GCSAM_MOUSE
ID GCSAM_MOUSE Reviewed; 181 AA.
AC Q6RFH4; Q60691; Q8CB90;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Germinal center-associated signaling and motility protein;
DE AltName: Full=Germinal center B-cell-expressed transcript 2 protein;
GN Name=Gcsam; Synonyms=Gcet, Gcet2, M17;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=7981148; DOI=10.1093/intimm/6.8.1203;
RA Christoph T., Rickert R., Rajewsky K.;
RT "M17: a novel gene expressed in germinal centers.";
RL Int. Immunol. 6:1203-1211(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Spleen;
RA Pan Z., Shen Y., Du C., Chan J.;
RT "Cloning of mouse M17 gene longer isoform, M17-L.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Bone;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Jaw, and Limb;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP MISCELLANEOUS.
RX PubMed=23299888; DOI=10.1038/ncomms2334;
RA Romero-Camarero I., Jiang X., Natkunam Y., Lu X., Vicente-Duenas C.,
RA Gonzalez-Herrero I., Flores T., Garcia J.L., McNamara G., Kunder C.,
RA Zhao S., Segura V., Fontan L., Martinez-Climent J.A., Garcia-Criado F.J.,
RA Theis J.D., Dogan A., Campos-Sanchez E., Green M.R., Alizadeh A.A.,
RA Cobaleda C., Sanchez-Garcia I., Lossos I.S.;
RT "Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis
RT via BCR-mediated Syk activation.";
RL Nat. Commun. 4:1338-1338(2013).
CC -!- FUNCTION: Involved in the negative regulation of lymphocyte motility.
CC It mediates the migration-inhibitory effects of IL6. Serves as a
CC positive regulator of the RhoA signaling pathway. Enhancement of RhoA
CC activation results in inhibition of lymphocyte and lymphoma cell
CC motility by activation of its downstream effector ROCK. Is a regulator
CC of B-cell receptor signaling, that acts through SYK kinase activation.
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with ACTB and MYH2; the interaction with MYH2 is
CC increased by IL6-induced phosphorylation. Interacts (via C-terminus)
CC with ARHGEF11 (via DH domain). Interacts with ARHGEF12. Interacts with
CC SYK; the interaction increases after B-cell receptor stimulation,
CC resulting in enhanced SYK autophosphorylation and activity.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=It relocalizes from the cytoplasm to podosome-like
CC structures upon cell treatment with IL6. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=M17-L;
CC IsoId=Q6RFH4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6RFH4-2; Sequence=VSP_021334;
CC -!- TISSUE SPECIFICITY: Highly expressed in normal germinal center (GC) B-
CC cells. Expressed in spleen and, to a lesser extent, bone marrow.
CC {ECO:0000269|PubMed:7981148, ECO:0000269|Ref.2}.
CC -!- PTM: Phosphorylation on tyrosine residues can be induced by IL6.
CC Phosphorylation is mediated by LYN. {ECO:0000250}.
CC -!- MISCELLANEOUS: GCSAM transgenic mice develop B-cell lymphoid
CC hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A
CC (AA) amyloidosis strating from 12 months of age.
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DR EMBL; U13263; AAA96821.1; -; mRNA.
DR EMBL; AY500830; AAR89181.1; -; mRNA.
DR EMBL; AK036553; BAC29474.1; -; mRNA.
DR EMBL; BC099585; AAH99585.1; -; mRNA.
DR CCDS; CCDS28199.1; -. [Q6RFH4-2]
DR CCDS; CCDS49861.1; -. [Q6RFH4-1]
DR RefSeq; NP_001152769.1; NM_001159297.1. [Q6RFH4-1]
DR RefSeq; NP_032125.3; NM_008099.4. [Q6RFH4-2]
DR AlphaFoldDB; Q6RFH4; -.
DR STRING; 10090.ENSMUSP00000123853; -.
DR iPTMnet; Q6RFH4; -.
DR PhosphoSitePlus; Q6RFH4; -.
DR MaxQB; Q6RFH4; -.
DR PaxDb; Q6RFH4; -.
DR PRIDE; Q6RFH4; -.
DR ProteomicsDB; 271202; -. [Q6RFH4-1]
DR ProteomicsDB; 271203; -. [Q6RFH4-2]
DR Antibodypedia; 1196; 180 antibodies from 30 providers.
DR DNASU; 14525; -.
DR Ensembl; ENSMUST00000023339; ENSMUSP00000023339; ENSMUSG00000022659. [Q6RFH4-2]
DR Ensembl; ENSMUST00000161347; ENSMUSP00000123853; ENSMUSG00000022659. [Q6RFH4-1]
DR GeneID; 14525; -.
DR KEGG; mmu:14525; -.
DR UCSC; uc007zir.2; mouse. [Q6RFH4-2]
DR UCSC; uc007zis.2; mouse. [Q6RFH4-1]
DR CTD; 257144; -.
DR MGI; MGI:102969; Gcsam.
DR VEuPathDB; HostDB:ENSMUSG00000022659; -.
DR eggNOG; ENOG502TDUK; Eukaryota.
DR GeneTree; ENSGT00940000158134; -.
DR HOGENOM; CLU_126867_0_0_1; -.
DR InParanoid; Q6RFH4; -.
DR OMA; CLPWKKM; -.
DR OrthoDB; 1401343at2759; -.
DR PhylomeDB; Q6RFH4; -.
DR TreeFam; TF338596; -.
DR BioGRID-ORCS; 14525; 1 hit in 107 CRISPR screens.
DR ChiTaRS; Gcsam; mouse.
DR PRO; PR:Q6RFH4; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q6RFH4; protein.
DR Bgee; ENSMUSG00000022659; Expressed in spermatocyte and 39 other tissues.
DR Genevisible; Q6RFH4; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0045159; F:myosin II binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:2000402; P:negative regulation of lymphocyte migration; ISO:MGI.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; ISO:MGI.
DR InterPro; IPR031364; GC_assoc_lym.
DR PANTHER; PTHR35351; PTHR35351; 1.
DR Pfam; PF15666; HGAL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..181
FT /note="Germinal center-associated signaling and motility
FT protein"
FT /id="PRO_0000256229"
FT REGION 117..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 150
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6F7"
FT VAR_SEQ 11..32
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:7981148"
FT /id="VSP_021334"
FT CONFLICT 102
FT /note="S -> L (in Ref. 3; BAC29474)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 181 AA; 20988 MW; 1B86F8E10454FC35 CRC64;
MGNCLQRTTR WQLDMQETPW NLRLSAKGRT CRYFRGWSCC HSVEGCSCLP WKNIRTFKAR
QESPKQNEGM TSAPVQDNAN ETYTEELCYI LVDHEAVRGR PSVNPAEGFY ENISNKAERH
KESSRGTETE YSVLRFPSPP QPLPSTDDEY ELLMPSRFSS HAFQQPRPLT TPYETHFSYP
Q
