmicSequence analysisAdd BLAST14
Transmembranei301 – 321HelicalSequence analysisAdd BLAST21
Topological domaini322 – 359LumenalSequence analysisAdd BLAST38
Transmembranei360 – 380HelicalSequence analysisAdd BLAST21
Topological domaini381 – 383CytoplasmicSequence analysis3
Transmembranei384 – 404HelicalSequence analysisAdd BLAST21
Topological domaini405LumenalSequence analysis1
Transmembranei406 – 426HelicalSequence analysisAdd BLAST21
Topological domaini427 – 453CytoplasmicSequence analysisAdd BLAST27
Transmembranei454 – 474HelicalSequence analysisAdd BLAST21
Topological domaini475 – 705LumenalSequence analysisAdd BLAST231

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Congenital disorder of glycosylation 1W (CDG1W)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
See also OMIM:615596
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070944626V → A in CDG1W; affects activity resulting in hypoglycosylation of STT3A-specific substrates. 1 PublicationCorresponds to variant dbSNP:rs587777216Ensembl.1

Keywords - Diseasei

Congenital disorder of glycosylation, Disease mutation

Organism-specific databases

DisGeNETi3703.
MalaCardsiSTT3A.
MIMi615596. phenotype.
OpenTargetsiENSG00000134910.
Orphaneti370921. STT3A-CDG.
PharmGKBiPA29969.

Polymorphism and mutation databases

DMDMi182676409.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000722901 – 705Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3AAdd BLAST705

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi537N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi544N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi548N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP46977.
MaxQBiP46977.
PaxDbiP46977.
PeptideAtlasiP46977.
PRIDEiP46977.

PTM databases

iPTMnetiP46977.
PhosphoSitePlusiP46977.
SwissPalmiP46977.

Expressioni

Tissue specificityi

Expressed at high levels in placenta, liver, muscle and pancreas, and at very low levels in brain, lung and kidney. Expressed in skin fibroblasts (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000134910.
CleanExiHS_STT3A.
ExpressionAtlasiP46977. baseline and differential.
GenevisibleiP46977. HS.

Organism-specific databases

HPAiHPA030735.

Interactioni

Subunit structurei

Component of the oligosaccharyltransferase (OST) complex. OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits. OST can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes.By similarityCurated2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109908. 23 interactors.
IntActiP46977. 40 interactors.
MINTiMINT-1407187.
STRINGi9606.ENSP00000376472.

Structurei

3D structure databases

ProteinModelPortaliP46977.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the STT3 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2292. Eukaryota.
COG1287. LUCA.
GeneTreeiENSGT00390000015238.
HOGENOMiHOG000157471.
HOVERGENiHBG010606.
InParanoidiP46977.
KOiK07151.
OMAiSWSSFYF.
OrthoDBiEOG091G02DB.
PhylomeDBiP46977.
TreeFamiTF300822.

Family and domain databases

InterProiView protein in InterPro
IPR003674. Oligo_trans_STT3.
PfamiView protein in Pfam
PF02516. STT3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P46977-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTKFGFLRLS YEKQDTLLKL LILSMAAVLS FSTRLFAVLR FESVIHEFDP 
        60         70         80         90        100
YFNYRTTRFL AEEGFYKFHN WFDDRAWYPL GRIIGGTIYP GLMITSAAIY 
       110        120        130        140        150
HVLHFFHITI DIRNVCVFLA PLFSSFTTIV TYHLTKELKD AGAGLLAAAM 
       160        170        180        190        200
IAVVPGYISR SVAGSYDNEG IAIFCMLLTY YMWIKAVKTG SICWAAKCAL 
       210        220        230        240        250
AYFYMVSSWG GYVFLINLIP LHVLVLMLTG RFSHRIYVAY CTVYCLGTIL 
       260        270        280        290        300
SMQISFVGFQ PVLSSEHMAA FGVFGLCQIH AFVDYLRSKL NPQQFEVLFR 
       310        320        330        340        350
SVISLVGFVL LTVGALLMLT GKISPWTGRF YSLLDPSYAK NNIPIIASVS 
       360        370        380        390        400
EHQPTTWSSY YFDLQLLVFM FPVGLYYCFS NLSDARIFII MYGVTSMYFS 
       410        420        430        440        450
AVMVRLMLVL APVMCILSGI GVSQVLSTYM KNLDISRPDK KSKKQQDSTY 
       460        470        480        490        500
PIKNEVASGM ILVMAFFLIT YTFHSTWVTS EAYSSPSIVL SARGGDGSRI 
       510        520        530        540        550
IFDDFREAYY WLRHNTPEDA KVMSWWDYGY QITAMANRTI LVDNNTWNNT 
       560        570        580        590        600
HISRVGQAMA STEEKAYEIM RELDVSYVLV IFGGLTGYSS DDINKFLWMV 
       610        620        630        640        650
RIGGSTDTGK HIKENDYYTP TGEFRVDREG SPVLLNCLMY KMCYYRFGQV 
       660        670        680        690        700
YTEAKRPPGF DRVRNAEIGN KDFELDVLEE AYTTEHWLVR IYKVKDLDNR 

GLSRT
Length:705
Mass (Da):80,530
Last modified:April 8, 2008 - v2
Checksum:i71426CA5598B51C4
GO
Isoform 2 (identifier: P46977-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-92: Missing.

Show »
Length:613
Mass (Da):69,589
Checksum:iB37EB58A0D0776FC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61A → S in AAL77539 (PubMed:8634329).Curated1
Sequence conflicti117V → M in BAG58686 (PubMed:14702039).Curated1
Sequence conflicti128T → S in AAB05994 (PubMed:8838310).Curated1
Sequence conflicti133H → L in AAB05994 (PubMed:8838310).Curated1
Sequence conflicti252M → R in AAB05994 (PubMed:8838310).Curated1
Sequence conflicti270A → G in AAB05994 (PubMed:8838310).Curated1
Sequence conflicti415C → S in AAB05994 (PubMed:8838310).Curated1
Sequence conflicti454N → I in AAB05994 (PubMed:8838310).Curated1
Sequence conflicti494G → D in AAL77539 (PubMed:8634329).Curated1
Sequence conflicti681A → G in AAB05994 (PubMed:8838310).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070944626V → A in CDG1W; affects activity resulting in hypoglycosylation of STT3A-specific substrates. 1 PublicationCorresponds to variant dbSNP:rs587777216Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0551061 – 92Missing in isoform 2. 1 PublicationAdd BLAST92

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L38961 mRNA. Translation: AAB05994.1.
L47337 mRNA. Translation: AAL77539.1.
AK290040 mRNA. Translation: BAF82729.1.
AK290657 mRNA. Translation: BAF83346.1.
AK295892 mRNA. Translation: BAG58686.1.
BT007100 mRNA. Translation: AAP35764.1.
AP001132 Genomic DNA. No translation available.
AP001494 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67647.1.
BC020965 mRNA. Translation: AAH20965.1.
BC048348 mRNA. Translation: AAH48348.2.
CCDSiCCDS60998.1. [P46977-2]
CCDS8458.1. [P46977-1]
PIRiS70029.
RefSeqiNP_001265432.1. NM_001278503.1. [P46977-1]
NP_001265433.1. NM_001278504.1. [P46977-2]
NP_689926.1. NM_152713.4. [P46977-1]
XP_011541109.1. XM_011542807.2. [P46977-1]
UniGeneiHs.504237.
Hs.659244.

Genome annotation databases

EnsembliENST00000392708; ENSP00000376472; ENSG00000134910. [P46977-1]
ENST00000529196; ENSP00000436962; ENSG00000134910. [P46977-1]
ENST00000531491; ENSP00000432820; ENSG00000134910. [P46977-2]
GeneIDi3703.
KEGGihsa:3703.
UCSCiuc001qcd.4. human. [P46977-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSTT3A_HUMAN
AccessioniPrimary (citable) accession number: P46977
Secondary accession number(s): B4DJ24
, E9PNQ1, Q86XU9, Q8TE35, Q8WUB4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: April 8, 2008
Last modified: June 7, 2017
This is version 147 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families