S61A2_HUMAN
ID S61A2_HUMAN Reviewed; 476 AA.
AC Q9H9S3; A8K8D0; B4DX72; F8W773;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Protein transport protein Sec61 subunit alpha isoform 2;
DE Short=Sec61 alpha-2;
GN Name=SEC61A2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Finke K., Prehn S., Hartmann E.;
RT "Sec61 alpha isoforms.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Appears to play a crucial role in the insertion of secretory
CC and membrane polypeptides into the ER. It is required for assembly of
CC membrane and secretory proteins. Found to be tightly associated with
CC membrane-bound ribosomes, either directly or through adaptor proteins
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterotrimeric complex composed of SEC61-alpha, SEC61-beta and
CC SEC61-gamma. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9H9S3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H9S3-2; Sequence=VSP_010472;
CC Name=3;
CC IsoId=Q9H9S3-3; Sequence=VSP_046380;
CC -!- SIMILARITY: Belongs to the SecY/SEC61-alpha family. {ECO:0000305}.
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DR EMBL; AF346603; AAK29084.1; -; mRNA.
DR EMBL; AK022640; BAB14148.1; -; mRNA.
DR EMBL; AK292295; BAF84984.1; -; mRNA.
DR EMBL; AK301841; BAG63284.1; -; mRNA.
DR EMBL; AC073160; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW86324.1; -; Genomic_DNA.
DR CCDS; CCDS44358.1; -. [Q9H9S3-2]
DR CCDS; CCDS44359.1; -. [Q9H9S3-3]
DR CCDS; CCDS7088.1; -. [Q9H9S3-1]
DR RefSeq; NP_001136099.1; NM_001142627.2. [Q9H9S3-2]
DR RefSeq; NP_001136100.1; NM_001142628.1. [Q9H9S3-3]
DR RefSeq; NP_060614.2; NM_018144.3. [Q9H9S3-1]
DR AlphaFoldDB; Q9H9S3; -.
DR SMR; Q9H9S3; -.
DR BioGRID; 120475; 39.
DR IntAct; Q9H9S3; 10.
DR STRING; 9606.ENSP00000298428; -.
DR TCDB; 3.A.5.9.1; the general secretory pathway (sec) family.
DR iPTMnet; Q9H9S3; -.
DR PhosphoSitePlus; Q9H9S3; -.
DR SwissPalm; Q9H9S3; -.
DR BioMuta; SEC61A2; -.
DR DMDM; 48477069; -.
DR EPD; Q9H9S3; -.
DR jPOST; Q9H9S3; -.
DR MassIVE; Q9H9S3; -.
DR MaxQB; Q9H9S3; -.
DR PaxDb; Q9H9S3; -.
DR PeptideAtlas; Q9H9S3; -.
DR PRIDE; Q9H9S3; -.
DR ProteomicsDB; 29899; -.
DR ProteomicsDB; 81357; -. [Q9H9S3-1]
DR ProteomicsDB; 81358; -. [Q9H9S3-2]
DR Antibodypedia; 71451; 7 antibodies from 5 providers.
DR DNASU; 55176; -.
DR Ensembl; ENST00000298428.14; ENSP00000298428.9; ENSG00000065665.21. [Q9H9S3-1]
DR Ensembl; ENST00000304267.12; ENSP00000302048.8; ENSG00000065665.21. [Q9H9S3-2]
DR Ensembl; ENST00000379033.7; ENSP00000368319.3; ENSG00000065665.21. [Q9H9S3-3]
DR GeneID; 55176; -.
DR KEGG; hsa:55176; -.
DR MANE-Select; ENST00000298428.14; ENSP00000298428.9; NM_018144.4; NP_060614.2.
DR UCSC; uc001ile.3; human. [Q9H9S3-1]
DR CTD; 55176; -.
DR DisGeNET; 55176; -.
DR GeneCards; SEC61A2; -.
DR HGNC; HGNC:17702; SEC61A2.
DR HPA; ENSG00000065665; Low tissue specificity.
DR MIM; 618271; gene.
DR neXtProt; NX_Q9H9S3; -.
DR OpenTargets; ENSG00000065665; -.
DR PharmGKB; PA134861382; -.
DR VEuPathDB; HostDB:ENSG00000065665; -.
DR eggNOG; KOG1373; Eukaryota.
DR GeneTree; ENSGT00390000003721; -.
DR HOGENOM; CLU_031763_2_0_1; -.
DR InParanoid; Q9H9S3; -.
DR OMA; KWGIGSG; -.
DR PhylomeDB; Q9H9S3; -.
DR TreeFam; TF300348; -.
DR PathwayCommons; Q9H9S3; -.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane.
DR SignaLink; Q9H9S3; -.
DR SIGNOR; Q9H9S3; -.
DR BioGRID-ORCS; 55176; 13 hits in 1078 CRISPR screens.
DR ChiTaRS; SEC61A2; human.
DR GenomeRNAi; 55176; -.
DR Pharos; Q9H9S3; Tdark.
DR PRO; PR:Q9H9S3; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9H9S3; protein.
DR Bgee; ENSG00000065665; Expressed in cortical plate and 134 other tissues.
DR ExpressionAtlas; Q9H9S3; baseline and differential.
DR Genevisible; Q9H9S3; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005784; C:Sec61 translocon complex; IBA:GO_Central.
DR GO; GO:0008320; F:protein transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0043022; F:ribosome binding; IBA:GO_Central.
DR GO; GO:0005048; F:signal sequence binding; IBA:GO_Central.
DR GO; GO:0031204; P:post-translational protein targeting to membrane, translocation; IBA:GO_Central.
DR GO; GO:0006616; P:SRP-dependent cotranslational protein targeting to membrane, translocation; IBA:GO_Central.
DR Gene3D; 1.10.3370.10; -; 1.
DR InterPro; IPR002208; SecY/SEC61-alpha.
DR InterPro; IPR030659; SecY_CS.
DR InterPro; IPR023201; SecY_dom_sf.
DR InterPro; IPR019561; Translocon_Sec61/SecY_plug_dom.
DR PANTHER; PTHR10906; PTHR10906; 1.
DR Pfam; PF10559; Plug_translocon; 1.
DR Pfam; PF00344; SecY; 1.
DR PIRSF; PIRSF004557; SecY; 1.
DR SUPFAM; SSF103491; SSF103491; 1.
DR TIGRFAMs; TIGR00967; 3a0501s007; 1.
DR PROSITE; PS00755; SECY_1; 1.
DR PROSITE; PS00756; SECY_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Endoplasmic reticulum; Membrane; Protein transport;
KW Reference proteome; Translocation; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..476
FT /note="Protein transport protein Sec61 subunit alpha
FT isoform 2"
FT /id="PRO_0000131795"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 54..76
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..117
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 139..144
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..240
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..354
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 376..420
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 421..441
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..445
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..462
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 463..476
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VAR_SEQ 26..47
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046380"
FT VAR_SEQ 416..476
FT /note="YIPTAAAFGGLCIGALSVLADFLGAIGSGTGILLAVTIIYQYFEIFVKEQAE
FT VGGMGALFF -> PKVKLRRWKGEGRHFTKRILFY (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_010472"
FT CONFLICT 16
FT /note="L -> P (in Ref. 2; BAB14148)"
FT /evidence="ECO:0000305"
FT CONFLICT 133
FT /note="M -> I (in Ref. 2; BAB14148)"
FT /evidence="ECO:0000305"
FT CONFLICT 370
FT /note="G -> E (in Ref. 2; BAG63284)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 52248 MW; 87CC8E7D366C2C37 CRC64;
MGIKFLEVIK PFCAVLPEIQ KPERKIQFRE KVLWTAITLF IFLVCCQIPL FGIMSSDSAD
PFYWMRVILA SNRGTLMELG ISPIVTSGLI MQLLAGAKII EVGDTPKDRA LFNGAQKLFG
MIITIGQAIV YVMTGMYGDP AEMGAGICLL IIIQLFVAGL IVLLLDELLQ KGYGLGSGIS
LFIATNICET IVWKAFSPTT INTGRGTEFE GAVIALFHLL ATRTDKVRAL REAFYRQNLP
NLMNLIATVF VFAVVIYFQG FRVDLPIKSA RYRGQYSSYP IKLFYTSNIP IILQSALVSN
LYVISQMLSV RFSGNFLVNL LGQWADVSGG GPARSYPVGG LCYYLSPPES MGAIFEDPVH
VVVYIIFMLG SCAFFSKTWI EVSGSSAKDV AKQLKEQQMV MRGHRDTSMV HELNRYIPTA
AAFGGLCIGA LSVLADFLGA IGSGTGILLA VTIIYQYFEI FVKEQAEVGG MGALFF
