CAN6_HUMAN
ID CAN6_HUMAN Reviewed; 641 AA.
AC Q9Y6Q1; D3DUY7; Q9UEQ1; Q9UJA8;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Calpain-6;
DE AltName: Full=Calpain-like protease X-linked;
DE AltName: Full=Calpamodulin;
DE Short=CalpM;
GN Name=CAPN6; Synonyms=CALPM, CANPX;
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].
RX PubMed=9339374; DOI=10.1006/geno.1997.4870;
RA Dear T.N., Matena K., Vingron M., Boehm T.;
RT "A new subfamily of vertebrate calpains lacking a calmodulin-like domain:
RT implications for calpain regulation and evolution.";
RL Genomics 45:175-184(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RA Crotty P.L.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Belsito A., Piluso G., Nigro V.;
RT "A novel X-linked calpain-like protease.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-277.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
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.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [8]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH MICROTUBULE.
RX PubMed=17210638; DOI=10.1128/mcb.00992-06;
RA Tonami K., Kurihara Y., Aburatani H., Uchijima Y., Asano T., Kurihara H.;
RT "Calpain 6 is involved in microtubule stabilization and cytoskeletal
RT organization.";
RL Mol. Cell. Biol. 27:2548-2561(2007).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-358.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Microtubule-stabilizing protein that may be involved in the
CC regulation of microtubule dynamics and cytoskeletal organization. May
CC act as a regulator of RAC1 activity through interaction with ARHGEF2 to
CC control lamellipodial formation and cell mobility. Does not seem to
CC have protease activity as it has lost the active site residues (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:17210638}.
CC -!- SUBUNIT: Interacts (via domain III) with microtubules. Interacts (via
CC domain II) with ARHGEF2 (via the N-terminal zinc finger).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q9Y6Q1; O43829: ZBTB14; NbExp=3; IntAct=EBI-7183095, EBI-10176632;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:17210638}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:17210638}. Note=During mitose associated with the
CC mitotic spindle. At telophase colocalized to the midbody spindle.
CC -!- TISSUE SPECIFICITY: Expressed only in placenta.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/capn6/";
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DR EMBL; AF029232; AAB86605.1; -; mRNA.
DR EMBL; AJ000388; CAA04051.1; -; mRNA.
DR EMBL; AY800242; AAV41896.1; -; Genomic_DNA.
DR EMBL; AL031117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471120; EAX02650.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02651.1; -; Genomic_DNA.
DR EMBL; BC000730; AAH00730.1; -; mRNA.
DR CCDS; CCDS14555.1; -.
DR RefSeq; NP_055104.2; NM_014289.3.
DR AlphaFoldDB; Q9Y6Q1; -.
DR SMR; Q9Y6Q1; -.
DR BioGRID; 107277; 27.
DR IntAct; Q9Y6Q1; 16.
DR MINT; Q9Y6Q1; -.
DR STRING; 9606.ENSP00000317214; -.
DR MEROPS; C02.971; -.
DR iPTMnet; Q9Y6Q1; -.
DR PhosphoSitePlus; Q9Y6Q1; -.
DR BioMuta; CAPN6; -.
DR DMDM; 13959315; -.
DR EPD; Q9Y6Q1; -.
DR jPOST; Q9Y6Q1; -.
DR MassIVE; Q9Y6Q1; -.
DR PaxDb; Q9Y6Q1; -.
DR PeptideAtlas; Q9Y6Q1; -.
DR PRIDE; Q9Y6Q1; -.
DR ProteomicsDB; 86759; -.
DR Antibodypedia; 29529; 218 antibodies from 33 providers.
DR DNASU; 827; -.
DR Ensembl; ENST00000324068.2; ENSP00000317214.1; ENSG00000077274.9.
DR GeneID; 827; -.
DR KEGG; hsa:827; -.
DR MANE-Select; ENST00000324068.2; ENSP00000317214.1; NM_014289.4; NP_055104.2.
DR UCSC; uc004epc.3; human.
DR CTD; 827; -.
DR DisGeNET; 827; -.
DR GeneCards; CAPN6; -.
DR HGNC; HGNC:1483; CAPN6.
DR HPA; ENSG00000077274; Group enriched (epididymis, placenta, seminal vesicle).
DR MIM; 300146; gene.
DR neXtProt; NX_Q9Y6Q1; -.
DR OpenTargets; ENSG00000077274; -.
DR PharmGKB; PA26063; -.
DR VEuPathDB; HostDB:ENSG00000077274; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000156128; -.
DR HOGENOM; CLU_010982_3_2_1; -.
DR InParanoid; Q9Y6Q1; -.
DR OMA; QKGRYTD; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; Q9Y6Q1; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.B26; 2681.
DR PathwayCommons; Q9Y6Q1; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR SignaLink; Q9Y6Q1; -.
DR BioGRID-ORCS; 827; 8 hits in 696 CRISPR screens.
DR ChiTaRS; CAPN6; human.
DR GenomeRNAi; 827; -.
DR Pharos; Q9Y6Q1; Tbio.
DR PRO; PR:Q9Y6Q1; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9Y6Q1; protein.
DR Bgee; ENSG00000077274; Expressed in cauda epididymis and 111 other tissues.
DR Genevisible; Q9Y6Q1; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0001578; P:microtubule bundle formation; ISS:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; ISS:UniProtKB.
DR CDD; cd04046; C2_Calpain; 1.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR033884; C2_Calpain.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR033883; C2_III.
DR InterPro; IPR022684; Calpain_cysteine_protease.
DR InterPro; IPR022682; Calpain_domain_III.
DR InterPro; IPR022683; Calpain_III.
DR InterPro; IPR036213; Calpain_III_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00239; C2; 1.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Microtubule; Reference proteome.
FT CHAIN 1..641
FT /note="Calpain-6"
FT /id="PRO_0000207717"
FT DOMAIN 26..343
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 498..621
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 344..495
FT /note="Domain III"
FT VARIANT 277
FT /note="V -> L (in dbSNP:rs12013711)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021084"
FT VARIANT 358
FT /note="G -> R (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036048"
FT VARIANT 518
FT /note="T -> I (in dbSNP:rs12851517)"
FT /id="VAR_051515"
FT CONFLICT 42
FT /note="N -> F (in Ref. 3; CAA04051)"
FT /evidence="ECO:0000305"
FT CONFLICT 415..416
FT /note="RP -> KT (in Ref. 2; AAB86605)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 641 AA; 74576 MW; A48E5291169B1028 CRC64;
MGPPLKLFKN QKYQELKQEC IKDSRLFCDP TFLPENDSLF YNRLLPGKVV WKRPQDICDD
PHLIVGNISN HQLTQGRLGH KPMVSAFSCL AVQESHWTKT IPNHKEQEWD PQKTEKYAGI
FHFRFWHFGE WTEVVIDDLL PTINGDLVFS FSTSMNEFWN ALLEKAYAKL LGCYEALDGL
TITDIIVDFT GTLAETVDMQ KGRYTELVEE KYKLFGELYK TFTKGGLICC SIESPNQEEQ
EVETDWGLLK GHTYTMTDIR KIRLGERLVE VFSAEKVYMV RLRNPLGRQE WSGPWSEISE
EWQQLTASDR KNLGLVMSDD GEFWMSLEDF CRNFHKLNVC RNVNNPIFGR KELESVLGCW
TVDDDPLMNR SGGCYNNRDT FLQNPQYIFT VPEDGHKVIM SLQQKDLRTY RRMGRPDNYI
IGFELFKVEM NRKFRLHHLY IQERAGTSTY IDTRTVFLSK YLKKGNYVLV PTMFQHGRTS
EFLLRIFSEV PVQLRELTLD MPKMSCWNLA RGYPKVVTQI TVHSAEDLEK KYANETVNPY
LVIKCGKEEV RSPVQKNTVH AIFDTQAIFY RRTTDIPIIV QVWNSRKFCD QFLGQVTLDA
DPSDCRDLKS LYLRKKGGPT AKVKQGHISF KVISSDDLTE L
