STAC2_HUMAN
ID STAC2_HUMAN Reviewed; 411 AA.
AC Q6ZMT1; Q32MA3;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=SH3 and cysteine-rich domain-containing protein 2;
DE AltName: Full=24b2/STAC2 {ECO:0000303|PubMed:14702039};
DE AltName: Full=Src homology 3 and cysteine-rich domain-containing protein 2;
GN Name=STAC2;
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).
RC TISSUE=Brain;
RA Rossner M., Faucheron N., Wuerz R., von Ahsen O., Kammandel B.,
RA Schwaninger M., Schneider A.;
RT "Cloning of 24b2/STAC2, a novel STAC-homologous gene up-regulated in
RT cerebral ischemia in mice.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0007744|PDB:6B26, ECO:0007744|PDB:6B27, ECO:0007744|PDB:6B28}
RP X-RAY CRYSTALLOGRAPHY (1.20 ANGSTROMS) OF 296-411 IN COMPLEX WITH CACNA1S
RP PEPTIDE, INTERACTION WITH CACNA1S AND CACNA1C, AND MUTAGENESIS OF GLN-306;
RP TRP-329 AND GLN-347.
RX PubMed=29078335; DOI=10.1073/pnas.1708852114;
RA Wong King Yuen S.M., Campiglio M., Tung C.C., Flucher B.E., Van Petegem F.;
RT "Structural insights into binding of STAC proteins to voltage-gated calcium
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E9520-E9528(2017).
CC -!- FUNCTION: Plays a redundant role in promoting the expression of calcium
CC channel CACNA1S at the cell membrane, and thereby contributes to
CC increased channel activity. Slows down the inactivation rate of the
CC calcium channel CACNA1C. {ECO:0000250|UniProtKB:Q8R1B0}.
CC -!- SUBUNIT: Interacts (via SH3 domains) with CACNA1S (PubMed:29078335).
CC Interacts (via SH3 domains) with CACNA1C (PubMed:29078335). Has much
CC lower affinity for CACNA1C than for CACNA1S (PubMed:29078335).
CC {ECO:0000269|PubMed:29078335}.
CC -!- INTERACTION:
CC Q6ZMT1; P54253: ATXN1; NbExp=4; IntAct=EBI-948802, EBI-930964;
CC Q6ZMT1; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-948802, EBI-739832;
CC Q6ZMT1; P54646: PRKAA2; NbExp=3; IntAct=EBI-948802, EBI-1383852;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8R1B0}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8R1B0}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8R1B0}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q8R1B0}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:Q8R1B0}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8R1B0}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q8R1B0}. Note=Colocalizes with CACNA1C at the
CC plasma membrane of transfected cells. {ECO:0000250|UniProtKB:Q8R1B0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZMT1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZMT1-2; Sequence=VSP_022742;
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DR EMBL; AJ608762; CAE75539.1; -; mRNA.
DR EMBL; AK131500; BAD18644.1; -; mRNA.
DR EMBL; BC109231; AAI09232.1; -; mRNA.
DR CCDS; CCDS11335.1; -. [Q6ZMT1-1]
DR RefSeq; NP_945344.1; NM_198993.3. [Q6ZMT1-1]
DR PDB; 6B26; X-ray; 1.20 A; A=296-411.
DR PDB; 6B27; X-ray; 1.73 A; A/B/C/D/E/F=296-411.
DR PDB; 6B28; X-ray; 2.55 A; A=296-411.
DR PDBsum; 6B26; -.
DR PDBsum; 6B27; -.
DR PDBsum; 6B28; -.
DR AlphaFoldDB; Q6ZMT1; -.
DR SMR; Q6ZMT1; -.
DR BioGRID; 131192; 18.
DR IntAct; Q6ZMT1; 3.
DR STRING; 9606.ENSP00000327509; -.
DR iPTMnet; Q6ZMT1; -.
DR PhosphoSitePlus; Q6ZMT1; -.
DR BioMuta; STAC2; -.
DR DMDM; 74749556; -.
DR MassIVE; Q6ZMT1; -.
DR PaxDb; Q6ZMT1; -.
DR PeptideAtlas; Q6ZMT1; -.
DR PRIDE; Q6ZMT1; -.
DR ProteomicsDB; 67911; -. [Q6ZMT1-1]
DR ProteomicsDB; 67912; -. [Q6ZMT1-2]
DR Antibodypedia; 2798; 162 antibodies from 25 providers.
DR DNASU; 342667; -.
DR Ensembl; ENST00000333461.6; ENSP00000327509.5; ENSG00000141750.7. [Q6ZMT1-1]
DR GeneID; 342667; -.
DR KEGG; hsa:342667; -.
DR MANE-Select; ENST00000333461.6; ENSP00000327509.5; NM_198993.5; NP_945344.1.
DR UCSC; uc002hrs.4; human. [Q6ZMT1-1]
DR CTD; 342667; -.
DR DisGeNET; 342667; -.
DR GeneCards; STAC2; -.
DR HGNC; HGNC:23990; STAC2.
DR HPA; ENSG00000141750; Tissue enhanced (brain, breast, retina, skin).
DR neXtProt; NX_Q6ZMT1; -.
DR OpenTargets; ENSG00000141750; -.
DR PharmGKB; PA134939947; -.
DR VEuPathDB; HostDB:ENSG00000141750; -.
DR eggNOG; ENOG502QW9G; Eukaryota.
DR GeneTree; ENSGT00950000183092; -.
DR HOGENOM; CLU_048120_0_0_1; -.
DR InParanoid; Q6ZMT1; -.
DR OMA; ICVGVGK; -.
DR OrthoDB; 584382at2759; -.
DR PhylomeDB; Q6ZMT1; -.
DR TreeFam; TF332878; -.
DR PathwayCommons; Q6ZMT1; -.
DR SignaLink; Q6ZMT1; -.
DR BioGRID-ORCS; 342667; 9 hits in 1060 CRISPR screens.
DR ChiTaRS; STAC2; human.
DR GenomeRNAi; 342667; -.
DR Pharos; Q6ZMT1; Tbio.
DR PRO; PR:Q6ZMT1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6ZMT1; protein.
DR Bgee; ENSG00000141750; Expressed in popliteal artery and 122 other tissues.
DR ExpressionAtlas; Q6ZMT1; baseline and differential.
DR Genevisible; Q6ZMT1; HS.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0003009; P:skeletal muscle contraction; IBA:GO_Central.
DR CDD; cd00029; C1; 1.
DR CDD; cd11985; SH3_Stac2_C; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR039688; STAC1/2/3.
DR InterPro; IPR035509; Stac2_SH3.
DR PANTHER; PTHR15135; PTHR15135; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50002; SH3; 2.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; SH3 domain;
KW Zinc; Zinc-finger.
FT CHAIN 1..411
FT /note="SH3 and cysteine-rich domain-containing protein 2"
FT /id="PRO_0000274413"
FT DOMAIN 292..351
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 354..411
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT ZN_FING 110..161
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 64..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 174..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..95
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 231..249
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R1B0"
FT VAR_SEQ 1..142
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022742"
FT MUTAGEN 306
FT /note="Q->L: Mildly decreased affinity for CACNA1S."
FT /evidence="ECO:0000269|PubMed:29078335"
FT MUTAGEN 329
FT /note="W->S: Loss of interaction with CACNA1S."
FT /evidence="ECO:0000269|PubMed:29078335"
FT MUTAGEN 347
FT /note="Q->I: No effect on the structure of the two SH3
FT domains."
FT /evidence="ECO:0000269|PubMed:29078335"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 318..323
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 326..334
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 337..342
FT /evidence="ECO:0007829|PDB:6B26"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 354..360
FT /evidence="ECO:0007829|PDB:6B26"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:6B26"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 390..396
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 399..404
FT /evidence="ECO:0007829|PDB:6B26"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:6B26"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:6B26"
SQ SEQUENCE 411 AA; 45009 MW; 878DD19AFC305D0E CRC64;
MTEMSEKENE PDDAATHSPP GTVSALQETK LQRFKRSLSL KTILRSKSLE NFFLRSGSEL
KCPTEVLLTP PTPLPPPSPP PTASDRGLAT PSPSPCPVPR PLAALKPVRL HSFQEHVFKR
ASPCELCHQL IVGNSKQGLR CKMCKVSVHL WCSEEISHQQ CPGKTSTSFR RNFSSPLLVH
EPPPVCATSK ESPPTGDSGK VDPVYETLRY GTSLALMNRS SFSSTSESPT RSLSERDELT
EDGEGSIRSS EEGPGDSASP VFTAPAESEG PGPEEKSPGQ QLPKATLRKD VGPMYSYVAL
YKFLPQENND LALQPGDRIM LVDDSNEDWW KGKIGDRVGF FPANFVQRVR PGENVWRCCQ
PFSGNKEQGY MSLKENQICV GVGRSKDADG FIRVSSGKKR GLVPVDALTE I
