WHAMM_HUMAN
ID WHAMM_HUMAN Reviewed; 809 AA.
AC Q8TF30; Q8N1J9;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=WASP homolog-associated protein with actin, membranes and microtubules;
DE AltName: Full=WAS protein homology region 2 domain-containing protein 1;
DE Short=WH2 domain-containing protein 1;
GN Name=WHAMM; Synonyms=KIAA1971, WHDC1;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 568-809.
RC TISSUE=Thymus;
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 [4]
RP FUNCTION, INTERACTION WITH ACTR3 AND MICROTUBULES, AND MUTAGENESIS OF
RP TRP-807.
RX PubMed=18614018; DOI=10.1016/j.cell.2008.05.032;
RA Campellone K.G., Webb N.J., Znameroski E.A., Welch M.D.;
RT "WHAMM is an Arp2/3 complex activator that binds microtubules and functions
RT in ER to Golgi transport.";
RL Cell 134:148-161(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-606, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION, AND INTERACTION WITH RHOD.
RX PubMed=23087206; DOI=10.1091/mbc.e12-07-0555;
RA Gad A.K., Nehru V., Ruusala A., Aspenstrom P.;
RT "RhoD regulates cytoskeletal dynamics via the actin nucleation-promoting
RT factor WASp homologue associated with actin Golgi membranes and
RT microtubules.";
RL Mol. Biol. Cell 23:4807-4819(2012).
RN [7]
RP FUNCTION, SUBUNIT, AND ELECTRON MICROSCOPY IN COMPLEX WITH MICROTUBULES.
RX PubMed=23027905; DOI=10.1083/jcb.201204010;
RA Shen Q.T., Hsiue P.P., Sindelar C.V., Welch M.D., Campellone K.G.,
RA Wang H.W.;
RT "Structural insights into WHAMM-mediated cytoskeletal coordination during
RT membrane remodeling.";
RL J. Cell Biol. 199:111-124(2012).
CC -!- FUNCTION: Acts as a nucleation-promoting factor (NPF) that stimulates
CC Arp2/3-mediated actin polymerization both at the Golgi apparatus and
CC along tubular membranes. Its activity in membrane tubulation requires
CC F-actin and interaction with microtubules. Proposed to use coordinated
CC actin-nucleating and microtubule-binding activities of distinct WHAMM
CC molecules to drive membrane tubule elongation; when MT-bound can
CC recruit and remodel membrane vesicles but is prevented to activate the
CC Arp2/3 complex. Involved as a regulator of Golgi positioning and
CC morphology. Participates in vesicle transport between the reticulum
CC endoplasmic and the Golgi complex. Required for RhoD-dependent actin
CC reorganization such as in cell adhesion and cell migration.
CC {ECO:0000269|PubMed:18614018, ECO:0000269|PubMed:23027905,
CC ECO:0000269|PubMed:23087206}.
CC -!- SUBUNIT: Interacts with ACTR3; indicative for an association with the
CC ARP2/3 complex. Associates with microtubules; in vitro binds to tubulin
CC heterodimer in a 1:1 stoichiometry; decorates microtubules with a
CC repeat of 80 A along protofilaments. Interacts with RHOD (in GTP-bound
CC form). {ECO:0000269|PubMed:18614018, ECO:0000269|PubMed:23027905,
CC ECO:0000269|PubMed:23087206}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18614018}.
CC Endoplasmic reticulum-Golgi intermediate compartment
CC {ECO:0000269|PubMed:18614018}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:18614018}. Golgi apparatus, cis-Golgi network
CC {ECO:0000269|PubMed:18614018}. Note=Localized to a perinuclear
CC compartment near the microtubule-organizing center (MTOC). Also
CC detected on tubulo-vesicular structures in the cell periphery that
CC frequently localized along microtubules. {ECO:0000269|PubMed:18614018}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung, heart, colon and kidney
CC (at protein level).
CC -!- DOMAIN: The N-terminal region associates with membranes, the coiled-
CC coil region binds to microtubules and the WH2 domains promotes actin
CC nucleation.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB85557.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB85557.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC05201.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
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DR EMBL; AB075851; BAB85557.1; ALT_INIT; mRNA.
DR EMBL; AC044907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK097947; BAC05201.1; ALT_SEQ; mRNA.
DR CCDS; CCDS45333.1; -.
DR RefSeq; NP_001073904.1; NM_001080435.2.
DR PDB; 5X1G; EM; 4.50 A; C=513-546.
DR PDBsum; 5X1G; -.
DR AlphaFoldDB; Q8TF30; -.
DR SMR; Q8TF30; -.
DR BioGRID; 125830; 6.
DR CORUM; Q8TF30; -.
DR IntAct; Q8TF30; 3.
DR STRING; 9606.ENSP00000286760; -.
DR iPTMnet; Q8TF30; -.
DR PhosphoSitePlus; Q8TF30; -.
DR BioMuta; WHAMM; -.
DR DMDM; 152112352; -.
DR EPD; Q8TF30; -.
DR jPOST; Q8TF30; -.
DR MassIVE; Q8TF30; -.
DR MaxQB; Q8TF30; -.
DR PaxDb; Q8TF30; -.
DR PeptideAtlas; Q8TF30; -.
DR PRIDE; Q8TF30; -.
DR ProteomicsDB; 74545; -.
DR Antibodypedia; 49806; 29 antibodies from 15 providers.
DR DNASU; 123720; -.
DR Ensembl; ENST00000286760.5; ENSP00000286760.4; ENSG00000156232.7.
DR GeneID; 123720; -.
DR KEGG; hsa:123720; -.
DR MANE-Select; ENST00000286760.5; ENSP00000286760.4; NM_001080435.3; NP_001073904.1.
DR UCSC; uc002bje.5; human.
DR CTD; 123720; -.
DR DisGeNET; 123720; -.
DR GeneCards; WHAMM; -.
DR HGNC; HGNC:30493; WHAMM.
DR HPA; ENSG00000156232; Tissue enhanced (bone).
DR MIM; 612393; gene.
DR neXtProt; NX_Q8TF30; -.
DR OpenTargets; ENSG00000156232; -.
DR PharmGKB; PA164727567; -.
DR VEuPathDB; HostDB:ENSG00000156232; -.
DR eggNOG; ENOG502QPSI; Eukaryota.
DR GeneTree; ENSGT00510000046704; -.
DR HOGENOM; CLU_012316_1_0_1; -.
DR InParanoid; Q8TF30; -.
DR OMA; CGQLERY; -.
DR OrthoDB; 183925at2759; -.
DR PhylomeDB; Q8TF30; -.
DR TreeFam; TF331023; -.
DR PathwayCommons; Q8TF30; -.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR SignaLink; Q8TF30; -.
DR SIGNOR; Q8TF30; -.
DR BioGRID-ORCS; 123720; 70 hits in 1081 CRISPR screens.
DR ChiTaRS; WHAMM; human.
DR GenomeRNAi; 123720; -.
DR Pharos; Q8TF30; Tbio.
DR PRO; PR:Q8TF30; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8TF30; protein.
DR Bgee; ENSG00000156232; Expressed in amniotic fluid and 175 other tissues.
DR Genevisible; Q8TF30; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0071933; F:Arp2/3 complex binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IDA:UniProtKB.
DR GO; GO:0090527; P:actin filament reorganization; IMP:UniProtKB.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; IBA:GO_Central.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IDA:UniProtKB.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0097320; P:plasma membrane tubulation; IDA:UniProtKB.
DR GO; GO:0051127; P:positive regulation of actin nucleation; IDA:UniProtKB.
DR InterPro; IPR031738; JMY/WHAMM.
DR InterPro; IPR031808; JMY/WHAMM_N.
DR InterPro; IPR003124; WH2_dom.
DR InterPro; IPR026688; WHAMM.
DR PANTHER; PTHR23330:SF6; PTHR23330:SF6; 1.
DR Pfam; PF15871; JMY; 1.
DR Pfam; PF15920; WHAMM-JMY_N; 1.
DR PROSITE; PS51082; WH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW Golgi apparatus; Membrane; Microtubule; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..809
FT /note="WASP homolog-associated protein with actin,
FT membranes and microtubules"
FT /id="PRO_0000295100"
FT DOMAIN 709..727
FT /note="WH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT DOMAIN 739..756
FT /note="WH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 1..260
FT /note="Mediates association with membranes"
FT /evidence="ECO:0000269|PubMed:18614018"
FT REGION 261..630
FT /note="Mediates interaction with microtubules"
FT /evidence="ECO:0000269|PubMed:23027905"
FT REGION 506..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 546..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 586..612
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 627..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 631..809
FT /note="Mediates actin nucleation"
FT /evidence="ECO:0000269|PubMed:18614018"
FT REGION 754..809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 271..298
FT /evidence="ECO:0000255"
FT COILED 384..479
FT /evidence="ECO:0000255"
FT COILED 512..542
FT /evidence="ECO:0000255"
FT COILED 770..797
FT /evidence="ECO:0000255"
FT COMPBIAS 551..571
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 636..661
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 772..796
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 606
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 795
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q571B6"
FT VARIANT 212
FT /note="N -> S (in dbSNP:rs35270670)"
FT /id="VAR_061721"
FT VARIANT 340
FT /note="Q -> K (in dbSNP:rs1055666)"
FT /id="VAR_033209"
FT VARIANT 345
FT /note="R -> Q (in dbSNP:rs1055667)"
FT /id="VAR_033210"
FT VARIANT 686
FT /note="R -> H (in dbSNP:rs3814281)"
FT /id="VAR_033211"
FT VARIANT 736
FT /note="H -> P (in dbSNP:rs11259953)"
FT /id="VAR_051489"
FT VARIANT 736
FT /note="H -> Q (in dbSNP:rs11259954)"
FT /id="VAR_051490"
FT MUTAGEN 807
FT /note="W->A: Decreases nucleation-promoting factor activity
FT and Arp2/3 complex activation."
FT /evidence="ECO:0000269|PubMed:18614018"
SQ SEQUENCE 809 AA; 90924 MW; 29EA39E81A2E309C CRC64;
MEDEQPDSLE GWVPVREGLF AEPERHRLRF LVAWNGAEGK FAVTCHDRTA QQRRLREGAR
LGPEPEPKPE AAVSPSSWAG LLSAAGLRGA HRQLAALWPP LERCFPRLPP ELDVGGGGAW
GLGLGLWALL WPTRAGPGEA ALQELCGQLE RYLGAAADGC GGATVRDALF PAEGGAADCE
SPREFRERAL RARWVEADAR LRQVIQGHGK ANTMVALMNV YQEEDEAYQE LVTVATMFFQ
YLLQPFRAMR EVATLCKLDI LKSLDEDDLG PRRVVALEKE AEEWTRRAEE AVVSIQDITV
NYFKETVKAL AGMQKEMEQD AKRFGQAAWA TAIPRLEKLQ LMLARETLQL MRAKELCLNH
KRAEIQGKME DLPEQEKNTN VVDELEIQFY EIQLELYEVK FEILKNEEIL LTTQLDSLKR
LIKEKQDEVV YYDPCENPEE LKVIDCVVGL QDDKNLEVKE LRRQCQQLES KRGRICAKRA
SLRSRKDQCK ENHRFRLQQA EESIRYSRQH HSIQMKRDKI KEEEQKKKEW INQERQKTLQ
RLRSFKDKRL AQSVRNTSGS EPVAPNLPSD LSQQMCLPAS HAVSVIHPSS RKTRGVPLSE
AGNVKSPKCQ NCHGNIPVQV FVPVGDQTHS KSSEELSLPP PPPPPPPPPP PPPPPPPPLR
ALSSSSQAAT HQNLGFRAPV KDDQPRPLVC ESPAERPRDS LESFSCPGSM DEVLASLRHG
RAPLRKVEVP AVRPPHASIN EHILAAIRQG VKLKKVHPDL GPNPSSKPTS NRRTSDLERS
IKAALQRIKR VSADSEEDSD EQDPGQWDG
